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We have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. We show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant.

We conclude that ferritin -induced iron biosynthesis is governed by multiple post-transcriptional regulatory mechanisms.

contradiction

We have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. We show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant.

We conclude that the increment in total ferritin subunit mRNAs in ferritin -producing K562 cells is a posttranscriptional event and that ferritin biosynthesis is positively regulated by the addition of the efficient iron donor hemin.

contradiction

We have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. We show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant.

We conclude that iron -induced ferritin biosynthesis is governed by multiple post-transcriptional regulatory mechanisms.

entailment

Isolated rat hepatocytes responded to a variety of Ca2+-mobilizing agents (vasopressin, angiotensin II, epinephrine, epidermal growth factor, ATP, and ADP) with a rapid increase in phosphatidate mass, as measured by a sensitive new method. When hepatocytes were incubated with vasopressin (10(-8) M), phosphatidate levels increased 2-3-fold in 2 min, but there was no significant increase in diacylglycerol at this time. Changes in the fatty acid composition of phosphatidate also preceded those in diacylglycerol. De novo synthesis of phosphatidate from [3H]glycerol was unaffected by vasopressin in short-term incubation. Incubation of washed rat liver plasma membranes with GTP gamma S caused a time-dependent increase in phosphatidate. When membranes were incubated with GTP gamma S and [gamma-32P]ATP, no incorporation of 32P into phosphatidate was observed. This excludes the phospholipase C-diacylglycerol kinase pathway and suggests that a phospholipase D activity produced the phosphatidate. At submaximal concentrations of GTP gamma S, ATP and ADP stimulated membrane phosphatidate formation, presumably by acting through P2-purinergic receptors. Only phosphatidylcholine, among the major phospholipids, decreased in the membranes in response to GTP gamma S. The fatty acid composition of the phosphatidate produced in response to vasopressin in hepatocytes also suggests that phosphatidylcholine may be the source of hormonally elicited phosphatidate.

We conclude that Ca2 +-mobilizing hormones mainly increase phosphatidate levels in hepatocytes by a mechanism that does not involve phosphorylation of diacylglycerol or de novo synthesis but involves a guanine nucleotide-binding protein coupled to phospholipase D.

entailment

Isolated rat hepatocytes responded to a variety of Ca2+-mobilizing agents (vasopressin, angiotensin II, epinephrine, epidermal growth factor, ATP, and ADP) with a rapid increase in phosphatidate mass, as measured by a sensitive new method. When hepatocytes were incubated with vasopressin (10(-8) M), phosphatidate levels increased 2-3-fold in 2 min, but there was no significant increase in diacylglycerol at this time. Changes in the fatty acid composition of phosphatidate also preceded those in diacylglycerol. De novo synthesis of phosphatidate from [3H]glycerol was unaffected by vasopressin in short-term incubation. Incubation of washed rat liver plasma membranes with GTP gamma S caused a time-dependent increase in phosphatidate. When membranes were incubated with GTP gamma S and [gamma-32P]ATP, no incorporation of 32P into phosphatidate was observed. This excludes the phospholipase C-diacylglycerol kinase pathway and suggests that a phospholipase D activity produced the phosphatidate. At submaximal concentrations of GTP gamma S, ATP and ADP stimulated membrane phosphatidate formation, presumably by acting through P2-purinergic receptors. Only phosphatidylcholine, among the major phospholipids, decreased in the membranes in response to GTP gamma S. The fatty acid composition of the phosphatidate produced in response to vasopressin in hepatocytes also suggests that phosphatidylcholine may be the source of hormonally elicited phosphatidate.

We conclude that phosphatidate +-mobilizing hormones mainly increase Ca2 levels in hepatocytes by a mechanism that does not involve phosphorylation of diacylglycerol or de novo synthesis but involves a guanine nucleotide-binding protein coupled to phospholipase D.

contradiction

Isolated rat hepatocytes responded to a variety of Ca2+-mobilizing agents (vasopressin, angiotensin II, epinephrine, epidermal growth factor, ATP, and ADP) with a rapid increase in phosphatidate mass, as measured by a sensitive new method. When hepatocytes were incubated with vasopressin (10(-8) M), phosphatidate levels increased 2-3-fold in 2 min, but there was no significant increase in diacylglycerol at this time. Changes in the fatty acid composition of phosphatidate also preceded those in diacylglycerol. De novo synthesis of phosphatidate from [3H]glycerol was unaffected by vasopressin in short-term incubation. Incubation of washed rat liver plasma membranes with GTP gamma S caused a time-dependent increase in phosphatidate. When membranes were incubated with GTP gamma S and [gamma-32P]ATP, no incorporation of 32P into phosphatidate was observed. This excludes the phospholipase C-diacylglycerol kinase pathway and suggests that a phospholipase D activity produced the phosphatidate. At submaximal concentrations of GTP gamma S, ATP and ADP stimulated membrane phosphatidate formation, presumably by acting through P2-purinergic receptors. Only phosphatidylcholine, among the major phospholipids, decreased in the membranes in response to GTP gamma S. The fatty acid composition of the phosphatidate produced in response to vasopressin in hepatocytes also suggests that phosphatidylcholine may be the source of hormonally elicited phosphatidate.

We conclude that Ca2 +-mobilizing hormones mainly decrease phosphatidate levels in hepatocytes by a mechanism that does not involve phosphorylation of diacylglycerol or de novo synthesis but involves a guanine nucleotide-binding protein coupled to phospholipase D.

contradiction

Isolated rat hepatocytes responded to a variety of Ca2+-mobilizing agents (vasopressin, angiotensin II, epinephrine, epidermal growth factor, ATP, and ADP) with a rapid increase in phosphatidate mass, as measured by a sensitive new method. When hepatocytes were incubated with vasopressin (10(-8) M), phosphatidate levels increased 2-3-fold in 2 min, but there was no significant increase in diacylglycerol at this time. Changes in the fatty acid composition of phosphatidate also preceded those in diacylglycerol. De novo synthesis of phosphatidate from [3H]glycerol was unaffected by vasopressin in short-term incubation. Incubation of washed rat liver plasma membranes with GTP gamma S caused a time-dependent increase in phosphatidate. When membranes were incubated with GTP gamma S and [gamma-32P]ATP, no incorporation of 32P into phosphatidate was observed. This excludes the phospholipase C-diacylglycerol kinase pathway and suggests that a phospholipase D activity produced the phosphatidate. At submaximal concentrations of GTP gamma S, ATP and ADP stimulated membrane phosphatidate formation, presumably by acting through P2-purinergic receptors. Only phosphatidylcholine, among the major phospholipids, decreased in the membranes in response to GTP gamma S. The fatty acid composition of the phosphatidate produced in response to vasopressin in hepatocytes also suggests that phosphatidylcholine may be the source of hormonally elicited phosphatidate.

We conclude that Ca2 +-mobilizing hormones mainly increase acetyl-Coenzyme A carboxylase levels in hepatocytes by a mechanism that does not involve phosphorylation of diacylglycerol or de novo synthesis but involves a guanine nucleotide-binding protein coupled to phospholipase D.

contradiction

Isolated rat hepatocytes responded to a variety of Ca2+-mobilizing agents (vasopressin, angiotensin II, epinephrine, epidermal growth factor, ATP, and ADP) with a rapid increase in phosphatidate mass, as measured by a sensitive new method. When hepatocytes were incubated with vasopressin (10(-8) M), phosphatidate levels increased 2-3-fold in 2 min, but there was no significant increase in diacylglycerol at this time. Changes in the fatty acid composition of phosphatidate also preceded those in diacylglycerol. De novo synthesis of phosphatidate from [3H]glycerol was unaffected by vasopressin in short-term incubation. Incubation of washed rat liver plasma membranes with GTP gamma S caused a time-dependent increase in phosphatidate. When membranes were incubated with GTP gamma S and [gamma-32P]ATP, no incorporation of 32P into phosphatidate was observed. This excludes the phospholipase C-diacylglycerol kinase pathway and suggests that a phospholipase D activity produced the phosphatidate. At submaximal concentrations of GTP gamma S, ATP and ADP stimulated membrane phosphatidate formation, presumably by acting through P2-purinergic receptors. Only phosphatidylcholine, among the major phospholipids, decreased in the membranes in response to GTP gamma S. The fatty acid composition of the phosphatidate produced in response to vasopressin in hepatocytes also suggests that phosphatidylcholine may be the source of hormonally elicited phosphatidate.

