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1 DNA replication by using exclusively the GA - 1 TP and DNA polymerase , Nf DNA polymerase , although provided with competent strand displacement and processivity features , required the presence of Nf DBP for an effective in vitro replication of Nf TP - DNA .", "entities": []}, {"sentence": "Results presented here show that Nf DBP strongly stimulates the formation of the TP - dAMP initiation complex by decreasing the Km for dATP and facilitates the transition from initiation to elongation , as it occurs in phi29 ( 76 ) .", "entities": []}, {"sentence": "These results point to either a specific and direct contact between DBP and DNA polymerase that promotes conformational changes at the polymerization active site or to an effect of DBP in conferring the optimal template structure to direct initiating nucleotide insertion .", "entities": []}, {"sentence": "A similar role has been proposed for adenovirus DBP , a DNA unwinding protein ( 77 ) .", "entities": []}, {"sentence": "As in the case of phi29 and Nf DBP , this protein stimulates the rate of initiation also by decreasing the Km for the initiating nucleotide ( 74 ) .", "entities": []}, {"sentence": "The fact that an adenovirus DBP mutant defective in unwinding can still stimulate initiation precludes the unwinding role as the one responsible for such an activation ( 77 , 78 ) .", "entities": []}, {"sentence": "In this case , contacts between DBP and pTP / DNA polymerase complex have been reported ( 77 ) .", "entities": []}, {"sentence": "The effect of Nf DBP in promoting elongation of the initiation products could be due to a decrease of the Km also for the incorporation of the dNMPs during the transition stage from initiation to elongation , to a different type of contact with the DNA polymerase that helps transition to elongation , or both .", "entities": []}, {"sentence": "The similarity in replication rates when comparing M13 DNA replication , performed in the absence of DBP ( 2400 nt / min ) , with Nf TP - 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- > ) = integraldzT ~ * ( 0 ; z ) T ~ ( rho - - > ; z ) exp [ ipilambda ( z0 + z ) rho2 ] circ ( rho / rhoMAX ) .", "entities": []}, {"sentence": "( 9 ) MathType @ MTEF @ 5 @ 5 @ + = feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY = wiFfYdH8Gipec8Eeeu0xXdbba9frFj0 = OqFfea0dXdd9vqai = hGuQ8kuc9pgc9s8qqaq = dirpe0xb9q8qiLsFr0 = vr0 = 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 = f8aYjabc + caViab = f8aYnaaBaaaleaacqWGnbqtcqWGbbqqcqWGybawaeqaaOGaeiykaKIaeiOla4IaaCzcaiaaxMaadaqadaqaaiabiMda5aGaayjkaiaawMcaaaaa @ 6F41 @", "entities": []}, {"sentence": "Aside from an inconsequential complex constant ( the first term under the integral ) , eq . 9 is the Fourier transform of the Fresnel hologram of the object ' s complex amplitude distribution .", "entities": []}, {"sentence": "Thus , the reconstruction of the hologram recorded in the coherent mode carries a quantitative measure of the object ' s phase distribution .", "entities": []}, {"sentence": "Step - wise logistic regression ( STEPLOG )", "entities": []}, {"sentence": "The group variable was considered as an ordinal ( or binary ) dependent variable and the feature vector ( multiple marker IBD estimates and covariates ) as the independent variables .", "entities": []}, {"sentence": "A nonlinear relationship ( logit ) between the dependent and independent variables was taken .", "entities": []}, {"sentence": "For binary data ( collapsing concordantly affected or unaffected sib pair into one group ) , a conventional logistic regression was used .", "entities": []}, {"sentence": "For ordinal data , the SAS LOGISTIC [ 8 ] procedure fits a parallel lines regression model based on the cumulative distribution probabilities of response categories , rather than on their individual probabilities .", "entities": []}, {"sentence": "The statistical P - value for each ( selected ) independent variable was obtained from the final model fitting with only selected variables included via an asymptotic chi - squared statistic .", "entities": []}, {"sentence": "Results", "entities": []}, {"sentence": "Here we include data obtained from active , oscillatory brain slices as well as from recordings during cortical slow oscillations in anesthetized animals .", "entities": [{"name": "brain slices", "type": "Anatomy", "pos": [56, 68]}, {"name": "cortical", "type": "Anatomy", "pos": [103, 111]}]}, {"sentence": "All recordings included in this study were obtained from the visual cortex of the ferret ( in vitro ) , cat ( in vivo ) and from barrel cortex of the rat ( in vivo ) .", "entities": [{"name": "visual cortex", "type": "Anatomy", "pos": [61, 74]}, {"name": "barrel cortex", "type": "Anatomy", "pos": [129, 142]}]}, {"sentence": "Twenty - nine neurons recorded from ferret cortical slices are included in this study ( 22 regular spiking ( RS ) ; 5 chattering ( CH ) and 2 intrinsic bursting ( IB ) ) , 27 neurons from cat visual cortex in vivo ( 14 RS ; 5 CH ; 2 IB ; 3 fast spiking ( FS ) ; plus 3 non classified ) and 14 neurons from rat barrel cortex in vivo ( 12 RS ; 1 CH ; 1 IB ) .", "entities": [{"name": "neurons", "type": "Anatomy", "pos": [14, 21]}, {"name": "cortical slices", "type": "Anatomy", "pos": [43, 58]}, {"name": "neurons", "type": "Anatomy", "pos": [175, 182]}, {"name": "visual cortex", "type": "Anatomy", "pos": [192, 205]}, {"name": "neurons", "type": "Anatomy", "pos": [293, 300]}, {"name": "barrel cortex", "type": "Anatomy", "pos": [310, 323]}]}, {"sentence": "Synaptic potentials were evoked by electric shocks ( intracortical or thalamocortical connections ) or by means of sensory ( visual or whisker ) stimulation .", "entities": [{"name": "Synaptic", "type": "Anatomy", "pos": [0, 8]}, {"name": "intracortical", "type": "Anatomy", "pos": [53, 66]}, {"name": "thalamocortical", "type": "Anatomy", "pos": [70, 85]}, {"name": "whisker", "type": "Anatomy", "pos": [135, 142]}]}, {"sentence": "The main results are : 1 ) Synaptic potentials show more paired pulsed facilitation and synaptic augmentation in active than in silent cortical networks and 2 ) Synaptic potentials occurring during up or activated states of the cortex increased their amplitude with respect to those occurring during down states .", "entities": [{"name": "Synaptic", "type": "Anatomy", "pos": [27, 35]}, {"name": "synaptic", "type": "Anatomy", "pos": [88, 96]}, {"name": "cortical networks", "type": "Anatomy", "pos": [135, 152]}, {"name": "Synaptic", "type": "Anatomy", "pos": [161, 169]}, {"name": "cortex", "type": "Anatomy", "pos": [228, 234]}]}, {"sentence": "Ca2 + Dependence of Slob57 Modulation of the Voltage Dependence of Activation of dSlo", "entities": []}, {"sentence": "Ca2 + plays a fundamental role in regulating the dSlo response to membrane depolarization .", "entities": [{"name": "membrane", "type": "Anatomy", "pos": [66, 74]}]}, {"sentence": "One of the three known Ca2 + binding sites ( Xia et al . , 2002 ; Bao et al . , 2002 ; Zeng et al . , 2005b ) , known as the calcium bowl ( Schreiber and Salkoff , 1997 ) , contributes to the high - affinity Ca2 + sensitivity of the channel ( Schreiber and Salkoff , 1997 ; Schreiber et al . , 1999 ; Braun and Sy , 2001 ; Bao et al . , 2002 ; Niu and Magleby , 2002 ; Xia et al . , 2002 ; Bao et al . , 2004 ; Zeng et al . , 2005b ) .", "entities": []}, {"sentence": "We used a mutated dSlo channel with substitution of Asp966 - Asp970 by Asn966 - Asn970 within its calcium bowl , which greatly reduces the channel ' s calcium sensitivity ( Bian et al . , 2001 ) , to determine whether Ca2 + participates in Slob57 modulation of dSlo .", "entities": []}, {"sentence": "This mutated channel , dSloD5N5 , still binds to full - length and truncated Slobs ( Fig . 1 B , lanes 4 - 6 ) .", "entities": []}, {"sentence": "During a 350 - ms test pulse ( Fig . 7 E ) , Slob57 causes dSloD5N5 inactivation ( Fig . 7 B ) , consistent with our previous finding that the inactivation caused by Slob57 is Ca2 + independent ( Zeng et al . , 2005a ) .", "entities": []}, {"sentence": "After deletion of the amino - terminal residues 2 - 6 of Slob57 , the inactivation of dSloD5N5 is eliminated ( Fig . 7 C ) , and further truncation of Slob57 to Arg16 also eliminates the inactivation ( Fig . 7 D ) , just as observed with wild - type dSlo ( Fig . 2 , C and D ) .", "entities": []}, {"sentence": "Figure 7 .", "entities": []}, {"sentence": "Slob57 causes inactivation of dSloD5N5 .", "entities": []}, {"sentence": "Same as Fig .", "entities": []}, {"sentence": "2 , except that the mutated channel dSloD5N5 was used instead of wild - type dSlo .", "entities": []}, {"sentence": "( A ) dSloD5N5 alone , ( B ) dSloD5N5 together with Slob57 , ( C ) dSloD5N5 together with Slob57DeltaN5 , ( D ) dSloD5N5 together with Slob57DeltaN15 , ( E ) pulse protocol .", "entities": []}, {"sentence": "We next used a 100 - ms test pulse ( during which no inactivation occurs ) to measure the voltage dependence of activation of dSloD5N5 in the presence of 110 muM free Ca2 + , as only at high concentrations of free Ca2 + can tail current saturation be achieved with the mutant channel ( Fig . 8 ) .", "entities": []}, {"sentence": "As shown in Fig .", "entities": []}, {"sentence": "8 , Slob57 does not rightward shift the conductance - voltage relationship of dSloD5N5 .", "entities": []}, {"sentence": "Because dSloD5N5 can still respond to an increment of free Ca2 + at high concentration ( Bian et al . , 2001 ) , we then increased the concentration of free Ca2 + to 300 muM .", "entities": []}, {"sentence": "As shown in Fig .", "entities": []}, {"sentence": "8 , the conductance - voltage relationship of dSloD5N5 shifts to less depolarized voltages when the concentration of free Ca2 + is increased from 110 to 300 muM , but again the V1 / 2 is not modulated by Slob57 .", "entities": []}, {"sentence": "Figure 8 .", "entities": []}, {"sentence": "Conductance - voltage relationships for dSloD5N5 .", "entities": []}, {"sentence": "Same protocol as Fig .", "entities": []}, {"sentence": "6 , except that the mutated channel dSloD5N5 was used in the presence ( circles ) or absence ( squares ) of Slob57 , and the concentration of free Ca2 + was either 110 muM ( filled symbols ) or 300 muM ( open symbols ) .", "entities": []}, {"sentence": "We next measured the voltage dependence of activation of wild - type dSlo , in the presence or absence of Slob57 , at free Ca2 + concentrations ranging from 20 to 300 muM .", "entities": []}, {"sentence": "As shown in Fig .", "entities": []}, {"sentence": "9 A ( and by many previous investigators ) , in the absence of Slob57 , the voltage - conductance relationship of dSlo shifts to less depolarized voltages as the free Ca2 + concentration is increased in this range .", "entities": []}, {"sentence": "The V1 / 2 decreases from 85 to - 22 mV , a change of 107 mV , when the concentration of free Ca2 + is increased from 20 to 300 muM .", "entities": []}, {"sentence": "In contrast , when dSlo is coexpressed with Slob57 , this increment of free Ca2 + concentration shifts the V1 / 2 to a much lesser extent ( Fig . 9 B and Fig . 10 A ) .", "entities": []}, {"sentence": "Note also that the effect of Slob57 on the V1 / 2 is more apparent at higher free Ca2 + concentrations ( Fig . 10 A ) .", "entities": []}, {"sentence": "To illustrate this better , we plotted the V1 / 2 change evoked by Slob57 ( DeltaV1 / 2 ) as a function of the free Ca2 + concentration ( Fig . 10 B ) to demonstrate that the magnitude of the modulatory shift in V1 / 2 evoked by Slob57 itself is calcium dependent .", "entities": []}, {"sentence": "Figure 9 .", "entities": []}, {"sentence": "Effect of calcium on dSlo voltage dependence of activation in the absence or presence of Slob57 .", "entities": []}, {"sentence": "Same as Fig .", "entities": []}, {"sentence": "6 , except that the measurements of dSlo expressed alone ( A ) or together with Slob57 ( B ) were performed in the presence of different concentrations of free Ca2 + : 20 muM ( diamonds ) , 40 muM ( inverted triangles ) , 80 muM ( triangles ) , 110 muM ( squares ) , and 300 muM ( circles ) .", "entities": []}, {"sentence": "Figure 10 .", "entities": []}, {"sentence": "Interaction between Slob57 and calcium .", "entities": []}, {"sentence": "The V1 / 2 ( A ) of the conductance - voltage relationship for dSlo expressed alone ( O ) or together with Slob57 ( * ) , taken from Fig .", "entities": []}, {"sentence": "9 , and the difference in V1 / 2 ( DeltaV1 / 2 ) evoked by Slob57 ( B ) are plotted as a function of the concentration of free Ca2 + .", "entities": []}, {"sentence": "Determination of As metabolites", "entities": []}, {"sentence": "We assessed As metabolism using the percentages of iAs , MMA , and DMA in urine , as well as two methylation indexes [ i . e . , primary methylation index ( PMI ) , defined as the ratio between MMA and iAs , and secondary methylation index ( SMI ) , defined as the ratio between DMA and MMA .", "entities": [{"name": "urine", "type": "Anatomy", "pos": [74, 79]}]}, {"sentence": "We used total urinary As [ U - As ; the sum of As metabolites ( iAs + MMA + DMA ) in urine ] as the measure of iAs exposure .", "entities": [{"name": "urinary", "type": "Anatomy", "pos": [14, 21]}, {"name": "urine", "type": "Anatomy", "pos": [85, 90]}]}, {"sentence": "Concentrations of As metabolites in urine were measured with an Agilent 1100 HPLC system ( Agilent Technologies , Waldbronn , Germany ) , coupled with hydride generation ( HG ) inductively coupled plasma mass spectrometry ( ICPMS ) ( Agilent 7500ce series ; Agilent Technologies , Japan ) .", "entities": [{"name": "urine", "type": "Anatomy", "pos": [36, 41]}, {"name": "plasma", "type": "Anatomy", "pos": [197, 203]}]}, {"sentence": "The method measures metabolites of iAs [ iAs ( III ) , iAs ( V ) , MMA , and DMA ] , but not organic As species ( e . g . , arsenobetaine , arsenocholine ) originating from the diet , because those arsenicals do not form volatile arsines ( hydride generation ) like iAs and its metabolites do .", "entities": []}, {"sentence": "The method was described in detail by Lindberg et al .", "entities": []}, {"sentence": "( 2006 ) .", "entities": []}, {"sentence": "Determination limits were 0 . 1 mug / L for arsenite [ As ( III ) ] and MMA and 0 . 2 mug / L for DMA and arsenate [ As ( V ) ] .", "entities": []}, {"sentence": "We adjusted As concentrations for variations in dilution by specific gravity ( to the mean value of 1 . 012 g / mL ) ; U - Cre , which is commonly used for dilution adjustment , was influenced more by age and nutrition than was specific gravity , and U - Cre was also associated with urinary As ( Nermell et al . 2007 ) .", "entities": [{"name": "urinary", "type": "Anatomy", "pos": [284, 291]}]}, {"sentence": "For quality control purposes , we analyzed the reference material ( CRM No . 18 ; National Institute for Environmental Studies , Ibaraki , Japan ) with a certified DMA concentration of 36 + / - 9 mug / L together with the collected urine samples .", "entities": [{"name": "urine samples", "type": "Anatomy", "pos": [232, 245]}]}, {"sentence": "The concentration of DMA was 41 + / - 3 . 4 mug / L ( mean + / - SD ; n = 18 ) .", "entities": []}, {"sentence": "Urine samples were also analyzed for As metabolites by atomic fluorescence spectrometry ( AFS ) and for the sum of As metabolites by atomic absorption spectrometry ( AAS ) , as reported by Lindberg et al .", "entities": [{"name": "Urine samples", "type": "Anatomy", "pos": [0, 13]}]}, {"sentence": "( 2007a ) .", "entities": []}, {"sentence": "The results of ICPMS and AFS showed good agreement for all metabolites ; for iAs [ As ( III ) + As ( V ) ] , MMA , and DMA , R2 = 0 . 91 , 0 . 91 , and 0 . 97 , respectively ( n = 221 ) .", "entities": []}, {"sentence": "Further , we obtained good agreement for the sum of As metabolites between the three different methods ( for ICPMS vs . AFS , R2 = 0 . 97 ; for ICPMS vs . AAS , R2 = 0 . 96 ( n = 221 ) .", "entities": []}, {"sentence": "Mean differences of scores with baseline of the 22 patients who competed all QLQ - C30 questionnaires - symptoms scores .", "entities": []}, {"sentence": "CA IX and response to PMRT", "entities": []}, {"sentence": "Kaplan - Meier probability plots of OS after PMRT among CA IX positive and CA IX negative patients revealed improved survival after PMRT in both subgroups of patients ( Figure 2 ) .", "entities": []}, {"sentence": "Fifteen - year OS probabilities were improved by 7 % and 9 % after PMRT for the subgroups of CA IX positive and CA IX negative patients , respectively .", "entities": []}, {"sentence": "The HR of overall mortality after PMRT was 0 . 87 ( 95 % CI 0 . 60 to 1 . 27 ) for the small subgroup of 151 CA IX positive patients and 0 . 82 ( 95 % CI 0 . 69 to 0 . 97 ) for the large subgroup of 813 CA IX negative patients .", "entities": []}, {"sentence": "HRs and 95 % CIs after PMRT did not differ significantly between CA IX positive and CA IX negative patients for OS , DSS , DM , or LRR ( Table 4 ) .", "entities": []}, {"sentence": "In multivariate analysis by Cox regression , no significant interaction was found between CA IX and randomization status for any of the four end - points .", "entities": []}, {"sentence": "Similar tendencies were observed when the women were separated into premenopausal and postmenopausal women , and into women with one to three positive nodes and those with more than three positive nodes .", "entities": [{"name": "nodes", "type": "Anatomy", "pos": [151, 156]}, {"name": "nodes", "type": "Anatomy", "pos": [197, 202]}]}, {"sentence": "Table 4", "entities": []}, {"sentence": "Hazard ratios", "entities": []}, {"sentence": "CA IX positive ( n = 151 ) CA IX negative ( n = 794 )", "entities": []}, {"sentence": "Overall mortality 0 . 87 ( 0 . 60 - 1 . 27 ) 0 . 82 ( 0 . 69 - 0 . 97 )", "entities": []}, {"sentence": "Disease - specific mortality 0 . 83 ( 0 . 55 - 1 . 27 ) 0 . 76 ( 0 . 63 - 0 . 93 )", "entities": []}, {"sentence": "Distant metastases 0 . 83 ( 0 . 54 - 1 . 25 ) 0 . 76 ( 0 . 63 - 0 . 91 )", "entities": [{"name": "metastases", "type": "Anatomy", "pos": [8, 18]}]}, {"sentence": "Locoregional recurrence 0 . 23 ( 0 . 08 - 0 . 61 ) 0 . 16 ( 0 . 09 - 0 . 28 )", "entities": []}, {"sentence": "Presented are hazard ratios ( 95 % confidence intervals ) of overall mortality , disease - specific mortality , distant metastases and loco - regional recurrence probabilities after postmastectomy radiotherapy in carbonic anhydrase ( CA ) IX positive and in CA IX negative high - risk breast cancer patients .", "entities": [{"name": "metastases", "type": "Anatomy", "pos": [120, 130]}, {"name": "breast cancer", "type": "Anatomy", "pos": [285, 298]}]}, {"sentence": "Figure 2", "entities": []}, {"sentence": "Overall survival in high - risk breast cancer patients .", "entities": [{"name": "breast cancer", "type": "Anatomy", "pos": [32, 45]}]}, {"sentence": "Shown are Kaplan - Meier probability plots of overall survival in high - risk breast cancer patients as a function of randomization to postmastectomy radiotherapy ( RT ) within the subgroups of carbonic anhydrase ( CA ) IX negative and CA IX positive patients .", "entities": [{"name": "breast cancer", "type": "Anatomy", "pos": [78, 91]}]}, {"sentence": "The values given in parentheses after hazard ratios ( HRs ) are the 95 % confidence intervals .", "entities": []}, {"sentence": "Changing the cutpoints to at least one tumour cell , or > = 20 % or > = 30 % invasive tumour staining did not improve the predictive value of positive CA IX staining ( data not presented ) .", "entities": [{"name": "tumour cell", "type": "Anatomy", "pos": [39, 50]}, {"name": "invasive tumour", "type": "Anatomy", "pos": [77, 92]}]}, {"sentence": "Acknowledgements", "entities": []}, {"sentence": "The authors would like to express their gratitude to Dr . Mahasti Alizadeh for her assistance in the data analysis and designing the questionnaire .", "entities": []}, {"sentence": "Methods", "entities": []}, {"sentence": "RESULTS", "entities": []}, {"sentence": "Forty Caucasians ( 19 females ) with essential hypertension were enrolled in the study .", "entities": []}, {"sentence": "Their mean age was 57 years .", "entities": []}, {"sentence": "Most of them were overweight , 17 had metabolic syndrome according to the updated AHA NHLBI statement ( defined as 3 or more of the following : waist circumference > 102 cm in men and > 88 cm in women , blood pressure > = 130 / 85 mmHg , triglycerides > 150 mg / dl , HDL - C < 40 mg / dl in men and < 50 mg / dl in women , and fasting glucose > = 100 mg / dl ) , 8 had type 2 diabetes and 18 were smokers ( Table 1 ) .", "entities": [{"name": "blood", "type": "Anatomy", "pos": [203, 208]}]}, {"sentence": "Eprosartan reduced SBP by 8 % ( p < 0 . 001 ) and DBP by 13 % ( p < 0 . 001 ) , while it had a neutral effect on the lipid profile and apolipoprotein levels ( Table2 ) .", "entities": []}, {"sentence": "Eprosartan did not affect plasma 8 - epiPGF2a levels , whereas it significantly increased by 24 % the lag time of total serum oxidation ( 145 + / - 54 min vs 180 + / - 58 min , p = 0 . 001 ) ( Table2 ) .", "entities": [{"name": "plasma", "type": "Anatomy", "pos": [26, 32]}, {"name": "serum", "type": "Anatomy", "pos": [120, 125]}]}, {"sentence": "Eprosartan reduced by 14 % the aspartate aminotransferase ( form 21 to 18 U / L , p = 0 . 04 ) and by 21 % the alanine aminotransferase ( from 24 to 19 U / L , p = 0 . 05 ) activity ( Table2 ) .", "entities": []}, {"sentence": "The administration of eprosartan had no influence on glucose homeostasis , as well as on creatinine and uric acid levels ( Table2 ) .", "entities": []}, {"sentence": "In addition , eprosartan did not affect clotting or fibrinolytic activity as this was estimated by PAI - 1 , tPA and a2 - antiplasmin ( Table2 ) .", "entities": []}, {"sentence": "The enzymatic activity of Lp - PLA2 and PON1 were not altered significantly following eprosartan treatment ( Table2 ) .", "entities": []}, {"sentence": "Comparison of the number of known complexes matched by the predicted clusters generated by IPCA and other previous algorithms", "entities": []}, {"sentence": "Authors ' contributions", "entities": []}, {"sentence": "OK and MG analyzed and interpreted the patient data regarding his hospitalization .", "entities": []}, {"sentence": "SP and PK performed the coronary angiography , and were the major contributors in writing the manuscript .", "entities": [{"name": "coronary", "type": "Anatomy", "pos": [24, 32]}]}, {"sentence": "All authors read and approved the final manuscript .", "entities": []}, {"sentence": "Fragmentation of the parent ion / TCE - sulfate moiety", "entities": []}, {"sentence": "The mass spectrum of compound 5 displays its molecular ion 5a with the typical isotope pattern [ 18 ] of a pentachlorinated compound at m / z 448 ( relative abundance , 15 % ) ( Figure 2 ) .", "entities": []}, {"sentence": "Scheme 1 illustrates the various fragmentation pathways of this precursor ion .", "entities": []}, {"sentence": "The molecular ion 5a loses a PCB sulfate ( ArOSO3 - ) group , thus yielding TCE group - derived fragment ions .", "entities": []}, {"sentence": "These ions , [ CH2CCl3 ] + and [ CH = CCl2 ] + , are observed at m / z 131 ( 6 % ) and 95 ( 7 % ) , respectively .", "entities": []}, {"sentence": "Scheme 1", "entities": []}, {"sentence": "Principal EI - MS fragmentation pathways of sulfuric acid 2 ' , 5 ' - dichlorobiphenyl - 4yl ester 2 , 2 , 2 - trichloroethyl ester 5 .", "entities": []}, {"sentence": "More complex fragmentation patterns are observed for the fragmentation of the - OSO3 - TCE group .", "entities": []}, {"sentence": "The abundant fragment ion 5g ( m / z 237 , 28 % ) can be formed by two fragmentation pathways from precursor ion 5a .", "entities": []}, {"sentence": "One pathway involves the release of HCl and Cl from precursor ion 5a , leading to an unstable cyclic fragment ion 5b ( m / z 377 , 5 % ) .", "entities": []}, {"sentence": "In turn , fragment ion 5b produces the fragment ion 5g after releasing chloroethyne and SO3 .", "entities": []}, {"sentence": "The other pathway resulting in the formation of fragment ion 5g involves the removal of two neutral molecules , HCHO and SO2 , from the daughter fragment ion 5c ( m / z 331 , 5 % ) , which is formed by releasing the free radical group CCl3 from fragment ion 5a .", "entities": []}, {"sentence": "Alternatively , the fragment ion 5c can also produce the daughter fragment ion 5e ( m / z 183 , 12 % ) by losing one molecule of SO3 .", "entities": []}, {"sentence": "In addition , precursor ion 5a yields the daughter ion 5d by losing a CHCCl3 fragment .", "entities": []}, {"sentence": "The basic fragment ion 5f at m / z 238 is produced from the daughter ion 5d ( m / z 318 , 20 % ) by releasing one molecule of SO3 .", "entities": []}, {"sentence": "Fragment ions 5f and 5g can produce the important fragment ion 5h at m / z 209 with a relative abundance of 26 % by losing a CHO or CO fragment , respectively .", "entities": []}, {"sentence": "The same fragmentation pathways are observed for the TCE PCB sulfates diesters 1 and 3 - 10 .", "entities": []}, {"sentence": "The only exception is compound 2 , which has the TCE sulfate group in ortho position to the other phenyl ring .", "entities": []}, {"sentence": "The mass spectrum of compounds 2 is distinctively different from the mass spectrum of its isomer , compound 3 ( Figures 3 and 4 ) .", "entities": []}, {"sentence": "As shown in Scheme 2 , the basic fragment ion of compound 2 is the stable dibenzofuran ion 2f .", "entities": []}, {"sentence": "Fragment ion 2f is formed from the parent ion 2a ( m / z 414 ; relative abundance , 21 % ) by sequential loss of CHCCl3 ( 2d , m / z 284 ; relative abundance , 10 % ) , SO3 ( 2e , m / z 204 ; relative abundance , 28 % ) and HCl ( 2f , m / z 168 ; relative abundance , 100 % ) .", "entities": []}, {"sentence": "The stable dibenzofuran cation 2f is also formed as the base peak ion in the fragmentation pathways of corresponding methoxylated PCB 11 ( Table 1 ) .", "entities": []}, {"sentence": "Similarly , other 2 - methoxy PCB derivatives also form a stable dibenzofuran cation after losing chlorine atom and methyl group [ 19 ] .", "entities": []}, {"sentence": "Scheme 2", "entities": []}, {"sentence": "Principal EI - MS fragmentation pathways of sulfuric acid 4 ' - dichlorobiphenyl - 2 - yl ester 2 , 2 , 2 - trichloroethyl ester 2 .", "entities": []}, {"sentence": "The relative abundance of several fragment ions depends on the position of the - OSO3 - TCE group and the chlorine substitution pattern .", "entities": []}, {"sentence": "The relative abundance of the [ M - HCl2 ] + and [ M - CCl3 ] + fragment ions of compound 2 , 9 and 10 are lower compared to all other TCE PCB sulfate diesters ( Table 1 ) .", "entities": []}, {"sentence": "This lower relative abundance is due to steric and / or electronic effects resulting from the ortho phenyl substituent in compound 2 or the two ortho chlorine substituents in compounds 9 and 10 .", "entities": []}, {"sentence": "In addition , the relative abundance of fragment ion [ ArOSO3H ] + of the TCE PCB sulfate diesters 9 and 10 is low compared to the corresponding fragment ion of the other TCE PCB sulfate diesters , with only a trace of the respective ions being observed ( Table 1 ) .", "entities": []}, {"sentence": "For example , the relative abundance of [ ArOSO3H ] + 5d is 20 % , whereas the abundance of the corresponding fragment ions of compounds 9 and 10 is < < 1 % .", "entities": []}, {"sentence": "Since compounds 9 and 10 have two chlorine substituents in the phenyl ring with the - OSO3TCE group , the low relative abundance of fragment ion [ ArOSO3H ] + suggests that the sulfate group of both compounds is less stable , possibly because of the comparatively high pKa value of the Ar - OH group [ 20 ] .", "entities": []}, {"sentence": "This observation is in agreement with the decreasing chemical stability of aryl sulfate monoesters with increasing acidity of the phenolic aryl group [ 21 ] .", "entities": []}, {"sentence": "Authors ' contributions", "entities": []}, {"sentence": "CM , JRH , HJP , and JH carried animal studies .", "entities": []}, {"sentence": "CM performed the statistical analysis .", "entities": []}, {"sentence": "JLK conceived of the study , participated in its design and coordination , and drafted and edited the manuscript .", "entities": []}, {"sentence": "All authors read and approved the final manuscript .", "entities": []}, {"sentence": "Disk preparation phase", "entities": []}, {"sentence": "o Adoption of a two - stage sampling scheme .", "entities": []}, {"sentence": "o Careful planning and choice of representative sampling groups and sites according to the adopted network sampling technique , and determining certain criteria such as control sites where major sampling groups exist ( i . e . surface water points , valleys , and wells ) , impact sites where contamination is expected , such as polygons , and outlets ( e . g . treated water discharges site ) to maximise understanding the quality of urban water sources , and with the least risk of missing the correct representative sampling groups and sites .", "entities": []}, {"sentence": "o Attention paid to ensure inclusion in the sampling frame of all groups and locations ( sites , roads , venues , and so on ) via screening , browsing , and delineation from a satellite digital map of the Khamis Mushait Governorate zone , because local pre - knowledge was preferred with regard to accessibility , safety , and permission .", "entities": []}, {"sentence": "o Approximation of the number of the target study population in each group and sampling location .", "entities": []}, {"sentence": "o Determination of the proportional allocation of samples between different groups and locations .", "entities": []}, {"sentence": "o Training of interviewers \\ sample collectors to follow and to use the sampling strategy and procedures .", "entities": []}, {"sentence": "o Implementation of ways to boost participation rates in the screening and core interviews and sample collection .", "entities": []}, {"sentence": "o Planning of logistic needs of timing , gathering , handling samples , and laboratory .", "entities": []}, {"sentence": "o Producing sampling cards to be completed to record observations at scene ( sample ID and data / information : date , time , temperature , group , locality , problems in the area , sketch map ) .", "entities": []}, {"sentence": "o Selection of an appropriate major sampling method [ 52 ] ( i . e . simple random sample ; network sampling ) .", "entities": []}, {"sentence": "o Planning of pilot visits to samples of each group in the field to review strategy .", "entities": []}, {"sentence": "Results", "entities": []}, {"sentence": "In the established adult rat NSC culture , FGF - 2 promotes self - renewal by increasing proliferation and inhibiting spontaneous differentiation of adult NSCs , accompanied with activation of MAPK and PLC pathways .", "entities": [{"name": "NSC culture", "type": "Anatomy", "pos": [29, 40]}, {"name": "NSCs", "type": "Anatomy", "pos": [155, 159]}]}, {"sentence": "Using a molecular genetic approach , we demonstrate that activation of FGF receptor 1 ( FGFR1 ) , largely through two key cytoplasmic amino acid residues that are linked to MAPK and PLC activation , suffices to promote adult NSC self - renewal .", "entities": [{"name": "cytoplasmic", "type": "Anatomy", "pos": [122, 133]}, {"name": "NSC", "type": "Anatomy", "pos": [225, 228]}]}, {"sentence": "The canonical MAPK , Erk1 / 2 activation , is both required and sufficient for the NSC expansion and anti - differentiation effects of FGF - 2 .", "entities": [{"name": "NSC", "type": "Anatomy", "pos": [83, 86]}]}, {"sentence": "In contrast , PLC activation is integral to the maintenance of adult NSC characteristics , including the full capacity for neuronal and oligodendroglial differentiation .", "entities": [{"name": "NSC", "type": "Anatomy", "pos": [69, 72]}, {"name": "neuronal", "type": "Anatomy", "pos": [123, 131]}, {"name": "oligodendroglial", "type": "Anatomy", "pos": [136, 152]}]}, {"sentence": "Stochastic models", "entities": []}, {"sentence": "Stochasticity inevitably emerges when molecular components are present at low cellular concentrations ( McAdams & Arkin , 1997 ; Kierzek et al . , 2001 ) .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [78, 86]}]}, {"sentence": "This physical phenomenon generates noise in synthetic and natural circuits ( Paulsson , 2004 ; Mettetal et al . , 2006 ) , and its consequences over the phenotype are starting to be explored ( Suel et al . , 2006 ) .", "entities": []}, {"sentence": "For example , noise constitutes the driving force behind differentiation in isogenetic colonies ( Colman - Lerner et al . , 2005 ) .", "entities": []}, {"sentence": "Biological and theoretical studies have aided to delineate the regulatory mechanism by which the cell handles noise efficiently and effectively to carry out its biological functions ( Gardner & Collins , 2000 ; Orrell & Bolouri , 2004 ; Raser & O ' Shea , 2005 ) .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [97, 101]}]}, {"sentence": "From a theoretical point of view , stochastic models are the most challenging but also the most realistic ones : there is a precise counting of how , through individual chemical reactions , the populations of every chemical species change .", "entities": []}, {"sentence": "The milestone to simulate stochastic processes is the Gillespie algorithm ( Gillespie , 1992 ) .", "entities": []}, {"sentence": "Because of their analytical and computational complexity , the present models do not surpass a handful of chemical species .", "entities": []}, {"sentence": "Two immediate problems must be solved to model systems with several dozens of genetic components : the systematic determination of kinetic constants and the efficient computation of thousands of chemical stochastic equations ( Kuwahara et al . , 2006 ; Sanchez & Kondev , 2008 ) .", "entities": []}, {"sentence": "Model of how estrogen induces DNA damage .", "entities": []}, {"sentence": "Estrogen enters the cell and is bound by the ER .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [20, 24]}]}, {"sentence": "The dimeric ER - estrogen complex enters the nucleus and induces AID expression .", "entities": [{"name": "nucleus", "type": "Anatomy", "pos": [45, 52]}]}, {"sentence": "This leads to an increase in mutations and translocations , and potentially cancer", "entities": []}, {"sentence": "8 . 2 .", "entities": []}, {"sentence": "Species Differences in PPARalpha - Associated Signaling", "entities": []}, {"sentence": "The PPARalpha isotype has prime importance for studies with animal models to predict the effects of hepatic PPs in humans , because PPARalpha agonists induce seemingly quite different actions in rodents and humans [ 53 ] .", "entities": [{"name": "hepatic", "type": "Anatomy", "pos": [100, 107]}]}, {"sentence": "Originally , as the name indicates , PPARs were studied because of their ability to bind PPs and consequently induce PP - metabolizing enzymes .", "entities": []}, {"sentence": "In rats and mice , but not in humans , PPs such as hypolipidemic drugs , industrial plasticizers , and herbicides are non - genotoxic carcinogens that cause liver tumors [ 54 ] .", "entities": [{"name": "liver tumors", "type": "Anatomy", "pos": [157, 169]}]}, {"sentence": "In humans , these drugs function to maintain lipid homeostasis and do not induce peroxisome proliferation .", "entities": [{"name": "peroxisome", "type": "Anatomy", "pos": [81, 91]}]}, {"sentence": "Thus , the toxicity and carcinogenicity of PPs are highly species specific [ 55 ] .", "entities": []}, {"sentence": "The species differences may be attributable to lower PPAR mRNA expression levels in h - hepatocytes compared with rodent cells [ 56 , 57 ] .", "entities": [{"name": "h - hepatocytes", "type": "Anatomy", "pos": [84, 99]}, {"name": "cells", "type": "Anatomy", "pos": [121, 126]}]}, {"sentence": "Alternatively , or additionally , species differences may be the result of different sensitivities of the genes associated with the peroxisome proliferation response to low levels of PPs , owing to structural differences in PPARalpha [ 54 ] .", "entities": [{"name": "peroxisome", "type": "Anatomy", "pos": [132, 142]}]}, {"sentence": "There are both similarities and differences in responses to xenobiotics among not only different species ( interspecies ) but also individuals of the same species ( intraspecies ) .", "entities": []}, {"sentence": "Interspecific PPARalpha diversity between rodents and humans is well known and has been studied with respect to drug metabolism .", "entities": []}, {"sentence": "NR subfamily 1 members have at least two functions in mammals .", "entities": []}, {"sentence": "One is to regulate peroxisome proliferation through binding to PPAR response elements ( PPREs ) in the promoters of genes such as ACO [ 58 , 59 ] , bifunctional dehydrogenase / hydratase ( BFE ) [ 60 ] , and microsomal CYP4A1 [ 61 ] .", "entities": [{"name": "peroxisome", "type": "Anatomy", "pos": [19, 29]}]}, {"sentence": "The other is to modulate the serum cholesterol level by targeting genes such as the lipoprotein lipase gene [ 62 ] and the apolipoprotein regulating genes AI , AII , and CII [ 63 ] .", "entities": [{"name": "serum", "type": "Anatomy", "pos": [29, 34]}]}, {"sentence": "The former mechanism appears to function in rodents , but not in humans , and is responsible for the induction of peroxisome proliferation and hepatocarcinogenesis , whereas the latter mechanism controls basic lipid metabolism in both rodents and humans [ 56 ] .", "entities": [{"name": "peroxisome", "type": "Anatomy", "pos": [114, 124]}]}, {"sentence": "This species difference in xenobiotic receptor / ligand signaling may be attributable to differences in the expression level of a receptor , or to differences in receptor / ligand binding affinity , and causes difficulty in determining responses in humans based on rodent data [ 56 ] .", "entities": []}, {"sentence": "Results :", "entities": []}, {"sentence": "In the total population ( N = 95 ) , median OS was significantly longer in patients with baseline CA 19 - 9 values at or below the median than in those with values above it ( 12 . 2 months [ 95 % confidence interval ( CI ) , 8 . 6 - 16 . 6 % ] vs 5 . 0 months [ 95 % CI , 3 . 9 - 5 . 7 % ] ; P < 0 . 0001 ) .", "entities": []}, {"sentence": "This also reached significance in the Gem + A arm ( median OS , 12 . 5 months [ 95 % CI , 8 . 6 - 16 . 6 % ] vs 4 . 9 months [ 95 % CI , 3 . 6 - 5 . 6 % ] ; P < 0 . 0001 ) .", "entities": []}, {"sentence": "Patients with any dBP > 90 mmHg had significantly longer OS than those who did not .", "entities": []}, {"sentence": "However , there was no predictive significance of CA 19 - 9 .", "entities": []}, {"sentence": "Reagents", "entities": []}, {"sentence": "CNQX , colchicine , forskolin , and carbenoxolone were purchased from Sigma .", "entities": []}, {"sentence": "DCG - IV , ZD7288 , CGP55845 and DPCPX were obtained from Tocris Cookson ( Ellisville , MO ) .", "entities": []}, {"sentence": "Results", "entities": []}, {"sentence": "Contrary to previous reports that PON1 activities plateau by 2 years of age , we observed an age - dependent increase in all three PON1 measures from birth through 7 years of age ( p < 0 . 0001 ) .", "entities": []}, {"sentence": "The PON1192 genotype significantly modified the effect of age on paraoxonase ( POase ) activity ( p < 0 . 0001 ) such that increases in enzyme activity with age were influenced by the number of R alleles in a dose - dependent manner .", "entities": []}, {"sentence": "Children with the PON1 - 108CC192RR diplotype had significantly higher mean PON1 activities and also experienced steeper increases of POase activity over time compared with children with the PON1 - 108TT192QQ diplotype .", "entities": []}, {"sentence": "Percentage reported purchasing intentions , comparing ITN - owning to non - owning households", "entities": []}, {"sentence": "School environment", "entities": []}, {"sentence": "At the majority of the schools a soft drink vending machine ( 91 % , n = 446 ) and / or a vending machine containing sweets and candy bars ( 81 % , n = 413 ) is present ( Table 2 ) .", "entities": []}, {"sentence": "At 78 % ( n = 393 ) of the schools there is a supermarket , gas station or a fast food restaurant in the neighbourhood ( within 1 km of the school ) .", "entities": []}, {"sentence": "At 68 % ( n = 345 ) of the schools there are facilities at or around the school property where the students can be physically active , for example a soccer field or a basketball field .", "entities": []}, {"sentence": "Table 2", "entities": []}, {"sentence": "The school environment", "entities": []}, {"sentence": "Total School level", "entities": []}, {"sentence": "Vocational education schools Mixed schools Higher education schools Vocational education schools versus higher education schools # Mixed schools versus higher education schools #", "entities": []}, {"sentence": "n = 515 n = 216 n = 232 n = 67", "entities": []}, {"sentence": "% ( n ) % ( n ) % ( n ) % ( n ) OR ( 95 % CI ) OR ( 95 % CI )", "entities": []}, {"sentence": "Soft drink vending machine present at school 91 . 4 ( 466 ) 90 . 2 ( 194 ) 91 . 3 ( 209 ) 95 . 5 ( 63 ) 1 . 0 ( 0 . 9 ; 1 . 1 ) 1 . 0 ( 0 . 9 ; 1 . 0 )", "entities": []}, {"sentence": "Percentage of soft drink vending machines present at school that contain light soft drinks 79 . 8 ( 372 ) 75 . 4 ( 147 ) 82 . 2 ( 171 ) 85 . 7 ( 54 ) 0 . 9 ( 0 . 8 ; 1 . 0 ) 1 . 0 ( 0 . 9 ; 1 . 1 )", "entities": []}, {"sentence": "Soft drink vending machines contain more unhealthy drinks than healthy drinks 57 . 9 ( 268 ) 61 . 9 ( 120 ) 58 . 5 ( 121 ) 43 . 6 ( 27 ) 1 . 4 ( 1 . 0 ; 1 . 9 ) 1 . 4 ( 1 . 0 ; 1 . 9 ) *", "entities": []}, {"sentence": "Vending machine present at school that contains sweets / candy bars 80 . 7 ( 413 ) 75 . 6 ( 161 ) 84 . 9 ( 197 ) 82 . 1 ( 55 ) 1 . 1 ( 0 . 9 ; 1 . 2 ) 1 . 1 ( 1 . 0 ; 1 . 2 )", "entities": []}, {"sentence": "Sweets / candy bars vending machines contain more unhealthy than healthy foods 63 . 7 ( 260 ) 70 . 6 ( 113 ) 64 . 4 ( 125 ) 40 . 7 ( 22 ) 1 . 7 ( 1 . 2 ; 2 . 4 ) * 1 . 6 ( 1 . 1 ; 2 . 3 ) *", "entities": []}, {"sentence": "There is a supermarket , gas station , or fast food restaurant in the neighbourhood of the school 78 . 3 ( 393 ) 76 . 7 ( 161 ) 79 . 7 ( 181 ) 78 . 5 ( 51 ) 1 . 1 ( 0 . 9 ; 1 . 2 ) 1 . 1 ( 0 . 9 ; 1 . 2 )", "entities": []}, {"sentence": "The students are allowed to leave the school property during school hours 57 . 4 ( 295 ) 42 . 6 ( 92 ) 65 . 8 ( 152 ) 76 . 1 ( 51 ) 0 . 6 ( 0 . 5 ; 0 . 8 ) * 0 . 9 ( 0 . 8 ; 1 . 0 )", "entities": []}, {"sentence": "There are facilities at and around the school property where the students can be physically active 68 . 1 ( 345 ) 63 . 1 ( 135 ) 70 . 3 ( 161 ) 76 . 6 ( 49 ) 0 . 8 ( 0 . 7 ; 1 . 0 ) 0 . 9 ( 0 . 8 ; 1 . 1 )", "entities": []}, {"sentence": "# Associations are adjusted for school size", "entities": []}, {"sentence": "* p < 0 . 05", "entities": []}, {"sentence": "The vocational education schools did not differ from the higher education schools with regard to the presence of vending machines and a canteen , but the vending machines and the canteen contained a less favourable selection of foods and drinks .", "entities": []}, {"sentence": "The vocational education schools indicated more often that the vending machines and the canteen contained more unhealthy foods and drinks than healthy foods and drinks .", "entities": []}, {"sentence": "Vocational education schools had fewer facilities at and around the school property to be physical than the higher education schools .", "entities": []}, {"sentence": "Most associations were attenuated after adjustment for school size .", "entities": []}, {"sentence": "For example , the association between school level and content of the soft drink vending machines was OR = 1 . 42 , 95 % CI : 1 . 05 - 1 . 93 in the crude analysis and OR = 1 . 35 , 95 % CI : 0 . 99 - 1 . 85 in the adjusted analysis .", "entities": []}, {"sentence": "Behavior", "entities": []}, {"sentence": "Across all participants , 50 % + / - 13 of studied high - complexity scene were later recognized as \" old \" ( hit rate ) , and 52 % + / - 18 of studied low - complexity scenes were later recognized as \" old \" .", "entities": []}, {"sentence": "For new scenes presented at test ( foils ) , 22 % + / - 16 of high - complexity scenes were falsely categorized as \" old \" ( false alarm rate ) , and 22 % + / - 14 of low - complexity scenes were falsely categorized as \" old \" .", "entities": []}, {"sentence": "Across all participants , adjusted hit rate ( hit rate - false alarm rate ) for high - complexity scenes ( 28 % + / - 13 ) did not differ from that for low - complexity scenes ( 30 % + / - 14 ) ( t ( 45 ) = 1 . 02 , p = 0 . 31 ) .", "entities": []}, {"sentence": "Critically , the adjusted hit rate increased with age for high - complexity ( r = 0 . 40 , p = 0 . 006 ) , but not for low - complexity ( r = 0 . 11 , p = 0 . 46 ) scenes .", "entities": []}, {"sentence": "Thus , overall participants had similar memory accuracy for high - and low - complexity scenes , but memory accuracy improved with age only for high - complexity scenes .", "entities": []}, {"sentence": "Participants categorized as \" remembered \" ( RHIT ) , 28 % + / - 12 of the studied high - complexity scenes , and 29 % + / - 15 of the studied low - complexity scenes .", "entities": []}, {"sentence": "Participants had similar rates of falsely categorizing as \" remembered \" ( RFA ) high ( 5 % + / - 6 ) and low ( 5 % + / - 6 ) complexity foils .", "entities": []}, {"sentence": "Across all participants , adjusted R rates ( RHIT - RFA ) for high - complexity scenes did not differ from that for low - complexity scenes ( t ( 45 ) = 1 . 41 , p = 0 . 17 ) .", "entities": []}, {"sentence": "Adjusted R rates increased with age for high - complexity ( r = 0 . 38 , p = 0 . 009 ) , but not for low - complexity ( r = 0 . 16 , p = 0 . 30 ) , scenes ( Figures 1C , D ) .", "entities": []}, {"sentence": "The difference between the adjusted R rates of high - and low - complexity scenes increased with age ( r = 0 . 27 , p = 0 . 03 ; 1 - tailed ) , suggesting that the age - related improvements in memory performance were more robust for recollected high - complexity scenes .", "entities": []}, {"sentence": "Thus , overall , participants had similar memory accuracy for recollected high - and low - complexity scenes , but accuracy for recollected high - complexity scenes improved with age , whereas accuracy for recollected low - complexity scenes did not change with age .", "entities": []}, {"sentence": "Participants categorized as \" familiar \" ( KHIT ) , 22 % + / - 9 of studied high - complexity scenes , and 22 % + / - 10 of studied low - complexity scenes .", "entities": []}, {"sentence": "Participants falsely categorized as \" familiar \" ( KFA ) 17 % + / - 11 of high - complexity , and 17 % + / - 12 of low - complexity foils .", "entities": []}, {"sentence": "Across all participants , adjusted K rates ( KHIT - KFA ) for high - complexity scenes did not differ from that for low - complexity scenes ( t ( 45 ) = 0 . 06 , p = 0 . 95 ) .", "entities": []}, {"sentence": "Adjusted K rates did not change with age for either high - complexity or low - complexity scenes ( | r | s < 0 . 09 , ps > 0 . 56 ) ( Figures 1C , D ) .", "entities": []}, {"sentence": "During the encoding task , participants were overall faster to respond to low - complexity scenes ( 1072 + / - 275 ms ) than to high - complexity scenes ( 1093 + / - 287 ms ) ( t ( 45 ) = 2 . 31 , p = 0 . 03 ) .", "entities": []}, {"sentence": "Response times decreased with age for low - ( r = - 0 . 37 , p = 0 . 01 ) and high - ( r = - 0 . 33 , p = 0 . 03 ) complexity scenes .", "entities": []}, {"sentence": "The difference between the response times for high - and low - complexity scenes , however , did not change with age ( r = 0 . 14 , p = 0 . 35 ) .", "entities": []}, {"sentence": "Response times decreased with age for R , K and F trial types for both high - and low - complexity scenes ( - 0 . 36 < r < - 0 . 30 , ps < 0 . 04 ) .", "entities": []}, {"sentence": "The difference between response times for R and F trial types , however , did not change with age for either high ( r = 0 . 12 , p = 0 . 43 ) or low complexity scenes ( r = 0 . 08 , p = 0 . 60 ) .", "entities": []}, {"sentence": "NSPCs protect against 30 minute MCAO .", "entities": [{"name": "NSPCs", "type": "Anatomy", "pos": [0, 5]}]}, {"sentence": "( A - D ) Coronal histological sections through the ischemic striatum 3 days following MCAO , stained for TUNEL ( A , B ) or NeuN ( C , D ) .", "entities": [{"name": "Coronal histological sections", "type": "Anatomy", "pos": [10, 39]}, {"name": "striatum", "type": "Anatomy", "pos": [61, 69]}]}, {"sentence": "Mice received intrastriatal injections of exogenous PBS ( A , C ) or EGFP + NSPCs ( B , D , E ) 72 hr prior to MCAO .", "entities": [{"name": "intrastriatal", "type": "Anatomy", "pos": [14, 27]}]}, {"sentence": "Inset in ( B ) shows 40x magnified view of the injection site .", "entities": [{"name": "site", "type": "Anatomy", "pos": [57, 61]}]}, {"sentence": "( E ) Monochrome conversion of image shown in B to demonstrate concentric ring structures used for Sholl analysis .", "entities": []}, {"sentence": "( F ) Quantification of TUNEL + cells using Sholl analysis performed on fluorescent images .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [32, 37]}]}, {"sentence": "* p < 0 . 05 , n = 5 mice per group .", "entities": []}, {"sentence": "Scale bar : A , B = 20 microm ; C , D = 10 microm .", "entities": []}, {"sentence": "Background", "entities": []}, {"sentence": "Over the past decades , extensive comparative mapping research has been performed in the plant family Solanaceae .", "entities": []}, {"sentence": "The recent identification of a large set of single - copy conserved orthologous ( COSII ) markers has greatly accelerated comparative mapping studies among major solanaceous species including tomato , potato , eggplant , pepper and diploid Nicotiana species ( as well as tetraploid tobacco ) .", "entities": []}, {"sentence": "The large amount of comparative data now available for these species provides the opportunity to describe the overall patterns of chromosomal evolution in this important plant family .", "entities": [{"name": "chromosomal", "type": "Anatomy", "pos": [130, 141]}]}, {"sentence": "The results of this investigation are described herein .", "entities": []}, {"sentence": "Introduction", "entities": []}, {"sentence": "Tea ( Camellia sinensis L . ) is one of the most widely consumed beverages in the world .", "entities": []}, {"sentence": "( - ) - Epigallocatechin - 3 - O - gallate ( EGCG ) , which is the major green tea catechin present in the leaves , is believed to the compound most responsible for the health benefits attributed to tea .", "entities": [{"name": "leaves", "type": "Anatomy", "pos": [107, 113]}]}, {"sentence": "EGCG was reported to have antioxidative [ 1 ] , [ 2 ] , antimutagenic [ 3 ] , anti - inflammatory [ 4 ] , and anticarcinogenic activities [ 5 ] .", "entities": []}, {"sentence": "Although the EGCG concentrations required to elicit the anticancer activity have been shown to be more than 1 microM , the blood level of EGCG after consuming the equivalent of 2 - 3 cups of green tea was 0 . 1 - 0 . 6 microM and for an equivalent of 7 - 9 cups was still lower than 1 microM [ 6 ] , [ 7 ] .", "entities": [{"name": "anticancer", "type": "Anatomy", "pos": [56, 66]}, {"name": "blood", "type": "Anatomy", "pos": [123, 128]}]}, {"sentence": "In a cohort study , daily consumption of ten cups of green tea was required for the cancer preventive effect [ 8 ] .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [84, 90]}]}, {"sentence": "Moreover , adverse effects of green tea , mainly hepatitis , by consumption of high doses of green tea have been reported [ 9 ] .", "entities": []}, {"sentence": "Therefore , it is important to enhance the pharmacologic effect of EGCG to obtain the health benefit in reasonable concentration in daily life .", "entities": []}, {"sentence": "We have reported that the cell - surface binding of EGCG and its derivatives is involved in their biological activities [ 10 ] - [ 15 ] .", "entities": [{"name": "cell - surface", "type": "Anatomy", "pos": [26, 40]}]}, {"sentence": "We have identified the 67 - kDa laminin receptor ( 67LR ) as a cell surface receptor for EGCG that mediates the anticancer activity of EGCG [ 16 ] .", "entities": [{"name": "cell surface", "type": "Anatomy", "pos": [63, 75]}]}, {"sentence": "67LR has been shown to be overexpressed on the cell surface of various tumor cells [ 17 ] .", "entities": [{"name": "cell surface", "type": "Anatomy", "pos": [47, 59]}, {"name": "tumor cells", "type": "Anatomy", "pos": [71, 82]}]}, {"sentence": "It was postulated that 67LR plays a significant role in the tumor progression and speculated that studies conducted to define the function of 67LR could provide a new approach to cancer prevention .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [60, 65]}, {"name": "cancer", "type": "Anatomy", "pos": [179, 185]}]}, {"sentence": "Indeed , expression of 67 LR confers EGCG responsiveness to tumor cells in vivo [ 18 ] .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [60, 71]}]}, {"sentence": "Vitamin A , also known as retinol , participates in physiological activities related to the immune system , maintenance of epithelial and mucosa tissues , growth , reproduction , and bone development .", "entities": [{"name": "immune system", "type": "Anatomy", "pos": [92, 105]}, {"name": "epithelial", "type": "Anatomy", "pos": [123, 133]}, {"name": "mucosa tissues", "type": "Anatomy", "pos": [138, 152]}, {"name": "bone", "type": "Anatomy", "pos": [183, 187]}]}, {"sentence": "It comes from animal sources , such as eggs , meat , milk , cheese , cream , liver , kidney , cod and halibut fish oil .", "entities": [{"name": "eggs", "type": "Anatomy", "pos": [39, 43]}, {"name": "meat", "type": "Anatomy", "pos": [46, 50]}, {"name": "milk", "type": "Anatomy", "pos": [53, 57]}, {"name": "liver", "type": "Anatomy", "pos": [77, 82]}, {"name": "kidney", "type": "Anatomy", "pos": [85, 91]}, {"name": "oil", "type": "Anatomy", "pos": [115, 118]}]}, {"sentence": "In vitro and in animal models , it has been demonstrated that vitamin A is involved in the regulation and promotion of growth and differentiation of many cells [ 19 ] .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [154, 159]}]}, {"sentence": "The visual function of vitamin A depends on its natural and synthetic derivatives , retinoids [ 20 ] .", "entities": []}, {"sentence": "All - trans - retinoic acid ( ATRA ) , the active derivative of vitamin A , has been well documented as a growth and differentiation factor in many tissues and cells , and proved to be an effective treatment to many diseases including cancers [ 21 ] , [ 22 ] .", "entities": [{"name": "tissues", "type": "Anatomy", "pos": [148, 155]}, {"name": "cells", "type": "Anatomy", "pos": [160, 165]}, {"name": "cancers", "type": "Anatomy", "pos": [235, 242]}]}, {"sentence": "Retinoids exert their physiological activities through retinoid receptor nuclear proteins that belong to the superfamily of steroid / thyroid hormone receptors , of which there are two classes , retinoic acid receptors ( RARs ) and the retinoic - X receptors ( RXRs ) , each of which has three subtypes , alpha , beta , and gamma [ 23 ] , [ 24 ] .", "entities": [{"name": "nuclear", "type": "Anatomy", "pos": [73, 80]}]}, {"sentence": "The natural ligands for the RARs are ATRA and its stereoisomers 9 - cis - RA and 13 - cis - RA , whereas RXRs are activated by 9 - cis - RA only .", "entities": []}, {"sentence": "ATRA acts through RAR to transcriptionally activate target genes , such as cytochrome P450 and CRABI [ 24 ] .", "entities": []}, {"sentence": "This study was designed to identify a food component that could be effectively used in combination with EGCG and to investigate the mechanism of action of this combination .", "entities": []}, {"sentence": "By using in vitro and in vivo systems involving a highly metastatic mouse B16 melanoma cell line [ 25 ] , we found that ATRA enhances the antitumor activity of EGCG by upregulating the 67 LR expression through RAR .", "entities": [{"name": "B16 melanoma cell line", "type": "Anatomy", "pos": [74, 96]}, {"name": "antitumor", "type": "Anatomy", "pos": [138, 147]}]}, {"sentence": "Titration of Ab - 01 inhibition of ex vivo response to rhIL21", "entities": []}, {"sentence": "Samples from 4 individual healthy human donors were pre - incubated for 2 hours at the indicated concentration of Ab - 01 or the control IgG1TM prior to addition of 10 ng / mL rhIL21 and 2 hr incubation , and the effect on the 6 biomarkers was then assessed ( Figures 4 and 5 ) .", "entities": [{"name": "Samples", "type": "Anatomy", "pos": [0, 7]}]}, {"sentence": "For the first 2 donors tested , even the lowest concentration of Ab - 01 ( 0 . 1 mug / mL , 0 . 66 nM ) resulted in complete inhibition of the rhIL21 response , therefore the two subsequent donors were tested at increasing concentrations of Ab - 01 starting at 0 . 003 mug / mL .", "entities": []}, {"sentence": "Ab - 01 inhibited the response of all 6 genes in all 4 donors .", "entities": []}, {"sentence": "IC50 values ranged between 0 . 003 and 0 . 015 mug / mL Ab - 01 ( Figure 5 ) .", "entities": []}, {"sentence": "Control IgG1TM had no significant effect on rhIL21 response ( Figure4B ) .", "entities": []}, {"sentence": "Figure 4", "entities": []}, {"sentence": "Average percent inhibition of the expression level of 6 IL21 - responsive genes .", "entities": []}, {"sentence": "Percent inhibition values were calculated based on RQ ( relative quantification ) values of untreated control and rhIL21 - treated samples for each of the 4 donors , and subsequently the mean and standard deviation were determined for each gene shown .", "entities": [{"name": "samples", "type": "Anatomy", "pos": [131, 138]}]}, {"sentence": "A : Percent inhibition in presence of Ab - 01 .", "entities": []}, {"sentence": "B : Percent inhibition in presence of control IgG1TM .", "entities": []}, {"sentence": "Data for the 0 . 1 mug / mL , 0 . 3 mug / mL and 1 mug / mL concentrations were generated using 4 donors .", "entities": []}, {"sentence": "Data for the higher and the lower concentrations were generated using 2 donors .", "entities": []}, {"sentence": "Figure 5", "entities": []}, {"sentence": "Inhibition by Ab - 01 at the indicated concentration is shown for 6 IL21 - responsive genes .", "entities": []}, {"sentence": "IC50 values of inhibition curves shown in Figure 4A were calculated using curve fit ( XLfit ) program for each of the referred biomarker genes .", "entities": []}, {"sentence": "Values for the 0 . 1 mug / mL , 0 . 3 mug / mL and 1 mug / mL concentrations were generated using 4 donors .", "entities": []}, {"sentence": "Data for the higher and the lower concentrations were generated using 2 donors each .", "entities": []}, {"sentence": "The effect of PCL elevation", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [14, 17]}]}, {"sentence": "Our hypothesis that the dynamics of the flexion gap depend on the orientation of the PCL was confirmed .", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [85, 88]}]}, {"sentence": "Distraction of the knee with a low PCL elevation angle ( i . e . a flat PCL ) resulted in greater increase in gap height than distraction of a knee with a steep PCL .", "entities": [{"name": "knee", "type": "Anatomy", "pos": [19, 23]}, {"name": "PCL", "type": "Anatomy", "pos": [35, 38]}, {"name": "PCL", "type": "Anatomy", "pos": [72, 75]}, {"name": "knee", "type": "Anatomy", "pos": [143, 147]}, {"name": "PCL", "type": "Anatomy", "pos": [161, 164]}]}, {"sentence": "This result was to be expected ; when the gap between the tibia and femur was increased , the increase in PCL tension resulted in the tibia pivoting around the femoral insertion of the PCL .", "entities": [{"name": "tibia", "type": "Anatomy", "pos": [58, 63]}, {"name": "femur", "type": "Anatomy", "pos": [68, 73]}, {"name": "PCL", "type": "Anatomy", "pos": [106, 109]}, {"name": "tibia", "type": "Anatomy", "pos": [134, 139]}, {"name": "femoral", "type": "Anatomy", "pos": [160, 167]}, {"name": "PCL", "type": "Anatomy", "pos": [185, 188]}]}, {"sentence": "Thus , the greatest increase in gap height will occur when the PCL is flat .", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [63, 66]}]}, {"sentence": "Taking this finding into consideration , the surgeon should be aware of the strong effect of PCL elevation on the relationship between gap height increase and tibial translation .", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [93, 96]}, {"name": "tibial", "type": "Anatomy", "pos": [159, 165]}]}, {"sentence": "A flat PCL will lead to a mean anterior tibial translation of 1 . 7 mm when the gap is distracted 1 mm .", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [7, 10]}, {"name": "anterior tibial", "type": "Anatomy", "pos": [31, 46]}]}, {"sentence": "A knee with a steep PCL will even translate 2 . 