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The total number of immunocytochemically identified vasopressin (AVP) cells was determined morphometrically in the paraventricular (PVN) and dorsolateral part of the supraoptic nucleus (dl-SON) of the human hypothalamus in 30 subjects ranging in age from 15 to 97 years, including 10 Alzheimer's disease (AD) patients. The aim of the present study was to test the hypothesis that the increased activity of AVP neurons reported earlier is accompanied by an absence of cell loss in these nuclei in senescence and AD. The results show that numbers of immunoreactive AVP cells in the PVN and dl-SON do not decline during aging or in AD. During aging, the number of neurons expressing AVP even increased in the PVN of control subjects. The nuclear diameter of the AVP cells in the PVN and dl-SON showed an increase in old AD patients. | In conclusion, our results do not support the hypothesis that aging and AD induce AVP neuron loss. | contradiction |
In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. | We conclude that beta-adrenoceptor prevents or reverses the myocardial enalapril abnormality seen in heart failure and promotes angiotensin II formation. | contradiction |
In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. | In conclusion, enalapril treatment increased myocardial beta-adrenoceptor density in pacing-induced heart failure . | contradiction |
In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. | We conclude that enalapril prevents or reverses the myocardial beta-adrenoceptor abnormality seen in heart failure and promotes angiotensin II formation. | entailment |
In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. | We conclude that enalapril prevents or reverses the myocardial pancreaticoduodenal vein abnormality seen in heart failure and promotes angiotensin II formation. | contradiction |
In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. | We conclude that beta-adrenoceptor prevents or reverses the myocardial enalapril abnormality seen in heart failure and promotes angiotensin II formation. | contradiction |
In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. | We conclude that enalapril prevents or reverses the myocardial beta-adrenoceptor abnormality seen in heart failure and inhibits angiotensin II formation. | contradiction |
In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. | In conclusion, enalapril treatment increased myocardial beta-adrenoceptor density in pacing-induced heart failure . | contradiction |
In order to assess the role of dietary sodium with or without chloride on the development of 2 kidney, 1 clip renovascular hypertension, 49 male Sprague-Dawley rats were fed 3 different diets for 4 weeks after clipping: ad libitum sodium chloride, sodium citrate or sodium-free diet. Sham operated rats were used as control. The final conscious systolic arterial pressure was similar in all hypertensive groups regardless of diet. No change in cardiac index occurred in clipped animals whereas total peripheral resistance raised to a similar extent. | In conclusion, hypertension restriction did not prevent sodium . | contradiction |
In order to assess the role of dietary sodium with or without chloride on the development of 2 kidney, 1 clip renovascular hypertension, 49 male Sprague-Dawley rats were fed 3 different diets for 4 weeks after clipping: ad libitum sodium chloride, sodium citrate or sodium-free diet. Sham operated rats were used as control. The final conscious systolic arterial pressure was similar in all hypertensive groups regardless of diet. No change in cardiac index occurred in clipped animals whereas total peripheral resistance raised to a similar extent. | In conclusion, glucose restriction did not prevent hypertension . | contradiction |
In order to assess the role of dietary sodium with or without chloride on the development of 2 kidney, 1 clip renovascular hypertension, 49 male Sprague-Dawley rats were fed 3 different diets for 4 weeks after clipping: ad libitum sodium chloride, sodium citrate or sodium-free diet. Sham operated rats were used as control. The final conscious systolic arterial pressure was similar in all hypertensive groups regardless of diet. No change in cardiac index occurred in clipped animals whereas total peripheral resistance raised to a similar extent. | In conclusion, hypertension restriction did not prevent sodium . | contradiction |
In order to assess the role of dietary sodium with or without chloride on the development of 2 kidney, 1 clip renovascular hypertension, 49 male Sprague-Dawley rats were fed 3 different diets for 4 weeks after clipping: ad libitum sodium chloride, sodium citrate or sodium-free diet. Sham operated rats were used as control. The final conscious systolic arterial pressure was similar in all hypertensive groups regardless of diet. No change in cardiac index occurred in clipped animals whereas total peripheral resistance raised to a similar extent. | In conclusion, sodium restriction did not prevent hypertension . | entailment |
In order to assess the role of dietary sodium with or without chloride on the development of 2 kidney, 1 clip renovascular hypertension, 49 male Sprague-Dawley rats were fed 3 different diets for 4 weeks after clipping: ad libitum sodium chloride, sodium citrate or sodium-free diet. Sham operated rats were used as control. The final conscious systolic arterial pressure was similar in all hypertensive groups regardless of diet. No change in cardiac index occurred in clipped animals whereas total peripheral resistance raised to a similar extent. | It is concluded that a high dietary sodium does not prevent the development of 2 kidney, 1 clip hypertension . | contradiction |
Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. | In conclusion, the concentrations of ubiquinone-10 in plasma and the synthesis of ubiquinone-10 in fibroblasts are decreased in mevalonate kinase deficiency . | contradiction |
Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. | We conclude that mevalonate kinase deficiency leads to a decreased synthesis of ubiquinone-10 and that ubiquinone-10 deficiency is responsible for the clinical progression of this disease characterized by increased lipid peroxidation, cerebellar atrophy, cataract development, and myopathy with increased creatine kinase activity. | entailment |
Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. | We conclude that mevalonate kinase deficiency leads to a decreased synthesis of ubiquinone-10 and that ubiquinone-10 deficiency is not responsible for the clinical progression of this disease characterized by increased lipid peroxidation, cerebellar atrophy, cataract development, and myopathy with increased creatine kinase activity. | contradiction |
Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. | We conclude that synthesis leads to a decreased mevalonate kinase deficiency of ubiquinone-10 and that ubiquinone-10 deficiency is responsible for the clinical progression of this disease characterized by increased lipid peroxidation, cerebellar atrophy, cataract development, and myopathy with increased creatine kinase activity. | contradiction |
Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. | We conclude that synthesis leads to a decreased mevalonate kinase deficiency of ubiquinone-10 and that ubiquinone-10 deficiency is responsible for the clinical progression of this disease characterized by increased lipid peroxidation, cerebellar atrophy, cataract development, and myopathy with increased creatine kinase activity. | contradiction |
Myasthenia gravis and its animal model experimental autoimmune myasthenia gravis (EAMG) represent T cell-dependent autoimmune diseases mediated by antibodies against the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction. Oral administration of Torpedo AChR to Lewis rats prior to immunization with the myasthenogenic Torpedo AChR and complete Freund's adjuvant results in the prevention of clinical EAMG, and the suppression of AChR-specific B cell responses. To examine the influence of oral tolerance to EAMG on AChR-reactive T cells, we determined and enumerated such cells in the popliteal, inguinal, and mesenteric lymph nodes, spleen, and thymus by a T cell immunospot assay that is based on the secretion of interferon-gamma (IFN-gamma) by antigen-reactive T cells. A diminution of such cells was detected in popliteal, inguinal, and mesenteric lymph nodes of rats orally tolerized to EAMG compared to unfed or vehicle-fed animals. | We conclude that oral administration of EAMG , in addition to preventing clinical signs of AChR and suppressing EAMG -specific B cell responses, also counteracts the development of EAMG -reactive IFN-gamma-secreting cells in certain lymphoid organs. | contradiction |
Myasthenia gravis and its animal model experimental autoimmune myasthenia gravis (EAMG) represent T cell-dependent autoimmune diseases mediated by antibodies against the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction. Oral administration of Torpedo AChR to Lewis rats prior to immunization with the myasthenogenic Torpedo AChR and complete Freund's adjuvant results in the prevention of clinical EAMG, and the suppression of AChR-specific B cell responses. To examine the influence of oral tolerance to EAMG on AChR-reactive T cells, we determined and enumerated such cells in the popliteal, inguinal, and mesenteric lymph nodes, spleen, and thymus by a T cell immunospot assay that is based on the secretion of interferon-gamma (IFN-gamma) by antigen-reactive T cells. A diminution of such cells was detected in popliteal, inguinal, and mesenteric lymph nodes of rats orally tolerized to EAMG compared to unfed or vehicle-fed animals. | We conclude that oral tolerance to EAMG suppresses AChR -specific T cell responses. | contradiction |
Myasthenia gravis and its animal model experimental autoimmune myasthenia gravis (EAMG) represent T cell-dependent autoimmune diseases mediated by antibodies against the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction. Oral administration of Torpedo AChR to Lewis rats prior to immunization with the myasthenogenic Torpedo AChR and complete Freund's adjuvant results in the prevention of clinical EAMG, and the suppression of AChR-specific B cell responses. To examine the influence of oral tolerance to EAMG on AChR-reactive T cells, we determined and enumerated such cells in the popliteal, inguinal, and mesenteric lymph nodes, spleen, and thymus by a T cell immunospot assay that is based on the secretion of interferon-gamma (IFN-gamma) by antigen-reactive T cells. A diminution of such cells was detected in popliteal, inguinal, and mesenteric lymph nodes of rats orally tolerized to EAMG compared to unfed or vehicle-fed animals. | We conclude that oral administration of AChR , in addition to preventing clinical signs of EAMG and suppressing AChR -specific B cell responses, also counteracts the development of AChR -reactive IFN-gamma-secreting cells in certain lymphoid organs. | entailment |
Myasthenia gravis and its animal model experimental autoimmune myasthenia gravis (EAMG) represent T cell-dependent autoimmune diseases mediated by antibodies against the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction. Oral administration of Torpedo AChR to Lewis rats prior to immunization with the myasthenogenic Torpedo AChR and complete Freund's adjuvant results in the prevention of clinical EAMG, and the suppression of AChR-specific B cell responses. To examine the influence of oral tolerance to EAMG on AChR-reactive T cells, we determined and enumerated such cells in the popliteal, inguinal, and mesenteric lymph nodes, spleen, and thymus by a T cell immunospot assay that is based on the secretion of interferon-gamma (IFN-gamma) by antigen-reactive T cells. A diminution of such cells was detected in popliteal, inguinal, and mesenteric lymph nodes of rats orally tolerized to EAMG compared to unfed or vehicle-fed animals. | We conclude that oral tolerance to EAMG suppresses AChR -specific T cell responses. | contradiction |
Myasthenia gravis and its animal model experimental autoimmune myasthenia gravis (EAMG) represent T cell-dependent autoimmune diseases mediated by antibodies against the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction. Oral administration of Torpedo AChR to Lewis rats prior to immunization with the myasthenogenic Torpedo AChR and complete Freund's adjuvant results in the prevention of clinical EAMG, and the suppression of AChR-specific B cell responses. To examine the influence of oral tolerance to EAMG on AChR-reactive T cells, we determined and enumerated such cells in the popliteal, inguinal, and mesenteric lymph nodes, spleen, and thymus by a T cell immunospot assay that is based on the secretion of interferon-gamma (IFN-gamma) by antigen-reactive T cells. A diminution of such cells was detected in popliteal, inguinal, and mesenteric lymph nodes of rats orally tolerized to EAMG compared to unfed or vehicle-fed animals. | We conclude that oral administration of zygotes , in addition to preventing clinical signs of EAMG and suppressing zygotes -specific B cell responses, also counteracts the development of zygotes -reactive IFN-gamma-secreting cells in certain lymphoid organs. | contradiction |
Myasthenia gravis and its animal model experimental autoimmune myasthenia gravis (EAMG) represent T cell-dependent autoimmune diseases mediated by antibodies against the nicotinic acetylcholine receptor (AChR) of the neuromuscular junction. Oral administration of Torpedo AChR to Lewis rats prior to immunization with the myasthenogenic Torpedo AChR and complete Freund's adjuvant results in the prevention of clinical EAMG, and the suppression of AChR-specific B cell responses. To examine the influence of oral tolerance to EAMG on AChR-reactive T cells, we determined and enumerated such cells in the popliteal, inguinal, and mesenteric lymph nodes, spleen, and thymus by a T cell immunospot assay that is based on the secretion of interferon-gamma (IFN-gamma) by antigen-reactive T cells. A diminution of such cells was detected in popliteal, inguinal, and mesenteric lymph nodes of rats orally tolerized to EAMG compared to unfed or vehicle-fed animals. | We conclude that oral administration of EAMG , in addition to preventing clinical signs of AChR and suppressing EAMG -specific B cell responses, also counteracts the development of EAMG -reactive IFN-gamma-secreting cells in certain lymphoid organs. | contradiction |