We conclude that the rapid Ca2 +-mobilizing action of vasopressin in rat hepatocytes results in the rapid production of phosphatidate .

contradiction

Isolated rat hepatocytes responded to a variety of Ca2+-mobilizing agents (vasopressin, angiotensin II, epinephrine, epidermal growth factor, ATP, and ADP) with a rapid increase in phosphatidate mass, as measured by a sensitive new method. When hepatocytes were incubated with vasopressin (10(-8) M), phosphatidate levels increased 2-3-fold in 2 min, but there was no significant increase in diacylglycerol at this time. Changes in the fatty acid composition of phosphatidate also preceded those in diacylglycerol. De novo synthesis of phosphatidate from [3H]glycerol was unaffected by vasopressin in short-term incubation. Incubation of washed rat liver plasma membranes with GTP gamma S caused a time-dependent increase in phosphatidate. When membranes were incubated with GTP gamma S and [gamma-32P]ATP, no incorporation of 32P into phosphatidate was observed. This excludes the phospholipase C-diacylglycerol kinase pathway and suggests that a phospholipase D activity produced the phosphatidate. At submaximal concentrations of GTP gamma S, ATP and ADP stimulated membrane phosphatidate formation, presumably by acting through P2-purinergic receptors. Only phosphatidylcholine, among the major phospholipids, decreased in the membranes in response to GTP gamma S. The fatty acid composition of the phosphatidate produced in response to vasopressin in hepatocytes also suggests that phosphatidylcholine may be the source of hormonally elicited phosphatidate.

We conclude that phosphatidate +-mobilizing hormones mainly increase Ca2 levels in hepatocytes by a mechanism that does not involve phosphorylation of diacylglycerol or de novo synthesis but involves a guanine nucleotide-binding protein coupled to phospholipase D.

contradiction

Isolated rat hepatocytes responded to a variety of Ca2+-mobilizing agents (vasopressin, angiotensin II, epinephrine, epidermal growth factor, ATP, and ADP) with a rapid increase in phosphatidate mass, as measured by a sensitive new method. When hepatocytes were incubated with vasopressin (10(-8) M), phosphatidate levels increased 2-3-fold in 2 min, but there was no significant increase in diacylglycerol at this time. Changes in the fatty acid composition of phosphatidate also preceded those in diacylglycerol. De novo synthesis of phosphatidate from [3H]glycerol was unaffected by vasopressin in short-term incubation. Incubation of washed rat liver plasma membranes with GTP gamma S caused a time-dependent increase in phosphatidate. When membranes were incubated with GTP gamma S and [gamma-32P]ATP, no incorporation of 32P into phosphatidate was observed. This excludes the phospholipase C-diacylglycerol kinase pathway and suggests that a phospholipase D activity produced the phosphatidate. At submaximal concentrations of GTP gamma S, ATP and ADP stimulated membrane phosphatidate formation, presumably by acting through P2-purinergic receptors. Only phosphatidylcholine, among the major phospholipids, decreased in the membranes in response to GTP gamma S. The fatty acid composition of the phosphatidate produced in response to vasopressin in hepatocytes also suggests that phosphatidylcholine may be the source of hormonally elicited phosphatidate.

We conclude that the rapid Ca2 +-mobilizing action of vasopressin in rat hepatocytes results in the rapid production of phosphatidate .

contradiction

The charcoal adsorption from aqueous solution of four weak bases (lidocaine, methadone, pilocarpine, and procaine) was studied at a variety of pH values representing large differences in percent ionization. The measure of charcoal adsorption used was percent of the ligand adsorbed (constant starting ligand concentrations of 3 X 10(-4) M) by a variety of quantities of charcoal ranging from 3 to 30 mg per 10 mL of mixture. In addition, moles of ligand adsorbed/gram of charcoal values were calculated. The data indicated that for a given ligand, charcoal adsorption was statistically the same (p = 0.05) at all pH values.

It is concluded that the generalization for weak bases that charcoal adsorption increases with increasing pH may not be universally valid.

entailment

The charcoal adsorption from aqueous solution of four weak bases (lidocaine, methadone, pilocarpine, and procaine) was studied at a variety of pH values representing large differences in percent ionization. The measure of charcoal adsorption used was percent of the ligand adsorbed (constant starting ligand concentrations of 3 X 10(-4) M) by a variety of quantities of charcoal ranging from 3 to 30 mg per 10 mL of mixture. In addition, moles of ligand adsorbed/gram of charcoal values were calculated. The data indicated that for a given ligand, charcoal adsorption was statistically the same (p = 0.05) at all pH values.

It was concluded that charcoal adsorption from aqueous solution is independent of the pH at which the ligand is adsorbed.

contradiction

The charcoal adsorption from aqueous solution of four weak bases (lidocaine, methadone, pilocarpine, and procaine) was studied at a variety of pH values representing large differences in percent ionization. The measure of charcoal adsorption used was percent of the ligand adsorbed (constant starting ligand concentrations of 3 X 10(-4) M) by a variety of quantities of charcoal ranging from 3 to 30 mg per 10 mL of mixture. In addition, moles of ligand adsorbed/gram of charcoal values were calculated. The data indicated that for a given ligand, charcoal adsorption was statistically the same (p = 0.05) at all pH values.

It is concluded that the generalization for weak bases that pH adsorption increases with increasing charcoal may not be universally valid.

contradiction

The charcoal adsorption from aqueous solution of four weak bases (lidocaine, methadone, pilocarpine, and procaine) was studied at a variety of pH values representing large differences in percent ionization. The measure of charcoal adsorption used was percent of the ligand adsorbed (constant starting ligand concentrations of 3 X 10(-4) M) by a variety of quantities of charcoal ranging from 3 to 30 mg per 10 mL of mixture. In addition, moles of ligand adsorbed/gram of charcoal values were calculated. The data indicated that for a given ligand, charcoal adsorption was statistically the same (p = 0.05) at all pH values.

It is concluded that the generalization for weak bases that Glucan adsorption increases with increasing pH may not be universally valid.

contradiction

The charcoal adsorption from aqueous solution of four weak bases (lidocaine, methadone, pilocarpine, and procaine) was studied at a variety of pH values representing large differences in percent ionization. The measure of charcoal adsorption used was percent of the ligand adsorbed (constant starting ligand concentrations of 3 X 10(-4) M) by a variety of quantities of charcoal ranging from 3 to 30 mg per 10 mL of mixture. In addition, moles of ligand adsorbed/gram of charcoal values were calculated. The data indicated that for a given ligand, charcoal adsorption was statistically the same (p = 0.05) at all pH values.

It is concluded that the generalization for weak bases that pH adsorption increases with increasing charcoal may not be universally valid.

contradiction

The charcoal adsorption from aqueous solution of four weak bases (lidocaine, methadone, pilocarpine, and procaine) was studied at a variety of pH values representing large differences in percent ionization. The measure of charcoal adsorption used was percent of the ligand adsorbed (constant starting ligand concentrations of 3 X 10(-4) M) by a variety of quantities of charcoal ranging from 3 to 30 mg per 10 mL of mixture. In addition, moles of ligand adsorbed/gram of charcoal values were calculated. The data indicated that for a given ligand, charcoal adsorption was statistically the same (p = 0.05) at all pH values.

It is not concluded that the generalization for weak bases that charcoal adsorption increases with increasing pH may not be universally valid.

contradiction

To investigate the possible role of adrenergic nerves in neurally mediated gastrin release, we evaluated the effect of selective adrenergic blockade on the serum gastrin response to gastric distention in healthy human subjects. On separate days, 2 mg of propranolol (beta-adrenergic antagonist), 5 mg of phentolamine (alpha-adrenergic antagonist), or saline (control) was injected intravenously just before distending the stomach with 700 ml of isotonic saline. For 30 min following distention, intragastric pH was kept constant at 5.0 by in vivo titration. Propranolol reduced distention-induced gastrin release by approximately 90% (p less than 0.02), whereas phentolamine had no significant effect on the gastrin response to distention. In additional experiments, we evaluated the effect of the same doses of propranolol or phentolamine on the exaggerated gastrin response to gastric distention that occurred during cholinergic blockade with atropine. In the presence of atropine (2.3 microgram/kg i.v.), propranolol significantly (p less than 0.01) reduced distention-induced gastrin release, whereas phentolamine significantly enhanced the gastrin response to distention (p less than 0.01).