3 mm on average with 1 mm of gap distraction .", "entities": [{"name": "knee", "type": "Anatomy", "pos": [2, 6]}, {"name": "PCL", "type": "Anatomy", "pos": [20, 23]}]}, {"sentence": "If the PCL were the only structure that was tensioned with distraction of the flexion gap , then at 100 N it would be oriented vertically .", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [7, 10]}]}, {"sentence": "This is not the case , and therefore other structures such as the collateral ligaments must have restrained the translation .", "entities": [{"name": "structures", "type": "Anatomy", "pos": [43, 53]}, {"name": "collateral ligaments", "type": "Anatomy", "pos": [66, 86]}]}, {"sentence": "From an anatomical point of view , the collateral structures are the only structures that could have had a restraining function on vertical movements .", "entities": [{"name": "collateral structures", "type": "Anatomy", "pos": [39, 60]}, {"name": "structures", "type": "Anatomy", "pos": [74, 84]}]}, {"sentence": "For obvious reasons , in this in vivo study we could not test what would have happened to the orientation of the PCL when the collateral structures were resected .", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [113, 116]}, {"name": "collateral structures", "type": "Anatomy", "pos": [126, 147]}]}, {"sentence": "In addition , the PCL elevation angle at 100 N influenced the increase in PCL elevation angle between 100 N and 200 N ( DeltaPCLe ) .", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [18, 21]}, {"name": "PCL", "type": "Anatomy", "pos": [74, 77]}]}, {"sentence": "This seems logical : a flat PCL can be recruited more easily whereas knees with a steep PCL might already be tensioned at 100 N so that a further increase in PCL elevation angle would be hard to achieve .", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [28, 31]}, {"name": "knees", "type": "Anatomy", "pos": [69, 74]}, {"name": "PCL", "type": "Anatomy", "pos": [88, 91]}, {"name": "PCL", "type": "Anatomy", "pos": [158, 161]}]}, {"sentence": "However , steep PCLs are not necessarily recruited more than flat PCLs .", "entities": [{"name": "PCLs", "type": "Anatomy", "pos": [16, 20]}, {"name": "PCLs", "type": "Anatomy", "pos": [66, 70]}]}, {"sentence": "Furthermore , the situation during implantation of a TKR is quite unnatural : we investigated the PCL elevation after the tibia was cut .", "entities": [{"name": "PCL", "type": "Anatomy", "pos": [98, 101]}, {"name": "tibia", "type": "Anatomy", "pos": [122, 127]}]}, {"sentence": "Differential expression of drug - induced drug targets", "entities": []}, {"sentence": "Integrating 4849 CMap arrays with 40 , 656 drug target relations from STITCH resulted in a set of 1 , 290 drug - target relations for which a genome - wide cellular response is available .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [156, 164]}]}, {"sentence": "We found that thirteen out of 167 distinct drug targets in this set ( 8 % ; 86 drug target relations ) are subjected to significant differential expression upon drug treatment ( Figure 3 ) by comparing the drug - induced expression changes of the drug target against all other treatments present in CMap ( see methods ) .", "entities": []}, {"sentence": "We found supporting evidence in the literature for seven out of thirteen ( q - value < 0 . 05 ) significant differential regulations of drug targets shown in Figure 3 , confirming the rationale and predictive power of our systematic approach .", "entities": []}, {"sentence": "For the remaining six targets we can predict a hitherto unknown drug - induced differential regulation .", "entities": []}, {"sentence": "10 . 1371 / journal . pcbi . 1000925 . g003 Figure 3", "entities": []}, {"sentence": "Drug - induced differentially regulated drug targets .", "entities": []}, {"sentence": "Anova is used to assess the significance of the differential expression of drug - induced drug targets against the mRNA changes of the same gene in the population of heterogeneous drug treatments from CMap .", "entities": []}, {"sentence": "The genes are mainly ordered based on their q - values as provided in Table S1 .", "entities": []}, {"sentence": "In the scatter plots , inhibitors / activators are labeled in red / green respectively and grey represents all other treatments present in CMap .", "entities": []}, {"sentence": "The identified , differentially regulated drug targets are enriched in G - protein coupled receptors ( GPCRs ) ( Figure S4 ) , in agreement with previous reports that members of the GPCR family are generally regulated by several mechanisms including receptor desensitization , endocytosis at the protein level and regulation of the cellular receptor content [ 18 ] , [ 19 ] .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [332, 340]}]}, {"sentence": "In the three cancer cell lines used , we observe agonist - induced down - regulation of GPCR mRNAs for beta - 2 adrenergic receptor ( ADRB2 ) , prostaglandin E2 receptor subtype EP2 and prostaglandin E4 receptor subtype EP4 ( Figure 3 , Genes 3 , 4 , 12 ) , which were previously reported in DDT1 MF - 2 smooth muscle cells ( ADRB2 ) and 293 - EBNA human embryonic kidney cells ( prostaglandin E2 / E4 receptor subtypes EP2 / EP4 ) [ 20 ] , [ 21 ] .", "entities": [{"name": "cancer cell lines", "type": "Anatomy", "pos": [13, 30]}, {"name": "DDT1 MF - 2 smooth muscle cells", "type": "Anatomy", "pos": [292, 323]}, {"name": "293 - EBNA human embryonic kidney cells", "type": "Anatomy", "pos": [338, 377]}]}, {"sentence": "This indicates that drugs can induce similar feedback loops in a wide variety of cell types .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [81, 85]}]}, {"sentence": "However , we cannot rule out that cross - regulation among signaling pathways may be responsible for the regulation of GPCR mRNAs as it has been described before [ 22 ] .", "entities": []}, {"sentence": "For example , it has been shown that a beta adrenergic mRNA - binding protein , ELAV - like protein 1 ( ELAVL1 ) can be induced by ADRB2 agonist or elevated levels of cyclic adenosine monophosphate ( cAMP ) [ 22 ] , [ 23 ] and destabilizes ADRB2 mRNA .", "entities": []}, {"sentence": "The ELAVL1 protein binds to GPCR mRNAs and recognizes a cognate sequence located at the 3 ' - UTR of ADRB2 , proteinase - activated receptor and M2 , M3 muscarinic acetylcholine receptor mRNAs [ 24 ] , [ 25 ] .", "entities": []}, {"sentence": "Therefore cAMP provides cross - talk among GPCR regulatory networks .", "entities": []}, {"sentence": "However , it is shown that intracellular cAMP accumulation is not the only factor contributing to the reduction of ADRB2 mRNA levels [ 20 ] .", "entities": [{"name": "intracellular", "type": "Anatomy", "pos": [27, 40]}]}, {"sentence": "Moreover , we find that GPCR - targeting drugs regulate the transcription of their specific targets ( Figure S5 ) .", "entities": []}, {"sentence": "We conclude that in addition to the cross - regulation of G - protein signaling pathways drug target - specific feedback loops are also responsible for the regulation of drug target mRNAs .", "entities": []}, {"sentence": "In addition to cross - regulation of multiple drugs through the same signaling pathways , promiscuous drugs targeting multiple proteins may cause complex regulatory networks .", "entities": []}, {"sentence": "In order to explore the cross - regulation of drug targets induced by a promiscuous drug , we searched and found that 259 out of 466 total drugs are multi - target drugs and 4 of these drugs act on multiple differentially regulated drug targets upon drug treatment .", "entities": []}, {"sentence": "For example , Podophyllotoxin used in various chemotherapies is known to target both tubulin beta 2C and DNA topoisomerase 2 - alpha .", "entities": []}, {"sentence": "The tubulin beta 2C and DNA topoisomerase 2 - alpha mRNAs are both down - regulated upon drug treatment in three cell lines ( Figure 3 , Genes 8 , 13 ) .", "entities": [{"name": "cell lines", "type": "Anatomy", "pos": [113, 123]}]}, {"sentence": "Tubulin beta 2C inhibitors induce microtubule depolymerization that leads to the specific down - regulation of tubulin beta 2C mRNAs preventing the translational synthesis and thus the further accumulation of abundant tubulin monomers [ 26 ] .", "entities": [{"name": "microtubule", "type": "Anatomy", "pos": [34, 45]}]}, {"sentence": "Moreover , we found that DNA topoisomerase 2 - alpha mRNAs are not down - regulated upon treatment of other tubulin inhibitors ( Figure S5 ) .", "entities": []}, {"sentence": "Therefore , we conclude that feedback loops of tubulin beta 2C and DNA topoisomerase 2 - alpha are not cross - regulated .", "entities": []}, {"sentence": "Two other examples of multi - target drugs are vorinostat used for the treatment of cutaneous T cell lymphoma and trichostatin A that serves as an antifungal antibiotic .", "entities": [{"name": "cutaneous T cell lymphoma", "type": "Anatomy", "pos": [84, 109]}]}, {"sentence": "Vorinostat and trichostatin A are considered to be nonspecific histone deacetylase inhibitors .", "entities": []}, {"sentence": "These drugs lead to the up - regulation of histone deacetylase 3 ( HDAC3 ) and down - regulation of histone deacetylase 7 ( HDAC7 ) ( Figure 3 , Genes 1 , 5 ) .", "entities": []}, {"sentence": "In this case it is unclear whether there is cross - regulation , although HDAC7 siRNA experiments failed to induce the up - regulation of HDAC3 mRNAs [ 27 ] , a result that is disfavoring the cross - regulation .", "entities": []}, {"sentence": "While the above cases only confirm literature reports in other cell lines or tissues , we also identified new cases of drug - induced expression regulation of drug targets .", "entities": [{"name": "cell lines", "type": "Anatomy", "pos": [63, 73]}, {"name": "tissues", "type": "Anatomy", "pos": [77, 84]}]}, {"sentence": "The significant novel findings are the inhibitor - induced down - regulation of calmodulin 1 , DNA topoisomerase 2 - alpha and up - regulation of endoplasmin , lanosterol 14 - alpha demethylase and cAMP - specific phosphodiesterase 4D ( Figure 3 , Genes 9 , 8 , 2 , 7 , 10 ) .", "entities": []}, {"sentence": "Lanosterol 14 - alpha demethylase is actually an off - target of antifungal drugs that bind the mammalian version with lower affinity than the fungal lanosterol 14 - alpha demethylase .", "entities": []}, {"sentence": "Probably , the up - regulation of the mammalian lanosterol 14 - alpha demethylase compensates for the undesired inhibition and modulates the adverse effects .", "entities": []}, {"sentence": "On the contrary , we observed a feedback loop that accelerates the down regulation of calmodulin 1 mRNA induced by calmodulin inhibitors .", "entities": []}, {"sentence": "Calmodulin targeting drugs can provide a rapid and effective therapeutic effect , while at the same time small variations of drug concentrations can increase adverse effects .", "entities": []}, {"sentence": "Therefore , it would be interesting to study further the functional effects upon target inhibition of lanosterol 14 - alpha demethylase , endoplasmin and calmodulin 1 to elucidate the roles of feedback loops in drug mode of action and adverse effects .", "entities": []}, {"sentence": "Drug - induced target regulation might be implicated in tolerance development and thus identifying potential target regulation should be an integral part of drug discovery to prevent failures in later stages of clinical trials .", "entities": []}, {"sentence": "For example , we have observed the inhibitor - induced up - regulation of ADRB2 and thymidylate synthetase ( TYMS ) ( Figure 3 , Genes 3 , 11 ) [ 28 ] .", "entities": []}, {"sentence": "TYMS is an essential enzyme for DNA replication / repair and an important drug target in cancerous cells .", "entities": [{"name": "cancerous cells", "type": "Anatomy", "pos": [89, 104]}]}, {"sentence": "Indeed , it has been shown that inhibitor - induced TYMS over - expression obstructs the clinical efficiency by inducing tumor drug resistance [ 29 ] .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [121, 126]}]}, {"sentence": "In addition to over - expression , down - regulation of drug targets upon agonist treatment may also cause treatment tolerance as observed for ADRB2 long - acting agonist treatment .", "entities": []}, {"sentence": "ADRB2 is a therapeutic target activated to treat the symptoms of asthma .", "entities": []}, {"sentence": "We observe the agonist - induced up - regulation of ADRB2 and already in 2005 , the FDA warned patients that ADRB2 might be down - regulated ( desensitization ) and be unresponsive for asthma treatment due to long - acting agonist exposure [ 20 ] , [ 30 ] .", "entities": []}, {"sentence": "Thus , robustness in biological systems could prevent the applicability of the long - term treatments via positive / negative feedback loops of the drug target affecting the clinical efficiency of drugs in trial and on the market .", "entities": []}, {"sentence": "Drug - induced regulation of drug targets can thus be linked to tolerance development , which restricts the efficiency of clinical treatments where the drug concentration is limited to avoid an excess of adverse drug reactions .", "entities": []}, {"sentence": "Taken together , we have identified drug - induced differential regulation of drug targets .", "entities": []}, {"sentence": "Due to the limited signal to noise ratio in the data at hand , the identified 8 % of all drug targets that show feedback loops has to be seen as a lower limit , i . e . target - regulation appears as a wide - spread biological phenomenon that has to be taken into account during drug development .", "entities": []}, {"sentence": "INTRODUCTION", "entities": []}, {"sentence": "For several years now , virtual microscopy has been utilized in medical teaching , research , proficiency testing , American Board of Pathology examinations , pathology meetings and conferences , and quality assurance programs .", "entities": []}, {"sentence": "In diagnostic practice , it is most widely and routinely used in image analysis .", "entities": []}, {"sentence": "Some practices are beginning to use it internally ( within their group ) for frozen section intraoperative consultations and subspecialty consultations due to geographic and time constrains .", "entities": []}, {"sentence": "Although diagnostic consultation for expert second opinion is a well - established practice in pathology for glass slides , similar consultation via virtual microscopy poses multiple controversial issues such as licensing , liability , security , reimbursement , and scanning quality and its validation .", "entities": []}, {"sentence": "Regulations and standardization are not yet in place that pathologists can use to allay these fears .", "entities": []}, {"sentence": "Nevertheless , if the virtual microscopy scans are of optimal quality , these can be simply substituted for glass slides and a microscope while maintaining all other practice guidelines for second opinion consultation .", "entities": []}, {"sentence": "Additionally , the cost and maintenance of scanning equipment is not currently affordable to most practitioners and consultants .", "entities": []}, {"sentence": "A practice model that offers tertiary consultation in gastrointestinal ( GI ) and liver pathology is presented that eliminates the cost and maintenance of scanners by the consultants and clients , minimizes the need for review of glass slides , facilitates clinicopathological and radiological correlation and serves the need of clients who need timely help with challenging liver and GI cases and to obtain expert opinion for dysplasia in Barrett ' s and ulcerative colitis surveillance biopsies required by the American Gastroenterology Association ( AGA ) .", "entities": [{"name": "gastrointestinal", "type": "Anatomy", "pos": [54, 70]}, {"name": "GI", "type": "Anatomy", "pos": [73, 75]}, {"name": "liver", "type": "Anatomy", "pos": [82, 87]}, {"name": "liver", "type": "Anatomy", "pos": [375, 380]}, {"name": "GI", "type": "Anatomy", "pos": [385, 387]}, {"name": "dysplasia", "type": "Anatomy", "pos": [427, 436]}, {"name": "ulcerative", "type": "Anatomy", "pos": [456, 466]}, {"name": "biopsies", "type": "Anatomy", "pos": [488, 496]}]}, {"sentence": "This model has been practiced for 3 years and applied to over 2000 cases by small pathology practices in the 50 United States and a single consultant GI and liver pathologist .", "entities": [{"name": "GI", "type": "Anatomy", "pos": [150, 152]}, {"name": "liver", "type": "Anatomy", "pos": [157, 162]}]}, {"sentence": "Click here for file", "entities": []}, {"sentence": "The right eye of a 50 - year - old patient with severe hypertension at the first visit .", "entities": [{"name": "right eye", "type": "Anatomy", "pos": [4, 13]}]}, {"sentence": "( a ) Fundus photograph shows serous retinal detachment .", "entities": [{"name": "serous retinal", "type": "Anatomy", "pos": [30, 44]}]}, {"sentence": "The optic disc is pale at the temporal side .", "entities": []}, {"sentence": "( b ) Optical coherence tomography ( OCT ) shows retinal detachment involving the fovea and cystic change of inner retina .", "entities": [{"name": "retinal", "type": "Anatomy", "pos": [49, 56]}, {"name": "fovea", "type": "Anatomy", "pos": [82, 87]}, {"name": "cystic", "type": "Anatomy", "pos": [92, 98]}, {"name": "inner retina", "type": "Anatomy", "pos": [109, 121]}]}, {"sentence": "( c ) Early phase images of fluorescein angiography ( FA ) ( left ) and indocyanine green angiography ( IA ) ( right ) .", "entities": []}, {"sentence": "( d ) Late phase images of FA ( left ) and IA ( right ) .", "entities": []}, {"sentence": "FA shows window defect associated with macular cystic change .", "entities": [{"name": "macular", "type": "Anatomy", "pos": [39, 46]}, {"name": "cystic", "type": "Anatomy", "pos": [47, 53]}]}, {"sentence": "Note that no active leakage is observed in the area with serous retinal detachment or cystoid edema .", "entities": [{"name": "area", "type": "Anatomy", "pos": [47, 51]}, {"name": "serous retinal", "type": "Anatomy", "pos": [57, 71]}, {"name": "cystoid edema", "type": "Anatomy", "pos": [86, 99]}]}, {"sentence": "IA shows decreased perfusion of the choroid at the macula and window defect with the damaged RPE .", "entities": [{"name": "choroid", "type": "Anatomy", "pos": [36, 43]}, {"name": "macula", "type": "Anatomy", "pos": [51, 57]}, {"name": "RPE", "type": "Anatomy", "pos": [93, 96]}]}, {"sentence": "Hypofluorescence ( arrow ) along the retinal artery are observed .", "entities": [{"name": "retinal artery", "type": "Anatomy", "pos": [37, 51]}]}, {"sentence": "These are unique findings .", "entities": []}, {"sentence": "Western blots showing C / EBPalpha ( top ) , adiponectin ( middle ) , and GAPDH ( bottom ) protein bands in confluent GO orbital fibroblast cultures exposed throughout 10 days in culture to the indicated treatments .", "entities": [{"name": "GO orbital fibroblast cultures", "type": "Anatomy", "pos": [118, 148]}]}, {"sentence": "Lane 1 ) no treatment ; 2 ) LY294002 ( 10 muM ) ; 3 ) M22 ( 10 ng / ml ) ; 4 ) M22 plus LY294002 .", "entities": []}, {"sentence": "5 .", "entities": []}, {"sentence": "Conclusion", "entities": []}, {"sentence": "RLs are new actors in animal and plant defense and their low toxicity and biodegradability make them promising molecules to be used against pathogens .", "entities": []}, {"sentence": "In this respect , there are some clues now available for the success of RL applications in greenhouses to fight phytopathogens .", "entities": []}, {"sentence": "A better understanding of RL mode of action , especially their perception and the signaling pathways activated , will be very important to potentiate their beneficial effects in plants .", "entities": []}, {"sentence": "RLs have a dual mode of action : they are antimicrobial and also stimulate plant defense responses .", "entities": []}, {"sentence": "This dual property is probably very important for the efficiency of new biopesticides .", "entities": []}, {"sentence": "In animals , the use of RLs is also at an advanced stage .", "entities": []}, {"sentence": "RLs are successfully used as antimicrobial agents , especially for skin disease treatment .", "entities": [{"name": "skin", "type": "Anatomy", "pos": [67, 71]}]}, {"sentence": "Deep insight into the physiochemical effects of RLs and their biological importance would reveal new dimensions in the fields of research like agriculture and medicine , precisely in plant defense , disease control and pathogenesis .", "entities": []}, {"sentence": "An understanding of bacterial genera producing RLs that are not yet well studied would provide light on these fascinating aspects .", "entities": []}, {"sentence": "Acknowledgements", "entities": []}, {"sentence": "We thank Dr . Neva Meyer for confocal imaging and generation of Z - stack projection , and the following members of the Seaver lab for their continued support of this project : Dr . Neva Meyer , Dr . Aldine Amiel , and Tyler Smith .", "entities": []}, {"sentence": "This work was supported by the National Science Foundation ( REU Supplement of 10B05 - 44869 to E . C . S . ) .", "entities": []}, {"sentence": "Cone beam geometry", "entities": []}, {"sentence": "Materials and Methods", "entities": []}, {"sentence": "Rate of distraction calculation ( Figs . 6 , 7 and 8 )", "entities": []}, {"sentence": "Ideal rate for new bone formation by distraction osteogenesis is known as 1 mm / day . 5 , 6 The slower rates may lead to premature consolidation , whereas the faster rates may result in poor regenerate bone formation .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [19, 23]}, {"name": "bone", "type": "Anatomy", "pos": [203, 207]}]}, {"sentence": "In simple longitudinal lengthening , the rate of distraction is equal at any point of the corticotomy , however , the rate of distraction at any given portion of the corticotomy varies during angular correction .", "entities": []}, {"sentence": "Usually , the gap between corticotomized bone ends is larger on the concave side , therefore , the rate of angular correction should be adjusted so that the rate of distraction of the concave side is closer to 1 mm / day .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [41, 45]}]}, {"sentence": "In cases with passive hinge system , the amount of daily angular correction can easily be calculated by the geometric methods using the rule of similar triangles and the rule of concentric circles , and can be expressed as the amount of daily lengthening of motor system .", "entities": []}, {"sentence": "In passive hinge system , the ACA is fixed on the frame in Ilizarov system or on the convex side of corticotomy in unilateral fixator system , and angular correction is achieved by changing the length of the motor ( Ilizarov system ) or the lengthener ( unilateral fixator ) which rotates the passive hinge .", "entities": []}, {"sentence": "However , in active hinge system , angulator directly corrects angular deformity , and the lengthener and translator adjust secondary displacement .", "entities": []}, {"sentence": "Therefore , the rate of angular correction cannot be determined by the simple geometric methods used for passive hinge system .", "entities": []}, {"sentence": "Regardless of types of fixators , the gap opens larger on the concave side of the deformity after realignment .", "entities": []}, {"sentence": "The rate of angular correction also should be adjusted so that the rate of distraction of concave side is 1 mm / day .", "entities": []}, {"sentence": "Theoretically , after realignment by Dyna - ATC with adjustment of secondary displacement , the convex side of the corticotomy does not change in length , but the cocave side opens to correct angular deformity .", "entities": []}, {"sentence": "The amount of lengthening on the concave side can be calculated with the thickness of the bone at the corticotomy site and the amount of angular deformity ( Fig . 6 ) .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [90, 94]}, {"name": "site", "type": "Anatomy", "pos": [114, 118]}]}, {"sentence": "If the corticotomy is performed on the CORA , no translation deformity happens , however , if not , translation results at the corticotomy site after realignment is achieved .", "entities": [{"name": "site", "type": "Anatomy", "pos": [139, 143]}]}, {"sentence": "The amount of translation can be calculated with the distance from the CORA to the corticotomy over the longitudinal bisecting line ( lBL ) ( Fig . 6 ) .", "entities": []}, {"sentence": "On the immediate post - operative radiographs , the gap distance of concave side after realignment can be calculated with the expected change in length and translation on the concave side of the corticotomy using the Pythaorean theorem .", "entities": []}, {"sentence": "The rate of angular correction should be given as the amount of daily correction angle , but not as the amount of length change of the fixator .", "entities": []}, {"sentence": "The angular change of angulator determines the secondary change of length and translation of the corticotomy site .", "entities": [{"name": "site", "type": "Anatomy", "pos": [109, 113]}]}, {"sentence": "The amount of secondary deformity during angular correction can be calculated with the thickness of bone at the corticotomy site , the distance between the ACA and the corticotomy , and tan ( a / 2 ) ( a is the amount of angular correction ) ( Fig . 6 ) .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [100, 104]}, {"name": "site", "type": "Anatomy", "pos": [124, 128]}]}, {"sentence": "The thickness of the bone at the corticotomy site and the distance between the ACA and the corticotomy do not change , once the corticotomy is performed after Dyna - ATC is applied .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [21, 25]}, {"name": "site", "type": "Anatomy", "pos": [45, 49]}]}, {"sentence": "Therefore , the amount of secondary deformities changes only with tan ( a / 2 ) value .", "entities": []}, {"sentence": "If tangent value varies proportionally with changes of angle , the gap distance increases constantly with the given amount of daily correction angle during angular correction .", "entities": []}, {"sentence": "If not , the gap distance varies continuously with changes of the angle , therefore , the amount of correction angle should be readjusted everyday to maintain 1 mm / day of distraction rate on the concave side of the corticotomy .", "entities": []}, {"sentence": "Fortunately , while the value of tangent angle increases exponentially especially over 45 degrees , tangent function curve is nearly straight , less than 30 degrees ( Fig . 7 ) .", "entities": []}, {"sentence": "Therefore , in cases with less than 60 degrees of angular deformity , the amount of daily correction angle which permits 1 mm / day of distraction rate on the concave side of the corticotomy can be obtained as the rate of angular correction without daily adjustment during angular correction .", "entities": []}, {"sentence": "Once the amount of daily angular correction is determined , the amount of daily length and translation compensation can also be calculated with the amount of daily angular correction .", "entities": []}, {"sentence": "Exact adjustment of secondary changes in length and translation at each angular correction opens the concave side of the corticotomy 1 mm per day , but allows minimal gap on the corticotomy of convex side especially in the early stage of angular correction .", "entities": []}, {"sentence": "Therefore , it is possible that the corticotomized bone ends of convex side , may abut each other and prevent angular correction or adjustment of secondary translation .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [51, 55]}]}, {"sentence": "For the cases where the concomitant lengthening is required , longitudinal lengthening prior to angular correction is recommended .", "entities": []}, {"sentence": "Otherwise , about 5 mm pre - lengthening and re - shortening after angular correction could be helpful in avoiding abutment on the convex side of the corticotomy site .", "entities": [{"name": "site", "type": "Anatomy", "pos": [162, 166]}]}, {"sentence": "Inappropriate sequence of angular correction and adjustment of secondary deformities could be one of the causes of the impingement .", "entities": []}, {"sentence": "Appropriate sequence of correction is lengthening - translation - angulation with Dyna - ATC on the concave side and angulation - translation - shortening with Dyna - ATC on the convex side .", "entities": []}, {"sentence": "Results", "entities": []}, {"sentence": "Table 1 shows the predicted new case detection rates at 25 years after the initiation of the interventions .", "entities": []}, {"sentence": "Under the baseline control program , the different mechanisms that determined susceptibility showed up to three - fold differences in the predicted number of cases per 100 , 000 people .", "entities": []}, {"sentence": "In Figure 1 , the trends in the new case detection rates over 50 years are shown for all seven interventions .", "entities": []}, {"sentence": "All susceptibility mechanisms give qualitatively comparable trends .", "entities": []}, {"sentence": "When the intervention scenarios were ordered after 50 years by the amount of reduction in new case detection rates , the order was as good as identical for all mechanisms ; i . e . early diagnosis lowest ; then no BCG & early diagnosis ; then chemoprophylaxis ; then baseline ; then no BCG & chemoprophylaxis together with no contact tracing ; and finally no BCG had the highest new case detection rate .", "entities": []}, {"sentence": "10 . 1371 / journal . pntd . 0001330 . g001 Figure 1", "entities": []}, {"sentence": "Predicted decline of the new case detection rate with seven intervention scenarios and six mechanisms of leprosy susceptiblity since start of intervention strategy .", "entities": []}, {"sentence": "The baseline program ( black line ) included passive detection , multidrug therapy , contact tracing , and an infant leprosy - preventative BCG vaccination given at the population level .", "entities": []}, {"sentence": "The other six intervention strategies included the baseline program and , introduction of a new tuberculosis vaccine ineffective against leprosy replacing BCG ( red ) ; no tracing of household contacts ( orange ) ; a single chemoprophylactic dose of rifampicin that cured 50 % of subclinically infected contacts ( yellow ) ; early diagnosis of 70 % of subclinically infected contacts in each of 3 consecutive annual examinations ( green ) ; chemoprophylaxis plus introduction of a tuberculosis vaccine ineffective against leprosy ( blue ) ; and detection of subclinically infected contacts plus introduction of a tuberculosis vaccine ineffective against le - pro - sy ( purple ) .", "entities": []}, {"sentence": "Results are the average of 100 runs of the simulation model for each scenario and susceptibilty mechanism .", "entities": []}, {"sentence": "10 . 1371 / journal . pntd . 0001330 . t001 Table 1", "entities": []}, {"sentence": "Predicted new case detection rates ( per 100 , 000 ) at 25 years after the introduction of the indicated intervention scenario for six mechanisms of leprosy susceptibility as described in [ 9 ] .", "entities": []}, {"sentence": "Intervention Mechanism determining susceptibilty", "entities": []}, {"sentence": "Random Household Dominant Recessive Household & dominant Household & recessive", "entities": []}, {"sentence": "Baseline control 3 . 4 4 . 0 10 . 4 8 . 2 5 . 6 4 . 6", "entities": []}, {"sentence": "No BCG 4 . 6 5 . 5 15 . 0 11 . 9 7 . 6 6 . 4", "entities": []}, {"sentence": "No contact tracing 3 . 8 4 . 1 10 . 5 8 . 5 5 . 5 4 . 8", "entities": []}, {"sentence": "Chemoprophylaxis 2 . 8 3 . 2 6 . 9 5 . 9 4 . 1 3 . 4", "entities": []}, {"sentence": "Early diagnosis 1 . 1 2 . 1 2 . 7 2 . 6 2 . 1 2 . 0", "entities": []}, {"sentence": "No BCG & chemoprophylaxis 3 . 6 4 . 0 10 . 5 8 . 5 5 . 9 5 . 1", "entities": []}, {"sentence": "No BCG & early diagnosis 1 . 2 2 . 5 3 . 7 3 . 7 2 . 9 2 . 8", "entities": []}, {"sentence": "The results are average of 100 runs of the simulation model .", "entities": []}, {"sentence": "Both the cessation of contact tracing and the replacement of BCG vaccine by a tuberculosis vaccine ineffective for leprosy ( no BCG ) would have detrimental effects on the rate of decline in leprosy ( Figure 2 ) .", "entities": []}, {"sentence": "Twenty - five years after introduction of the ineffective vaccine ( no BCG ) , the new case detection of leprosy was approximately 1 . 5 times higher than the baseline ( Table 1 ) .", "entities": []}, {"sentence": "The cessation of contact tracing was predicted to have a smaller impact , with a marked drop in detection of new leprosy cases during the first few years .", "entities": []}, {"sentence": "This sudden drop was due to the reduced number of examinations of people in contact with patients ; thus , these cases would not be detected until later , through passive detection ( self - reporting ) .", "entities": []}, {"sentence": "10 . 1371 / journal . pntd . 0001330 . g002 Figure 2", "entities": []}, {"sentence": "Predicted new case detection rates for six intervention scenarios relative to the baseline control program .", "entities": []}, {"sentence": "For each intervention scenario simulations with different mechanisms of susceptibility to leprosy , as defined in our previous paper [ 9 ] are performed .", "entities": []}, {"sentence": "For each intervention scenario , the two dotted lines show the smallest and largest deviations from the baseline control program .", "entities": []}, {"sentence": "The solid line shows the median of all susceptibility mechanisms .", "entities": []}, {"sentence": "Results are the average of 100 runs of the simulation model .", "entities": []}, {"sentence": "Both chemoprophylaxis and early diagnosis were predicted to have substantial effects on the new case detection of leprosy ( Figure 2 ) .", "entities": []}, {"sentence": "With no BCG , chemoprophylaxis would partially compensate for the predicted increase in new case detection rates .", "entities": []}, {"sentence": "Furthermore , early diagnosis was predicted to more than compensate for the adverse effects of a leprosy - ineffective tuberculosis vaccine , and reduce the rate of new case detection compared to the baseline .", "entities": []}, {"sentence": "The effects were more promising with the ongoing presence of the BCG vaccine .", "entities": []}, {"sentence": "Under those conditions , at 25 years after the introduction of chemoprophylaxis , the new case detection rate was predicted to be 25 % lower than baseline control .", "entities": []}, {"sentence": "Moreover , with the introduction of early diagnosis , the new case detection rate was predicted to halve the baseline incidence after 25 years ( Table 1 ) .", "entities": []}, {"sentence": "Early diagnosis of infection allows the detection of subclinical cases , of which part would be detected later or never at all .", "entities": []}, {"sentence": "These subclinical cases are added to the number of detected cases .", "entities": []}, {"sentence": "This is seen in the results of this intervention .", "entities": []}, {"sentence": "The introduction of early diagnosis would increase the total number of detected cases in the first 18 years , simply because of the detection of previously undetectable subclinical cases .", "entities": []}, {"sentence": "Over time however , the total number of new cases ( subclinical and clinical ) would finally drop below the number detected in the baseline control program ( Figure 3 ) .", "entities": []}, {"sentence": "In Figure 3 , we show that the new cases detected under the chemoprophylaxis intervention strategy drop immediately below the level of the baseline control program .", "entities": []}, {"sentence": "The additional effect of chemoprophylaxis is that additional new infections are prevented on top of the cure of subclinical infections .", "entities": []}, {"sentence": "These additional prevented infections are due to a shorter infectious period of the cured subclinical infections .", "entities": []}, {"sentence": "To illustrate this effect we show in Figure 3 the clinical and the subclinical cases that were cured by the chemoprophylactic intervention .", "entities": []}, {"sentence": "During the first 10 years , this total number of newly detected cases plus cured cases is equal to the number of newly detected cases under the baseline control program , but afterwards the number of cases plus cured subclinical cases in the chemoprophylaxis intervention group drops under the baseline control program , indicating the prevention of new infections .", "entities": []}, {"sentence": "10 . 1371 / journal . pntd . 0001330 . g003 Figure 3", "entities": []}, {"sentence": "Cumulative New cases detected of leprosy per person - year since start of the interventions .", "entities": []}, {"sentence": "Results are the average of 100 runs of the simulation model .", "entities": []}, {"sentence": "Effects of rule - breakers on intermediary - based networks .", "entities": []}, {"sentence": "Individuals using rule - breaking strategy primarily affected ( A ) their own social position ( H ( 2 ) = 213 . 18 , p < 0 . 0001 ) , but also made an impact on the other aspects of the social system , affecting ( B ) the social position of others ( H ( 2 ) = 6 . 79 , p = 0 . 034 ) and ( C ) group organization ( H ( 2 ) = 125 . 3 , p < 0 . 0001 ) as their frequency in a population increased .", "entities": []}, {"sentence": "The boxes show medians , quartiles , minima and maxima .", "entities": []}, {"sentence": "Results significantly different from a relevant uniform network with no rule - breaking behavior ( p < 0 . 05 in Dunn ' s multiple comparison test for comparing each group with control ) are designated with * .", "entities": []}, {"sentence": "Objectives", "entities": []}, {"sentence": "Evaluate relationships between MRI and clinical / laboratory / radiographic findings in rheumatoid arthritis ( RA ) .", "entities": []}, {"sentence": "Assessment instruments", "entities": []}, {"sentence": "The SCID - I / P was administered by psychiatrists trained and certified in the use of all instruments in this study .", "entities": []}, {"sentence": "The ICG is a self - report instrument that can be used to identify CG when the total score is > 25 , that demonstrated high internal consistency ( Cronbach ' s alpha = 0 . 94 ) , and convergent and criterion validity [ 27 ] .", "entities": []}, {"sentence": "The ICG total score also showed a fairly high association with the Beck Depression Inventory ( BDI ) [ 32 ] total score ( r = 0 . 67 , P < 0 . 001 ) , the Texas Revised Inventory of Grief ( TRIG ) [ 33 ] score ( r = 0 . 87 , P < 0 . 001 ) , and the Grief Measurement Scale ( GMS ) [ 34 ] score ( r = 0 . 70 , P < 0 . 001 ) .", "entities": []}, {"sentence": "The ASA - 27 is a self - report measure developed to rate separation anxiety symptoms in adult life ( from 18 years of age ) .", "entities": []}, {"sentence": "Principal components analysis revealed a coherent construct of adult separation anxiety with high internal consistency ( Cronbach ' s alpha = 0 . 95 ) and sound test - retest reliability ( r = 0 . 86 ; P < 0 . 001 ) .", "entities": []}, {"sentence": "Further , a receiver operation characteristic ( ROC ) analysis against the semistructured interview yielded a high area under the curve ( AUC ) index of 0 . 9 , suggesting that the questionnaire is an adequate alternative measure of adult separation anxiety [ 29 ] .", "entities": []}, {"sentence": "The WSAS is a self - report scale of functional impairment that includes five questions rating interference of psychiatric symptoms in work , home management , social or private leisure activities , and ability to form and maintain close relationships with others .", "entities": []}, {"sentence": "Each question is rated on a 0 to 8 scale with 0 indicating no impairment at all and 8 indicating very severe impairment .", "entities": []}, {"sentence": "The Cronbach ' s alpha measure of internal scale consistency ranged from 0 . 70 to 0 . 94 , the test - retest correlation was 0 . 73 , and the WSAS interactive voice response administrations gave correlations of 0 . 81 and 0 . 86 with clinician interviews [ 30 ] .", "entities": []}, {"sentence": "Correlations of WSAS with severity of depression and obsessive - compulsive disorder symptoms were 0 . 76 and 0 . 61 , respectively , and the scores were sensitive to patient differences in disorder severity and treatment - related change [ 30 ] .", "entities": []}, {"sentence": "The MOODS - SR is an instrument developed and validated to assess lifetime mood spectrum symptoms [ 35 ] , including manic and depressive features , rhythmicity and vegetative functions .", "entities": []}, {"sentence": "The manic and depressive components are subtyped into mood , energy and cognition domains , focusing on manic or depressive symptoms , respectively .", "entities": []}, {"sentence": "The rhythmicity and vegetative functions domain include changes in energy , physical wellbeing , mental and physical efficiency , related to the weather and season , and changes in appetite , sleep and sexual activities .", "entities": []}, {"sentence": "The sum of the scores on the 3 manic domains ( mood , energy , cognition ) constitutes the ' manic component ' ( 62 items ) and that of the 3 depressive domains the ' depressive component ' ( 63 items ) .", "entities": []}, {"sentence": "The rhythmicity and vegetative functions domain includes 29 items .", "entities": []}, {"sentence": "The instrument can be downloaded from http : / / www . spectrum - project . org .", "entities": []}, {"sentence": "Methods", "entities": []}, {"sentence": "Thirteen focus group discussions with first - time parents and female and male informal supporters were analysed by discourse analysis .", "entities": []}, {"sentence": "[ Epidemiology of respiratory allergy in children ] .", "entities": [{"name": "respiratory", "type": "Anatomy", "pos": [18, 29]}]}, {"sentence": "Epidemiology of paediatric respiratory allergic disorders allows the approach to causal and preventive risk factors by studying groups or sub groups of children in different locations and under different conditions .", "entities": [{"name": "respiratory", "type": "Anatomy", "pos": [27, 38]}]}, {"sentence": "This is , however , complicated by the lack of consensus on disease definitions , which renders comparisons between studies difficult .", "entities": []}, {"sentence": "Atopy is usually defined by the presence of positive skin tests ( wheal size of at least a mean diameter > or = 3 mm ) , by the presence of specific IgE , or by the presence of increased total IgE ( > or = 100 UI / mL ) .", "entities": [{"name": "skin", "type": "Anatomy", "pos": [53, 57]}]}, {"sentence": "Infantile asthma is not well defined , complicated by the high prevalence of bronchiolitis ; one thus questions between wheezing or wheezy bronchitis .", "entities": []}, {"sentence": "Prevalence is high : among early wheezers , two populations will be defined by the medium term evolution : transient wheezers and persistent wheezers .", "entities": []}, {"sentence": "Risk factors for these two conditions are different .", "entities": []}, {"sentence": "Childhood asthma may be defined by the diagnosis of asthma ( specific but fairly non - sensitive ) , by asthmatic symptoms ( wheezing , waking by an attack of shortness of breath ) ( sensitive but not very specific ) , or by the combination of symptoms and airway hyperresponsiveness .", "entities": [{"name": "airway", "type": "Anatomy", "pos": [257, 263]}]}, {"sentence": "The ISAAC study has standardised a questionnaire to assess the prevalence of asthma .", "entities": []}, {"sentence": "The preliminary results show that there are wide variations across the world .", "entities": []}, {"sentence": "The prevalence is low in Africa and Asia , intermediate in Europe , and high in Anglo - Saxon countries .", "entities": []}, {"sentence": "The prevalence of asthma has gradually increased over the past 20 years in developed countries .", "entities": []}, {"sentence": "Asthma and atopy are closely associated in children .", "entities": []}, {"sentence": "Risk factors are genetic , associated with sex and environmental factors .", "entities": []}, {"sentence": "Among these , allergic sensitisation is associated with the degree of exposure to allergens .", "entities": []}, {"sentence": "Westernization of way of life is associated with increased prevalence of atopy , allergic rhinitis and asthma .", "entities": []}, {"sentence": "Atopy seems inversely correlated to certain infections .", "entities": []}, {"sentence": "Passive smoking is clearly associated with early wheezing .", "entities": []}, {"sentence": "This and atmospheric pollution aggravate childhood asthma .", "entities": []}, {"sentence": "However , the inducing role of pollution on asthma is still controversial .", "entities": []}, {"sentence": "Novel mechanism for the impairment of cell proliferation in HIV - 1 infection .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [38, 42]}]}, {"sentence": "The synthesis of ribonucleotides is essential to cell proliferation .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [49, 53]}]}, {"sentence": "Defects in the relevant metabolic pathways have been demonstrated in stimulated T cells from AIDS patients and are associated with lymphocyte necrotic death .", "entities": [{"name": "T cells", "type": "Anatomy", "pos": [80, 87]}, {"name": "lymphocyte", "type": "Anatomy", "pos": [131, 141]}]}, {"sentence": "Here , Margarita Bofill and colleagues discuss the possibility that an impaired ribonucleotide metabolism might be common to all rapidly dividing cells and thus contribute to other recognized symptoms of HIV - 1 infection .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [146, 151]}]}, {"sentence": "UFT and its metabolites inhibit the angiogenesis induced by murine renal cell carcinoma , as determined by a dorsal air sac assay in mice .", "entities": [{"name": "renal cell carcinoma", "type": "Anatomy", "pos": [67, 87]}, {"name": "dorsal air sac", "type": "Anatomy", "pos": [109, 123]}]}, {"sentence": "UFT , an anticancer agent that is composed of tegafur ( FT ) and uracil at a molar ratio of 1 : 4 , is widely used in clinical practice in Japan to treat cancer patients requiring a long - term chemotherapy , and it is associated with few side effects , if any .", "entities": [{"name": "anticancer", "type": "Anatomy", "pos": [9, 19]}, {"name": "cancer", "type": "Anatomy", "pos": [154, 160]}]}, {"sentence": "In this study , we have evaluated the inhibitory effect of UFT against RENCA cell - induced angiogenesis by a dorsal air sac assay .", "entities": [{"name": "RENCA cell", "type": "Anatomy", "pos": [71, 81]}, {"name": "dorsal air sac", "type": "Anatomy", "pos": [110, 124]}]}, {"sentence": "Marked angiogenesis is induced by implantation of a chamber containing RENCA cells into mice .", "entities": [{"name": "RENCA cells", "type": "Anatomy", "pos": [71, 82]}]}, {"sentence": "In this model , UFT showed a strong angiogenesis - inhibitory effect , whereas 5 - fluorouracil ( 5 - FU ) and doxifluridine were less effective .", "entities": []}, {"sentence": "Additional experiments revealed FT to be effective component of UFT ; uracil remained ineffective in the inhibition of angiogenesis .", "entities": []}, {"sentence": "Moreover , we have found that gamma - hydroxybutyric acid and gamma - butyrolactone , the metabolites of FT , possess a potent angiogenesis inhibitory effect that is amplified when the compounds are administered by a continuous infusion .", "entities": []}, {"sentence": "This may reflect a transition in blood concentration of each metabolite resulting from the administration of UFT .", "entities": [{"name": "blood", "type": "Anatomy", "pos": [33, 38]}]}, {"sentence": "Similar results were also obtained with respect to 5 - FU .", "entities": []}, {"sentence": "It was suggested that UFT has a stronger angiogenesis - inhibitory effect than did other fluorinated pyrimidines , partly due to its pharmacokinetic properties characterized by maintaining of higher and long - lasting blood levels of 5 - FU and partly due the inhibitory effects derived from gamma - hydroxybutyric acid and gamma - butyrolactone , UFT - specific metabolites .", "entities": [{"name": "blood", "type": "Anatomy", "pos": [218, 223]}]}, {"sentence": "Nitric oxide synthase inhibition results in synergistic anti - tumour activity with melphalan and tumour necrosis factor alpha - based isolated limb perfusions .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [63, 69]}, {"name": "limb", "type": "Anatomy", "pos": [144, 148]}]}, {"sentence": "Nitric oxide ( NO ) is an important molecule in regulating tumour blood flow and stimulating tumour angiogenesis .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [59, 65]}, {"name": "blood", "type": "Anatomy", "pos": [66, 71]}, {"name": "tumour", "type": "Anatomy", "pos": [93, 99]}]}, {"sentence": "Inhibition of NO synthase by L - NAME might induce an anti - tumour effect by limiting nutrients and oxygen to reach tumour tissue or affecting vascular growth .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [61, 67]}, {"name": "tumour tissue", "type": "Anatomy", "pos": [117, 130]}, {"name": "vascular", "type": "Anatomy", "pos": [144, 152]}]}, {"sentence": "The anti - tumour effect of L - NAME after systemic administration was studied in a renal subcapsular CC531 adenocarcinoma model in rats .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [11, 17]}, {"name": "renal subcapsular CC531 adenocarcinoma", "type": "Anatomy", "pos": [84, 122]}]}, {"sentence": "Moreover , regional administration of L - NAME , in combination with TNF and melphalan , was studied in an isolated limb perfusion ( ILP ) model using BN175 soft - tissue sarcomas .", "entities": [{"name": "limb", "type": "Anatomy", "pos": [116, 120]}, {"name": "BN175 soft - tissue sarcomas", "type": "Anatomy", "pos": [151, 179]}]}, {"sentence": "Systemic treatment with L - NAME inhibited growth of adenocarcinoma significantly but was accompanied by impaired renal function .", "entities": [{"name": "adenocarcinoma", "type": "Anatomy", "pos": [53, 67]}, {"name": "renal", "type": "Anatomy", "pos": [114, 119]}]}, {"sentence": "In ILP , reduced tumour growth was observed when L - NAME was used alone .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [17, 23]}]}, {"sentence": "In combination with TNF or melphalan , L - NAME increased response rates significantly compared to perfusions without L - NAME ( 0 - 64 % and 0 - 63 % respectively ) .", "entities": []}, {"sentence": "An additional anti - tumour effect was demonstrated when L - NAME was added to the synergistic combination of melphalan and TNF ( responses increased from 70 to 100 % ) .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [21, 27]}]}, {"sentence": "Inhibition of NO synthase reduces tumour growth both after systemic and regional ( ILP ) treatment .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [34, 40]}]}, {"sentence": "A synergistic anti - tumour effect of L - NAME is observed in combination with melphalan and / or TNF using ILP .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [21, 27]}]}, {"sentence": "These results indicate a possible role of L - NAME for the treatment of solid tumours in a systemic or regional setting .", "entities": [{"name": "tumours", "type": "Anatomy", "pos": [78, 85]}]}, {"sentence": "Apoptosis induced by 1 ' - acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase - 3 activation .", "entities": [{"name": "Ehrlich ascites tumor cells", "type": "Anatomy", "pos": [54, 81]}]}, {"sentence": "The efficacy of the antitumor activity of 1 ' - acetoxychavicol acetate ( ACA ) , reported to be a suppressor of chemically induced carcinogenesis , was evaluated in Ehrlich ascites tumor cells .", "entities": [{"name": "antitumor", "type": "Anatomy", "pos": [20, 29]}, {"name": "Ehrlich ascites tumor cells", "type": "Anatomy", "pos": [166, 193]}]}, {"sentence": "ACA treatment resulted in changes in morphology and a dose - dependent suppression of cell viability .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [86, 90]}]}, {"sentence": "Apoptosis , characterized by nuclear condensation , membrane blebbing , cell shrinkage and a significant induction of caspase - 3 - like protease activity at 8 h in a time - course study were observed .", "entities": [{"name": "nuclear", "type": "Anatomy", "pos": [29, 36]}, {"name": "membrane", "type": "Anatomy", "pos": [52, 60]}, {"name": "cell", "type": "Anatomy", "pos": [72, 76]}]}, {"sentence": "Formation of apoptotic bodies was preceded by lowering of intracellular polyamines , particularly putrescine , and both dose - and time - dependent inhibitory and activation effect by ACA on ornithine decarboxylase ( ODC ) and spermidine / spermine N ( 1 ) - acetyltransferase ( SSAT ) , respectively .", "entities": [{"name": "apoptotic bodies", "type": "Anatomy", "pos": [13, 29]}, {"name": "intracellular", "type": "Anatomy", "pos": [58, 71]}]}, {"sentence": "Administration of exogenous polyamines prevented ACA - induced apoptosis represented by a reduction in the number of apoptotic bodies and also caused reduction in the induced caspase - 3 - like protease activity at 8 h .", "entities": [{"name": "apoptotic bodies", "type": "Anatomy", "pos": [117, 133]}]}, {"sentence": "These findings suggest that the anticarcinogenic effects of ACA might be partly due to perturbation of the polyamine metabolic pathway and triggering of caspase - 3 - like activity , which result in apoptosis .", "entities": []}, {"sentence": "A pancreatic beta - cell - specific enhancer in the human PDX - 1 gene is regulated by hepatocyte nuclear factor 3beta ( HNF - 3beta ) , HNF - 1alpha , and SPs transcription factors .", "entities": [{"name": "pancreatic beta - cell", "type": "Anatomy", "pos": [2, 24]}]}, {"sentence": "The PDX - 1 transcription factor plays a key role in pancreas development .", "entities": [{"name": "pancreas", "type": "Anatomy", "pos": [53, 61]}]}, {"sentence": "Although expressed in all cells at the early stages , in the adult it is mainly restricted to the beta - cell .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [26, 31]}, {"name": "beta - cell", "type": "Anatomy", "pos": [98, 109]}]}, {"sentence": "To characterize the regulatory elements and potential transcription factors necessary for human PDX - 1 gene expression in beta - cells , we constructed a series of 5 ' and 3 ' deletion fragments of the 5 ' - flanking region of the gene , fused to the luciferase reporter gene .", "entities": [{"name": "beta - cells", "type": "Anatomy", "pos": [123, 135]}]}, {"sentence": "In this report , we identify by transient transfections in beta - and non - beta - cells a novel beta - cell - specific distal enhancer element located between - 3 . 7 and - 3 . 45 kilobases .", "entities": [{"name": "beta -", "type": "Anatomy", "pos": [59, 65]}, {"name": "non - beta - cells", "type": "Anatomy", "pos": [70, 88]}, {"name": "beta - cell", "type": "Anatomy", "pos": [97, 108]}]}, {"sentence": "DNase I footprinting analysis revealed two protected regions , one binding the transcription factors SP1 and SP3 and the other hepatocyte nuclear factor 3beta ( HNF - 3beta ) and HNF - 1alpha .", "entities": []}, {"sentence": "Cotransfection experiments suggest that HNF - 3beta , HNF - 1alpha , and SP1 are positive regulators of the herein - described human PDX - 1 enhancer element .", "entities": []}, {"sentence": "Furthermore , mutations within each motif abolished the binding of the corresponding factor ( s ) and dramatically impaired the enhancer activity , therefore suggesting cooperativity between these factors .", "entities": []}, {"sentence": "Vascular endothelial growth factor - B and vascular endothelial growth factor - C expression in renal cell carcinomas : regulation by the von Hippel - Lindau gene and hypoxia .", "entities": [{"name": "renal cell carcinomas", "type": "Anatomy", "pos": [96, 117]}]}, {"sentence": "Angiogenesis is essential for tumor growth and metastasis .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [30, 35]}]}, {"sentence": "It is regulated by numerous angiogenic factors , one of the most important being vascular endothelial growth factor ( VEGF ) .", "entities": []}, {"sentence": "Recently VEGF - B and VEGF - C , two new VEGF family members , have been identified that bind to the tyrosine kinase receptors flt - 1 ( VEGFR1 ) , KDR ( VEGFR2 ) , and flt - 4 ( VEGFR3 ) .", "entities": []}, {"sentence": "Although the importance of VEGF - A has been shown in renal carcinomas , the contribution of these new ligands in kidney tumors is not clear .", "entities": [{"name": "renal carcinomas", "type": "Anatomy", "pos": [54, 70]}, {"name": "kidney tumors", "type": "Anatomy", "pos": [114, 127]}]}, {"sentence": "We have , therefore , measured the mRNA level of VEGF - B and VEGF - C together with their receptors by RNase protection assay ( RPA ) in 26 normal kidney samples and 45 renal cell cancers .", "entities": [{"name": "kidney samples", "type": "Anatomy", "pos": [148, 162]}, {"name": "renal cell cancers", "type": "Anatomy", "pos": [170, 188]}]}, {"sentence": "We observed a significant up - regulation of VEGF - B ( P = 0 . 002 ) but not VEGF - C ( P = 0 . 3 ) in neoplastic kidney compared with normal tissues .", "entities": [{"name": "neoplastic kidney", "type": "Anatomy", "pos": [104, 121]}, {"name": "tissues", "type": "Anatomy", "pos": [143, 150]}]}, {"sentence": "In addition , although VEGF receptors were higher in tumors than normal kidney , there was a significant up - regulation of only flt - 1 ( P = 0 . 003 ) but not KDR ( P = 0 . 12 ) or flt - 4 ( P = 0 . 09 ) .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [53, 59]}, {"name": "kidney", "type": "Anatomy", "pos": [72, 78]}]}, {"sentence": "There was also a significant correlation between VEGF - C and both of its receptors flt - 4 ( P = 0 . 006 ) and KDR ( P = 0 . 03 ) but no association between VEGF - B and its receptor flt - 1 ( P = 0 . 23 ) .", "entities": []}, {"sentence": "A significant increase was observed in flt - 1 ( P less than 0 . 001 ) , KDR ( P = 0 . 02 ) , and flt - 4 ( P = 0 . 01 ) but not VEGF - B ( P = 0 . 82 ) or VEGF - C ( P = 0 . 52 ) expression in clear cell compared with chromophil ( papillary ) carcinomas .", "entities": [{"name": "clear cell", "type": "Anatomy", "pos": [194, 204]}, {"name": "chromophil ( papillary ) carcinomas", "type": "Anatomy", "pos": [219, 254]}]}, {"sentence": "No significant association was demonstrated between VEGF - B , VEGF - C , flt - 1 , KDR , and flt - 4 with patient sex , patient age , or tumor size ( P greater than 0 . 05 ) .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [138, 143]}]}, {"sentence": "The effect of von Hippel - Lindau ( VHL ) gene and hypoxia on VEGF - B and VEGF - C expression in the renal carcinoma cell line 786 - 0 transfected with wild - type and mutant VHL was determined by growing cells under 21 % O2 - and 0 . 1 % O2 .", "entities": [{"name": "renal carcinoma cell line 786 - 0", "type": "Anatomy", "pos": [102, 135]}, {"name": "cells", "type": "Anatomy", "pos": [206, 211]}]}, {"sentence": "In wild - type VHL cells , whereas VEGF - A was significantly up - regulated under hypoxic compared with normoxic conditions ( P less than 0 . 001 ) , expression of VEGF - C was reduced ( P less than 0 . 002 ) .", "entities": [{"name": "wild - type VHL cells", "type": "Anatomy", "pos": [3, 24]}]}, {"sentence": "Nevertheless , the repression of VEGF - C was lost in mutant VHL cell lines under hypoxia .", "entities": [{"name": "mutant VHL cell lines", "type": "Anatomy", "pos": [54, 75]}]}, {"sentence": "In contrast VEGF - B was not regulated by VHL despite clear up - regulation in vivo .", "entities": []}, {"sentence": "These findings strongly support an enhanced role for this pathway in clear cell carcinomas by regulating angiogenesis and / or lymphangiogenesis .", "entities": [{"name": "clear cell carcinomas", "type": "Anatomy", "pos": [69, 90]}]}, {"sentence": "The study shows that clear cell tumors are able to up - regulate angiogenic growth factor receptors more efficiently than chromophil ( papillary ) , that clear cell tumors can use pathways independent of VHL to regulate angiogenesis , and that this combined regulation may account for their more aggressive phenotype , which suggests that targeting VEGFR1 ( flt - l ) may be particularly effective in these tumor types .", "entities": [{"name": "clear cell tumors", "type": "Anatomy", "pos": [21, 38]}, {"name": "chromophil", "type": "Anatomy", "pos": [122, 132]}, {"name": "papillary", "type": "Anatomy", "pos": [135, 144]}, {"name": "clear cell tumors", "type": "Anatomy", "pos": [154, 171]}, {"name": "tumor", "type": "Anatomy", "pos": [407, 412]}]}, {"sentence": "Glucose catabolism in cancer cells : identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions .", "entities": [{"name": "cancer cells", "type": "Anatomy", "pos": [22, 34]}]}, {"sentence": "One of the most common signatures of highly malignant tumors is their capacity to metabolize more glucose to lactic acid than their tissues of origin .", "entities": [{"name": "malignant tumors", "type": "Anatomy", "pos": [44, 60]}, {"name": "tissues", "type": "Anatomy", "pos": [132, 139]}]}, {"sentence": "Hepatomas exhibiting this phenotype are dependent on the high expression of type II hexokinase , which supplies such tumors with abundant amounts of glucose 6 - phosphate , a significant carbon and energy source especially under hypoxic conditions .", "entities": [{"name": "Hepatomas", "type": "Anatomy", "pos": [0, 9]}, {"name": "tumors", "type": "Anatomy", "pos": [117, 123]}]}, {"sentence": "Here we report that the distal region of the hepatoma type II hexokinase promoter displays consensus motifs for hypoxia - inducible factor ( HIF - 1 ) that overlap E - box sequences known to be related in other gene promoters to glucose response .", "entities": [{"name": "hepatoma", "type": "Anatomy", "pos": [45, 53]}]}, {"sentence": "Moreover , we show that subjecting transfected hepatoma cells to hypoxic conditions activates the type II hexokinase promoter almost 3 - fold , a value that approaches 7 - fold in the presence of glucose .", "entities": [{"name": "hepatoma cells", "type": "Anatomy", "pos": [47, 61]}]}, {"sentence": "Consistent with these findings is the induction under hypoxic conditions of the HIF - 1 protein .", "entities": []}, {"sentence": "Reporter gene analyses with a series of nested deletion mutants of the hepatoma type II hexokinase promoter show that a significant fraction of the total activation observed under hypoxic conditions localizes to the distal region where the overlapping HIF - 1 / E - box sequences are located .", "entities": [{"name": "hepatoma", "type": "Anatomy", "pos": [71, 79]}]}, {"sentence": "Finally , DNase I footprint analysis with a segment of the promoter containing these elements reveals the binding of several nuclear proteins .", "entities": [{"name": "nuclear", "type": "Anatomy", "pos": [125, 132]}]}, {"sentence": "In summary , these novel studies identify and characterize a marked glucose - modulated activation response of the type II hexokinase gene to hypoxic conditions within highly glycolytic hepatoma cells , a property that may help assure that such cells exhibit a growth and survival advantage over their parental cells of origin .", "entities": [{"name": "hepatoma cells", "type": "Anatomy", "pos": [186, 200]}, {"name": "cells", "type": "Anatomy", "pos": [245, 250]}, {"name": "cells", "type": "Anatomy", "pos": [311, 316]}]}, {"sentence": "[ Decreased stimulation of glycosaminoglycan synthesis by human skin fibroblasts by interleukin 6 within the scope of in vitro aging ] .", "entities": [{"name": "skin fibroblasts", "type": "Anatomy", "pos": [64, 80]}]}, {"sentence": "Addition of human recombinant interleukin 6 ( IL - 6 ) to culture medium ( supplemented MEM without or with 10 % fetal calf serum ( FCS ) ) of human skin fibroblasts exerted a stimulating effect in a dose - dependent manner on glycosaminoglycan ( GAG ) synthesis , including hyaluronic acid ( hyaluronan ) synthesis , of young ( phase - II ) skin fibroblasts in concentrations of 1 ng / ml and 10 ng / ml .", "entities": [{"name": "fetal calf serum", "type": "Anatomy", "pos": [113, 129]}, {"name": "FCS", "type": "Anatomy", "pos": [132, 135]}, {"name": "skin fibroblasts", "type": "Anatomy", "pos": [149, 165]}, {"name": "skin fibroblasts", "type": "Anatomy", "pos": [342, 358]}]}, {"sentence": "Stimulation was mainly due to an increase in extracellular GAGs ( secreted into culture medium ) , and to a lesser extent to an increase in peri - and intracellular GAGs .", "entities": [{"name": "extracellular", "type": "Anatomy", "pos": [45, 58]}, {"name": "peri", "type": "Anatomy", "pos": [140, 144]}, {"name": "intracellular", "type": "Anatomy", "pos": [151, 164]}]}, {"sentence": "Stimulation with 1 ng / ml and 10 ng / ml IL - 6 led to an increase in hyaluronic acid from 48 % to 61 % ( - FCS ) and from 77 % to 90 % ( + 10 % FCS ) , respectively .", "entities": [{"name": "FCS", "type": "Anatomy", "pos": [109, 112]}, {"name": "FCS", "type": "Anatomy", "pos": [146, 149]}]}, {"sentence": "Maximum stimulation , with and without FCS , was achieved by 10 ng / ml IL - 6 .", "entities": [{"name": "FCS", "type": "Anatomy", "pos": [39, 42]}]}, {"sentence": "Compared to young ( phase - II ) cells , senescent ( phase - III ) cells , showed no significant stimulation of total GAG ( including hyaluronic acid ) synthesis by IL - 6 .