A prospective study was undertaken to evaluate pudendal neuropathy in fecal incontinence. Fifty-two patients (38 women and 14 men) with fecal incontinence underwent manometric and electromyographic evaluation (measurement of pudendal nerve terminal motor latency [PNTML] and sphincter muscle mapping). The average age of all patients was 54 +/- 17 years. Fifty-two percent (27/52) were found to have a pudendal neuropathy (PNTML > 2.1 milliseconds). Seventeen of these 27 patients (63 percent) had a bilateral pudendal neuropathy. Patients with a pudendal neuropathy were older than those without a neuropathy (63.7 years vs. 51.9 years; P = 0.01). Women were significantly more likely than men to have a pudendal neuropathy (P = 0.03). Nine patients had an anatomic sphincter defect identified, and six of these (67 percent) had a neuropathy; 4/6 (67 percent) had a bilateral pudendal neuropathy. In the 43 patients who did not have an anatomic sphincter defect, there was no difference in resting pressure (69 mmHg vs. 60 mmHg; P = 0.4) or maximum voluntary contraction (95 mmHg vs. 86 mmHg; P = 0.5) when patients without a neuropathy were compared with those with a neuropathy. Patients with a pudendal neuropathy had a shorter sphincter length than those without a neuropathy (3.0 cm vs. 3.9 cm; P = 0.01). Bilateral pudendal neuropathy tended to occur more frequently in women (P = 0.08) and was not associated with poorer resting pressure, maximum voluntary contraction, or shorter sphincter length. | We conclude that pudendal neuropathy is a common cause of fecal incontinence , particularly in older women, and frequently occurs in association with a sphincter defect. | entailment |
A prospective study was undertaken to evaluate pudendal neuropathy in fecal incontinence. Fifty-two patients (38 women and 14 men) with fecal incontinence underwent manometric and electromyographic evaluation (measurement of pudendal nerve terminal motor latency [PNTML] and sphincter muscle mapping). The average age of all patients was 54 +/- 17 years. Fifty-two percent (27/52) were found to have a pudendal neuropathy (PNTML > 2.1 milliseconds). Seventeen of these 27 patients (63 percent) had a bilateral pudendal neuropathy. Patients with a pudendal neuropathy were older than those without a neuropathy (63.7 years vs. 51.9 years; P = 0.01). Women were significantly more likely than men to have a pudendal neuropathy (P = 0.03). Nine patients had an anatomic sphincter defect identified, and six of these (67 percent) had a neuropathy; 4/6 (67 percent) had a bilateral pudendal neuropathy. In the 43 patients who did not have an anatomic sphincter defect, there was no difference in resting pressure (69 mmHg vs. 60 mmHg; P = 0.4) or maximum voluntary contraction (95 mmHg vs. 86 mmHg; P = 0.5) when patients without a neuropathy were compared with those with a neuropathy. Patients with a pudendal neuropathy had a shorter sphincter length than those without a neuropathy (3.0 cm vs. 3.9 cm; P = 0.01). Bilateral pudendal neuropathy tended to occur more frequently in women (P = 0.08) and was not associated with poorer resting pressure, maximum voluntary contraction, or shorter sphincter length. | We conclude that fecal incontinence is a common cause of pudendal neuropathy , particularly in older women, and frequently occurs in association with a sphincter defect. | contradiction |
A prospective study was undertaken to evaluate pudendal neuropathy in fecal incontinence. Fifty-two patients (38 women and 14 men) with fecal incontinence underwent manometric and electromyographic evaluation (measurement of pudendal nerve terminal motor latency [PNTML] and sphincter muscle mapping). The average age of all patients was 54 +/- 17 years. Fifty-two percent (27/52) were found to have a pudendal neuropathy (PNTML > 2.1 milliseconds). Seventeen of these 27 patients (63 percent) had a bilateral pudendal neuropathy. Patients with a pudendal neuropathy were older than those without a neuropathy (63.7 years vs. 51.9 years; P = 0.01). Women were significantly more likely than men to have a pudendal neuropathy (P = 0.03). Nine patients had an anatomic sphincter defect identified, and six of these (67 percent) had a neuropathy; 4/6 (67 percent) had a bilateral pudendal neuropathy. In the 43 patients who did not have an anatomic sphincter defect, there was no difference in resting pressure (69 mmHg vs. 60 mmHg; P = 0.4) or maximum voluntary contraction (95 mmHg vs. 86 mmHg; P = 0.5) when patients without a neuropathy were compared with those with a neuropathy. Patients with a pudendal neuropathy had a shorter sphincter length than those without a neuropathy (3.0 cm vs. 3.9 cm; P = 0.01). Bilateral pudendal neuropathy tended to occur more frequently in women (P = 0.08) and was not associated with poorer resting pressure, maximum voluntary contraction, or shorter sphincter length. | In conclusion, a majority (57 percent) of patients with fecal incontinence have a pudendal neuropathy . | contradiction |
A prospective study was undertaken to evaluate pudendal neuropathy in fecal incontinence. Fifty-two patients (38 women and 14 men) with fecal incontinence underwent manometric and electromyographic evaluation (measurement of pudendal nerve terminal motor latency [PNTML] and sphincter muscle mapping). The average age of all patients was 54 +/- 17 years. Fifty-two percent (27/52) were found to have a pudendal neuropathy (PNTML > 2.1 milliseconds). Seventeen of these 27 patients (63 percent) had a bilateral pudendal neuropathy. Patients with a pudendal neuropathy were older than those without a neuropathy (63.7 years vs. 51.9 years; P = 0.01). Women were significantly more likely than men to have a pudendal neuropathy (P = 0.03). Nine patients had an anatomic sphincter defect identified, and six of these (67 percent) had a neuropathy; 4/6 (67 percent) had a bilateral pudendal neuropathy. In the 43 patients who did not have an anatomic sphincter defect, there was no difference in resting pressure (69 mmHg vs. 60 mmHg; P = 0.4) or maximum voluntary contraction (95 mmHg vs. 86 mmHg; P = 0.5) when patients without a neuropathy were compared with those with a neuropathy. Patients with a pudendal neuropathy had a shorter sphincter length than those without a neuropathy (3.0 cm vs. 3.9 cm; P = 0.01). Bilateral pudendal neuropathy tended to occur more frequently in women (P = 0.08) and was not associated with poorer resting pressure, maximum voluntary contraction, or shorter sphincter length. | We conclude that pudendal neuropathy is not a common cause of fecal incontinence , particularly in older women, and frequently occurs in association with a sphincter defect. | contradiction |
A prospective study was undertaken to evaluate pudendal neuropathy in fecal incontinence. Fifty-two patients (38 women and 14 men) with fecal incontinence underwent manometric and electromyographic evaluation (measurement of pudendal nerve terminal motor latency [PNTML] and sphincter muscle mapping). The average age of all patients was 54 +/- 17 years. Fifty-two percent (27/52) were found to have a pudendal neuropathy (PNTML > 2.1 milliseconds). Seventeen of these 27 patients (63 percent) had a bilateral pudendal neuropathy. Patients with a pudendal neuropathy were older than those without a neuropathy (63.7 years vs. 51.9 years; P = 0.01). Women were significantly more likely than men to have a pudendal neuropathy (P = 0.03). Nine patients had an anatomic sphincter defect identified, and six of these (67 percent) had a neuropathy; 4/6 (67 percent) had a bilateral pudendal neuropathy. In the 43 patients who did not have an anatomic sphincter defect, there was no difference in resting pressure (69 mmHg vs. 60 mmHg; P = 0.4) or maximum voluntary contraction (95 mmHg vs. 86 mmHg; P = 0.5) when patients without a neuropathy were compared with those with a neuropathy. Patients with a pudendal neuropathy had a shorter sphincter length than those without a neuropathy (3.0 cm vs. 3.9 cm; P = 0.01). Bilateral pudendal neuropathy tended to occur more frequently in women (P = 0.08) and was not associated with poorer resting pressure, maximum voluntary contraction, or shorter sphincter length. | We conclude that fecal incontinence is a common cause of pudendal neuropathy , particularly in older women, and frequently occurs in association with a sphincter defect. | contradiction |
A prospective study was undertaken to evaluate pudendal neuropathy in fecal incontinence. Fifty-two patients (38 women and 14 men) with fecal incontinence underwent manometric and electromyographic evaluation (measurement of pudendal nerve terminal motor latency [PNTML] and sphincter muscle mapping). The average age of all patients was 54 +/- 17 years. Fifty-two percent (27/52) were found to have a pudendal neuropathy (PNTML > 2.1 milliseconds). Seventeen of these 27 patients (63 percent) had a bilateral pudendal neuropathy. Patients with a pudendal neuropathy were older than those without a neuropathy (63.7 years vs. 51.9 years; P = 0.01). Women were significantly more likely than men to have a pudendal neuropathy (P = 0.03). Nine patients had an anatomic sphincter defect identified, and six of these (67 percent) had a neuropathy; 4/6 (67 percent) had a bilateral pudendal neuropathy. In the 43 patients who did not have an anatomic sphincter defect, there was no difference in resting pressure (69 mmHg vs. 60 mmHg; P = 0.4) or maximum voluntary contraction (95 mmHg vs. 86 mmHg; P = 0.5) when patients without a neuropathy were compared with those with a neuropathy. Patients with a pudendal neuropathy had a shorter sphincter length than those without a neuropathy (3.0 cm vs. 3.9 cm; P = 0.01). Bilateral pudendal neuropathy tended to occur more frequently in women (P = 0.08) and was not associated with poorer resting pressure, maximum voluntary contraction, or shorter sphincter length. | In conclusion, a majority (57 percent) of patients with fecal incontinence have a pudendal neuropathy . | contradiction |
A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. | Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD , these preliminary data do not not conclusively document a beneficial effect of dietary vitamin E on PD occurrence. | contradiction |
A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. | Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental saline in preventing PD , these preliminary data do not conclusively document a beneficial effect of dietary saline on PD occurrence. | contradiction |
A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. | Though consistent with prior reports of vitamin E protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental PD in preventing vitamin E , these preliminary data do not conclusively document a beneficial effect of dietary PD on vitamin E occurrence. | contradiction |
A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. | Though consistent with prior reports of vitamin E protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental PD in preventing vitamin E , these preliminary data do not conclusively document a beneficial effect of dietary PD on vitamin E occurrence. | contradiction |
A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. | We conclude that in this Honolulu Heart Study population, usual dietary vitamin E intake did not increase the risk of PD . | contradiction |
A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. | Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD , these preliminary data do not conclusively document a beneficial effect of dietary vitamin E on PD occurrence. | entailment |
With the use of isolated perfused rabbit lungs (n = 152), roles of endothelium-derived relaxing factor (EDRF) in pulmonary vascular responses to hypocapnia and hypercapnia were studied. Lungs were ventilated with a gas mixture containing 1, 5, or 10% CO2 and 21% O2, adjusting the perfusate pH to 7.8, 7.4, or 7.1, respectively. Methemoglobin (MetHb), hemoglobin (Hb), methylene blue (MB), and L-argininosuccinic acid (L-ASA) were used as modulators of EDRF. To eliminate augmented shear stress, we used papaverine during hypercapnia. As a measure of EDRF, we spectrophotometrically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnia and hypercapnia evoked, respectively, unsustainable vasodilatation and vasoconstriction. Hb, MB, and L-ASA, but not MetHb, produced an increase in baseline pulmonary arterial pressure (Ppa). These agents also exacerbated vasoconstriction during hypercapnia. Hypercapnia and hypocapnia caused an increase and decrease, respectively, in EDRF production. L-ASA suppressed EDRF production in hypercapnic lungs. Papaverine did not suppress EDRF production under hypercapnia. | We conclude that the unsustainable vasodilatation and vasoconstriction evoked by hypercapnia are not mediated by EDRF . | contradiction |