We conclude that: (1) distention-induced gastrin release was reduced by malate , suggesting that gastric distention releases gastrin by a beta-adrenergic mechanism and (2) distention-induced gastrin release was enhanced by phentolamine, but only in the presence of atropine.

contradiction

To investigate the possible role of adrenergic nerves in neurally mediated gastrin release, we evaluated the effect of selective adrenergic blockade on the serum gastrin response to gastric distention in healthy human subjects. On separate days, 2 mg of propranolol (beta-adrenergic antagonist), 5 mg of phentolamine (alpha-adrenergic antagonist), or saline (control) was injected intravenously just before distending the stomach with 700 ml of isotonic saline. For 30 min following distention, intragastric pH was kept constant at 5.0 by in vivo titration. Propranolol reduced distention-induced gastrin release by approximately 90% (p less than 0.02), whereas phentolamine had no significant effect on the gastrin response to distention. In additional experiments, we evaluated the effect of the same doses of propranolol or phentolamine on the exaggerated gastrin response to gastric distention that occurred during cholinergic blockade with atropine. In the presence of atropine (2.3 microgram/kg i.v.), propranolol significantly (p less than 0.01) reduced distention-induced gastrin release, whereas phentolamine significantly enhanced the gastrin response to distention (p less than 0.01).

We conclude that propranolol inhibits neurally mediated gastrin release in man.

contradiction

To investigate the possible role of adrenergic nerves in neurally mediated gastrin release, we evaluated the effect of selective adrenergic blockade on the serum gastrin response to gastric distention in healthy human subjects. On separate days, 2 mg of propranolol (beta-adrenergic antagonist), 5 mg of phentolamine (alpha-adrenergic antagonist), or saline (control) was injected intravenously just before distending the stomach with 700 ml of isotonic saline. For 30 min following distention, intragastric pH was kept constant at 5.0 by in vivo titration. Propranolol reduced distention-induced gastrin release by approximately 90% (p less than 0.02), whereas phentolamine had no significant effect on the gastrin response to distention. In additional experiments, we evaluated the effect of the same doses of propranolol or phentolamine on the exaggerated gastrin response to gastric distention that occurred during cholinergic blockade with atropine. In the presence of atropine (2.3 microgram/kg i.v.), propranolol significantly (p less than 0.01) reduced distention-induced gastrin release, whereas phentolamine significantly enhanced the gastrin response to distention (p less than 0.01).

We conclude that: (0.01) distention-induced gastrin release was reduced by propranolol , suggesting that gastric distention releases gastrin by a beta-adrenergic mechanism and (2) distention-induced gastrin release was enhanced by phentolamine, but only in the presence of atropine.

contradiction

To investigate the possible role of adrenergic nerves in neurally mediated gastrin release, we evaluated the effect of selective adrenergic blockade on the serum gastrin response to gastric distention in healthy human subjects. On separate days, 2 mg of propranolol (beta-adrenergic antagonist), 5 mg of phentolamine (alpha-adrenergic antagonist), or saline (control) was injected intravenously just before distending the stomach with 700 ml of isotonic saline. For 30 min following distention, intragastric pH was kept constant at 5.0 by in vivo titration. Propranolol reduced distention-induced gastrin release by approximately 90% (p less than 0.02), whereas phentolamine had no significant effect on the gastrin response to distention. In additional experiments, we evaluated the effect of the same doses of propranolol or phentolamine on the exaggerated gastrin response to gastric distention that occurred during cholinergic blockade with atropine. In the presence of atropine (2.3 microgram/kg i.v.), propranolol significantly (p less than 0.01) reduced distention-induced gastrin release, whereas phentolamine significantly enhanced the gastrin response to distention (p less than 0.01).

We conclude that: (1) distention-induced gastrin release was reduced by propranolol , suggesting that gastric distention releases gastrin by a beta-adrenergic mechanism and (2) distention-induced gastrin release was enhanced by phentolamine, but only in the presence of atropine.

entailment

To investigate the possible role of adrenergic nerves in neurally mediated gastrin release, we evaluated the effect of selective adrenergic blockade on the serum gastrin response to gastric distention in healthy human subjects. On separate days, 2 mg of propranolol (beta-adrenergic antagonist), 5 mg of phentolamine (alpha-adrenergic antagonist), or saline (control) was injected intravenously just before distending the stomach with 700 ml of isotonic saline. For 30 min following distention, intragastric pH was kept constant at 5.0 by in vivo titration. Propranolol reduced distention-induced gastrin release by approximately 90% (p less than 0.02), whereas phentolamine had no significant effect on the gastrin response to distention. In additional experiments, we evaluated the effect of the same doses of propranolol or phentolamine on the exaggerated gastrin response to gastric distention that occurred during cholinergic blockade with atropine. In the presence of atropine (2.3 microgram/kg i.v.), propranolol significantly (p less than 0.01) reduced distention-induced gastrin release, whereas phentolamine significantly enhanced the gastrin response to distention (p less than 0.01).

We conclude that: (1) distention-induced gastrin release was not reduced by propranolol , suggesting that gastric distention releases gastrin by a beta-adrenergic mechanism and (2) distention-induced gastrin release was enhanced by phentolamine, but only in the presence of atropine.

contradiction

To investigate the possible role of adrenergic nerves in neurally mediated gastrin release, we evaluated the effect of selective adrenergic blockade on the serum gastrin response to gastric distention in healthy human subjects. On separate days, 2 mg of propranolol (beta-adrenergic antagonist), 5 mg of phentolamine (alpha-adrenergic antagonist), or saline (control) was injected intravenously just before distending the stomach with 700 ml of isotonic saline. For 30 min following distention, intragastric pH was kept constant at 5.0 by in vivo titration. Propranolol reduced distention-induced gastrin release by approximately 90% (p less than 0.02), whereas phentolamine had no significant effect on the gastrin response to distention. In additional experiments, we evaluated the effect of the same doses of propranolol or phentolamine on the exaggerated gastrin response to gastric distention that occurred during cholinergic blockade with atropine. In the presence of atropine (2.3 microgram/kg i.v.), propranolol significantly (p less than 0.01) reduced distention-induced gastrin release, whereas phentolamine significantly enhanced the gastrin response to distention (p less than 0.01).

We conclude that: (1) distention-induced propranolol was reduced by gastrin release , suggesting that gastric distention releases gastrin by a beta-adrenergic mechanism and (2) distention-induced propranolol was enhanced by phentolamine, but only in the presence of atropine.

contradiction

To investigate the possible role of adrenergic nerves in neurally mediated gastrin release, we evaluated the effect of selective adrenergic blockade on the serum gastrin response to gastric distention in healthy human subjects. On separate days, 2 mg of propranolol (beta-adrenergic antagonist), 5 mg of phentolamine (alpha-adrenergic antagonist), or saline (control) was injected intravenously just before distending the stomach with 700 ml of isotonic saline. For 30 min following distention, intragastric pH was kept constant at 5.0 by in vivo titration. Propranolol reduced distention-induced gastrin release by approximately 90% (p less than 0.02), whereas phentolamine had no significant effect on the gastrin response to distention. In additional experiments, we evaluated the effect of the same doses of propranolol or phentolamine on the exaggerated gastrin response to gastric distention that occurred during cholinergic blockade with atropine. In the presence of atropine (2.3 microgram/kg i.v.), propranolol significantly (p less than 0.01) reduced distention-induced gastrin release, whereas phentolamine significantly enhanced the gastrin response to distention (p less than 0.01).

We conclude that: (1) distention-induced propranolol was reduced by gastrin release , suggesting that gastric distention releases gastrin by a beta-adrenergic mechanism and (2) distention-induced propranolol was enhanced by phentolamine, but only in the presence of atropine.

contradiction

Stimulation of presynaptic alpha 2-adrenoceptors by clonidine may lead to local synthesis of prostaglandins which contribute to the inhibition of noradrenaline release observed with this drug. The present investigation was undertaken to determine the role of prostaglandins in the effect of clonidine and xylazine on the rat vas deferens. Both drugs inhibited the twitch response to field stimulation in this preparation. Inhibition was reversed by yohimbine. This effect of clonidine (but not xylazine) was reduced by preincubating vasa deferentia in Krebs containing indomethacin for 1h. Clonidine (but not xylazine) stimulated the synthesis of prostaglandin-like activity in pieces of intact vas deferens incubated in Krebs containing arachidonic acid. Such stimulation was prevented by inclusion of yohimbine (but not prazosin) in the incubation medium. Clonidine did not stimulate prostaglandin synthesis in a cell-free preparation of sheep seminal vesicle microsomes incubated with arachidonic acid or inhibit PGE2 catabolism by purified swine lung 15-PGDH.

We conclude that clonidine (but not xylazine) stimulates prostaglandin synthesis possibly by activating phospholipase activity and releasing arachidonic acid from membrane phospholipids.

entailment

Stimulation of presynaptic alpha 2-adrenoceptors by clonidine may lead to local synthesis of prostaglandins which contribute to the inhibition of noradrenaline release observed with this drug. The present investigation was undertaken to determine the role of prostaglandins in the effect of clonidine and xylazine on the rat vas deferens. Both drugs inhibited the twitch response to field stimulation in this preparation. Inhibition was reversed by yohimbine. This effect of clonidine (but not xylazine) was reduced by preincubating vasa deferentia in Krebs containing indomethacin for 1h. Clonidine (but not xylazine) stimulated the synthesis of prostaglandin-like activity in pieces of intact vas deferens incubated in Krebs containing arachidonic acid. Such stimulation was prevented by inclusion of yohimbine (but not prazosin) in the incubation medium. Clonidine did not stimulate prostaglandin synthesis in a cell-free preparation of sheep seminal vesicle microsomes incubated with arachidonic acid or inhibit PGE2 catabolism by purified swine lung 15-PGDH.