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [33, 38]}, {"name": "cells", "type": "Anatomy", "pos": [67, 72]}]}, {"sentence": "The diminished response of GAG - and hyaluronic acid synthesis during aging of these in vitro cultured fibroblasts should motivate further research if similar processes occur during aging in an organism .", "entities": [{"name": "fibroblasts", "type": "Anatomy", "pos": [103, 114]}]}, {"sentence": "Membrane - anchored Cbl suppresses Hck protein - tyrosine kinase mediated cellular transformation .", "entities": [{"name": "Membrane", "type": "Anatomy", "pos": [0, 8]}, {"name": "cellular", "type": "Anatomy", "pos": [74, 82]}]}, {"sentence": "The mammalian proto - oncogene Cbl and its cellular homologues in Caenorhabditis elegans ( Sli - 1 ) and Drosophila ( D - Cbl ) are negative regulators of some growth factor receptor signaling pathways .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [43, 51]}]}, {"sentence": "Herein we show that Cbl can negatively regulate another signaling molecule , namely theSrc - family kinase Hck by targeting it for degradation .", "entities": []}, {"sentence": "Hck - mediated cellular transformation of murine fibroblasts is reverted by ectopic expression of a membrane - anchored allele of Cbl as assessed by the cellular morphology , suppression of anchorage independent growth , and an overall reduction in the total tyrosine phosphorylation levels within the cells .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [15, 23]}, {"name": "fibroblasts", "type": "Anatomy", "pos": [49, 60]}, {"name": "membrane", "type": "Anatomy", "pos": [100, 108]}, {"name": "cellular", "type": "Anatomy", "pos": [153, 161]}, {"name": "cells", "type": "Anatomy", "pos": [302, 307]}]}, {"sentence": "The expression of Cbl at the plasma membrane targets both Hck and itself for ubiquitination and degradation , requiring an intact RING finger .", "entities": [{"name": "plasma membrane", "type": "Anatomy", "pos": [29, 44]}]}, {"sentence": "Pharmacological inhibition of the proteasome prevents the degradation of Hck correlating with an increase in the phosphotyrosine levels within the cells .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [147, 152]}]}, {"sentence": "Activated Hck and membrane - anchored Cbl are present in similar subcellular localizations and co - immunoprecipitate , suggesting that their interaction is required for subsequent ubiquitination and degradation .", "entities": [{"name": "membrane", "type": "Anatomy", "pos": [18, 26]}, {"name": "subcellular", "type": "Anatomy", "pos": [65, 76]}]}, {"sentence": "Interestingly , both constitutively active and kinase - inactive Hck interact with and are targeted for degradation by Cbl .", "entities": []}, {"sentence": "This work illustrates alternate means to regulate Src - family kinases , and suggests that Cbl may be able to suppress many signaling pathways that are activated in various proliferative syndromes including cancer .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [207, 213]}]}, {"sentence": "Multiple stages of malignant transformation of human endothelial cells modelled by co - expression of telomerase reverse transcriptase , SV40 T antigen and oncogenic N - ras .", "entities": [{"name": "endothelial cells", "type": "Anatomy", "pos": [53, 70]}]}, {"sentence": "We have modelled multiple stages of malignant transformation of human endothelial cells ( ECs ) by overexpressing the catalytic subunit of human telomerase ( hTERT ) , together with SV40 T antigen ( SV40T ) and oncogenic N - ras .", "entities": [{"name": "endothelial cells", "type": "Anatomy", "pos": [70, 87]}, {"name": "ECs", "type": "Anatomy", "pos": [90, 93]}]}, {"sentence": "Transfection with hTERT alone , led to the immortalization of two out of three cultures of bone marrow - derived ECs ( BMECs ) .", "entities": [{"name": "cultures", "type": "Anatomy", "pos": [79, 87]}, {"name": "bone marrow - derived ECs", "type": "Anatomy", "pos": [91, 116]}, {"name": "BMECs", "type": "Anatomy", "pos": [119, 124]}]}, {"sentence": "One hTERT transduced BMEC culture underwent a long proliferative lag before resuming proliferation .", "entities": [{"name": "BMEC culture", "type": "Anatomy", "pos": [21, 33]}]}, {"sentence": "BMECs transfected with hTERT alone were functionally and phenotypically normal .", "entities": [{"name": "BMECs", "type": "Anatomy", "pos": [0, 5]}]}, {"sentence": "BMECs transfected with SV40T ( BMSVTs ) had an extended lifespan , but eventually succumbed to crisis .", "entities": [{"name": "BMECs", "type": "Anatomy", "pos": [0, 5]}, {"name": "BMSVTs", "type": "Anatomy", "pos": [31, 37]}]}, {"sentence": "BMSVTs exhibited a partially transformed phenotype , demonstrating growth factor independence , altered antigen expression and forming tiny , infrequent colonies in vitro .", "entities": [{"name": "BMSVTs", "type": "Anatomy", "pos": [0, 6]}, {"name": "colonies", "type": "Anatomy", "pos": [153, 161]}]}, {"sentence": "Transduction of BMSVTs with hTERT resulted in immortalization of 4 out of 4 cultures .", "entities": [{"name": "BMSVTs", "type": "Anatomy", "pos": [16, 22]}, {"name": "cultures", "type": "Anatomy", "pos": [76, 84]}]}, {"sentence": "BMSVTs immortalized with hTERT formed large colonies in vitro and small transient tumours in vivo .", "entities": [{"name": "BMSVTs", "type": "Anatomy", "pos": [0, 6]}, {"name": "colonies", "type": "Anatomy", "pos": [44, 52]}, {"name": "tumours", "type": "Anatomy", "pos": [82, 89]}]}, {"sentence": "BMECs co - expressing SV40T , hTERT and N - ras exhibited an overtly transformed phenotype ; forming very large colonies with an altered morphology and generating rapidly growing tumours in vivo .", "entities": [{"name": "BMECs", "type": "Anatomy", "pos": [0, 5]}, {"name": "colonies", "type": "Anatomy", "pos": [112, 120]}, {"name": "tumours", "type": "Anatomy", "pos": [179, 186]}]}, {"sentence": "These investigations demonstrate transformation of human ECs to an overtly malignant phenotype .", "entities": [{"name": "ECs", "type": "Anatomy", "pos": [57, 60]}]}, {"sentence": "This model will be useful for understanding mechanisms underlying vascular and angiogenic neoplasias , as well as for testing drugs designed to curtail aberrant EC growth .", "entities": [{"name": "vascular", "type": "Anatomy", "pos": [66, 74]}, {"name": "angiogenic neoplasias", "type": "Anatomy", "pos": [79, 100]}, {"name": "EC", "type": "Anatomy", "pos": [161, 163]}]}, {"sentence": "Prenatal hypoxia decreases lung extracellular superoxide dismutase expression and activity .", "entities": [{"name": "lung extracellular", "type": "Anatomy", "pos": [27, 45]}]}, {"sentence": "Extracellular superoxide dismutase ( EC - SOD ) , which scavenges extracellular superoxide ( O . ) , is highly regulated in the developing lung .", "entities": [{"name": "Extracellular", "type": "Anatomy", "pos": [0, 13]}, {"name": "EC", "type": "Anatomy", "pos": [37, 39]}, {"name": "extracellular", "type": "Anatomy", "pos": [66, 79]}, {"name": "lung", "type": "Anatomy", "pos": [139, 143]}]}, {"sentence": "In the prenatal rabbit , EC - SOD is predominantly intracellular and inactive , and postnatally , active EC - SOD is secreted .", "entities": [{"name": "EC", "type": "Anatomy", "pos": [25, 27]}, {"name": "intracellular", "type": "Anatomy", "pos": [51, 64]}, {"name": "EC", "type": "Anatomy", "pos": [105, 107]}]}, {"sentence": "We hypothesized that prenatal hypoxia would delay the normal postnatal secretion of active EC - SOD in the lung .", "entities": [{"name": "EC", "type": "Anatomy", "pos": [91, 93]}, {"name": "lung", "type": "Anatomy", "pos": [107, 111]}]}, {"sentence": "Pregnant New Zealand White rabbits were exposed to hypobaric hypoxia ( 15 , 000 ft x 36 h ) to alter fetal O ( 2 ) tension or were maintained in room air .", "entities": [{"name": "fetal", "type": "Anatomy", "pos": [101, 106]}]}, {"sentence": "Lungs were harvested from preterm ( 28 days ) , term ( 30 + / - 1 day ) , and 1 - wk - old kits .", "entities": [{"name": "Lungs", "type": "Anatomy", "pos": [0, 5]}]}, {"sentence": "After prenatal hypobaric hypoxia , EC - SOD mRNA expression was significantly decreased in lungs of full - term kits , whereas EC - SOD protein decreased at all ages .", "entities": [{"name": "EC", "type": "Anatomy", "pos": [35, 37]}, {"name": "lungs", "type": "Anatomy", "pos": [91, 96]}, {"name": "EC", "type": "Anatomy", "pos": [127, 129]}]}, {"sentence": "Immunohistochemical staining for EC - SOD showed that hypoxia delayed secretion of the isoenzyme in the airways and pulmonary vasculature .", "entities": [{"name": "EC", "type": "Anatomy", "pos": [33, 35]}, {"name": "airways", "type": "Anatomy", "pos": [104, 111]}, {"name": "pulmonary vasculature", "type": "Anatomy", "pos": [116, 137]}]}, {"sentence": "Furthermore , pulmonary EC - SOD enzyme activity was significantly decreased in the 1 - wk - old kits exposed to prenatal hypoxia .", "entities": [{"name": "pulmonary EC", "type": "Anatomy", "pos": [14, 26]}]}, {"sentence": "We conclude that prenatal hypoxia downregulates EC - SOD expression at both the transcriptional and posttranslational levels .", "entities": [{"name": "EC", "type": "Anatomy", "pos": [48, 50]}]}, {"sentence": "Furthermore , prenatal hypoxia delays secretion of active EC - SOD enzyme .", "entities": [{"name": "EC", "type": "Anatomy", "pos": [58, 60]}]}, {"sentence": "These findings have important implications for the effects of prenatal asphyxia on postnatal response to oxidant stress .", "entities": []}, {"sentence": "Retinal microangiopathies overlying pigment epithelial detachment in age - related macular degeneration .", "entities": [{"name": "Retinal", "type": "Anatomy", "pos": [0, 7]}, {"name": "pigment epithelial", "type": "Anatomy", "pos": [36, 54]}, {"name": "macular", "type": "Anatomy", "pos": [83, 90]}]}, {"sentence": "PURPOSE : To evaluate alterations in the retinal vasculature overlying pigment epithelial detachments ( PED ) in exudative age - related macular degeneration ( ARMD ) using indocyanine green and fluorescein angiography .", "entities": [{"name": "retinal vasculature", "type": "Anatomy", "pos": [41, 60]}, {"name": "pigment epithelial detachments", "type": "Anatomy", "pos": [71, 101]}, {"name": "PED", "type": "Anatomy", "pos": [104, 107]}, {"name": "macular", "type": "Anatomy", "pos": [137, 144]}]}, {"sentence": "METHODS : Forty - one patients ( 41 eyes ) with a clinical diagnosis of exudative ARMD with PED underwent simultaneous fluorescein and indocyanine green angiography , also under high ( 10 degrees ) magnification .", "entities": [{"name": "eyes", "type": "Anatomy", "pos": [36, 40]}, {"name": "PED", "type": "Anatomy", "pos": [92, 95]}]}, {"sentence": "Vascular abnormalities in the retina were compared between patients with vascularized ( n = 34 , group 1 ) and nonvascularized ( n = 7 , group 2 ) PED on indocyanine green angiography and correlated with the size of the PED and the presence of serous retinal detachment .", "entities": [{"name": "Vascular", "type": "Anatomy", "pos": [0, 8]}, {"name": "retina", "type": "Anatomy", "pos": [30, 36]}, {"name": "PED", "type": "Anatomy", "pos": [147, 150]}, {"name": "PED", "type": "Anatomy", "pos": [220, 223]}, {"name": "serous retinal", "type": "Anatomy", "pos": [244, 258]}]}, {"sentence": "RESULTS : In all , 67 vascular abnormalities were found by indocyanine green angiography and only 22 by fluorescein angiography ; this finding was statistically significant ( P less than 0 . 0001 ) .", "entities": [{"name": "vascular", "type": "Anatomy", "pos": [22, 30]}]}, {"sentence": "The finding of retinal vasculopathy ( 32 patients in group 1 and two patients in group 2 ) was directly correlated with the presence of choroidal neovascularizations ( P = 0 . 002 ) .", "entities": [{"name": "retinal", "type": "Anatomy", "pos": [15, 22]}, {"name": "choroidal", "type": "Anatomy", "pos": [136, 145]}]}, {"sentence": "There was also a direct correlation between the presence of choroidal neovascularization and size of the PED ( P = 0 . 03 ) .", "entities": [{"name": "choroidal", "type": "Anatomy", "pos": [60, 69]}, {"name": "PED", "type": "Anatomy", "pos": [105, 108]}]}, {"sentence": "The number of retinal vascular findings was not significantly correlated with serous elevation of the retina .", "entities": [{"name": "retinal vascular", "type": "Anatomy", "pos": [14, 30]}, {"name": "serous", "type": "Anatomy", "pos": [78, 84]}, {"name": "retina", "type": "Anatomy", "pos": [102, 108]}]}, {"sentence": "CONCLUSIONS : Retinal vasculopathies may be observed in eyes with PED and are detectable by indocyanine green and fluorescein angiography .", "entities": [{"name": "Retinal", "type": "Anatomy", "pos": [14, 21]}, {"name": "eyes", "type": "Anatomy", "pos": [56, 60]}, {"name": "PED", "type": "Anatomy", "pos": [66, 69]}]}, {"sentence": "Fas - Fas ligand signaling pathway mediates an interleukin - 12 - induced rejection of a murine prostate tumor system .", "entities": [{"name": "prostate tumor", "type": "Anatomy", "pos": [96, 110]}]}, {"sentence": "BACKGROUND : Recent data suggest that anti - tumor activities of interleukin - 12 ( IL - 12 ) involve the induction of apoptosis .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [45, 50]}]}, {"sentence": "Fas ( APO - 1 / CD95 ) is a type I membrane protein that is capable of initiating an apoptosis signaling pathway when bound to its ligand ( FasL ) .", "entities": [{"name": "membrane", "type": "Anatomy", "pos": [35, 43]}]}, {"sentence": "We undertook this study to test the hypothesis that Fas - FasL - mediated apoptosis plays a role in IL - 12 - induced tumor regression .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [118, 123]}]}, {"sentence": "METHODS : An mIL - 12 expression vector driven by cytomegalovirus promoter was used to express murine IL - 12 cDNA in the RM - 9 murine prostate carcinoma cell line .", "entities": [{"name": "RM - 9 murine prostate carcinoma cell line", "type": "Anatomy", "pos": [122, 164]}]}, {"sentence": "Control RM - 9 cells and RM - 9 cells stably transfected with IL - 12 gene ( RM - 9 - IL12 ) were inoculated subcutaneously in 4 - to 6 - week - old male C57BL / J6 mice .", "entities": [{"name": "RM - 9 cells", "type": "Anatomy", "pos": [8, 20]}, {"name": "RM - 9 cells", "type": "Anatomy", "pos": [25, 37]}, {"name": "RM - 9 - IL12", "type": "Anatomy", "pos": [77, 90]}, {"name": "subcutaneously", "type": "Anatomy", "pos": [109, 123]}]}, {"sentence": "Tumor size was measured every 3 days .", "entities": [{"name": "Tumor", "type": "Anatomy", "pos": [0, 5]}]}, {"sentence": "Western blot and immunohistochemical assays were used to evaluate Fas and FasL protein expression .", "entities": []}, {"sentence": "In situ fluorescent end labeling was used to label apoptotic cells .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [61, 66]}]}, {"sentence": "RESULTS : IL - 12 - expressing RM - 9 prostate carcinoma cells transplanted into C57BL / J6 mice grew more slowly than control RM - 9 cells and vector control RM - 9 - Luc cells .", "entities": [{"name": "RM - 9 prostate carcinoma cells", "type": "Anatomy", "pos": [31, 62]}, {"name": "RM - 9 cells", "type": "Anatomy", "pos": [127, 139]}, {"name": "RM - 9 - Luc cells", "type": "Anatomy", "pos": [159, 177]}]}, {"sentence": "The average survival time of the RM - 9 - IL12 mice was longer than 53 days , whereas the mean survival for mice transplanted with control RM - 9 cells was only 16 days .", "entities": [{"name": "RM - 9 - IL12", "type": "Anatomy", "pos": [33, 46]}, {"name": "RM - 9 cells", "type": "Anatomy", "pos": [139, 151]}]}, {"sentence": "Apoptotic cells were more numerous in RM - 9 - IL12 tumors : 10 . 3 % vs . 1 . 5 % in control ( P = 0 . 001 ) .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [10, 15]}, {"name": "RM - 9 - IL12 tumors", "type": "Anatomy", "pos": [38, 58]}]}, {"sentence": "Fas and FasL proteins were increased approximately twofold in the RM - 9 - IL12 tumors compared with the RM - 9 control tumors as determined by Western blot and immunohistochemical analyses ( P < 0 . 05 ) .", "entities": [{"name": "RM - 9 - IL12 tumors", "type": "Anatomy", "pos": [66, 86]}, {"name": "RM - 9 control tumors", "type": "Anatomy", "pos": [105, 126]}]}, {"sentence": "CONCLUSION : The Fas - FasL - mediated apoptosis pathway may contribute to the IL - 12 - induced rejection of prostate carcinoma .", "entities": [{"name": "prostate carcinoma", "type": "Anatomy", "pos": [110, 128]}]}, {"sentence": "Genetic differences in susceptibility to ulcerative enteritis in Japanese quail .", "entities": [{"name": "ulcerative", "type": "Anatomy", "pos": [41, 51]}]}, {"sentence": "Six lines of Japanese quail were derived from a single foundation population .", "entities": []}, {"sentence": "Four of the lines were selected on the basis of family mean three week body weight , two were unselected and all lines were randomly mated .", "entities": [{"name": "body", "type": "Anatomy", "pos": [71, 75]}]}, {"sentence": "Quail were housed in wire batteries during the brooding , rearing and laying periods .", "entities": []}, {"sentence": "During the brooding period , hover temperature and floor space per chick were similar from line to line .", "entities": []}, {"sentence": "For the rearing and laying periods , floor space per chick was approximately the same from line to line .", "entities": []}, {"sentence": "During an outbreak of ulcerative enteritis ( diagnosed on the basis of gross and histopathology ) in generation 31 and again in generation 34 , mortality ranged from zero for males of one control line to approximately 50 percent for females of one selected line .", "entities": [{"name": "ulcerative", "type": "Anatomy", "pos": [22, 32]}]}, {"sentence": "Analysis of variance showed that incidence of mortality differed significantly among lines and between sexes .", "entities": []}, {"sentence": "Mortality was generally higher in selected than in control lines and in females than in males .", "entities": []}, {"sentence": "It is suggested that susceptibility to ulcerative enteritis in quail may be a polygenically inherited trait and that the breeding which accompanied selection for body size may have made some loci homozygous for susceptibility alleles .", "entities": [{"name": "ulcerative", "type": "Anatomy", "pos": [39, 49]}, {"name": "body", "type": "Anatomy", "pos": [162, 166]}]}, {"sentence": "[ A decline in the French demographic situation in the context of a Europe also in demographic decline ] .", "entities": []}, {"sentence": "The author analyzes the decline in French fertility which has occurred over the past two years using data from official sources .", "entities": []}, {"sentence": "Some comparisons are made with fertility trends in other European countries .", "entities": []}, {"sentence": "The patterns of internal migration in Maharashtra : an analysis of 1971 census data .", "entities": []}, {"sentence": "Patterns of internal migration in the state of Maharashtra , India , for the period 1961 - 1971 are analyzed using 1971 census data .", "entities": []}, {"sentence": "The nature , volume , and direction of migration are examined .", "entities": []}, {"sentence": "Migrants are characterized according to factors including age , sex , marital status , occupation , and areas of origin and destination .", "entities": []}, {"sentence": "Adaptor protein Crk is required for ephrin - B1 - induced membrane ruffling and focal complex assembly of human aortic endothelial cells .", "entities": [{"name": "membrane", "type": "Anatomy", "pos": [58, 66]}, {"name": "focal complex", "type": "Anatomy", "pos": [80, 93]}, {"name": "aortic endothelial cells", "type": "Anatomy", "pos": [112, 136]}]}, {"sentence": "Endothelial cell migration is an essential step in vasculogenesis and angiogenesis , in which receptor tyrosine kinases play a pivotal role .", "entities": [{"name": "Endothelial cell", "type": "Anatomy", "pos": [0, 16]}]}, {"sentence": "We investigated the mechanism by which ephrin - B1 promotes membrane ruffling in human aortic endothelial cells , because membrane ruffling heralds cell body migration .", "entities": [{"name": "membrane", "type": "Anatomy", "pos": [60, 68]}, {"name": "aortic endothelial cells", "type": "Anatomy", "pos": [87, 111]}, {"name": "membrane", "type": "Anatomy", "pos": [122, 130]}, {"name": "cell body", "type": "Anatomy", "pos": [148, 157]}]}, {"sentence": "We especially focused on the role of Crk adaptor protein in EphB - mediated signaling .", "entities": []}, {"sentence": "Using DsRed - tagged Crk and a fluorescent time - lapse microscope , we showed that Crk was recruited to the nascent focal complex after ephrin - B1 stimulation .", "entities": [{"name": "nascent focal complex", "type": "Anatomy", "pos": [109, 130]}]}, {"sentence": "Furthermore , we found that p130 ( Cas ) , but not paxillin , recruited Crk to the nascent focal complex .", "entities": [{"name": "nascent focal complex", "type": "Anatomy", "pos": [83, 104]}]}, {"sentence": "The necessity of Crk in ephrin - B1 - induced membrane ruffling was shown both by the overexpression of dominant negative Crk mutants and by the depletion of Crk by using RNA interference .", "entities": [{"name": "membrane", "type": "Anatomy", "pos": [46, 54]}]}, {"sentence": "Then , we examined the role of two major downstream molecules of Crk , Rac1 and Rap1 .", "entities": []}, {"sentence": "The dominant negative mutant of Rac1 completely inhibited ephrin - B1 - induced membrane ruffling and focal complex assembly .", "entities": [{"name": "membrane", "type": "Anatomy", "pos": [80, 88]}, {"name": "focal complex", "type": "Anatomy", "pos": [102, 115]}]}, {"sentence": "In contrast , rap1GAPII , a negative regulator of Rap1 , did not inhibit ephrin - B1 - induced membrane ruffling .", "entities": [{"name": "membrane", "type": "Anatomy", "pos": [95, 103]}]}, {"sentence": "However , in rap1GAPII - expressing cells , ephrin - B1 did not induce membrane spreading , probably due to instability of the focal complex .", "entities": [{"name": "rap1GAPII - expressing cells", "type": "Anatomy", "pos": [13, 41]}, {"name": "membrane", "type": "Anatomy", "pos": [71, 79]}, {"name": "focal complex", "type": "Anatomy", "pos": [127, 140]}]}, {"sentence": "These results indicated that Crk plays a critical role in Rac1 - induced membrane ruffling and Rap1 - mediated nascent focal complex stabilization contributing to ephrin - B1 - induced human aortic endothelial cells migration .", "entities": [{"name": "membrane", "type": "Anatomy", "pos": [73, 81]}, {"name": "nascent focal complex", "type": "Anatomy", "pos": [111, 132]}, {"name": "aortic endothelial cells", "type": "Anatomy", "pos": [191, 215]}]}, {"sentence": "Postoperative progression of pulmonary metastasis in osteosarcoma .", "entities": [{"name": "pulmonary", "type": "Anatomy", "pos": [29, 38]}, {"name": "osteosarcoma", "type": "Anatomy", "pos": [53, 65]}]}, {"sentence": "Early relapse with distant metastasis often is observed in patients with cancer after resection of the primary tumor .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [73, 79]}, {"name": "primary tumor", "type": "Anatomy", "pos": [103, 116]}]}, {"sentence": "It is considered that resection of the primary tumor induces activation of systemic angiogenesis and enhances progression of remote metastasis .", "entities": [{"name": "primary tumor", "type": "Anatomy", "pos": [39, 52]}]}, {"sentence": "The authors show that resection of the primary osteosarcoma tumor enhances progression of pulmonary metastasis in animal osteosarcoma models .", "entities": [{"name": "primary osteosarcoma tumor", "type": "Anatomy", "pos": [39, 65]}, {"name": "pulmonary", "type": "Anatomy", "pos": [90, 99]}, {"name": "osteosarcoma", "type": "Anatomy", "pos": [121, 133]}]}, {"sentence": "Matrigel plug neovascularization assay revealed that systemic angiogenic activity was elevated after primary tumor removal ( tumor intact group , 1 . 61 + / - 0 . 21 g / dL ; tumor removed group , 4 . 92 + / - 0 . 35 g / dL ) .", "entities": [{"name": "primary tumor", "type": "Anatomy", "pos": [101, 114]}, {"name": "tumor", "type": "Anatomy", "pos": [125, 130]}, {"name": "tumor", "type": "Anatomy", "pos": [175, 180]}]}, {"sentence": "In addition , serum concentration of the angiogenesis inhibitor , endostatin , decreased significantly after primary tumor removal .", "entities": [{"name": "serum", "type": "Anatomy", "pos": [14, 19]}, {"name": "primary tumor", "type": "Anatomy", "pos": [109, 122]}]}, {"sentence": "Treatment with the antiangiogenic reagent TNP - 470 suppressed postoperative progression of pulmonary metastasis .", "entities": [{"name": "pulmonary", "type": "Anatomy", "pos": [92, 101]}]}, {"sentence": "These results indicate the possibility that activation of angiogenic activity after resection of osteosarcoma tumors enhances progression of pulmonary metastasis .", "entities": [{"name": "osteosarcoma tumors", "type": "Anatomy", "pos": [97, 116]}, {"name": "pulmonary", "type": "Anatomy", "pos": [141, 150]}]}, {"sentence": "The current data also suggest that administration of antiangiogenic reagents can prevent progression of pulmonary metastasis in osteosarcoma postoperatively .", "entities": [{"name": "pulmonary", "type": "Anatomy", "pos": [104, 113]}, {"name": "osteosarcoma", "type": "Anatomy", "pos": [128, 140]}]}, {"sentence": "Antiapoptotic effect of coagulation factor VIIa .", "entities": []}, {"sentence": "Binding of factor VIIa ( FVIIa ) to its cellular receptor tissue factor ( TF ) was previously shown to induce various intracellular signaling events , which were thought to be responsible for TF - mediated biologic effects , including angiogenesis , tumor metastasis , and restenosis .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [40, 48]}, {"name": "intracellular", "type": "Anatomy", "pos": [118, 131]}, {"name": "tumor", "type": "Anatomy", "pos": [250, 255]}]}, {"sentence": "To understand the mechanisms behind these processes , we have examined the effect of FVIIa on apoptosis .", "entities": []}, {"sentence": "Serum deprivation - induced apoptosis of BHK ( + TF ) cells was characterized by apoptotic blebs , nuclei with chromatin - condensed bodies , DNA degradation , and activation of caspase 3 .", "entities": [{"name": "Serum", "type": "Anatomy", "pos": [0, 5]}, {"name": "BHK ( + TF ) cells", "type": "Anatomy", "pos": [41, 59]}, {"name": "blebs", "type": "Anatomy", "pos": [91, 96]}, {"name": "nuclei", "type": "Anatomy", "pos": [99, 105]}, {"name": "chromatin", "type": "Anatomy", "pos": [111, 120]}]}, {"sentence": "FVIIa markedly decreased the number of cells with apoptotic morphology and prevented the DNA degradation as measured by means of TdT - mediated dUTP nick end labeling ( TUNEL ) .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [39, 44]}]}, {"sentence": "The antiapoptotic effect of FVIIa was confirmed by the observation that FVIIa attenuated caspase 3 activation .", "entities": []}, {"sentence": "FVIIa - induced antiapoptotic effect was dependent on its proteolytic activity and TF but independent of factor Xa and thrombin .", "entities": []}, {"sentence": "FVIIa - induced cell survival correlated with the activation of Akt and was inhibited markedly by the specific PI3 - kinase inhibitor , LY294002 .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [16, 20]}]}, {"sentence": "Blocking the activation of p44 / 42 mitogen - activated protein kinase ( MAPK ) by the specific mitogen - induced extracellular kinase ( MEK ) inhibitor , U0126 , impaired modestly the ability of FVIIa to promote cell survival .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [119, 123]}]}, {"sentence": "In conclusion , FVIIa binding to TF provided protection against apoptosis induced by growth factor deprivation , primarily through activation of PI3 - kinase / Akt pathway , and to a lesser extent , p44 / 42 MAPK pathway .", "entities": []}, {"sentence": "Cloning and characterization of the latent membrane protein ( LMP ) of a specific Epstein - Barr virus variant derived from the nasopharyngeal carcinoma in the Taiwanese population .", "entities": [{"name": "nasopharyngeal carcinoma", "type": "Anatomy", "pos": [128, 152]}]}, {"sentence": "A DNA fragment containing Epstein - Barr virus ( EBV ) terminal fragment sequence was obtained from a genomic library of nasopharyngeal carcinoma ( NPC ) .", "entities": [{"name": "nasopharyngeal carcinoma", "type": "Anatomy", "pos": [121, 145]}, {"name": "NPC", "type": "Anatomy", "pos": [148, 151]}]}, {"sentence": "One of the clones ( clone 1510 ) contained the gene encoding latent membrane protein ( LMP ) .", "entities": []}, {"sentence": "Sequence analysis revealed that this gene had 95 % homology with the LMP sequence of the B95 - 8 strain .", "entities": []}, {"sentence": "Among the sequence variations , there was a change from G to T at nucleotide position 169 , 426 , resulting in the loss of an XhoI site in exon 1 of the LMP gene .", "entities": []}, {"sentence": "A pair of primers bracketing the XhoI site were designed to synthesize the EBV DNA fragment from nucleotides 169 , 081 - 169 , 577 by using the polymerase chain reaction ( PCR ) method .", "entities": []}, {"sentence": "The PCR products were then subject to XhoI digestion and to DNA sequencing analysis .", "entities": []}, {"sentence": "This restriction enzyme site polymorphism along with the sequence variations were also observed in 50 biopsy tissues as well as in the throat washings of 6 out of 20 healthy individuals that we examined , indicating that the EBV strain predominantly existing in these biopsy tissues was different from strains of B95 - 8 , Jijoye or nude mouse passaged cells ( C15 ) with an African origin , but closely resembled other nude mouse passaged CAO cells which were originally derived from China .", "entities": [{"name": "biopsy tissues", "type": "Anatomy", "pos": [102, 116]}, {"name": "throat", "type": "Anatomy", "pos": [135, 141]}, {"name": "biopsy tissues", "type": "Anatomy", "pos": [268, 282]}, {"name": "cells", "type": "Anatomy", "pos": [353, 358]}, {"name": "C15", "type": "Anatomy", "pos": [361, 364]}, {"name": "CAO cells", "type": "Anatomy", "pos": [440, 449]}]}, {"sentence": "Balb / c 3T3 cells carrying this NPC - LMP gene showed a transformed cell morphology and were tumorigenic in nude mice .", "entities": [{"name": "Balb / c 3T3 cells", "type": "Anatomy", "pos": [0, 18]}, {"name": "NPC", "type": "Anatomy", "pos": [33, 36]}, {"name": "cell", "type": "Anatomy", "pos": [69, 73]}]}, {"sentence": "The relationship between this unique type of EBV and NPC has yet to be established .", "entities": [{"name": "NPC", "type": "Anatomy", "pos": [53, 56]}]}, {"sentence": "Laser treatment of eccentric leaks in central serous chorioretinopathy resulting in disappearance of untreated juxtafoveal leaks .", "entities": [{"name": "serous", "type": "Anatomy", "pos": [46, 52]}, {"name": "juxtafoveal", "type": "Anatomy", "pos": [111, 122]}]}, {"sentence": "In central serous chorioretinopathy ( CSCR ) laser treatment of leaking points close to the macular center should be avoided because of the possibility of producing juxtafoveal scotoma and stimulating choroidal neovascularization .", "entities": [{"name": "serous", "type": "Anatomy", "pos": [11, 17]}, {"name": "macular center", "type": "Anatomy", "pos": [92, 106]}, {"name": "juxtafoveal scotoma", "type": "Anatomy", "pos": [165, 184]}, {"name": "choroidal", "type": "Anatomy", "pos": [201, 210]}]}, {"sentence": "Nine eyes of nine consecutive patients with CSCR had two or more leaking points within a macular detachment , one of which was foveal or near to the fovea .", "entities": [{"name": "eyes", "type": "Anatomy", "pos": [5, 9]}, {"name": "macular", "type": "Anatomy", "pos": [89, 96]}, {"name": "foveal", "type": "Anatomy", "pos": [127, 133]}, {"name": "fovea", "type": "Anatomy", "pos": [149, 154]}]}, {"sentence": "Photocoagulation with green argon laser was performed in all eyes , treating all the leaking points except for the central one .", "entities": [{"name": "eyes", "type": "Anatomy", "pos": [61, 65]}]}, {"sentence": "Visual symptoms regressed after treatment , and the serous detachment was resolved 10 days to 4 weeks after photocoagulation in all cases .", "entities": [{"name": "serous", "type": "Anatomy", "pos": [52, 58]}]}, {"sentence": "Fluorescein angiography showed no leakage at either the central leakage point or the leakage point that had been treated .", "entities": []}, {"sentence": "These results led us to believe that the central or dependent leak in our cases was not sufficient to maintain the serous detachment by itself .", "entities": [{"name": "serous", "type": "Anatomy", "pos": [115, 121]}]}, {"sentence": "An alternative hypothesis is that the untreated leak did not represent real fluid movement but only diffusion of fluorescein molecules , or a false leak .", "entities": [{"name": "fluid", "type": "Anatomy", "pos": [76, 81]}]}, {"sentence": "In cases of CSCR with multiple leaks within a single macular detachment , we believe that a foveal leak may be a dependent or false leak and that direct treatment is not necessary .", "entities": [{"name": "macular", "type": "Anatomy", "pos": [53, 60]}, {"name": "foveal", "type": "Anatomy", "pos": [92, 98]}]}, {"sentence": "Maternal antenatal anxiety and behavioural / emotional problems in children : a test of a programming hypothesis .", "entities": []}, {"sentence": "BACKGROUND :", "entities": []}, {"sentence": "Previous animal investigations link antenatal stress with a range of persistent behavioural abnormalities in the offspring .", "entities": []}, {"sentence": "The current study examined if the effect was also found in humans through middle childhood .", "entities": []}, {"sentence": "METHODS :", "entities": []}, {"sentence": "The current study is based on the Avon Longitudinal Study of Parents and Children ( ALSPAC ) , a prospective , community - based study that has followed a cohort of women from pregnancy .", "entities": []}, {"sentence": "Self - report measures of maternal anxiety and depression were assessed at repeated intervals in pregnancy and the postnatal period .", "entities": []}, {"sentence": "Children ' s behavioural / emotional problems were assessed by parent report at age 47 and 81 months .", "entities": []}, {"sentence": "Information on obstetric and psychosocial factors was obtained at several points in pregnancy and the postnatal period .", "entities": []}, {"sentence": "RESULTS :", "entities": []}, {"sentence": "Children whose mothers experienced high levels of anxiety in late pregnancy exhibited higher rates of behavioural / emotional problems at 81 months of age after controlling for obstetric risks , psychosocial disadvantage , and postnatal anxiety and depression ( for girls , OR = 1 . 91 , 95 % CI = 1 . 26 - 2 . 89 ; for boys , OR = 2 . 16 , 95 % CI = 1 . 41 - 3 . 30 ) .", "entities": []}, {"sentence": "Furthermore , the effect at 81 months was comparable to what was previously obtained at 47 months , suggesting the kind of persistent effect proposed in the animal literature .", "entities": []}, {"sentence": "CONCLUSIONS :", "entities": []}, {"sentence": "There is evidence that antenatal stress / anxiety has a programming effect on the fetus which lasts at least until middle childhood .", "entities": [{"name": "fetus", "type": "Anatomy", "pos": [82, 87]}]}, {"sentence": "Endogenous thyroid hormones modulate pituitary somatotroph differentiation during chicken embryonic development .", "entities": [{"name": "pituitary somatotroph", "type": "Anatomy", "pos": [37, 58]}, {"name": "embryonic", "type": "Anatomy", "pos": [90, 99]}]}, {"sentence": "Growth hormone cell differentiation normally occurs between day 14 and day 16 of chicken embryonic development .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [15, 19]}, {"name": "embryonic", "type": "Anatomy", "pos": [89, 98]}]}, {"sentence": "We reported previously that corticosterone ( CORT ) could induce somatotroph differentiation in vitro and in vivo and that thyroid hormones could act in combination with CORT to further augment the abundance of somatotrophs in vitro .", "entities": [{"name": "somatotroph", "type": "Anatomy", "pos": [65, 76]}, {"name": "somatotrophs", "type": "Anatomy", "pos": [211, 223]}]}, {"sentence": "The objective of the present study was to test our hypothesis that endogenous thyroid hormones regulate the abundance of somatotrophs during chicken embryonic development .", "entities": [{"name": "somatotrophs", "type": "Anatomy", "pos": [121, 133]}, {"name": "embryonic", "type": "Anatomy", "pos": [149, 158]}]}, {"sentence": "Plasma samples were collected on embryonic day ( e ) 9 - 14 .", "entities": [{"name": "Plasma samples", "type": "Anatomy", "pos": [0, 14]}, {"name": "embryonic", "type": "Anatomy", "pos": [33, 42]}]}, {"sentence": "We found that plasma CORT and thyroid hormone levels increased progressively in mid - embryogenesis to e 13 or e 14 , immediately before normal somatotroph differentiation .", "entities": [{"name": "plasma", "type": "Anatomy", "pos": [14, 20]}, {"name": "somatotroph", "type": "Anatomy", "pos": [144, 155]}]}, {"sentence": "Administration of thyroxine ( T4 ) and triiodothyronine ( T3 ) into the albumen of fertile eggs on e 11 increased somatotroph proportions prematurely on e 13 in the developing chick embryos in vivo .", "entities": [{"name": "albumen", "type": "Anatomy", "pos": [72, 79]}, {"name": "fertile eggs", "type": "Anatomy", "pos": [83, 95]}, {"name": "somatotroph", "type": "Anatomy", "pos": [114, 125]}, {"name": "embryos", "type": "Anatomy", "pos": [182, 189]}]}, {"sentence": "Furthermore , administration of methimazole , the thyroid hormone synthesis inhibitor , on e 9 inhibited somatotroph differentiation in vivo , as assessed on e 14 ; this suppression was completely reversed by T3 replacement on e 11 .", "entities": [{"name": "somatotroph", "type": "Anatomy", "pos": [105, 116]}]}, {"sentence": "Since we reported that T3 alone was ineffective in vitro , we interpret these findings to indicate that the effects of treatments in vivo were due to interactions with endogenous glucocorticoids .", "entities": []}, {"sentence": "These results indicate that treatment with exogenous thyroid hormones can modulate somatotroph abundance and that endogenous thyroid hormone synthesis likely contributes to normal somatotroph differentiation .", "entities": [{"name": "somatotroph", "type": "Anatomy", "pos": [83, 94]}, {"name": "somatotroph", "type": "Anatomy", "pos": [180, 191]}]}, {"sentence": "Angiopoietin / tie - 2 as mediators of angiogenesis : a role in congestive heart failure ?", "entities": [{"name": "heart", "type": "Anatomy", "pos": [75, 80]}]}, {"sentence": "Angiogenic factors , in particular vascular endothelial growth factor ( VEGF ) and the angiopoietins , Ang - 1 and - 2 , have recently generated significant interest , especially in oncology .", "entities": []}, {"sentence": "The process of angiogenesis is also thought to occur in response to ischaemic conditions , which lie at the core of cardiovascular disease states such as coronary artery disease and congestive heart failure .", "entities": [{"name": "cardiovascular", "type": "Anatomy", "pos": [116, 130]}, {"name": "coronary artery", "type": "Anatomy", "pos": [154, 169]}, {"name": "heart", "type": "Anatomy", "pos": [193, 198]}]}, {"sentence": "However , current data do not conclusively show evidence of angiogenesis per se in these conditions , despite ( for example ) the presence of high levels of VEGF and Ang - 2 .", "entities": []}, {"sentence": "High levels of these angiogenic factors in heart disease also have not translated into clinically significant new vessel formation , as in accelerated cancer growth or proliferative retinopathy .", "entities": [{"name": "heart", "type": "Anatomy", "pos": [43, 48]}, {"name": "vessel", "type": "Anatomy", "pos": [114, 120]}, {"name": "cancer", "type": "Anatomy", "pos": [151, 157]}]}, {"sentence": "Indeed , we would hypothesize that these angiogenic markers - - especially the angiopoietins - - do not necessarily translate into new vessel formation in congestive heart failure ( CHF ) , but may well reflect disturbances of endothelial integrity in CHF .", "entities": [{"name": "vessel", "type": "Anatomy", "pos": [135, 141]}, {"name": "heart", "type": "Anatomy", "pos": [166, 171]}, {"name": "endothelial", "type": "Anatomy", "pos": [227, 238]}]}, {"sentence": "[ Correlation between expression of vascular endothelial growth factor - C in tumor - associated macrophages and lymphatic metastasis in oral cancer ] .", "entities": [{"name": "tumor - associated macrophages", "type": "Anatomy", "pos": [78, 108]}, {"name": "lymphatic", "type": "Anatomy", "pos": [113, 122]}, {"name": "oral cancer", "type": "Anatomy", "pos": [137, 148]}]}, {"sentence": "BACKGROUND & # 38 ; OBJECTIVE : Previous study shows that both vascular endothelial growth - C ( VEGF - C ) and tumor - associated macrophages ( TAMs ) are related to lymphatic metastasis .", "entities": [{"name": "tumor - associated macrophages", "type": "Anatomy", "pos": [112, 142]}, {"name": "TAMs", "type": "Anatomy", "pos": [145, 149]}, {"name": "lymphatic", "type": "Anatomy", "pos": [167, 176]}]}, {"sentence": "This study aimed to explore the correlation between the expression of VEGF - C in TAMs and lymphatic metastasis in human oral squamous - cell carcinoma ( OSCC ) .", "entities": [{"name": "TAMs", "type": "Anatomy", "pos": [82, 86]}, {"name": "lymphatic", "type": "Anatomy", "pos": [91, 100]}, {"name": "oral squamous - cell carcinoma", "type": "Anatomy", "pos": [121, 151]}, {"name": "OSCC", "type": "Anatomy", "pos": [154, 158]}]}, {"sentence": "METHODS : After immunohistochemical staining , light microscope was used for counting macrophages and automated image analysis quantification was used to determine VEGF - C expression , which was reflected by positive index ( PI ) .", "entities": [{"name": "macrophages", "type": "Anatomy", "pos": [86, 97]}]}, {"sentence": "In addition , the double staining was also used to determine VEGF - C expression in TAMs .", "entities": [{"name": "TAMs", "type": "Anatomy", "pos": [84, 88]}]}, {"sentence": "RESULTS : VEGF - C expression was higher in lymphatic metastasis group ( PI = 12 . 169 + / - 2 . 778 ) than in no - metastasis group ( PI = 8 . 498 + / - 2 . 674 , P < 0 . 05 ) .", "entities": [{"name": "lymphatic", "type": "Anatomy", "pos": [44, 53]}]}, {"sentence": "TAMs counts was related to VEGF - C expression in OSCC ( r = 0 . 370 , P < 0 . 05 ) .", "entities": [{"name": "TAMs", "type": "Anatomy", "pos": [0, 4]}, {"name": "OSCC", "type": "Anatomy", "pos": [50, 54]}]}, {"sentence": "The result of double staining indicated that macrophage with positive VEGF - C expression accounted for about 22 . 8 % of the total .", "entities": [{"name": "macrophage", "type": "Anatomy", "pos": [45, 55]}]}, {"sentence": "CONCLUSION : Not only tumor cells but also TAMs secrete the VEGF - C in OSCC , and TAMs may play a major role in peritumoral lymphatic neoangiogenesis and lymphatic metastasis .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [22, 33]}, {"name": "TAMs", "type": "Anatomy", "pos": [43, 47]}, {"name": "OSCC", "type": "Anatomy", "pos": [72, 76]}, {"name": "TAMs", "type": "Anatomy", "pos": [83, 87]}, {"name": "peritumoral lymphatic", "type": "Anatomy", "pos": [113, 134]}, {"name": "lymphatic", "type": "Anatomy", "pos": [155, 164]}]}, {"sentence": "Deletion of guanine nucleotide binding protein alpha z subunit in mice induces a gene dose dependent tolerance to morphine .", "entities": []}, {"sentence": "The mechanism underlying the development of tolerance to morphine is still incompletely understood .", "entities": []}, {"sentence": "Morphine binds to opioid receptors , which in turn activates downstream second messenger cascades through heterotrimeric guanine nucleotide binding proteins ( G proteins ) .", "entities": []}, {"sentence": "In this paper , we show that G ( z ) , a member of the inhibitory G protein family , plays an important role in mediating the analgesic and lethality effects of morphine after tolerance development .", "entities": []}, {"sentence": "We blocked signaling through the G ( z ) second messenger cascade by genetic ablation of the alpha subunit of the G protein in mice .", "entities": []}, {"sentence": "The Galpha ( z ) knockout mouse develops significantly increased tolerance to morphine , which depends on Galpha ( z ) gene dosage .", "entities": []}, {"sentence": "Further experiments demonstrate that the enhanced morphine tolerance is not caused by pharmacokinetic and behavioural learning mechanisms .", "entities": []}, {"sentence": "The results suggest that G ( z ) signaling pathways are involved in transducing the analgesic and lethality effects of morphine following chronic morphine treatment .", "entities": []}, {"sentence": "Effects of buffer properties on cyclodextrin glucanotransferase reactions and cyclodextrin production from raw sago ( Cycas revoluta ) starch .", "entities": [{"name": "starch", "type": "Anatomy", "pos": [135, 141]}]}, {"sentence": "Results from the present study have shown that the ionic species of buffers , pH values and reaction temperature can affect the enzyme unit activities and product specificity of Toruzyme ( Novo Nordisk A / S Bagsvaerd , Denmark ) CGTase ( cyclodextrin glucanotransferase ) .", "entities": []}, {"sentence": "Applying a similar reaction environment ( acetate buffer , pH 6 . 0 ; temperature , 60 degrees C ) , the CGTase was found to be capable of producing pre dominantly beta - cyclodextrin from either raw or gelatinized sago ( Cycas revoluta ) starch .", "entities": [{"name": "starch", "type": "Anatomy", "pos": [239, 245]}]}, {"sentence": "Changing the buffer from acetate to phosphate reduced the yield of beta - cyclodextrin from 2 . 48 to 1 . 42 mg / ml and also affected the product specificity , where production of both alpha - and beta - cyclodextrins were more pronounced .", "entities": []}, {"sentence": "The decrease in the production of cyclodextrins in phosphate buffer was significant at both pH 6 . 0 and 7 . 0 .", "entities": []}, {"sentence": "However , changing the buffer to Tris / HCl ( pH 7 . 0 ) showed a significant increase in beta - cyclodextrin production .", "entities": []}, {"sentence": "Increasing the ionic strength of sodium acetate and Tris / HCl buffers at pH 6 . 0 and 7 . 0 to equivalent ionic strength of phosphate buffers showed no significant effects on cyclodextrin production .", "entities": []}, {"sentence": "Higher yield of cyclodextrins at pH 7 . 0 when Tris / HCl was used might be due to the binding of chloride ions at the calcium - binding sites of the CGTase , resulting in the shift of the optimum pH close to physiological environment , leading to an increase in the activities and specificity .", "entities": []}, {"sentence": "Hypothesis : Induced angiogenesis after surgery in premenopausal node - positive breast cancer patients is a major underlying reason why adjuvant chemotherapy works particularly well for those patients .", "entities": [{"name": "node", "type": "Anatomy", "pos": [65, 69]}, {"name": "breast cancer", "type": "Anatomy", "pos": [81, 94]}]}, {"sentence": "BACKGROUND : We suggest that surgical extirpation of primary breast cancer among other effects accelerates relapse for some premenopausal node - positive patients .", "entities": [{"name": "primary breast cancer", "type": "Anatomy", "pos": [53, 74]}, {"name": "node", "type": "Anatomy", "pos": [138, 142]}]}, {"sentence": "These accelerated relapses occur within 10 months of surgery for untreated patients .", "entities": []}, {"sentence": "The mechanism proposed is a stimulation of angiogenesis for distant dormant micrometastases .", "entities": [{"name": "distant dormant micrometastases", "type": "Anatomy", "pos": [60, 91]}]}, {"sentence": "This has been suggested as one of the mechanisms to explain the mammography paradox for women aged 40 - 49 years .", "entities": []}, {"sentence": "We could imagine that it also plays a role in adjuvant chemotherapy effectiveness since , perhaps not coincidentally , this is most beneficial for premenopausal node - positive patients .", "entities": [{"name": "node", "type": "Anatomy", "pos": [161, 165]}]}, {"sentence": "HYPOTHESIS : We speculate that there is a burst of angiogenesis of distant dormant micrometastases after surgery in approximately 20 % of premenopausal node - positive patients .", "entities": [{"name": "distant dormant micrometastases", "type": "Anatomy", "pos": [67, 98]}, {"name": "node", "type": "Anatomy", "pos": [152, 156]}]}, {"sentence": "We also speculate that this synchronizes them into a temporal highly chemosensitive state and is the underlying reason why adjuvant chemotherapy works particularly well for that patient category .", "entities": []}, {"sentence": "Furthermore , this may explain why cancer in younger patients is more often ' aggressive ' .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [35, 41]}]}, {"sentence": "TESTING THE HYPOTHESIS : Stimulation of dormant micrometastases by primary tumor removal is known to occur in animal models .", "entities": [{"name": "dormant micrometastases", "type": "Anatomy", "pos": [40, 63]}, {"name": "primary tumor", "type": "Anatomy", "pos": [67, 80]}]}, {"sentence": "However , we need to determine whether it happens in breast cancer .", "entities": [{"name": "breast cancer", "type": "Anatomy", "pos": [53, 66]}]}, {"sentence": "Transient circulating levels of angioactive molecules and serial high - resolution imaging studies of focal angiogenesis might help .", "entities": []}, {"sentence": "IMPLICATIONS : Short - course cytotoxic chemotherapy after surgery has probably reached its zenith , and other strategies , perhaps antiangiogenic methods , are needed to successfully treat more patients .", "entities": []}, {"sentence": "In addition , the hypothesis predicts that early detection , which is designed to find more patients without involved lymph nodes , may not be a synergistic strategy with adjuvant chemotherapy , which works best with positive lymph node patients .", "entities": [{"name": "lymph nodes", "type": "Anatomy", "pos": [118, 129]}, {"name": "lymph node", "type": "Anatomy", "pos": [226, 236]}]}, {"sentence": "Rational synthesis of multicyclic bis [ 2 ] catenanes .", "entities": []}, {"sentence": "Bis - loop tetraurea calix [ 4 ] arene 6 has been prepared by acylation of the wide - rim calix [ 4 ] arene tetraamine 1 with the activated bis ( urethane ) 8 under dilution conditions .", "entities": []}, {"sentence": "Similarly the bis ( Boc - protected ) tetraamine 2 is converted into the mono - loop derivative 3 which after deprotection and acylation gives the bisalkenyl derivative 5 .", "entities": []}, {"sentence": "In apolar solvents this tetraurea calix [ 4 ] arene 5 forms regioselectively a single hydrogen - bonded homodimer , from which the bis [ 2 ] catenane 10a is formed in 49 % by a metathesis reaction followed by hydrogenation .", "entities": []}, {"sentence": "Bis - loop derivative 6 forms no homodimers for steric reasons , but a stoichiometric mixture with the open - chain tetraalkenyl derivative 7a contains exclusively the heterodimer .", "entities": []}, {"sentence": "Metathesis and subsequent hydrogenation now yields 65 % of the pure bis [ 2 ] catenane 10a which could not be isolated from the complex reaction mixture obtained from the homodimer 7a . 7a .", "entities": []}, {"sentence": "The chirality of 10a ( D ( 2 ) symmetry ) has been verified by optical resolution using HPLC on a chiral stationary phase .", "entities": []}, {"sentence": "The learning curve : the advantages and disadvantages in the use of focus groups as a method of data collection .", "entities": []}, {"sentence": "Focus groups are not simply a discussion between people , but are focused interviews exploring interactions between participants .", "entities": []}, {"sentence": "In this paper , Ian Mansell , Glynis Bennett , Ruth Northway , Donna Mead and Laurie Moseley explore the complexities and practicalities of using focus groups in research , with reference to a study of palliative care services .", "entities": []}, {"sentence": "Vascular endothelial growth factor ( VEGF ) in seizures : a double - edged sword .", "entities": []}, {"sentence": "Vascular endothelial growth factor ( VEGF ) is a vascular growth factor which induces angiogenesis ( the development of new blood vessels ) , vascular permeability , and inflammation .", "entities": [{"name": "vascular", "type": "Anatomy", "pos": [49, 57]}, {"name": "blood vessels", "type": "Anatomy", "pos": [124, 137]}, {"name": "vascular", "type": "Anatomy", "pos": [142, 150]}]}, {"sentence": "In brain , receptors for VEGF have been localized to vascular endothelium , neurons , and glia .", "entities": [{"name": "brain", "type": "Anatomy", "pos": [3, 8]}, {"name": "vascular endothelium", "type": "Anatomy", "pos": [53, 73]}, {"name": "neurons", "type": "Anatomy", "pos": [76, 83]}, {"name": "glia", "type": "Anatomy", "pos": [90, 94]}]}, {"sentence": "VEGF is upregulated after hypoxic injury to the brain , which can occur during cerebral ischemia or high - altitude edema , and has been implicated in the blood - brain barrier breakdown associated with these conditions .", "entities": [{"name": "brain", "type": "Anatomy", "pos": [48, 53]}, {"name": "cerebral", "type": "Anatomy", "pos": [79, 87]}, {"name": "edema", "type": "Anatomy", "pos": [116, 121]}, {"name": "blood - brain barrier", "type": "Anatomy", "pos": [155, 176]}]}, {"sentence": "Given its recently - described role as an inflammatory mediator , VEGF could also contribute to the inflammatory responses observed in cerebral ischemia .", "entities": [{"name": "cerebral", "type": "Anatomy", "pos": [135, 143]}]}, {"sentence": "After seizures , blood - brain barrier breakdown and inflammation is also observed in brain , albeit on a lower scale than that observed after stroke .", "entities": [{"name": "blood - brain barrier", "type": "Anatomy", "pos": [17, 38]}, {"name": "brain", "type": "Anatomy", "pos": [86, 91]}]}, {"sentence": "Recent evidence has suggested a role for inflammation in seizure disorders .", "entities": []}, {"sentence": "We have described striking increases in VEGF protein in both neurons and glia after pilocarpine - induced status epilepticus in the brain .", "entities": [{"name": "neurons", "type": "Anatomy", "pos": [61, 68]}, {"name": "glia", "type": "Anatomy", "pos": [73, 77]}, {"name": "brain", "type": "Anatomy", "pos": [132, 137]}]}, {"sentence": "Increases in VEGF could contribute to the blood - brain barrier breakdown and inflammation observed after seizures .", "entities": [{"name": "blood - brain barrier", "type": "Anatomy", "pos": [42, 63]}]}, {"sentence": "However , VEGF has also been shown to be neuroprotective across several experimental paradigms , and hence could potentially protect vulnerable cells from damage associated with seizures .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [144, 149]}]}, {"sentence": "Therefore , the role of VEGF after seizures could be either protective or destructive .", "entities": []}, {"sentence": "Although only further research will determine the exact nature of VEGF ' s role after seizures , preliminary data indicate that VEGF plays a protective role after seizures .", "entities": []}, {"sentence": "Safety of verteporfin for treatment of subfoveal choroidal neovascular membranes associated with age - related macular degeneration .", "entities": [{"name": "subfoveal choroidal neovascular membranes", "type": "Anatomy", "pos": [39, 80]}, {"name": "macular", "type": "Anatomy", "pos": [111, 118]}]}, {"sentence": "Photodynamic therapy ( PDT ) is a novel treatment entity that exploits the photophysical properties of various photosensitive chemical entities which , upon light activation , results in targeted photooxidation and subsequent tissue destruction .", "entities": [{"name": "tissue", "type": "Anatomy", "pos": [226, 232]}]}, {"sentence": "The antiangiogenic properties of PDT have been adapted for treatment of subfoveal choroidal neovascular membranes due to disease states such as age - related macular degeneration ( AMD ) .", "entities": [{"name": "subfoveal choroidal neovascular membranes", "type": "Anatomy", "pos": [72, 113]}, {"name": "macular", "type": "Anatomy", "pos": [158, 165]}]}, {"sentence": "Historically , PDT has been limited by a lack of suitable photosensitive dyes .", "entities": []}, {"sentence": "However , agents such as verteporfin , a second - generation benzoporphyrin derivative , appear to be free from the extensive phototoxicity that limited the success of previous agents .", "entities": []}, {"sentence": "Verteporfin has a high affinity for choroidal neovascular membranes , typically found with exudative AMD , and upon photoactivation results in targeted microvascular damage and thrombus formation with resultant vessel occlusion .", "entities": [{"name": "choroidal neovascular membranes", "type": "Anatomy", "pos": [36, 67]}, {"name": "microvascular", "type": "Anatomy", "pos": [152, 165]}, {"name": "thrombus", "type": "Anatomy", "pos": [177, 185]}, {"name": "vessel", "type": "Anatomy", "pos": [211, 217]}]}, {"sentence": "Scrutiny of diagnostic indicators for verteporfin administration , including critical angiographic evaluation of lesion size and visual acuity , is essential to treatment success .", "entities": [{"name": "lesion", "type": "Anatomy", "pos": [113, 119]}]}, {"sentence": "Large lesions with relatively good visual acuity ( 20 / 50 or better ) may be at particular risk for marked vision loss following verteporfin administration .", "entities": [{"name": "lesions", "type": "Anatomy", "pos": [6, 13]}]}, {"sentence": "Lesion composition also appears to influence visual outcome with verteporfin use .", "entities": [{"name": "Lesion", "type": "Anatomy", "pos": [0, 6]}]}, {"sentence": "The safety of verteporfin is directly dependent upon the appropriate integration of dosage , infusion and light activation required for a suitable pharmacotherapeutic outcome .", "entities": []}, {"sentence": "When used appropriately , and with adequate patient education regarding photosensitivity , the risk - benefit of verteporfin for the medical treatment of neovascular AMD is favourable .", "entities": []}, {"sentence": "Retrospective case series of juxtafoveal choroidal neovascularization treated with photodynamic therapy with verteporfin .", "entities": [{"name": "juxtafoveal choroidal", "type": "Anatomy", "pos": [29, 50]}]}, {"sentence": "PURPOSE : To describe visual acuity and angiographic outcomes of juxtafoveal choroidal neovascularization ( CNV ) treated with photodynamic therapy and verteporfin ( PDT ) .", "entities": [{"name": "juxtafoveal choroidal", "type": "Anatomy", "pos": [65, 86]}]}, {"sentence": "METHODS : Four hundred eighty - four consecutive eyes of 446 patients treated with PDT from January 1 , 2001 , to June 30 , 2002 , were identified from billing records .", "entities": [{"name": "eyes", "type": "Anatomy", "pos": [49, 53]}]}, {"sentence": "Fluorescein angiograms were reviewed retrospectively to identify juxtafoveal CNV .", "entities": [{"name": "juxtafoveal", "type": "Anatomy", "pos": [65, 76]}]}, {"sentence": "Eligible patients had CNV in which the central boundary of the lesion was between 1 and 199 microm from the geometric center of the foveal avascular zone ( FAZ ) .", "entities": [{"name": "lesion", "type": "Anatomy", "pos": [63, 69]}, {"name": "foveal avascular zone", "type": "Anatomy", "pos": [132, 153]}, {"name": "FAZ", "type": "Anatomy", "pos": [156, 159]}]}, {"sentence": "Patient charts were reviewed for visual acuity of the treated eye before PDT and at 6 - and 12 - month follow - up examinations .", "entities": [{"name": "eye", "type": "Anatomy", "pos": [62, 65]}]}, {"sentence": "Presence of subfoveal CNV at 6 and 12 months of follow - up was determined by review of fluorescein angiograms .", "entities": []}, {"sentence": "A lesion was considered subfoveal if it extended underneath the geometric center of the FAZ .", "entities": [{"name": "lesion", "type": "Anatomy", "pos": [2, 8]}, {"name": "FAZ", "type": "Anatomy", "pos": [88, 91]}]}, {"sentence": "RESULTS : Twenty - one eyes had juxtafoveal CNV .", "entities": [{"name": "eyes", "type": "Anatomy", "pos": [23, 27]}, {"name": "juxtafoveal", "type": "Anatomy", "pos": [32, 43]}]}, {"sentence": "Median change in visual acuity both 6 and 12 months after the initial PDT was 0 lines ( n = 18 at 6 months , range - 14 to + 8 lines ; n = 17 at 12 months , range - 18 to + 7 lines ) .", "entities": []}, {"sentence": "Eleven lesions progressed to a subfoveal location by 12 months .", "entities": [{"name": "lesions", "type": "Anatomy", "pos": [7, 14]}]}, {"sentence": "Visual acuity in eyes with progressive lesions decreased a median of 4 lines of vision .", "entities": [{"name": "eyes", "type": "Anatomy", "pos": [17, 21]}, {"name": "lesions", "type": "Anatomy", "pos": [39, 46]}]}, {"sentence": "CONCLUSIONS : Despite a small sample size and limited length of follow - up , this study shows that visual acuity on average can remain stable for at least 12 months after PDT of juxtafoveal lesions .", "entities": [{"name": "juxtafoveal lesions", "type": "Anatomy", "pos": [179, 198]}]}, {"sentence": "Growth through the foveal center still can occur , however , and this can be associated with substantial visual loss .", "entities": [{"name": "foveal center", "type": "Anatomy", "pos": [19, 32]}]}, {"sentence": "[ Epidemiology of fractures of the proximal femur ] .", "entities": [{"name": "femur", "type": "Anatomy", "pos": [44, 49]}]}, {"sentence": "Fractures of the upper end of the femur constitute a major public health problem which , for demographic reasons , will become worse during the next decades .", "entities": [{"name": "femur", "type": "Anatomy", "pos": [34, 39]}]}, {"sentence": "The clinical determination of femoral neck fractures is imperfectly known .", "entities": [{"name": "femoral neck", "type": "Anatomy", "pos": [30, 42]}]}, {"sentence": "Two factors seem to be determinant : bone fragility and fall , but these factors are frequent in the elderly and other factors seem to intervene , notably the modality of the impact and the protection reflexes during the fall .