With the use of isolated perfused rabbit lungs (n = 152), roles of endothelium-derived relaxing factor (EDRF) in pulmonary vascular responses to hypocapnia and hypercapnia were studied. Lungs were ventilated with a gas mixture containing 1, 5, or 10% CO2 and 21% O2, adjusting the perfusate pH to 7.8, 7.4, or 7.1, respectively. Methemoglobin (MetHb), hemoglobin (Hb), methylene blue (MB), and L-argininosuccinic acid (L-ASA) were used as modulators of EDRF. To eliminate augmented shear stress, we used papaverine during hypercapnia. As a measure of EDRF, we spectrophotometrically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnia and hypercapnia evoked, respectively, unsustainable vasodilatation and vasoconstriction. Hb, MB, and L-ASA, but not MetHb, produced an increase in baseline pulmonary arterial pressure (Ppa). These agents also exacerbated vasoconstriction during hypercapnia. Hypercapnia and hypocapnia caused an increase and decrease, respectively, in EDRF production. L-ASA suppressed EDRF production in hypercapnic lungs. Papaverine did not suppress EDRF production under hypercapnia. | In conclusion, 1) the effects of pH on pulmonary circulation are transient, 2) the decrease in Ppa caused by hypercapnia is modulated by EDRF , and 3) the pulmonary EDRF genesis is activated by hypercapnic acidosis but suppressed by hypocapnic alkalosis. | contradiction |
With the use of isolated perfused rabbit lungs (n = 152), roles of endothelium-derived relaxing factor (EDRF) in pulmonary vascular responses to hypocapnia and hypercapnia were studied. Lungs were ventilated with a gas mixture containing 1, 5, or 10% CO2 and 21% O2, adjusting the perfusate pH to 7.8, 7.4, or 7.1, respectively. Methemoglobin (MetHb), hemoglobin (Hb), methylene blue (MB), and L-argininosuccinic acid (L-ASA) were used as modulators of EDRF. To eliminate augmented shear stress, we used papaverine during hypercapnia. As a measure of EDRF, we spectrophotometrically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnia and hypercapnia evoked, respectively, unsustainable vasodilatation and vasoconstriction. Hb, MB, and L-ASA, but not MetHb, produced an increase in baseline pulmonary arterial pressure (Ppa). These agents also exacerbated vasoconstriction during hypercapnia. Hypercapnia and hypocapnia caused an increase and decrease, respectively, in EDRF production. L-ASA suppressed EDRF production in hypercapnic lungs. Papaverine did not suppress EDRF production under hypercapnia. | In conclusion, 1) the effects of pH on pulmonary circulation are transient, 2) the increase in Ppa caused by hypercapnia is modulated by EDRF , and 3) the pulmonary EDRF genesis is activated by hypercapnic acidosis but suppressed by hypocapnic alkalosis. | entailment |
With the use of isolated perfused rabbit lungs (n = 152), roles of endothelium-derived relaxing factor (EDRF) in pulmonary vascular responses to hypocapnia and hypercapnia were studied. Lungs were ventilated with a gas mixture containing 1, 5, or 10% CO2 and 21% O2, adjusting the perfusate pH to 7.8, 7.4, or 7.1, respectively. Methemoglobin (MetHb), hemoglobin (Hb), methylene blue (MB), and L-argininosuccinic acid (L-ASA) were used as modulators of EDRF. To eliminate augmented shear stress, we used papaverine during hypercapnia. As a measure of EDRF, we spectrophotometrically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnia and hypercapnia evoked, respectively, unsustainable vasodilatation and vasoconstriction. Hb, MB, and L-ASA, but not MetHb, produced an increase in baseline pulmonary arterial pressure (Ppa). These agents also exacerbated vasoconstriction during hypercapnia. Hypercapnia and hypocapnia caused an increase and decrease, respectively, in EDRF production. L-ASA suppressed EDRF production in hypercapnic lungs. Papaverine did not suppress EDRF production under hypercapnia. | In conclusion, 1) the effects of pH on pulmonary circulation are transient, 2) the increase in Ppa caused by EDRF is modulated by hypercapnia , and 3) the pulmonary hypercapnia genesis is activated by hypercapnic acidosis but suppressed by hypocapnic alkalosis. | contradiction |
With the use of isolated perfused rabbit lungs (n = 152), roles of endothelium-derived relaxing factor (EDRF) in pulmonary vascular responses to hypocapnia and hypercapnia were studied. Lungs were ventilated with a gas mixture containing 1, 5, or 10% CO2 and 21% O2, adjusting the perfusate pH to 7.8, 7.4, or 7.1, respectively. Methemoglobin (MetHb), hemoglobin (Hb), methylene blue (MB), and L-argininosuccinic acid (L-ASA) were used as modulators of EDRF. To eliminate augmented shear stress, we used papaverine during hypercapnia. As a measure of EDRF, we spectrophotometrically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnia and hypercapnia evoked, respectively, unsustainable vasodilatation and vasoconstriction. Hb, MB, and L-ASA, but not MetHb, produced an increase in baseline pulmonary arterial pressure (Ppa). These agents also exacerbated vasoconstriction during hypercapnia. Hypercapnia and hypocapnia caused an increase and decrease, respectively, in EDRF production. L-ASA suppressed EDRF production in hypercapnic lungs. Papaverine did not suppress EDRF production under hypercapnia. | In conclusion, 1) the effects of pH on pulmonary circulation are transient, 2) the increase in Ppa caused by hypercapnia is not modulated by EDRF , and 3) the pulmonary EDRF genesis is activated by hypercapnic acidosis but suppressed by hypocapnic alkalosis. | contradiction |
With the use of isolated perfused rabbit lungs (n = 152), roles of endothelium-derived relaxing factor (EDRF) in pulmonary vascular responses to hypocapnia and hypercapnia were studied. Lungs were ventilated with a gas mixture containing 1, 5, or 10% CO2 and 21% O2, adjusting the perfusate pH to 7.8, 7.4, or 7.1, respectively. Methemoglobin (MetHb), hemoglobin (Hb), methylene blue (MB), and L-argininosuccinic acid (L-ASA) were used as modulators of EDRF. To eliminate augmented shear stress, we used papaverine during hypercapnia. As a measure of EDRF, we spectrophotometrically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnia and hypercapnia evoked, respectively, unsustainable vasodilatation and vasoconstriction. Hb, MB, and L-ASA, but not MetHb, produced an increase in baseline pulmonary arterial pressure (Ppa). These agents also exacerbated vasoconstriction during hypercapnia. Hypercapnia and hypocapnia caused an increase and decrease, respectively, in EDRF production. L-ASA suppressed EDRF production in hypercapnic lungs. Papaverine did not suppress EDRF production under hypercapnia. | In conclusion, 1) the effects of pH on pulmonary circulation are transient, 2) the increase in Ppa caused by EDRF is modulated by hypercapnia , and 3) the pulmonary hypercapnia genesis is activated by hypercapnic acidosis but suppressed by hypocapnic alkalosis. | contradiction |
Low-density lipoprotein (LDL) oxidation by arterial wall cells, a key event during early atherogenesis, was suggested to involve the activation of 15-lipoxygenase and/or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We sought to analyze the role of these oxygenases in macrophage-mediated oxidation of LDL under oxidative stress. Upon incubation of LDL with the J-774 A.1 macrophage-like cell line or with human monocyte-derived macrophages (HMDM) in the presence of 1 micromol/L CuSO4, the release of superoxide anions to the medium was demonstrated. Under these conditions, the cytosolic protein components of the NADPH oxidase complex, P-47 and P-67, translocated to the plasma membrane, indicating LDL-mediated activation of the NADPH oxidase complex. Under the above-mentioned experimental conditions, the macrophage 15-lipoxygenase was also activated, as determined by the release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) to the medium. Inhibition of the macrophage NADPH oxidase with apocynin or dismutation of superoxide anions, the product of NADPH oxidase activation, with superoxide dismutase (SOD) significantly inhibited macrophage-mediated oxidation of LDL (by 61% to 89%) under these conditions. Phorbol myristate acetate (PMA), which causes NADPH oxidase activation in J-774 A.1 macrophages, had no significant effect on 15-lipoxygenase activity, but still resulted in cell-mediated oxidation of LDL. Finally, HMDM from two patients with chronic granulomatous disease (CGD) that were shown to lack active NADPH oxidase, but to possess almost normal 15-lipoxygenase activity failed to oxidize LDL. | We thus conclude that LDL -induced NADPH oxidase activation (under oxidative stress) is not required for macrophage-mediated oxidation of LDL , whereas activation of 15-lipoxygenase may not be sufficient for LDL oxidation under these conditions. | contradiction |
Low-density lipoprotein (LDL) oxidation by arterial wall cells, a key event during early atherogenesis, was suggested to involve the activation of 15-lipoxygenase and/or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We sought to analyze the role of these oxygenases in macrophage-mediated oxidation of LDL under oxidative stress. Upon incubation of LDL with the J-774 A.1 macrophage-like cell line or with human monocyte-derived macrophages (HMDM) in the presence of 1 micromol/L CuSO4, the release of superoxide anions to the medium was demonstrated. Under these conditions, the cytosolic protein components of the NADPH oxidase complex, P-47 and P-67, translocated to the plasma membrane, indicating LDL-mediated activation of the NADPH oxidase complex. Under the above-mentioned experimental conditions, the macrophage 15-lipoxygenase was also activated, as determined by the release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) to the medium. Inhibition of the macrophage NADPH oxidase with apocynin or dismutation of superoxide anions, the product of NADPH oxidase activation, with superoxide dismutase (SOD) significantly inhibited macrophage-mediated oxidation of LDL (by 61% to 89%) under these conditions. Phorbol myristate acetate (PMA), which causes NADPH oxidase activation in J-774 A.1 macrophages, had no significant effect on 15-lipoxygenase activity, but still resulted in cell-mediated oxidation of LDL. Finally, HMDM from two patients with chronic granulomatous disease (CGD) that were shown to lack active NADPH oxidase, but to possess almost normal 15-lipoxygenase activity failed to oxidize LDL. | We thus conclude that NADPH oxidase -induced LDL activation (under oxidative stress) is required for macrophage-mediated oxidation of NADPH oxidase , whereas activation of 15-lipoxygenase may not be sufficient for NADPH oxidase oxidation under these conditions. | contradiction |
Low-density lipoprotein (LDL) oxidation by arterial wall cells, a key event during early atherogenesis, was suggested to involve the activation of 15-lipoxygenase and/or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We sought to analyze the role of these oxygenases in macrophage-mediated oxidation of LDL under oxidative stress. Upon incubation of LDL with the J-774 A.1 macrophage-like cell line or with human monocyte-derived macrophages (HMDM) in the presence of 1 micromol/L CuSO4, the release of superoxide anions to the medium was demonstrated. Under these conditions, the cytosolic protein components of the NADPH oxidase complex, P-47 and P-67, translocated to the plasma membrane, indicating LDL-mediated activation of the NADPH oxidase complex. Under the above-mentioned experimental conditions, the macrophage 15-lipoxygenase was also activated, as determined by the release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) to the medium. Inhibition of the macrophage NADPH oxidase with apocynin or dismutation of superoxide anions, the product of NADPH oxidase activation, with superoxide dismutase (SOD) significantly inhibited macrophage-mediated oxidation of LDL (by 61% to 89%) under these conditions. Phorbol myristate acetate (PMA), which causes NADPH oxidase activation in J-774 A.1 macrophages, had no significant effect on 15-lipoxygenase activity, but still resulted in cell-mediated oxidation of LDL. Finally, HMDM from two patients with chronic granulomatous disease (CGD) that were shown to lack active NADPH oxidase, but to possess almost normal 15-lipoxygenase activity failed to oxidize LDL. | We thus conclude that LDL -induced fibroblast growth factor activation (under oxidative stress) is required for macrophage-mediated oxidation of LDL , whereas activation of 15-lipoxygenase may not be sufficient for LDL oxidation under these conditions. | contradiction |
Low-density lipoprotein (LDL) oxidation by arterial wall cells, a key event during early atherogenesis, was suggested to involve the activation of 15-lipoxygenase and/or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We sought to analyze the role of these oxygenases in macrophage-mediated oxidation of LDL under oxidative stress. Upon incubation of LDL with the J-774 A.1 macrophage-like cell line or with human monocyte-derived macrophages (HMDM) in the presence of 1 micromol/L CuSO4, the release of superoxide anions to the medium was demonstrated. Under these conditions, the cytosolic protein components of the NADPH oxidase complex, P-47 and P-67, translocated to the plasma membrane, indicating LDL-mediated activation of the NADPH oxidase complex. Under the above-mentioned experimental conditions, the macrophage 15-lipoxygenase was also activated, as determined by the release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) to the medium. Inhibition of the macrophage NADPH oxidase with apocynin or dismutation of superoxide anions, the product of NADPH oxidase activation, with superoxide dismutase (SOD) significantly inhibited macrophage-mediated oxidation of LDL (by 61% to 89%) under these conditions. Phorbol myristate acetate (PMA), which causes NADPH oxidase activation in J-774 A.1 macrophages, had no significant effect on 15-lipoxygenase activity, but still resulted in cell-mediated oxidation of LDL. Finally, HMDM from two patients with chronic granulomatous disease (CGD) that were shown to lack active NADPH oxidase, but to possess almost normal 15-lipoxygenase activity failed to oxidize LDL. | We conclude that the macrophage-mediated oxidation of LDL under oxidative stress is, at least in part, mediated by NADPH oxidase activation. | contradiction |