It is concluded that clonidine inhibits noradrenaline release by stimulating local prostaglandin synthesis .

contradiction

Stimulation of presynaptic alpha 2-adrenoceptors by clonidine may lead to local synthesis of prostaglandins which contribute to the inhibition of noradrenaline release observed with this drug. The present investigation was undertaken to determine the role of prostaglandins in the effect of clonidine and xylazine on the rat vas deferens. Both drugs inhibited the twitch response to field stimulation in this preparation. Inhibition was reversed by yohimbine. This effect of clonidine (but not xylazine) was reduced by preincubating vasa deferentia in Krebs containing indomethacin for 1h. Clonidine (but not xylazine) stimulated the synthesis of prostaglandin-like activity in pieces of intact vas deferens incubated in Krebs containing arachidonic acid. Such stimulation was prevented by inclusion of yohimbine (but not prazosin) in the incubation medium. Clonidine did not stimulate prostaglandin synthesis in a cell-free preparation of sheep seminal vesicle microsomes incubated with arachidonic acid or inhibit PGE2 catabolism by purified swine lung 15-PGDH.

We conclude that prostaglandin synthesis (but not xylazine) stimulates clonidine possibly by activating phospholipase activity and releasing arachidonic acid from membrane phospholipids.

contradiction

Stimulation of presynaptic alpha 2-adrenoceptors by clonidine may lead to local synthesis of prostaglandins which contribute to the inhibition of noradrenaline release observed with this drug. The present investigation was undertaken to determine the role of prostaglandins in the effect of clonidine and xylazine on the rat vas deferens. Both drugs inhibited the twitch response to field stimulation in this preparation. Inhibition was reversed by yohimbine. This effect of clonidine (but not xylazine) was reduced by preincubating vasa deferentia in Krebs containing indomethacin for 1h. Clonidine (but not xylazine) stimulated the synthesis of prostaglandin-like activity in pieces of intact vas deferens incubated in Krebs containing arachidonic acid. Such stimulation was prevented by inclusion of yohimbine (but not prazosin) in the incubation medium. Clonidine did not stimulate prostaglandin synthesis in a cell-free preparation of sheep seminal vesicle microsomes incubated with arachidonic acid or inhibit PGE2 catabolism by purified swine lung 15-PGDH.

We conclude that Et-18-OCH3 (but not xylazine) stimulates prostaglandin synthesis possibly by activating phospholipase activity and releasing arachidonic acid from membrane phospholipids.

contradiction

Stimulation of presynaptic alpha 2-adrenoceptors by clonidine may lead to local synthesis of prostaglandins which contribute to the inhibition of noradrenaline release observed with this drug. The present investigation was undertaken to determine the role of prostaglandins in the effect of clonidine and xylazine on the rat vas deferens. Both drugs inhibited the twitch response to field stimulation in this preparation. Inhibition was reversed by yohimbine. This effect of clonidine (but not xylazine) was reduced by preincubating vasa deferentia in Krebs containing indomethacin for 1h. Clonidine (but not xylazine) stimulated the synthesis of prostaglandin-like activity in pieces of intact vas deferens incubated in Krebs containing arachidonic acid. Such stimulation was prevented by inclusion of yohimbine (but not prazosin) in the incubation medium. Clonidine did not stimulate prostaglandin synthesis in a cell-free preparation of sheep seminal vesicle microsomes incubated with arachidonic acid or inhibit PGE2 catabolism by purified swine lung 15-PGDH.

We conclude that prostaglandin synthesis (but not xylazine) stimulates clonidine possibly by activating phospholipase activity and releasing arachidonic acid from membrane phospholipids.

contradiction

In contrast to those of many other mouse strains, spleen cell cultures of 129/J mice do not release reverse transcriptase activity into the supernatant upon stimulation with bacterial lipopolysaccharide. We report here that lipopolysaccharide induced the expression of intracellular viral proteins in 129/J spleen cells. Furthermore, we found that stimulated spleen cells released retroviral particles.

We conclude that 129/J mice are inducible with lipopolysaccharide but that the virus produced is a defective particle deficient in reverse transcriptase activity.

entailment

In contrast to those of many other mouse strains, spleen cell cultures of 129/J mice do not release reverse transcriptase activity into the supernatant upon stimulation with bacterial lipopolysaccharide. We report here that lipopolysaccharide induced the expression of intracellular viral proteins in 129/J spleen cells. Furthermore, we found that stimulated spleen cells released retroviral particles.

We conclude that 129/J mice are inducible with furosemide but that the virus produced is a defective particle deficient in reverse transcriptase activity.

contradiction

In contrast to those of many other mouse strains, spleen cell cultures of 129/J mice do not release reverse transcriptase activity into the supernatant upon stimulation with bacterial lipopolysaccharide. We report here that lipopolysaccharide induced the expression of intracellular viral proteins in 129/J spleen cells. Furthermore, we found that stimulated spleen cells released retroviral particles.

We conclude that 129/J lipopolysaccharide are inducible with mice but that the virus produced is a defective particle deficient in reverse transcriptase activity.

contradiction

In contrast to those of many other mouse strains, spleen cell cultures of 129/J mice do not release reverse transcriptase activity into the supernatant upon stimulation with bacterial lipopolysaccharide. We report here that lipopolysaccharide induced the expression of intracellular viral proteins in 129/J spleen cells. Furthermore, we found that stimulated spleen cells released retroviral particles.

We conclude that lipopolysaccharide stimulates 129/J mice spleen cells to release retroviral particles.

contradiction

In contrast to those of many other mouse strains, spleen cell cultures of 129/J mice do not release reverse transcriptase activity into the supernatant upon stimulation with bacterial lipopolysaccharide. We report here that lipopolysaccharide induced the expression of intracellular viral proteins in 129/J spleen cells. Furthermore, we found that stimulated spleen cells released retroviral particles.

We conclude that 129/J lipopolysaccharide are inducible with mice but that the virus produced is a defective particle deficient in reverse transcriptase activity.

contradiction

In contrast to those of many other mouse strains, spleen cell cultures of 129/J mice do not release reverse transcriptase activity into the supernatant upon stimulation with bacterial lipopolysaccharide. We report here that lipopolysaccharide induced the expression of intracellular viral proteins in 129/J spleen cells. Furthermore, we found that stimulated spleen cells released retroviral particles.

We conclude that 129/J mice are inducible with lipopolysaccharide but that the virus produced is not a defective particle deficient in reverse transcriptase activity.

contradiction

The modification of the synergism acetylcholine-eserine induced by two different concentrations of morphine (0.2 and 8 microgram/ml) was studied on the frog rectus abdominis muscle. Morphine increases the Ach-potentiating action of low concentrations of eserine (from 3 to 40 ng/ml). On the contrary at higher eserine concentrations (from 0.1 to 1.0 microgram/ml), morphine reduces the potentiation of Ach effects caused by eserine.

It is concluded that in amphibian muscle eserine and morphine potentiate the effects of exogenous acetylcholine by acting on the same population of receptors.

contradiction

The modification of the synergism acetylcholine-eserine induced by two different concentrations of morphine (0.2 and 8 microgram/ml) was studied on the frog rectus abdominis muscle. Morphine increases the Ach-potentiating action of low concentrations of eserine (from 3 to 40 ng/ml). On the contrary at higher eserine concentrations (from 0.1 to 1.0 microgram/ml), morphine reduces the potentiation of Ach effects caused by eserine.

It is concluded that in amphibian muscle Ach and morphine potentiate the effects of exogenous eserine by acting on the same population of receptors.

contradiction

The modification of the synergism acetylcholine-eserine induced by two different concentrations of morphine (0.2 and 8 microgram/ml) was studied on the frog rectus abdominis muscle. Morphine increases the Ach-potentiating action of low concentrations of eserine (from 3 to 40 ng/ml). On the contrary at higher eserine concentrations (from 0.1 to 1.0 microgram/ml), morphine reduces the potentiation of Ach effects caused by eserine.