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [37, 41]}]}, {"sentence": "The epidemiology of proximal femur fractures therefore cannot be restricted to the diminution of bone mass .", "entities": [{"name": "femur", "type": "Anatomy", "pos": [29, 34]}, {"name": "bone", "type": "Anatomy", "pos": [97, 101]}]}, {"sentence": "Beside age and female sex , the confirmed risk factors for these fractures are : ethnic origin , absence of replacement hormonal therapy in menopausal women , slight build and absorption of certain psychotropic drugs .", "entities": []}, {"sentence": "To be efficient , preventive measures must rest on a better knowledge of the determinant factors .", "entities": []}, {"sentence": "Epidemiological research should develop rationally and aim at identifying more accurate risk factors , taking into account the mechanisms responsible for proximal femur fractures : fall , lack of cushioning and protection during the fall , and bone fragility .", "entities": [{"name": "femur", "type": "Anatomy", "pos": [163, 168]}, {"name": "bone", "type": "Anatomy", "pos": [244, 248]}]}, {"sentence": "Expression of DCC and netrin - 1 in normal human endometrium and its implication in endometrial carcinogenesis .", "entities": [{"name": "endometrium", "type": "Anatomy", "pos": [49, 60]}, {"name": "endometrial", "type": "Anatomy", "pos": [84, 95]}]}, {"sentence": "OBJECTIVE : Although DCC has been considered as a candidate tumor suppressor , the roles it plays in the uterine endometrium and in the carcinogenic process remains unclear .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [60, 65]}, {"name": "uterine endometrium", "type": "Anatomy", "pos": [105, 124]}]}, {"sentence": "To define these roles more clearly , we examined the expression of DCC and its ligand , netrin - 1 , in the normal endometrium and in endometrial cancer .", "entities": [{"name": "endometrium", "type": "Anatomy", "pos": [115, 126]}, {"name": "endometrial cancer", "type": "Anatomy", "pos": [134, 152]}]}, {"sentence": "METHODS : The expression of DCC and netrin - 1 in normal endometrial glands and in cancer cell lines was examined by RT - PCR and immunohistochemistry .", "entities": [{"name": "endometrial glands", "type": "Anatomy", "pos": [57, 75]}, {"name": "cancer cell lines", "type": "Anatomy", "pos": [83, 100]}]}, {"sentence": "The effects of exogenous DCC and netrin - 1 expression were observed together with the respective expression vector transfection .", "entities": []}, {"sentence": "RESULTS : Endometrial glands in the proliferative and early secretory phase expressed both DCC and netrin - 1 , but glands in the late - secretory phase tended to silence DCC expression .", "entities": [{"name": "Endometrial glands", "type": "Anatomy", "pos": [10, 28]}, {"name": "glands", "type": "Anatomy", "pos": [116, 122]}]}, {"sentence": "In addition , all of the endometrial cancer cell lines lost normal DCC expression .", "entities": [{"name": "endometrial cancer cell lines", "type": "Anatomy", "pos": [25, 54]}]}, {"sentence": "Restored DCC expression in the cancer cell lines in the absence of netrin - 1 induced apoptosis .", "entities": [{"name": "cancer cell lines", "type": "Anatomy", "pos": [31, 48]}]}, {"sentence": "However , no changes were observed in the presence of netrin - 1 .", "entities": []}, {"sentence": "CONCLUSION : Our observations suggest that DCC / netrin - 1 signaling may commit cells to the transition of endometrial gland architecture or function from a proliferating to a secretory phase .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [81, 86]}, {"name": "endometrial gland", "type": "Anatomy", "pos": [108, 125]}]}, {"sentence": "In addition , the silencing of DCC expression may contribute to the escape of endometrial cancer cells from a DCC - regulated apoptotic program , thereby promoting malignant phenotypes .", "entities": [{"name": "endometrial cancer cells", "type": "Anatomy", "pos": [78, 102]}]}, {"sentence": "Structural evolution in cationic micelles upon incorporation of a polar organic dopant .", "entities": []}, {"sentence": "Micelles of cetyltrimethylammonium bromide ( CTAB ) , when doped with increasing levels of 4 - ethylphenol , show microstructural transitions from spherical micelles to elongated wormlike micelles , disks , and subsequently to globular and then to tubular vesicles .", "entities": []}, {"sentence": "Wormlike micelles are observed at a dopant - to - CTAB molar ratio of 1 : 3 .", "entities": []}, {"sentence": "At higher dopant ratios ( 1 : 1 ) , globular vesicles are observed which transition to tubular vesicles when the dopant becomes the predominant species at a ratio of 3 : 1 .", "entities": []}, {"sentence": "These transitions are reflected in small - angle neutron scattering analysis and , interestingly , can be directly observed through cryo - transmission electron microscopy .", "entities": []}, {"sentence": "The para - substituted phenol is interfacially active and modulates interfacial curvature of the micelles .", "entities": []}, {"sentence": "The observations of microstructure modifications have relevance to the synthesis of mesoporous materials using CTAB as the template .", "entities": []}, {"sentence": "An evaluation of low molecular weight heparin and hyperbaric oxygen treatment in the prevention of intra - abdominal adhesions and wound healing .", "entities": [{"name": "wound", "type": "Anatomy", "pos": [131, 136]}]}, {"sentence": "BACKGROUND : Abdominal surgery can lead to intra - abdominal adhesions with significant morbidity and mortality .", "entities": [{"name": "Abdominal", "type": "Anatomy", "pos": [13, 22]}]}, {"sentence": "To prevent adhesions , an experimental study was planned to designate the effects of low molecular weight ( LMW ) heparins and hyperbaric oxygen ( HBO ) therapy both on the formation of adhesions and wound healing .", "entities": [{"name": "wound", "type": "Anatomy", "pos": [200, 205]}]}, {"sentence": "METHODS : Thirty - eight Wistar albino rats underwent laparotomy to cause intra - abdominal adhesions by mechanical abrasion of the cecum and ethanol application .", "entities": [{"name": "cecum", "type": "Anatomy", "pos": [132, 137]}]}, {"sentence": "The rats were divided into 4 groups .", "entities": []}, {"sentence": "In the control group ( group 1 ) no further management was undertaken .", "entities": []}, {"sentence": "Group 2 was treated by Enoxaparine Na , group 3 received HBO therapy , and group 4 was given both enoxaparine Na and HBO treatment .", "entities": []}, {"sentence": "RESULTS : There was a statistically significant difference between the control and enoxaparine Na groups regarding adhesions .", "entities": []}, {"sentence": "Statistically significant differences were observed between groups 1 and 4 and between groups 1 and 3 regarding the hydroxyproline content of the abdominal wounds .", "entities": [{"name": "abdominal wounds", "type": "Anatomy", "pos": [146, 162]}]}, {"sentence": "In the pathologic analysis of the abdominal wounds , there was no statistically significant difference between any of the groups , including the control group , regarding inflammation .", "entities": [{"name": "abdominal wounds", "type": "Anatomy", "pos": [34, 50]}]}, {"sentence": "Statistically significant differences were observed regarding angiogenesis between the control group and groups 3 and 4 .", "entities": []}, {"sentence": "There was also a statistically significant difference regarding fibrosis between groups 1 and 4 .", "entities": []}, {"sentence": "CONCLUSIONS : Enoxaparine Na decreased intra - abdominal adhesions , and HBO therapy had no beneficial effect on adhesions .", "entities": []}, {"sentence": "Enoxaparine Na had no harmful effects on wound healing , and HBO therapy increased the process of wound healing .", "entities": [{"name": "wound", "type": "Anatomy", "pos": [41, 46]}, {"name": "wound", "type": "Anatomy", "pos": [98, 103]}]}, {"sentence": "Treatment of transplanted CT26 tumour with dendritic cell vaccine in combination with blockade of vascular endothelial growth factor receptor 2 and CTLA - 4 .", "entities": [{"name": "CT26 tumour", "type": "Anatomy", "pos": [26, 37]}, {"name": "dendritic cell", "type": "Anatomy", "pos": [43, 57]}]}, {"sentence": "We investigated the anti CT26 tumour effect of dendritic cell based vaccination with the MuLV gp70 envelope protein - derived peptides AH1 and p320 - 333 .", "entities": [{"name": "CT26 tumour", "type": "Anatomy", "pos": [25, 36]}, {"name": "dendritic cell", "type": "Anatomy", "pos": [47, 61]}, {"name": "envelope", "type": "Anatomy", "pos": [99, 107]}]}, {"sentence": "Vaccination lead to generation of AH1 specific cytotoxic lymphocytes ( CTL ) and some decrease in tumour growth of simultaneously inoculated CT26 cells .", "entities": [{"name": "cytotoxic lymphocytes", "type": "Anatomy", "pos": [47, 68]}, {"name": "CTL", "type": "Anatomy", "pos": [71, 74]}, {"name": "tumour", "type": "Anatomy", "pos": [98, 104]}, {"name": "CT26 cells", "type": "Anatomy", "pos": [141, 151]}]}, {"sentence": "After combination with an antibody against VEGF receptor 2 ( DC101 ) , a significant increase in survival of the tumour cell recipients was observed .", "entities": [{"name": "tumour cell", "type": "Anatomy", "pos": [113, 124]}]}, {"sentence": "Also , monotherapy with an antibody against CTLA - 4 ( 9H10 ) , led to approximately 100 % survival of tumour cell recipients .", "entities": [{"name": "tumour cell", "type": "Anatomy", "pos": [103, 114]}]}, {"sentence": "However , effective treatment of mice with already established tumours was only obtained after combination of vaccination , DC101 and 9H10 treatment in which setting 80 % of the mice rejected their tumours .", "entities": [{"name": "tumours", "type": "Anatomy", "pos": [63, 70]}, {"name": "tumours", "type": "Anatomy", "pos": [198, 205]}]}, {"sentence": "VEGF - targeted therapy : therapeutic potential and recent advances .", "entities": []}, {"sentence": "After over 30 years of theorizing , the use of angiogenesis inhibitors as anticancer therapy has finally moved from the realm of research to reality .", "entities": [{"name": "anticancer", "type": "Anatomy", "pos": [74, 84]}]}, {"sentence": "Normal adult vasculature is generally quiescent in nature , with endothelial cells dividing approximately every 10 years .", "entities": [{"name": "vasculature", "type": "Anatomy", "pos": [13, 24]}, {"name": "endothelial cells", "type": "Anatomy", "pos": [65, 82]}]}, {"sentence": "In contrast , the growth of tumors requires constant vascular growth and remodeling in order for solid tumors to grow beyond 1 - 2 mm ( 3 ) in size .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [28, 34]}, {"name": "vascular", "type": "Anatomy", "pos": [53, 61]}, {"name": "solid tumors", "type": "Anatomy", "pos": [97, 109]}]}, {"sentence": "Vascular endothelial growth factor ( VEGF ) and its receptors are key regulators of the process of angiogenesis , which makes them attractive therapeutic targets .", "entities": []}, {"sentence": "A multitude of VEGF - targeted inhibitory agents are currently being investigated for the treatment of cancer .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [103, 109]}]}, {"sentence": "This review article focuses on recent developments in the use of angiogenesis inhibitors for the treatment of breast , lung , and colorectal cancers .", "entities": [{"name": "breast", "type": "Anatomy", "pos": [110, 116]}, {"name": "lung", "type": "Anatomy", "pos": [119, 123]}, {"name": "colorectal cancers", "type": "Anatomy", "pos": [130, 148]}]}, {"sentence": "MDM2 as a predictor of prostate carcinoma outcome : an analysis of Radiation Therapy Oncology Group Protocol 8610 .", "entities": [{"name": "prostate carcinoma", "type": "Anatomy", "pos": [23, 41]}]}, {"sentence": "BACKGROUND : The MDM2 oncoprotein promotes p53 degradation via ubiquitin , establishing negative feedback control of p53 and consequently affecting cell cycle arrest and apoptosis .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [148, 152]}]}, {"sentence": "The authors evaluated the association between MDM2 expression and local failure , distant metastasis ( DM ) , cause - specific mortality , and overall mortality in men treated in Radiation Therapy Oncology Group 8610 with radiotherapy , with or without androgen deprivation .", "entities": []}, {"sentence": "METHODS : Of the 456 eligible and analyzable patients ( parent cohort ) , adequate archival diagnostic tissue specimens from 108 patients were available for MDM2 analysis ( MDM2 cohort ) .", "entities": [{"name": "tissue specimens", "type": "Anatomy", "pos": [103, 119]}]}, {"sentence": "Cox proportional hazards multivariate analysis ( MVA ) was used to determine the relation of MDM2 to the endpoints .", "entities": []}, {"sentence": "MDM2 overexpression was manually classified as > 5 % nuclear staining .", "entities": [{"name": "nuclear", "type": "Anatomy", "pos": [53, 60]}]}, {"sentence": "An image analysis system was also used to quantify the proportion of tumor nuclei with MDM2 staining ( ACIS index ) and staining intensity .", "entities": [{"name": "tumor nuclei", "type": "Anatomy", "pos": [69, 81]}]}, {"sentence": "RESULTS : Overexpression of MDM2 by manual counts was seen in 44 % ( n = 47 ) of the patients .", "entities": []}, {"sentence": "In the manual count analysis , there was no significant relation between MDM2 overexpression and outcome .", "entities": []}, {"sentence": "The ACIS index , using a cutoff point defined by the median value , < or = 3 % versus > 3 % , was related to 5 - year DM rates in univariate analyses ( 32 . 6 % vs . 45 . 8 % ; P = 0 . 057 ) and MVA ( P = 0 . 06 ) .", "entities": []}, {"sentence": "The intensity of MDM2 staining was not significant .", "entities": []}, {"sentence": "CONCLUSIONS : MDM2 expression quantified by image analysis was weakly associated with DM .", "entities": []}, {"sentence": "The cohort examined was relatively small and with larger patient numbers , MDM2 overexpression may emerge as a more significant covariate .", "entities": []}, {"sentence": "Thrombospondins , metallo proteases and thrombospondin receptors messenger RNA and protein expression in different tumour sublines of the Dunning prostate cancer model .", "entities": [{"name": "tumour sublines", "type": "Anatomy", "pos": [115, 130]}, {"name": "Dunning prostate cancer", "type": "Anatomy", "pos": [138, 161]}]}, {"sentence": "Thrombospondin is a potent inhibitor of angiogenesis and might therefore be important in controlling tumour growth .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [101, 107]}]}, {"sentence": "TSP interacts with a number of proteases and receptors and in this way inhibits stimulation of angiogenesis .", "entities": []}, {"sentence": "An earlier study showed that thrombospondin is expressed in benign prostatic hyperplasia ( BPH ) and high - grade prostatic intraepithelial neoplasia ( PIN ) but is absent in prostate cancer .", "entities": [{"name": "benign prostatic hyperplasia", "type": "Anatomy", "pos": [60, 88]}, {"name": "BPH", "type": "Anatomy", "pos": [91, 94]}, {"name": "high - grade prostatic intraepithelial neoplasia", "type": "Anatomy", "pos": [101, 149]}, {"name": "PIN", "type": "Anatomy", "pos": [152, 155]}, {"name": "prostate cancer", "type": "Anatomy", "pos": [175, 190]}]}, {"sentence": "The present study was therefore designed to evaluate the expression of thrombospondin 1 and 2 ( TSP - 1 , TSP - 2 ) , TSP receptors CD36 and CD47 , and matrix - metalloproteases 2 and 9 ( MMP - , MMP - 9 ) in a rat prostate cancer model .", "entities": [{"name": "prostate cancer", "type": "Anatomy", "pos": [215, 230]}]}, {"sentence": "By using immunohistochemistry , Western blot , and real - time PCR the expression patterns of TSP - 1 , TSP - 2 , CD36 , CD47 , MMP - 2 , and MMP - 9 were investigated in normal rat prostate tissue and five malignant Dunning sublines tissue .", "entities": [{"name": "prostate tissue", "type": "Anatomy", "pos": [182, 197]}, {"name": "malignant Dunning sublines tissue", "type": "Anatomy", "pos": [207, 240]}]}, {"sentence": "TSP - 1 mRNA levels were decreased in all tumours compared with normal prostate .", "entities": [{"name": "tumours", "type": "Anatomy", "pos": [42, 49]}, {"name": "prostate", "type": "Anatomy", "pos": [71, 79]}]}, {"sentence": "However , there was no difference in expression of TSP - 2 and CD36 mRNA in these samples .", "entities": [{"name": "samples", "type": "Anatomy", "pos": [82, 89]}]}, {"sentence": "MMP - 2 was increased with malignancy , but no expression of MMP - 9 was seen .", "entities": []}, {"sentence": "The CD47 receptor did slightly increase with malignancy except for H3327 .", "entities": [{"name": "H3327", "type": "Anatomy", "pos": [67, 72]}]}, {"sentence": "The results showed that thrombospondin is expressed in normal prostate but not in prostate tumours in a rat model .", "entities": [{"name": "prostate", "type": "Anatomy", "pos": [62, 70]}, {"name": "prostate tumours", "type": "Anatomy", "pos": [82, 98]}]}, {"sentence": "Simultaneously , MMP - 2 expression increases with malignancy .", "entities": []}, {"sentence": "Bovine papillomavirus E7 transformation function correlates with cellular p600 protein binding .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [65, 73]}]}, {"sentence": "The E7 oncoprotein of bovine papillomavirus type 1 ( BPV - 1 ) is required for the full transformation activity of the virus .", "entities": []}, {"sentence": "However , the mechanism by which E7 contributes to cellular transformation is unknown .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [51, 59]}]}, {"sentence": "To address this question , we used the proteomic approach of tandem affinity purification to identify cellular proteins that are in complex with E7 , and identified the 600 - kDa protein , p600 , as a binding partner of E7 .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [102, 110]}]}, {"sentence": "The ability of E7 to complex with p600 correlated with its ability to enhance anchorage independence of BPV - 1 E6 - expressing cells .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [128, 133]}]}, {"sentence": "Furthermore , E7 mutant proteins impaired in their ability to bind p600 were transformation defective .", "entities": []}, {"sentence": "Additionally , knockdown of p600 reduced transformation of cells expressing both BPV - 1 E6 and E7 , as well as E6 alone , suggesting that the ability of E7 to transformed cells is mediated , at least in part , through its ability to bind p600 .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [59, 64]}, {"name": "cells", "type": "Anatomy", "pos": [172, 177]}]}, {"sentence": "These data complement work that shows that HPV16 E7 also interacts with p600 , and that this interaction correlates with the ability of HPV16 E7 to transform cells .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [158, 163]}]}, {"sentence": "These studies thus identify p600 as a shared target of the E7 proteins of multiple papillomaviruses .", "entities": []}, {"sentence": "Molecular requirements for epithelial - mesenchymal transition during tumor progression .", "entities": [{"name": "epithelial", "type": "Anatomy", "pos": [27, 37]}, {"name": "mesenchymal", "type": "Anatomy", "pos": [40, 51]}, {"name": "tumor", "type": "Anatomy", "pos": [70, 75]}]}, {"sentence": "Epithelial - mesenchymal transitions ( EMTs ) occur as key steps during embryonic morphogenesis , and are now implicated in the progression of primary tumors towards metastases .", "entities": [{"name": "Epithelial", "type": "Anatomy", "pos": [0, 10]}, {"name": "mesenchymal", "type": "Anatomy", "pos": [13, 24]}, {"name": "embryonic", "type": "Anatomy", "pos": [72, 81]}, {"name": "primary tumors", "type": "Anatomy", "pos": [143, 157]}, {"name": "metastases", "type": "Anatomy", "pos": [166, 176]}]}, {"sentence": "Recent advances have fostered a more detailed understanding of molecular mechanisms and networks governing EMT in tumor progression .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [114, 119]}]}, {"sentence": "Besides TGFbeta and RTK / Ras signaling , autocrine factors and Wnt - , Notch - , Hedgehog - and NF - kappaB - dependent pathways were found to contribute to EMT .", "entities": []}, {"sentence": "Repression of E - cadherin by transcriptional regulators such as Snail or Twist emerges as one critical step driving EMT , and this stage is currently being molecularly linked with many of the new players .", "entities": []}, {"sentence": "Increasing evidence suggests that EMT plays a specific role in the migration of cells from a primary tumor into the circulation and may provide a rationale for developing more effective cancer therapies .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [80, 85]}, {"name": "primary tumor", "type": "Anatomy", "pos": [93, 106]}, {"name": "cancer", "type": "Anatomy", "pos": [186, 192]}]}, {"sentence": "Minimal contribution of marrow - derived endothelial precursors to tumor vasculature .", "entities": [{"name": "marrow - derived endothelial precursors", "type": "Anatomy", "pos": [24, 63]}, {"name": "tumor vasculature", "type": "Anatomy", "pos": [67, 84]}]}, {"sentence": "During embryogenesis , vascular and hemopoietic cells originate from a common precursor , the hemangioblast .", "entities": [{"name": "vascular", "type": "Anatomy", "pos": [23, 31]}, {"name": "hemopoietic cells", "type": "Anatomy", "pos": [36, 53]}, {"name": "precursor", "type": "Anatomy", "pos": [78, 87]}, {"name": "hemangioblast", "type": "Anatomy", "pos": [94, 107]}]}, {"sentence": "Recent evidence suggests the existence of endothelial precursors in adult bone marrow cells , but it is unclear whether those precursors have a role in tumor neovascularization .", "entities": [{"name": "endothelial precursors", "type": "Anatomy", "pos": [42, 64]}, {"name": "bone marrow cells", "type": "Anatomy", "pos": [74, 91]}, {"name": "precursors", "type": "Anatomy", "pos": [126, 136]}, {"name": "tumor", "type": "Anatomy", "pos": [152, 157]}]}, {"sentence": "In this report , we demonstrate that murine bone marrow contains endothelial progenitors , which arise from a cell with self - renewing capacity , and can integrate into tumor microvasculature , albeit at a very low frequency .", "entities": [{"name": "bone marrow", "type": "Anatomy", "pos": [44, 55]}, {"name": "endothelial progenitors", "type": "Anatomy", "pos": [65, 88]}, {"name": "cell", "type": "Anatomy", "pos": [110, 114]}, {"name": "tumor microvasculature", "type": "Anatomy", "pos": [170, 192]}]}, {"sentence": "A transgenic double - reporter strategy allowed us to demonstrate definitively that tumor bone marrow - derived endothelial cells arise by transdifferentiation of marrow progenitors rather than by cell fusion .", "entities": [{"name": "tumor bone marrow - derived endothelial cells", "type": "Anatomy", "pos": [84, 129]}, {"name": "marrow progenitors", "type": "Anatomy", "pos": [163, 181]}, {"name": "cell", "type": "Anatomy", "pos": [197, 201]}]}, {"sentence": "Single cell transplants showed that a common precursor contributes to both the hemopoietic and endothelial lineages , thus demonstrating the presence of an adult hemangioblast .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [7, 11]}, {"name": "precursor", "type": "Anatomy", "pos": [45, 54]}, {"name": "hemopoietic", "type": "Anatomy", "pos": [79, 90]}, {"name": "endothelial lineages", "type": "Anatomy", "pos": [95, 115]}, {"name": "hemangioblast", "type": "Anatomy", "pos": [162, 175]}]}, {"sentence": "Furthermore , we demonstrate that increased vascular endothelial growth factor ( VEGF ) - A secretion by tumor cells , as well as activation of VEGF receptor - 2 in bone marrow cells does not alter the mobilization and incorporation of marrow - derived endothelial progenitors into tumor vasculature .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [105, 116]}, {"name": "bone marrow cells", "type": "Anatomy", "pos": [165, 182]}, {"name": "marrow - derived endothelial progenitors", "type": "Anatomy", "pos": [236, 276]}, {"name": "tumor vasculature", "type": "Anatomy", "pos": [282, 299]}]}, {"sentence": "Finally , in human umbilical cord blood cells , we show that endothelial precursors make up only approximately 1 in 10 ( 7 ) mononuclear cells but are highly enriched in the CD133 + cell population .", "entities": [{"name": "umbilical cord blood cells", "type": "Anatomy", "pos": [19, 45]}, {"name": "endothelial precursors", "type": "Anatomy", "pos": [61, 83]}, {"name": "mononuclear cells", "type": "Anatomy", "pos": [125, 142]}, {"name": "CD133 + cell population", "type": "Anatomy", "pos": [174, 197]}]}, {"sentence": "By ruling out cell fusion , we clearly demonstrate the existence of an adult hemangioblast , but the differentiation of marrow stem cells toward the endothelial lineage is an extremely rare event .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [14, 18]}, {"name": "hemangioblast", "type": "Anatomy", "pos": [77, 90]}, {"name": "marrow stem cells", "type": "Anatomy", "pos": [120, 137]}, {"name": "endothelial lineage", "type": "Anatomy", "pos": [149, 168]}]}, {"sentence": "Furthermore , we show that VEGF - A stimulation of hemopoietic cells does not significantly alter this process .", "entities": [{"name": "hemopoietic cells", "type": "Anatomy", "pos": [51, 68]}]}, {"sentence": "Histopathological development of gastric tumors induced by N - methyl - N ' - nitro - N - nitrosoguanidine in rats .", "entities": [{"name": "gastric tumors", "type": "Anatomy", "pos": [33, 47]}]}, {"sentence": "The development of carcinoma was examined in male Wistar rats ( n = 120 ) exposed to N - methyl - N ' - nitro - N - nitrosoguanidine ( MNNG ) in the drinking water ( 83 micrograms / ml ) for 16 weeks .", "entities": [{"name": "carcinoma", "type": "Anatomy", "pos": [19, 28]}]}, {"sentence": "After MNNG administration , rats were investigated by endoscopic observation , visualization of microvascular structure , and estimation of lectin binding sites .", "entities": [{"name": "microvascular", "type": "Anatomy", "pos": [96, 109]}]}, {"sentence": "Changes of bile reflux to the stomach was observed endoscopically at 24 weeks as well as the development of gastric mucosal erosions .", "entities": [{"name": "bile", "type": "Anatomy", "pos": [11, 15]}, {"name": "stomach", "type": "Anatomy", "pos": [30, 37]}, {"name": "gastric mucosal erosions", "type": "Anatomy", "pos": [108, 132]}]}, {"sentence": "Protruding and expansive ulcerating carcinomas developed at 36 weeks and had a microvascular pattern similar to that of human adenocarcinoma .", "entities": [{"name": "ulcerating carcinomas", "type": "Anatomy", "pos": [25, 46]}, {"name": "microvascular", "type": "Anatomy", "pos": [79, 92]}, {"name": "adenocarcinoma", "type": "Anatomy", "pos": [126, 140]}]}, {"sentence": "Estimation of lectin binding site and pattern was useful to evaluate the malignant potential of cell proliferation .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [96, 100]}]}, {"sentence": "We postulate that endoscopic observation is valuable in investigating the development of gastric carcinoma , and microvascular structure and lectin binding pattern may be useful to demonstrate the mechanism of growth of gastric carcinoma .", "entities": [{"name": "gastric carcinoma", "type": "Anatomy", "pos": [89, 106]}, {"name": "microvascular", "type": "Anatomy", "pos": [113, 126]}, {"name": "gastric carcinoma", "type": "Anatomy", "pos": [220, 237]}]}, {"sentence": "Decrease in c - Myc activity enhances cancer cell sensitivity to vinblastine .", "entities": [{"name": "cancer cell", "type": "Anatomy", "pos": [38, 49]}]}, {"sentence": "The c - myc oncogene encodes for a transcriptional factor involved in many cellular processes such as proliferation , differentiation and apoptosis .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [75, 83]}]}, {"sentence": "According to these different functions , the role of c - Myc protein in cellular sensitivity to anti - cancer drugs is controversial .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [72, 80]}, {"name": "cancer", "type": "Anatomy", "pos": [103, 109]}]}, {"sentence": "We defined the role of c - Myc in cancer cell sensitivity to vinblastine ( VLB ) using human colon cancer cells : LoVo wild - type or transfected with a plasmid containing the human c - myc gene in antisense orientation ( LoVo - mycANS ) .", "entities": [{"name": "cancer cell", "type": "Anatomy", "pos": [34, 45]}, {"name": "colon cancer cells", "type": "Anatomy", "pos": [93, 111]}, {"name": "LoVo", "type": "Anatomy", "pos": [114, 118]}, {"name": "plasmid", "type": "Anatomy", "pos": [153, 160]}, {"name": "LoVo - mycANS", "type": "Anatomy", "pos": [222, 235]}]}, {"sentence": "Analysis of VLB cytotoxicity demonstrated a 3 - fold increase in VLB sensitivity in LoVo - mycANS cells .", "entities": [{"name": "LoVo - mycANS cells", "type": "Anatomy", "pos": [84, 103]}]}, {"sentence": "Comparison between cells revealed different apoptosis kinetics : accumulation of cells in sub - G1 phase and poly ( ADP - ribose ) polymerase cleavage occurred earlier in LoVo - mycANS .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [19, 24]}, {"name": "cells", "type": "Anatomy", "pos": [81, 86]}, {"name": "LoVo - mycANS", "type": "Anatomy", "pos": [171, 184]}]}, {"sentence": "Then , we demonstrated a mitochondrial membrane potential disruption followed by cytochrome c release that indicates the involvement of mitochondria in this apoptotic signaling pathway .", "entities": [{"name": "mitochondrial membrane", "type": "Anatomy", "pos": [25, 47]}, {"name": "mitochondria", "type": "Anatomy", "pos": [136, 148]}]}, {"sentence": "This earlier apoptosis was accompanied by a Bcl - 2 decrease and a p53 increase .", "entities": []}, {"sentence": "In conclusion , the decrease in c - Myc expression enhanced the VLB sensitivity , triggering earlier apoptosis through induction of the intrinsic pathway .", "entities": []}, {"sentence": "Thus , c - myc induction is a resistance factor and our findings suggest that tumors carrying low levels of c - Myc protein could be more responsive to vinca alkaloids treatment .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [78, 84]}]}, {"sentence": "Moreover , the downregulation of c - myc oncogene by an antisense strategy might represent a useful goal for improving the efficacy of this anti - neoplastic drug family .", "entities": [{"name": "neoplastic", "type": "Anatomy", "pos": [147, 157]}]}, {"sentence": "Complications after plate fixation of phalangeal fractures .", "entities": [{"name": "phalangeal", "type": "Anatomy", "pos": [38, 48]}]}, {"sentence": "PURPOSE :", "entities": []}, {"sentence": "To assess the complications after plate fixation of phalangeal fractures , their correlation with the type of injury , and the outcome .", "entities": [{"name": "phalangeal", "type": "Anatomy", "pos": [52, 62]}]}, {"sentence": "METHODS :", "entities": []}, {"sentence": "We retrospectively reviewed the clinical records and the x - rays of 54 consecutive patients with 64 phalangeal fractures treated by open reduction and plate fixation with regard to fracture healing , plate loosening or failure , infection , complex regional pain syndrome , pain , return to work , and range of motion .", "entities": [{"name": "phalangeal", "type": "Anatomy", "pos": [101, 111]}]}, {"sentence": "RESULTS :", "entities": []}, {"sentence": "In 31 out of 54 patients ( 57 % ) and 33 out of 64 fractures ( 52 % ) , one or more major complications occurred .", "entities": []}, {"sentence": "Stiffness ( definition is composite range of motion of metaphalangeal , proximal interphalangeal , and distal interphalangeal joints added together equaling < 180 degrees ) contributed the highest number ( 22 patients , 24 fractures ) .", "entities": [{"name": "metaphalangeal", "type": "Anatomy", "pos": [55, 69]}, {"name": "proximal interphalangeal", "type": "Anatomy", "pos": [72, 96]}, {"name": "distal interphalangeal joints", "type": "Anatomy", "pos": [103, 132]}]}, {"sentence": "The complication rates were not different whether the fracture was open or closed , if it was located in the proximal or middle phalanx , the presence or absence of an associated soft tissue lesion , and the patient ' s occupation .", "entities": [{"name": "middle phalanx", "type": "Anatomy", "pos": [121, 135]}, {"name": "soft tissue lesion", "type": "Anatomy", "pos": [179, 197]}]}, {"sentence": "CONCLUSIONS :", "entities": []}, {"sentence": "In spite of early mobilization , stiffness is the most frequent complication after open reduction and plate fixation of phalangeal fractures .", "entities": [{"name": "phalangeal", "type": "Anatomy", "pos": [120, 130]}]}, {"sentence": "The undue amount of scarring and adhesion may arise from the implant itself or the difficulty in finding the perfect mixture between the minimal surgical invasiveness and a sufficient restoration of skeletal stability .", "entities": [{"name": "skeletal", "type": "Anatomy", "pos": [199, 207]}]}, {"sentence": "Otherwise , plate fixation of unstable and complex phalangeal fractures proved efficient and reliable , although not free of potential problems .", "entities": [{"name": "phalangeal", "type": "Anatomy", "pos": [51, 61]}]}, {"sentence": "Alteration of homeobox gene expression by N - ras transformation of PA - 1 human teratocarcinoma cells .", "entities": [{"name": "PA - 1 human teratocarcinoma cells", "type": "Anatomy", "pos": [68, 102]}]}, {"sentence": "We used a series of cell clones from a human teratocarcinoma cell line , PA - 1 , to study the effect of transformation by an activated N - ras oncogene on the expression of genes involved in retinoic acid ( RA ) - induced differentiation and growth regulation .", "entities": [{"name": "cell clones", "type": "Anatomy", "pos": [20, 31]}, {"name": "teratocarcinoma cell line", "type": "Anatomy", "pos": [45, 70]}, {"name": "PA - 1", "type": "Anatomy", "pos": [73, 79]}]}, {"sentence": "Recently , it has been shown that expression of human HOX 2 genes is sequentially activated by RA beginning from Hox 2 . 9 at the 3 ' end of the HOX 2 cluster ( A . Simeone , D . Acampora , L . Arcioni , P . W . Andrews , E . Boncinelli , and F . Mavilio , Nature [ London ] 346 : 763 - 766 , 1990 ) .", "entities": []}, {"sentence": "We now report that six different genes of the cluster HOX 1 are sequentially induced by RA in a similar temporal pattern , beginning with genes at the 3 ' end of the cluster .", "entities": []}, {"sentence": "However , in N - ras - transformed cell clones , RA - induced expression of these homeobox genes is delayed .", "entities": [{"name": "cell clones", "type": "Anatomy", "pos": [35, 46]}]}, {"sentence": "Hox 1 . 4 and Hox 1 . 3 , genes abundantly induced in nontransformed clones after 3 days of RA treatment , are expressed in N - ras - transformed cells only after 10 days of RA treatment .", "entities": [{"name": "clones", "type": "Anatomy", "pos": [69, 75]}, {"name": "cells", "type": "Anatomy", "pos": [146, 151]}]}, {"sentence": "At this time , the cells ' growth is arrested at very high density , and no differentiated morphologic characteristics are observed .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [19, 24]}]}, {"sentence": "Constitutive expression of a transfected Hox 1 . 4 gene under the control of a simian virus 40 promotor leads to differentiated cell morphology similar to that of the RA - induced phenotype and restores the growth - inhibitory effects of RA in N - ras - transformed cells .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [128, 132]}, {"name": "cells", "type": "Anatomy", "pos": [266, 271]}]}, {"sentence": "These observations provide evidence that enhanced proliferation in N - ras - transformed cells compromises teratocarcinoma cell differentiation by a mechanism that transiently suppresses homeobox gene induction and implies a central role for homeobox genes in RA - induced cell differentiation .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [89, 94]}, {"name": "teratocarcinoma cell", "type": "Anatomy", "pos": [107, 127]}, {"name": "cell", "type": "Anatomy", "pos": [273, 277]}]}, {"sentence": "We conclude that stimulation of a putative growth factor signal pathway , associated with ras - induced proliferation , transiently suppresses the induction of transcription factors functionally involved in cell growth and differentiation .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [207, 211]}]}, {"sentence": "High - Dose celecoxib and metronomic \" low - dose \" cyclophosphamide is an effective and safe therapy in patients with relapsed and refractory aggressive histology non - Hodgkin ' s lymphoma .", "entities": [{"name": "non - Hodgkin ' s lymphoma", "type": "Anatomy", "pos": [164, 190]}]}, {"sentence": "PURPOSE : Angiogenesis is increased in aggressive histology non - Hodgkin ' s lymphoma and may be a target with selective cyclooxygenase - 2 inhibition and metronomic chemotherapy .", "entities": [{"name": "non - Hodgkin ' s lymphoma", "type": "Anatomy", "pos": [60, 86]}]}, {"sentence": "EXPERIMENTAL DESIGN : We assessed response , toxicity , and biomarkers of angiogenesis to low - dose cyclophosphamide ( 50 mg p . o . o . d . ) and high - dose celecoxib ( 400 mg p . o . b . i . d . ) in adult patients with relapsed or refractory aggressive non - Hodgkin ' s lymphoma in a multicenter phase II prospective study .", "entities": [{"name": "non - Hodgkin ' s lymphoma", "type": "Anatomy", "pos": [258, 284]}]}, {"sentence": "RESULTS : Thirty - two of 35 patients ( median age , 62 years ) are evaluable for response .", "entities": []}, {"sentence": "Patients had primarily relapsed diffuse large B - cell lymphoma ( 63 % ) were heavily pretreated ( median of three regimens ) and high risk ( 79 % international prognostic index , greater than or = 2 ) and 34 % were relapsed after autologous stem cell transplant .", "entities": [{"name": "B - cell lymphoma", "type": "Anatomy", "pos": [46, 63]}, {"name": "stem cell", "type": "Anatomy", "pos": [242, 251]}]}, {"sentence": "With a median follow - up of 8 . 4 months , the overall best response rate is 37 % ( 2 complete clinical response / complete clinical response unconfirmed and 9 partial response ) , with 22 % achieving stable disease .", "entities": []}, {"sentence": "Median overall and progression - free survivals are 14 . 4 and 4 . 7 months , respectively .", "entities": []}, {"sentence": "The median response duration was 8 . 2 months .", "entities": []}, {"sentence": "The most common toxicity was skin rash ( 40 % ) ; myelosuppression and gastrointestinal side effects were uncommon .", "entities": [{"name": "skin", "type": "Anatomy", "pos": [29, 33]}, {"name": "gastrointestinal", "type": "Anatomy", "pos": [71, 87]}]}, {"sentence": "Three patients developed deep vein thromboses and two heavily pretreated patients developed treatment - related acute myelogenous leukemia or myelodysplasia after 3 . 7 and 12 months of therapy .", "entities": [{"name": "deep vein thromboses", "type": "Anatomy", "pos": [25, 45]}, {"name": "acute myelogenous leukemia", "type": "Anatomy", "pos": [112, 138]}, {"name": "myelodysplasia", "type": "Anatomy", "pos": [142, 156]}]}, {"sentence": "Circulating endothelial cells and their precursors declined and remained low in responders , whereas plasma vascular endothelial growth factor trended to decline in responding patients but increase in nonresponders .", "entities": [{"name": "endothelial cells", "type": "Anatomy", "pos": [12, 29]}, {"name": "precursors", "type": "Anatomy", "pos": [40, 50]}, {"name": "plasma", "type": "Anatomy", "pos": [101, 107]}]}, {"sentence": "Trough celecoxib levels achieved targeted \" antiangiogenic \" levels .", "entities": []}, {"sentence": "CONCLUSIONS : Low - dose cyclophosphamide and high - dose celecoxib is well tolerated and active in pretreated aggressive non - Hodgkin ' s lymphoma .", "entities": [{"name": "non - Hodgkin ' s lymphoma", "type": "Anatomy", "pos": [122, 148]}]}, {"sentence": "Close surveillance for arterial and venous thrombotic events is recommended .", "entities": [{"name": "arterial", "type": "Anatomy", "pos": [23, 31]}, {"name": "venous", "type": "Anatomy", "pos": [36, 42]}]}, {"sentence": "The decline in circulating endothelial cells and their precursors suggests that this combination may be working by inhibiting angiogenesis but should be validated in a larger patient sample .", "entities": [{"name": "circulating endothelial cells", "type": "Anatomy", "pos": [15, 44]}, {"name": "precursors", "type": "Anatomy", "pos": [55, 65]}]}, {"sentence": "Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization secondary to pathologic myopia : long - term study .", "entities": [{"name": "subfoveal choroidal", "type": "Anatomy", "pos": [42, 61]}]}, {"sentence": "PURPOSE : To assess the safety and effectiveness of photodynamic therapy ( PDT ) with verteporfin for subfoveal choroidal neovascularization ( CNV ) secondary to pathologic myopia ( PM ) .", "entities": [{"name": "subfoveal choroidal", "type": "Anatomy", "pos": [102, 121]}]}, {"sentence": "METHODS : Sixty - two patients ( 62 eyes ) with PM underwent PDT according to the guidelines of the Verteporfin in Photodynamic Therapy Study .", "entities": [{"name": "eyes", "type": "Anatomy", "pos": [36, 40]}]}, {"sentence": "Clinical evaluations performed at all study visits included measurement of best - corrected Snellen visual acuity , slit - lamp biomicroscopy , and fundus fluorescein angiography .", "entities": [{"name": "fundus", "type": "Anatomy", "pos": [148, 154]}]}, {"sentence": "Patients were followed up at 1 month and 3 months after treatment and thereafter at 3 - month intervals .", "entities": []}, {"sentence": "RESULTS : The final visual acuity of the study patients , after a median follow - up of 31 months , improved by greater than or = 1 Snellen lines in 8 patients ( 13 % ) , deteriorated in 20 ( 32 % ) , and remained stable in 34 ( 55 % ) .", "entities": []}, {"sentence": "The baseline visual acuity was similar in the various study groups .", "entities": []}, {"sentence": "The final mean visual acuity in group A ( 55 years of age or younger ) was 20 / 80 and significantly ( P = 0 . 006 ) better than that ( 20 / 138 ) in group B ( older than 55 years of age ) .", "entities": []}, {"sentence": "The mean final visual acuity in eyes with higher refractive error at baseline ( greater than - 17 diopters ) was significantly better ( P = 0 . 014 ) than that in eyes with lower refractive error ( - 6 to - 10 diopters ) .", "entities": [{"name": "eyes", "type": "Anatomy", "pos": [32, 36]}, {"name": "eyes", "type": "Anatomy", "pos": [163, 167]}]}, {"sentence": "CNV size did not affect visual outcomes .", "entities": []}, {"sentence": "CONCLUSION : PDT preserves vision in patients with CNV associated with PM .", "entities": []}, {"sentence": "Younger patients and eyes with higher refractive error appear more likely to benefit from PDT with verteporfin .", "entities": [{"name": "eyes", "type": "Anatomy", "pos": [21, 25]}]}, {"sentence": "Carcinogenesis and transcriptional regulation through Maf recognition elements .", "entities": []}, {"sentence": "Many studies on carcinogenesis carried out early in the last century are united on the consensus that cancer is a genetic disease .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [102, 108]}]}, {"sentence": "Cancer cells typically display gene dysfunction and endogenous or exogenous insults resulting in gene dysfunction are often carcinogenic .", "entities": [{"name": "Cancer cells", "type": "Anatomy", "pos": [0, 12]}]}, {"sentence": "Recent advances in stem cell biology added the new concept that cancer originates from a single cancer - initiating cell .", "entities": [{"name": "stem cell", "type": "Anatomy", "pos": [19, 28]}, {"name": "cancer", "type": "Anatomy", "pos": [64, 70]}, {"name": "cancer", "type": "Anatomy", "pos": [96, 102]}, {"name": "cell", "type": "Anatomy", "pos": [116, 120]}]}, {"sentence": "To understand the molecular basis of carcinogenesis from the beginning to the full acquirement of malignancy , factors concerned with carcinogenesis were categorized into three groups : those guarding and stabilizing genomes , those regulating cell proliferation , and those conferring resistance to various micro - environmental stresses .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [244, 248]}]}, {"sentence": "One example of particular interest is the Keap1 - Nrf2 system since , according to recent studies , it has turned out to be ambivalent .", "entities": []}, {"sentence": "Nrf2 heterodimerizes with small Maf protein to strongly activate transcription through the Maf recognition element ( MARE ) and Keap1 is an inhibitory regulator of Nrf2 .", "entities": []}, {"sentence": "The genes regulated by Nrf2 are very important for cellular protection of the genome from xenobiotic and oxidative stresses and , consequently , for preventing carcinogenesis .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [51, 59]}]}, {"sentence": "This implies that enhancing Nrf2 activity is a promising method for thwarting cancer .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [78, 84]}]}, {"sentence": "On the contrary , the constitutive activation of Nrf2 due to mutations in the keap1 gene is characteristically observed in lung cancer cells , suggesting that induced expression of Nrf2 target genes favors the prevalence of cancer cells .", "entities": [{"name": "lung cancer cells", "type": "Anatomy", "pos": [123, 140]}, {"name": "cancer cells", "type": "Anatomy", "pos": [224, 236]}]}, {"sentence": "Angiotensin II induces soluble fms - Like tyrosine kinase - 1 release via calcineurin signaling pathway in pregnancy .", "entities": []}, {"sentence": "Maternal endothelial dysfunction in preeclampsia is associated with increased soluble fms - like tyrosine kinase - 1 ( sFlt - 1 ) , a circulating antagonist of vascular endothelial growth factor and placental growth factor .", "entities": [{"name": "endothelial", "type": "Anatomy", "pos": [9, 20]}]}, {"sentence": "Angiotensin II ( Ang II ) is a potent vasoconstrictor that increases concomitant with sFlt - 1 during pregnancy .", "entities": []}, {"sentence": "Therefore , we speculated that Ang II may promote the expression of sFlt - 1 in pregnancy .", "entities": []}, {"sentence": "Here we report that infusion of Ang II significantly increases circulating levels of sFlt - 1 in pregnant mice , thereby demonstrating that Ang II is a regulator of sFlt - 1 secretion in vivo .", "entities": []}, {"sentence": "Furthermore , Ang II stimulated sFlt - 1 production in a dose - and time - dependent manner from human villous explants and cultured trophoblasts but not from endothelial cells , suggesting that trophoblasts are the primary source of sFlt - 1 during pregnancy .", "entities": [{"name": "trophoblasts", "type": "Anatomy", "pos": [133, 145]}, {"name": "endothelial cells", "type": "Anatomy", "pos": [159, 176]}, {"name": "trophoblasts", "type": "Anatomy", "pos": [195, 207]}]}, {"sentence": "As expected , Ang II - induced sFlt - 1 secretion resulted in the inhibition of endothelial cell migration and in vitro tube formation .", "entities": [{"name": "endothelial cell", "type": "Anatomy", "pos": [80, 96]}, {"name": "tube", "type": "Anatomy", "pos": [120, 124]}]}, {"sentence": "In vitro and in vivo studies with losartan , small interfering RNA specific for calcineurin and FK506 demonstrated that Ang II - mediated sFlt - 1 release was via Ang II type 1 receptor activation and calcineurin signaling , respectively .", "entities": []}, {"sentence": "These findings reveal a previously unrecognized regulatory role for Ang II on sFlt - 1 expression in murine and human pregnancy and suggest that elevated sFlt - 1 levels in preeclampsia may be caused by a dysregulation of the local renin / angiotensin system .", "entities": []}, {"sentence": "p21 delays tumor onset by preservation of chromosomal stability .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [11, 16]}, {"name": "chromosomal", "type": "Anatomy", "pos": [42, 53]}]}, {"sentence": "The p53 protein suppresses tumorigenesis by initiating cellular functions such as cell cycle arrest and apoptosis in response to DNA damage .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [55, 63]}, {"name": "cell", "type": "Anatomy", "pos": [82, 86]}]}, {"sentence": "A p53 mutant , p53R172P , which is deficient for apoptosis but retains a partial cell cycle arrest function , delays tumor onset in mice .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [81, 85]}, {"name": "tumor", "type": "Anatomy", "pos": [117, 122]}]}, {"sentence": "Remarkably , lymphomas arising in Trp53 ( 515C / 515C ) mice ( encoding p53R172P ) retain stable genomes .", "entities": [{"name": "lymphomas", "type": "Anatomy", "pos": [13, 22]}]}, {"sentence": "Given the dominant role of p21 in p53 cell cycle control , we crossed Trp53 ( 515C / 515C ) mice onto a p21 - null background to determine whether p21 was required for maintaining chromosomal stability and delaying tumor onset .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [38, 42]}, {"name": "chromosomal", "type": "Anatomy", "pos": [180, 191]}, {"name": "tumor", "type": "Anatomy", "pos": [215, 220]}]}, {"sentence": "Loss of p21 completely abolished the cell cycle arrest function of p53R172P and accelerated tumor onset in Trp53 ( 515C / 515C ) mice .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [37, 41]}, {"name": "tumor", "type": "Anatomy", "pos": [92, 97]}]}, {"sentence": "Cytogenetic examination of Trp53 ( 515C / 515C ) p21 ( - / - ) sarcomas and lymphomas revealed aneuploidy and chromosomal aberrations that were absent in Trp53 ( 515C / 515C ) malignancies .", "entities": [{"name": "sarcomas", "type": "Anatomy", "pos": [63, 71]}, {"name": "lymphomas", "type": "Anatomy", "pos": [76, 85]}, {"name": "chromosomal aberrations", "type": "Anatomy", "pos": [110, 133]}, {"name": "malignancies", "type": "Anatomy", "pos": [176, 188]}]}, {"sentence": "Thus , p21 coupled p53 - dependent checkpoint control and preservation of chromosomal stability , and cooperated with apoptosis in suppressing tumor onset in mice .", "entities": [{"name": "chromosomal", "type": "Anatomy", "pos": [74, 85]}, {"name": "tumor", "type": "Anatomy", "pos": [143, 148]}]}, {"sentence": "[ Diagnostic value of DNA , RNA and proliferating cell nuclear antigen examination in malignant pleural effusions by flow cytometry ] .", "entities": [{"name": "malignant pleural effusions", "type": "Anatomy", "pos": [86, 113]}]}, {"sentence": "OBJECTIVE :", "entities": []}, {"sentence": "To study the diagnostic value of DNA , RNA and proliferating cell nuclear antigen ( PCNA ) examination in malignant effusion by multiparametric flow cytometry , and therefore to provide proof for clinical application .", "entities": [{"name": "malignant effusion", "type": "Anatomy", "pos": [106, 124]}]}, {"sentence": "METHODS :", "entities": []}, {"sentence": "Forty seven patients with pleural effusions in our hospital from August 2003 to February 2004 were divided into two groups : 19 suffering from benign pleural effusions and 28 from malignant effusions confirmed by pathologic examination .", "entities": [{"name": "pleural effusions", "type": "Anatomy", "pos": [26, 43]}, {"name": "benign pleural effusions", "type": "Anatomy", "pos": [143, 167]}, {"name": "malignant effusions", "type": "Anatomy", "pos": [180, 199]}]}, {"sentence": "The cells for diagnosis were divided into four groups stained by PI ( Propidium - iodide ) , PY ( Pyronin ) , PCNA - FITC and PCNA - mouse - alpha - 2a .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [4, 9]}]}, {"sentence": "The specimens were analyzed by a flow cytometer ( FacS Caliber , Becton Dickinson ) .", "entities": [{"name": "specimens", "type": "Anatomy", "pos": [4, 13]}]}, {"sentence": "The sensitivity and the specificity of each examination and combined examination were calculated by statistic software SPSS 13 . 0 .", "entities": []}, {"sentence": "RESULTS :", "entities": []}, {"sentence": "( 1 ) The expression of DI , RI , and PI in benign pleural effusion was 1 . 03 + / - 0 . 06 , 10 . 03 + / - 0 . 54 , and ( 4 . 86 + / - 0 . 72 ) % , respectively , and those in malignant ones was 1 . 26 + / - 0 . 17 , 11 . 65 + / - 1 . 45 , and ( 11 . 97 + / - 1 . 50 ) % , respectively , the difference being statistically significant .", "entities": [{"name": "benign pleural effusion", "type": "Anatomy", "pos": [44, 67]}, {"name": "malignant ones", "type": "Anatomy", "pos": [177, 191]}]}, {"sentence": "The cutoff value of DI , RI and PI was 1 . 10 % , 10 . 75 % and 4 . 56 % , and the sensitivity of DI examination was 89 . 3 % , 78 . 6 % , 75 . 0 % , and the specificity was 89 . 5 % , 98 . 5 % , 84 . 2 % , respectively .", "entities": []}, {"sentence": "( 2 ) In 6 cases suffering from malignant pleural effusions , RI was positive but DI was negative , indicating that DI combined with RI examination was better than DI examination alone .", "entities": [{"name": "malignant pleural effusions", "type": "Anatomy", "pos": [32, 59]}]}, {"sentence": "( 3 ) In 5 cases suffering from malignant pleural effusions confirmed by tissue examination , the cytology was negative , but the result of DI and RI was abnormal , indicating that flow cytometry was complementary to pathologic examination .", "entities": [{"name": "malignant pleural effusions", "type": "Anatomy", "pos": [32, 59]}, {"name": "tissue", "type": "Anatomy", "pos": [73, 79]}]}, {"sentence": "( 4 ) The sensitivity of DI + RI , DI + PI , RI + PI and DI + RI + PI combined examination was 98 . 2 % , 89 . 3 % , 89 . 3 % , 92 . 9 % ; the specificity was 84 . 2 % , 89 . 5 % , 84 . 2 % , 94 . 2 % respectively .", "entities": []}, {"sentence": "The results demonstrated that DI + RI + PI combined examination was the best , which showed the least false negative and false positive results .", "entities": []}, {"sentence": "The sensitivity of DI + RI combined examination was 98 . 2 % , but the specificity was 84 . 2 % , the false positive rate being higher than DI + RI + PI combined examination .", "entities": []}, {"sentence": "In none of the benign pleural effusions was the DI + RI + PI higher than the cutoff value , suggesting that combined examination can exclude benign pleural effusions .", "entities": [{"name": "benign pleural effusions", "type": "Anatomy", "pos": [15, 39]}, {"name": "benign pleural effusions", "type": "Anatomy", "pos": [141, 165]}]}, {"sentence": "CONCLUSIONS :", "entities": []}, {"sentence": "DNA , RNA and PCNA examinations by flow cytometry are of value in the diagnosis of malignant effusion , especially for cases which can not be diagnosed by cytological examination .", "entities": [{"name": "malignant effusion", "type": "Anatomy", "pos": [83, 101]}]}, {"sentence": "DI + RI + PI combined examination showed better results with the lowest false negative and false positive rates .", "entities": []}, {"sentence": "Schizophrenia : a common disease caused by multiple rare alleles .", "entities": []}, {"sentence": "Schizophrenia is widely held to stem from the combined effects of multiple common polymorphisms , each with a small impact on disease risk .", "entities": []}, {"sentence": "We suggest an alternative view : that schizophrenia is highly heterogeneous genetically and that many predisposing mutations are highly penetrant and individually rare , even specific to single cases or families .", "entities": []}, {"sentence": "This \" common disease - - rare alleles \" hypothesis is supported by recent findings in human genomics and by allelic and locus heterogeneity for other complex traits .", "entities": []}, {"sentence": "We review the implications of this model for gene discovery research in schizophrenia .", "entities": []}, {"sentence": "Mechanisms for the magnolol - induced cell death of CGTH W - 2 thyroid carcinoma cells .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [38, 42]}, {"name": "CGTH W - 2 thyroid carcinoma cells", "type": "Anatomy", "pos": [52, 86]}]}, {"sentence": "Magnolol , a substance purified from the bark of Magnolia officialis , inhibits cell proliferation and induces apoptosis in a variety of cancer cells .", "entities": [{"name": "bark", "type": "Anatomy", "pos": [41, 45]}, {"name": "cell", "type": "Anatomy", "pos": [80, 84]}, {"name": "cancer cells", "type": "Anatomy", "pos": [137, 149]}]}, {"sentence": "The aim of this study was to study the effects of magnolol on CGTH W - 2 thyroid carcinoma cells .", "entities": [{"name": "CGTH W - 2 thyroid carcinoma cells", "type": "Anatomy", "pos": [62, 96]}]}, {"sentence": "After 24 h treatment with 80 microM magnolol in serum - containing medium , about 50 % of the cells exhibited apoptotic features and 20 % necrotic features .", "entities": [{"name": "serum", "type": "Anatomy", "pos": [48, 53]}, {"name": "cells", "type": "Anatomy", "pos": [94, 99]}]}, {"sentence": "Cytochrome - c staining was diffused in the cytoplasm of the apoptotic cells , but restricted to the mitochondria in control cells .", "entities": [{"name": "cytoplasm", "type": "Anatomy", "pos": [44, 53]}, {"name": "cells", "type": "Anatomy", "pos": [71, 76]}, {"name": "mitochondria", "type": "Anatomy", "pos": [101, 113]}, {"name": "cells", "type": "Anatomy", "pos": [125, 130]}]}, {"sentence": "Western blot analyses showed an increase in levels of activated caspases ( caspase - 3 and - 7 ) and of cleaved poly ( ADP - ribose ) polymerase ( PARP ) by magnolol .", "entities": []}, {"sentence": "Concomitantly , immunostaining for apoptosis inducing factor ( AIF ) showed a time - dependent translocation from the mitochondria to the nucleus .", "entities": [{"name": "mitochondria", "type": "Anatomy", "pos": [118, 130]}, {"name": "nucleus", "type": "Anatomy", "pos": [138, 145]}]}, {"sentence": "Inhibition of either PARP or caspase activity blocked magnolol - induced apoptosis , supporting the involvement of the caspases and PARP .", "entities": []}, {"sentence": "In addition , magnolol activated phosphatase and tensin homolog deleted on chromosome 10 ( PTEN ) and inactivated Akt by decreasing levels of phosphorylated PTEN and phosphorylated Akt .", "entities": []}, {"sentence": "These data suggest that magnolol promoted apoptosis probably by alleviating the inhibitory effect of Akt on caspase 9 .", "entities": []}, {"sentence": "Furthermore , inhibition of PARP activity , but not of caspase activity , completely prevented magnolol - induced necrosis , suggesting the notion that it might be caused by depletion of intracellular ATP levels due to PARP activation .", "entities": [{"name": "intracellular", "type": "Anatomy", "pos": [187, 200]}]}, {"sentence": "These results show that magnolol initiates apoptosis via the cytochrome - c / caspase 3 / PARP / AIF and PTEN / Akt / caspase 9 / PARP pathways and necrosis via PARP activation .", "entities": []}, {"sentence": "Antimicrobial prophylaxis in vaginal gynecologic surgery : a prospective randomized study comparing amoxicillin - clavulanic acid with cefazolin .", "entities": [{"name": "vaginal", "type": "Anatomy", "pos": [29, 36]}]}, {"sentence": "The aim of this prospective , randomized study was to compare amoxicillin - clavulanic acid with cefazolin as ultra - short term prophylaxis in vaginal gynecologic surgery .", "entities": [{"name": "vaginal", "type": "Anatomy", "pos": [144, 151]}]}, {"sentence": "It was conducted at the Department of Obstetrics and Gynecology , University of Bari .", "entities": []}, {"sentence": "Patients were randomly allocated to receive amoxicillin - clavulanic acid ( 2 . 2 g ) [ Group A ] or cefazolin ( 2 g ) [ Group B ] as a single dose 30 minutes before surgery .", "entities": []}, {"sentence": "Each patient was assessed daily until discharge to evidence febrile status and the presence of infections at the operative site , urinary tract and respiratory tract .", "entities": [{"name": "site", "type": "Anatomy", "pos": [123, 127]}, {"name": "urinary tract", "type": "Anatomy", "pos": [130, 143]}, {"name": "respiratory tract", "type": "Anatomy", "pos": [148, 165]}]}, {"sentence": "In the amoxicillin - clavulanic acid ( Group A ) and cefazolin ( Group B ) groups , overall 88 and 90 patients , respectively , were evaluable for prophylactic efficacy at hospital discharge .", "entities": []}, {"sentence": "Infectious complications were infrequent in both arms , with febrile morbidity occurring in 4 ( 4 . 5 % ) and 16 ( 8 . 9 % ) patients respectively in the amoxicillin - clavulanic acid and cefazolin groups ( p = 0 . 016 ) .", "entities": [{"name": "arms", "type": "Anatomy", "pos": [49, 53]}]}, {"sentence": "Urinary tract infections were higher but not significantly in the amoxicillin - clavulanic acid group ( 6 . 8 % versus 4 . 4 % ) , whereas asymptomatic bacteriuria was detected in 2 . 