Low-density lipoprotein (LDL) oxidation by arterial wall cells, a key event during early atherogenesis, was suggested to involve the activation of 15-lipoxygenase and/or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We sought to analyze the role of these oxygenases in macrophage-mediated oxidation of LDL under oxidative stress. Upon incubation of LDL with the J-774 A.1 macrophage-like cell line or with human monocyte-derived macrophages (HMDM) in the presence of 1 micromol/L CuSO4, the release of superoxide anions to the medium was demonstrated. Under these conditions, the cytosolic protein components of the NADPH oxidase complex, P-47 and P-67, translocated to the plasma membrane, indicating LDL-mediated activation of the NADPH oxidase complex. Under the above-mentioned experimental conditions, the macrophage 15-lipoxygenase was also activated, as determined by the release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) to the medium. Inhibition of the macrophage NADPH oxidase with apocynin or dismutation of superoxide anions, the product of NADPH oxidase activation, with superoxide dismutase (SOD) significantly inhibited macrophage-mediated oxidation of LDL (by 61% to 89%) under these conditions. Phorbol myristate acetate (PMA), which causes NADPH oxidase activation in J-774 A.1 macrophages, had no significant effect on 15-lipoxygenase activity, but still resulted in cell-mediated oxidation of LDL. Finally, HMDM from two patients with chronic granulomatous disease (CGD) that were shown to lack active NADPH oxidase, but to possess almost normal 15-lipoxygenase activity failed to oxidize LDL. | We thus conclude that NADPH oxidase -induced LDL activation (under oxidative stress) is required for macrophage-mediated oxidation of NADPH oxidase , whereas activation of 15-lipoxygenase may not be sufficient for NADPH oxidase oxidation under these conditions. | contradiction |
Low-density lipoprotein (LDL) oxidation by arterial wall cells, a key event during early atherogenesis, was suggested to involve the activation of 15-lipoxygenase and/or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We sought to analyze the role of these oxygenases in macrophage-mediated oxidation of LDL under oxidative stress. Upon incubation of LDL with the J-774 A.1 macrophage-like cell line or with human monocyte-derived macrophages (HMDM) in the presence of 1 micromol/L CuSO4, the release of superoxide anions to the medium was demonstrated. Under these conditions, the cytosolic protein components of the NADPH oxidase complex, P-47 and P-67, translocated to the plasma membrane, indicating LDL-mediated activation of the NADPH oxidase complex. Under the above-mentioned experimental conditions, the macrophage 15-lipoxygenase was also activated, as determined by the release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) to the medium. Inhibition of the macrophage NADPH oxidase with apocynin or dismutation of superoxide anions, the product of NADPH oxidase activation, with superoxide dismutase (SOD) significantly inhibited macrophage-mediated oxidation of LDL (by 61% to 89%) under these conditions. Phorbol myristate acetate (PMA), which causes NADPH oxidase activation in J-774 A.1 macrophages, had no significant effect on 15-lipoxygenase activity, but still resulted in cell-mediated oxidation of LDL. Finally, HMDM from two patients with chronic granulomatous disease (CGD) that were shown to lack active NADPH oxidase, but to possess almost normal 15-lipoxygenase activity failed to oxidize LDL. | We conclude that the macrophage-mediated oxidation of LDL under oxidative stress is, at least in part, mediated by NADPH oxidase activation. | contradiction |
Low-density lipoprotein (LDL) oxidation by arterial wall cells, a key event during early atherogenesis, was suggested to involve the activation of 15-lipoxygenase and/or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We sought to analyze the role of these oxygenases in macrophage-mediated oxidation of LDL under oxidative stress. Upon incubation of LDL with the J-774 A.1 macrophage-like cell line or with human monocyte-derived macrophages (HMDM) in the presence of 1 micromol/L CuSO4, the release of superoxide anions to the medium was demonstrated. Under these conditions, the cytosolic protein components of the NADPH oxidase complex, P-47 and P-67, translocated to the plasma membrane, indicating LDL-mediated activation of the NADPH oxidase complex. Under the above-mentioned experimental conditions, the macrophage 15-lipoxygenase was also activated, as determined by the release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) to the medium. Inhibition of the macrophage NADPH oxidase with apocynin or dismutation of superoxide anions, the product of NADPH oxidase activation, with superoxide dismutase (SOD) significantly inhibited macrophage-mediated oxidation of LDL (by 61% to 89%) under these conditions. Phorbol myristate acetate (PMA), which causes NADPH oxidase activation in J-774 A.1 macrophages, had no significant effect on 15-lipoxygenase activity, but still resulted in cell-mediated oxidation of LDL. Finally, HMDM from two patients with chronic granulomatous disease (CGD) that were shown to lack active NADPH oxidase, but to possess almost normal 15-lipoxygenase activity failed to oxidize LDL. | We thus conclude that LDL -induced NADPH oxidase activation (under oxidative stress) is required for macrophage-mediated oxidation of LDL , whereas activation of 15-lipoxygenase may not be sufficient for LDL oxidation under these conditions. | entailment |
Low-density lipoprotein (LDL) oxidation by arterial wall cells, a key event during early atherogenesis, was suggested to involve the activation of 15-lipoxygenase and/or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We sought to analyze the role of these oxygenases in macrophage-mediated oxidation of LDL under oxidative stress. Upon incubation of LDL with the J-774 A.1 macrophage-like cell line or with human monocyte-derived macrophages (HMDM) in the presence of 1 micromol/L CuSO4, the release of superoxide anions to the medium was demonstrated. Under these conditions, the cytosolic protein components of the NADPH oxidase complex, P-47 and P-67, translocated to the plasma membrane, indicating LDL-mediated activation of the NADPH oxidase complex. Under the above-mentioned experimental conditions, the macrophage 15-lipoxygenase was also activated, as determined by the release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) to the medium. Inhibition of the macrophage NADPH oxidase with apocynin or dismutation of superoxide anions, the product of NADPH oxidase activation, with superoxide dismutase (SOD) significantly inhibited macrophage-mediated oxidation of LDL (by 61% to 89%) under these conditions. Phorbol myristate acetate (PMA), which causes NADPH oxidase activation in J-774 A.1 macrophages, had no significant effect on 15-lipoxygenase activity, but still resulted in cell-mediated oxidation of LDL. Finally, HMDM from two patients with chronic granulomatous disease (CGD) that were shown to lack active NADPH oxidase, but to possess almost normal 15-lipoxygenase activity failed to oxidize LDL. | We thus conclude that LDL -induced NADPH oxidase activation (under oxidative stress) is required for macrophage-mediated oxidation of LDL , whereas activation of 89-lipoxygenase may not be sufficient for LDL oxidation under these conditions. | contradiction |
Pseudomyotonic electromyographic (FMG) activity recorded from the female external urethal sphincter called decelerating bursts and complex repetitive discharges (CRD), are assumed to reflect pathology which may cause disturbances in micturition. Out of 477 consecutive neurological and non-neurological patients referred to neuro-urological evaluation, as many as 50 presented such bizarre EMG potentials. These were not only found in female sphincter, but also in the bulbocavernosus muscle and the external and sphincter. A particularly high percentage was detected of patients with urinary stress incontinence or peripheral affection of the pelvic floor muscles. | It is concluded that micturition may inhibit the normal CRD reflex, and detrusor contraction in particular. | contradiction |
Pseudomyotonic electromyographic (FMG) activity recorded from the female external urethal sphincter called decelerating bursts and complex repetitive discharges (CRD), are assumed to reflect pathology which may cause disturbances in micturition. Out of 477 consecutive neurological and non-neurological patients referred to neuro-urological evaluation, as many as 50 presented such bizarre EMG potentials. These were not only found in female sphincter, but also in the bulbocavernosus muscle and the external and sphincter. A particularly high percentage was detected of patients with urinary stress incontinence or peripheral affection of the pelvic floor muscles. | It is concluded that insulin may inhibit the normal micturition reflex, and detrusor contraction in particular. | contradiction |
Pseudomyotonic electromyographic (FMG) activity recorded from the female external urethal sphincter called decelerating bursts and complex repetitive discharges (CRD), are assumed to reflect pathology which may cause disturbances in micturition. Out of 477 consecutive neurological and non-neurological patients referred to neuro-urological evaluation, as many as 50 presented such bizarre EMG potentials. These were not only found in female sphincter, but also in the bulbocavernosus muscle and the external and sphincter. A particularly high percentage was detected of patients with urinary stress incontinence or peripheral affection of the pelvic floor muscles. | It is concluded that micturition may inhibit the normal CRD reflex, and detrusor contraction in particular. | contradiction |
Pseudomyotonic electromyographic (FMG) activity recorded from the female external urethal sphincter called decelerating bursts and complex repetitive discharges (CRD), are assumed to reflect pathology which may cause disturbances in micturition. Out of 477 consecutive neurological and non-neurological patients referred to neuro-urological evaluation, as many as 50 presented such bizarre EMG potentials. These were not only found in female sphincter, but also in the bulbocavernosus muscle and the external and sphincter. A particularly high percentage was detected of patients with urinary stress incontinence or peripheral affection of the pelvic floor muscles. | It is not concluded that CRD may inhibit the normal micturition reflex, and detrusor contraction in particular. | contradiction |
Pseudomyotonic electromyographic (FMG) activity recorded from the female external urethal sphincter called decelerating bursts and complex repetitive discharges (CRD), are assumed to reflect pathology which may cause disturbances in micturition. Out of 477 consecutive neurological and non-neurological patients referred to neuro-urological evaluation, as many as 50 presented such bizarre EMG potentials. These were not only found in female sphincter, but also in the bulbocavernosus muscle and the external and sphincter. A particularly high percentage was detected of patients with urinary stress incontinence or peripheral affection of the pelvic floor muscles. | It is concluded that CRD , as well as decelerating bursts and CRD , reflect disturbances in micturition . | contradiction |
Pseudomyotonic electromyographic (FMG) activity recorded from the female external urethal sphincter called decelerating bursts and complex repetitive discharges (CRD), are assumed to reflect pathology which may cause disturbances in micturition. Out of 477 consecutive neurological and non-neurological patients referred to neuro-urological evaluation, as many as 50 presented such bizarre EMG potentials. These were not only found in female sphincter, but also in the bulbocavernosus muscle and the external and sphincter. A particularly high percentage was detected of patients with urinary stress incontinence or peripheral affection of the pelvic floor muscles. | It is concluded that CRD may inhibit the normal micturition reflex, and detrusor contraction in particular. | entailment |
Pseudomyotonic electromyographic (FMG) activity recorded from the female external urethal sphincter called decelerating bursts and complex repetitive discharges (CRD), are assumed to reflect pathology which may cause disturbances in micturition. Out of 477 consecutive neurological and non-neurological patients referred to neuro-urological evaluation, as many as 50 presented such bizarre EMG potentials. These were not only found in female sphincter, but also in the bulbocavernosus muscle and the external and sphincter. A particularly high percentage was detected of patients with urinary stress incontinence or peripheral affection of the pelvic floor muscles. | It is concluded that CRD , as well as decelerating bursts and CRD , reflect disturbances in micturition . | contradiction |
Activation of protein kinase C (PKC) by the active phorbol ester 12-myristate 13-acetate (PMA, 100 nM) or phorbol-12, 13-dibutyrate (100 nM) reduced taurine uptake by 80% in oocytes given injections with cRNA from and expressing the Madin-Darby canine kidney cell taurine transporter pNCT. Inhibition of PKC by calphostin C or staurosporine increased taurine uptake by 20% and 400%, respectively. The inhibitory effect of PMA on taurine uptake was blocked by calphostin C, a specific inhibitor of PKC. Modulation by PMA mainly affected the apparent affinity K(m) (from 5.6 microM to 18.1 microM) with minimal effect on the maximal velocity (25% decrease) of the transporter. A polyclonal antibody (AbS4) directed against a conserved intracellular segment (S4) of the Madin-Darby canine kidney cell taurine transporter enhanced taurine uptake by pNCT cRNA-treated oocytes. The effect of AbS4 was blocked by incubation with the corresponding peptide antigen. Preimmune IgG and peptide antigen had no effect on taurine transporter activity expressed in oocytes. Modulation seemed to occur through phosphorylation of a consensus PKC site located on segment S4 of the transporter, because downregulation of the transporter by PMA (100 nM) was abolished by preinjection of AbS4 (12 ng/ oocyte). In contrast, downregulation of the transporter by PMA could not be restored by AbS4 when pNCT-expressing oocytes were pretreated with PMA (50 nM). | In conclusion, the peptide segment recognized by this antibody appears to participate directly in taurine transporter inactivation that is not modulated by PKC phosphorylation. | contradiction |