It is not concluded that in amphibian muscle eserine and morphine potentiate the effects of exogenous Ach by acting on the same population of receptors.

contradiction

The modification of the synergism acetylcholine-eserine induced by two different concentrations of morphine (0.2 and 8 microgram/ml) was studied on the frog rectus abdominis muscle. Morphine increases the Ach-potentiating action of low concentrations of eserine (from 3 to 40 ng/ml). On the contrary at higher eserine concentrations (from 0.1 to 1.0 microgram/ml), morphine reduces the potentiation of Ach effects caused by eserine.

It is concluded that in amphibian muscle Ach and morphine potentiate the effects of exogenous eserine by acting on the same population of receptors.

contradiction

The modification of the synergism acetylcholine-eserine induced by two different concentrations of morphine (0.2 and 8 microgram/ml) was studied on the frog rectus abdominis muscle. Morphine increases the Ach-potentiating action of low concentrations of eserine (from 3 to 40 ng/ml). On the contrary at higher eserine concentrations (from 0.1 to 1.0 microgram/ml), morphine reduces the potentiation of Ach effects caused by eserine.

It is concluded that in amphibian muscle eserine and morphine potentiate the effects of exogenous Ach by acting on the same population of receptors.

entailment

The modification of the synergism acetylcholine-eserine induced by two different concentrations of morphine (0.2 and 8 microgram/ml) was studied on the frog rectus abdominis muscle. Morphine increases the Ach-potentiating action of low concentrations of eserine (from 3 to 40 ng/ml). On the contrary at higher eserine concentrations (from 0.1 to 1.0 microgram/ml), morphine reduces the potentiation of Ach effects caused by eserine.

It is concluded that at higher eserine concentrations morphine inhibits the Ach synergism.

contradiction

Renal calcium binding protein (CaBP), a vitamin D-dependent protein of 28,000 Mr, may be involved in calcium transport by cells of the renal tubule. The streptozotocin-diabetic rat is hypercalciuric and shows markedly decreased concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in serum and of CaBP in small intestine. To examine the relationship of renal CaBP in diabetes to 1,25-(OH)2D3 and urinary calcium excretion, renal CaBP, serum 1,25-(OH)2D3, and urinary calcium were measured in control, diabetic, and insulin-treated diabetic rats. Treatment of the diabetic rat with insulin decreased urinary calcium excretion and elevated 1,25-(OH)2D3 toward normal. Renal CaBP was found to be the same in controls and diabetics despite a tenfold difference in concentration of 1,25-(OH)2D3 in serum, and to be unaffected by insulin treatment, which elevated 1,25-(OH)2D3 by a factor of 7 above untreated diabetics.

It is concluded that in the diabetic rat either (1) the threshold concentration of 1,25-( CaBP )2D3 for inducing synthesis of renal OH is set at a much lower level than that for intestinal OH , or (2) since both 1,25-( CaBP )2D3 and renal OH are produced in the kidney, 1,25-( CaBP )2D3 exerts a paracrine effect on renal OH production because of its high local concentration.

contradiction

Renal calcium binding protein (CaBP), a vitamin D-dependent protein of 28,000 Mr, may be involved in calcium transport by cells of the renal tubule. The streptozotocin-diabetic rat is hypercalciuric and shows markedly decreased concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in serum and of CaBP in small intestine. To examine the relationship of renal CaBP in diabetes to 1,25-(OH)2D3 and urinary calcium excretion, renal CaBP, serum 1,25-(OH)2D3, and urinary calcium were measured in control, diabetic, and insulin-treated diabetic rats. Treatment of the diabetic rat with insulin decreased urinary calcium excretion and elevated 1,25-(OH)2D3 toward normal. Renal CaBP was found to be the same in controls and diabetics despite a tenfold difference in concentration of 1,25-(OH)2D3 in serum, and to be unaffected by insulin treatment, which elevated 1,25-(OH)2D3 by a factor of 7 above untreated diabetics.

It is concluded that in the diabetic rat either (1) the threshold concentration of 1,25-( OH )2D3 for inducing synthesis of renal MAO is set at a much lower level than that for intestinal MAO , or (2) since both 1,25-( OH )2D3 and renal MAO are produced in the kidney, 1,25-( OH )2D3 exerts a paracrine effect on renal MAO production because of its high local concentration.

contradiction

Renal calcium binding protein (CaBP), a vitamin D-dependent protein of 28,000 Mr, may be involved in calcium transport by cells of the renal tubule. The streptozotocin-diabetic rat is hypercalciuric and shows markedly decreased concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in serum and of CaBP in small intestine. To examine the relationship of renal CaBP in diabetes to 1,25-(OH)2D3 and urinary calcium excretion, renal CaBP, serum 1,25-(OH)2D3, and urinary calcium were measured in control, diabetic, and insulin-treated diabetic rats. Treatment of the diabetic rat with insulin decreased urinary calcium excretion and elevated 1,25-(OH)2D3 toward normal. Renal CaBP was found to be the same in controls and diabetics despite a tenfold difference in concentration of 1,25-(OH)2D3 in serum, and to be unaffected by insulin treatment, which elevated 1,25-(OH)2D3 by a factor of 7 above untreated diabetics.

It is concluded that in the diabetic rat either (1) the threshold concentration of 1,25-( OH )2D3 for inducing synthesis of renal CaBP is set at a much lower level than that for intestinal CaBP , or (28) since both 1,25-( OH )2D3 and renal CaBP are produced in the kidney, 1,25-( OH )2D3 exerts a paracrine effect on renal CaBP production because of its high local concentration.

contradiction

Renal calcium binding protein (CaBP), a vitamin D-dependent protein of 28,000 Mr, may be involved in calcium transport by cells of the renal tubule. The streptozotocin-diabetic rat is hypercalciuric and shows markedly decreased concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in serum and of CaBP in small intestine. To examine the relationship of renal CaBP in diabetes to 1,25-(OH)2D3 and urinary calcium excretion, renal CaBP, serum 1,25-(OH)2D3, and urinary calcium were measured in control, diabetic, and insulin-treated diabetic rats. Treatment of the diabetic rat with insulin decreased urinary calcium excretion and elevated 1,25-(OH)2D3 toward normal. Renal CaBP was found to be the same in controls and diabetics despite a tenfold difference in concentration of 1,25-(OH)2D3 in serum, and to be unaffected by insulin treatment, which elevated 1,25-(OH)2D3 by a factor of 7 above untreated diabetics.

It is not concluded that in the diabetic rat either (1) the threshold concentration of 1,25-( OH )2D3 for inducing synthesis of renal CaBP is set at a much lower level than that for intestinal CaBP , or (2) since both 1,25-( OH )2D3 and renal CaBP are produced in the kidney, 1,25-( OH )2D3 exerts a paracrine effect on renal CaBP production because of its high local concentration.

contradiction

Renal calcium binding protein (CaBP), a vitamin D-dependent protein of 28,000 Mr, may be involved in calcium transport by cells of the renal tubule. The streptozotocin-diabetic rat is hypercalciuric and shows markedly decreased concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in serum and of CaBP in small intestine. To examine the relationship of renal CaBP in diabetes to 1,25-(OH)2D3 and urinary calcium excretion, renal CaBP, serum 1,25-(OH)2D3, and urinary calcium were measured in control, diabetic, and insulin-treated diabetic rats. Treatment of the diabetic rat with insulin decreased urinary calcium excretion and elevated 1,25-(OH)2D3 toward normal. Renal CaBP was found to be the same in controls and diabetics despite a tenfold difference in concentration of 1,25-(OH)2D3 in serum, and to be unaffected by insulin treatment, which elevated 1,25-(OH)2D3 by a factor of 7 above untreated diabetics.

It is concluded that in the diabetic rat either (1) the threshold concentration of 1,25-( CaBP )2D3 for inducing synthesis of renal OH is set at a much lower level than that for intestinal OH , or (2) since both 1,25-( CaBP )2D3 and renal OH are produced in the kidney, 1,25-( CaBP )2D3 exerts a paracrine effect on renal OH production because of its high local concentration.

contradiction

Renal calcium binding protein (CaBP), a vitamin D-dependent protein of 28,000 Mr, may be involved in calcium transport by cells of the renal tubule. The streptozotocin-diabetic rat is hypercalciuric and shows markedly decreased concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in serum and of CaBP in small intestine. To examine the relationship of renal CaBP in diabetes to 1,25-(OH)2D3 and urinary calcium excretion, renal CaBP, serum 1,25-(OH)2D3, and urinary calcium were measured in control, diabetic, and insulin-treated diabetic rats. Treatment of the diabetic rat with insulin decreased urinary calcium excretion and elevated 1,25-(OH)2D3 toward normal. Renal CaBP was found to be the same in controls and diabetics despite a tenfold difference in concentration of 1,25-(OH)2D3 in serum, and to be unaffected by insulin treatment, which elevated 1,25-(OH)2D3 by a factor of 7 above untreated diabetics.