2 % of the patients in both groups .", "entities": [{"name": "Urinary tract", "type": "Anatomy", "pos": [0, 13]}]}, {"sentence": "There was no respiratory tract infection or septic death in either group .", "entities": [{"name": "respiratory tract", "type": "Anatomy", "pos": [13, 30]}]}, {"sentence": "It is concluded that ultra - short term prophylaxis with both amoxicillin - clavulanic acid and cefazolin is safe and effective in elective vaginal gynecologic surgery .", "entities": [{"name": "vaginal", "type": "Anatomy", "pos": [140, 147]}]}, {"sentence": "Quantitative sequencing of complex mixtures of heterochitooligosaccharides by vMALDI - linear ion trap mass spectrometry .", "entities": []}, {"sentence": "Heterochitooligosaccharides possess interesting biological properties .", "entities": []}, {"sentence": "Isobaric mixtures of such linear heterochitooligosaccharides can be obtained by chemical or enzymatic degradation of chitosan .", "entities": []}, {"sentence": "However , the separation of such mixtures is a challenging analytical problem which is so far unresolved .", "entities": []}, {"sentence": "It is shown that these isobaric mixtures can be sequenced and quantified simultaneously using standard derivatization and multistage tandem mass spectrometric techniques .", "entities": []}, {"sentence": "A linear ion trap mass spectrometer equipped with a vacuum matrix - assisted laser desorption ionization ( vMALDI ) source is used to perform MS2 as well as MS3 experiments .", "entities": []}, {"sentence": "Adaptive landscapes and emergent phenotypes : why do cancers have high glycolysis ?", "entities": [{"name": "cancers", "type": "Anatomy", "pos": [53, 60]}]}, {"sentence": "Investigating the causes of increased aerobic glycolysis in tumors ( Warburg Effect ) has gone in and out of fashion many times since it was first described almost a century ago .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [60, 66]}]}, {"sentence": "The field is currently in ascendance due to two factors .", "entities": []}, {"sentence": "Over a million FDG - PET studies have unequivocally identified increased glucose uptake as a hallmark of metastatic cancer in humans .", "entities": [{"name": "metastatic cancer", "type": "Anatomy", "pos": [105, 122]}]}, {"sentence": "These observations , combined with new molecular insights with HIF - 1alpha and c - myc , have rekindled an interest in this important phenotype .", "entities": []}, {"sentence": "A preponderance of work has been focused on the molecular mechanisms underlying this effect , with the expectation that a mechanistic understanding may lead to novel therapeutic approaches .", "entities": []}, {"sentence": "There is also an implicit assumption that a mechanistic understanding , although fundamentally reductionist , will nonetheless lead to a more profound teleological understanding of the need for altered metabolism in invasive cancers .", "entities": [{"name": "invasive cancers", "type": "Anatomy", "pos": [216, 232]}]}, {"sentence": "In this communication , we describe an alternative approach that begins with teleology ; i . e . adaptive landscapes and selection pressures that promote emergence of aerobic glycolysis during the somatic evolution of invasive cancer .", "entities": [{"name": "invasive cancer", "type": "Anatomy", "pos": [218, 233]}]}, {"sentence": "Mathematical models and empirical observations are used to define the adaptive advantage of aerobic glycolysis that would explain its remarkable prevalence in human cancers .", "entities": [{"name": "cancers", "type": "Anatomy", "pos": [165, 172]}]}, {"sentence": "These studies have led to the hypothesis that increased consumption of glucose in metastatic lesions is not used for substantial energy production via Embden - Meyerhoff glycolysis , but rather for production of acid , which gives the cancer cells a competitive advantage for invasion .", "entities": [{"name": "metastatic lesions", "type": "Anatomy", "pos": [82, 100]}, {"name": "cancer cells", "type": "Anatomy", "pos": [235, 247]}]}, {"sentence": "Alternative hypotheses , wherein the glucose is used for generation of reducing equivalents ( NADPH ) or anabolic precursors ( ribose ) are also discussed .", "entities": []}, {"sentence": "Ectopic decorin expression up - regulates VEGF expression in mouse cerebral endothelial cells via activation of the transcription factors Sp1 , HIF1alpha , and Stat3 .", "entities": [{"name": "cerebral endothelial cells", "type": "Anatomy", "pos": [67, 93]}]}, {"sentence": "We demonstrate that a proteoglycan decorin ( DCN ) up - regulates the vascular endothelial growth factor ( VEGF ) expression with activation of VEGF regulating transcription factors Sp1 , hypoxia - inducible factor 1alpha ( HIF1alpha ) , and signal transducer and activator of transcription 3 ( Stat3 ) via epidermal growth factor receptor ( EGFR ) , mitogen - activated protein kinase extracellular signal - regulated kinase 1 / 2 ( ERK1 / 2 ) , and protein kinase B ( AKT ) pathways in DCN transfected mouse cerebral endothelial ( MCE ) cells .", "entities": [{"name": "cerebral endothelial ( MCE ) cells", "type": "Anatomy", "pos": [510, 544]}]}, {"sentence": "Treatment with pharmacological inhibitors and small interfering RNAs reveal that induction and activation of Sp1 , HIF1alpha , and Stat3 facilitate their nuclear localization and binding to their specific motifs of the VEGF promoter and induce VEGF expression via two independent pathways , DCN / EGFR / phosphoinositide - 3 kinase / AKT and DCN / EGFR / ERK1 / 2 , respectively , in DCN synthesizing MCE cells .", "entities": [{"name": "nuclear", "type": "Anatomy", "pos": [154, 161]}, {"name": "MCE cells", "type": "Anatomy", "pos": [401, 410]}]}, {"sentence": "The cell type specific glycosylation protects Sp1 and HIF1alpha from proteosome degradation and plays an important and novel role in the regulation of VEGF in DCN transfected MCE cells .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [4, 8]}, {"name": "MCE cells", "type": "Anatomy", "pos": [175, 184]}]}, {"sentence": "Induction of gelatinases ( matrix metalloproteinase 2 and 9 ) , the serine protease tissue plasminogen activator and plasmin by DCN transfection in MCE cells leads to extracellular proteolysis and to release of matrix - bound VEGF and activation of angiogenesis .", "entities": [{"name": "MCE cells", "type": "Anatomy", "pos": [148, 157]}, {"name": "extracellular", "type": "Anatomy", "pos": [167, 180]}]}, {"sentence": "In this study , we demonstrate that two independent downstream signal pathways , DCN / EGFR / ERK1 / 2 and DCN / EGFR / phosphoinositide - 3 kinase / AKT , mediate up - regulation and activation of transcription factors of VEGF such as HIF1alpha , Stat3 , and Sp1 and increase VEGF transcription and angiogenesis in MCE cells .", "entities": [{"name": "MCE cells", "type": "Anatomy", "pos": [316, 325]}]}, {"sentence": "Effects of spironolactone on corneal allograft survival in the rat .", "entities": [{"name": "corneal allograft", "type": "Anatomy", "pos": [29, 46]}]}, {"sentence": "PURPOSE : Spironolactone has recently been shown to have suppressive effects on several immunoactive and proinflammatory cytokines .", "entities": []}, {"sentence": "In this study , we investigated the effects of spironolactone on the prevention of corneal allograft rejection in a MHC class I / II mismatch rat corneal transplant model .", "entities": [{"name": "corneal allograft", "type": "Anatomy", "pos": [83, 100]}, {"name": "corneal", "type": "Anatomy", "pos": [146, 153]}]}, {"sentence": "METHODS : Grafted animals for corneal survival analysis were assigned to receive either spironolactone suspension ( orally , 100 mg / kg / day , n = 7 ) , phosphate - buffered saline ( PBS , orally , same volume as spironolactone , n = 9 ) or remained untreated ( n = 16 ) .", "entities": [{"name": "corneal", "type": "Anatomy", "pos": [30, 37]}, {"name": "orally", "type": "Anatomy", "pos": [116, 122]}, {"name": "orally", "type": "Anatomy", "pos": [191, 197]}]}, {"sentence": "Additional grafted rats treated with spironolactone ( n = 6 ) or PBS ( n = 8 ) were sacrificed on day 12 for quantitative RT - PCR analysis for mechanistic studies .", "entities": []}, {"sentence": "RESULTS : Mean ( + / - SEM ) graft survival was significantly prolonged in animals receiving spironolactone ( 14 . 9 + / - 2 . 0 days ) compared with both PBS - treated ( 12 . 3 + / - 1 . 2 days , p = 0 . 007 ) and untreated controls ( 13 . 0 + / - 1 . 0 days , p = 0 . 01 ) .", "entities": [{"name": "graft", "type": "Anatomy", "pos": [29, 34]}]}, {"sentence": "We found a decrease in corneal neovascularization in spironolactone - treated rats compared with the PBS - treated group , although the difference was not statistically significant .", "entities": [{"name": "corneal", "type": "Anatomy", "pos": [23, 30]}]}, {"sentence": "Spironolactone affected both systemic ( down - regulation of CD25 + cells in spleen ) and local immune response ( up - regulation of IL - 10 in cornea ) .", "entities": [{"name": "CD25 + cells", "type": "Anatomy", "pos": [61, 73]}, {"name": "spleen", "type": "Anatomy", "pos": [77, 83]}, {"name": "cornea", "type": "Anatomy", "pos": [144, 150]}]}, {"sentence": "CONCLUSION : We present initial results demonstrating anti - inflammatory effects of spironolactone .", "entities": []}, {"sentence": "FAS - 1377 G / A polymorphism and the risk of lymph node metastasis in cervical cancer .", "entities": [{"name": "lymph node", "type": "Anatomy", "pos": [46, 56]}, {"name": "cervical cancer", "type": "Anatomy", "pos": [71, 86]}]}, {"sentence": "Single - nucleotide polymorphisms of the FAS - 1377G / A , FAS - 670A / G , and FASL - 844T / C genes may alter transcriptional activity of these genes .", "entities": []}, {"sentence": "Recent evidence suggests an association of these polymorphisms with an increased risk of cervical cancer , so we explored this relationship .", "entities": [{"name": "cervical cancer", "type": "Anatomy", "pos": [89, 104]}]}, {"sentence": "Genotypes of 155 patients with cervical cancer and 160 healthy control subjects were determined using polymerase chain reaction - based restriction fragment length polymorphism ( PCR - RFLP ) .", "entities": [{"name": "cervical cancer", "type": "Anatomy", "pos": [31, 46]}]}, {"sentence": "Associations with cancer risk were estimated using two - sided logistic regression .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [18, 24]}]}, {"sentence": "We observed a significantly increased risk of lymph node metastasis associated with the FAS - 1377 GA or AA polymorphism [ odds ratio ( OR ) = 4 . 16 , 95 % confidence interval ( CI ) = 1 . 10 to 15 . 74 ; P = 0 . 036 ] .", "entities": [{"name": "lymph node", "type": "Anatomy", "pos": [46, 56]}]}, {"sentence": "In addition , the FAS - 670AG or GG genotype showed an increased incidence of node metastasis , but these findings were not statistically significant ( OR = 3 . 67 , 95 % CI = 0 . 96 - 14 . 00 , P = 0 . 059 ) .", "entities": [{"name": "node", "type": "Anatomy", "pos": [78, 82]}]}, {"sentence": "There was no significant association between an increased risk of cervical cancer and polymorphisms of the death pathway genes FAS and FASL .", "entities": [{"name": "cervical cancer", "type": "Anatomy", "pos": [66, 81]}]}, {"sentence": "None of the polymorphisms were associated with risk of advanced stage or histologic subtype of cervical cancer .", "entities": [{"name": "cervical cancer", "type": "Anatomy", "pos": [95, 110]}]}, {"sentence": "In conclusion , FAS - 1377 G - - > A polymorphism may be associated with an increased risk of lymph node metastasis in Korean cervical cancer patients .", "entities": [{"name": "lymph node", "type": "Anatomy", "pos": [94, 104]}, {"name": "cervical cancer", "type": "Anatomy", "pos": [126, 141]}]}, {"sentence": "Detection of lymphovascular invasion in early breast cancer by D2 - 40 ( podoplanin ) : a clinically useful predictor for axillary lymph node metastases .", "entities": [{"name": "lymphovascular", "type": "Anatomy", "pos": [13, 27]}, {"name": "breast cancer", "type": "Anatomy", "pos": [46, 59]}, {"name": "axillary lymph node metastases", "type": "Anatomy", "pos": [122, 152]}]}, {"sentence": "PURPOSE : The aim of this study was to investigate the use of D2 - 40 for the detection of lymphovascular invasion ( LVI ) in node positive and negative early breast cancer .", "entities": [{"name": "lymphovascular", "type": "Anatomy", "pos": [91, 105]}, {"name": "node", "type": "Anatomy", "pos": [126, 130]}, {"name": "breast cancer", "type": "Anatomy", "pos": [159, 172]}]}, {"sentence": "LVI is associated with axillary lymph node metastases ( ALNM ) and a long - term prognostic factor .", "entities": [{"name": "axillary lymph node metastases", "type": "Anatomy", "pos": [23, 53]}, {"name": "ALNM", "type": "Anatomy", "pos": [56, 60]}]}, {"sentence": "A precise identification of LVI would have a strong clinical impact for breast cancer patients .", "entities": [{"name": "breast cancer", "type": "Anatomy", "pos": [72, 85]}]}, {"sentence": "METHODS : Immunohistochemical staining with D2 - 40 and CD34 was performed on formalin - fixed , paraffin - embedded tissue sections of 254 invasive breast tumors of 247 patients with node negative and node positive early breast cancer .", "entities": [{"name": "tissue sections", "type": "Anatomy", "pos": [117, 132]}, {"name": "invasive breast tumors", "type": "Anatomy", "pos": [140, 162]}, {"name": "node", "type": "Anatomy", "pos": [184, 188]}, {"name": "node", "type": "Anatomy", "pos": [202, 206]}, {"name": "breast cancer", "type": "Anatomy", "pos": [222, 235]}]}, {"sentence": "All slides were screened for the presence of LVI .", "entities": []}, {"sentence": "Correlation with clinico - pathological factors including LVI as retrieved by routine haematoxylin and eosin ( H . E . ) stained sections and the eligibility for the prediction of ALNM was assessed .", "entities": [{"name": "sections", "type": "Anatomy", "pos": [129, 137]}]}, {"sentence": "RESULTS : Using the D2 - 40 antibody for immunostaining , our results demonstrate a significant higher detection ( P < 0 . 001 ) of LVI as compared with routine H . E . - staining in early breast cancer .", "entities": [{"name": "breast cancer", "type": "Anatomy", "pos": [189, 202]}]}, {"sentence": "LVI was correctly identified by D2 - 40 ( D2 - 40 + ) in 70 out of 254 tumors ( 28 % ) as compared to 40 tumors ( 16 % ) by routine HE staining ( HE + ) .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [71, 77]}, {"name": "tumors", "type": "Anatomy", "pos": [105, 111]}]}, {"sentence": "There was a significant correlation between D2 - 40 + LVI and age , t - stage , nodal status , grading and hormonreceptor - status .", "entities": [{"name": "nodal", "type": "Anatomy", "pos": [80, 85]}]}, {"sentence": "Correlation between D2 - 40 + LVI and menopausal - status , HER2 - status and histological type was not significant , while there was a significant correlation of D2 - 40 and so called \" triple negative \" tumors ( ER / PR and HER2neu - negative ) .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [205, 211]}]}, {"sentence": "In a multivariate analysis D2 - 40 + was the strongest predictor for ALNM with an odds ratio of 3 . 489 and a P - value of P = 0 . 0003 , followed only by T - stage and grading with odds ratios of 3 . 167 and 1 . 953 and P - values P = 0 . 0003 and P = 0 . 0352 .", "entities": []}, {"sentence": "CONCLUSION : Immunostaining with D2 - 40 significantly increased the frequency of detection of lymphatic invasion compared to conventional H . E . - staining in early breast cancer .", "entities": [{"name": "lymphatic", "type": "Anatomy", "pos": [95, 104]}, {"name": "breast cancer", "type": "Anatomy", "pos": [167, 180]}]}, {"sentence": "As LVI is a strong predictive and prognostic marker , the monoclonal antibody D2 - 40 has the potential to play a significant role in pathological routine workup of breast tumors .", "entities": [{"name": "breast tumors", "type": "Anatomy", "pos": [165, 178]}]}, {"sentence": "Further prospective studies are needed to prove the clinical impact of D2 - 40 .", "entities": []}, {"sentence": "N - myc augments death and attenuates protective effects of Bcl - 2 in trophically stressed neuroblastoma cells .", "entities": [{"name": "neuroblastoma cells", "type": "Anatomy", "pos": [92, 111]}]}, {"sentence": "N - myc has proapoptotic functions , yet it acts as an oncogene in neuroblastoma .", "entities": [{"name": "neuroblastoma", "type": "Anatomy", "pos": [67, 80]}]}, {"sentence": "Thus , antiapoptotic mechanisms have to be operative in neuroblastoma cells that antagonize the proapoptotic effects of N - myc .", "entities": [{"name": "neuroblastoma cells", "type": "Anatomy", "pos": [56, 75]}]}, {"sentence": "We conditionally activated N - myc in SH - EP neuroblastoma cells subjected to the trophic stress of serum or nutrient deprivation while changing the expression of Bcl - 2 , survivin and FLIP ( L ) , antiapoptotic molecules often overexpressed in poor prognosis neuroblastomas .", "entities": [{"name": "SH - EP neuroblastoma cells", "type": "Anatomy", "pos": [38, 65]}, {"name": "serum", "type": "Anatomy", "pos": [101, 106]}, {"name": "neuroblastomas", "type": "Anatomy", "pos": [262, 276]}]}, {"sentence": "Bcl - 2 protected SH - EP cells from death during nutritional deprivation by activating energetically advantageous oxidative phosphorylation .", "entities": [{"name": "SH - EP cells", "type": "Anatomy", "pos": [18, 31]}]}, {"sentence": "N - myc overrode the metabolic protection provided by Bcl - 2 - induced oxidative phosphorylation by reestablishing the glycolytic phenotype and attenuated the antiapoptotic effect of Bcl - 2 during metabolic stress .", "entities": []}, {"sentence": "Survivin partially antagonized the growth suppressive function of N - myc in SH - EP neuroblastoma cells during serum deprivation whereas FLIP ( L ) did not .", "entities": [{"name": "SH - EP neuroblastoma cells", "type": "Anatomy", "pos": [77, 104]}, {"name": "serum", "type": "Anatomy", "pos": [112, 117]}]}, {"sentence": "These findings advance our understanding of the functions of N - myc in neuroblastoma cells .", "entities": [{"name": "neuroblastoma cells", "type": "Anatomy", "pos": [72, 91]}]}, {"sentence": "A new autosomal dominant vascular retinopathy syndrome .", "entities": [{"name": "vascular", "type": "Anatomy", "pos": [25, 33]}]}, {"sentence": "We describe a new syndrome with autosomal dominant transmission whose most striking feature is vascular retinopathy .", "entities": [{"name": "vascular", "type": "Anatomy", "pos": [95, 103]}]}, {"sentence": "The retinopathy is often associated with migraine , Raynaud ' s phenomenon and mental changes , mainly forgetfulness , aggression and depression .", "entities": []}, {"sentence": "To define this syndrome we collected medical data on 110 family members .", "entities": []}, {"sentence": "General ophthalmological examination and fluorescein angiography were performed in 61 persons .", "entities": []}, {"sentence": "The retinopathy , as diagnosed in 22 persons , is characterized by central and peripheral microangiopathy , areas of capillary non - perfusion , haemorrhages , cotton wool spots and , in a more advanced stage , occlusion of large retinal vessels , which can induce a neovascular response .", "entities": [{"name": "capillary", "type": "Anatomy", "pos": [117, 126]}, {"name": "retinal vessels", "type": "Anatomy", "pos": [230, 245]}]}, {"sentence": "A vascular occlusive disorder may be the common aetiological factor of the various manifestation of this syndrome .", "entities": [{"name": "vascular", "type": "Anatomy", "pos": [2, 10]}]}, {"sentence": "The element effect and nucleophilicity in nucleophilic aromatic photosubstitution ( SN2Ar * ) .", "entities": []}, {"sentence": "Local atom effects as mechanistic probes of very fast reactions .", "entities": []}, {"sentence": "Photoreactions of 4 - nitroanisole and the 2 - halo - 4 - nitroanisoles ( halogen = F , Cl , Br , and I ) with the nucleophiles hydroxide ion and pyridine have been investigated quantitatively to extend the findings recently communicated for cyanide ion .", "entities": []}, {"sentence": "The halonitroanisoles on excitation form triplet pi , pi * states , which undergo substitution of the halogen by nucleophiles .", "entities": []}, {"sentence": "Chemical yields of photoproducts , Stern - Volmer kinetic plots , triplet lifetimes , and triplet yields are reported for the five compounds with the three nucleophiles .", "entities": []}, {"sentence": "Following a standard kinetic treatment , 73 rate constants are determined for elementary reactions of the triplets including quenching and various nucleophilic addition processes .", "entities": []}, {"sentence": "The photoadditions are roughly 14 orders of magnitude faster than thermal counterparts .", "entities": []}, {"sentence": "Rate constants for attack at the fluorine - bearing carbon of triplet 2 - fluoro - 4 - nitroanisole are 2 . 9 x 10 ( 9 ) , 1 . 3 x 10 ( 9 ) , and 6 . 3 x 10 ( 8 ) M ( - 1 ) s ( - 1 ) for cyanide ion , hydroxide ion , and pyridine , respectively .", "entities": []}, {"sentence": "The relative rates for attack at the halogen - bearing carbons for F / Cl / Br / I are 27 : 1 . 9 : 1 . 9 : 1 ( cyanide ion ) , 29 : 2 . 6 : 2 . 4 : 1 ( hydroxide ion ) , and 39 : 3 . 9 : 3 . 5 : 1 ( pyridine ) , respectively .", "entities": []}, {"sentence": "The relative nucleophilicities vary somewhat with the attack site ; they are about 5 : 2 : 1 for cyanide ion , hydroxide ion , and pyridine for attack at the halogen - bearing carbons .", "entities": []}, {"sentence": "The trend of the element effect opposes that of aliphatic substitution and elimination but is similar in size and parallel to that of thermal nucleophilic aromatic substitution .", "entities": []}, {"sentence": "Relative nucleophilicities in the photoreactions are also similar to those of comparable but vastly slower thermal reactions .", "entities": []}, {"sentence": "The findings imply that the efficiency - determining step of the halogen photosubstitution is simple formation of a sigma - complex through electron - paired bonding within the triplet manifold .", "entities": []}, {"sentence": "Sciatic nerve repair by microgrooved nerve conduits made of chitosan - gold nanocomposites .", "entities": [{"name": "Sciatic nerve", "type": "Anatomy", "pos": [0, 13]}, {"name": "nerve", "type": "Anatomy", "pos": [37, 42]}]}, {"sentence": "BACKGROUND :", "entities": []}, {"sentence": "To better direct the repair of peripheral nerve after injury , an implant consisting of a multicomponent micropatterned conduit seeded with NSC was designed .", "entities": [{"name": "peripheral nerve", "type": "Anatomy", "pos": [31, 47]}, {"name": "NSC", "type": "Anatomy", "pos": [140, 143]}]}, {"sentence": "METHODS :", "entities": []}, {"sentence": "The mechanical properties of the chi - Au nanocomposites were tested .", "entities": []}, {"sentence": "In vitro , the effect of chi - Au on cell behavior ( NSC and glial cell line C6 ) and the influence of micropattern on cell alignment were evaluated .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [37, 41]}, {"name": "NSC", "type": "Anatomy", "pos": [53, 56]}, {"name": "glial cell line C6", "type": "Anatomy", "pos": [61, 79]}, {"name": "cell", "type": "Anatomy", "pos": [119, 123]}]}, {"sentence": "In vivo , the micropatterned conduits with / without the preseeded NSC were implanted to bridge a 10 - mm - long defect of the sciatic nerve in 9 male Sprague - Dawley rats .", "entities": [{"name": "NSC", "type": "Anatomy", "pos": [67, 70]}, {"name": "sciatic nerve", "type": "Anatomy", "pos": [127, 140]}]}, {"sentence": "The repair outcome was investigated 6 weeks after the surgery .", "entities": []}, {"sentence": "RESULTS :", "entities": []}, {"sentence": "Based on the dynamic modulus , chitosan with 50 ppm or more gold was a stronger material than others .", "entities": []}, {"sentence": "In vitro , gold at 25 or 50 ppm led to better cell performance for NSC ; and gold at 50 ppm gave better cell performance for C6 .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [46, 50]}, {"name": "NSC", "type": "Anatomy", "pos": [67, 70]}, {"name": "cell", "type": "Anatomy", "pos": [104, 108]}, {"name": "C6", "type": "Anatomy", "pos": [125, 127]}]}, {"sentence": "On the microgrooved substrate , the NSC had elongated processes oriented parallel to the grooves , whereas the NSC on the nonpatterned surfaces did not exhibit a particular bias in alignment .", "entities": [{"name": "NSC", "type": "Anatomy", "pos": [36, 39]}, {"name": "NSC", "type": "Anatomy", "pos": [111, 114]}]}, {"sentence": "In vivo , the number of regenerated axons , the regenerated area , and the number of blood vessels were significantly higher in the NSC - preseeded conduit .", "entities": [{"name": "axons", "type": "Anatomy", "pos": [36, 41]}, {"name": "area", "type": "Anatomy", "pos": [60, 64]}, {"name": "blood vessels", "type": "Anatomy", "pos": [85, 98]}, {"name": "NSC", "type": "Anatomy", "pos": [132, 135]}]}, {"sentence": "CONCLUSION :", "entities": []}, {"sentence": "Modification of the chitosan matrix by gold nanoparticles not only provides the mechanical strength but also affects the cellular response .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [121, 129]}]}, {"sentence": "The preliminary in vivo data demonstrated that the biodegradable micropatterned conduits preseeded with NSC provided a combination of physical and biological guidance cues for regenerating axons at the cellular level and offered a better alternative for repairing sciatic nerve transactions .", "entities": [{"name": "NSC", "type": "Anatomy", "pos": [104, 107]}, {"name": "axons", "type": "Anatomy", "pos": [189, 194]}, {"name": "cellular", "type": "Anatomy", "pos": [202, 210]}, {"name": "sciatic nerve", "type": "Anatomy", "pos": [264, 277]}]}, {"sentence": "[ Parotid gland ' s tumors in children ] .", "entities": [{"name": "Parotid gland ' s tumors", "type": "Anatomy", "pos": [2, 26]}]}, {"sentence": "The tumors of the salivary glands are infrequent in children , and parotid gland is involved in 80 % of them .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [4, 10]}, {"name": "salivary glands", "type": "Anatomy", "pos": [18, 33]}, {"name": "parotid gland", "type": "Anatomy", "pos": [67, 80]}]}, {"sentence": "When a salivary gland tumor is present , the chance of malignancy is greater in the child than in the adult .", "entities": [{"name": "salivary gland tumor", "type": "Anatomy", "pos": [7, 27]}]}, {"sentence": "We reviewed 8 cases identified in patients aged 14 years and younger in our hospital , analyzing its antecedents , signs and symptoms , histological features , diagnosis , treatment and evolution .", "entities": []}, {"sentence": "All the patients displayed preauricular painless , non - inflammatory and slow - growing masses to an age between 10 months and 14 years .", "entities": [{"name": "preauricular", "type": "Anatomy", "pos": [27, 39]}, {"name": "masses", "type": "Anatomy", "pos": [89, 95]}]}, {"sentence": "Four or them were pleomorphic adenomas , two haemangiomas , one epidermal cysts and one myoepithelial carcinoma .", "entities": [{"name": "pleomorphic adenomas", "type": "Anatomy", "pos": [18, 38]}, {"name": "haemangiomas", "type": "Anatomy", "pos": [45, 57]}, {"name": "epidermal cysts", "type": "Anatomy", "pos": [64, 79]}, {"name": "myoepithelial carcinoma", "type": "Anatomy", "pos": [88, 111]}]}, {"sentence": "We emphasize the exceptional nature of the carcinoma for its rareness and for the high degree of malignancy expressed .", "entities": [{"name": "carcinoma", "type": "Anatomy", "pos": [43, 52]}]}, {"sentence": "We made a fine needle aspiration biopsy in four cases but they were conclusive only in three .", "entities": []}, {"sentence": "All were treated by surgical resection of the tumour except for the myoepithelial carcinoma and the recurrent pleomorphic adenoma that were treated by total parotidectomy .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [46, 52]}, {"name": "myoepithelial carcinoma", "type": "Anatomy", "pos": [68, 91]}, {"name": "pleomorphic adenoma", "type": "Anatomy", "pos": [110, 129]}]}, {"sentence": "The malignant tumours of the parotid gland are clinically indistinguishable of the benign ones , thus when any palpable mass appears in the zone of the parotid gland , an accurate diagnosis should be made without delay .", "entities": [{"name": "malignant tumours", "type": "Anatomy", "pos": [4, 21]}, {"name": "parotid gland", "type": "Anatomy", "pos": [29, 42]}, {"name": "benign ones", "type": "Anatomy", "pos": [83, 94]}, {"name": "palpable mass", "type": "Anatomy", "pos": [111, 124]}, {"name": "parotid gland", "type": "Anatomy", "pos": [152, 165]}]}, {"sentence": "The treatment of choice is the surgical excision with wide margins , being other adjuvant treatments less useful to this age than in the adult age .", "entities": []}, {"sentence": "The tyrosine kinase inhibitor cediranib blocks ligand - induced vascular endothelial growth factor receptor - 3 activity and lymphangiogenesis .", "entities": []}, {"sentence": "Solid tumors express a range of factors required to sustain their growth and promote their dissemination .", "entities": [{"name": "Solid tumors", "type": "Anatomy", "pos": [0, 12]}]}, {"sentence": "Among these are vascular endothelial growth factor - A ( VEGF - A ) , the key angiogenic stimulant , and VEGF - C , a primary mediator of lymphangiogenesis .", "entities": []}, {"sentence": "Small molecule tyrosine kinase inhibitors offer the potential to inhibit more than one kinase and impede tumor growth by multiple mechanisms .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [105, 110]}]}, {"sentence": "However , their potency toward individual targets can vary .", "entities": []}, {"sentence": "Cediranib ( RECENTIN ; AZD2171 ) is an inhibitor of VEGF signaling that has been shown in experimental models to prevent VEGF - A - induced angiogenesis and primary tumor growth , yet the effects of cediranib on VEGF receptor ( VEGFR ) - 3 - mediated endothelial cell function and lymphangiogenesis are unknown .", "entities": [{"name": "primary tumor", "type": "Anatomy", "pos": [157, 170]}, {"name": "endothelial cell", "type": "Anatomy", "pos": [251, 267]}]}, {"sentence": "To better understand the activity of cediranib against VEGFR - 3 and its associated signaling events compared with its activity against VEGFR - 2 , we used the receptor - specific ligands VEGF - E and VEGF - C156S .", "entities": []}, {"sentence": "In human endothelial cells , cediranib inhibited VEGF - E - induced phosphorylation of VEGFR - 2 and VEGF - C156S - induced phosphorylation of VEGFR - 3 at concentrations of less than / = 1nmol / L and inhibited activation of downstream signaling molecules .", "entities": [{"name": "endothelial cells", "type": "Anatomy", "pos": [9, 26]}]}, {"sentence": "Additionally , cediranib blocked VEGF - C156S - induced and VEGF - E - induced proliferation , survival , and migration of lymphatic and blood vascular endothelial cells .", "entities": [{"name": "lymphatic", "type": "Anatomy", "pos": [123, 132]}, {"name": "blood vascular endothelial cells", "type": "Anatomy", "pos": [137, 169]}]}, {"sentence": "In vivo , cediranib ( 6 mg / kg / d ) prevented angiogenesis and lymphangiogenesis induced by VEGF - E - expressing and VEGF - C156S - expressing adenoviruses , respectively .", "entities": []}, {"sentence": "Cediranib ( 6 mg / kg / day ) also blocked angiogenesis and lymphangiogenesis induced by adenoviruses expressing VEGF - A or VEGF - C and compromised the blood and lymphatic vasculatures of VEGF - C - expressing tumors .", "entities": [{"name": "blood", "type": "Anatomy", "pos": [154, 159]}, {"name": "lymphatic vasculatures", "type": "Anatomy", "pos": [164, 186]}, {"name": "tumors", "type": "Anatomy", "pos": [212, 218]}]}, {"sentence": "Cediranib may , therefore , be an effective means of preventing tumor progression , not only by inhibiting VEGFR - 2 activity and angiogenesis , but also by concomitantly inhibiting VEGFR - 3 activity and lymphangiogenesis .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [64, 69]}]}, {"sentence": "Artemisinin inhibits tumor lymphangiogenesis by suppression of vascular endothelial growth factor C .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [21, 26]}]}, {"sentence": "We have previously reported that dihydroartemisinin is found to have a potent ability in influencing lymphatic endothelial cell migration and tube formation .", "entities": [{"name": "lymphatic endothelial cell", "type": "Anatomy", "pos": [101, 127]}, {"name": "tube", "type": "Anatomy", "pos": [142, 146]}]}, {"sentence": "In this study , we investigated the effect of artemisinin on tumor growth , lymphangiogenesis , metastasis and survival in mouse Lewis lung carcinoma ( LLC ) models .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [61, 66]}, {"name": "Lewis lung carcinoma", "type": "Anatomy", "pos": [129, 149]}, {"name": "LLC", "type": "Anatomy", "pos": [152, 155]}]}, {"sentence": "We found that orally administered artemisinin inhibited lymph node and lung metastasis and prolonged survival without retarding tumor growth .", "entities": [{"name": "orally", "type": "Anatomy", "pos": [14, 20]}, {"name": "lymph node", "type": "Anatomy", "pos": [56, 66]}, {"name": "lung", "type": "Anatomy", "pos": [71, 75]}, {"name": "tumor", "type": "Anatomy", "pos": [128, 133]}]}, {"sentence": "Consistent with the decrease in lymph node metastasis , tumor lymphangiogenesis and expression of vascular endothelial growth factor C ( VEGF - C ) was significantly decreased in artemisinin - treated mice , as compared to control mice .", "entities": [{"name": "lymph node", "type": "Anatomy", "pos": [32, 42]}, {"name": "tumor", "type": "Anatomy", "pos": [56, 61]}]}, {"sentence": "Furthermore , IL - 1beta - induced p38 mitogen - activated protein kinase ( MAPK ) activation and upregulation of VEGF - C mRNA and protein in LLC cells was also suppressed by artemisinin or by the p38 MAPK inhibitor SB - 203580 , suggesting that p38 MAPK could serve as a mediator of proinflammatory cytokine - induced VEGF - C expression .", "entities": [{"name": "LLC cells", "type": "Anatomy", "pos": [143, 152]}]}, {"sentence": "These data indicate that artemisinin may be useful for the prevention of lymph node metastasis by downregulating VEGF - C and reducing tumor lymphangiogenesis .", "entities": [{"name": "lymph node", "type": "Anatomy", "pos": [73, 83]}, {"name": "tumor", "type": "Anatomy", "pos": [135, 140]}]}, {"sentence": "Bevacizumab and irinotecan therapy in glioblastoma multiforme : a series of 13 cases .", "entities": [{"name": "glioblastoma multiforme", "type": "Anatomy", "pos": [38, 61]}]}, {"sentence": "OBJECT : Endothelial proliferation has been recognized as a marker of high - grade or aggressive glioma .", "entities": [{"name": "Endothelial", "type": "Anatomy", "pos": [9, 20]}, {"name": "high - grade", "type": "Anatomy", "pos": [70, 82]}, {"name": "aggressive glioma", "type": "Anatomy", "pos": [86, 103]}]}, {"sentence": "Bevacizumab is a humanized immunoglobulin G1 monoclonal antibody to vascular endothelial growth factor that has been shown to have activity in malignant gliomas when combined with irinotecan .", "entities": [{"name": "malignant gliomas", "type": "Anatomy", "pos": [143, 160]}]}, {"sentence": "The authors report on a case series of 13 patients with recurrent heavily pretreated malignant glioma that was treated with the combination of bevacizumab and irinotecan .", "entities": [{"name": "malignant glioma", "type": "Anatomy", "pos": [85, 101]}]}, {"sentence": "METHODS : Standard therapy with primary resection followed by adjuvant chemotherapy and radiation had failed in all patients .", "entities": []}, {"sentence": "The median number of therapies applied , including initial surgery , was 5 ( range 3 - 7 therapies ) .", "entities": []}, {"sentence": "Nine patients were started on bevacizumab at a dose of 5 mg / m2 every 2 weeks .", "entities": []}, {"sentence": "Four patients received bevacizumab at a dose of 10 mg / m2 ; irinotecan was given at a dose of 125 mg / m2 every week for 3 weeks .", "entities": []}, {"sentence": "RESULTS : Of the 13 treated patients , 10 ( 77 % ) had a radiologically demonstrated partial response and 3 ( 23 % ) had stable disease .", "entities": []}, {"sentence": "Six patients ( 46 % ) had a clinical response .", "entities": []}, {"sentence": "The median time to disease progression while on treatment was 24 weeks .", "entities": []}, {"sentence": "The median overall survival was 27 weeks .", "entities": []}, {"sentence": "The disease progressed in 8 patients , despite an initial response .", "entities": []}, {"sentence": "Five patients are still responding to therapy .", "entities": []}, {"sentence": "Six of the 8 patients whose disease progressed have died .", "entities": []}, {"sentence": "Bevacizumab was discontinued in 2 patients because of nonfatal intracranial bleeding .", "entities": [{"name": "intracranial", "type": "Anatomy", "pos": [63, 75]}]}, {"sentence": "CONCLUSIONS : The combination of bevacizumab and irinotecan is safe and has excellent activity even in this relapsed , heavily pretreated population of patients with high - grade malignant glioma , most of whom would not be candidates for clinical trials .", "entities": [{"name": "high - grade malignant glioma", "type": "Anatomy", "pos": [166, 195]}]}, {"sentence": "Demographic consequences of terrestrial habitat loss for pool - breeding amphibians : predicting extinction risks associated with inadequate size of buffer zones .", "entities": []}, {"sentence": "Much of the biodiversity associated with isolated wetlands requires aquatic and terrestrial habitat to maintain viable populations .", "entities": []}, {"sentence": "Current federal wetland regulations in the United States do not protect isolated wetlands or extend protection to surrounding terrestrial habitat .", "entities": []}, {"sentence": "Consequently , some land managers , city planners , and policy makers at the state and local levels are making an effort to protect these wetland and neighboring upland habitats .", "entities": []}, {"sentence": "Balancing human land - use and habitat conservation is challenging , and well - informed land - use policy is hindered by a lack of knowledge of the specific risks of varying amounts of habitat loss .", "entities": []}, {"sentence": "Using projections of wood frog ( Rana sylvatica ) and spotted salamander ( Ambystoma maculatum ) populations , we related the amount of high - quality terrestrial habitat surrounding isolated wetlands to the decline and risk of extinction of local amphibian populations .", "entities": []}, {"sentence": "These simulations showed that current state - level wetland regulations protecting 30 m or less of surrounding terrestrial habitat are inadequate to support viable populations of pool - breeding amphibians .", "entities": []}, {"sentence": "We also found that species with different life - history strategies responded differently to the loss and degradation of terrestrial habitat .", "entities": []}, {"sentence": "The wood frog , with a short life span and high fecundity , was most sensitive to habitat loss and isolation , whereas the longer - lived spotted salamander with lower fecundity was most sensitive to habitat degradation that lowered adult survival rates .", "entities": []}, {"sentence": "Our model results demonstrate that a high probability of local amphibian population persistence requires sufficient terrestrial habitat , the maintenance of habitat quality , and connectivity among local populations .", "entities": []}, {"sentence": "Our results emphasize the essential role of adequate terrestrial habitat to the maintenance of wetland biodiversity and ecosystem function and offer a means of quantifying the risks associated with terrestrial habitat loss and degradation .", "entities": []}, {"sentence": "Endosialin / TEM 1 / CD248 is a pericyte marker of embryonic and tumor neovascularization .", "entities": [{"name": "pericyte", "type": "Anatomy", "pos": [32, 40]}, {"name": "embryonic", "type": "Anatomy", "pos": [51, 60]}, {"name": "tumor", "type": "Anatomy", "pos": [65, 70]}]}, {"sentence": "The formation of functional , mature blood vessels depends on the interaction between endothelial cells and pericytes .", "entities": [{"name": "blood vessels", "type": "Anatomy", "pos": [37, 50]}, {"name": "endothelial cells", "type": "Anatomy", "pos": [86, 103]}, {"name": "pericytes", "type": "Anatomy", "pos": [108, 117]}]}, {"sentence": "Commonality exists in the processes involved in vasculature development between tissues whether healthy or diseased .", "entities": [{"name": "vasculature", "type": "Anatomy", "pos": [48, 59]}, {"name": "tissues", "type": "Anatomy", "pos": [80, 87]}]}, {"sentence": "Endosialin / TEM 1 is a cell membrane protein that is expressed in blood vessels during embryogenesis and tumorigenesis but not in normal mature vessels .", "entities": [{"name": "cell membrane", "type": "Anatomy", "pos": [24, 37]}, {"name": "blood vessels", "type": "Anatomy", "pos": [67, 80]}, {"name": "mature vessels", "type": "Anatomy", "pos": [138, 152]}]}, {"sentence": "Antibodies developed to human endosialin were used to investigate endosialin expression and function in human prenatal brain pericytes and pericytes residing in tumors .", "entities": [{"name": "prenatal brain pericytes", "type": "Anatomy", "pos": [110, 134]}, {"name": "pericytes", "type": "Anatomy", "pos": [139, 148]}, {"name": "tumors", "type": "Anatomy", "pos": [161, 167]}]}, {"sentence": "Anti - endosialin was capable of preventing pericyte tube formation in culture and inhibited migration .", "entities": [{"name": "pericyte tube", "type": "Anatomy", "pos": [44, 57]}]}, {"sentence": "Brain pericytes in culture had higher levels of endosialin / TEM 1 than TEMs - 2 , - 3 , - 4 , - 5 , - 7 , and - 8 .", "entities": [{"name": "Brain pericytes", "type": "Anatomy", "pos": [0, 15]}]}, {"sentence": "Immunocytochemistry revealed that endosialin was present in the cytoplasmic body and in the elongated extensions essential to pericyte function .", "entities": [{"name": "cytoplasmic body", "type": "Anatomy", "pos": [64, 80]}, {"name": "pericyte", "type": "Anatomy", "pos": [126, 134]}]}, {"sentence": "Transgenic mice engineered to express human endosialin bred on an immunocompromised background allowed the growth of human tumor xenografts .", "entities": [{"name": "tumor xenografts", "type": "Anatomy", "pos": [123, 139]}]}, {"sentence": "In human colon carcinoma Colo205 and HT29 xenografts grown in human endosialin - transgenic mice , endosialin expression was largely confined to NG2 - expressing perivascular cells and not CD31 - positive endothelial cells .", "entities": [{"name": "colon carcinoma Colo205", "type": "Anatomy", "pos": [9, 32]}, {"name": "HT29 xenografts", "type": "Anatomy", "pos": [37, 52]}, {"name": "perivascular cells", "type": "Anatomy", "pos": [162, 180]}, {"name": "CD31 - positive endothelial cells", "type": "Anatomy", "pos": [189, 222]}]}, {"sentence": "Similar methods applied to human ovarian and colon tumors confirmed endosialin expression by pericytes .", "entities": [{"name": "ovarian", "type": "Anatomy", "pos": [33, 40]}, {"name": "colon tumors", "type": "Anatomy", "pos": [45, 57]}, {"name": "pericytes", "type": "Anatomy", "pos": [93, 102]}]}, {"sentence": "The data indicate that endosialin is strongly expressed by pericytes during periods of active angiogenesis during embryonic and tumor development .", "entities": [{"name": "pericytes", "type": "Anatomy", "pos": [59, 68]}, {"name": "embryonic", "type": "Anatomy", "pos": [114, 123]}, {"name": "tumor", "type": "Anatomy", "pos": [128, 133]}]}, {"sentence": "Anti - endosialin antibodies may have value in identifying vasculature in malignant tissues .", "entities": [{"name": "vasculature", "type": "Anatomy", "pos": [59, 70]}, {"name": "malignant tissues", "type": "Anatomy", "pos": [74, 91]}]}, {"sentence": "With the appropriate agent , targeting endosialin may interfere with blood vessel growth during tumor development .", "entities": [{"name": "blood vessel", "type": "Anatomy", "pos": [69, 81]}, {"name": "tumor", "type": "Anatomy", "pos": [96, 101]}]}, {"sentence": "Efficient inhibition of ovarian cancer growth and prolonged survival by transfection with a novel pro - apoptotic gene , hPNAS - 4 , in a mouse model .", "entities": [{"name": "ovarian cancer", "type": "Anatomy", "pos": [24, 38]}]}, {"sentence": "In vivo and in vitro results .", "entities": []}, {"sentence": "OBJECTIVE : We transfected ovarian cancer cells and administered recombinant plasmid encoding hPNAS - 4 to nude mice bearing ovarian cancer , aiming to evaluate the effect of hPNAS - 4 against ovarian cancer in vitro and in vivo .", "entities": [{"name": "ovarian cancer cells", "type": "Anatomy", "pos": [27, 47]}, {"name": "plasmid", "type": "Anatomy", "pos": [77, 84]}, {"name": "ovarian cancer", "type": "Anatomy", "pos": [125, 139]}, {"name": "ovarian cancer", "type": "Anatomy", "pos": [193, 207]}]}, {"sentence": "METHODS : Ovarian cancer SKOV3 cells were transfected with hPNAS - 4 - plasmid , and cell proliferation was evaluated by MTT assay ; apoptosis was examined by DNA ladder , Hoechst33258 staining and flow - cytometric assays .", "entities": [{"name": "Ovarian cancer SKOV3 cells", "type": "Anatomy", "pos": [10, 36]}, {"name": "plasmid", "type": "Anatomy", "pos": [71, 78]}, {"name": "cell", "type": "Anatomy", "pos": [85, 89]}]}, {"sentence": "Nude mice bearing ovarian cancers were treated with hPNAS - 4 - p / liposome .", "entities": [{"name": "ovarian cancers", "type": "Anatomy", "pos": [18, 33]}, {"name": "liposome", "type": "Anatomy", "pos": [68, 76]}]}, {"sentence": "Tumor growth was determined and survival was recorded .", "entities": [{"name": "Tumor", "type": "Anatomy", "pos": [0, 5]}]}, {"sentence": "TUNEL assay and microvessel density was assessed to evaluate apoptosis and angiogenesis .", "entities": [{"name": "microvessel", "type": "Anatomy", "pos": [16, 27]}]}, {"sentence": "RESULTS : Both inhibition of proliferation ( p < 0 . 05 ) and induction of apoptosis ( p < 0 . 05 ) were observed in SKOV3 cells transfected with hPNAS - 4 - p in vitro .", "entities": [{"name": "SKOV3 cells", "type": "Anatomy", "pos": [117, 128]}]}, {"sentence": "In hPNAS - 4 - p - treated tumor cells in vivo , tumor growth significantly decreased , while the survival time of tumor - bearing mice was prolonged compared with control groups ( p < 0 . 05 ) .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [27, 38]}, {"name": "tumor", "type": "Anatomy", "pos": [49, 54]}, {"name": "tumor", "type": "Anatomy", "pos": [115, 120]}]}, {"sentence": "Increased apoptosis of tumor cells and decreased angiogenesis in tumor tissue were also observed .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [23, 34]}, {"name": "tumor tissue", "type": "Anatomy", "pos": [65, 77]}]}, {"sentence": "CONCLUSIONS : Our promising results on the potential antitumor effects of hPNAS - 4 on ovarian cancer in vitro and in vivo may be explained , in part , by the induction of apoptosis and inhibition of angiogenesis .", "entities": [{"name": "antitumor", "type": "Anatomy", "pos": [53, 62]}, {"name": "ovarian cancer", "type": "Anatomy", "pos": [87, 101]}]}, {"sentence": "Consequently , hPNAS - 4 has potential as a new gene therapy for human ovarian cancer .", "entities": [{"name": "ovarian cancer", "type": "Anatomy", "pos": [71, 85]}]}, {"sentence": "The in vivo properties of STX243 : a potent angiogenesis inhibitor in breast cancer .", "entities": [{"name": "breast cancer", "type": "Anatomy", "pos": [70, 83]}]}, {"sentence": "The steroidal - based drug 2 - ethyloestradiol - 3 , 17 - O , O - bis - sulphamate ( STX243 ) has been developed as a potent antiangiogenic and antitumour compound .", "entities": [{"name": "antitumour", "type": "Anatomy", "pos": [144, 154]}]}, {"sentence": "The objective of this study was to ascertain whether STX243 is more active in vivo than the clinically relevant drug 2 - methoxyoestradiol ( 2 - MeOE2 ) and the structurally similar compound 2 - MeOE2 - 3 , 17 - O , O - bis - sulphamate ( STX140 ) .", "entities": []}, {"sentence": "The tumour growth inhibition efficacy , antiangiogenic potential and pharmacokinetics of STX243 were examined using four in vivo models .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [4, 10]}]}, {"sentence": "Both STX243 and STX140 were capable of retarding the growth of MDA - MB - 231 xenograft tumours ( 72 and 63 % , respectively ) , whereas no inhibition was observed for animals treated with 2 - MeOE2 .", "entities": [{"name": "MDA - MB - 231 xenograft tumours", "type": "Anatomy", "pos": [63, 95]}]}, {"sentence": "Further tumour inhibition studies showed that STX243 was also active against MCF - 7 paclitaxel - resistant tumours .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [8, 14]}, {"name": "MCF - 7 paclitaxel - resistant tumours", "type": "Anatomy", "pos": [77, 115]}]}, {"sentence": "Using a Matrigel plug - based model , in vivo angiogenesis was restricted with STX243 and STX140 ( 50 and 72 % , respectively , using a 10 mg kg ( - 1 ) oral dose ) , thereby showing the antiangiogenic activity of both compounds .", "entities": [{"name": "oral", "type": "Anatomy", "pos": [153, 157]}]}, {"sentence": "The pharmacokinetics of STX243 were examined at two different doses using adult female rats .", "entities": []}, {"sentence": "The compound was orally bioavailable ( 31 % after a single 10 mg kg ( - 1 ) dose ) and resistant to metabolism .", "entities": [{"name": "orally", "type": "Anatomy", "pos": [17, 23]}]}, {"sentence": "These results show that STX243 is a potent in vivo drug and could be clinically effective at treating a number of oncological conditions .", "entities": []}, {"sentence": "[ The clinical and laboratory features of acute promyelocytic leukemia : an analysis of 513 cases ] .", "entities": [{"name": "acute promyelocytic leukemia", "type": "Anatomy", "pos": [42, 70]}]}, {"sentence": "OBJECTIVE :", "entities": []}, {"sentence": "To investigate the clinical and laboratory features of acute promyelocytic leukemia ( APL ) .", "entities": [{"name": "acute promyelocytic leukemia", "type": "Anatomy", "pos": [55, 83]}, {"name": "APL", "type": "Anatomy", "pos": [86, 89]}]}, {"sentence": "METHODS :", "entities": []}, {"sentence": "513 APL patients in the last two decades were retrospectively analyzed in this research .", "entities": [{"name": "APL", "type": "Anatomy", "pos": [4, 7]}]}, {"sentence": "We investigated the clinical features including age , sex , abnormality of peripheral hemogram before treatment , therapeutic effect and follow - up and laboratory data such as morphology , immunology , cytogenetics and molecular biology ( MICM ) .", "entities": []}, {"sentence": "RESULTS :", "entities": []}, {"sentence": "The median age of the APL patients was 33 years old and the ratio of male and female was 1 . 21 : 1 .", "entities": [{"name": "APL", "type": "Anatomy", "pos": [22, 25]}]}, {"sentence": "Before treatment , the median level of WBC was 4 . 3 x 10 ( 9 ) / L and the detection rate of abnormal promyelocyte on blood film was 85 . 8 % ; with immunophenotypic detection , the expression levels of CD117 , CD34 , HLA - DR , CD7 , CD14 and CD19 in APL were found to be lower and the expression levels of CD2 , CD33 and MPO higher than those in other subtypes of acute myelocytic leukemia ( AML ) ( both P < 0 . 01 ) .", "entities": [{"name": "WBC", "type": "Anatomy", "pos": [39, 42]}, {"name": "promyelocyte", "type": "Anatomy", "pos": [103, 115]}, {"name": "blood", "type": "Anatomy", "pos": [119, 124]}, {"name": "APL", "type": "Anatomy", "pos": [253, 256]}, {"name": "acute myelocytic leukemia", "type": "Anatomy", "pos": [367, 392]}, {"name": "AML", "type": "Anatomy", "pos": [395, 398]}]}, {"sentence": "Specific abnormal chromosome t ( 15 ; 17 ) was detected in 91 . 7 % of the patients , of whom 75 . 9 % had standard translocation of t ( 15 ; 17 ) , being the most common one and 15 . 8 % of the patients had t ( 15 ; 17 ) with additional abnormal chromosome .", "entities": [{"name": "chromosome", "type": "Anatomy", "pos": [18, 28]}, {"name": "chromosome", "type": "Anatomy", "pos": [247, 257]}]}, {"sentence": "There was only 7 . 5 % of the patients with normal karyotype .", "entities": []}, {"sentence": "However , the presence of both simple translocation and complex translocation was seldom seen .", "entities": []}, {"sentence": "With molecular biological detection , PML / RARalpha fusion gene positive rate was 99 . 6 % .", "entities": []}, {"sentence": "In a relatively long clinical follow - up , we found that the complete remission ( CR ) rate in APL patients was 84 . 7 % , incidence of DIC was 13 . 4 % and five - year survival rate was 30 . 7 % .", "entities": [{"name": "APL", "type": "Anatomy", "pos": [96, 99]}]}, {"sentence": "The median count of WBC in CR group was lower than that non - remission group ( P < 0 . 01 ) .", "entities": [{"name": "WBC", "type": "Anatomy", "pos": [20, 23]}]}, {"sentence": "There were no significant differences on expressions of CD34 and CD2 and changes of cytogenetics between the two groups ( P > 0 . 05 ) .", "entities": []}, {"sentence": "CONCLUSIONS :", "entities": []}, {"sentence": "Comprehensive evaluation of MICM could be of important significance in the diagnosis and prognosis judgment for APL patients .", "entities": [{"name": "APL", "type": "Anatomy", "pos": [112, 115]}]}, {"sentence": "The CR rate in these patients with high WBC count was considerable low .", "entities": [{"name": "WBC", "type": "Anatomy", "pos": [40, 43]}]}, {"sentence": "Grape seed extract inhibits angiogenesis via suppression of the vascular endothelial growth factor receptor signaling pathway .", "entities": [{"name": "Grape seed extract", "type": "Anatomy", "pos": [0, 18]}]}, {"sentence": "Blockade of angiogenesis is an important approach for cancer treatment and prevention .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [54, 60]}]}, {"sentence": "Vascular endothelial growth factor ( VEGF ) is one of the most critical factors that induce angiogenesis and has thus become an attractive target for antiangiogenesis treatment .", "entities": []}, {"sentence": "However , most current anti - VEGF agents often cause some side effects when given chronically .", "entities": []}, {"sentence": "Identification of naturally occurring VEGF inhibitors derived from diet would be one alternative approach with an advantage of known safety .", "entities": []}, {"sentence": "Grape seed extract ( GSE ) , a widely used dietary supplement , is known to have antitumor activity .", "entities": [{"name": "Grape seed extract", "type": "Anatomy", "pos": [0, 18]}, {"name": "GSE", "type": "Anatomy", "pos": [21, 24]}, {"name": "antitumor", "type": "Anatomy", "pos": [81, 90]}]}, {"sentence": "In this study , we have explored the activity of GSE on VEGF receptor and angiogenesis .", "entities": [{"name": "GSE", "type": "Anatomy", "pos": [49, 52]}]}, {"sentence": "We found that GSE could directly inhibit the kinase activity of purified VEGF receptor 2 , a novel activity of GSE that has not been characterized .", "entities": [{"name": "GSE", "type": "Anatomy", "pos": [14, 17]}, {"name": "GSE", "type": "Anatomy", "pos": [111, 114]}]}, {"sentence": "GSE could also inhibit the VEGF receptor / mitogen - activated protein kinase - mediated signaling pathway in endothelial cells .", "entities": [{"name": "GSE", "type": "Anatomy", "pos": [0, 3]}, {"name": "endothelial cells", "type": "Anatomy", "pos": [110, 127]}]}, {"sentence": "As a result , GSE could inhibit VEGF - induced endothelial cell proliferation and migration as well as sprout formation from aorta ring .", "entities": [{"name": "GSE", "type": "Anatomy", "pos": [14, 17]}, {"name": "endothelial cell", "type": "Anatomy", "pos": [47, 63]}, {"name": "sprout", "type": "Anatomy", "pos": [103, 109]}, {"name": "aorta ring", "type": "Anatomy", "pos": [125, 135]}]}, {"sentence": "In vivo assay further showed that GSE could inhibit tumor growth and tumor angiogenesis of MDA - MB - 231 breast cancer cells in mice .", "entities": [{"name": "GSE", "type": "Anatomy", "pos": [34, 37]}, {"name": "tumor", "type": "Anatomy", "pos": [52, 57]}, {"name": "tumor", "type": "Anatomy", "pos": [69, 74]}, {"name": "MDA - MB - 231 breast cancer cells", "type": "Anatomy", "pos": [91, 125]}]}, {"sentence": "Consistent with the in vitro data , GSE treatment of tumor - bearing mice led to concomitant reduction of blood vessel density and phosphorylation of mitogen - activated protein kinase .", "entities": [{"name": "GSE", "type": "Anatomy", "pos": [36, 39]}, {"name": "tumor", "type": "Anatomy", "pos": [53, 58]}, {"name": "blood vessel", "type": "Anatomy", "pos": [106, 118]}]}, {"sentence": "Depletion of polyphenol with polyvinylpyrrolidone abolished the antiangiogenic activity of GSE , suggesting a water - soluble fraction of polyphenol in GSE is responsible for the antiangiogenic activity .", "entities": [{"name": "GSE", "type": "Anatomy", "pos": [91, 94]}, {"name": "GSE", "type": "Anatomy", "pos": [152, 155]}]}, {"sentence": "Taken together , this study indicates that GSE is a well - tolerated and inexpensive natural VEGF inhibitor and could potentially be useful in cancer prevention or treatment .", "entities": [{"name": "GSE", "type": "Anatomy", "pos": [43, 46]}, {"name": "cancer", "type": "Anatomy", "pos": [143, 149]}]}, {"sentence": "Role of the interferon - inducible IFI16 gene in the induction of ICAM - 1 by TNF - alpha .", "entities": []}, {"sentence": "The Interferon - inducible gene IFI16 , a member of the HIN200 family , is activated by oxidative stress and cell density , in addition to Interferons , and it is implicated in the regulation of endothelial cell proliferation and vessel formation in vitro .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [109, 113]}, {"name": "endothelial cell", "type": "Anatomy", "pos": [195, 211]}, {"name": "vessel", "type": "Anatomy", "pos": [230, 236]}]}, {"sentence": "We have previously shown that IFI16 is required for proinflammatory gene stimulation by IFN - gamma through the NF - kappaB complex .", "entities": []}, {"sentence": "To examine whether IFI16 induction might be extended to other proinflammatory cytokines such as tumor necrosis factor ( TNF ) - alpha , we used the strategy of the RNA interference to knock down IFI16 expression , and analyze the capability of TNF - alpha to stimulate intercellular adhesion molecule - 1 ( ICAM - 1 or CD54 ) expression in the absence of functional IFI16 .", "entities": []}, {"sentence": "Our studies demonstrate that IFI16 mediates ICAM - 1 stimulation by TNF - alpha through the NF - kappaB pathway , thus reinforcing the role of the IFI16 molecule in the inflammation process .", "entities": []}, {"sentence": "Impact of tumor cell VEGF expression on the in vivo efficacy of vandetanib ( ZACTIMA ; ZD6474 ) .", "entities": [{"name": "tumor cell", "type": "Anatomy", "pos": [10, 20]}]}, {"sentence": "VEGF is the key player in tumor angiogenesis .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [26, 31]}]}, {"sentence": "In the current study , the impact of VEGF expression on the response of tumors to the VEGFR2 associated tyrosine kinase inhibitor vandetanib was evaluated .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [72, 78]}]}, {"sentence": "MATERIALS AND METHODS : Human colon carcinoma ( HT29 ) and murine squamous carcinoma ( SCCVII ) clonal cell lines expressing varying levels of VEGF were established and their response to vandetanib was assessed in tissue culture and as solid tumors .", "entities": [{"name": "colon carcinoma ( HT29 )", "type": "Anatomy", "pos": [30, 54]}, {"name": "squamous carcinoma ( SCCVII ) clonal cell lines", "type": "Anatomy", "pos": [66, 113]}, {"name": "tissue", "type": "Anatomy", "pos": [214, 220]}, {"name": "solid tumors", "type": "Anatomy", "pos": [236, 248]}]}, {"sentence": "RESULTS : Vandetanib treatment had no effect on tumor cell clonogenic cell survival in vitro but doses > or = 10 nM significantly reduced endothelial cell migration .", "entities": [{"name": "tumor cell", "type": "Anatomy", "pos": [48, 58]}, {"name": "cell", "type": "Anatomy", "pos": [70, 74]}, {"name": "endothelial cell", "type": "Anatomy", "pos": [138, 154]}]}, {"sentence": "In vivo , tumors derived from cell clones expressing high levels of VEGF displayed significantly enhanced angiogenesis and more aggressive growth .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [10, 16]}, {"name": "cell clones", "type": "Anatomy", "pos": [30, 41]}]}, {"sentence": "An intradermal angiogenesis assay was used to demonstrate that a 4 - day treatment with vandetanib ( 50 mg / kg / day ) was able to significantly inhibit blood vessel growth induced by both parental and high VEGF - expressing tumor cell clones .", "entities": [{"name": "intradermal", "type": "Anatomy", "pos": [3, 14]}, {"name": "blood vessel", "type": "Anatomy", "pos": [154, 166]}, {"name": "tumor cell clones", "type": "Anatomy", "pos": [226, 243]}]}, {"sentence": "In the HT29 tumor model , treatment response to vandetanib ( 50 mg / kg / day , Monday - Friday for 2 weeks ) was greatest in xenografts derived from the highest VEGF - expressing cell clones .", "entities": [{"name": "HT29 tumor", "type": "Anatomy", "pos": [7, 17]}, {"name": "xenografts", "type": "Anatomy", "pos": [126, 136]}, {"name": "cell clones", "type": "Anatomy", "pos": [180, 191]}]}, {"sentence": "A similar trend was noted in the SCCVII tumor model .", "entities": [{"name": "SCCVII tumor", "type": "Anatomy", "pos": [33, 45]}]}, {"sentence": "The present findings indicate that vandetanib therapy effectively counteracted the aggressive feature of tumor growth resulting from VEGF over - expressing tumor cells and suggest that such tumors may be particularly well suited for anti - VEGF interventions .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [105, 110]}, {"name": "tumor cells", "type": "Anatomy", "pos": [156, 167]}, {"name": "tumors", "type": "Anatomy", "pos": [190, 196]}]}, {"sentence": "The Down syndrome critical region gene 1 short variant promoters direct vascular bed - specific gene expression during inflammation in mice .", "entities": [{"name": "vascular bed", "type": "Anatomy", "pos": [72, 84]}]}, {"sentence": "Down syndrome critical region gene 1 ( DSCR - 1 ) short variant ( DSCR - 1s ) is an inhibitor of calcineurin / NFAT signaling encoded by exons 4 - 7 of DSCR1 .", "entities": []}, {"sentence": "We previously reported that VEGF induces DSCR - 1s expression in endothelial cells , which in turn negatively feeds back to attenuate endothelial cell activation .", "entities": [{"name": "endothelial cells", "type": "Anatomy", "pos": [65, 82]}, {"name": "endothelial cell", "type": "Anatomy", "pos": [134, 150]}]}, {"sentence": "Here , in order to characterize the role of the promoter that drives DSCR - 1s expression in mediating inducible expression in vivo and to determine the functional relevance of DSCR - 1s in inflammation , we targeted a DNA construct containing 1 . 