Activation of protein kinase C (PKC) by the active phorbol ester 12-myristate 13-acetate (PMA, 100 nM) or phorbol-12, 13-dibutyrate (100 nM) reduced taurine uptake by 80% in oocytes given injections with cRNA from and expressing the Madin-Darby canine kidney cell taurine transporter pNCT. Inhibition of PKC by calphostin C or staurosporine increased taurine uptake by 20% and 400%, respectively. The inhibitory effect of PMA on taurine uptake was blocked by calphostin C, a specific inhibitor of PKC. Modulation by PMA mainly affected the apparent affinity K(m) (from 5.6 microM to 18.1 microM) with minimal effect on the maximal velocity (25% decrease) of the transporter. A polyclonal antibody (AbS4) directed against a conserved intracellular segment (S4) of the Madin-Darby canine kidney cell taurine transporter enhanced taurine uptake by pNCT cRNA-treated oocytes. The effect of AbS4 was blocked by incubation with the corresponding peptide antigen. Preimmune IgG and peptide antigen had no effect on taurine transporter activity expressed in oocytes. Modulation seemed to occur through phosphorylation of a consensus PKC site located on segment S4 of the transporter, because downregulation of the transporter by PMA (100 nM) was abolished by preinjection of AbS4 (12 ng/ oocyte). In contrast, downregulation of the transporter by PMA could not be restored by AbS4 when pNCT-expressing oocytes were pretreated with PMA (50 nM). | In conclusion, the peptide segment recognized by this antibody appears to participate directly in PKC transporter inactivation that is modulated by taurine phosphorylation. | contradiction |
Activation of protein kinase C (PKC) by the active phorbol ester 12-myristate 13-acetate (PMA, 100 nM) or phorbol-12, 13-dibutyrate (100 nM) reduced taurine uptake by 80% in oocytes given injections with cRNA from and expressing the Madin-Darby canine kidney cell taurine transporter pNCT. Inhibition of PKC by calphostin C or staurosporine increased taurine uptake by 20% and 400%, respectively. The inhibitory effect of PMA on taurine uptake was blocked by calphostin C, a specific inhibitor of PKC. Modulation by PMA mainly affected the apparent affinity K(m) (from 5.6 microM to 18.1 microM) with minimal effect on the maximal velocity (25% decrease) of the transporter. A polyclonal antibody (AbS4) directed against a conserved intracellular segment (S4) of the Madin-Darby canine kidney cell taurine transporter enhanced taurine uptake by pNCT cRNA-treated oocytes. The effect of AbS4 was blocked by incubation with the corresponding peptide antigen. Preimmune IgG and peptide antigen had no effect on taurine transporter activity expressed in oocytes. Modulation seemed to occur through phosphorylation of a consensus PKC site located on segment S4 of the transporter, because downregulation of the transporter by PMA (100 nM) was abolished by preinjection of AbS4 (12 ng/ oocyte). In contrast, downregulation of the transporter by PMA could not be restored by AbS4 when pNCT-expressing oocytes were pretreated with PMA (50 nM). | In conclusion, the peptide segment recognized by this antibody appears to participate directly in atropine transporter inactivation that is modulated by PKC phosphorylation. | contradiction |
Activation of protein kinase C (PKC) by the active phorbol ester 12-myristate 13-acetate (PMA, 100 nM) or phorbol-12, 13-dibutyrate (100 nM) reduced taurine uptake by 80% in oocytes given injections with cRNA from and expressing the Madin-Darby canine kidney cell taurine transporter pNCT. Inhibition of PKC by calphostin C or staurosporine increased taurine uptake by 20% and 400%, respectively. The inhibitory effect of PMA on taurine uptake was blocked by calphostin C, a specific inhibitor of PKC. Modulation by PMA mainly affected the apparent affinity K(m) (from 5.6 microM to 18.1 microM) with minimal effect on the maximal velocity (25% decrease) of the transporter. A polyclonal antibody (AbS4) directed against a conserved intracellular segment (S4) of the Madin-Darby canine kidney cell taurine transporter enhanced taurine uptake by pNCT cRNA-treated oocytes. The effect of AbS4 was blocked by incubation with the corresponding peptide antigen. Preimmune IgG and peptide antigen had no effect on taurine transporter activity expressed in oocytes. Modulation seemed to occur through phosphorylation of a consensus PKC site located on segment S4 of the transporter, because downregulation of the transporter by PMA (100 nM) was abolished by preinjection of AbS4 (12 ng/ oocyte). In contrast, downregulation of the transporter by PMA could not be restored by AbS4 when pNCT-expressing oocytes were pretreated with PMA (50 nM). | In conclusion, activation of PKC reduces taurine uptake by oocytes expressing the taurine transporter pNCT. | contradiction |
Activation of protein kinase C (PKC) by the active phorbol ester 12-myristate 13-acetate (PMA, 100 nM) or phorbol-12, 13-dibutyrate (100 nM) reduced taurine uptake by 80% in oocytes given injections with cRNA from and expressing the Madin-Darby canine kidney cell taurine transporter pNCT. Inhibition of PKC by calphostin C or staurosporine increased taurine uptake by 20% and 400%, respectively. The inhibitory effect of PMA on taurine uptake was blocked by calphostin C, a specific inhibitor of PKC. Modulation by PMA mainly affected the apparent affinity K(m) (from 5.6 microM to 18.1 microM) with minimal effect on the maximal velocity (25% decrease) of the transporter. A polyclonal antibody (AbS4) directed against a conserved intracellular segment (S4) of the Madin-Darby canine kidney cell taurine transporter enhanced taurine uptake by pNCT cRNA-treated oocytes. The effect of AbS4 was blocked by incubation with the corresponding peptide antigen. Preimmune IgG and peptide antigen had no effect on taurine transporter activity expressed in oocytes. Modulation seemed to occur through phosphorylation of a consensus PKC site located on segment S4 of the transporter, because downregulation of the transporter by PMA (100 nM) was abolished by preinjection of AbS4 (12 ng/ oocyte). In contrast, downregulation of the transporter by PMA could not be restored by AbS4 when pNCT-expressing oocytes were pretreated with PMA (50 nM). | In conclusion, the peptide segment recognized by this antibody appears to participate directly in PKC transporter inactivation that is modulated by taurine phosphorylation. | contradiction |
Activation of protein kinase C (PKC) by the active phorbol ester 12-myristate 13-acetate (PMA, 100 nM) or phorbol-12, 13-dibutyrate (100 nM) reduced taurine uptake by 80% in oocytes given injections with cRNA from and expressing the Madin-Darby canine kidney cell taurine transporter pNCT. Inhibition of PKC by calphostin C or staurosporine increased taurine uptake by 20% and 400%, respectively. The inhibitory effect of PMA on taurine uptake was blocked by calphostin C, a specific inhibitor of PKC. Modulation by PMA mainly affected the apparent affinity K(m) (from 5.6 microM to 18.1 microM) with minimal effect on the maximal velocity (25% decrease) of the transporter. A polyclonal antibody (AbS4) directed against a conserved intracellular segment (S4) of the Madin-Darby canine kidney cell taurine transporter enhanced taurine uptake by pNCT cRNA-treated oocytes. The effect of AbS4 was blocked by incubation with the corresponding peptide antigen. Preimmune IgG and peptide antigen had no effect on taurine transporter activity expressed in oocytes. Modulation seemed to occur through phosphorylation of a consensus PKC site located on segment S4 of the transporter, because downregulation of the transporter by PMA (100 nM) was abolished by preinjection of AbS4 (12 ng/ oocyte). In contrast, downregulation of the transporter by PMA could not be restored by AbS4 when pNCT-expressing oocytes were pretreated with PMA (50 nM). | In conclusion, the peptide segment recognized by this antibody appears to participate directly in taurine transporter inactivation that is modulated by PKC phosphorylation. | entailment |
1. The GABA modulating and GABA-mimetic actions of the general anaesthetic etomidate were examined in voltage-clamp recordings performed on Xenopus laevis oocytes induced, by cRNA injection, to express human recombinant gamma-aminobutyric acidA (GABAA) receptor subunits. 2. Currents mediated by recombinant receptors with the ternary subunit composition alpha x beta y gamma 2L (where x = 1,2,3 or 6 and y = 1 or 2), in response to GABA applied at the appropriate EC10, were enhanced by etomidate in a manner that was dependent upon the identity of both the alpha and beta subunit isoforms. 3. For the beta 2-subunit containing receptors tested, the EC50 for the potentiation of GABA-evoked currents by etomidate (range 0.6 to 1.2 microM) was little affected by the nature of the alpha subunit present within the hetero-oligomeric complex. However, replacement of the beta 2 by the beta 1 subunit produced a 9-12 fold increase in the etomidate EC50 (6 to 11 microM) for all alpha-isoforms tested. 4. For alpha 1, alpha 2 and alpha 6, but not alpha 3-subunit containing receptors, the maximal potentiation of GABA-evoked currents by etomidate was greater for beta 2- than for beta 1-subunit containing receptors. This was most clearly exemplified by receptors composed of alpha 6 beta 1 gamma 2L compared to alpha 6 beta 2 gamma 2L subunits, where a maximally effective concentration of etomidate potentiated currents evoked by GABA at EC10 to 28 +/- 2% and 169 +/- 4% of the maximal GABA response, respectively. 5. For alpha 1 subunit-containing receptors, the potency and maximal potentiating effect of either pentobarbitone or propofol was essentially unaffected by the beta subunit isoform contained within the receptor complex. The potency of the anaesthetic neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one was marginally higher for beta 1 rather than the beta 2 subunit-containing receptor, although its maximal effect was similar at the two receptor isoforms. 6. The GABA-mimetic action of etomidate was supported by beta 2- but not beta 1-subunit containing receptors, whereas that of pentobarbitone or propofol was evident with either beta isoform. For beta 2-subunit containing receptors, both the agonist EC50 and the maximal current produced by etomidate were additionally influenced by the alpha isoform. 7. | It is concluded that the subtype of beta-subunit influences the potency with which GABA potentiates etomidate -evoked currents and that the beta isoform is a crucial determinant of the etomidate -mimetic activity of this compound. | contradiction |
1. The GABA modulating and GABA-mimetic actions of the general anaesthetic etomidate were examined in voltage-clamp recordings performed on Xenopus laevis oocytes induced, by cRNA injection, to express human recombinant gamma-aminobutyric acidA (GABAA) receptor subunits. 2. Currents mediated by recombinant receptors with the ternary subunit composition alpha x beta y gamma 2L (where x = 1,2,3 or 6 and y = 1 or 2), in response to GABA applied at the appropriate EC10, were enhanced by etomidate in a manner that was dependent upon the identity of both the alpha and beta subunit isoforms. 3. For the beta 2-subunit containing receptors tested, the EC50 for the potentiation of GABA-evoked currents by etomidate (range 0.6 to 1.2 microM) was little affected by the nature of the alpha subunit present within the hetero-oligomeric complex. However, replacement of the beta 2 by the beta 1 subunit produced a 9-12 fold increase in the etomidate EC50 (6 to 11 microM) for all alpha-isoforms tested. 4. For alpha 1, alpha 2 and alpha 6, but not alpha 3-subunit containing receptors, the maximal potentiation of GABA-evoked currents by etomidate was greater for beta 2- than for beta 1-subunit containing receptors. This was most clearly exemplified by receptors composed of alpha 6 beta 1 gamma 2L compared to alpha 6 beta 2 gamma 2L subunits, where a maximally effective concentration of etomidate potentiated currents evoked by GABA at EC10 to 28 +/- 2% and 169 +/- 4% of the maximal GABA response, respectively. 5. For alpha 1 subunit-containing receptors, the potency and maximal potentiating effect of either pentobarbitone or propofol was essentially unaffected by the beta subunit isoform contained within the receptor complex. The potency of the anaesthetic neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one was marginally higher for beta 1 rather than the beta 2 subunit-containing receptor, although its maximal effect was similar at the two receptor isoforms. 6. The GABA-mimetic action of etomidate was supported by beta 2- but not beta 1-subunit containing receptors, whereas that of pentobarbitone or propofol was evident with either beta isoform. For beta 2-subunit containing receptors, both the agonist EC50 and the maximal current produced by etomidate were additionally influenced by the alpha isoform. 7. | It is concluded that the subtype of beta-subunit influences the potency with which etomidate potentiates Fluid -evoked currents and that the beta isoform is a crucial determinant of the Fluid -mimetic activity of this compound. | contradiction |