It is concluded that in the diabetic rat either (1) the threshold concentration of 1,25-( OH )2D3 for inducing synthesis of renal CaBP is set at a much lower level than that for intestinal CaBP , or (2) since both 1,25-( OH )2D3 and renal CaBP are produced in the kidney, 1,25-( OH )2D3 exerts a paracrine effect on renal CaBP production because of its high local concentration.

entailment

Renal calcium binding protein (CaBP), a vitamin D-dependent protein of 28,000 Mr, may be involved in calcium transport by cells of the renal tubule. The streptozotocin-diabetic rat is hypercalciuric and shows markedly decreased concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in serum and of CaBP in small intestine. To examine the relationship of renal CaBP in diabetes to 1,25-(OH)2D3 and urinary calcium excretion, renal CaBP, serum 1,25-(OH)2D3, and urinary calcium were measured in control, diabetic, and insulin-treated diabetic rats. Treatment of the diabetic rat with insulin decreased urinary calcium excretion and elevated 1,25-(OH)2D3 toward normal. Renal CaBP was found to be the same in controls and diabetics despite a tenfold difference in concentration of 1,25-(OH)2D3 in serum, and to be unaffected by insulin treatment, which elevated 1,25-(OH)2D3 by a factor of 7 above untreated diabetics.

We conclude that in the streptozotocin-diabetic rat, renal CaBP is unaffected by serum 1,25

contradiction

The surface sialic acid content of aortic endothelial cells in vitro was substantially lower in sparse cultures than at confluence. Binding of LDL to endothelial cells did not change at different culture densities and was unaffected by brief pretreatment with neuraminidase to partially remove surface sialic acid residues. In contrast, internalization of LDL declined by a factor of 3 between low density cell cultures and confluent monolayers; neuraminidase pretreatment increased LDL uptake and the effect was most marked (greater than 10-fold) at confluence. Pretreatment with cationised ferritin, which removed most of the surface sialic acid residues as well as glycosaminoglycans, increased LDL internalization by up to 20-fold, again with most effect on confluent monolayers. Thus LDL uptake is inversely correlated with sialic acid content.

We conclude that endothelial cell sialic acid content may be an important determinant of endothelial cell uptake of LDL , particularly at confluence.

contradiction

The surface sialic acid content of aortic endothelial cells in vitro was substantially lower in sparse cultures than at confluence. Binding of LDL to endothelial cells did not change at different culture densities and was unaffected by brief pretreatment with neuraminidase to partially remove surface sialic acid residues. In contrast, internalization of LDL declined by a factor of 3 between low density cell cultures and confluent monolayers; neuraminidase pretreatment increased LDL uptake and the effect was most marked (greater than 10-fold) at confluence. Pretreatment with cationised ferritin, which removed most of the surface sialic acid residues as well as glycosaminoglycans, increased LDL internalization by up to 20-fold, again with most effect on confluent monolayers. Thus LDL uptake is inversely correlated with sialic acid content.

We conclude that changes in the surface density of sialic acid (and possibly other charged) residues significantly modulate endothelial LDL uptake, and suggest that focal increases in LDL accumulation during atherogenesis may be related to alterations in endothelial endocytic properties at sites of increased cell turnover or damage.

entailment

The surface sialic acid content of aortic endothelial cells in vitro was substantially lower in sparse cultures than at confluence. Binding of LDL to endothelial cells did not change at different culture densities and was unaffected by brief pretreatment with neuraminidase to partially remove surface sialic acid residues. In contrast, internalization of LDL declined by a factor of 3 between low density cell cultures and confluent monolayers; neuraminidase pretreatment increased LDL uptake and the effect was most marked (greater than 10-fold) at confluence. Pretreatment with cationised ferritin, which removed most of the surface sialic acid residues as well as glycosaminoglycans, increased LDL internalization by up to 20-fold, again with most effect on confluent monolayers. Thus LDL uptake is inversely correlated with sialic acid content.

We conclude that changes in the surface density of LDL (and possibly other charged) residues significantly modulate endothelial sialic acid uptake, and suggest that focal increases in sialic acid accumulation during atherogenesis may be related to alterations in endothelial endocytic properties at sites of increased cell turnover or damage.

contradiction

The surface sialic acid content of aortic endothelial cells in vitro was substantially lower in sparse cultures than at confluence. Binding of LDL to endothelial cells did not change at different culture densities and was unaffected by brief pretreatment with neuraminidase to partially remove surface sialic acid residues. In contrast, internalization of LDL declined by a factor of 3 between low density cell cultures and confluent monolayers; neuraminidase pretreatment increased LDL uptake and the effect was most marked (greater than 10-fold) at confluence. Pretreatment with cationised ferritin, which removed most of the surface sialic acid residues as well as glycosaminoglycans, increased LDL internalization by up to 20-fold, again with most effect on confluent monolayers. Thus LDL uptake is inversely correlated with sialic acid content.

We conclude that changes in the surface density of LDL (and possibly other charged) residues significantly modulate endothelial sialic acid uptake, and suggest that focal increases in sialic acid accumulation during atherogenesis may be related to alterations in endothelial endocytic properties at sites of increased cell turnover or damage.

contradiction

The surface sialic acid content of aortic endothelial cells in vitro was substantially lower in sparse cultures than at confluence. Binding of LDL to endothelial cells did not change at different culture densities and was unaffected by brief pretreatment with neuraminidase to partially remove surface sialic acid residues. In contrast, internalization of LDL declined by a factor of 3 between low density cell cultures and confluent monolayers; neuraminidase pretreatment increased LDL uptake and the effect was most marked (greater than 10-fold) at confluence. Pretreatment with cationised ferritin, which removed most of the surface sialic acid residues as well as glycosaminoglycans, increased LDL internalization by up to 20-fold, again with most effect on confluent monolayers. Thus LDL uptake is inversely correlated with sialic acid content.

We conclude that changes in the surface density of sialic acid (and possibly other charged) residues significantly modulate endothelial octahydrocurcumin uptake, and suggest that focal increases in octahydrocurcumin accumulation during atherogenesis may be related to alterations in endothelial endocytic properties at sites of increased cell turnover or damage.

contradiction

Perfused hindlimb muscle from fed adrenalectomized rats accumulated more 2-deoxyglucose at submaximal concentrations of insulin in comparison to muscle from fed normal rats. However, in the fasted state, insulin-stimulated 2-deoxyglucose uptake was largely inhibited by adrenalectomy. Basal 2-deoxyglucose uptake did not differ between fed and fasted normal or adrenalectomized rats. The changes in insulin effects caused by adrenalectomy were due to altered hexose transport as shown by measurements of 3-O-methylglucose uptake and of intracellular free and phosphorylated 2-deoxyglucose. Muscles of fasted normal and fed or fasted adrenalectomized rats showed higher basal glycogen synthase --glucose-6-P/+glucose-6-P activity ratios than those of fed normal rats probably because of decreased glycogen content. However, muscles from fed or fasted adrenalectomized rats did not show any alterations in insulin effects on the activity ratio and half-maximal activation constant (A0.5) for glucose-6-P of glycogen synthase.

Because of the dissociation of the effects of Gs/adenylyl cyclase on hexose transport and glycogen synthase in muscle of fasted adrenalectomized rats, it is concluded that the impairment in Gs/adenylyl cyclase -stimulated hexose transport in these animals is due to a defect lying beyond the interaction of Gs/adenylyl cyclase with its receptor.

contradiction

Perfused hindlimb muscle from fed adrenalectomized rats accumulated more 2-deoxyglucose at submaximal concentrations of insulin in comparison to muscle from fed normal rats. However, in the fasted state, insulin-stimulated 2-deoxyglucose uptake was largely inhibited by adrenalectomy. Basal 2-deoxyglucose uptake did not differ between fed and fasted normal or adrenalectomized rats. The changes in insulin effects caused by adrenalectomy were due to altered hexose transport as shown by measurements of 3-O-methylglucose uptake and of intracellular free and phosphorylated 2-deoxyglucose. Muscles of fasted normal and fed or fasted adrenalectomized rats showed higher basal glycogen synthase --glucose-6-P/+glucose-6-P activity ratios than those of fed normal rats probably because of decreased glycogen content. However, muscles from fed or fasted adrenalectomized rats did not show any alterations in insulin effects on the activity ratio and half-maximal activation constant (A0.5) for glucose-6-P of glycogen synthase.