7 kb of the human DSCR1s promoter coupled to the lacZ reporter to the hypoxanthine guanine phosphoribosyl transferase ( Hprt ) locus of mice .", "entities": []}, {"sentence": "We determined that lacZ was uniformly expressed in the endothelium of transgenic embryos but was markedly downregulated postnatally .", "entities": [{"name": "endothelium", "type": "Anatomy", "pos": [55, 66]}, {"name": "embryos", "type": "Anatomy", "pos": [81, 88]}]}, {"sentence": "Systemic administration of VEGF or LPS in adult mice resulted in cyclosporine A - sensitive reactivation of the DSCR1s promoter and endogenous gene expression in a subset of organs , including the heart and brain .", "entities": [{"name": "organs", "type": "Anatomy", "pos": [174, 180]}, {"name": "heart", "type": "Anatomy", "pos": [197, 202]}, {"name": "brain", "type": "Anatomy", "pos": [207, 212]}]}, {"sentence": "The DSCR1s promoter was similarly induced in the endothelium of tumor xenografts .", "entities": [{"name": "endothelium", "type": "Anatomy", "pos": [49, 60]}, {"name": "tumor xenografts", "type": "Anatomy", "pos": [64, 80]}]}, {"sentence": "In a mouse model of endotoxemia , DSCR - 1s - deficient mice demonstrated increased sepsis mortality , whereas adenovirus - mediated DSCR - 1s overexpression protected against LPS - induced lethality .", "entities": []}, {"sentence": "Collectively , these data suggest that the DSCR1s promoter directs vascular bed - specific expression in activated endothelium and that DSCR - 1s serves to dampen the host response to infection .", "entities": [{"name": "vascular bed", "type": "Anatomy", "pos": [67, 79]}, {"name": "endothelium", "type": "Anatomy", "pos": [115, 126]}]}, {"sentence": "Nicked { beta } 2 - glycoprotein I binds angiostatin 4 . 5 ( plasminogen kringle 1 - 5 ) and attenuates its antiangiogenic property .", "entities": []}, {"sentence": "Angiostatin was first discovered as a plasminogen fragment with antitumor / antiangiogenic property .", "entities": [{"name": "antitumor", "type": "Anatomy", "pos": [64, 73]}]}, {"sentence": "One of the angiostatin isoforms , that is , angiostatin 4 . 5 ( AS4 . 5 ) , consisting of plasminogen kringle 1 to 4 and a most part of kringle 5 , is produced by autoproteolysis and present in human plasma .", "entities": [{"name": "plasma", "type": "Anatomy", "pos": [200, 206]}]}, {"sentence": "beta2 - glycoprotein I ( beta2GPI ) is proteolytically cleaved by plasmin in its domain V ( nicked beta2GPI ) , resulting in binding to plasminogen .", "entities": []}, {"sentence": "Antiangiogenic properties have been recently reported in nicked beta2GPI as well as in intact beta2GPI at higher concentrations .", "entities": []}, {"sentence": "In the present study , we found significant binding of nicked beta2GPI to AS4 . 5 ( K ( D ) = 3 . 27 x 10 ( 6 ) M ( - 1 ) ) .", "entities": []}, {"sentence": "Via this binding , nicked beta2GPI attenuates the antiangiogenic functions of AS4 . 5 in the proliferation of arterial / venous endothelial cells , in the extracellular matrix invasion and the tube formation of venous endothelial cells , and in vivo angiogenesis .", "entities": [{"name": "arterial", "type": "Anatomy", "pos": [110, 118]}, {"name": "venous endothelial cells", "type": "Anatomy", "pos": [121, 145]}, {"name": "extracellular matrix", "type": "Anatomy", "pos": [155, 175]}, {"name": "tube", "type": "Anatomy", "pos": [193, 197]}, {"name": "venous endothelial cells", "type": "Anatomy", "pos": [211, 235]}]}, {"sentence": "In contrast , intact beta2GPI does not bind to AS4 . 5 or inhibit its antiangiogenic activity .", "entities": []}, {"sentence": "Thus , nicked beta2GPI exerts dual effects on angiogenesis , that is , nicked beta2GPI promotes angiogenesis in the presence of AS4 . 5 , whereas nicked beta2GPI inhibits angiogenesis at concentrations high enough to neutralize AS4 . 5 .", "entities": []}, {"sentence": "Our data suggest that plasmin - nicked beta2GPI promotes angiogenesis by interacting with plasmin - generated AS4 . 5 in sites of increased fibrinolysis such as thrombus .", "entities": [{"name": "thrombus", "type": "Anatomy", "pos": [161, 169]}]}, {"sentence": "[ An experimental study on angiogenesis of non - vascularized autogenous bone graft with vascular bundle implantation ]", "entities": [{"name": "autogenous bone graft", "type": "Anatomy", "pos": [62, 83]}, {"name": "vascular bundle", "type": "Anatomy", "pos": [89, 104]}]}, {"sentence": "OBJECTIVE : To investigate the effect of vascular bundle implantation in autogenous bone graft on angiogenesis .", "entities": [{"name": "vascular bundle", "type": "Anatomy", "pos": [41, 56]}, {"name": "autogenous bone graft", "type": "Anatomy", "pos": [73, 94]}]}, {"sentence": "METHODS : Thirty - six New Zealand white rabbits were evaluated in this study .", "entities": []}, {"sentence": "A portion of bilateral radial bones of a rabbit were removed as free bone grafts , whose periostea were peeled off .", "entities": [{"name": "bilateral radial bones", "type": "Anatomy", "pos": [13, 35]}, {"name": "bone grafts", "type": "Anatomy", "pos": [69, 80]}, {"name": "periostea", "type": "Anatomy", "pos": [89, 98]}]}, {"sentence": "In test group , the external maxillary artery bundle was passed through the marrow cavity of the bone .", "entities": [{"name": "external maxillary artery bundle", "type": "Anatomy", "pos": [20, 52]}, {"name": "marrow cavity", "type": "Anatomy", "pos": [76, 89]}, {"name": "bone", "type": "Anatomy", "pos": [97, 101]}]}, {"sentence": "In control group , there was no vascular bundle implantation .", "entities": [{"name": "vascular bundle", "type": "Anatomy", "pos": [32, 47]}]}, {"sentence": "Each bone was placed in masseter muscle separately .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [5, 9]}, {"name": "masseter muscle", "type": "Anatomy", "pos": [24, 39]}]}, {"sentence": "The rabbits were sacrificed and the specimens were procured at 3 days , 1 , 2 , 3 , 4 and 6 weeks after surgery for histological observation , Chinese ink perfusion and CD34 immunohistochemistry .", "entities": [{"name": "specimens", "type": "Anatomy", "pos": [36, 45]}]}, {"sentence": "Microvessel density ( MVD ) was assessed in order to evaluate angiogenesis of autogenous bone grafts .", "entities": [{"name": "Microvessel", "type": "Anatomy", "pos": [0, 11]}, {"name": "autogenous bone grafts", "type": "Anatomy", "pos": [78, 100]}]}, {"sentence": "RESULTS : The bone grafts were found revascularization in 3 days after surgery in the test group , whereas at 2 weeks in the control group .", "entities": [{"name": "bone grafts", "type": "Anatomy", "pos": [14, 25]}]}, {"sentence": "In 3 days , 1 week , 2 weeks , 3 weeks and 4 weeks after surgery , the MVD of test group was significantly higher than that of control group .", "entities": []}, {"sentence": "In 4 weeks after surgery , angiogenesis of test group reached to peak .", "entities": []}, {"sentence": "CONCLUSION : Vascular bundle implantation improved angiogenesis in non - vascularized autogenous bone graft in this study .", "entities": [{"name": "Vascular bundle", "type": "Anatomy", "pos": [13, 28]}, {"name": "autogenous bone graft", "type": "Anatomy", "pos": [86, 107]}]}, {"sentence": "Targeting glucose consumption and autophagy in myeloma with the novel nucleoside analogue 8 - aminoadenosine .", "entities": [{"name": "myeloma", "type": "Anatomy", "pos": [47, 54]}]}, {"sentence": "Multiple myeloma , an incurable plasma cell malignancy , is characterized by altered cellular metabolism and resistance to apoptosis .", "entities": [{"name": "myeloma", "type": "Anatomy", "pos": [9, 16]}, {"name": "plasma cell malignancy", "type": "Anatomy", "pos": [32, 54]}, {"name": "cellular", "type": "Anatomy", "pos": [85, 93]}]}, {"sentence": "Recent connections between glucose metabolism and resistance to apoptosis provide a compelling rationale for targeting metabolic changes in cancer .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [140, 146]}]}, {"sentence": "In this study , we have examined the ability of the purine analogue 8 - aminoadenosine to acutely reduce glucose consumption by regulating localization and expression of key glucose transporters .", "entities": []}, {"sentence": "Myeloma cells counteracted the metabolic stress by activating autophagy .", "entities": [{"name": "Myeloma cells", "type": "Anatomy", "pos": [0, 13]}]}, {"sentence": "Co - treatment with inhibitors of autophagy results in marked enhancement of cell death .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [77, 81]}]}, {"sentence": "Glucose consumption by drug - resistant myeloma cells was unaffected by 8 - aminoadenosine , and accordingly , no activation of autophagy was observed .", "entities": [{"name": "myeloma cells", "type": "Anatomy", "pos": [40, 53]}]}, {"sentence": "However , these cells can be sensitized to 8 - aminoadenosine under glucose - limiting conditions .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [16, 21]}]}, {"sentence": "The prosurvival autophagic response of myeloma to nutrient deprivation or to nucleoside analogue treatment has not been described previously .", "entities": [{"name": "myeloma", "type": "Anatomy", "pos": [39, 46]}]}, {"sentence": "This study establishes the potential of metabolic targeting as a broader means to kill and sensitize myeloma and identifies a compound that can achieve this goal .", "entities": [{"name": "myeloma", "type": "Anatomy", "pos": [101, 108]}]}, {"sentence": "Dopamine regulates phosphorylation of VEGF receptor 2 by engaging Src - homology - 2 - domain - containing protein tyrosine phosphatase 2 .", "entities": []}, {"sentence": "Vascular endothelial growth factor ( VEGF ) - induced receptor phosphorylation is the crucial step for initiating downstream signaling pathways that lead to angiogenesis or related pathophysiological outcomes .", "entities": []}, {"sentence": "Our previous studies have shown that the neurotransmitter dopamine could inhibit VEGF - induced phosphorylation of VEGF receptor 2 ( VEGFR - 2 ) , endothelial cell proliferation , migration , microvascular permeability , and thus , angiogenesis .", "entities": [{"name": "endothelial cell", "type": "Anatomy", "pos": [147, 163]}, {"name": "microvascular", "type": "Anatomy", "pos": [192, 205]}]}, {"sentence": "In this study , we address the mechanism by which VEGFR - 2 phosphorylation is regulated by dopamine .", "entities": []}, {"sentence": "Here , we demonstrate that D2 dopamine receptor ( D2DR ) colocalizes with VEGFR - 2 at the cell surface .", "entities": [{"name": "cell surface", "type": "Anatomy", "pos": [91, 103]}]}, {"sentence": "Dopamine pretreatment increases the translocation and colocalization of Src - homology - 2 - domain - containing protein tyrosine phosphatase ( SHP - 2 ) with D2DR at the cell surface .", "entities": [{"name": "cell surface", "type": "Anatomy", "pos": [171, 183]}]}, {"sentence": "Dopamine administration leads to increased VEGF - induced phosphorylation of SHP - 2 and this increased phosphorylation parallels the increased phosphatase activity of SHP - 2 .", "entities": []}, {"sentence": "Active SHP - 2 then dephosphorylates VEGFR - 2 at Y951 , Y996 and Y1059 , but not Y1175 .", "entities": []}, {"sentence": "We also observe that SHP - 2 knockdown impairs the dopamine - regulated inhibition of VEGF - induced phosphorylation of VEGFR - 2 and , subsequently , Src phosphorylation and migration .", "entities": []}, {"sentence": "Our data establish a novel role for SHP - 2 phosphatase in the dopamine - mediated regulation of VEGFR - 2 phosphorylation .", "entities": []}, {"sentence": "Glioma tumor stem - like cells promote tumor angiogenesis and vasculogenesis via vascular endothelial growth factor and stromal - derived factor 1 .", "entities": [{"name": "Glioma tumor stem - like cells", "type": "Anatomy", "pos": [0, 30]}, {"name": "tumor", "type": "Anatomy", "pos": [39, 44]}]}, {"sentence": "Cancer stem cells ( CSC ) are predicted to be critical drivers of tumor progression due to their self - renewal capacity and limitless proliferative potential .", "entities": [{"name": "Cancer stem cells", "type": "Anatomy", "pos": [0, 17]}, {"name": "CSC", "type": "Anatomy", "pos": [20, 23]}, {"name": "tumor", "type": "Anatomy", "pos": [66, 71]}]}, {"sentence": "An emerging area of research suggests that CSC may also support tumor progression by promoting tumor angiogenesis .", "entities": [{"name": "CSC", "type": "Anatomy", "pos": [43, 46]}, {"name": "tumor", "type": "Anatomy", "pos": [64, 69]}, {"name": "tumor", "type": "Anatomy", "pos": [95, 100]}]}, {"sentence": "To investigate how CSC contribute to tumor vascular development , we used an approach comparing tumor xenografts of the C6 glioma cell line containing either a low or a high fraction of CSC .", "entities": [{"name": "CSC", "type": "Anatomy", "pos": [19, 22]}, {"name": "tumor vascular", "type": "Anatomy", "pos": [37, 51]}, {"name": "tumor xenografts", "type": "Anatomy", "pos": [96, 112]}, {"name": "C6 glioma cell line", "type": "Anatomy", "pos": [120, 139]}, {"name": "CSC", "type": "Anatomy", "pos": [186, 189]}]}, {"sentence": "Compared with CSC - low tumors , CSC - high tumors exhibited increased microvessel density and blood perfusion and induced increased mobilization and tumor recruitment of bone marrow - derived endothelial progenitor cells ( EPC ) .", "entities": [{"name": "CSC - low tumors", "type": "Anatomy", "pos": [14, 30]}, {"name": "CSC - high tumors", "type": "Anatomy", "pos": [33, 50]}, {"name": "microvessel", "type": "Anatomy", "pos": [71, 82]}, {"name": "blood", "type": "Anatomy", "pos": [95, 100]}, {"name": "tumor", "type": "Anatomy", "pos": [150, 155]}, {"name": "bone marrow", "type": "Anatomy", "pos": [171, 182]}, {"name": "endothelial progenitor cells", "type": "Anatomy", "pos": [193, 221]}, {"name": "EPC", "type": "Anatomy", "pos": [224, 227]}]}, {"sentence": "CSC - high C6 cell cultures also induced higher levels of endothelial cell proliferation and tubule organization in vitro compared with CSC - low cultures .", "entities": [{"name": "CSC - high C6 cell cultures", "type": "Anatomy", "pos": [0, 27]}, {"name": "endothelial cell", "type": "Anatomy", "pos": [58, 74]}, {"name": "tubule", "type": "Anatomy", "pos": [93, 99]}, {"name": "CSC - low cultures", "type": "Anatomy", "pos": [136, 154]}]}, {"sentence": "CSC - high cultures and tumors expressed increased levels of the proangiogenic factors vascular endothelial growth factor and stromal - derived factor 1 , and when signaling by either factor was blocked , all aspects of angiogenesis observed in CSC - high cultures and tumors , including microvessel density , perfusion , EPC mobilization / recruitment , and stimulation of endothelial cell activity , were reduced to levels comparable with those observed in CSC - low cultures / tumors .", "entities": [{"name": "CSC - high cultures", "type": "Anatomy", "pos": [0, 19]}, {"name": "tumors", "type": "Anatomy", "pos": [24, 30]}, {"name": "CSC - high cultures", "type": "Anatomy", "pos": [245, 264]}, {"name": "tumors", "type": "Anatomy", "pos": [269, 275]}, {"name": "microvessel", "type": "Anatomy", "pos": [288, 299]}, {"name": "EPC", "type": "Anatomy", "pos": [322, 325]}, {"name": "endothelial cell", "type": "Anatomy", "pos": [374, 390]}, {"name": "CSC - low cultures", "type": "Anatomy", "pos": [459, 477]}, {"name": "tumors", "type": "Anatomy", "pos": [480, 486]}]}, {"sentence": "These results suggest that CSC contribute to tumor angiogenesis by promoting both local endothelial cell activity and systemic angiogenic processes involving bone marrow - derived EPC in a vascular endothelial growth factor - dependent and stromal - derived factor 1 - dependent manner .", "entities": [{"name": "CSC", "type": "Anatomy", "pos": [27, 30]}, {"name": "tumor", "type": "Anatomy", "pos": [45, 50]}, {"name": "endothelial cell", "type": "Anatomy", "pos": [88, 104]}, {"name": "bone marrow", "type": "Anatomy", "pos": [158, 169]}, {"name": "EPC", "type": "Anatomy", "pos": [180, 183]}]}, {"sentence": "Cognitive function and number of teeth in a community - dwelling elderly population without dementia .", "entities": [{"name": "teeth", "type": "Anatomy", "pos": [33, 38]}]}, {"sentence": "Although the number of sound or decayed teeth has been reported to be associated with cognitive function in elderly populations with dementia , little is known about this association in elderly populations without dementia .", "entities": [{"name": "teeth", "type": "Anatomy", "pos": [40, 45]}]}, {"sentence": "We evaluated this relationship , with adjustment for confounding factors , in Japanese populations of 60 - year - old ( n = 270 ; 120 males and 150 females ) and 65 - year - old ( n = 123 ; 57 males and 66 females ) individuals residing in Fukuoka Prefecture of Japan .", "entities": []}, {"sentence": "Dental examinations were performed in all subjects , along with the Mini - mental state examination ( MMSE ) for assessing cognitive function .", "entities": [{"name": "Dental", "type": "Anatomy", "pos": [0, 6]}]}, {"sentence": "Among the total of 393 subjects , the mean MMSE score was 27 . 9 + / - 1 . 9 , and 391 subjects scored 24 or higher .", "entities": []}, {"sentence": "The mean numbers of sound and decayed teeth were 12 . 0 + / - 6 . 3 and 0 . 5 + / - 1 . 2 , respectively .", "entities": [{"name": "teeth", "type": "Anatomy", "pos": [38, 43]}]}, {"sentence": "Associations were found between the numbers of sound and decayed teeth and MMSE in total subjects and males , but not in females , by multiple regression analysis adjusted for gender , age , level of education , marital status , smoking , alcohol drinking , working status , systolic blood pressure and blood glucose .", "entities": [{"name": "teeth", "type": "Anatomy", "pos": [65, 70]}, {"name": "blood", "type": "Anatomy", "pos": [284, 289]}, {"name": "blood", "type": "Anatomy", "pos": [303, 308]}]}, {"sentence": "An association was also found between MMSE and the number of sound teeth in a logistic regression analysis .", "entities": [{"name": "teeth", "type": "Anatomy", "pos": [67, 72]}]}, {"sentence": "In conclusion , associations were found between normal - range cognitive function and the numbers of sound and decayed teeth , after adjustment for various confounding factors , in an elderly Japanese population .", "entities": [{"name": "teeth", "type": "Anatomy", "pos": [119, 124]}]}, {"sentence": "Inducible nitric oxide synthase modulates angiogenesis in ischemic hindlimb of rat .", "entities": [{"name": "hindlimb", "type": "Anatomy", "pos": [67, 75]}]}, {"sentence": "BACKGROUND : Angiogenesis plays an important role in maintaining adequate oxygen delivery , and nitric oxide ( NO ) is a potential regulator of angiogenesis .", "entities": []}, {"sentence": "NO is synthesized through three isoforms of NO synthase ( NOS ) .", "entities": []}, {"sentence": "It is hypothesized that the NO derived from inducible NOS ( iNOS ) may promote survival of ischemic tissue through angiogenesis .", "entities": [{"name": "tissue", "type": "Anatomy", "pos": [100, 106]}]}, {"sentence": "To test this hypothesis , we investigated the effect of iNOS deficiency ( by L - NIL ) on angiogenesis in a hindlimb ischemia model .", "entities": [{"name": "hindlimb", "type": "Anatomy", "pos": [108, 116]}]}, {"sentence": "METHODS : Thirty - two male wistar rats randomly divided into four groups .", "entities": []}, {"sentence": "In groups 1 & 2 , hindlimb ischemia was induced by ligation of femoral artery and they received L - NIL and saline respectively .", "entities": [{"name": "hindlimb", "type": "Anatomy", "pos": [18, 26]}, {"name": "femoral artery", "type": "Anatomy", "pos": [63, 77]}]}, {"sentence": "The animals in groups 3 and 4 also received L - NIL and saline respectively without surgical procedure .", "entities": []}, {"sentence": "After 21 days , the serum concentration of nitrite , capillary density and expression of HIF1alpha were determined .", "entities": [{"name": "serum", "type": "Anatomy", "pos": [20, 25]}, {"name": "capillary", "type": "Anatomy", "pos": [53, 62]}]}, {"sentence": "RESULTS : Serum nitrite levels were significantly lower in L - NIL groups ( p < 0 . 05 ) .", "entities": [{"name": "Serum", "type": "Anatomy", "pos": [10, 15]}]}, {"sentence": "The capillary density in group 1 ( ischemia + L - NIL ) was significantly different from group 2 ( ischemia + saline ) ; group 1 : 360 . 33 + / - 77 . 02 , group 2 : 549 + / - 81 . 85 / mm2 , p < 0 . 05 ) . In addition , expression of HIF1alpha was significantly increased in ischemic groups ( p < 0 . 05 ) .", "entities": [{"name": "capillary", "type": "Anatomy", "pos": [4, 13]}]}, {"sentence": "CONCLUSION : Selective inhibition of iNOS by L - NIL inhibits angiogenesis in a hindlimb ischemic rat model .", "entities": [{"name": "hindlimb", "type": "Anatomy", "pos": [80, 88]}]}, {"sentence": "In addition , ischemia induces expression of HIF1alpha in hypoxic tissue .", "entities": [{"name": "hypoxic tissue", "type": "Anatomy", "pos": [58, 72]}]}, {"sentence": "Phenolic fraction of tobacco smoke condensate potentiates benzo [ a ] pyerene diol epoxide - induced cell transformation : role of protein kinase C .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [101, 105]}]}, {"sentence": "In this study we separated weakly acidic phenolic components from other neutral , acidic and basic components of tobacco smoke condensate ( TSC ) and observed that phenolic fraction of TSC significantly increased the number of colonies of promotion - sensitive JB6 Cl41 cells that showed anchorage - independent growth on soft agar in response to BPDE ( an ultimate carcinogen produced by metabolic activation of the PAH benzo [ a ] pyrene ) .", "entities": [{"name": "colonies", "type": "Anatomy", "pos": [227, 235]}, {"name": "JB6 Cl41 cells", "type": "Anatomy", "pos": [261, 275]}]}, {"sentence": "Anchorage - independent cell growth is indicative of cell transformation resulting in acquisition of tumorigenic potential .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [24, 28]}, {"name": "cell", "type": "Anatomy", "pos": [53, 57]}]}, {"sentence": "In order to understand the underlying mechanism by which TSC phenolic fraction potentiates BPDE - induced tumorigenicity , we examined its effect on the activation of two transcription factors AP - 1 and NF - kappaB which are known to be influenced by established tumor promoter TPA .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [106, 111]}]}, {"sentence": "BPDE treatment caused induction of both AP - 1 and NF - kappaB activity as determined by luciferase reporter assay and only NF - kappaB induction in response to BPDE was significantly attenuated by TSC phenolic fraction whereas AP - 1 induction remains unaltered .", "entities": []}, {"sentence": "Attenuation of NF - kappaB activation by TSC phenolic fraction was associated with significant decrease of intracellular PKC substrate phosphorylation in BPDE treated cells .", "entities": [{"name": "intracellular", "type": "Anatomy", "pos": [107, 120]}, {"name": "cells", "type": "Anatomy", "pos": [167, 172]}]}, {"sentence": "Non - specific PKC inhibitors staurosporine and bisindolylmaleimide II as well as inhibitors specific to conventional PKCs ( Go6976 ) and PKC - delta ( rottlerin ) attenuated NF - kappaB activation in BPDE treated cells to a varying degree indicating a possible link between PKC down - regulation and the attenuation of NF - kappaB activity by TSC phenolic fraction .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [214, 219]}]}, {"sentence": "Treatment of cells with PKC inhibitors also potentiated anchorage - independent growth of BPDE treated cells on soft agar .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [13, 18]}, {"name": "cells", "type": "Anatomy", "pos": [103, 108]}]}, {"sentence": "Our data suggest a possible role of PKC down - regulation in potentiation of BPDE - induced tumorogenicity by TSC phenolic fraction .", "entities": []}, {"sentence": "Killing tumor cells through their surface beta ( 2 ) - microglobulin or major histocompatibility complex class I molecules .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [8, 19]}, {"name": "surface", "type": "Anatomy", "pos": [34, 41]}]}, {"sentence": "Targeted antibody - based therapy has been used successfully to treat cancers .", "entities": [{"name": "cancers", "type": "Anatomy", "pos": [70, 77]}]}, {"sentence": "Recent studies have demonstrated that tumor cells treated with antibodies specific for beta ( 2 ) - microglobulin ( beta ( 2 ) M ) or major histocompatibility complex ( MHC ) class I molecules undergo apoptosis in vitro and in vivo ( mouse models ) .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [38, 49]}]}, {"sentence": "Antibodies against beta ( 2 ) M or MHC class I induce tumor cell apoptosis by 1 ) recruiting MHC class I molecules to lipid rafts and activating LYN kinase and the signal - transducing enzyme phospholipase C - gamma2 - dependent c - Jun N - terminal kinase signaling pathway and 2 ) expelling interleukin 6 and insulin - like growth factor 1 receptors out of lipid rafts and inhibiting the growth and survival factor - induced activation of the phosphatidylinositol 3 - kinase / Akt and extracellular signal - related kinase pathways .", "entities": [{"name": "tumor cell", "type": "Anatomy", "pos": [54, 64]}, {"name": "lipid rafts", "type": "Anatomy", "pos": [118, 129]}, {"name": "lipid rafts", "type": "Anatomy", "pos": [359, 370]}]}, {"sentence": "Consequently , mitochondrial integrity is compromised , and the caspase - 9 - dependent cascade is activated in treated tumor cells .", "entities": [{"name": "mitochondrial", "type": "Anatomy", "pos": [15, 28]}, {"name": "tumor cells", "type": "Anatomy", "pos": [120, 131]}]}, {"sentence": "However , although beta ( 2 ) M and MHC class I are expressed on normal hematopoietic cells , which is a potential safety concern , the monoclonal antibodies were selective to tumor cells and did not damage normal cells in vitro or in human - like mouse models .", "entities": [{"name": "hematopoietic cells", "type": "Anatomy", "pos": [72, 91]}, {"name": "tumor cells", "type": "Anatomy", "pos": [176, 187]}, {"name": "cells", "type": "Anatomy", "pos": [214, 219]}]}, {"sentence": "These findings suggest that targeting beta ( 2 ) M or MHC class I by using antibodies or other agents offers a potential therapeutic approach for beta ( 2 ) M / MHC class I - expressing malignancies .", "entities": [{"name": "malignancies", "type": "Anatomy", "pos": [186, 198]}]}, {"sentence": "Cancer 2010 .", "entities": []}, {"sentence": "( c ) 2010 American Cancer Society .", "entities": []}, {"sentence": "Comment on \" Why reduced - form regression models of health effects versus exposures should not replace QRA : livestock production and infant mortality as an example , \" by Louis Anthony ( Tony ) Cox , Jr . , Risk Analysis 2009 , Vol .", "entities": []}, {"sentence": "29 , No . 12 .", "entities": []}, {"sentence": "While a recent paper by Cox in this journal uses as its motivating factor the benefits of quantitative risk assessment , its content is entirely devoted to critiquing Sneeringer ' s article in the American Journal of Agricultural Economics .", "entities": []}, {"sentence": "Cox ' s two main critiques of Sneeringer are fundamentally flawed and misrepresent the original article .", "entities": []}, {"sentence": "Cox posits that Sneeringer did A and B , and then argues why A and B are incorrect .", "entities": []}, {"sentence": "However , Sneeringer in fact did C and D ; thus critiques of A and B are not applicable to Sneeringer ' s analysis .", "entities": []}, {"sentence": "Loss of CDC4 / FBXW7 in gastric carcinoma .", "entities": [{"name": "gastric carcinoma", "type": "Anatomy", "pos": [24, 41]}]}, {"sentence": "BACKGROUND : CDC4 / FBXW7 , encoding a ubiquitin ligase , maps to 4q32 and has been implicated as a tumor suppressor gene and therapeutic target in many tumor types .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [100, 105]}, {"name": "tumor", "type": "Anatomy", "pos": [153, 158]}]}, {"sentence": "Mutations in colonic adenomas , and the frequent losses on 4q described in gastric cancer prompt speculation about the role of CDC4 / FBXW7 in gastric carcinogenesis .", "entities": [{"name": "colonic adenomas", "type": "Anatomy", "pos": [13, 29]}, {"name": "4q", "type": "Anatomy", "pos": [59, 61]}, {"name": "gastric cancer", "type": "Anatomy", "pos": [75, 89]}, {"name": "gastric", "type": "Anatomy", "pos": [143, 150]}]}, {"sentence": "METHODS : We assessed the role of CDC4 / FBXW7 in gastric cancer , through loss of heterozygosity ( LOH ) and multiplex ligation - dependent probe amplification ( MLPA ) on 47 flow - sorted gastric carcinomas including early - onset gastric cancers ( EOGC ) and xenografted conventional gastric carcinomas .", "entities": [{"name": "gastric cancer", "type": "Anatomy", "pos": [50, 64]}, {"name": "gastric carcinomas", "type": "Anatomy", "pos": [190, 208]}, {"name": "early - onset gastric cancers", "type": "Anatomy", "pos": [219, 248]}, {"name": "EOGC", "type": "Anatomy", "pos": [251, 255]}, {"name": "gastric carcinomas", "type": "Anatomy", "pos": [287, 305]}]}, {"sentence": "Ploidy analysis was carried out on 39 EOGCs and immunohistochemistry of CDC4 / FBXW7 and its substrates c - myc , c - jun , Notch and cyclin E was performed on 204 gastric carcinomas using tissue microarrays ( TMAs ) .", "entities": [{"name": "EOGCs", "type": "Anatomy", "pos": [38, 43]}, {"name": "gastric carcinomas", "type": "Anatomy", "pos": [164, 182]}, {"name": "tissue", "type": "Anatomy", "pos": [189, 195]}]}, {"sentence": "Sequence analysis of CDC4 / FBXW7 was carried out on gastric carcinoma cell lines and xenografts .", "entities": [{"name": "gastric carcinoma cell lines", "type": "Anatomy", "pos": [53, 81]}, {"name": "xenografts", "type": "Anatomy", "pos": [86, 96]}]}, {"sentence": "RESULTS : Loss of heterozygosity of CDC4 / FBXW7 occurred in 32 % of EOGCs , and correlated with loss of expression in 26 % .", "entities": [{"name": "EOGCs", "type": "Anatomy", "pos": [69, 74]}]}, {"sentence": "Loss of expression was frequent in both EOGC and conventional gastric cancers .", "entities": [{"name": "EOGC", "type": "Anatomy", "pos": [40, 44]}, {"name": "gastric cancers", "type": "Anatomy", "pos": [62, 77]}]}, {"sentence": "No CDC4 / FBXW7 mutations were found and loss of CDC4 / FBXW7 did not correlate with ploidy status .", "entities": []}, {"sentence": "There was a significant correlation between loss of CDC4 / FBXW7 expression and upregulation of c - myc .", "entities": []}, {"sentence": "CONCLUSION : Loss of CDC4 / FBXW7 appears to play a role in both EOGC and conventional gastric carcinogenesis , and c - myc overexpression is likely to be an important oncogenic consequence of CDC4 / FBXW7 loss .", "entities": [{"name": "EOGC", "type": "Anatomy", "pos": [65, 69]}, {"name": "gastric", "type": "Anatomy", "pos": [87, 94]}]}, {"sentence": "Angiogenesis inhibitors : current strategies and future prospects .", "entities": []}, {"sentence": "Angiogenesis has become an attractive target for drug therapy because of its key role in tumor growth .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [89, 94]}]}, {"sentence": "An extensive array of compounds is currently in preclinical development , with many now entering the clinic and / or achieving approval from the US Food and Drug Administration .", "entities": []}, {"sentence": "Several regulatory and signaling molecules governing angiogenesis are of interest , including growth factors ( eg , vascular endothelial growth factor , platelet - derived growth factor , fibroblast growth factor , and epidermal growth factor ) , receptor tyrosine kinases , and transcription factors such as hypoxia inducible factor , as well as molecules involved in mitogen - activated protein kinase ( MAPK ) and phosphoinositide 3 - kinase ( PI3K ) signaling .", "entities": []}, {"sentence": "Pharmacologic agents have been identified that target these pathways , yet for some agents ( notably thalidomide ) , an understanding of the specific mechanisms of antitumor action has proved elusive .", "entities": [{"name": "antitumor", "type": "Anatomy", "pos": [164, 173]}]}, {"sentence": "The following review describes key molecular mechanisms and novel therapies that are on the horizon for antiangiogenic tumor therapy .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [119, 124]}]}, {"sentence": "Prognostic significance of TRAIL signaling molecules in stage II and III colorectal cancer .", "entities": [{"name": "stage II and III colorectal cancer", "type": "Anatomy", "pos": [56, 90]}]}, {"sentence": "PURPOSE :", "entities": []}, {"sentence": "We previously found that cellular FLICE - inhibitory protein ( c - FLIP ) , caspase 8 , and tumor necrosis factor - related apoptosis - inducing ligand ( TRAIL ) receptor 2 ( DR5 ) are major regulators of cell viability and chemotherapy - induced apoptosis in colorectal cancer .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [25, 29]}, {"name": "colorectal cancer", "type": "Anatomy", "pos": [260, 277]}]}, {"sentence": "In this study , we determined the prognostic significance of c - FLIP , caspase 8 , TRAIL and DR5 expression in tissues from patients with stage II and III colorectal cancer .", "entities": [{"name": "tissues", "type": "Anatomy", "pos": [112, 119]}, {"name": "stage II and III colorectal cancer", "type": "Anatomy", "pos": [139, 173]}]}, {"sentence": "EXPERIMENTAL DESIGN :", "entities": []}, {"sentence": "Tissue microarrays were constructed from matched normal and tumor tissue derived from patients ( n = 253 ) enrolled in a phase III trial of adjuvant 5 - fluorouracil - based chemotherapy versus postoperative observation alone .", "entities": [{"name": "Tissue", "type": "Anatomy", "pos": [0, 6]}, {"name": "tumor tissue", "type": "Anatomy", "pos": [60, 72]}]}, {"sentence": "TRAIL , DR5 , caspase 8 , and c - FLIP expression levels were determined by immunohistochemistry .", "entities": []}, {"sentence": "RESULTS :", "entities": []}, {"sentence": "Colorectal tumors displayed significantly higher expression levels of c - FLIP ( P < 0 . 001 ) , caspase 8 ( P = 0 . 01 ) , and DR5 ( P < 0 . 001 ) , but lower levels of TRAIL ( P < 0 . 001 ) compared with matched normal tissue .", "entities": [{"name": "Colorectal tumors", "type": "Anatomy", "pos": [0, 17]}, {"name": "tissue", "type": "Anatomy", "pos": [221, 227]}]}, {"sentence": "In univariate analysis , higher TRAIL expression in the tumor was associated with worse overall survival ( P = 0 . 026 ) , with a trend to decreased relapse - free survival ( RFS ; P = 0 . 06 ) , and higher tumor c - FLIP expression was associated with a significantly decreased RFS ( P = 0 . 015 ) .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [56, 61]}, {"name": "tumor", "type": "Anatomy", "pos": [207, 212]}]}, {"sentence": "Using multivariate predictive modeling for RFS in all patients and including all biomarkers , age , treatment , and stage , we found that the model was significant when the mean tumor c - FLIP expression score and disease stage were included ( P < 0 . 001 ) .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [178, 183]}]}, {"sentence": "As regards overall survival , the overall model was predictive when both TRAIL expression and disease stage were included ( P < 0 . 001 ) .", "entities": []}, {"sentence": "CONCLUSIONS :", "entities": []}, {"sentence": "High c - FLIP and TRAIL expression may be independent adverse prognostic markers in stage II and III colorectal cancer and might identify patients most at risk of relapse .", "entities": [{"name": "stage II and III colorectal cancer", "type": "Anatomy", "pos": [84, 118]}]}, {"sentence": "Overexpression of Bax inhibitor - 1 ( BI - 1 ) induces cell transformation in NIH3T3 cells .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [55, 59]}, {"name": "NIH3T3 cells", "type": "Anatomy", "pos": [78, 90]}]}, {"sentence": "BI - 1 ( Bax inhibitor - 1 ) , an apoptosis - inhibiting gene belonging to the Bcl - 2 protein family , plays an important role in mitochondrial apoptosis pathway to suppress Bax - induced apoptosis .", "entities": [{"name": "mitochondrial", "type": "Anatomy", "pos": [131, 144]}]}, {"sentence": "To investigate the potential role of BI - 1 in promoting cell growth and tumorigenesis , in the present study we overexpressed the BI - 1 gene in NIH3T3 cells using the lentivirus - mediated gene expression system .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [57, 61]}, {"name": "NIH3T3 cells", "type": "Anatomy", "pos": [146, 158]}]}, {"sentence": "Our in vitro studies showed that NIH3T3 cells overexpressing BI - 1 displayed a significantly higher growth rate and formed more and larger colonies than the control cells .", "entities": [{"name": "NIH3T3 cells", "type": "Anatomy", "pos": [33, 45]}, {"name": "colonies", "type": "Anatomy", "pos": [140, 148]}, {"name": "cells", "type": "Anatomy", "pos": [166, 171]}]}, {"sentence": "In addition , our in vivo studies indicated that the lenti - BI - 1 - infected cells formed obvious tumours , while no tumours were formed by the control cells after subcutaneously injected into nude mice .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [79, 84]}, {"name": "tumours", "type": "Anatomy", "pos": [100, 107]}, {"name": "tumours", "type": "Anatomy", "pos": [119, 126]}, {"name": "cells", "type": "Anatomy", "pos": [154, 159]}, {"name": "subcutaneously", "type": "Anatomy", "pos": [166, 180]}]}, {"sentence": "These results strongly suggested that the BI - 1 gene might play a crucial role in neoplastic genesis and development .", "entities": [{"name": "neoplastic", "type": "Anatomy", "pos": [83, 93]}]}, {"sentence": "Anti - metastasis effects of gallic acid on gastric cancer cells involves inhibition of NF - kappaB activity and downregulation of PI3K / AKT / small GTPase signals .", "entities": [{"name": "gastric cancer cells", "type": "Anatomy", "pos": [44, 64]}]}, {"sentence": "Polyphenols are natural antioxidants that are thought to contribute to prevention of cardiovascular disease and malignancy .", "entities": [{"name": "cardiovascular", "type": "Anatomy", "pos": [85, 99]}, {"name": "malignancy", "type": "Anatomy", "pos": [112, 122]}]}, {"sentence": "Although many studies have been carried out to investigate the chemopreventive role of flavonoids , less attention has been focused on phenolic acids .", "entities": []}, {"sentence": "In this study , the aim was to investigate the effect of phenolic acids found abundantly in vegetables , i . e . gallic acid ( GA ) , caffeic acid ( CA ) and protocatechuic acid ( PCA ) , on the inhibition of gastric adenocarcinoma ( AGS ) cell metastasis .", "entities": [{"name": "vegetables", "type": "Anatomy", "pos": [92, 102]}, {"name": "gastric adenocarcinoma ( AGS ) cell", "type": "Anatomy", "pos": [209, 244]}]}, {"sentence": "The results showed 0 . 01 mM GA induced the same level of cell toxicity as 4 . 0mM PCA .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [58, 62]}]}, {"sentence": "Using wound - healing assay and Boyden chamber assay , GA had potent inhibitory effects on AGS cell migration .", "entities": [{"name": "wound", "type": "Anatomy", "pos": [6, 11]}, {"name": "AGS cell", "type": "Anatomy", "pos": [91, 99]}]}, {"sentence": "The expression of MMP - 2 / 9 of AGS cells was inhibited by 2 . 0 microM of GA .", "entities": [{"name": "AGS cells", "type": "Anatomy", "pos": [33, 42]}]}, {"sentence": "It is possible that the suppressive effect of GA on MMP - 2 / 9 might involve the inhibition of NF - kappaB activity .", "entities": []}, {"sentence": "Multiple proteins involved in metastasis and the cytoskeletal reorganization signal pathway , including Ras , Cdc42 , Rac1 , RhoA , RhoB , PI3K and p38MAPK , were also inhibited by GA .", "entities": [{"name": "cytoskeletal", "type": "Anatomy", "pos": [49, 61]}]}, {"sentence": "Furthermore , immunoreactivity assay of cytoskeletal F - actin demonstrated a significant inhibitory effect of GA treatment .", "entities": [{"name": "cytoskeletal", "type": "Anatomy", "pos": [40, 52]}]}, {"sentence": "In conclusion , GA may have the potential to be an effective agent for prevention and treatment of gastric cancer metastasis .", "entities": [{"name": "gastric cancer", "type": "Anatomy", "pos": [99, 113]}]}, {"sentence": "1 , 4 - phenylenebis ( methylene ) selenocyanate , but not selenomethionine , inhibits androgen receptor and Akt signaling in human prostate cancer cells .", "entities": [{"name": "prostate cancer cells", "type": "Anatomy", "pos": [132, 153]}]}, {"sentence": "The lack of treatment for worried - well patients with high - grade prostatic intraepithelial neoplasia combined with issues of recurrence and hormone resistance in prostate cancer survivors remains a major public health obstacle .", "entities": [{"name": "high - grade prostatic intraepithelial neoplasia", "type": "Anatomy", "pos": [55, 103]}, {"name": "prostate cancer", "type": "Anatomy", "pos": [165, 180]}]}, {"sentence": "The long latency of prostate cancer development provides an opportunity to intervene with agents of known mechanisms at various stages of disease progression .", "entities": [{"name": "prostate cancer", "type": "Anatomy", "pos": [20, 35]}]}, {"sentence": "A number of signaling cascades have been shown to play important roles in prostate cancer development and progression , including the androgen receptor ( AR ) and phosphatidylinositol 3 - kinase / Akt signaling pathways .", "entities": [{"name": "prostate cancer", "type": "Anatomy", "pos": [74, 89]}]}, {"sentence": "Crosstalk between these two pathways is also thought to contribute to progression and hormone - refractory prostate disease .", "entities": [{"name": "prostate disease", "type": "Anatomy", "pos": [107, 123]}]}, {"sentence": "Our initial investigations show that the naturally occurring organoselenium compound selenomethionine ( SM ) and the synthetic 1 , 4 - phenylenebis ( methylene ) selenocyanate ( p - XSC ) can inhibit human prostate cancer cell viability ; however , in contrast to SM , p - XSC is active at physiologically relevant doses .", "entities": [{"name": "prostate cancer cell", "type": "Anatomy", "pos": [206, 226]}]}, {"sentence": "In the current investigation , we show that p - XSC , but not an equivalent dose of SM , alters molecular targets and induces apoptosis in androgen - responsive LNCaP and androgen - independent LNCaP C4 - 2 human prostate cancer cells .", "entities": [{"name": "LNCaP", "type": "Anatomy", "pos": [161, 166]}, {"name": "LNCaP C4 - 2 human prostate cancer cells", "type": "Anatomy", "pos": [194, 234]}]}, {"sentence": "p - XSC effectively inhibits AR expression and transcriptional activity in both cell lines .", "entities": [{"name": "cell lines", "type": "Anatomy", "pos": [80, 90]}]}, {"sentence": "p - XSC also decreases Akt phosphorylation as well as Akt - specific phosphorylation of the AR .", "entities": []}, {"sentence": "Inhibition of Akt , however , does not fully attenuate p - XSC - mediated downregulation of AR activity , suggesting that inhibition of AR signaling by p - XSC does not occur solely through alterations in the phosphatidylinositol 3 - kinase / Akt survival pathway .", "entities": []}, {"sentence": "Our data suggest that p - XSC inhibits multiple signaling pathways in prostate cancer , likely accounting for the downstream effects on proliferation and apoptosis .", "entities": [{"name": "prostate cancer", "type": "Anatomy", "pos": [70, 85]}]}, {"sentence": "Sanguinarine induces apoptosis of human osteosarcoma cells through the extrinsic and intrinsic pathways .", "entities": [{"name": "osteosarcoma cells", "type": "Anatomy", "pos": [40, 58]}]}, {"sentence": "The quaternary benzo [ c ] phenanthridine alkaloid sanguinarine inhibits the proliferation of cancerous cells from different origins , including lung , breast , pancreatic and colon , but nothing is known of its effects on osteosarcoma , a primary malignant bone tumour .", "entities": [{"name": "cancerous cells", "type": "Anatomy", "pos": [94, 109]}, {"name": "lung", "type": "Anatomy", "pos": [145, 149]}, {"name": "breast", "type": "Anatomy", "pos": [152, 158]}, {"name": "pancreatic", "type": "Anatomy", "pos": [161, 171]}, {"name": "colon", "type": "Anatomy", "pos": [176, 181]}, {"name": "osteosarcoma", "type": "Anatomy", "pos": [223, 235]}, {"name": "primary malignant bone tumour", "type": "Anatomy", "pos": [240, 269]}]}, {"sentence": "We have found that sanguinarine alters the morphology and reduces the viability of MG - 63 and SaOS - 2 human osteosarcoma cell lines in concentration - and time - dependent manner .", "entities": [{"name": "MG - 63", "type": "Anatomy", "pos": [83, 90]}, {"name": "SaOS - 2 human osteosarcoma cell lines", "type": "Anatomy", "pos": [95, 133]}]}, {"sentence": "Incubation with 1 micromol / L sanguinarine for 4 and 24h killed more efficiently MG - 63 cells than SaOS - 2 cells , while incubation with 5 micromol / L sanguinarine killed almost 100 % of both cell populations within 24h .", "entities": [{"name": "MG - 63 cells", "type": "Anatomy", "pos": [82, 95]}, {"name": "SaOS - 2 cells", "type": "Anatomy", "pos": [101, 115]}, {"name": "cell populations", "type": "Anatomy", "pos": [196, 212]}]}, {"sentence": "This treatment also changed the mitochondrial membrane potential in both MG - 63 and SaOS - 2 cells within 1h , caused chromatin condensation and the formation of apoptotic bodies .", "entities": [{"name": "mitochondrial membrane", "type": "Anatomy", "pos": [32, 54]}, {"name": "MG - 63", "type": "Anatomy", "pos": [73, 80]}, {"name": "SaOS - 2 cells", "type": "Anatomy", "pos": [85, 99]}, {"name": "chromatin", "type": "Anatomy", "pos": [119, 128]}, {"name": "apoptotic bodies", "type": "Anatomy", "pos": [163, 179]}]}, {"sentence": "It activated multicaspases , and increased the activities of caspase - 8 and caspase - 9 in both MG - 63 and SaOS - 2 cells .", "entities": [{"name": "MG - 63", "type": "Anatomy", "pos": [97, 104]}, {"name": "SaOS - 2 cells", "type": "Anatomy", "pos": [109, 123]}]}, {"sentence": "These data highlight sanguinarine as a novel potential agent for bone cancer therapy .", "entities": [{"name": "bone cancer", "type": "Anatomy", "pos": [65, 76]}]}, {"sentence": "Actin - sequestering protein , thymosin beta - 4 , is a novel hypoxia responsive regulator .", "entities": []}, {"sentence": "Angiogenesis is induced by soluble factors such as vascular endothelial growth factor ( VEGF ) released from tumor cells in hypoxia .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [109, 120]}]}, {"sentence": "It enhances solid tumor growth and provides an ability to establish metastasis at peripheral sites by tumor cell migration .", "entities": [{"name": "solid tumor", "type": "Anatomy", "pos": [12, 23]}, {"name": "peripheral sites", "type": "Anatomy", "pos": [82, 98]}, {"name": "tumor cell", "type": "Anatomy", "pos": [102, 112]}]}, {"sentence": "Thymosin beta - 4 ( TB4 ) is an actin - sequestering protein to control cytoskeletal reorganization .", "entities": [{"name": "cytoskeletal", "type": "Anatomy", "pos": [72, 84]}]}, {"sentence": "Here , we investigated whether angiogenesis and tumor metastasis are dependent on hypoxia conditioning - induced TB4 expression in B16F10 melanoma cells .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [48, 53]}, {"name": "B16F10 melanoma cells", "type": "Anatomy", "pos": [131, 152]}]}, {"sentence": "TB4 expression in B16F10 cells was increased by hypoxia conditioning in a time - dependent manner .", "entities": [{"name": "B16F10 cells", "type": "Anatomy", "pos": [18, 30]}]}, {"sentence": "In addition , we found an increase of angiogenesis and HIF - 1alpha expression in TB4 - transgenic ( Tg ) mice as compared to wildtype mice .", "entities": []}, {"sentence": "When wound healing assay was used to assess in vitro tumor cell migration , hypoxia conditioning for 1 h enhanced B16F10 cell migration .", "entities": [{"name": "wound", "type": "Anatomy", "pos": [5, 10]}, {"name": "tumor cell", "type": "Anatomy", "pos": [53, 63]}, {"name": "B16F10 cell", "type": "Anatomy", "pos": [114, 125]}]}, {"sentence": "When TB4 expression in B16F10 cells was inhibited by the infection with small hairpin ( sh ) RNA of TB4 cloned in lentiviral vector , tumor cell migration was retarded .", "entities": [{"name": "B16F10 cells", "type": "Anatomy", "pos": [23, 35]}, {"name": "tumor cell", "type": "Anatomy", "pos": [134, 144]}]}, {"sentence": "In addition , hypoxia conditioning - induced tumor cell migration was reduced by the infection of lentiviral shRNA of TB4 .", "entities": [{"name": "tumor cell", "type": "Anatomy", "pos": [45, 55]}]}, {"sentence": "HIF - 1alpha stabilization and the expression of VEGF isoform 165 and 121 in hypoxia were also reduced by the infection of lentiviral shRNA of TB4 in B16F10 cells .", "entities": [{"name": "B16F10 cells", "type": "Anatomy", "pos": [150, 162]}]}, {"sentence": "We also found an increase of tumor growth and lung metastasis count in TB4 - Tg mice as compared to wildtype mice .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [29, 34]}, {"name": "lung", "type": "Anatomy", "pos": [46, 50]}]}, {"sentence": "Collectively , hypoxia conditioning induced tumor cell migration by TB4 expression - dependent HIF - 1alpha stabilization .", "entities": [{"name": "tumor cell", "type": "Anatomy", "pos": [44, 54]}]}, {"sentence": "It suggests that TB4 could be a hypoxia responsive regulator to control tumor cell migration in angiogenesis and tumor metastasis .", "entities": [{"name": "tumor cell", "type": "Anatomy", "pos": [72, 82]}, {"name": "tumor", "type": "Anatomy", "pos": [113, 118]}]}, {"sentence": "Androgen stimulates glycolysis for de novo lipid synthesis by increasing the activities of hexokinase 2 and 6 - phosphofructo - 2 - kinase / fructose - 2 , 6 - bisphosphatase 2 in prostate cancer cells .", "entities": [{"name": "prostate cancer cells", "type": "Anatomy", "pos": [180, 201]}]}, {"sentence": "Up - regulation of lipogenesis by androgen is one of the most characteristic metabolic features of LNCaP prostate cancer cells .", "entities": [{"name": "LNCaP prostate cancer cells", "type": "Anatomy", "pos": [99, 126]}]}, {"sentence": "The present study revealed that androgen increases glucose utilization for de novo lipogenesis in LNCaP cells through the activation of HK2 ( hexokinase 2 ) and activation of the cardiac isoform of PFKFB2 ( 6 - phosphofructo - 2 - kinase / fructose - 2 , 6 - bisphosphatase ) .", "entities": [{"name": "LNCaP cells", "type": "Anatomy", "pos": [98, 109]}, {"name": "cardiac", "type": "Anatomy", "pos": [179, 186]}]}, {"sentence": "Activation of PKA ( cAMP - dependent protein kinase ) by androgen increased phosphorylation of CREB [ CRE ( cAMP - response element ) - binding protein ] , which in turn bound to CRE on the promoter of the HK2 gene resulting in transcriptional activation of the HK2 gene .", "entities": []}, {"sentence": "Up - regulation of PFKFB2 expression was mediated by the direct binding of ligand - activated androgen receptor to the PFKFB2 promoter .", "entities": []}, {"sentence": "The activated PI3K ( phosphoinositide 3 - kinase ) / Akt signalling pathway in LNCaP cells contributes to the phosphorylation of PFKFB2 at Ser466 and Ser483 , resulting in the constitutive activation of PFK - 2 ( 6 - phosphofructo - 2 - kinase ) activity .", "entities": [{"name": "LNCaP cells", "type": "Anatomy", "pos": [79, 90]}]}, {"sentence": "Glucose uptake and lipogenesis were severely blocked by knocking - down of PFKFB2 using siRNA ( small interfering RNA ) or by inhibition of PFK - 2 activity with LY294002 treatment .", "entities": []}, {"sentence": "Taken together , our results suggest that the induction of de novo lipid synthesis by androgen requires the transcriptional up - regulation of HK2 and PFKFB2 , and phosphorylation of PFKFB2 generated by the PI3K / Akt signalling pathway to supply the source for lipogenesis from glucose in prostate cancer cells .", "entities": [{"name": "prostate cancer cells", "type": "Anatomy", "pos": [290, 311]}]}, {"sentence": "Influences on the pharmacokinetics of oxycodone : a multicentre cross - sectional study in 439 adult cancer patients .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [101, 107]}]}, {"sentence": "OBJECTIVE :", "entities": []}, {"sentence": "Oxycodone is widely used for the treatment of cancer pain , but little is known of its pharmacokinetics in cancer pain patients .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [46, 52]}, {"name": "cancer", "type": "Anatomy", "pos": [107, 113]}]}, {"sentence": "The aim of this study was to explore the relationships between ordinary patient characteristics and serum concentrations of oxycodone and the ratios noroxycodone or oxymorphone / oxycodone in cancer patients .", "entities": [{"name": "serum", "type": "Anatomy", "pos": [100, 105]}, {"name": "cancer", "type": "Anatomy", "pos": [192, 198]}]}, {"sentence": "METHODS :", "entities": []}, {"sentence": "Four hundred and thirty - nine patients using oral oxycodone for cancer pain were included .", "entities": [{"name": "oral", "type": "Anatomy", "pos": [46, 50]}, {"name": "cancer", "type": "Anatomy", "pos": [65, 71]}]}, {"sentence": "The patients ' characteristics ( sex , age , body mass index [ BMI ] , Karnofsky performance status , \" time since starting opioids \" , \" oxycodone total daily dose \" , \" time from last oxycodone dose \" , use of CYP3A4 inducer / inhibitor , \" use of systemic steroids \" , \" number of medications taken in the last 24 h \" , glomerular filtration rate ( GFR ) and albumin serum concentrations ) influence on oxycodone serum concentrations or metabolite / oxycodone ratios were explored by multiple regression analyses .", "entities": [{"name": "body", "type": "Anatomy", "pos": [45, 49]}, {"name": "glomerular", "type": "Anatomy", "pos": [323, 333]}, {"name": "serum", "type": "Anatomy", "pos": [370, 375]}, {"name": "serum", "type": "Anatomy", "pos": [416, 421]}]}, {"sentence": "RESULTS :", "entities": []}, {"sentence": "Sex , CYP3A4 inducers / inhibitors , total daily dose , and \" time from last oxycodone dose \" predicted oxycodone concentrations .", "entities": []}, {"sentence": "CYP3A4 inducers , total daily dose , and \" number of medications taken in the last 24 h \" predicted the oxymorphone / oxycodone ratio .", "entities": []}, {"sentence": "Total daily dose , \" time from last dose to blood sample \" , albumin , sex , CYP3A4 inducers / inhibitors , steroids , BMI and GFR predicted the noroxycodone / oxycodone ratio .", "entities": [{"name": "blood sample", "type": "Anatomy", "pos": [44, 56]}]}, {"sentence": "CONCLUSION :", "entities": []}, {"sentence": "Women had lower oxycodone serum concentrations than men .", "entities": [{"name": "serum", "type": "Anatomy", "pos": [26, 31]}]}, {"sentence": "CYP3A4 inducers / inhibitors should be used with caution as these are predicted to have a significant impact on oxycodone pharmacokinetics .", "entities": []}, {"sentence": "Other characteristics explained only minor parts of the variability of the outcomes .", "entities": []}, {"sentence": "Geometric correlations and breakdown of mesoscopic universality in spin transport .", "entities": []}, {"sentence": "We construct a unified semiclassical theory of charge and spin transport in chaotic ballistic and disordered diffusive mesoscopic systems with spin - orbit interaction .", "entities": []}, {"sentence": "Neglecting dynamic effects of spin - orbit interaction , we reproduce the random matrix theory results that the spin conductance fluctuates universally around zero average .", "entities": []}, {"sentence": "Incorporating these effects into the theory , we show that geometric correlations generate finite average spin conductances , but that they do not affect the charge conductance to leading order .", "entities": []}, {"sentence": "The theory , which is confirmed by numerical transport calculations , allows us to investigate the entire range from the weak to the previously unexplored strong spin - orbit regime , where the spin rotation time is shorter than the momentum relaxation time .", "entities": []}, {"sentence": "Development and validation of an approach to produce large - scale quantities of CpG - methylated plasmid DNA .", "entities": [{"name": "plasmid", "type": "Anatomy", "pos": [98, 105]}]}, {"sentence": "The prokaryotic CpG - specific DNA methylase from Spiroplasma , SssI methylase , has been extensively used to methylate plasmid DNA in vitro to investigate the effects of methylation in vertebrate systems .", "entities": [{"name": "plasmid", "type": "Anatomy", "pos": [120, 127]}]}, {"sentence": "Currently available methods to produce CpG - methylated plasmid DNA have certain limitations and cannot generate large quantities of methylated DNA without cost or problems of purity .", "entities": [{"name": "plasmid", "type": "Anatomy", "pos": [56, 63]}]}, {"sentence": "Here we describe an approach in which the SssI methylase gene has been introduced into the Escherichia coli bacterial genome under the control of an inducible promoter .", "entities": []}, {"sentence": "Plasmid DNA propagated in this bacterium under conditions which induce the methylase gene result in significant ( > 90 % ) CpG methylation .", "entities": [{"name": "Plasmid", "type": "Anatomy", "pos": [0, 7]}]}, {"sentence": "Methylated DNA produced by this approach behaves similarly to methylated DNA produced in vitro using the purified methylase .", "entities": []}, {"sentence": "The approach is scalable allowing for the production of milligram quantities of methylated plasmid DNA .", "entities": [{"name": "plasmid", "type": "Anatomy", "pos": [91, 98]}]}, {"sentence": "Diallyl trisulfide ( DATS ) inhibits mouse colon tumor in mouse CT - 26 cells allograft model in vivo .", "entities": [{"name": "colon tumor", "type": "Anatomy", "pos": [43, 54]}, {"name": "CT - 26 cells", "type": "Anatomy", "pos": [64, 77]}]}, {"sentence": "Our earlier studies showed that DATS induced apoptosis in human colon cancer HT29 and colo 205 cell lines in vitro .", "entities": [{"name": "colon cancer HT29", "type": "Anatomy", "pos": [64, 81]}, {"name": "colo 205 cell lines", "type": "Anatomy", "pos": [86, 105]}]}, {"sentence": "However , there is no report to show that DATS induced apoptosis in vitro and inhibited CT26 cancer cells in vivo on a murine allograft animal model .", "entities": [{"name": "CT26 cancer cells", "type": "Anatomy", "pos": [88, 105]}]}, {"sentence": "In vitro studies , the results indicated that DATS induced morphological changes and induction of apoptosis in CT26 cells .", "entities": [{"name": "CT26 cells", "type": "Anatomy", "pos": [111, 121]}]}, {"sentence": "In vivo studies , CT26 cancer cells were implanted into BALB / c mice and groups of mice were treated with vehicle , DATS ( 10 and 50 mg / kg of body weight ) .", "entities": [{"name": "CT26 cancer cells", "type": "Anatomy", "pos": [18, 35]}, {"name": "body", "type": "Anatomy", "pos": [145, 149]}]}, {"sentence": "DATS were injected once per four days intraperitoneally ( i . p . ) , with treatment starting 4 weeks prior to cells inoculation .", "entities": [{"name": "intraperitoneally", "type": "Anatomy", "pos": [38, 55]}, {"name": "cells", "type": "Anatomy", "pos": [111, 116]}]}, {"sentence": "Treatment with vehicle or with 10 and 50 mg / kg of DATS resulted in a reduction in tumor volume and weight .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [84, 89]}]}, {"sentence": "Tumor volume and total hemoglobin in allograft mice treated with 50 mg / kg DATS were significantly smaller than that in the control group .", "entities": [{"name": "Tumor", "type": "Anatomy", "pos": [0, 5]}]}, {"sentence": "These findings indicated that DATS inhibits tumor growth in an allograft animal model .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [44, 49]}]}, {"sentence": "Thus , DATS may represent a colon cancer preventive agent and can be used in the future .", "entities": [{"name": "colon cancer", "type": "Anatomy", "pos": [28, 40]}]}, {"sentence": "High - mobility group A2 protein modulates hTERT transcription to promote tumorigenesis .", "entities": []}, {"sentence": "The high - mobility group A2 gene ( HMGA2 ) is one of the most frequently amplified genes in human cancers .", "entities": [{"name": "cancers", "type": "Anatomy", "pos": [99, 106]}]}, {"sentence": "However , functions of HMGA2 in tumorigenesis are not fully understood due to limited knowledge of its targets in tumor cells .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [114, 125]}]}, {"sentence": "Our study reveals a novel link between HMGA2 and the regulation of human telomerase reverse transcriptase ( hTERT ) , the catalytic subunit of telomerase , which offers critical insight into how HMGA2 contributes to tumorigenesis .", "entities": []}, {"sentence": "The expression of HMGA2 modulates the expression of hTERT , resulting in cells with enhanced telomerase activities and increased telomere length .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [73, 78]}, {"name": "telomere", "type": "Anatomy", "pos": [129, 137]}]}, {"sentence": "Treatment with suberoylanilide hydroxamide ( SAHA ) , a histone deacetylase ( HDAC ) inhibitor , causes dose - dependent hTERT reporter activation , mimicking HMGA2 overexpression .", "entities": []}, {"sentence": "By interacting with Sp1 , HMGA2 interferes with the recruitment of HDAC2 to the hTERT proximal promoter , enhancing localized histone H3 - K9 acetylation and thereby stimulating hTERT expression and telomerase activity .", "entities": []}, {"sentence": "Moreover , HMGA2 knockdown by short hairpin HMGA2 in HepG2 cells leads to progressive telomere shortening and a concurrent decrease of steady - state hTERT mRNA levels , attenuating their ability to form colonies in soft agar .", "entities": [{"name": "HepG2 cells", "type": "Anatomy", "pos": [53, 64]}, {"name": "telomere", "type": "Anatomy", "pos": [86, 94]}, {"name": "colonies", "type": "Anatomy", "pos": [204, 212]}]}, {"sentence": "Importantly , HMGA2 partially replaces the function of hTERT during the tumorigenic transformation of normal human fibroblasts .", "entities": [{"name": "fibroblasts", "type": "Anatomy", "pos": [115, 126]}]}, {"sentence": "These findings are potentially clinically relevant , because HMGA2 expression is reported to be upregulated in a number of human cancers as telomere maintenance is essential for tumorigenesis .", "entities": [{"name": "cancers", "type": "Anatomy", "pos": [129, 136]}, {"name": "telomere", "type": "Anatomy", "pos": [140, 148]}]}, {"sentence": "Hedgehog signaling : networking to nurture a promalignant tumor microenvironment .", "entities": [{"name": "promalignant tumor", "type": "Anatomy", "pos": [45, 63]}]}, {"sentence": "In addition to its role in embryonic development , the Hedgehog pathway has been shown to be an active participant in cancer development , progression , and metastasis .", "entities": [{"name": "embryonic", "type": "Anatomy", "pos": [27, 36]}, {"name": "cancer", "type": "Anatomy", "pos": [118, 124]}]}, {"sentence": "Although this pathway is activated by autocrine signaling by Hedgehog ligands , it can also initiate paracrine signaling with cells in the microenvironment .