1. The GABA modulating and GABA-mimetic actions of the general anaesthetic etomidate were examined in voltage-clamp recordings performed on Xenopus laevis oocytes induced, by cRNA injection, to express human recombinant gamma-aminobutyric acidA (GABAA) receptor subunits. 2. Currents mediated by recombinant receptors with the ternary subunit composition alpha x beta y gamma 2L (where x = 1,2,3 or 6 and y = 1 or 2), in response to GABA applied at the appropriate EC10, were enhanced by etomidate in a manner that was dependent upon the identity of both the alpha and beta subunit isoforms. 3. For the beta 2-subunit containing receptors tested, the EC50 for the potentiation of GABA-evoked currents by etomidate (range 0.6 to 1.2 microM) was little affected by the nature of the alpha subunit present within the hetero-oligomeric complex. However, replacement of the beta 2 by the beta 1 subunit produced a 9-12 fold increase in the etomidate EC50 (6 to 11 microM) for all alpha-isoforms tested. 4. For alpha 1, alpha 2 and alpha 6, but not alpha 3-subunit containing receptors, the maximal potentiation of GABA-evoked currents by etomidate was greater for beta 2- than for beta 1-subunit containing receptors. This was most clearly exemplified by receptors composed of alpha 6 beta 1 gamma 2L compared to alpha 6 beta 2 gamma 2L subunits, where a maximally effective concentration of etomidate potentiated currents evoked by GABA at EC10 to 28 +/- 2% and 169 +/- 4% of the maximal GABA response, respectively. 5. For alpha 1 subunit-containing receptors, the potency and maximal potentiating effect of either pentobarbitone or propofol was essentially unaffected by the beta subunit isoform contained within the receptor complex. The potency of the anaesthetic neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one was marginally higher for beta 1 rather than the beta 2 subunit-containing receptor, although its maximal effect was similar at the two receptor isoforms. 6. The GABA-mimetic action of etomidate was supported by beta 2- but not beta 1-subunit containing receptors, whereas that of pentobarbitone or propofol was evident with either beta isoform. For beta 2-subunit containing receptors, both the agonist EC50 and the maximal current produced by etomidate were additionally influenced by the alpha isoform. 7. | It is not concluded that the subtype of beta-subunit influences the potency with which etomidate potentiates GABA -evoked currents and that the beta isoform is a crucial determinant of the GABA -mimetic activity of this compound. | contradiction |
1. The GABA modulating and GABA-mimetic actions of the general anaesthetic etomidate were examined in voltage-clamp recordings performed on Xenopus laevis oocytes induced, by cRNA injection, to express human recombinant gamma-aminobutyric acidA (GABAA) receptor subunits. 2. Currents mediated by recombinant receptors with the ternary subunit composition alpha x beta y gamma 2L (where x = 1,2,3 or 6 and y = 1 or 2), in response to GABA applied at the appropriate EC10, were enhanced by etomidate in a manner that was dependent upon the identity of both the alpha and beta subunit isoforms. 3. For the beta 2-subunit containing receptors tested, the EC50 for the potentiation of GABA-evoked currents by etomidate (range 0.6 to 1.2 microM) was little affected by the nature of the alpha subunit present within the hetero-oligomeric complex. However, replacement of the beta 2 by the beta 1 subunit produced a 9-12 fold increase in the etomidate EC50 (6 to 11 microM) for all alpha-isoforms tested. 4. For alpha 1, alpha 2 and alpha 6, but not alpha 3-subunit containing receptors, the maximal potentiation of GABA-evoked currents by etomidate was greater for beta 2- than for beta 1-subunit containing receptors. This was most clearly exemplified by receptors composed of alpha 6 beta 1 gamma 2L compared to alpha 6 beta 2 gamma 2L subunits, where a maximally effective concentration of etomidate potentiated currents evoked by GABA at EC10 to 28 +/- 2% and 169 +/- 4% of the maximal GABA response, respectively. 5. For alpha 1 subunit-containing receptors, the potency and maximal potentiating effect of either pentobarbitone or propofol was essentially unaffected by the beta subunit isoform contained within the receptor complex. The potency of the anaesthetic neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one was marginally higher for beta 1 rather than the beta 2 subunit-containing receptor, although its maximal effect was similar at the two receptor isoforms. 6. The GABA-mimetic action of etomidate was supported by beta 2- but not beta 1-subunit containing receptors, whereas that of pentobarbitone or propofol was evident with either beta isoform. For beta 2-subunit containing receptors, both the agonist EC50 and the maximal current produced by etomidate were additionally influenced by the alpha isoform. 7. | We conclude that the GABA -mimetic action of the general anaesthetic etomidate is dependent upon the presence of the beta 2-subunit within the hetero-oligomeric complex. | contradiction |
1. The GABA modulating and GABA-mimetic actions of the general anaesthetic etomidate were examined in voltage-clamp recordings performed on Xenopus laevis oocytes induced, by cRNA injection, to express human recombinant gamma-aminobutyric acidA (GABAA) receptor subunits. 2. Currents mediated by recombinant receptors with the ternary subunit composition alpha x beta y gamma 2L (where x = 1,2,3 or 6 and y = 1 or 2), in response to GABA applied at the appropriate EC10, were enhanced by etomidate in a manner that was dependent upon the identity of both the alpha and beta subunit isoforms. 3. For the beta 2-subunit containing receptors tested, the EC50 for the potentiation of GABA-evoked currents by etomidate (range 0.6 to 1.2 microM) was little affected by the nature of the alpha subunit present within the hetero-oligomeric complex. However, replacement of the beta 2 by the beta 1 subunit produced a 9-12 fold increase in the etomidate EC50 (6 to 11 microM) for all alpha-isoforms tested. 4. For alpha 1, alpha 2 and alpha 6, but not alpha 3-subunit containing receptors, the maximal potentiation of GABA-evoked currents by etomidate was greater for beta 2- than for beta 1-subunit containing receptors. This was most clearly exemplified by receptors composed of alpha 6 beta 1 gamma 2L compared to alpha 6 beta 2 gamma 2L subunits, where a maximally effective concentration of etomidate potentiated currents evoked by GABA at EC10 to 28 +/- 2% and 169 +/- 4% of the maximal GABA response, respectively. 5. For alpha 1 subunit-containing receptors, the potency and maximal potentiating effect of either pentobarbitone or propofol was essentially unaffected by the beta subunit isoform contained within the receptor complex. The potency of the anaesthetic neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one was marginally higher for beta 1 rather than the beta 2 subunit-containing receptor, although its maximal effect was similar at the two receptor isoforms. 6. The GABA-mimetic action of etomidate was supported by beta 2- but not beta 1-subunit containing receptors, whereas that of pentobarbitone or propofol was evident with either beta isoform. For beta 2-subunit containing receptors, both the agonist EC50 and the maximal current produced by etomidate were additionally influenced by the alpha isoform. 7. | It is concluded that the subtype of beta-subunit influences the potency with which etomidate potentiates GABA -evoked currents and that the beta isoform is a crucial determinant of the GABA -mimetic activity of this compound. | entailment |
1. The GABA modulating and GABA-mimetic actions of the general anaesthetic etomidate were examined in voltage-clamp recordings performed on Xenopus laevis oocytes induced, by cRNA injection, to express human recombinant gamma-aminobutyric acidA (GABAA) receptor subunits. 2. Currents mediated by recombinant receptors with the ternary subunit composition alpha x beta y gamma 2L (where x = 1,2,3 or 6 and y = 1 or 2), in response to GABA applied at the appropriate EC10, were enhanced by etomidate in a manner that was dependent upon the identity of both the alpha and beta subunit isoforms. 3. For the beta 2-subunit containing receptors tested, the EC50 for the potentiation of GABA-evoked currents by etomidate (range 0.6 to 1.2 microM) was little affected by the nature of the alpha subunit present within the hetero-oligomeric complex. However, replacement of the beta 2 by the beta 1 subunit produced a 9-12 fold increase in the etomidate EC50 (6 to 11 microM) for all alpha-isoforms tested. 4. For alpha 1, alpha 2 and alpha 6, but not alpha 3-subunit containing receptors, the maximal potentiation of GABA-evoked currents by etomidate was greater for beta 2- than for beta 1-subunit containing receptors. This was most clearly exemplified by receptors composed of alpha 6 beta 1 gamma 2L compared to alpha 6 beta 2 gamma 2L subunits, where a maximally effective concentration of etomidate potentiated currents evoked by GABA at EC10 to 28 +/- 2% and 169 +/- 4% of the maximal GABA response, respectively. 5. For alpha 1 subunit-containing receptors, the potency and maximal potentiating effect of either pentobarbitone or propofol was essentially unaffected by the beta subunit isoform contained within the receptor complex. The potency of the anaesthetic neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one was marginally higher for beta 1 rather than the beta 2 subunit-containing receptor, although its maximal effect was similar at the two receptor isoforms. 6. The GABA-mimetic action of etomidate was supported by beta 2- but not beta 1-subunit containing receptors, whereas that of pentobarbitone or propofol was evident with either beta isoform. For beta 2-subunit containing receptors, both the agonist EC50 and the maximal current produced by etomidate were additionally influenced by the alpha isoform. 7. | It is concluded that the subtype of beta-subunit influences the potency with which GABA potentiates etomidate -evoked currents and that the beta isoform is a crucial determinant of the etomidate -mimetic activity of this compound. | contradiction |
1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects. 2. Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by 1 microM bradykinin. U73122 10 microM caused total and irreversible inhibition. The inactive analogue U73343 was without effect. 3. Resting levels of Ins(1,4,5)P3 were not affected. However, resting [Ca2+]i was increased by 10 microM U73122, but not by U73343. Individual cells responded to 10 microM U73122 with a small increase in [Ca2+]i, followed in some cells by a large further rise. 4. Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size. To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required. Again, U73343 was without effect. 5. U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels. The decrease was often preceded by a transient increase. 6. M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase. The bradykinin-induced inhibition of IM was not affected by U73122. 7. Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by bradykinin. Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size. 8. | The four main conclusions drawn from the results are: (a) U73122 suppresses bradykinin -induced estrogen-induced activation and IK(Ca), but not IM inhibition. | contradiction |
1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects. 2. Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by 1 microM bradykinin. U73122 10 microM caused total and irreversible inhibition. The inactive analogue U73343 was without effect. 3. Resting levels of Ins(1,4,5)P3 were not affected. However, resting [Ca2+]i was increased by 10 microM U73122, but not by U73343. Individual cells responded to 10 microM U73122 with a small increase in [Ca2+]i, followed in some cells by a large further rise. 4. Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size. To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required. Again, U73343 was without effect. 5. U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels. The decrease was often preceded by a transient increase. 6. M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase. The bradykinin-induced inhibition of IM was not affected by U73122. 7. Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by bradykinin. Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size. 8. | The four main conclusions drawn from the results are: (a) U73122 suppresses bradykinin -induced PLC activation and IK(Ca), but not IM promotion. | contradiction |
1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects. 2. Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by 1 microM bradykinin. U73122 10 microM caused total and irreversible inhibition. The inactive analogue U73343 was without effect. 3. Resting levels of Ins(1,4,5)P3 were not affected. However, resting [Ca2+]i was increased by 10 microM U73122, but not by U73343. Individual cells responded to 10 microM U73122 with a small increase in [Ca2+]i, followed in some cells by a large further rise. 4. Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size. To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required. Again, U73343 was without effect. 5. U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels. The decrease was often preceded by a transient increase. 6. M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase. The bradykinin-induced inhibition of IM was not affected by U73122. 7. Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by bradykinin. Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size. 8. | We conclude that 5-10 microM bradykinin activates PLC in NG108-15 cells. | contradiction |