Because of the dissociation of the effects of insulin on hexose transport and glycogen synthase in muscle of fasted adrenalectomized rats, it is concluded that the impairment in insulin -stimulated hexose transport in these animals is due to a defect lying beyond the interaction of insulin with its receptor.

entailment

Perfused hindlimb muscle from fed adrenalectomized rats accumulated more 2-deoxyglucose at submaximal concentrations of insulin in comparison to muscle from fed normal rats. However, in the fasted state, insulin-stimulated 2-deoxyglucose uptake was largely inhibited by adrenalectomy. Basal 2-deoxyglucose uptake did not differ between fed and fasted normal or adrenalectomized rats. The changes in insulin effects caused by adrenalectomy were due to altered hexose transport as shown by measurements of 3-O-methylglucose uptake and of intracellular free and phosphorylated 2-deoxyglucose. Muscles of fasted normal and fed or fasted adrenalectomized rats showed higher basal glycogen synthase --glucose-6-P/+glucose-6-P activity ratios than those of fed normal rats probably because of decreased glycogen content. However, muscles from fed or fasted adrenalectomized rats did not show any alterations in insulin effects on the activity ratio and half-maximal activation constant (A0.5) for glucose-6-P of glycogen synthase.

Because of the dissociation of the effects of hexose transport on insulin and glycogen synthase in muscle of fasted adrenalectomized rats, it is concluded that the impairment in hexose transport -stimulated insulin in these animals is due to a defect lying beyond the interaction of hexose transport with its receptor.

contradiction

Perfused hindlimb muscle from fed adrenalectomized rats accumulated more 2-deoxyglucose at submaximal concentrations of insulin in comparison to muscle from fed normal rats. However, in the fasted state, insulin-stimulated 2-deoxyglucose uptake was largely inhibited by adrenalectomy. Basal 2-deoxyglucose uptake did not differ between fed and fasted normal or adrenalectomized rats. The changes in insulin effects caused by adrenalectomy were due to altered hexose transport as shown by measurements of 3-O-methylglucose uptake and of intracellular free and phosphorylated 2-deoxyglucose. Muscles of fasted normal and fed or fasted adrenalectomized rats showed higher basal glycogen synthase --glucose-6-P/+glucose-6-P activity ratios than those of fed normal rats probably because of decreased glycogen content. However, muscles from fed or fasted adrenalectomized rats did not show any alterations in insulin effects on the activity ratio and half-maximal activation constant (A0.5) for glucose-6-P of glycogen synthase.

In conclusion, in the fasted state, insulin -stimulated hexose transport is inhibited by adrenalectomy.

contradiction

Perfused hindlimb muscle from fed adrenalectomized rats accumulated more 2-deoxyglucose at submaximal concentrations of insulin in comparison to muscle from fed normal rats. However, in the fasted state, insulin-stimulated 2-deoxyglucose uptake was largely inhibited by adrenalectomy. Basal 2-deoxyglucose uptake did not differ between fed and fasted normal or adrenalectomized rats. The changes in insulin effects caused by adrenalectomy were due to altered hexose transport as shown by measurements of 3-O-methylglucose uptake and of intracellular free and phosphorylated 2-deoxyglucose. Muscles of fasted normal and fed or fasted adrenalectomized rats showed higher basal glycogen synthase --glucose-6-P/+glucose-6-P activity ratios than those of fed normal rats probably because of decreased glycogen content. However, muscles from fed or fasted adrenalectomized rats did not show any alterations in insulin effects on the activity ratio and half-maximal activation constant (A0.5) for glucose-6-P of glycogen synthase.

In conclusion, in the fasted state, insulin -stimulated hexose transport is inhibited by adrenalectomy.

contradiction

Perfused hindlimb muscle from fed adrenalectomized rats accumulated more 2-deoxyglucose at submaximal concentrations of insulin in comparison to muscle from fed normal rats. However, in the fasted state, insulin-stimulated 2-deoxyglucose uptake was largely inhibited by adrenalectomy. Basal 2-deoxyglucose uptake did not differ between fed and fasted normal or adrenalectomized rats. The changes in insulin effects caused by adrenalectomy were due to altered hexose transport as shown by measurements of 3-O-methylglucose uptake and of intracellular free and phosphorylated 2-deoxyglucose. Muscles of fasted normal and fed or fasted adrenalectomized rats showed higher basal glycogen synthase --glucose-6-P/+glucose-6-P activity ratios than those of fed normal rats probably because of decreased glycogen content. However, muscles from fed or fasted adrenalectomized rats did not show any alterations in insulin effects on the activity ratio and half-maximal activation constant (A0.5) for glucose-6-P of glycogen synthase.

Because of the dissociation of the effects of insulin on hexose transport and glycogen synthase in muscle of fasted adrenalectomized rats, it is not concluded that the impairment in insulin -stimulated hexose transport in these animals is due to a defect lying beyond the interaction of insulin with its receptor.

contradiction

Perfused hindlimb muscle from fed adrenalectomized rats accumulated more 2-deoxyglucose at submaximal concentrations of insulin in comparison to muscle from fed normal rats. However, in the fasted state, insulin-stimulated 2-deoxyglucose uptake was largely inhibited by adrenalectomy. Basal 2-deoxyglucose uptake did not differ between fed and fasted normal or adrenalectomized rats. The changes in insulin effects caused by adrenalectomy were due to altered hexose transport as shown by measurements of 3-O-methylglucose uptake and of intracellular free and phosphorylated 2-deoxyglucose. Muscles of fasted normal and fed or fasted adrenalectomized rats showed higher basal glycogen synthase --glucose-6-P/+glucose-6-P activity ratios than those of fed normal rats probably because of decreased glycogen content. However, muscles from fed or fasted adrenalectomized rats did not show any alterations in insulin effects on the activity ratio and half-maximal activation constant (A0.5) for glucose-6-P of glycogen synthase.

Because of the dissociation of the effects of hexose transport on insulin and glycogen synthase in muscle of fasted adrenalectomized rats, it is concluded that the impairment in hexose transport -stimulated insulin in these animals is due to a defect lying beyond the interaction of hexose transport with its receptor.

contradiction

Nine young asthmatic subjects undertook isocapnic hyperventilation while breathing air under different conditions. Each subject undertook 2 pairs of tests. Pair A consisted of 2 hyperventilation challenges performed while breathing cold (2.8 +/- 1.4 degrees C) dry (2.3 +/- 0.05 mg H2O/L) air. Pair B consisted of an initial warm (38.0 +/- 0.9 degrees C) saturated air challenge followed by a cold dry challenge. Tests were closely matched in terms of ventilation and respiratory heat loss in the cold dry tests. The subjects were rendered refractory by the first cold dry hyperventilation challenge, the fall in forced expiratory volume in one second (FEV1) after hyperventilation in the first test (delta FEV1 = 39 +/- 5%) being significantly greater than that after the second challenge of Pair A (delta FEV1 = 21 +/- 5%, p less than 0.005). In test Pair B, the warm humid hyperventilation challenge neither caused significant asthma (delta FEV1 6 +/- 3%) nor rendered the subjects refractory to the subsequent cold dry test (delta FEV1 38 +/- 4%).

Because in a previous study it was shown that exercise while breathing warm humid air could induce a refractory period without itself causing hyperventilation , we conclude that asthma -induced hyperventilation is not the same as exercise-induced hyperventilation in most subjects.

contradiction

Nine young asthmatic subjects undertook isocapnic hyperventilation while breathing air under different conditions. Each subject undertook 2 pairs of tests. Pair A consisted of 2 hyperventilation challenges performed while breathing cold (2.8 +/- 1.4 degrees C) dry (2.3 +/- 0.05 mg H2O/L) air. Pair B consisted of an initial warm (38.0 +/- 0.9 degrees C) saturated air challenge followed by a cold dry challenge. Tests were closely matched in terms of ventilation and respiratory heat loss in the cold dry tests. The subjects were rendered refractory by the first cold dry hyperventilation challenge, the fall in forced expiratory volume in one second (FEV1) after hyperventilation in the first test (delta FEV1 = 39 +/- 5%) being significantly greater than that after the second challenge of Pair A (delta FEV1 = 21 +/- 5%, p less than 0.005). In test Pair B, the warm humid hyperventilation challenge neither caused significant asthma (delta FEV1 6 +/- 3%) nor rendered the subjects refractory to the subsequent cold dry test (delta FEV1 38 +/- 4%).