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [126, 131]}]}, {"sentence": "This creates a network of Hedgehog signaling that determines the malignant behavior of the tumor cells .", "entities": [{"name": "tumor cells", "type": "Anatomy", "pos": [91, 102]}]}, {"sentence": "As a result of paracrine signal transmission , the effects of Hedgehog signaling most profoundly influence the stromal cells that constitute the tumor microenvironment .", "entities": [{"name": "stromal cells", "type": "Anatomy", "pos": [111, 124]}, {"name": "tumor", "type": "Anatomy", "pos": [145, 150]}]}, {"sentence": "The stromal cells in turn produce factors that nurture the tumor .", "entities": [{"name": "stromal cells", "type": "Anatomy", "pos": [4, 17]}, {"name": "tumor", "type": "Anatomy", "pos": [59, 64]}]}, {"sentence": "Thus , such a resonating cross - talk can amplify Hedgehog signaling , resulting in molecular chatter that overall promotes tumor progression .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [124, 129]}]}, {"sentence": "Inhibitors of Hedgehog signaling have been the subject of intense research .", "entities": []}, {"sentence": "Several of these inhibitors are currently being evaluated in clinical trials .", "entities": []}, {"sentence": "Here , we review the role of the Hedgehog pathway in the signature characteristics of cancer cells that determine tumor development , progression , and metastasis .", "entities": [{"name": "cancer cells", "type": "Anatomy", "pos": [86, 98]}, {"name": "tumor", "type": "Anatomy", "pos": [114, 119]}]}, {"sentence": "This review condenses the latest findings on the signaling pathways that are activated and / or regulated by molecules generated from Hedgehog signaling in cancer and cites promising clinical interventions .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [156, 162]}]}, {"sentence": "Finally , we discuss future directions for identifying the appropriate patients for therapy , developing reliable markers of efficacy of treatment , and combating resistance to Hedgehog pathway inhibitors .", "entities": []}, {"sentence": "Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population .", "entities": [{"name": "colorectal cancer", "type": "Anatomy", "pos": [63, 80]}]}, {"sentence": "The development and progression of colorectal cancer ( CRC ) is a multi - step process , and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli ( APC ) and beta - catenin plays an important role in transforming a normal tissue into a malignant one .", "entities": [{"name": "colorectal cancer", "type": "Anatomy", "pos": [35, 52]}, {"name": "CRC", "type": "Anatomy", "pos": [55, 58]}, {"name": "tissue", "type": "Anatomy", "pos": [247, 253]}, {"name": "malignant one", "type": "Anatomy", "pos": [261, 274]}]}, {"sentence": "In this study , we aimed to investigate the role of aberrations in the APC and beta - catenin genes in the pathogenesis of CRC in the Kashmir valley , and to correlate it with various clinicopathological variables .", "entities": [{"name": "CRC", "type": "Anatomy", "pos": [123, 126]}]}, {"sentence": "We examined the paired tumour and normal - tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region ( MCR ) of the APC gene and exon 3 of the beta - catenin gene by polymerase chain reaction - single - strand conformation polymorphism ( PCR - SSCP ) and / or PCR - direct sequencing .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [23, 29]}, {"name": "tissue specimens", "type": "Anatomy", "pos": [43, 59]}, {"name": "CRC", "type": "Anatomy", "pos": [66, 69]}]}, {"sentence": "Analysis of promoter hypermethylation of the APC gene was also carried out using methylation - specific PCR ( MS - PCR ) .", "entities": []}, {"sentence": "The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12 . 8 per cent ( 11 of 86 ) .", "entities": [{"name": "CRC", "type": "Anatomy", "pos": [62, 65]}]}, {"sentence": "Promoter hypermethylation of APC was observed in 54 . 65 per cent ( 47 of 86 ) of cases .", "entities": []}, {"sentence": "Furthermore , we found a significant association between tumour location , tumour grade and node status and the methylation status of the APC gene ( p < = 0 . 05 ) .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [57, 63]}, {"name": "tumour", "type": "Anatomy", "pos": [75, 81]}, {"name": "node", "type": "Anatomy", "pos": [92, 96]}]}, {"sentence": "Although the number of mutations in the APC and beta - catenin genes in our CRC cases was very low , the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator , APC , of the Wnt pathway in the development of CRC in the Kashmiri population .", "entities": [{"name": "CRC", "type": "Anatomy", "pos": [76, 79]}, {"name": "CRC", "type": "Anatomy", "pos": [242, 245]}]}, {"sentence": "Aglycon of rhizochalin from the Rhizochalina incrustata induces apoptosis via activation of AMP - activated protein kinase in HT - 29 colon cancer cells .", "entities": [{"name": "HT - 29 colon cancer cells", "type": "Anatomy", "pos": [126, 152]}]}, {"sentence": "Rhizochalin is a two - headed sphingolipid - like compound isolated from the sponge Rhizochalina incrustata .", "entities": []}, {"sentence": "It has been reported that rhizocalin and its derivates have a chemopreventive and chemotherapeutic effect .", "entities": []}, {"sentence": "However , the molecular mechanism of these effects is not understood .", "entities": []}, {"sentence": "Here , we demonstrate that aglycon of rhizochalin ( AglRhz ) from the Rhizochalina incrustata induces AMP - activated protein kinase ( AMPK ) phosphorylation , and thereby inhibits mammalian target of rapamycin ( mTOR ) - p70S6 kinase - extracellular signal - regulated kinase ( ERK ) signaling and activator protein 1 ( AP - 1 ) activity via phosphorylation of Raptor in HT - 29 cells .", "entities": [{"name": "HT - 29 cells", "type": "Anatomy", "pos": [372, 385]}]}, {"sentence": "In addition , AglRhz induced activation of caspase - 3 and poly ( ADP - ribose ) polymerase ( PARP ) , and DNA fragmentation in HT - 29 cells , leads to induction of apoptosis as well as suppression of tumorigenicity of HT - 29 cells .", "entities": [{"name": "HT - 29 cells", "type": "Anatomy", "pos": [128, 141]}, {"name": "HT - 29 cells", "type": "Anatomy", "pos": [220, 233]}]}, {"sentence": "Notably , AglRhz inhibits insulin - like growth factor ( IGF ) - 1 - induced AP - 1 activity and cell transformation in JB6 Cl41 cells .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [97, 101]}, {"name": "JB6 Cl41 cells", "type": "Anatomy", "pos": [120, 134]}]}, {"sentence": "Overall , our findings identify AMPK as an important target protein for mediating the anti - tumor properties of AglRhz in HT - 29 colon cancer cells and have important implication for sponges , the most important marine source , in colon cancer .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [93, 98]}, {"name": "HT - 29 colon cancer cells", "type": "Anatomy", "pos": [123, 149]}, {"name": "colon cancer", "type": "Anatomy", "pos": [233, 245]}]}, {"sentence": "Expression of thymidylate synthase and dihydropyrimidine dehydrogenase in primary oral squamous cell carcinoma and corresponding metastases in cervical lymph nodes : association with the metastasis suppressor CD82 .", "entities": [{"name": "primary oral squamous cell carcinoma", "type": "Anatomy", "pos": [74, 110]}, {"name": "metastases", "type": "Anatomy", "pos": [129, 139]}, {"name": "cervical lymph nodes", "type": "Anatomy", "pos": [143, 163]}]}, {"sentence": "Thymidylate synthase ( TS ) and dihydropyrimidine dehydrogenase ( DPD ) are 5 - fluorouracil ( 5 - FU ) metabolizing enzymes and are involved in the sensitivity of carcinoma patients to 5 - FU .", "entities": [{"name": "carcinoma", "type": "Anatomy", "pos": [164, 173]}]}, {"sentence": "Although 5 - FU is often used for the treatment of oral carcinoma , there has not been any investigation into the expression of these enzymes in metastatic lymph nodes or of their roles in the effectiveness of 5 - FU in treating lymph node - metastatic cancer .", "entities": [{"name": "oral carcinoma", "type": "Anatomy", "pos": [51, 65]}, {"name": "metastatic lymph nodes", "type": "Anatomy", "pos": [145, 167]}, {"name": "lymph node - metastatic cancer", "type": "Anatomy", "pos": [229, 259]}]}, {"sentence": "Oral squamous cell carcinoma ( OSCC ) often metastasizes to the lymph nodes , and these enzymes may be significant in the survival of patients with this disease .", "entities": [{"name": "Oral squamous cell carcinoma", "type": "Anatomy", "pos": [0, 28]}, {"name": "OSCC", "type": "Anatomy", "pos": [31, 35]}, {"name": "lymph nodes", "type": "Anatomy", "pos": [64, 75]}]}, {"sentence": "This study investigated the expression of TS and DPD in cervical lymph node metastases and its relationship with primary OSCC , as well as the interaction between these enzymes and Kangai 1 ( KAI1 / CD82 ) which is a metastasis suppressor protein .", "entities": [{"name": "cervical lymph node metastases", "type": "Anatomy", "pos": [56, 86]}, {"name": "primary OSCC", "type": "Anatomy", "pos": [113, 125]}]}, {"sentence": "Surgical specimens from 20 cases of OSCC with lymph node metastasis , 20 cases of OSCC without lymph node metastasis , and 10 cases of normal mucosa were examined by immunohistochemistry .", "entities": [{"name": "Surgical specimens", "type": "Anatomy", "pos": [0, 18]}, {"name": "OSCC", "type": "Anatomy", "pos": [36, 40]}, {"name": "lymph node", "type": "Anatomy", "pos": [46, 56]}, {"name": "OSCC", "type": "Anatomy", "pos": [82, 86]}, {"name": "lymph node", "type": "Anatomy", "pos": [95, 105]}, {"name": "mucosa", "type": "Anatomy", "pos": [142, 148]}]}, {"sentence": "The relationship between TS and DPD expression and clinicopathological data was analyzed .", "entities": []}, {"sentence": "TS and DPD proteins were overexpressed in primary OSCC compared to that in normal mucosa .", "entities": [{"name": "primary OSCC", "type": "Anatomy", "pos": [42, 54]}, {"name": "mucosa", "type": "Anatomy", "pos": [82, 88]}]}, {"sentence": "TS expression of the primary oral cancer cells in the group with lymph node metastasis was higher than that of those without .", "entities": [{"name": "primary oral cancer cells", "type": "Anatomy", "pos": [21, 46]}, {"name": "lymph node", "type": "Anatomy", "pos": [65, 75]}]}, {"sentence": "DPD expression did not significantly correlate with the occurrence of lymph node metastasis , nor was it different between primary oral cancer cells and cervical metastases .", "entities": [{"name": "lymph node", "type": "Anatomy", "pos": [70, 80]}, {"name": "primary oral cancer cells", "type": "Anatomy", "pos": [123, 148]}, {"name": "cervical metastases", "type": "Anatomy", "pos": [153, 172]}]}, {"sentence": "CD82 expression was significantly reduced in lymph node metastases .", "entities": [{"name": "lymph node metastases", "type": "Anatomy", "pos": [45, 66]}]}, {"sentence": "These findings indicate that TS and CD82 may be of great value in assessing lymph node metastasis of OSCC , and could be taken as new targets for therapy of metastatic OSCC .", "entities": [{"name": "lymph node", "type": "Anatomy", "pos": [76, 86]}, {"name": "OSCC", "type": "Anatomy", "pos": [101, 105]}, {"name": "metastatic OSCC", "type": "Anatomy", "pos": [157, 172]}]}, {"sentence": "Impaired CK1 delta activity attenuates SV40 - induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [54, 62]}, {"name": "mammary", "type": "Anatomy", "pos": [97, 104]}]}, {"sentence": "Simian virus 40 ( SV40 ) is a powerful tool to study cellular transformation in vitro , as well as tumor development and progression in vivo .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [53, 61]}, {"name": "tumor", "type": "Anatomy", "pos": [99, 104]}]}, {"sentence": "Various cellular kinases , among them members of the CK1 family , play an important role in modulating the transforming activity of SV40 , including the transforming activity of T - Ag , the major transforming protein of SV40 , itself .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [8, 16]}]}, {"sentence": "Here we characterized the effects of mutant CK1delta variants with impaired kinase activity on SV40 - induced cell transformation in vitro , and on SV40 - induced mammary carcinogenesis in vivo in a transgenic / bi - transgenic mouse model .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [110, 114]}, {"name": "mammary", "type": "Anatomy", "pos": [163, 170]}]}, {"sentence": "CK1delta mutants exhibited a reduced kinase activity compared to wtCK1delta in in vitro kinase assays .", "entities": []}, {"sentence": "Molecular modeling studies suggested that mutation N172D , located within the substrate binding region , is mainly responsible for impaired mutCK1delta activity .", "entities": []}, {"sentence": "When stably over - expressed in maximal transformed SV - 52 cells , CK1delta mutants induced reversion to a minimal transformed phenotype by dominant - negative interference with endogenous wtCK1delta .", "entities": [{"name": "SV - 52 cells", "type": "Anatomy", "pos": [52, 65]}]}, {"sentence": "To characterize the effects of CK1delta on SV40 - induced mammary carcinogenesis , we generated transgenic mice expressing mutant CK1delta under the control of the whey acidic protein ( WAP ) gene promoter , and crossed them with SV40 transgenic WAP - T - antigen ( WAP - T ) mice .", "entities": [{"name": "mammary", "type": "Anatomy", "pos": [58, 65]}]}, {"sentence": "Both WAP - T mice as well as WAP - mutCK1delta / WAP - T bi - transgenic mice developed breast cancer .", "entities": [{"name": "breast cancer", "type": "Anatomy", "pos": [88, 101]}]}, {"sentence": "However , tumor incidence was lower and life span was significantly longer in WAP - mutCK1delta / WAP - T bi - transgenic animals .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [10, 15]}]}, {"sentence": "The reduced CK1delta activity did not affect early lesion formation during tumorigenesis , suggesting that impaired CK1delta activity reduces the probability for outgrowth of in situ carcinomas to invasive carcinomas .", "entities": [{"name": "lesion", "type": "Anatomy", "pos": [51, 57]}, {"name": "in situ carcinomas", "type": "Anatomy", "pos": [175, 193]}, {"name": "invasive carcinomas", "type": "Anatomy", "pos": [197, 216]}]}, {"sentence": "The different tumorigenic potential of SV40 in WAP - T and WAP - mutCK1delta / WAP - T tumors was also reflected by a significantly different expression of various genes known to be involved in tumor progression , specifically of those involved in wnt - signaling and DNA repair .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [87, 93]}, {"name": "tumor", "type": "Anatomy", "pos": [194, 199]}]}, {"sentence": "Our data show that inactivating mutations in CK1delta impair SV40 - induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [76, 84]}, {"name": "mammary", "type": "Anatomy", "pos": [119, 126]}]}, {"sentence": "Amplification of mineralocorticoid activity of aldosterone by 18 - hydroxy - corticosterone and 18 - hydroxy - 19 - nor - corticosterone in adrenalectomized rats .", "entities": []}, {"sentence": "A combination of aldosterone ( 1 micrograms ) with either 18 - OH - corticosterone ( 1 micrograms ) or 18 - OH - 19 - norcorticosterone ( 1 micrograms ) injected to adrenalectomized rats indicated an amplification of mineralocorticoid activity as expressed by Na / K ratio in urine .", "entities": [{"name": "urine", "type": "Anatomy", "pos": [276, 281]}]}, {"sentence": "Without aldosterone their mineralocorticoid potency was negligible .", "entities": []}, {"sentence": "Osteonectin transcript and metastatic behavior in v - Ki - ras transformed fibroblasts .", "entities": [{"name": "fibroblasts", "type": "Anatomy", "pos": [75, 86]}]}, {"sentence": "Osteonectin is one of the major non - collagenous proteins of bone .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [62, 66]}]}, {"sentence": "However , its transcript has been found in many soft , extracellular matrix - producing tissues ; an osteonectin - related protein was detected in tumor basement membrane .", "entities": [{"name": "soft , extracellular matrix - producing tissues", "type": "Anatomy", "pos": [48, 95]}, {"name": "tumor basement membrane", "type": "Anatomy", "pos": [147, 170]}]}, {"sentence": "We have investigated the expression of osteonectin gene in fresh BALB / c fibroblasts transformed by v - Ki - ras .", "entities": [{"name": "BALB / c fibroblasts", "type": "Anatomy", "pos": [65, 85]}]}, {"sentence": "Transformed cells exhibited lower levels of RNA as compared with normal fibroblasts .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [12, 17]}, {"name": "fibroblasts", "type": "Anatomy", "pos": [72, 83]}]}, {"sentence": "The transformed cells were cloned after in vivo tumorigenic assay , and 4 clones were analyzed for osteonectin expression by Northern blots .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [16, 21]}, {"name": "clones", "type": "Anatomy", "pos": [74, 80]}]}, {"sentence": "Two of them were selected for high or low osteonectin expression and tested in vivo in spontaneous and artificial metastasis assays .", "entities": []}, {"sentence": "High osteonectin expression was correlated with high lung colonization .", "entities": [{"name": "lung", "type": "Anatomy", "pos": [53, 57]}]}, {"sentence": "When 10 ( 5 ) cells were injected i . v . , median colony value was 55 and 20 in higher expressor vs . lower expressor respectively ( p less than 0 . 005 ) .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [14, 19]}, {"name": "i . v .", "type": "Anatomy", "pos": [34, 41]}, {"name": "colony", "type": "Anatomy", "pos": [51, 57]}]}, {"sentence": "Spontaneous metastasis indicates a possible reverse correlation .", "entities": []}, {"sentence": "Our data align osteonectin with other matrix - components and adhesion molecules in affecting potential metastatic spreading of transformed cells .", "entities": [{"name": "matrix", "type": "Anatomy", "pos": [38, 44]}, {"name": "cells", "type": "Anatomy", "pos": [140, 145]}]}, {"sentence": "[ Intraepithelial neoplasm of the uterine cervix and angiogenesis : morphologic study ]", "entities": [{"name": "Intraepithelial neoplasm", "type": "Anatomy", "pos": [2, 26]}, {"name": "uterine cervix", "type": "Anatomy", "pos": [34, 48]}]}, {"sentence": "Thirty uterine cervix specimens sampled following conization or total hysterectomy were studied using histology , histoenzymology ( vessel phosphatase alkaline activity ) , and immunohistochemistry ( demonstration of laminin and type IV collagen in epithelium and vessel basement membranes ) .", "entities": [{"name": "uterine cervix specimens", "type": "Anatomy", "pos": [7, 31]}, {"name": "vessel", "type": "Anatomy", "pos": [132, 138]}, {"name": "epithelium", "type": "Anatomy", "pos": [249, 259]}, {"name": "vessel basement membranes", "type": "Anatomy", "pos": [264, 289]}]}, {"sentence": "Pathologic conditions included dystrophia , moderate dysplasia , severe dysplasia , and intraepithelial carcinoma .", "entities": [{"name": "dysplasia", "type": "Anatomy", "pos": [53, 62]}, {"name": "dysplasia", "type": "Anatomy", "pos": [72, 81]}, {"name": "intraepithelial carcinoma", "type": "Anatomy", "pos": [88, 113]}]}, {"sentence": "Results were compared to findings in a control group .", "entities": []}, {"sentence": "We found that the severity of vascular abnormalities correlated positively with the severity of histologic epithelial lesions ; this finding is consistent with colposcopic results .", "entities": [{"name": "vascular", "type": "Anatomy", "pos": [30, 38]}, {"name": "epithelial lesions", "type": "Anatomy", "pos": [107, 125]}]}, {"sentence": "Anarchic angiogenesis with large , moniliform , tortuous vessels was seen in severe dysplasias and carcinomas .", "entities": [{"name": "tortuous vessels", "type": "Anatomy", "pos": [48, 64]}, {"name": "carcinomas", "type": "Anatomy", "pos": [99, 109]}]}, {"sentence": "The vascular anomalies seem to precede the development of histologic lesions in some instances .", "entities": [{"name": "vascular", "type": "Anatomy", "pos": [4, 12]}, {"name": "histologic lesions", "type": "Anatomy", "pos": [58, 76]}]}, {"sentence": "Histogenesis of the abnormal vessels may involve production of an angiogenic factor by the cancerized epithelia .", "entities": [{"name": "abnormal vessels", "type": "Anatomy", "pos": [20, 36]}, {"name": "cancerized epithelia", "type": "Anatomy", "pos": [91, 111]}]}, {"sentence": "Glycolysis and glutaminolysis in perifused Ehrlich ascites tumour cells .", "entities": [{"name": "Ehrlich ascites tumour cells", "type": "Anatomy", "pos": [43, 71]}]}, {"sentence": "A perifusion system was designed in order to study glucose and glutamine metabolism by freshly harvested Ehrlich ascites tumour cells in steady state conditions .", "entities": [{"name": "Ehrlich ascites tumour cells", "type": "Anatomy", "pos": [105, 133]}]}, {"sentence": "Cells were perifused in the presence of 5 mM glucose , 0 . 5 mM glutamine or 5 mM glucose and 0 . 5 mM glutamine .", "entities": [{"name": "Cells", "type": "Anatomy", "pos": [0, 5]}]}, {"sentence": "The results in steady state reveal that both substrates glucose and glutamine are continuously wasted by tumour cells , excreting two moles of lactate per mol of glucose and one mol of glutamate and ammonia per mol of glutamine consumed into the medium .", "entities": [{"name": "tumour cells", "type": "Anatomy", "pos": [105, 117]}]}, {"sentence": "Glutamine consumption in the presence of glucose was higher than with glutamine alone .", "entities": []}, {"sentence": "Phase II trial with D - Trp - 6 - LH - RH in prostatic carcinoma : comparison with other hormonal agents .", "entities": [{"name": "prostatic carcinoma", "type": "Anatomy", "pos": [45, 64]}]}, {"sentence": "Various approaches to hormonal treatment of prostate carcinoma are discussed .", "entities": [{"name": "prostate carcinoma", "type": "Anatomy", "pos": [44, 62]}]}, {"sentence": "Eighty - one patients with prostatic carcinoma , eight with stage B , nine with stage C , and 64 with stage D disease , were treated subcutaneously daily for 3 months with the LH - RH agonist D - Trp - 6 - LH - RH ( Decapeptyl ) in order to evaluate the incidence of remissions according to WHO recommendations for oncologic trials .", "entities": [{"name": "prostatic carcinoma", "type": "Anatomy", "pos": [27, 46]}, {"name": "subcutaneously", "type": "Anatomy", "pos": [133, 147]}]}, {"sentence": "The findings were compared to those obtained with other hormonal therapies of prostatic carcinoma according to the statistical method of \" expected response rate \" as adapted by Lee and Wesley for phase II trials .", "entities": [{"name": "prostatic carcinoma", "type": "Anatomy", "pos": [78, 97]}]}, {"sentence": "Treatment with D - Trp - 6 - LH - RH greatly reduced serum LH and testosterone levels without raising serum prolactin .", "entities": [{"name": "serum", "type": "Anatomy", "pos": [53, 58]}, {"name": "serum", "type": "Anatomy", "pos": [102, 107]}]}, {"sentence": "After 1 - 2 weeks of therapy , there was relief of subjective symptoms and a reversal of the signs of prostatism as well as a marked decrease in bone pain .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [145, 149]}]}, {"sentence": "At 90 days 52 patients had complete relief of prostatism and 21 had only mild signs and symptoms .", "entities": []}, {"sentence": "Seventy patients were experiencing no bone pain and an additional six had only mild pain .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [38, 42]}]}, {"sentence": "Prostatic size , evaluated by rectal examination and transabdominal ultrasonography , reverted to normal in 26 . 4 % of patients ( complete remission ) and was reduced by more than 50 % in an additional 17 . 6 % ( partial remission ) , the overall rate of complete plus partial regression of prostatic enlargement being 44 % .", "entities": [{"name": "Prostatic", "type": "Anatomy", "pos": [0, 9]}, {"name": "transabdominal", "type": "Anatomy", "pos": [53, 67]}, {"name": "prostatic", "type": "Anatomy", "pos": [292, 301]}]}, {"sentence": "Scans showed a major improvement of bone lesions in 14 . 8 % of cases .", "entities": [{"name": "bone lesions", "type": "Anatomy", "pos": [36, 48]}]}, {"sentence": "This response increased to 37 % after more than 6 months of follow - up .", "entities": []}, {"sentence": "Prostatic acid phosphatase levels were decreased by more than 50 % in 61 % of the patients , but this test appears to be a less valid marker than the lipid - associated sialic acid ( LASA ) .", "entities": [{"name": "Prostatic", "type": "Anatomy", "pos": [0, 9]}]}, {"sentence": "The increase in LASA before treatment and a reduction after treatment can frequently be correlated with the objective volume of the neoplasms .", "entities": [{"name": "neoplasms", "type": "Anatomy", "pos": [132, 141]}]}, {"sentence": "No flare - up of the disease was encountered , and there were no side effects except for impotence .", "entities": []}, {"sentence": "Statistical analyses of results by the method of Lee and Wesley indicated that the incidence of complete and partial regression ( CR and PR ) observed with D - Trp - 6 - LH - RH was not significantly different from that recorded in previous studies for another LH - RH analog , Buserelin .", "entities": []}, {"sentence": "However , CR and PR obtained with D - Trp - 6 - LH - RH ( 44 % ) were significantly higher than with subcapsular orchiectomy ( 22 % ) .", "entities": []}, {"sentence": "Hormonal effects and some other actions of D - Trp - 6 - LH - RH were compared and contrasted with those produced by castration , estrogens , antiandrogens , and progestogens . ( ABSTRACT TRUNCATED AT 400 WORDS )", "entities": []}, {"sentence": "Multi - step neoplastic transformation of normal human fibroblasts by Co - 60 gamma rays and Ha - ras oncogenes .", "entities": [{"name": "neoplastic", "type": "Anatomy", "pos": [13, 23]}, {"name": "fibroblasts", "type": "Anatomy", "pos": [55, 66]}]}, {"sentence": "As reported previously ( Namba et al . , 1985 ; Namba , 1985 ) , normal human fibroblasts were transformed into immortal cells with abnormal karyotypes by Co - 60 gamma - ray irradiation .", "entities": [{"name": "fibroblasts", "type": "Anatomy", "pos": [78, 89]}, {"name": "immortal cells", "type": "Anatomy", "pos": [112, 126]}]}, {"sentence": "These immortally transformed cells ( KMST - 6 ) showed no clonability in soft agar and were not tumorigenic .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [29, 34]}, {"name": "KMST - 6", "type": "Anatomy", "pos": [37, 45]}]}, {"sentence": "However , by treatment with Ha - ras oncogenes derived from a human lung carcinoma or Harvey murine sarcoma virus , the KMST - 6 cells acquired elevated clonability in soft agar and transplantability in nude mice .", "entities": [{"name": "lung carcinoma", "type": "Anatomy", "pos": [68, 82]}, {"name": "KMST - 6 cells", "type": "Anatomy", "pos": [120, 134]}]}, {"sentence": "All the tumors produced grew progressively without showing regression and killed the mice .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [8, 14]}]}, {"sentence": "The tumors were also serially transplantable into other mice .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [4, 10]}]}, {"sentence": "The Ha - ras oncogene alone did not convert normal human fibroblasts into either immortal or tumorigenic cells .", "entities": [{"name": "fibroblasts", "type": "Anatomy", "pos": [57, 68]}, {"name": "immortal", "type": "Anatomy", "pos": [81, 89]}, {"name": "tumorigenic cells", "type": "Anatomy", "pos": [93, 110]}]}, {"sentence": "Our current data suggest that gamma rays worked as an initiator of carcinogenesis in normal human cells , giving rise to chromosome aberrations and immortality , and the Ha - ras oncogene played a role in the progression of the immortally transformed cell population to a neoplastic one showing enhanced colony formation in soft agar and tumorigenicity in nude mice .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [98, 103]}, {"name": "chromosome", "type": "Anatomy", "pos": [121, 131]}, {"name": "cell", "type": "Anatomy", "pos": [251, 255]}, {"name": "neoplastic", "type": "Anatomy", "pos": [272, 282]}, {"name": "colony", "type": "Anatomy", "pos": [304, 310]}]}, {"sentence": "Cigarette smoking and alveolar bone height in subjects with a high standard of oral hygiene .", "entities": [{"name": "alveolar bone", "type": "Anatomy", "pos": [22, 35]}, {"name": "oral", "type": "Anatomy", "pos": [79, 83]}]}, {"sentence": "Smokers and non - smokers were compared with respect to alveolar bone height .", "entities": [{"name": "alveolar bone", "type": "Anatomy", "pos": [56, 69]}]}, {"sentence": "The study covered 235 subjects aged 21 - 60 years , 72 of whom were smokers .", "entities": []}, {"sentence": "Oral hygiene status and dental care habits were above average and of equal standard in both groups ( PlI = 0 . 9 ) .", "entities": [{"name": "Oral", "type": "Anatomy", "pos": [0, 4]}, {"name": "dental", "type": "Anatomy", "pos": [24, 30]}]}, {"sentence": "Alveolar bone height was assessed on radiographs and expressed as % of the root length .", "entities": [{"name": "Alveolar bone", "type": "Anatomy", "pos": [0, 13]}, {"name": "root", "type": "Anatomy", "pos": [75, 79]}]}, {"sentence": "Alveolar bone height was significantly reduced in smokers as compared to non - smokers , the mean + / - SEM being 77 . 9 + / - 1 . 3 % and 82 . 8 + / - 0 . 6 % , respectively ( P less than 0 . 001 ) .", "entities": [{"name": "Alveolar bone", "type": "Anatomy", "pos": [0, 13]}]}, {"sentence": "Regression analysis suggested that periodontal breakdown judged from loss of alveolar bone over time was more accelerated in smokers than non - smokers .", "entities": [{"name": "periodontal", "type": "Anatomy", "pos": [35, 46]}, {"name": "alveolar bone", "type": "Anatomy", "pos": [77, 90]}]}, {"sentence": "The lower bone height in smokers remained when age and oral hygiene were allowed for .", "entities": [{"name": "lower bone", "type": "Anatomy", "pos": [4, 14]}, {"name": "oral", "type": "Anatomy", "pos": [55, 59]}]}, {"sentence": "It is concluded that smoking is a risk factor for periodontal health .", "entities": [{"name": "periodontal", "type": "Anatomy", "pos": [50, 61]}]}, {"sentence": "Combined aortic , mitral and tricuspid surgery : results in 78 patients .", "entities": [{"name": "aortic", "type": "Anatomy", "pos": [9, 15]}, {"name": "mitral", "type": "Anatomy", "pos": [18, 24]}, {"name": "tricuspid", "type": "Anatomy", "pos": [29, 38]}]}, {"sentence": "Between 1968 and 1984 , 78 patients ( mean age 43 , range 14 to 65 years ) underwent combined aortic , mitral and tricuspid surgery ( 22 triple valve replacements , 56 aortic valve replacements with tricuspid conservative surgery and mitral valve replacement ( N = 48 ) , or commissuroplasty ( N = 8 ) .", "entities": [{"name": "aortic", "type": "Anatomy", "pos": [94, 100]}, {"name": "mitral", "type": "Anatomy", "pos": [103, 109]}, {"name": "tricuspid", "type": "Anatomy", "pos": [114, 123]}, {"name": "triple valve", "type": "Anatomy", "pos": [137, 149]}, {"name": "aortic valve", "type": "Anatomy", "pos": [168, 180]}, {"name": "tricuspid", "type": "Anatomy", "pos": [199, 208]}, {"name": "mitral valve", "type": "Anatomy", "pos": [234, 246]}]}, {"sentence": "Pre - operative consequences of valvular disease ( mainly mixed valve disease ) were severe as assessed by functional class ( 72 pts in III or IV NYHA ) , cardiomegaly ( CTR : 62 + / - 6 % ) , increase of mean pulmonary arterial and wedge pressures ( respectively 30 + / - 12 and 19 + / - 6 mmHg ) decrease in cardiac index ( 2 . 1 + / - 0 . 5 l min - 1 m - 2 ) , LV dilatation ( LV end diastolic volume : 184 + / - 86 ml m - 2 ) and impairment of LV systolic function ( LV ejection fraction : 50 + / - 12 % ) .", "entities": [{"name": "valvular", "type": "Anatomy", "pos": [32, 40]}, {"name": "valve", "type": "Anatomy", "pos": [64, 69]}, {"name": "pulmonary arterial", "type": "Anatomy", "pos": [210, 228]}, {"name": "cardiac", "type": "Anatomy", "pos": [310, 317]}, {"name": "LV", "type": "Anatomy", "pos": [364, 366]}, {"name": "LV", "type": "Anatomy", "pos": [380, 382]}, {"name": "LV", "type": "Anatomy", "pos": [448, 450]}, {"name": "LV", "type": "Anatomy", "pos": [471, 473]}]}, {"sentence": "Operative mortality rate was 11 . 5 % .", "entities": []}, {"sentence": "The 69 survivors were all followed up , for a mean of 56 months ( 2 to 207 ) .", "entities": []}, {"sentence": "16 late deaths occurred .", "entities": []}, {"sentence": "Actuarial survival rate at 10 years was 58 . 4 % , and greatly influenced by pre - operative NYHA class .", "entities": []}, {"sentence": "Linearized rates of thromboembolic events , valve thrombosis and haemorrhage were respectively 6 . 4 , 1 . 5 and 1 . 2 % pt - 1 yr - 1 .", "entities": [{"name": "valve", "type": "Anatomy", "pos": [44, 49]}]}, {"sentence": "Those of infective endocarditis , periprosthetic leak , reoperation and valve failure were 0 . 6 , 3 . 3 and 4 . 9 % pt - 1 yr - 1 respectively .", "entities": [{"name": "valve", "type": "Anatomy", "pos": [72, 77]}]}, {"sentence": "At 9 years , 42 % of the patients were in NYHA class I or II and free from complications .", "entities": []}, {"sentence": "Conjunctival hypoxia in diabetes mellitus .", "entities": [{"name": "Conjunctival", "type": "Anatomy", "pos": [0, 12]}]}, {"sentence": "A frequently cited theory for the pathogenesis of neovascularization in diabetic retinopathy is that retinal hypoxia and / or ischemia release a factor which stimulates neovascularization .", "entities": [{"name": "retinal", "type": "Anatomy", "pos": [101, 108]}]}, {"sentence": "To the authors ' knowledge , there is no direct in vivo evidence in the human proving this theory .", "entities": []}, {"sentence": "One hundred and twenty - two diabetic subjects were studied to see whether worsening retinopathy was associated with changes in conjunctival oxygen tension ( pO2 ) .", "entities": [{"name": "conjunctival", "type": "Anatomy", "pos": [128, 140]}]}, {"sentence": "Diabetics without retinopathy had a conjunctival pO2 which was similar to an age - matched normal population .", "entities": [{"name": "conjunctival", "type": "Anatomy", "pos": [36, 48]}]}, {"sentence": "Diabetics with only background retinopathy had a significantly lower conjunctival pO2 than those without retinopathy ( P less than 0 . 01 ) .", "entities": [{"name": "conjunctival", "type": "Anatomy", "pos": [69, 81]}]}, {"sentence": "Diabetics with proliferative retinopathy showed a conjunctival pO2 that was significantly lower than either of the first two groups ( P less than 0 . 05 ) .", "entities": [{"name": "conjunctival", "type": "Anatomy", "pos": [50, 62]}]}, {"sentence": "The lowest value of all was found in patients with rubeosis iridis .", "entities": []}, {"sentence": "Duration of diabetes alone did not correlate significantly to conjunctival pO2 .", "entities": [{"name": "conjunctival", "type": "Anatomy", "pos": [62, 74]}]}, {"sentence": "These findings support the hypoxic theory of diabetic neovascular retinopathy .", "entities": []}, {"sentence": "New functions of epidermal growth factor : stimulation of capillary endothelial cell migration and matrix dependent proliferation .", "entities": [{"name": "capillary endothelial cell", "type": "Anatomy", "pos": [58, 84]}, {"name": "matrix", "type": "Anatomy", "pos": [99, 105]}]}, {"sentence": "The proliferative response of bovine retinal capillary endothelial cells to EGF is dependent upon attaching the cells to a matrix of fibronectin .", "entities": [{"name": "retinal capillary endothelial cells", "type": "Anatomy", "pos": [37, 72]}, {"name": "cells", "type": "Anatomy", "pos": [112, 117]}, {"name": "matrix", "type": "Anatomy", "pos": [123, 129]}]}, {"sentence": "Bovine capillary endothelial cells are also stimulated to actively migrate when exposed to EGF in vitro .", "entities": [{"name": "capillary endothelial cells", "type": "Anatomy", "pos": [7, 34]}]}, {"sentence": "These activities provide an explanation for the angiogenic properties of EGF in vivo .", "entities": []}, {"sentence": "Capillary cell migration and proliferation are proposed as sensitive quantifiable bioassays to explore the functional domains of the EGF molecule .", "entities": [{"name": "Capillary cell", "type": "Anatomy", "pos": [0, 14]}]}, {"sentence": "Studies on the inactivation of these properties of EGF by specific cleavage of the molecule with CNBr or proteases suggest that an intact loop composed in part by amino acid residues 20 to 31 is essential for at least some functions .", "entities": []}, {"sentence": "[ Histophysiology and histopathology of the adrenals in experimental hypokinesia ] .", "entities": [{"name": "adrenals", "type": "Anatomy", "pos": [44, 52]}]}, {"sentence": "In experiments on male rats in the course of 3 - month hypokinesia phasic changes were observed in the relative adrenal gland weight , in the volume of the cell nuclei of the glomerular , fasicular zones and the medulla , in the activity of the succinic dehydrogenase , alkaline and acid phosphatases , in the RNA and catecholamine content .", "entities": [{"name": "adrenal gland", "type": "Anatomy", "pos": [112, 125]}, {"name": "cell nuclei", "type": "Anatomy", "pos": [156, 167]}, {"name": "glomerular", "type": "Anatomy", "pos": [175, 185]}, {"name": "fasicular zones", "type": "Anatomy", "pos": [188, 203]}, {"name": "medulla", "type": "Anatomy", "pos": [212, 219]}]}, {"sentence": "These changes are associated with variations in the secretion and biosynthesis of the hormones of the cortical and the medullary layer of the adrenal glands during the hypokinetic stress development .", "entities": [{"name": "cortical", "type": "Anatomy", "pos": [102, 110]}, {"name": "medullary layer", "type": "Anatomy", "pos": [119, 134]}, {"name": "adrenal glands", "type": "Anatomy", "pos": [142, 156]}]}, {"sentence": "Dynorphin is contained within hippocampal mossy fibers : immunochemical alterations after kainic acid administration and colchicine - induced neurotoxicity .", "entities": [{"name": "hippocampal mossy fibers", "type": "Anatomy", "pos": [30, 54]}]}, {"sentence": "Antisera raised against synthetic dynorphin or [ Leu5 ] enkephalin demonstrate immunostaining in hippocampal mossy fibers and in dentate granule cells .", "entities": [{"name": "Antisera", "type": "Anatomy", "pos": [0, 8]}, {"name": "hippocampal mossy fibers", "type": "Anatomy", "pos": [97, 121]}, {"name": "dentate granule cells", "type": "Anatomy", "pos": [129, 150]}]}, {"sentence": "However , dynorphin immunoreactivity ( ir ) appears to be denser in immunocytochemical preparations and is quantitatively greater by radioimmunoassay than enkephalin - ir .", "entities": []}, {"sentence": "Immunostaining with dynorphin antisera is eliminated by adsorption with 1 - 100 microM dynorphin - 17 whereas immunostaining with enkephalin antisera is eliminated by adsorption with 1 - 100 microM [ Leu5 ] enkephalin , dynorphin - 17 , dynorphin - ( 1 - 13 ) , or alpha - neo - endorphin .", "entities": []}, {"sentence": "Intrahippocampal colchicine injections , which selectively destroy dentate granule cells , significantly decrease the dynorphin - ir and enkephalin - ir levels in rat hippocampus .", "entities": [{"name": "Intrahippocampal", "type": "Anatomy", "pos": [0, 16]}, {"name": "dentate granule cells", "type": "Anatomy", "pos": [67, 88]}, {"name": "hippocampus", "type": "Anatomy", "pos": [167, 178]}]}, {"sentence": "Intraventricularly administered kainic acid , which selectively destroys CA3 - 4 pyramidal cells , results in an increase of enkephalin immunostaining in mossy fibers and a significant increase in enkephalin - ir by radioimmunoassay in whole hippocampus .", "entities": [{"name": "Intraventricularly", "type": "Anatomy", "pos": [0, 18]}, {"name": "CA3 - 4 pyramidal cells", "type": "Anatomy", "pos": [73, 96]}, {"name": "mossy fibers", "type": "Anatomy", "pos": [154, 166]}, {"name": "hippocampus", "type": "Anatomy", "pos": [242, 253]}]}, {"sentence": "The enkephalin - ir cells and fibers in entorhinal / perirhinal cortex , which innervate rat hippocampus and dentate gyrus , do not contain dynorphin - ir .", "entities": [{"name": "enkephalin - ir cells", "type": "Anatomy", "pos": [4, 25]}, {"name": "fibers", "type": "Anatomy", "pos": [30, 36]}, {"name": "entorhinal", "type": "Anatomy", "pos": [40, 50]}, {"name": "perirhinal cortex", "type": "Anatomy", "pos": [53, 70]}, {"name": "hippocampus", "type": "Anatomy", "pos": [93, 104]}, {"name": "dentate gyrus", "type": "Anatomy", "pos": [109, 122]}]}, {"sentence": "Angiogenesis : initiation and control .", "entities": []}, {"sentence": "From in vivo experiments using new methods such as the rabbit cornea , it is now becoming clear that the growth of a capillary involves an ordered sequence of events that includes lysis of the basement membrane of a parent venule , directional migration of capillary endothelial cells toward the angiogenic stimulus , lumen formation , development of branches , and anastomosis of the tip of one tube with another to form a loop .", "entities": [{"name": "cornea", "type": "Anatomy", "pos": [62, 68]}, {"name": "capillary", "type": "Anatomy", "pos": [117, 126]}, {"name": "basement membrane", "type": "Anatomy", "pos": [193, 210]}, {"name": "venule", "type": "Anatomy", "pos": [223, 229]}, {"name": "capillary endothelial cells", "type": "Anatomy", "pos": [257, 284]}, {"name": "lumen", "type": "Anatomy", "pos": [318, 323]}, {"name": "branches", "type": "Anatomy", "pos": [351, 359]}, {"name": "tube", "type": "Anatomy", "pos": [396, 400]}]}, {"sentence": "It is also clear that diffusible angiogenic stimuli can be released not only from most solid tumors , but also from at least three non - neoplastic cells .", "entities": [{"name": "solid tumors", "type": "Anatomy", "pos": [87, 99]}, {"name": "non - neoplastic cells", "type": "Anatomy", "pos": [131, 153]}]}, {"sentence": "These include activated macrophages , sensitized lymphocytes , and adipocytes .", "entities": [{"name": "macrophages", "type": "Anatomy", "pos": [24, 35]}, {"name": "lymphocytes", "type": "Anatomy", "pos": [49, 60]}, {"name": "adipocytes", "type": "Anatomy", "pos": [67, 77]}]}, {"sentence": "Other normal tissues can also stimulate angiogenesis , but the type of cell giving rise to the angiogenic stimulus is unknown , and the period of angiogenic stimulation is brief .", "entities": [{"name": "tissues", "type": "Anatomy", "pos": [13, 20]}, {"name": "cell", "type": "Anatomy", "pos": [71, 75]}]}, {"sentence": "With the recent ability to clone capillary endothelial cells and to carry them in long - term culture , it has been possible to further delineate the mechanism of capillary growth .", "entities": [{"name": "capillary endothelial cells", "type": "Anatomy", "pos": [33, 60]}, {"name": "capillary", "type": "Anatomy", "pos": [163, 172]}]}, {"sentence": "In vitro studies have shown that the mast cell seems to behave as a helper cell for capillary endothelial cells , in some way speeding up their rate of directional migration .", "entities": [{"name": "mast cell", "type": "Anatomy", "pos": [37, 46]}, {"name": "helper cell", "type": "Anatomy", "pos": [68, 79]}, {"name": "capillary endothelial cells", "type": "Anatomy", "pos": [84, 111]}]}, {"sentence": "At this writing , heparin appears to be the principal mast cell factor responsible for this effect on capillary endothelial cells .", "entities": [{"name": "mast cell", "type": "Anatomy", "pos": [54, 63]}, {"name": "capillary endothelial cells", "type": "Anatomy", "pos": [102, 129]}]}, {"sentence": "One theoretical possibility is that mast cells may prepare the matrix , perhaps by slow release of heparin , so that capillary sprouts can more easily move through it toward their angiogenic target .", "entities": [{"name": "mast cells", "type": "Anatomy", "pos": [36, 46]}, {"name": "matrix", "type": "Anatomy", "pos": [63, 69]}, {"name": "capillary sprouts", "type": "Anatomy", "pos": [117, 134]}]}, {"sentence": "While the study of angiogenesis as a phenomenon is still in an early phase , it has become possible , by using a combination of in vitro and in vivo techniques , to more thoroughly understand the initiation and control of capillary growth .", "entities": [{"name": "capillary", "type": "Anatomy", "pos": [222, 231]}]}, {"sentence": "Protection from experimental ocular herpetic keratitis by a heat - killed virus vaccine .", "entities": [{"name": "ocular", "type": "Anatomy", "pos": [29, 35]}]}, {"sentence": "New Zealand white rabbits were given limbal inoculations of a heat - killed suspension of herpes simplex virus ( HSV ) in a lysate of human embryonic kidney cells .", "entities": [{"name": "limbal", "type": "Anatomy", "pos": [37, 43]}, {"name": "embryonic kidney cells", "type": "Anatomy", "pos": [140, 162]}]}, {"sentence": "At intervals of four to 14 days , the animals were challenged by intrastromal inoculation with 10 , 000 plaque - forming units of viable HSV .", "entities": [{"name": "intrastromal", "type": "Anatomy", "pos": [65, 77]}]}, {"sentence": "Epithelial keratitis , disciform edema , and necrotizing keratitis with neovascularization of the cornea developed in control animals .", "entities": [{"name": "Epithelial", "type": "Anatomy", "pos": [0, 10]}, {"name": "disciform edema", "type": "Anatomy", "pos": [23, 38]}, {"name": "cornea", "type": "Anatomy", "pos": [98, 104]}]}, {"sentence": "Epithelial keratitis and corneal edema also developed in the immunized animals during the first week after virus challenge , but these symptoms rapidly resolved during the following weeks .", "entities": [{"name": "Epithelial", "type": "Anatomy", "pos": [0, 10]}, {"name": "corneal edema", "type": "Anatomy", "pos": [25, 38]}]}, {"sentence": "The absence of iritis , neovascularization , and necrotizing keratitis in the corneas of the immunized animals was particularly striking .", "entities": [{"name": "corneas", "type": "Anatomy", "pos": [78, 85]}]}, {"sentence": "Effects of growth temperature , 47 - megadalton plasmid , and calcium deficiency on the outer membrane protein porin and lipopolysaccharide composition of Yersinia pestis EV76 .", "entities": [{"name": "plasmid", "type": "Anatomy", "pos": [48, 55]}, {"name": "outer membrane", "type": "Anatomy", "pos": [88, 102]}]}, {"sentence": "The expression of several virulence determinants of Yersinia pestis is known to be dependent on the in vitro growth temperature .", "entities": []}, {"sentence": "One of these , calcium dependence , is associated with the presence of a 47 - megadalton plasmid .", "entities": [{"name": "plasmid", "type": "Anatomy", "pos": [89, 96]}]}, {"sentence": "We have examined the effects of incubation temperature , calcium in the growth medium , the presence of the 47 - megadalton plasmid on the outer membrane protein , and the lipopolysaccharide composition of Y . pestis EV76 .", "entities": [{"name": "plasmid", "type": "Anatomy", "pos": [124, 131]}, {"name": "outer membrane", "type": "Anatomy", "pos": [139, 153]}]}, {"sentence": "When cells were grown at 37 degrees C as opposed to 26 degrees C , a change in lipopolysaccharide composition and a decrease in the amount of an outer membrane protein ( protein E ) were observed .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [5, 10]}, {"name": "outer membrane", "type": "Anatomy", "pos": [145, 159]}]}, {"sentence": "The lipopolysaccharide obtained from cells incubated at 37 degrees C had a lower proportion of 2 keto - 3 - deoxyoctanate , a lower phosphate to 2 - keto - 3 - deoxyoctanate ratio , and an increased gel mobility upon sodium dodecyl sulfate - polyacrylamide gel electrophoresis when compared with lipopolysaccharide obtained from cells grown at 26 degrees C .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [37, 42]}, {"name": "cells", "type": "Anatomy", "pos": [329, 334]}]}, {"sentence": "Because of its growth temperature - related abundance , we investigated the nature of protein E .", "entities": []}, {"sentence": "This protein had physical properties similar to those of other enterobacterial porins , including apparent formation of an oligomer on sodium dodecyl sulfate - polyacrylamide gels when solubilized at low temperature , acidic isoelectric point , and strong noncovalent association with the peptidoglycan .", "entities": []}, {"sentence": "Protein E was purified and shown to form an aqueous channel in planar lipid membranes with a conductance of 1 . 1 nS in 1 M KCl .", "entities": [{"name": "lipid membranes", "type": "Anatomy", "pos": [70, 85]}]}, {"sentence": "In addition to growth temperature - related alterations in the lipopolysaccharide and porin components of the outer membrane , the amount of three spots in two - dimensional polyacrylamide gels was shown to be related to the temperature or the presence of calcium during growth .", "entities": [{"name": "outer membrane", "type": "Anatomy", "pos": [110, 124]}]}, {"sentence": "One of these spots was shown to contain residual unmodified portions of two major heat - modifiable proteins which failed to shift to their heat - modified positions on gels , despite solubilization at 100 degrees C for 10 min before electrophoresis .", "entities": []}, {"sentence": "The other two spots were the heat - modified and unmodified forms of another outer membrane protein ( J ) which did not appear in the isoelectric focusing gel of cells grown at 37 degrees C .", "entities": [{"name": "outer membrane", "type": "Anatomy", "pos": [77, 91]}, {"name": "cells", "type": "Anatomy", "pos": [162, 167]}]}, {"sentence": "It is proposed that the appearance of these spots in two - dimensional analyses is related to the lipopolysaccharide composition of the cells from which the outer membrane is derived and reflects lipopolysaccharide - protein interactions or calcium - protein interactions .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [136, 141]}, {"name": "outer membrane", "type": "Anatomy", "pos": [157, 171]}]}, {"sentence": "Protein kinase activities in immune complexes of simian virus 40 large T - antigen and transformation - associated cellular p53 protein .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [115, 123]}]}, {"sentence": "Immune complex kinase assays in the simian virus 40 system were performed by incubation of immunoprecipitates containing tumor antigens with [ gamma - 32P ] ATP , followed by analysis of any phosphoacceptor proteins .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [121, 126]}]}, {"sentence": "These assays yielded mainly the viral large T - antigen and , in particular , the associated cellular p53 as endogenous substrates .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [93, 101]}]}, {"sentence": "The nature of these substrates was confirmed by proteolysis techniques .", "entities": []}, {"sentence": "Under specific conditions , casein could be used as an exogenous substrate as well .", "entities": []}, {"sentence": "The kinase reactions showed preference for ATP and MgCl2 instead of GTP or MnCl2 .", "entities": []}, {"sentence": "Both phosphoserine and phosphothreonine , but in no case phosphotyrosine , were detected after an immune complex kinase reaction .", "entities": []}, {"sentence": "Apparently , several in vivo phosphorylation sites were recognized in vitro in both large T - antigen and p53 , but the presence of some artifactual sites could not be completely excluded .", "entities": []}, {"sentence": "Although contaminating kinases were detectable in the immune complexes , at least the p53 molecules were phosphorylated in vitro in a more specific way .", "entities": []}, {"sentence": "This followed from several characteristics of the immune complex kinase reactions and especially from the strong inhibition of p53 phosphorylation by two anti - large - T monoclonal antibodies .", "entities": []}, {"sentence": "It was shown that large T - antigen showed associated kinase activity , although none of our results could unambiguously demonstrate an intrinsic kinase activity of this protein .", "entities": []}, {"sentence": "Finally , anti - p53 monoclonal antibodies only slightly affected in vitro phosphorylation reactions , whereas a p53 molecule from a simian virus 40 - free , chemically transformed human cell line was not phosphorylated in vitro under any condition tested .", "entities": [{"name": "cell line", "type": "Anatomy", "pos": [187, 196]}]}, {"sentence": "Thus , it is highly unlikely that the p53 molecule per se carries intrinsic or even associated kinase activities .", "entities": []}, {"sentence": "Preparation and physicochemical and immunological characterization of polysaccharide - outer membrane protein complexes of Neisseria meningitidis .", "entities": [{"name": "outer membrane", "type": "Anatomy", "pos": [87, 101]}]}, {"sentence": "A crude complex containing group C polysaccharide , outer membrane proteins , and lipopolysaccharide ( LPS ) was isolated from the cell - free culture liquid of Neisseria meningitidis serogroup C , serotype 2a .", "entities": [{"name": "outer membrane", "type": "Anatomy", "pos": [52, 66]}, {"name": "cell", "type": "Anatomy", "pos": [131, 135]}]}, {"sentence": "Group C polysaccharide and LPS were removed from this complex , resulting in an outer membrane complex and a purified complex , respectively .", "entities": [{"name": "outer membrane", "type": "Anatomy", "pos": [80, 94]}]}, {"sentence": "Analysis by electron microscopy showed the outer membrane origin of the crude complex and the outer membrane complex , whereas such a structure was absent in the purified complex .", "entities": [{"name": "outer membrane", "type": "Anatomy", "pos": [43, 57]}, {"name": "outer membrane", "type": "Anatomy", "pos": [94, 108]}]}, {"sentence": "Sodium dodecyl sulfate - polyacrylamide gel electrophoresis patterns of the three complexes were identical .", "entities": []}, {"sentence": "Pyrolysis - mass spectrometry data correlated well with those obtained by the biochemical assays and suggested a low LPS content in the purified complex and a low polysaccharide content in the outer membrane complex .", "entities": [{"name": "outer membrane", "type": "Anatomy", "pos": [193, 207]}]}, {"sentence": "The purified complex was shown to be nonpyrogenic and could be prepared with the same yield as that of purified polysaccharide .", "entities": []}, {"sentence": "The immunogenic activities of the complexes were studied in mice .", "entities": []}, {"sentence": "The antibodies were measured by the enzyme - linked immunosorbent assay ; and the bactericidal antibody assay .", "entities": []}, {"sentence": "All complexes induced immunoglobulin G antibodies to group C polysaccharide as well as to the serotype antigen , although the removal of polysaccharide and LPS resulted in a reduction of the immunogenic activities of outer membrane complex and purified complex , respectively .", "entities": [{"name": "outer membrane", "type": "Anatomy", "pos": [217, 231]}]}, {"sentence": "A second dose of all complexes produced a clear booster effect of both antibody responses .", "entities": []}, {"sentence": "The antibodies were bactericidal .", "entities": []}, {"sentence": "Differential reactivity of the functional sulfhydryl groups of cysteine - 32 and cysteine - 35 present in the reduced form of thioredoxin from Escherichia coli .", "entities": []}, {"sentence": "Only one of the sulfhydryl groups from Cys - 32 and Cys - 35 in the active center of native Escherichia coli thioredoxin - ( SH ) 2 was alkylated by excess iodoacetic acid at pH values below 8 . 0 .", "entities": []}, {"sentence": "Both groups reacted in the protein denatured with 4 . 5 M guanidine hydrochloride .", "entities": []}, {"sentence": "The second order rate of alkylation of thioredoxin - ( SH ) 2 with 1 eq of iodoacetic acid was pH - dependent and showed independent initial reactions of one thiolate ion with a pK value of 6 . 7 and a second with a pK value close to 9 . 0 .", "entities": []}, {"sentence": "The same pH dependence was observed for alkylation with iodoacetamide but the apparent rate constant , 107 M - 1 S - 1 at pH 7 . 2 , was about 20 - fold higher than the corresponding rate with iodoacetate .", "entities": []}, {"sentence": "The sulfhydryl group with a pK value of 6 . 7 was shown to belong to Cys - 32 by labeling thioredoxin with [ 14C ] iodoacetic acid followed by complete alkylation with [ 3H ] iodoacetate and amino acid sequence analysis of peptides from the active center .", "entities": []}, {"sentence": "The abnormally low pK value of Cys - 32 is suggested to arise by electrostatic influence from a positive charge on the amino group of Lys - 36 .", "entities": []}, {"sentence": "A mechanism of action for thioredoxin - ( SH ) 2 as a protein disulfide reductase has been formulated .", "entities": []}, {"sentence": "This is based on an initial nucleophilic attack by the thiolate of Cys - 32 with the formation of an unstable transient mixed disulfide involving Cys - 32 and one of the sulfurs in the substrate .", "entities": []}, {"sentence": "This is followed by a conformational change and a nucleophilic attack of Cys - 35 to give the 14 - membered disulfide ring in thioredoxin - S2 and the dithiol of the substrate .", "entities": []}, {"sentence": "Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis .", "entities": [{"name": "extracellular matrix components", "type": "Anatomy", "pos": [41, 72]}]}, {"sentence": "Metastasis and tumor angiogenesis are invasive phenomena and share many common properties at the physiological level and some similarities at the molecular level .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [15, 20]}]}, {"sentence": "Each consists of repetitive cycles of interaction with adjacent extracellular matrix components by mediating cellular adhesion , matrix dissolution , and cellular motility to achieve metastasis of cancer cells or neovascularization of tumors .", "entities": [{"name": "extracellular matrix components", "type": "Anatomy", "pos": [64, 95]}, {"name": "cellular", "type": "Anatomy", "pos": [109, 117]}, {"name": "matrix", "type": "Anatomy", "pos": [129, 135]}, {"name": "cellular", "type": "Anatomy", "pos": [154, 162]}, {"name": "cancer cells", "type": "Anatomy", "pos": [197, 209]}, {"name": "tumors", "type": "Anatomy", "pos": [235, 241]}]}, {"sentence": "Molecular factors which implement this triad of events are reviewed , as are several signal transduction components which may regulate them .", "entities": []}, {"sentence": "Some potentially promising prognostic , diagnostic , and therapeutic modalities for tumor angiogenesis and metastatic disease are also discussed .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [84, 89]}, {"name": "metastatic disease", "type": "Anatomy", "pos": [107, 125]}]}, {"sentence": "Suppressed transformation and induced differentiation of HER - 2 / neu - overexpressing breast cancer cells by emodin .", "entities": [{"name": "breast cancer cells", "type": "Anatomy", "pos": [88, 107]}]}, {"sentence": "The amplification and overexpression of the HER - 2 / neu proto - oncogene , which encodes the tyrosine kinase receptor p185neu , have been observed frequently in tumors from human breast cancer patients and are correlated with poor prognosis .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [163, 169]}, {"name": "breast cancer", "type": "Anatomy", "pos": [181, 194]}]}, {"sentence": "To explore the potential of chemotherapy directed at the tyrosine kinase of p185neu , we have found that emodin ( 3 - methyl - 1 , 6 , 8 - trihydroxyanthraquinone ) , a tyrosine kinase inhibitor , suppresses autophosphorylation and transphosphorylation activities of HER - 2 / neu tyrosine kinase , resulting in tyrosine hypophosphorylation of p185neu in HER - 2 / neu - overexpressing breast cancer cells .", "entities": [{"name": "breast cancer cells", "type": "Anatomy", "pos": [386, 405]}]}, {"sentence": "Emodin , at a 40 - microM concentration , which repressed tyrosine kinase of p185neu , efficiently inhibited both anchorage - dependent and anchorage - independent growth of HER - 2 / neu - overexpressing breast cancer cells .", "entities": [{"name": "breast cancer cells", "type": "Anatomy", "pos": [205, 224]}]}, {"sentence": "However , the inhibition was much less effective for those cells expressing basal levels of p185neu under the same conditions .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [59, 64]}]}, {"sentence": "Emodin also induced differentiation of HER - 2 / neu - overexpressing breast cancer cells by exhibiting a morphological maturation property of large lacy nuclei surrounded by sizable flat cytoplasm and by showing a measurable production of large lipid droplets , which is a marker of mature breast cells .", "entities": [{"name": "breast cancer cells", "type": "Anatomy", "pos": [70, 89]}, {"name": "nuclei", "type": "Anatomy", "pos": [154, 160]}, {"name": "flat cytoplasm", "type": "Anatomy", "pos": [183, 197]}, {"name": "mature breast cells", "type": "Anatomy", "pos": [284, 303]}]}, {"sentence": "Therefore , our results indicate that emodin inhibits HER - 2 / neu tyrosine kinase activity and preferentially suppresses growth and induces differentiation of HER - 2 / neu - overexpressing cancer cells .", "entities": [{"name": "cancer cells", "type": "Anatomy", "pos": [192, 204]}]}, {"sentence": "These results may have chemotherapeutic implications for using emodin to target HER - 2 / neu - overexpressing cancer cells .", "entities": [{"name": "cancer cells", "type": "Anatomy", "pos": [111, 123]}]}, {"sentence": "Identification of NAB1 , a repressor of NGFI - A - and Krox20 - mediated transcription .", "entities": []}, {"sentence": "NGFI - A ( also called Egr1 , Zif268 , or Krox24 ) and the closely related proteins Krox20 , NGFI - C , and Egr3 are zinc - finger transcription factors encoded by immediate - early genes which are induced by a wide variety of extracellular stimuli .", "entities": [{"name": "extracellular", "type": "Anatomy", "pos": [227, 240]}]}, {"sentence": "NGFI - A has been implicated in cell proliferation , macrophage differentiation , synaptic activation , and long - term potentiation , whereas Krox20 is critical for proper hindbrain segmentation and peripheral nerve myelination .