1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects. 2. Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by 1 microM bradykinin. U73122 10 microM caused total and irreversible inhibition. The inactive analogue U73343 was without effect. 3. Resting levels of Ins(1,4,5)P3 were not affected. However, resting [Ca2+]i was increased by 10 microM U73122, but not by U73343. Individual cells responded to 10 microM U73122 with a small increase in [Ca2+]i, followed in some cells by a large further rise. 4. Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size. To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required. Again, U73343 was without effect. 5. U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels. The decrease was often preceded by a transient increase. 6. M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase. The bradykinin-induced inhibition of IM was not affected by U73122. 7. Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by bradykinin. Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size. 8. | We conclude that 5-10 microM bradykinin activates PLC in NG108-15 cells. | contradiction |
1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects. 2. Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by 1 microM bradykinin. U73122 10 microM caused total and irreversible inhibition. The inactive analogue U73343 was without effect. 3. Resting levels of Ins(1,4,5)P3 were not affected. However, resting [Ca2+]i was increased by 10 microM U73122, but not by U73343. Individual cells responded to 10 microM U73122 with a small increase in [Ca2+]i, followed in some cells by a large further rise. 4. Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size. To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required. Again, U73343 was without effect. 5. U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels. The decrease was often preceded by a transient increase. 6. M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase. The bradykinin-induced inhibition of IM was not affected by U73122. 7. Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by bradykinin. Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size. 8. | The four main conclusions drawn from the results are: (a) U73122 suppresses PLC -induced bradykinin activation and IK(Ca), but not IM inhibition. | contradiction |
1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects. 2. Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by 1 microM bradykinin. U73122 10 microM caused total and irreversible inhibition. The inactive analogue U73343 was without effect. 3. Resting levels of Ins(1,4,5)P3 were not affected. However, resting [Ca2+]i was increased by 10 microM U73122, but not by U73343. Individual cells responded to 10 microM U73122 with a small increase in [Ca2+]i, followed in some cells by a large further rise. 4. Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size. To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required. Again, U73343 was without effect. 5. U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels. The decrease was often preceded by a transient increase. 6. M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase. The bradykinin-induced inhibition of IM was not affected by U73122. 7. Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by bradykinin. Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size. 8. | The four main conclusions drawn from the results are: (a) U73122 suppresses bradykinin -induced PLC activation and IK(Ca), but not IM inhibition. | entailment |
1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects. 2. Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by 1 microM bradykinin. U73122 10 microM caused total and irreversible inhibition. The inactive analogue U73343 was without effect. 3. Resting levels of Ins(1,4,5)P3 were not affected. However, resting [Ca2+]i was increased by 10 microM U73122, but not by U73343. Individual cells responded to 10 microM U73122 with a small increase in [Ca2+]i, followed in some cells by a large further rise. 4. Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size. To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required. Again, U73343 was without effect. 5. U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels. The decrease was often preceded by a transient increase. 6. M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase. The bradykinin-induced inhibition of IM was not affected by U73122. 7. Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by bradykinin. Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size. 8. | The four main conclusions drawn from the results are: (a) U73122 suppresses PLC -induced bradykinin activation and IK(Ca), but not IM inhibition. | contradiction |
C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. | We conclude that (1) circulating CNP achieved by exogenous CNP infusion is regulated by NEP in vivo, (2) regional MCRs are heterogeneous with NEP promotion, (3) NEP inhibition does not potentiate acute cardiovascular actions of CNP , and (4) a mild natriuretic and diuretic effect observed with CNP and NEP inhibition may be ANP dependent. | contradiction |
C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. | We conclude that (1) circulating CNP achieved by exogenous CNP infusion is regulated by NEP in vivo, (2) regional MCRs are heterogeneous with NEP inhibition, (3) NEP inhibition does not potentiate acute cardiovascular actions of CNP , and (8) a mild natriuretic and diuretic effect observed with CNP and NEP inhibition may be ANP dependent. | contradiction |
C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. | We conclude that (1) circulating BSEP achieved by exogenous BSEP infusion is regulated by NEP in vivo, (2) regional MCRs are heterogeneous with NEP inhibition, (3) NEP inhibition does not potentiate acute cardiovascular actions of BSEP , and (4) a mild natriuretic and diuretic effect observed with BSEP and NEP inhibition may be ANP dependent. | contradiction |
C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. | We conclude that (1) circulating NEP achieved by exogenous NEP infusion is regulated by CNP in vivo, (2) regional MCRs are heterogeneous with CNP inhibition, (3) CNP inhibition does not potentiate acute cardiovascular actions of NEP , and (4) a mild natriuretic and diuretic effect observed with NEP and CNP inhibition may be ANP dependent. | contradiction |
C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. | In conclusion, the selective NEP inhibition increased circulating and regional CNP MCRs. | contradiction |
C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. | In conclusion, the selective NEP inhibition increased circulating and regional CNP MCRs. | contradiction |
C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. | We conclude that (1) circulating CNP achieved by exogenous CNP infusion is regulated by NEP in vivo, (2) regional MCRs are heterogeneous with NEP inhibition, (3) NEP inhibition does not potentiate acute cardiovascular actions of CNP , and (4) a mild natriuretic and diuretic effect observed with CNP and NEP inhibition may be ANP dependent. | entailment |
C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. | We conclude that (1) circulating CNP achieved by exogenous CNP infusion is not regulated by NEP in vivo, (2) regional MCRs are heterogeneous with NEP inhibition, (3) NEP inhibition does not potentiate acute cardiovascular actions of CNP , and (4) a mild natriuretic and diuretic effect observed with CNP and NEP inhibition may be ANP dependent. | contradiction |
C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial and renal cell origin with selective cardiovascular actions. Recent in vitro studies have reported that CNP is the most susceptible of all natriuretic peptides to enzymatic degradation by neutral endopeptidase 24.11 (NEP). The present study was undertaken to define the role of NEP in total and regional CNP metabolism and the modulatory actions of NEP inhibition on the biological actions of CNP. CNP (10 ng x kg(-1) x min(-1)) followed by candoxatrilat (240 microg x kg(-1) bolus and 8 microg x kg(-1) x min(-1)), a potent and selective NEP inhibitor, was administered intravenously to a group of anesthetized mongrel dogs (group 1) to permit calculation of total metabolic clearance rate (MCR); results were compared with those in a group receiving vehicle infusion followed by candoxatrilat (group 2; both groups, n=7). NEP inhibition increased circulating CNP achieved by exogenous infusion and reduced total MCR in group 1. The regional CNP MCRs increased after CNP administration. While the pulmonary MCR did not change during concomitant candoxatrilat infusion, renal MCR was suppressed. Hemodynamic changes were not different between groups. A mild natriuretic and diuretic effect in association with an increase in circulating and urinary ANP levels was not different between groups. Urinary CNP excretion did not change with CNP infusion but markedly increased after NEP inhibition. | We conclude that (1) circulating NEP achieved by exogenous NEP infusion is regulated by CNP in vivo, (2) regional MCRs are heterogeneous with CNP inhibition, (3) CNP inhibition does not potentiate acute cardiovascular actions of NEP , and (4) a mild natriuretic and diuretic effect observed with NEP and CNP inhibition may be ANP dependent. | contradiction |
Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase ongoing afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. | We conclude that phenytoin is not able to suppress focal seizure activity in the amygdala kindling model of the rat. | contradiction |
Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase ongoing afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. | We conclude that DM NE is able to suppress focal seizure activity in the amygdala kindling model of the rat. | contradiction |
Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase ongoing afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. | We conclude that seizure is able to suppress focal phenytoin activity in the amygdala kindling model of the rat. | contradiction |
Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase ongoing afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. | We conclude that phenytoin is able to suppress focal seizure activity in the amygdala kindling model of the rat. | entailment |
Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase ongoing afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. | In conclusion, phenytoin increases the afterdischarge threshold for generation of focal seizure activity, but it does not prevent the spread of ongoing seizure activity within the limbic system. | contradiction |
Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase ongoing afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. | In conclusion, phenytoin increases the afterdischarge threshold for generation of focal seizure activity, but it does not prevent the spread of ongoing seizure activity within the limbic system. | contradiction |
Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase ongoing afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. | We conclude that seizure is able to suppress focal phenytoin activity in the amygdala kindling model of the rat. | contradiction |
Based on the knowledge that diagnostic fine needle biopsy of the thyroid (FNAB) results in a prompt increase in circulating thyroglobulin (Tg); we evaluated whether Tg is indeed the postulated antigen for circulating antibodies against thyroid hormones (THAb). Preliminarily, we verified that FNAB causes the release into the bloodstream of iodinated, heterologous, and thus potentially immunogenic, molecules of Tg. Of the initially enrolled 400 patients, 214 had a number of blood drawings sufficient to evaluate over time (before FNAB and 1-3 h, 3 days, 15 days, 30 days, 3 months, 6 months, and 12 months after FNAB) the following parameters: THAb of both IgM and IgG classes, Tg antibodies (TgAb; by a sensitive immunoradiometric assay), and Tg (in the 156 patients who were TgAb negative). We found the following. 1) Serum Tg most often peaks 1-3 h after FNAB (61 +/- 45% of the baseline level; mean +/- SD). 2) Only 7% of the initially TgAb-negative patients converted to positive, and only 12% of those initially positive had an increase in the levels of TgAb. 3) THAb were detected in 0 of 400 patients before FNAB, but were found in 9 of 214 (4.2%) after FNAB. This proportion is 2 orders of magnitude higher than that (149 of 369,000 or 0.04%) found in consecutive patients attending European thyroid clinics. Of the 9 cases, 6 had Hashimoto's thyroiditis (HT), 2 had euthyroid colloid goiter, and 1 had Hurthle cell carcinoma. In the 5 of 9 cases who were TgAb negative, the post-FNAB increment in Tg was 21-99%, i.e. lower than that of the majority of patients (101-12,500%). 4) THAb were of the IgM class in all 9 (6 against T3 and 3 against T4), and were accompanied and/or followed up to 3 months after FNAB by IgG-THAb of the same specificity (2 against T3 and 1 against T4) in 3 cases. In a fourth case, IgM-T3 were followed by a long-lasting synthesis of IgG-T3 (i.e. up to 1 yr post-FNAB). All 4 cases with IgG-THAb had HT and remained TgAb positive. 5) In the 2 HT and the 3 non-HT patients with undetectable TgAb, THAb were of the IgM class only. 6) In the HT group, 2 risk factors for the development of post-FNAB THAb appeared to be pre-FNAB TgAb levels below 400 U/mL that did not increase after FNAB and Tg released from a colloid nodule. | We conclude that THAb release from the thyroid is sufficient to elicit Tg synthesis. | contradiction |
Based on the knowledge that diagnostic fine needle biopsy of the thyroid (FNAB) results in a prompt increase in circulating thyroglobulin (Tg); we evaluated whether Tg is indeed the postulated antigen for circulating antibodies against thyroid hormones (THAb). Preliminarily, we verified that FNAB causes the release into the bloodstream of iodinated, heterologous, and thus potentially immunogenic, molecules of Tg. Of the initially enrolled 400 patients, 214 had a number of blood drawings sufficient to evaluate over time (before FNAB and 1-3 h, 3 days, 15 days, 30 days, 3 months, 6 months, and 12 months after FNAB) the following parameters: THAb of both IgM and IgG classes, Tg antibodies (TgAb; by a sensitive immunoradiometric assay), and Tg (in the 156 patients who were TgAb negative). We found the following. 1) Serum Tg most often peaks 1-3 h after FNAB (61 +/- 45% of the baseline level; mean +/- SD). 2) Only 7% of the initially TgAb-negative patients converted to positive, and only 12% of those initially positive had an increase in the levels of TgAb. 3) THAb were detected in 0 of 400 patients before FNAB, but were found in 9 of 214 (4.2%) after FNAB. This proportion is 2 orders of magnitude higher than that (149 of 369,000 or 0.04%) found in consecutive patients attending European thyroid clinics. Of the 9 cases, 6 had Hashimoto's thyroiditis (HT), 2 had euthyroid colloid goiter, and 1 had Hurthle cell carcinoma. In the 5 of 9 cases who were TgAb negative, the post-FNAB increment in Tg was 21-99%, i.e. lower than that of the majority of patients (101-12,500%). 4) THAb were of the IgM class in all 9 (6 against T3 and 3 against T4), and were accompanied and/or followed up to 3 months after FNAB by IgG-THAb of the same specificity (2 against T3 and 1 against T4) in 3 cases. In a fourth case, IgM-T3 were followed by a long-lasting synthesis of IgG-T3 (i.e. up to 1 yr post-FNAB). All 4 cases with IgG-THAb had HT and remained TgAb positive. 5) In the 2 HT and the 3 non-HT patients with undetectable TgAb, THAb were of the IgM class only. 6) In the HT group, 2 risk factors for the development of post-FNAB THAb appeared to be pre-FNAB TgAb levels below 400 U/mL that did not increase after FNAB and Tg released from a colloid nodule. | We conclude that Tg release from the thyroid is not sufficient to elicit THAb synthesis. | contradiction |
Based on the knowledge that diagnostic fine needle biopsy of the thyroid (FNAB) results in a prompt increase in circulating thyroglobulin (Tg); we evaluated whether Tg is indeed the postulated antigen for circulating antibodies against thyroid hormones (THAb). Preliminarily, we verified that FNAB causes the release into the bloodstream of iodinated, heterologous, and thus potentially immunogenic, molecules of Tg. Of the initially enrolled 400 patients, 214 had a number of blood drawings sufficient to evaluate over time (before FNAB and 1-3 h, 3 days, 15 days, 30 days, 3 months, 6 months, and 12 months after FNAB) the following parameters: THAb of both IgM and IgG classes, Tg antibodies (TgAb; by a sensitive immunoradiometric assay), and Tg (in the 156 patients who were TgAb negative). We found the following. 1) Serum Tg most often peaks 1-3 h after FNAB (61 +/- 45% of the baseline level; mean +/- SD). 2) Only 7% of the initially TgAb-negative patients converted to positive, and only 12% of those initially positive had an increase in the levels of TgAb. 3) THAb were detected in 0 of 400 patients before FNAB, but were found in 9 of 214 (4.2%) after FNAB. This proportion is 2 orders of magnitude higher than that (149 of 369,000 or 0.04%) found in consecutive patients attending European thyroid clinics. Of the 9 cases, 6 had Hashimoto's thyroiditis (HT), 2 had euthyroid colloid goiter, and 1 had Hurthle cell carcinoma. In the 5 of 9 cases who were TgAb negative, the post-FNAB increment in Tg was 21-99%, i.e. lower than that of the majority of patients (101-12,500%). 4) THAb were of the IgM class in all 9 (6 against T3 and 3 against T4), and were accompanied and/or followed up to 3 months after FNAB by IgG-THAb of the same specificity (2 against T3 and 1 against T4) in 3 cases. In a fourth case, IgM-T3 were followed by a long-lasting synthesis of IgG-T3 (i.e. up to 1 yr post-FNAB). All 4 cases with IgG-THAb had HT and remained TgAb positive. 5) In the 2 HT and the 3 non-HT patients with undetectable TgAb, THAb were of the IgM class only. 6) In the HT group, 2 risk factors for the development of post-FNAB THAb appeared to be pre-FNAB TgAb levels below 400 U/mL that did not increase after FNAB and Tg released from a colloid nodule. | We conclude that THAb release from the thyroid is sufficient to elicit Tg synthesis. | contradiction |
Based on the knowledge that diagnostic fine needle biopsy of the thyroid (FNAB) results in a prompt increase in circulating thyroglobulin (Tg); we evaluated whether Tg is indeed the postulated antigen for circulating antibodies against thyroid hormones (THAb). Preliminarily, we verified that FNAB causes the release into the bloodstream of iodinated, heterologous, and thus potentially immunogenic, molecules of Tg. Of the initially enrolled 400 patients, 214 had a number of blood drawings sufficient to evaluate over time (before FNAB and 1-3 h, 3 days, 15 days, 30 days, 3 months, 6 months, and 12 months after FNAB) the following parameters: THAb of both IgM and IgG classes, Tg antibodies (TgAb; by a sensitive immunoradiometric assay), and Tg (in the 156 patients who were TgAb negative). We found the following. 1) Serum Tg most often peaks 1-3 h after FNAB (61 +/- 45% of the baseline level; mean +/- SD). 2) Only 7% of the initially TgAb-negative patients converted to positive, and only 12% of those initially positive had an increase in the levels of TgAb. 3) THAb were detected in 0 of 400 patients before FNAB, but were found in 9 of 214 (4.2%) after FNAB. This proportion is 2 orders of magnitude higher than that (149 of 369,000 or 0.04%) found in consecutive patients attending European thyroid clinics. Of the 9 cases, 6 had Hashimoto's thyroiditis (HT), 2 had euthyroid colloid goiter, and 1 had Hurthle cell carcinoma. In the 5 of 9 cases who were TgAb negative, the post-FNAB increment in Tg was 21-99%, i.e. lower than that of the majority of patients (101-12,500%). 4) THAb were of the IgM class in all 9 (6 against T3 and 3 against T4), and were accompanied and/or followed up to 3 months after FNAB by IgG-THAb of the same specificity (2 against T3 and 1 against T4) in 3 cases. In a fourth case, IgM-T3 were followed by a long-lasting synthesis of IgG-T3 (i.e. up to 1 yr post-FNAB). All 4 cases with IgG-THAb had HT and remained TgAb positive. 5) In the 2 HT and the 3 non-HT patients with undetectable TgAb, THAb were of the IgM class only. 6) In the HT group, 2 risk factors for the development of post-FNAB THAb appeared to be pre-FNAB TgAb levels below 400 U/mL that did not increase after FNAB and Tg released from a colloid nodule. | We conclude that Tg is indeed the postulated antigen for THAb . | contradiction |
Based on the knowledge that diagnostic fine needle biopsy of the thyroid (FNAB) results in a prompt increase in circulating thyroglobulin (Tg); we evaluated whether Tg is indeed the postulated antigen for circulating antibodies against thyroid hormones (THAb). Preliminarily, we verified that FNAB causes the release into the bloodstream of iodinated, heterologous, and thus potentially immunogenic, molecules of Tg. Of the initially enrolled 400 patients, 214 had a number of blood drawings sufficient to evaluate over time (before FNAB and 1-3 h, 3 days, 15 days, 30 days, 3 months, 6 months, and 12 months after FNAB) the following parameters: THAb of both IgM and IgG classes, Tg antibodies (TgAb; by a sensitive immunoradiometric assay), and Tg (in the 156 patients who were TgAb negative). We found the following. 1) Serum Tg most often peaks 1-3 h after FNAB (61 +/- 45% of the baseline level; mean +/- SD). 2) Only 7% of the initially TgAb-negative patients converted to positive, and only 12% of those initially positive had an increase in the levels of TgAb. 3) THAb were detected in 0 of 400 patients before FNAB, but were found in 9 of 214 (4.2%) after FNAB. This proportion is 2 orders of magnitude higher than that (149 of 369,000 or 0.04%) found in consecutive patients attending European thyroid clinics. Of the 9 cases, 6 had Hashimoto's thyroiditis (HT), 2 had euthyroid colloid goiter, and 1 had Hurthle cell carcinoma. In the 5 of 9 cases who were TgAb negative, the post-FNAB increment in Tg was 21-99%, i.e. lower than that of the majority of patients (101-12,500%). 4) THAb were of the IgM class in all 9 (6 against T3 and 3 against T4), and were accompanied and/or followed up to 3 months after FNAB by IgG-THAb of the same specificity (2 against T3 and 1 against T4) in 3 cases. In a fourth case, IgM-T3 were followed by a long-lasting synthesis of IgG-T3 (i.e. up to 1 yr post-FNAB). All 4 cases with IgG-THAb had HT and remained TgAb positive. 5) In the 2 HT and the 3 non-HT patients with undetectable TgAb, THAb were of the IgM class only. 6) In the HT group, 2 risk factors for the development of post-FNAB THAb appeared to be pre-FNAB TgAb levels below 400 U/mL that did not increase after FNAB and Tg released from a colloid nodule. | We conclude that Tg release from the thyroid is sufficient to elicit THAb synthesis. | entailment |
Based on the knowledge that diagnostic fine needle biopsy of the thyroid (FNAB) results in a prompt increase in circulating thyroglobulin (Tg); we evaluated whether Tg is indeed the postulated antigen for circulating antibodies against thyroid hormones (THAb). Preliminarily, we verified that FNAB causes the release into the bloodstream of iodinated, heterologous, and thus potentially immunogenic, molecules of Tg. Of the initially enrolled 400 patients, 214 had a number of blood drawings sufficient to evaluate over time (before FNAB and 1-3 h, 3 days, 15 days, 30 days, 3 months, 6 months, and 12 months after FNAB) the following parameters: THAb of both IgM and IgG classes, Tg antibodies (TgAb; by a sensitive immunoradiometric assay), and Tg (in the 156 patients who were TgAb negative). We found the following. 1) Serum Tg most often peaks 1-3 h after FNAB (61 +/- 45% of the baseline level; mean +/- SD). 2) Only 7% of the initially TgAb-negative patients converted to positive, and only 12% of those initially positive had an increase in the levels of TgAb. 3) THAb were detected in 0 of 400 patients before FNAB, but were found in 9 of 214 (4.2%) after FNAB. This proportion is 2 orders of magnitude higher than that (149 of 369,000 or 0.04%) found in consecutive patients attending European thyroid clinics. Of the 9 cases, 6 had Hashimoto's thyroiditis (HT), 2 had euthyroid colloid goiter, and 1 had Hurthle cell carcinoma. In the 5 of 9 cases who were TgAb negative, the post-FNAB increment in Tg was 21-99%, i.e. lower than that of the majority of patients (101-12,500%). 4) THAb were of the IgM class in all 9 (6 against T3 and 3 against T4), and were accompanied and/or followed up to 3 months after FNAB by IgG-THAb of the same specificity (2 against T3 and 1 against T4) in 3 cases. In a fourth case, IgM-T3 were followed by a long-lasting synthesis of IgG-T3 (i.e. up to 1 yr post-FNAB). All 4 cases with IgG-THAb had HT and remained TgAb positive. 5) In the 2 HT and the 3 non-HT patients with undetectable TgAb, THAb were of the IgM class only. 6) In the HT group, 2 risk factors for the development of post-FNAB THAb appeared to be pre-FNAB TgAb levels below 400 U/mL that did not increase after FNAB and Tg released from a colloid nodule. | We conclude that SPF NC/Tnd release from the thyroid is sufficient to elicit THAb synthesis. | contradiction |
Cholera toxin (CT) is a potent mucosal immunogen and adjuvant that can strongly prime mucosal T cells. The present study was undertaken to investigate the effects of CT on the expression and functional activity of the costimulatory molecules B7.1 and B7.2 on macrophages and the relationship of these effects to the mucosal adjuvanticity of CT. Bone marrow macrophages (BMM) were generated by culturing bone marrow with macrophage CSF or granulocyte-macrophage CSF. After treatment with either CT alone or IFN-gamma alone, B7.2 expression on BMM was moderately up-regulated and was further increased when BMM were treated with both CT and IFN-gamma together. Interestingly, CT had no effect on B7.1 expression despite the close relationship between these two molecules. Up-regulation of B7.2 expression by CT was mediated by intracellular cAMP production, in that CT-B subunit had no effect and dibutyryl cAMP could mimic the effect. CT increased functional costimulatory activity of macrophages for both anti-CD3-stimulated and allostimulated T cells, an increase that was blocked by anti-B7.2, but not anti-B7.1, Ab. B7.2 expression by Mac1+ Peyer's patch cells was increased after intraluminal exposure to CT in vivo. | Treatment of mice with anti-B7.2 Ab in vivo inhibited both the mucosal adjuvanticity and the immunogenicity of B7.2 expression . We conclude that B7.2 expression enhances the costimulatory activity of mucosal APC by differentially up-regulating CT , an effect that appears to be important for its mucosal adjuvanticity and immunogenicity. | contradiction |
Cholera toxin (CT) is a potent mucosal immunogen and adjuvant that can strongly prime mucosal T cells. The present study was undertaken to investigate the effects of CT on the expression and functional activity of the costimulatory molecules B7.1 and B7.2 on macrophages and the relationship of these effects to the mucosal adjuvanticity of CT. Bone marrow macrophages (BMM) were generated by culturing bone marrow with macrophage CSF or granulocyte-macrophage CSF. After treatment with either CT alone or IFN-gamma alone, B7.2 expression on BMM was moderately up-regulated and was further increased when BMM were treated with both CT and IFN-gamma together. Interestingly, CT had no effect on B7.1 expression despite the close relationship between these two molecules. Up-regulation of B7.2 expression by CT was mediated by intracellular cAMP production, in that CT-B subunit had no effect and dibutyryl cAMP could mimic the effect. CT increased functional costimulatory activity of macrophages for both anti-CD3-stimulated and allostimulated T cells, an increase that was blocked by anti-B7.2, but not anti-B7.1, Ab. B7.2 expression by Mac1+ Peyer's patch cells was increased after intraluminal exposure to CT in vivo. | In conclusion, CT up-regulates B7.2 expression on macrophages and this up-regulation contributes to the mucosal adjuvanticity of CT . | contradiction |