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [32, 36]}, {"name": "macrophage", "type": "Anatomy", "pos": [53, 63]}, {"name": "synaptic", "type": "Anatomy", "pos": [82, 90]}, {"name": "hindbrain", "type": "Anatomy", "pos": [173, 182]}, {"name": "peripheral nerve", "type": "Anatomy", "pos": [200, 216]}]}, {"sentence": "In previous work , a structure / function analysis of NGFI - A revealed a 34 - aa inhibitory domain that was hypothesized to be the target of a cellular factor that represses NGFI - A transcriptional activity .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [144, 152]}]}, {"sentence": "Using the yeast two - hybrid system , we have isolated a cDNA clone which encodes a protein that interacts with this inhibitory domain and inhibits the ability of NGFI - A to activate transcription .", "entities": []}, {"sentence": "This NGFI - A - binding protein , NAB1 , is a 570 - aa nuclear protein that bears no obvious sequence homology to known proteins .", "entities": [{"name": "nuclear", "type": "Anatomy", "pos": [55, 62]}]}, {"sentence": "NAB1 also represses Krox20 activity , but it does not influence Egr3 or NGFI - G , thus providing a mechanism for the differential regulation of this family of immediate - early transcription factors .", "entities": []}, {"sentence": "Metastatic NIH 3T3 x LTA cell hybrids express 72 kDa type IV collagenase .", "entities": [{"name": "Metastatic NIH 3T3 x LTA cell hybrids", "type": "Anatomy", "pos": [0, 37]}]}, {"sentence": "We previously reported that the murine fibroblast cell line LTA is tumorigenic but non - metastatic , and is non - responsive to a transfected H - ras oncogene .", "entities": [{"name": "fibroblast cell line LTA", "type": "Anatomy", "pos": [39, 63]}]}, {"sentence": "In contrast , NIH 3T3 cells are non - tumorigenic but are ras - responsive and become metastatic when transfected with ras .", "entities": [{"name": "NIH 3T3 cells", "type": "Anatomy", "pos": [14, 27]}]}, {"sentence": "Somatic cell hybrids between LTA and NIH 3T3 cells are tumorigenic , metastatic and ras - responsive .", "entities": [{"name": "Somatic cell hybrids", "type": "Anatomy", "pos": [0, 20]}, {"name": "LTA", "type": "Anatomy", "pos": [29, 32]}, {"name": "NIH 3T3 cells", "type": "Anatomy", "pos": [37, 50]}]}, {"sentence": "Here we examined expression of type IV collagenases in parental LTA and NIH 3T3 cells ( with and without ras ) and four metastatic LTA x NIH 3T3 hybrids ( also with and without ras ) .", "entities": [{"name": "LTA", "type": "Anatomy", "pos": [64, 67]}, {"name": "NIH 3T3 cells", "type": "Anatomy", "pos": [72, 85]}, {"name": "metastatic LTA x NIH 3T3 hybrids", "type": "Anatomy", "pos": [120, 152]}]}, {"sentence": "Parental NIH 3T3 - derived cells had both 72 kDa and 92 kDa gelatinase activities , and LTA - derived cells had either aberrantly sized approximately 90 kDa activity alone or neither enzyme activity .", "entities": [{"name": "NIH 3T3 - derived cells", "type": "Anatomy", "pos": [9, 32]}, {"name": "LTA", "type": "Anatomy", "pos": [88, 91]}, {"name": "cells", "type": "Anatomy", "pos": [102, 107]}]}, {"sentence": "All four metastatic hybrids expressed 60 - 72 kDa gelatinase activity , while three of them also had 92 kDa activity and one had only minimal 92 kDa activity .", "entities": [{"name": "metastatic hybrids", "type": "Anatomy", "pos": [9, 27]}]}, {"sentence": "Thus the metastatic phenotype of the hybrids was associated with expression of 72 kDa gelatinase .", "entities": [{"name": "hybrids", "type": "Anatomy", "pos": [37, 44]}]}, {"sentence": "Levels of RNA for tissue inhibitors of metalloproteinases ( TIMP - 1 , TIMP - 2 ) were relatively constant , suggesting independent regulation of type IV collagenases and their inhibitors .", "entities": [{"name": "tissue", "type": "Anatomy", "pos": [18, 24]}]}, {"sentence": "Southern blotting and probing with PCR - synthesized cDNA fragments of the mouse 72 kDa type IV collagenase gene showed that this gene was present in all cells although the structure of this gene in one of the three LTA cell lines differed from that of the other cells .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [154, 159]}, {"name": "LTA cell lines", "type": "Anatomy", "pos": [216, 230]}, {"name": "cells", "type": "Anatomy", "pos": [263, 268]}]}, {"sentence": "Our results suggest that a key change in the metastatic hybrids , relative to non - metastatic parental LTA cells , is induction of expression of 72 kDa type IV collagenase .", "entities": [{"name": "metastatic hybrids", "type": "Anatomy", "pos": [45, 63]}, {"name": "non - metastatic parental LTA cells", "type": "Anatomy", "pos": [78, 113]}]}, {"sentence": "Neoplastic progression of human colorectal cancer is associated with overexpression of the stromelysin - 3 and BM - 40 / SPARC genes .", "entities": [{"name": "Neoplastic", "type": "Anatomy", "pos": [0, 10]}, {"name": "colorectal cancer", "type": "Anatomy", "pos": [32, 49]}]}, {"sentence": "The interaction of neoplastic cells with the extracellular matrix is a critical event for the initiation of cancer invasion and metastasis .", "entities": [{"name": "neoplastic cells", "type": "Anatomy", "pos": [19, 35]}, {"name": "extracellular matrix", "type": "Anatomy", "pos": [45, 65]}, {"name": "cancer", "type": "Anatomy", "pos": [108, 114]}]}, {"sentence": "This study was designed to evaluate the potential implication of stromelysin - 3 ( ST3 ) , a newly identified member of the matrix - degrading metalloproteinase family , and of BM - 40 / SPARC , a glycoprotein associated with the extracellular matrix , during the progression of human colorectal cancers .", "entities": [{"name": "extracellular matrix", "type": "Anatomy", "pos": [230, 250]}, {"name": "colorectal cancers", "type": "Anatomy", "pos": [285, 303]}]}, {"sentence": "We analyzed the relative abundance of ST3 and BM - 40 / SPARC transcripts by Northern blot , and their distribution by in situ hybridization , in normal mucosa , benign adenomas , and primary colorectal adenocarcinomas and their liver metastases .", "entities": [{"name": "mucosa", "type": "Anatomy", "pos": [153, 159]}, {"name": "benign adenomas", "type": "Anatomy", "pos": [162, 177]}, {"name": "primary colorectal adenocarcinomas", "type": "Anatomy", "pos": [184, 218]}, {"name": "liver metastases", "type": "Anatomy", "pos": [229, 245]}]}, {"sentence": "The ST3 and BM - 40 / SPARC transcripts were overexpressed in primary colorectal cancers and their liver metastases compared to non - neoplastic mucosa .", "entities": [{"name": "primary colorectal cancers", "type": "Anatomy", "pos": [62, 88]}, {"name": "liver metastases", "type": "Anatomy", "pos": [99, 115]}, {"name": "non - neoplastic mucosa", "type": "Anatomy", "pos": [128, 151]}]}, {"sentence": "These transcripts were localized in stromal fibroblasts adjacent to the neoplastic foci .", "entities": [{"name": "stromal fibroblasts", "type": "Anatomy", "pos": [36, 55]}, {"name": "neoplastic foci", "type": "Anatomy", "pos": [72, 87]}]}, {"sentence": "Overexpression of ST3 correlated with the progression of human colorectal tumors toward local invasion and liver metastasis .", "entities": [{"name": "colorectal tumors", "type": "Anatomy", "pos": [63, 80]}, {"name": "liver", "type": "Anatomy", "pos": [107, 112]}]}, {"sentence": "Induction of these genes also occurred in diverticulitis and digestive neoplasms such as gastric and esophageal carcinomas .", "entities": [{"name": "neoplasms", "type": "Anatomy", "pos": [71, 80]}, {"name": "gastric", "type": "Anatomy", "pos": [89, 96]}, {"name": "esophageal carcinomas", "type": "Anatomy", "pos": [101, 122]}]}, {"sentence": "Childhood conscientiousness and longevity : health behaviors and cause of death .", "entities": []}, {"sentence": "Previous research showed that conscientiousness ( social dependability ) in childhood predicted longevity in an archival prospective cohort study of bright children first studied by Terman in the 1920s ( H . S . Friedman et al . , 1993 ) .", "entities": []}, {"sentence": "Possible behavioral mechanisms for this robust association are now examined by gathering cause of death information and by considering the possible mediating influences of drinking alcohol , smoking , and overeating .", "entities": []}, {"sentence": "Survival analyses ( N = 1 , 215 ) suggest that the protective effect of conscientiousness is not primarily due to accident avoidance and cannot be mostly explained by abstinence from unhealthy substance intake .", "entities": []}, {"sentence": "Conscientiousness may have more wide - ranging effects on health - relevant activities .", "entities": []}, {"sentence": "Down - regulation of collagen XII in transformed mesenchymal cells .", "entities": [{"name": "mesenchymal cells", "type": "Anatomy", "pos": [49, 66]}]}, {"sentence": "Collagen XII is a complex multidomain protein associated with the surface of interstitial collagen fibrils .", "entities": [{"name": "surface", "type": "Anatomy", "pos": [66, 73]}, {"name": "interstitial", "type": "Anatomy", "pos": [77, 89]}, {"name": "fibrils", "type": "Anatomy", "pos": [99, 106]}]}, {"sentence": "This protein is produced in large amounts by fibroblasts cultivated in vitro .", "entities": [{"name": "fibroblasts", "type": "Anatomy", "pos": [45, 56]}]}, {"sentence": "However , it is completely absent from cells transformed by the oncogene v - myc or v - src and from cells derived from a methylcholanthrene - induced fibrosarcoma .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [39, 44]}, {"name": "cells", "type": "Anatomy", "pos": [101, 106]}, {"name": "fibrosarcoma", "type": "Anatomy", "pos": [151, 163]}]}, {"sentence": "Since all these cells lack any mRNA for collagen , XII , it seems likely that the synthesis is blocked at the transcriptional level .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [16, 21]}]}, {"sentence": "Experiments with a temperature - sensitive mutant of Rous sarcoma virus demonstrated that a single oncogene product is sufficient to inhibit the synthesis .", "entities": []}, {"sentence": "A reduction in the expression of collagen XII might have profound effects on the stability of the extracellular matrix of transformed cells .", "entities": [{"name": "extracellular matrix", "type": "Anatomy", "pos": [98, 118]}, {"name": "cells", "type": "Anatomy", "pos": [134, 139]}]}, {"sentence": "Comparative NMR study of a differentiated rat hepatoma and its dedifferentiated subclone cultured as spheroids and as implanted tumors .", "entities": [{"name": "hepatoma", "type": "Anatomy", "pos": [46, 54]}, {"name": "subclone", "type": "Anatomy", "pos": [80, 88]}, {"name": "spheroids", "type": "Anatomy", "pos": [101, 110]}, {"name": "tumors", "type": "Anatomy", "pos": [128, 134]}]}, {"sentence": "H4IIEC3 ( H4 ) , a differentiated rat hepatoma line and H5 , its dedifferentiated subclone , were investigated as proliferating spheroids and as implanted subcutaneous tumors in juvenile rats .", "entities": [{"name": "H4IIEC3", "type": "Anatomy", "pos": [0, 7]}, {"name": "H4", "type": "Anatomy", "pos": [10, 12]}, {"name": "hepatoma line", "type": "Anatomy", "pos": [38, 51]}, {"name": "H5", "type": "Anatomy", "pos": [56, 58]}, {"name": "subclone", "type": "Anatomy", "pos": [82, 90]}, {"name": "spheroids", "type": "Anatomy", "pos": [128, 137]}, {"name": "subcutaneous tumors", "type": "Anatomy", "pos": [155, 174]}]}, {"sentence": "H4 cells formed tight , round spheroids whereas H5 cells formed loose , grape - like structures .", "entities": [{"name": "H4 cells", "type": "Anatomy", "pos": [0, 8]}, {"name": "spheroids", "type": "Anatomy", "pos": [30, 39]}, {"name": "H5 cells", "type": "Anatomy", "pos": [48, 56]}, {"name": "grape - like structures", "type": "Anatomy", "pos": [72, 95]}]}, {"sentence": "31P MR spectra showed that phosphocreatine was present in H5 spheroids but not in H4 spheroids or tumors .", "entities": [{"name": "H5 spheroids", "type": "Anatomy", "pos": [58, 70]}, {"name": "H4 spheroids", "type": "Anatomy", "pos": [82, 94]}, {"name": "tumors", "type": "Anatomy", "pos": [98, 104]}]}, {"sentence": "[ 13C ] Lactate production from [ 13C ] glucose , with no detectable uptake of [ 13C ] alanine , indicated that energy production in H5 spheroids was primarily via glycolysis .", "entities": [{"name": "H5 spheroids", "type": "Anatomy", "pos": [133, 145]}]}, {"sentence": "No [ 13C ] glucose utilization was detected in H4 spheroids , but uptake of alanine and accumulation of labeled lactate , glutamate and glutamine indicated oxidation via the tricarboxylic acid ( TCA ) cycle .", "entities": [{"name": "H4 spheroids", "type": "Anatomy", "pos": [47, 59]}]}, {"sentence": "Tumors of H4 cells were well perfused , unlike tumors of H5 cells which were highly necrotic .", "entities": [{"name": "Tumors", "type": "Anatomy", "pos": [0, 6]}, {"name": "H4 cells", "type": "Anatomy", "pos": [10, 18]}, {"name": "tumors", "type": "Anatomy", "pos": [47, 53]}, {"name": "H5 cells", "type": "Anatomy", "pos": [57, 65]}]}, {"sentence": "Following i . v . infusion with [ 13C ] alanine , [ 13C ] lactate and glutamate , evidence of oxidation via the TCA cycle , were observed in H4 tumors .", "entities": [{"name": "i . v .", "type": "Anatomy", "pos": [10, 17]}, {"name": "H4 tumors", "type": "Anatomy", "pos": [141, 150]}]}, {"sentence": "Thus the results obtained by 31P and 13C MRS correlated with the differentiation state of H4 and H5 spheroids and tumors .", "entities": [{"name": "H4", "type": "Anatomy", "pos": [90, 92]}, {"name": "H5 spheroids", "type": "Anatomy", "pos": [97, 109]}, {"name": "tumors", "type": "Anatomy", "pos": [114, 120]}]}, {"sentence": "[ The erbB gene family : significance for tumor development , prognosis and new therapeutic modalities ] .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [42, 47]}]}, {"sentence": "RNA and DNA viruses can be transforming and tumourigenic agents .", "entities": []}, {"sentence": "The transformation is a consequence of the ability of viruses to integrate into the host cell ' s DNA and to produce transforming proteins .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [89, 93]}]}, {"sentence": "These proteins are mainly produced by specific integral parts of the viral genome , the oncogenes .", "entities": []}, {"sentence": "Comparison between RNA / DNA sequence of viral oncogenes and normal human genome of non - transformed cells revealed high sequence similarities in specific genomic areas , which were named cellular proto - oncogens .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [102, 107]}, {"name": "cellular", "type": "Anatomy", "pos": [189, 197]}]}, {"sentence": "They are important components of the growth regulatory pathways in normal cells .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [74, 79]}]}, {"sentence": "The accumulation of genetic alterations of some proto - oncogens , like the erbB - family , may be part of the mechanism , by which malignant cells can acquire a selective growth advantage .", "entities": [{"name": "malignant cells", "type": "Anatomy", "pos": [132, 147]}]}, {"sentence": "The epidermal growth factor receptor ( EGF - R , c - erbB1 ) , Her - 2 / neu ( c - erbB2 ) , and c - erbB3 are members of the erbB - family .", "entities": []}, {"sentence": "The detection of increased abundance of EGF - R or Her - 2 / neu proteins in human tumours can provide additional information on the disease - free survival and overall survival for patients with breast , ovarian , endometrial or cervical cancer .", "entities": [{"name": "tumours", "type": "Anatomy", "pos": [83, 90]}, {"name": "breast", "type": "Anatomy", "pos": [196, 202]}, {"name": "ovarian", "type": "Anatomy", "pos": [205, 212]}, {"name": "endometrial", "type": "Anatomy", "pos": [215, 226]}, {"name": "cervical cancer", "type": "Anatomy", "pos": [230, 245]}]}, {"sentence": "Molecular and cell - physiological analyses have improved the understanding of tumour biology and provide the opportunity for new therapeutic approaches .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [14, 18]}, {"name": "tumour", "type": "Anatomy", "pos": [79, 85]}]}, {"sentence": "Monoclonal antibody targeted therapy directed against EGF - R or Her - 2 / neu , the use of anti - sense oligonucleotides and oligodeoxynucleotides , and the application of tyrosine kinase and protein C - kinase inhibitors are currently being investigated .", "entities": []}, {"sentence": "Human cytomegalovirus elevates levels of the cellular protein p53 in infected fibroblasts .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [45, 53]}, {"name": "fibroblasts", "type": "Anatomy", "pos": [78, 89]}]}, {"sentence": "Human cytomegalovirus ( HCMV ) , like other DNA tumor viruses , induces morphological transformation of cells in vitro and stimulates host cell macromolecular synthesis in infected cells .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [48, 53]}, {"name": "cells", "type": "Anatomy", "pos": [104, 109]}, {"name": "cell", "type": "Anatomy", "pos": [139, 143]}, {"name": "cells", "type": "Anatomy", "pos": [181, 186]}]}, {"sentence": "Since other DNA tumor viruses , such as simian virus 40 and adenovirus , have previously been shown to interact with cellular protein p53 , we investigated whether infection of cells by HCMV would modulate cellular p53 levels .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [16, 21]}, {"name": "cellular", "type": "Anatomy", "pos": [117, 125]}, {"name": "cells", "type": "Anatomy", "pos": [177, 182]}, {"name": "cellular", "type": "Anatomy", "pos": [206, 214]}]}, {"sentence": "Our results indicate that HCMV elevates cellular p53 levels on the order of 10 - to 20 - fold in infected fibroblasts .", "entities": [{"name": "cellular", "type": "Anatomy", "pos": [40, 48]}, {"name": "fibroblasts", "type": "Anatomy", "pos": [106, 117]}]}, {"sentence": "The induction of elevated p53 levels was dependent upon the presence of active virus and was prevented by neutralizing antibody .", "entities": []}, {"sentence": "The induction of elevated p53 levels was determined not to be due to virus - receptor interactions or HCMV late events .", "entities": []}, {"sentence": "The induction of elevated p53 levels commenced at immediate - early times of the HCMV multiplication cycle ( 6 h postinfection ) and reached maximal levels by 24 h postinfection , before most of the HCMV DNA synthesis was initiated .", "entities": []}, {"sentence": "HCMV immediate - early proteins were clearly shown to be responsible for elevating p53 levels in infected fibroblasts ; expression of HCMV immediate - early region 1 and 2 proteins resulted in elevation of p53 levels in transfected human fibroblasts .", "entities": [{"name": "fibroblasts", "type": "Anatomy", "pos": [106, 117]}, {"name": "fibroblasts", "type": "Anatomy", "pos": [238, 249]}]}, {"sentence": "This is the first report of increased p53 levels caused by HCMV in infected fibroblasts .", "entities": [{"name": "fibroblasts", "type": "Anatomy", "pos": [76, 87]}]}, {"sentence": "Comparison of image ( CAS 200 ) and flow cytometry determined DNA content of paraffin - embedded Hodgkin ' s disease tissue .", "entities": [{"name": "Hodgkin ' s disease tissue", "type": "Anatomy", "pos": [97, 123]}]}, {"sentence": "To assess the reliability of DNA estimation using image cytometry , deparaffinized lymph nodes from 70 patients with Hodgkin ' s disease were examined and the results obtained were compared with those from flow cytometry .", "entities": [{"name": "lymph nodes", "type": "Anatomy", "pos": [83, 94]}]}, {"sentence": "Image analysis without discriminating between the various cell types , as found in Hodgkin ' s disease , revealed no separate aneuploid peak .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [58, 62]}]}, {"sentence": "Selecting on morphologically defined nuclear types DNA aneuploidy was detected in 20 % of the cases ( 14 / 70 ) .", "entities": [{"name": "nuclear", "type": "Anatomy", "pos": [37, 44]}]}, {"sentence": "The aneuploid populations were limited to the population of nuclei defined as Reed - Sternberg ( RS ) - like or medium - sized lymphocytes .", "entities": [{"name": "nuclei", "type": "Anatomy", "pos": [60, 66]}, {"name": "lymphocytes", "type": "Anatomy", "pos": [127, 138]}]}, {"sentence": "Benign lymph nodes DNA aneuploidy was not found in any of the controls .", "entities": [{"name": "lymph nodes", "type": "Anatomy", "pos": [7, 18]}]}, {"sentence": "Comparison of DNA histograms obtained by image and flow cytometry showed aneuploid peaks using image cytometry in 4 of 30 diploid and 10 of 40 aneuploid flow histograms .", "entities": []}, {"sentence": "In conclusion , image analysis using the CAS 200 system as compared to flow cytometry is more time - consuming and less sensitive to assess ploidy status , although it may provide extra information in some selected cases .", "entities": []}, {"sentence": "Evidence is obtained that DNA aneuploidy in Hodgkin ' s disease is preferentially expressed by cells with the RS / H - like and medium - sized lymphocyte morphology .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [95, 100]}, {"name": "lymphocyte", "type": "Anatomy", "pos": [143, 153]}]}, {"sentence": "Imaging techniques for the assessment of body composition .", "entities": [{"name": "body", "type": "Anatomy", "pos": [41, 45]}]}, {"sentence": "Three imaging methods , ultrasound imaging ( UI ) , computer - assisted axial tomography ( CAT ) and magnetic resonance imaging ( MRI ) , are widely used in medicine .", "entities": []}, {"sentence": "Their application to the assessment of body composition in nutrition research is still being explored and developed .", "entities": [{"name": "body", "type": "Anatomy", "pos": [39, 43]}]}, {"sentence": "Ultrasound imaging yields poor image quality but , because it is cheap and safe , deserves further exploration .", "entities": []}, {"sentence": "Both CAT and MRI can produce images with good discrimination among bone , muscle and adipose tissue .", "entities": [{"name": "bone", "type": "Anatomy", "pos": [67, 71]}, {"name": "muscle", "type": "Anatomy", "pos": [74, 80]}, {"name": "adipose tissue", "type": "Anatomy", "pos": [85, 99]}]}, {"sentence": "Movement artifacts tend to be more serious in MRI than in CAT due to the longer imaging time .", "entities": []}, {"sentence": "On the other hand , the X - ray exposure in CAT is likely to limit its use in human nutrition research .", "entities": []}, {"sentence": "Repeated measurements of tissue volumes by CAT and MRI give similar CV .", "entities": [{"name": "tissue", "type": "Anatomy", "pos": [25, 31]}]}, {"sentence": "In both CAT and MRI , intra - abdominal adipose tissue presents greater problems of measurement than subcutaneous adipose tissue .", "entities": [{"name": "abdominal adipose tissue", "type": "Anatomy", "pos": [30, 54]}, {"name": "subcutaneous adipose tissue", "type": "Anatomy", "pos": [101, 128]}]}, {"sentence": "Validation studies with 77 - kg pigs of MRI , using 13 slices , predicted total body lipid with residual standard deviation of 1 . 9 % .", "entities": [{"name": "body", "type": "Anatomy", "pos": [80, 84]}]}, {"sentence": "In validating any of these methods , account should be take of the extent to which the information they give can augment that given by more simple measures like age and weight .", "entities": []}, {"sentence": "H - ras mutations in human pituitary carcinoma metastases .", "entities": [{"name": "pituitary carcinoma metastases", "type": "Anatomy", "pos": [27, 57]}]}, {"sentence": "Molecular mechanisms of pituitary tumorigenesis were studied using Polymerase chain reaction - single stranded conformational polymorphism with DNA sequencing to identify potential mutations in the ras protooncogenes and the tumor suppressor gene p53 in invasive pituitary adenomas and carcinomas .", "entities": [{"name": "pituitary", "type": "Anatomy", "pos": [24, 33]}, {"name": "tumor", "type": "Anatomy", "pos": [34, 39]}, {"name": "invasive pituitary adenomas", "type": "Anatomy", "pos": [254, 281]}, {"name": "carcinomas", "type": "Anatomy", "pos": [286, 296]}]}, {"sentence": "Sequencing of exons 5 through 8 of the p53 gene revealed no mutations , nor were mutations detected in the N - or K - ras protooncogenes in four of the carcinomas and their respective metastatic deposits .", "entities": [{"name": "carcinomas", "type": "Anatomy", "pos": [152, 162]}, {"name": "metastatic deposits", "type": "Anatomy", "pos": [184, 203]}]}, {"sentence": "Point mutations of H - ras however , were identified in three distant metastatic pituitary tumor secondaries , but not in their respective primary pituitary carcinomas , or in six invasive adenomas .", "entities": [{"name": "metastatic pituitary tumor secondaries", "type": "Anatomy", "pos": [70, 108]}, {"name": "primary pituitary carcinomas", "type": "Anatomy", "pos": [139, 167]}, {"name": "invasive adenomas", "type": "Anatomy", "pos": [180, 197]}]}, {"sentence": "Two of the mutations included a G to C substitution at codon 12 , and a G to A substitution at codon 18 , resulting in a glycine to arginine , and an alanine to threonine change at these amino acids , respectively .", "entities": []}, {"sentence": "A third mutation involved a single base pair ( adenine ) deletion in codon 3 of H - ras which causes a frame shift , resulting in a termination signal at codon 19 .", "entities": []}, {"sentence": "These results suggest that point mutations in p53 and ras are not associated with pituitary tumorigenesis , however , point mutations of the H - ras gene may be important in the formation and or growth of pituitary metastases .", "entities": [{"name": "pituitary", "type": "Anatomy", "pos": [82, 91]}, {"name": "pituitary metastases", "type": "Anatomy", "pos": [205, 225]}]}, {"sentence": "This observed genomic instability will be of value in predicting the potential metastatic behavior of these aggressive pituitary tumors .", "entities": [{"name": "pituitary tumors", "type": "Anatomy", "pos": [119, 135]}]}, {"sentence": "Overexpression of Glut - 1 glucose transporter in human breast cancer .", "entities": [{"name": "breast cancer", "type": "Anatomy", "pos": [56, 69]}]}, {"sentence": "An immunohistochemical study .", "entities": []}, {"sentence": "BACKGROUND : Breast cancers have higher than normal glucose metabolism , but the mechanism of glucose entry into these tumors is not well understood .", "entities": [{"name": "Breast cancers", "type": "Anatomy", "pos": [13, 27]}, {"name": "tumors", "type": "Anatomy", "pos": [119, 125]}]}, {"sentence": "METHODS : The expression of five facilitative glucose transporters , Glut - 1 ( erythrocyte type ) , Glut - 2 ( liver type ) , Glut - 3 ( brain type ) , Glut - 4 ( muscle / fat type ) , and Glut - 5 ( small intestine type ) , was studied by immunohistochemistry of paraffin sections from 12 primary human breast cancers and 8 lymph node metastases from 2 patients .", "entities": [{"name": "erythrocyte", "type": "Anatomy", "pos": [80, 91]}, {"name": "liver", "type": "Anatomy", "pos": [112, 117]}, {"name": "brain", "type": "Anatomy", "pos": [138, 143]}, {"name": "muscle", "type": "Anatomy", "pos": [164, 170]}, {"name": "fat", "type": "Anatomy", "pos": [173, 176]}, {"name": "small intestine", "type": "Anatomy", "pos": [201, 216]}, {"name": "paraffin sections", "type": "Anatomy", "pos": [265, 282]}, {"name": "primary human breast cancers", "type": "Anatomy", "pos": [291, 319]}, {"name": "lymph node metastases", "type": "Anatomy", "pos": [326, 347]}]}, {"sentence": "Rat tissues known to express these glucose transporters were used as controls .", "entities": [{"name": "tissues", "type": "Anatomy", "pos": [4, 11]}]}, {"sentence": "RESULTS : All the primary breast cancers and the lymph node metastases were positive for Glut - 1 .", "entities": [{"name": "primary breast cancers", "type": "Anatomy", "pos": [18, 40]}, {"name": "lymph node metastases", "type": "Anatomy", "pos": [49, 70]}]}, {"sentence": "This transporter was expressed on the cell membrane and in the cytoplasm of the tumor cells , but exhibited marked intratumoral and intertumoral variability in the proportions of positive cells and the intensity of staining .", "entities": [{"name": "cell membrane", "type": "Anatomy", "pos": [38, 51]}, {"name": "cytoplasm", "type": "Anatomy", "pos": [63, 72]}, {"name": "tumor cells", "type": "Anatomy", "pos": [80, 91]}, {"name": "intratumoral", "type": "Anatomy", "pos": [115, 127]}, {"name": "intertumoral", "type": "Anatomy", "pos": [132, 144]}, {"name": "cells", "type": "Anatomy", "pos": [188, 193]}]}, {"sentence": "Staining of the normal mammary epithelium , if present , was much lower than observed in tumor cells from the same patient .", "entities": [{"name": "mammary epithelium", "type": "Anatomy", "pos": [23, 41]}, {"name": "tumor cells", "type": "Anatomy", "pos": [89, 100]}]}, {"sentence": "Glut - 2 was expressed in all of the tumors , but the intensity of staining was not consistently stronger than that seen in healthy breast .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [37, 43]}, {"name": "healthy breast", "type": "Anatomy", "pos": [124, 138]}]}, {"sentence": "Clusters of Glut - 4 - positive granule were observed in cells in six of the tumors .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [57, 62]}, {"name": "tumors", "type": "Anatomy", "pos": [77, 83]}]}, {"sentence": "None of the tumors or the healthy breast in the tissues studied expressed Glut - 3 or Glut - 5 .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [12, 18]}, {"name": "healthy breast", "type": "Anatomy", "pos": [26, 40]}, {"name": "tissues", "type": "Anatomy", "pos": [48, 55]}]}, {"sentence": "CONCLUSIONS : Higher expression of the glucose transporter Glut - 1 by breast cancer cells compared with the healthy breast tissue is common .", "entities": [{"name": "breast cancer cells", "type": "Anatomy", "pos": [71, 90]}, {"name": "healthy breast tissue", "type": "Anatomy", "pos": [109, 130]}]}, {"sentence": "Increased glucose transporter protein expression may contribute to the increased uptake of 2 - [ 18F ] - fluoro - 2 - deoxy - D - glucose ( FDG ) by these tumors observed by positron emission tomography ( PET ) imaging .", "entities": [{"name": "tumors", "type": "Anatomy", "pos": [155, 161]}]}, {"sentence": "High density of somatostatin receptors in veins surrounding human cancer tissue : role in tumor - host interaction ?", "entities": [{"name": "veins", "type": "Anatomy", "pos": [42, 47]}, {"name": "cancer tissue", "type": "Anatomy", "pos": [66, 79]}, {"name": "tumor", "type": "Anatomy", "pos": [90, 95]}]}, {"sentence": "Somatostatin receptors were detected in peritumoral veins of various human cancer tissue specimens .", "entities": [{"name": "peritumoral veins", "type": "Anatomy", "pos": [40, 57]}, {"name": "cancer tissue specimens", "type": "Anatomy", "pos": [75, 98]}]}, {"sentence": "Vascular and neoplastic tissue from 14 colonic adenocarcinomas , 13 carcinoids , 6 renal - cell carcinomas and 7 malignant lymphomas were analyzed for somatostatin receptors by use of quantitative receptor autoradiography .", "entities": [{"name": "Vascular", "type": "Anatomy", "pos": [0, 8]}, {"name": "neoplastic tissue", "type": "Anatomy", "pos": [13, 30]}, {"name": "colonic adenocarcinomas", "type": "Anatomy", "pos": [39, 62]}, {"name": "carcinoids", "type": "Anatomy", "pos": [68, 78]}, {"name": "renal - cell carcinomas", "type": "Anatomy", "pos": [83, 106]}, {"name": "malignant lymphomas", "type": "Anatomy", "pos": [113, 132]}]}, {"sentence": "In colonic carcinoma specimens , the peritumoral vessels expressed a high density of somatostatin receptors , whereas the neoplastic tissue itself was receptor - negative in many cases .", "entities": [{"name": "colonic carcinoma specimens", "type": "Anatomy", "pos": [3, 30]}, {"name": "peritumoral vessels", "type": "Anatomy", "pos": [37, 56]}, {"name": "neoplastic tissue", "type": "Anatomy", "pos": [122, 139]}]}, {"sentence": "In contrast , the incidence and density of somatostatin receptors in peritumoral vessels was low in well - differentiated gastrointestinal and bronchial carcinoids , in contrast to the high density of such receptors in the carcinoid tumor tissue .", "entities": [{"name": "peritumoral vessels", "type": "Anatomy", "pos": [69, 88]}, {"name": "gastrointestinal", "type": "Anatomy", "pos": [122, 138]}, {"name": "bronchial carcinoids", "type": "Anatomy", "pos": [143, 163]}, {"name": "carcinoid tumor tissue", "type": "Anatomy", "pos": [223, 245]}]}, {"sentence": "Autochthonous vessels surrounding other tumors such as renal - cell carcinomas or malignant lymphomas also frequently expressed somatostatin receptors .", "entities": [{"name": "vessels", "type": "Anatomy", "pos": [14, 21]}, {"name": "tumors", "type": "Anatomy", "pos": [40, 46]}, {"name": "renal - cell carcinomas", "type": "Anatomy", "pos": [55, 78]}, {"name": "malignant lymphomas", "type": "Anatomy", "pos": [82, 101]}]}, {"sentence": "In all cases , the somatostatin receptors were localized in veins , particularly in the smooth - muscle cell layer .", "entities": [{"name": "veins", "type": "Anatomy", "pos": [60, 65]}, {"name": "smooth - muscle cell layer", "type": "Anatomy", "pos": [88, 114]}]}, {"sentence": "They exhibited specific and high - affinity binding of somatostatin - 14 , somatostatin - 28 and octreotide , suggesting a preferential expression of the SSTR2 receptor subtype .", "entities": []}, {"sentence": "Since the vessels of normal non - neoplastic human tissues , e . g . of intestine or lymphatic organs , have few somatostatin receptors , the increased somatostatin receptor expression in peritumoral vessels observed in this study may be linked to the neoplastic process itself .", "entities": [{"name": "vessels", "type": "Anatomy", "pos": [10, 17]}, {"name": "non - neoplastic human tissues", "type": "Anatomy", "pos": [28, 58]}, {"name": "intestine", "type": "Anatomy", "pos": [72, 81]}, {"name": "lymphatic organs", "type": "Anatomy", "pos": [85, 101]}, {"name": "peritumoral vessels", "type": "Anatomy", "pos": [188, 207]}, {"name": "neoplastic", "type": "Anatomy", "pos": [252, 262]}]}, {"sentence": "The results suggest that somatostatin and somatostatin receptors may play a regulatory role for hemodynamic tumor - host interactions , possibly involving tumor stroma generation , tumor environment , angiogenesis and , particularly , vascular drainage of poorly differentiated neoplasms .", "entities": [{"name": "tumor", "type": "Anatomy", "pos": [108, 113]}, {"name": "tumor stroma", "type": "Anatomy", "pos": [155, 167]}, {"name": "tumor", "type": "Anatomy", "pos": [181, 186]}, {"name": "vascular", "type": "Anatomy", "pos": [235, 243]}, {"name": "neoplasms", "type": "Anatomy", "pos": [278, 287]}]}, {"sentence": "Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome : what we do and do not know about cytokine regulation .", "entities": []}, {"sentence": "OBJECTIVES :", "entities": []}, {"sentence": "The systemic inflammatory response syndrome ( SIRS ) is the massive inflammatory reaction resulting from systemic mediator release that may lead to multiple organ dysfunction .", "entities": [{"name": "organ", "type": "Anatomy", "pos": [157, 162]}]}, {"sentence": "The objective of this review article is to analyze the roles of cytokines , cytokine production , and the relationship of cytokine production to the development of SIRS .", "entities": []}, {"sentence": "DATA SOURCES :", "entities": []}, {"sentence": "Previous research and clinical studies related to cytokines and their relationship to SIRS .", "entities": []}, {"sentence": "STUDY SELECTION :", "entities": []}, {"sentence": "From the studies reviewed , three critical questions are addressed .", "entities": []}, {"sentence": "First , what is the definition of increased cytokine concentrations ?", "entities": []}, {"sentence": "Second , what other systemic illnesses besides sepsis can alter cytokine concentrations ?", "entities": []}, {"sentence": "Third , what are the right cytokines to measure ?", "entities": []}, {"sentence": "DATA SYNTHESIS :", "entities": []}, {"sentence": "This article postulates a three - stage development of SIRS , in which stage 1 is a local production of cytokines in response to an injury or infection .", "entities": []}, {"sentence": "Stage 2 is the protective release of a small amount of cytokines into the body ' s circulation .", "entities": [{"name": "body", "type": "Anatomy", "pos": [74, 78]}]}, {"sentence": "Stage 3 is the massive systemic reaction where cytokines turn destructive by compromising the integrity of the capillary walls and flooding end organs .", "entities": [{"name": "capillary walls", "type": "Anatomy", "pos": [111, 126]}, {"name": "organs", "type": "Anatomy", "pos": [144, 150]}]}, {"sentence": "CONCLUSIONS :", "entities": []}, {"sentence": "While cytokines are generally viewed as a destructive development in the patient that generally leads to multiple organ dysfunction , cytokines also protect the body when localized .", "entities": [{"name": "organ", "type": "Anatomy", "pos": [114, 119]}, {"name": "body", "type": "Anatomy", "pos": [161, 165]}]}, {"sentence": "It will be necessary to study the positive effects of cytokines while also studying their role in causing SIRS .", "entities": []}, {"sentence": "It will also be important to investigate the relationship between cytokines and their blockers in SIRS .", "entities": []}, {"sentence": "Syndecan - 1 expression in mammary epithelial tumor cells is E - cadherin - dependent .", "entities": [{"name": "mammary epithelial tumor cells", "type": "Anatomy", "pos": [27, 57]}]}, {"sentence": "E - cadherin is a Ca ( 2 + ) - dependent cell - cell adhesion molecule , which is mainly expressed in epithelial cells .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [41, 45]}, {"name": "cell", "type": "Anatomy", "pos": [48, 52]}, {"name": "epithelial cells", "type": "Anatomy", "pos": [102, 118]}]}, {"sentence": "Recent studies have shown that E - cadherin has an important role as an invasion suppressor molecule in epithelial tumor cells .", "entities": [{"name": "epithelial tumor cells", "type": "Anatomy", "pos": [104, 126]}]}, {"sentence": "Syndecan - 1 is a cell surface proteoglycan that has been implicated in a number of cellular functions including cell - cell adhesion , cell - matrix anchorage and growth factor presentation for signalling receptors .", "entities": [{"name": "cell surface", "type": "Anatomy", "pos": [18, 30]}, {"name": "cellular", "type": "Anatomy", "pos": [84, 92]}, {"name": "cell", "type": "Anatomy", "pos": [113, 117]}, {"name": "cell", "type": "Anatomy", "pos": [120, 124]}, {"name": "cell", "type": "Anatomy", "pos": [136, 140]}, {"name": "matrix", "type": "Anatomy", "pos": [143, 149]}]}, {"sentence": "Its suppression has also been shown to be associated with malignant transformation of epithelial cells .", "entities": [{"name": "epithelial cells", "type": "Anatomy", "pos": [86, 102]}]}, {"sentence": "In order to better understand the coordinated regulation of cell - cell and cell - matrix interactions during malignant transformation , we have studied the expression of syndecan - 1 in malignant mammary tumor cells genetically manipulated for E - cadherin expression .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [60, 64]}, {"name": "cell", "type": "Anatomy", "pos": [67, 71]}, {"name": "cell", "type": "Anatomy", "pos": [76, 80]}, {"name": "matrix", "type": "Anatomy", "pos": [83, 89]}, {"name": "malignant mammary tumor cells", "type": "Anatomy", "pos": [187, 216]}]}, {"sentence": "In invasive NM - e - ras - MAC1 cells , where E - cadherin was partially downregulated by specific antisense RNA , syndecan - 1 expression was suppressed .", "entities": [{"name": "NM - e - ras - MAC1 cells", "type": "Anatomy", "pos": [12, 37]}]}, {"sentence": "Furthermore , transfection of E - cadherin cDNA into invasive NM - f - ras - TD cells resulted in the upregulation of syndecan - 1 expression in association with decreased invasiveness .", "entities": [{"name": "NM - f - ras - TD cells", "type": "Anatomy", "pos": [62, 85]}]}, {"sentence": "In both cases , regulation of syndecan - 1 occurred post - transcriptionally , since syndecan - 1 mRNA levels remained unchanged .", "entities": []}, {"sentence": "Instead , a translational regulation is suggested , since syndecan - 1 core protein synthesis was E - cadherin dependent .", "entities": []}, {"sentence": "Another cell adhesion protein , beta 1 - integrin was not affected by E - cadherin expression .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [8, 12]}]}, {"sentence": "The data provide an example of coordinated changes in the expression of two cell adhesion molecules , syndecan - 1 and E - cadherin during epithelial cell transformation .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [76, 80]}, {"name": "epithelial cell", "type": "Anatomy", "pos": [139, 154]}]}, {"sentence": "Metastasis - associated 5T4 antigen disrupts cell - cell contacts and induces cellular motility in epithelial cells .", "entities": [{"name": "cell - cell contacts", "type": "Anatomy", "pos": [45, 65]}, {"name": "cellular", "type": "Anatomy", "pos": [78, 86]}, {"name": "epithelial cells", "type": "Anatomy", "pos": [99, 115]}]}, {"sentence": "The 5T4 antigen is defined by a monoclonal antibody ( MAb ) specific for human trophoblast .", "entities": [{"name": "trophoblast", "type": "Anatomy", "pos": [79, 90]}]}, {"sentence": "It is also expressed by many types of tumour cell and has been associated with metastasis and poor clinical outcome in a number of cancers .", "entities": [{"name": "tumour cell", "type": "Anatomy", "pos": [38, 49]}, {"name": "cancers", "type": "Anatomy", "pos": [131, 138]}]}, {"sentence": "This pattern of expression is consistent with a mechanistic involvement of 5T4 molecules in the spread of cancer cells .", "entities": [{"name": "cancer cells", "type": "Anatomy", "pos": [106, 118]}]}, {"sentence": "The 5T4 antigen is a transmembrane glycoprotein with a 310 amino acid extracellular domain and a 44 amino acid cytoplasmic domain .", "entities": [{"name": "transmembrane", "type": "Anatomy", "pos": [21, 34]}, {"name": "extracellular", "type": "Anatomy", "pos": [70, 83]}, {"name": "cytoplasmic", "type": "Anatomy", "pos": [111, 122]}]}, {"sentence": "Transfection of full - length 5T4 cDNA into epithelial cells alters cell - cell contacts and cellular motility .", "entities": [{"name": "epithelial cells", "type": "Anatomy", "pos": [44, 60]}, {"name": "cell - cell contacts", "type": "Anatomy", "pos": [68, 88]}, {"name": "cellular", "type": "Anatomy", "pos": [93, 101]}]}, {"sentence": "Thus , in 5T4 - transfected CL - S1 murine mammary cells , 5T4 expression is associated with dendritic morphology , accompanied by abrogation of actin / cadherin - containing contacts and increased motility .", "entities": [{"name": "CL - S1 murine mammary cells", "type": "Anatomy", "pos": [28, 56]}, {"name": "dendritic", "type": "Anatomy", "pos": [93, 102]}]}, {"sentence": "In transfected MDCK canine kidney epithelial cells , 5T4 over - expression also results in increased motility , but disruption of cell - cell contacts , either by culturing cells in low calcium medium or by addition of HGF / SF , is needed .", "entities": [{"name": "MDCK canine kidney epithelial cells", "type": "Anatomy", "pos": [15, 50]}, {"name": "cell - cell contacts", "type": "Anatomy", "pos": [130, 150]}, {"name": "cells", "type": "Anatomy", "pos": [173, 178]}]}, {"sentence": "The effects of 5T4 expression on morphology and motility are separable since cells transfected with a truncated form of 5T4 cDNA in which the cytoplasmic domain is deleted reveal that the latter is necessary to abrogate actin / cadherin - containing contacts but does not influence the effects on motility .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [77, 82]}, {"name": "cytoplasmic", "type": "Anatomy", "pos": [142, 153]}]}, {"sentence": "Thus , 5T4 molecules can deliver signals through both the extracellular and intracellular domains , and the resultant effects are consistent with a role for 5T4 molecules in invasion processes .", "entities": [{"name": "extracellular", "type": "Anatomy", "pos": [58, 71]}, {"name": "intracellular", "type": "Anatomy", "pos": [76, 89]}]}, {"sentence": "Defective biliary copper excretion in Wilson ' s disease : the role of caeruloplasmin .", "entities": []}, {"sentence": "Previous studies have failed to explain the link between copper accumulation and abnormal caeruloplasmin expression in Wilson ' s disease .", "entities": []}, {"sentence": "Furthermore , despite the isolation of a candidate gene for Wilson ' s disease , which predicts a defective copper transport protein , the localization of this putative protein and its relationship to the pathway involved in copper excretion and to caeruloplasmin remain unknown .", "entities": []}, {"sentence": "We now present evidence that caeruloplasmin , the major plasma copper - carrying protein , is present in the liver in Wilson ' s disease , and thus that reduced circulating levels of the protein result from a post - translational defect in the secretory pathway .", "entities": [{"name": "plasma", "type": "Anatomy", "pos": [56, 62]}, {"name": "liver", "type": "Anatomy", "pos": [109, 114]}]}, {"sentence": "We have also identified a novel form of caeruloplasmin , molecular weight 125 kD , which we propose may act as the carrier for excretory copper into bile , since it is normally present in both liver and bile , although largely absent from serum , and undetectable in bile from Wilson ' s disease patients .", "entities": [{"name": "bile", "type": "Anatomy", "pos": [149, 153]}, {"name": "liver", "type": "Anatomy", "pos": [193, 198]}, {"name": "bile", "type": "Anatomy", "pos": [203, 207]}, {"name": "serum", "type": "Anatomy", "pos": [239, 244]}, {"name": "bile", "type": "Anatomy", "pos": [267, 271]}]}, {"sentence": "The presence of this form of caeruloplasmin in Wilson ' s disease liver suggests that a related post - translational defect may also be responsible for its absence from bile in Wilson ' s disease .", "entities": [{"name": "liver", "type": "Anatomy", "pos": [66, 71]}, {"name": "bile", "type": "Anatomy", "pos": [169, 173]}]}, {"sentence": "This study thus provides the first plausible explanation of a link between the defective copper excretion and the reduced plasma caeruloplasmin , which characterize Wilson ' s disease .", "entities": [{"name": "plasma", "type": "Anatomy", "pos": [122, 128]}]}, {"sentence": "[ Effects of carcinostatic agents in the hematogenous metastasis of cancer ] .", "entities": [{"name": "cancer", "type": "Anatomy", "pos": [68, 74]}]}, {"sentence": "The experimental studies in vitro and in vivo were performed to investigate the effects of carcinostatic agents in the adhesion of cancer cells to endothelial cells .", "entities": [{"name": "cancer cells", "type": "Anatomy", "pos": [131, 143]}, {"name": "endothelial cells", "type": "Anatomy", "pos": [147, 164]}]}, {"sentence": "Certain carcinostatic agents induce the expression of E - selectin on endothelial cells and enhance the expression of carbohydrate ligands on cancer cells .", "entities": [{"name": "endothelial cells", "type": "Anatomy", "pos": [70, 87]}, {"name": "cancer cells", "type": "Anatomy", "pos": [142, 154]}]}, {"sentence": "Consequently , increased adhesion of cancer cells to endothelial cells was observed by the treatment of carcinostatic agents .", "entities": [{"name": "cancer cells", "type": "Anatomy", "pos": [37, 49]}, {"name": "endothelial cells", "type": "Anatomy", "pos": [53, 70]}]}, {"sentence": "In the trans - splenic hepatic metastasis model using nude mice , the augmentation of cancer metastasis was observed by the treatment of carcinostatic agents .", "entities": [{"name": "trans - splenic", "type": "Anatomy", "pos": [7, 22]}, {"name": "hepatic", "type": "Anatomy", "pos": [23, 30]}, {"name": "cancer", "type": "Anatomy", "pos": [86, 92]}]}, {"sentence": "From the above , we concluded that carcinostatic agents may increase the metastatic ability of cancer cells in patients with cancer .", "entities": [{"name": "cancer cells", "type": "Anatomy", "pos": [95, 107]}, {"name": "cancer", "type": "Anatomy", "pos": [125, 131]}]}, {"sentence": "Changes in plasminogen activator inhibitor - 1 levels in non - small cell lung cancer .", "entities": [{"name": "non - small cell lung cancer", "type": "Anatomy", "pos": [57, 85]}]}, {"sentence": "Increased urokinase plasminogen activator ( uPA ) levels are increased in a number of malignancies and have been correlated with decreased disease - free interval and decreased overall survival .", "entities": [{"name": "malignancies", "type": "Anatomy", "pos": [86, 98]}]}, {"sentence": "We have , therefore , examined components of this plasminogen activating system in patients with Non - Small Cell Lung Cancer ( NSCLC ) .", "entities": [{"name": "Non - Small Cell Lung Cancer", "type": "Anatomy", "pos": [97, 125]}, {"name": "NSCLC", "type": "Anatomy", "pos": [128, 133]}]}, {"sentence": "Levels of uPA , urokinase - plasminogen activator receptor ( uPAR ) and plasminogen activator inhibitor - 1 ( PAI - 1 ) were measured semiquantitatively in paraffin sections of tumours from 147 patients with NSCLC .", "entities": [{"name": "paraffin sections", "type": "Anatomy", "pos": [156, 173]}, {"name": "tumours", "type": "Anatomy", "pos": [177, 184]}, {"name": "NSCLC", "type": "Anatomy", "pos": [208, 213]}]}, {"sentence": "Immunohistochemically stained sections of tumour were allocated a score for stain intensity and results correlated to : survival ; tumour stage ( T ) ; nodal stage ( N ) ; stage grouping ( I to IIIb ) , survival status and sex .", "entities": [{"name": "sections", "type": "Anatomy", "pos": [30, 38]}, {"name": "tumour", "type": "Anatomy", "pos": [42, 48]}, {"name": "tumour", "type": "Anatomy", "pos": [131, 137]}, {"name": "nodal", "type": "Anatomy", "pos": [152, 157]}]}, {"sentence": "Increased levels of PAI - 1 were associated with a decreased survival in squamous cell carcinoma ( SCC ) X2 = 5 . 72 , p = 0 . 017 ( n = 74 ) .", "entities": [{"name": "squamous cell carcinoma", "type": "Anatomy", "pos": [73, 96]}, {"name": "SCC", "type": "Anatomy", "pos": [99, 102]}]}, {"sentence": "There was a significant positive relationship between PAI - 1 levels and N - stage ( p = < 0 . 05 ) , presence of nodal metastases ( p = < 0 . 05 ) , stage grouping ( p = < 0 . 01 ) and extent of disease ( p = < 0 . 05 ) in the total group and the SCC subgroup , but not adenocarcinoma .", "entities": [{"name": "nodal metastases", "type": "Anatomy", "pos": [114, 130]}, {"name": "SCC", "type": "Anatomy", "pos": [248, 251]}, {"name": "adenocarcinoma", "type": "Anatomy", "pos": [271, 285]}]}, {"sentence": "There was a significant positive relationship between PAI - 1 levels and T - stage ( p = < 0 . 05 ) in the total group , and survival status ( p = < 0 . 05 ) in the SCC subgroup alone .", "entities": [{"name": "SCC", "type": "Anatomy", "pos": [165, 168]}]}, {"sentence": "uPA and uPAR levels were not significantly associated with tumour staging or survival .", "entities": [{"name": "tumour", "type": "Anatomy", "pos": [59, 65]}]}, {"sentence": "We conclude that increased PAI - 1 antigen levels may be associated with a decreased survival in patients with SCC .", "entities": [{"name": "SCC", "type": "Anatomy", "pos": [111, 114]}]}, {"sentence": "Conservative treatment of endometriosis : the effects of limited surgery and hormonal pseudopregnancy .", "entities": []}, {"sentence": "This study compares the effects of limited surgery or hormonal pseudopregnancy , or a combination of these two , upon fertility and the need for subsequent surgery with respect to the extent of the disease at the time of initial diagnosis in patients with endometriosis externa .", "entities": []}, {"sentence": "Of the 61 patients who desired to enhance or preserve reproductive capacity , 20 patients became pregnant , for a pregnancy rate of 33 % .", "entities": []}, {"sentence": "The pregnancy rate in all categories , that is , those patients treated with pseudopregnancy , conservative surgery , and combined pseudopregnancy and surgery , was found to be in direct relationship to the initial extent of disease .", "entities": []}, {"sentence": "In such patients , conservative surgery alone seemed to give the best results in the achievement of pregnancy .", "entities": []}, {"sentence": "There seemed to be little difference between pseudopregnancy alone and conservative surgery in regard to the need for subsequent surgery after initial therapy , although there seemed to be a significantly greater chance for the need for subsequent surgery in patients receiving a combination of the two forms of therapy .", "entities": []}, {"sentence": "The need for subsequent surgery after initial therapy in 80 patients increased in direct relationship to the initial extent of disease present , despite the form of therapy used .", "entities": []}, {"sentence": "Fifty - nine other patients with endometriosis , who did not desire to preserve fertility and presented for relief of other symptoms , underwent initial \" radical \" therapy .", "entities": []}, {"sentence": "Forty - six patients underwent complete operation , including removal of uterus , tubes and ovaries , and none required subsequent reoperation .", "entities": [{"name": "uterus", "type": "Anatomy", "pos": [73, 79]}, {"name": "tubes", "type": "Anatomy", "pos": [82, 87]}, {"name": "ovaries", "type": "Anatomy", "pos": [92, 99]}]}, {"sentence": "Of the 13 remaining patients , who underwent incomplete surgical removal , leaving one or both ovaries in situ , 11 required subsequent reoperation for recurrent pelvic endometriosis .", "entities": [{"name": "ovaries", "type": "Anatomy", "pos": [95, 102]}]}, {"sentence": "Lack of developmental and reproductive toxicity of 2 , 3 , 3 ' , 4 , 4 ' - pentachlorobiphenyl ( PCB 105 ) in ring - necked pheasants .", "entities": []}, {"sentence": "Mono - ortho PCBs are global contaminants of wildlife with the potential to produce toxicity by an aryl hydrocarbon receptor ( AhR ) - mediated mechanism .", "entities": []}, {"sentence": "To determine the potency of 2 , 3 , 3 ' , 4 , 4 ' - pentachlorobiphenyl ( PCB 105 ) for producing reproductive and developmental toxicity , adult ring - necked pheasant hens ( Phasianus colchicus ) were orally dosed with 0 , 0 . 06 , 0 . 6 , or 6 mg PCB 105 / kg hen / week for 10 weeks to achieve cumulative doses of 0 , 0 . 6 , 6 , or 60 mg PCB 105 / kg hen after which hens were bred with untreated roosters once per week for 8 weeks .", "entities": [{"name": "necked", "type": "Anatomy", "pos": [153, 159]}, {"name": "orally", "type": "Anatomy", "pos": [203, 209]}]}, {"sentence": "Except at week 6 of the egg - laying period when cumulative egg production in the 6 mg PCB 105 / kg hen group was greater than controls , fertilized egg production was not significantly different between treatment groups .", "entities": [{"name": "egg", "type": "Anatomy", "pos": [24, 27]}, {"name": "egg", "type": "Anatomy", "pos": [60, 63]}, {"name": "egg", "type": "Anatomy", "pos": [149, 152]}]}, {"sentence": "Embryo mortality and chick mortality were not significantly different between treatment groups .", "entities": [{"name": "Embryo", "type": "Anatomy", "pos": [0, 6]}]}, {"sentence": "Total body and heart weights of all chicks 1 day posthatch ( dph ) were not different between groups , however , liver weights of chicks from the 60 mg / kg treatment group were greater than controls at 1 dph .", "entities": [{"name": "body", "type": "Anatomy", "pos": [6, 10]}, {"name": "heart", "type": "Anatomy", "pos": [15, 20]}, {"name": "liver", "type": "Anatomy", "pos": [113, 118]}]}, {"sentence": "The first chick to hatch from each hen was reared to 21 dph and among these birds , the total body , liver , and heart weights were not different between groups .", "entities": [{"name": "body", "type": "Anatomy", "pos": [94, 98]}, {"name": "liver", "type": "Anatomy", "pos": [101, 106]}, {"name": "heart", "type": "Anatomy", "pos": [113, 118]}]}, {"sentence": "There were no dose - related malformations of the beak or limbs , and no signs of subcutaneous edema , ascites , or pericardial edema in chicks at 1 or 21 dph .", "entities": [{"name": "beak", "type": "Anatomy", "pos": [50, 54]}, {"name": "limbs", "type": "Anatomy", "pos": [58, 63]}, {"name": "subcutaneous edema", "type": "Anatomy", "pos": [82, 100]}, {"name": "ascites", "type": "Anatomy", "pos": [103, 110]}, {"name": "pericardial edema", "type": "Anatomy", "pos": [116, 133]}]}, {"sentence": "Hepatic microsomal monooxygenase activities [ ethoxyresorufin - O - dealkylase ( EROD ) , benzyloxyresorufin - O - dealkylase ( BROD ) , and methyloxyresorufin - O - dealkylase ( MROD ) ] were significantly elevated in chicks at 1 dph from hens given a cumulative PCB 105 dose of 6 mg / kg and in chicks at 21 dph from hens given a cumulative PCB dose of 60 mg / kg .", "entities": [{"name": "Hepatic", "type": "Anatomy", "pos": [0, 7]}]}, {"sentence": "These results indicate that a cumulative PCB 105 dose up to 60 mg / kg hen does not decrease the production of fertilized eggs or increase embryo or chick mortality in ring - necked pheasants , but does increase chick hepatic monooxygenase activity .", "entities": [{"name": "eggs", "type": "Anatomy", "pos": [122, 126]}, {"name": "embryo", "type": "Anatomy", "pos": [139, 145]}, {"name": "hepatic", "type": "Anatomy", "pos": [218, 225]}]}, {"sentence": "Detection of total assist and sucking points based on the pulsatility of a continuous flow artificial heart : in vivo evaluation .", "entities": []}, {"sentence": "Our novel control strategy for a continuous flow artificial heart by detecting the total assist and sucking points based on pump pulsatility was evaluated in acute animal experiments using beagle dogs and our mixed flow pump .", "entities": []}, {"sentence": "The pump was installed as a left ventricular ( LV ) bypass through a left thoracotomy .", "entities": [{"name": "left ventricular", "type": "Anatomy", "pos": [28, 44]}, {"name": "LV", "type": "Anatomy", "pos": [47, 49]}]}, {"sentence": "To change LV contractility , the left coronary arteries were occluded for 30 min , followed by a 120 min reperfusion .", "entities": [{"name": "LV", "type": "Anatomy", "pos": [10, 12]}, {"name": "left coronary arteries", "type": "Anatomy", "pos": [33, 55]}]}, {"sentence": "To change LV end diastolic pressure ( LVEDP ) , dextran solution was rapidly infused .", "entities": [{"name": "LV", "type": "Anatomy", "pos": [10, 12]}]}, {"sentence": "To estimate the pump pulsatility without any specific sensor , we calculated the index of current amplitude ( ICA ) , which was obtained from the amplitude of the motor current waveform divided by the simultaneous mean value .", "entities": []}, {"sentence": "To investigate the basic characteristics of the ICA , the pump speed was changed temporarily from 2 , 300 rpm to 5 , 000 rpm .", "entities": []}, {"sentence": "In 92 % of all measurements , the ICA plotted against the pump speed had a peak point ( t - point ) that corresponded highly with the turning point from partial to total assistance .", "entities": []}, {"sentence": "The ICA also had a trough ( s - point ) that corresponded with the beginning of severe sucking in most cases .", "entities": []}, {"sentence": "Only preload significantly influenced pump flow rate at the t - point from among preload ( LVEDP ) , afterload ( SAoP ) , and contractility ( max LV dP / dt ) , by which we can simulate Starling ' s law of the natural heart .", "entities": [{"name": "LV", "type": "Anatomy", "pos": [91, 93]}, {"name": "heart", "type": "Anatomy", "pos": [218, 223]}]}, {"sentence": "We concluded that a continuous flow artificial heart could be well controlled by detecting the t - point and s - point .", "entities": []}, {"sentence": "Potential roles for focal adhesion kinase in development .", "entities": []}, {"sentence": "Focal adhesion kinase ( pp125FAK or FAK ) is a protein tyrosine kinase which is associated with intracellular signalling cascades which are initiated when the integrin family of cell adhesion molecules engage extracellular matrix molecules .", "entities": [{"name": "intracellular", "type": "Anatomy", "pos": [96, 109]}, {"name": "extracellular matrix", "type": "Anatomy", "pos": [209, 229]}]}, {"sentence": "In cultured cells , this molecule is physically associated with focal adhesions , which are well - defined regions of intimate cell - to - substratum adhesion .", "entities": [{"name": "cells", "type": "Anatomy", "pos": [12, 17]}, {"name": "focal adhesions", "type": "Anatomy", "pos": [64, 79]}, {"name": "cell", "type": "Anatomy", "pos": [127, 131]}]}, {"sentence": "In this location , it interacts with other proteins of the focal adhesion to activate intracellular signalling events associated with cell adhesion .", "entities": [{"name": "focal adhesion", "type": "Anatomy", "pos": [59, 73]}, {"name": "intracellular", "type": "Anatomy", "pos": [86, 99]}, {"name": "cell", "type": "Anatomy", "pos": [134, 138]}]}, {"sentence": "The in vitro expression of FAK and its level of phosphorylation appear to be related to several physiological phenomena , including cell spreading , cell differentiation , cell locomotion and cell death .", "entities": [{"name": "cell", "type": "Anatomy", "pos": [132, 136]}, {"name": "cell", "type": "Anatomy", "pos": [149, 153]}, {"name": "cell", "type": "Anatomy", "pos": [172, 176]}, {"name": "cell", "type": "Anatomy", "pos": [192, 196]}]}, {"sentence": "Because these phenomena are all of critical importance during morphogenesis , and because FAK is expressed in embryonic cells , evidence has been accumulating to indicate that FAK may be an important modulator of developmental processes .", "entities": [{"name": "embryonic cells", "type": "Anatomy", "pos": [110, 125]}]}, {"sentence": "In this review , this evidence is surveyed together with evidence from analogous situations , such as tumour cell migration and invasiveness .", "entities": [{"name": "tumour cell", "type": "Anatomy", "pos": [102, 113]}]}, {"sentence": "Although evidence suggesting a role for FAK in morphogenesis is accumulating , current uncertainties regarding its cytoplasmic location and its molecular interactions in vivo make it difficult to reach definitive conclusions regarding the significance of its contributions to developmental processes .", "entities": [{"name": "cytoplasmic", "type": "Anatomy", "pos": [115, 126]}]}]
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