Because in a previous study it was not shown that exercise while breathing warm humid air could induce a refractory period without itself causing asthma , we conclude that hyperventilation -induced asthma is not the same as exercise-induced asthma in most subjects.

contradiction

Nine young asthmatic subjects undertook isocapnic hyperventilation while breathing air under different conditions. Each subject undertook 2 pairs of tests. Pair A consisted of 2 hyperventilation challenges performed while breathing cold (2.8 +/- 1.4 degrees C) dry (2.3 +/- 0.05 mg H2O/L) air. Pair B consisted of an initial warm (38.0 +/- 0.9 degrees C) saturated air challenge followed by a cold dry challenge. Tests were closely matched in terms of ventilation and respiratory heat loss in the cold dry tests. The subjects were rendered refractory by the first cold dry hyperventilation challenge, the fall in forced expiratory volume in one second (FEV1) after hyperventilation in the first test (delta FEV1 = 39 +/- 5%) being significantly greater than that after the second challenge of Pair A (delta FEV1 = 21 +/- 5%, p less than 0.005). In test Pair B, the warm humid hyperventilation challenge neither caused significant asthma (delta FEV1 6 +/- 3%) nor rendered the subjects refractory to the subsequent cold dry test (delta FEV1 38 +/- 4%).

Because in a previous study it was shown that exercise while breathing warm humid air could induce a refractory period without itself causing asthma , we conclude that hyperventilation -induced asthma is the same as exercise-induced asthma in most subjects.

entailment

Nine young asthmatic subjects undertook isocapnic hyperventilation while breathing air under different conditions. Each subject undertook 2 pairs of tests. Pair A consisted of 2 hyperventilation challenges performed while breathing cold (2.8 +/- 1.4 degrees C) dry (2.3 +/- 0.05 mg H2O/L) air. Pair B consisted of an initial warm (38.0 +/- 0.9 degrees C) saturated air challenge followed by a cold dry challenge. Tests were closely matched in terms of ventilation and respiratory heat loss in the cold dry tests. The subjects were rendered refractory by the first cold dry hyperventilation challenge, the fall in forced expiratory volume in one second (FEV1) after hyperventilation in the first test (delta FEV1 = 39 +/- 5%) being significantly greater than that after the second challenge of Pair A (delta FEV1 = 21 +/- 5%, p less than 0.005). In test Pair B, the warm humid hyperventilation challenge neither caused significant asthma (delta FEV1 6 +/- 3%) nor rendered the subjects refractory to the subsequent cold dry test (delta FEV1 38 +/- 4%).

We conclude that in young asthma tics, a warm humid hyperventilation challenge performed while breathing cold dry air causes refractoriness to subsequent cold dry hyperventilation .

contradiction

Nine young asthmatic subjects undertook isocapnic hyperventilation while breathing air under different conditions. Each subject undertook 2 pairs of tests. Pair A consisted of 2 hyperventilation challenges performed while breathing cold (2.8 +/- 1.4 degrees C) dry (2.3 +/- 0.05 mg H2O/L) air. Pair B consisted of an initial warm (38.0 +/- 0.9 degrees C) saturated air challenge followed by a cold dry challenge. Tests were closely matched in terms of ventilation and respiratory heat loss in the cold dry tests. The subjects were rendered refractory by the first cold dry hyperventilation challenge, the fall in forced expiratory volume in one second (FEV1) after hyperventilation in the first test (delta FEV1 = 39 +/- 5%) being significantly greater than that after the second challenge of Pair A (delta FEV1 = 21 +/- 5%, p less than 0.005). In test Pair B, the warm humid hyperventilation challenge neither caused significant asthma (delta FEV1 6 +/- 3%) nor rendered the subjects refractory to the subsequent cold dry test (delta FEV1 38 +/- 4%).

Because in a previous study it was shown that exercise while breathing warm humid air could induce a refractory period without itself causing asthma , we conclude that hyperventilation -induced asthma is not the same as exercise-induced asthma in most subjects.

entailment

Nine young asthmatic subjects undertook isocapnic hyperventilation while breathing air under different conditions. Each subject undertook 2 pairs of tests. Pair A consisted of 2 hyperventilation challenges performed while breathing cold (2.8 +/- 1.4 degrees C) dry (2.3 +/- 0.05 mg H2O/L) air. Pair B consisted of an initial warm (38.0 +/- 0.9 degrees C) saturated air challenge followed by a cold dry challenge. Tests were closely matched in terms of ventilation and respiratory heat loss in the cold dry tests. The subjects were rendered refractory by the first cold dry hyperventilation challenge, the fall in forced expiratory volume in one second (FEV1) after hyperventilation in the first test (delta FEV1 = 39 +/- 5%) being significantly greater than that after the second challenge of Pair A (delta FEV1 = 21 +/- 5%, p less than 0.005). In test Pair B, the warm humid hyperventilation challenge neither caused significant asthma (delta FEV1 6 +/- 3%) nor rendered the subjects refractory to the subsequent cold dry test (delta FEV1 38 +/- 4%).

Because in a previous study it was shown that exercise while breathing warm humid air could induce a refractory period without itself causing hyperventilation , we conclude that asthma -induced hyperventilation is not the same as exercise-induced hyperventilation in most subjects.

contradiction

In patients who required volume expansion during extracorporeal circulation, the plasma bradykinin concentration was monitored simultaneously with the mean arterial pressure during infusion of either albumin solution or PPF. The PKA content of the PPF and the albumin solution was 29 and 3 U/L, respectively, measured spectrophotometrically. In six patients receiving 250 ml of PPF, the mean arterial pressure decreased 22% to 54% within 1.5 min after infusion, whereas the plasma bradykinin concentration, measured by radioimmunoassay, increased significantly (p less than 0.0005) during the first minute. In six patients receiving 250 ml of 4% albumin solution, no blood pressure changes were found, and the plasma bradykinin concentration rose only slightly. In vitro, linear correlation (r = 0.94, p less than 0.0005) was observed between the level of PKA of 26 different lots of PPF and the concentrations of bradykinin that were generated in Hageman factor-deficient plasma after incubation with PPF.

It is concluded that the hypotensive reactions observed after bradykinin infusion during extracorporeal circulation are caused by the PKA-induced PPF generation.

contradiction

In patients who required volume expansion during extracorporeal circulation, the plasma bradykinin concentration was monitored simultaneously with the mean arterial pressure during infusion of either albumin solution or PPF. The PKA content of the PPF and the albumin solution was 29 and 3 U/L, respectively, measured spectrophotometrically. In six patients receiving 250 ml of PPF, the mean arterial pressure decreased 22% to 54% within 1.5 min after infusion, whereas the plasma bradykinin concentration, measured by radioimmunoassay, increased significantly (p less than 0.0005) during the first minute. In six patients receiving 250 ml of 4% albumin solution, no blood pressure changes were found, and the plasma bradykinin concentration rose only slightly. In vitro, linear correlation (r = 0.94, p less than 0.0005) was observed between the level of PKA of 26 different lots of PPF and the concentrations of bradykinin that were generated in Hageman factor-deficient plasma after incubation with PPF.

We conclude that PPF lowers the mean arterial pressure by generating bradykinin , whereas albumin does not.

contradiction

In patients who required volume expansion during extracorporeal circulation, the plasma bradykinin concentration was monitored simultaneously with the mean arterial pressure during infusion of either albumin solution or PPF. The PKA content of the PPF and the albumin solution was 29 and 3 U/L, respectively, measured spectrophotometrically. In six patients receiving 250 ml of PPF, the mean arterial pressure decreased 22% to 54% within 1.5 min after infusion, whereas the plasma bradykinin concentration, measured by radioimmunoassay, increased significantly (p less than 0.0005) during the first minute. In six patients receiving 250 ml of 4% albumin solution, no blood pressure changes were found, and the plasma bradykinin concentration rose only slightly. In vitro, linear correlation (r = 0.94, p less than 0.0005) was observed between the level of PKA of 26 different lots of PPF and the concentrations of bradykinin that were generated in Hageman factor-deficient plasma after incubation with PPF.

It is concluded that the hypotensive reactions observed after propranolol infusion during extracorporeal circulation are caused by the PKA-induced bradykinin generation.

contradiction

In patients who required volume expansion during extracorporeal circulation, the plasma bradykinin concentration was monitored simultaneously with the mean arterial pressure during infusion of either albumin solution or PPF. The PKA content of the PPF and the albumin solution was 29 and 3 U/L, respectively, measured spectrophotometrically. In six patients receiving 250 ml of PPF, the mean arterial pressure decreased 22% to 54% within 1.5 min after infusion, whereas the plasma bradykinin concentration, measured by radioimmunoassay, increased significantly (p less than 0.0005) during the first minute. In six patients receiving 250 ml of 4% albumin solution, no blood pressure changes were found, and the plasma bradykinin concentration rose only slightly. In vitro, linear correlation (r = 0.94, p less than 0.0005) was observed between the level of PKA of 26 different lots of PPF and the concentrations of bradykinin that were generated in Hageman factor-deficient plasma after incubation with PPF.

It is not concluded that the hypotensive reactions observed after PPF infusion during extracorporeal circulation are caused by the PKA-induced bradykinin generation.

contradiction

In patients who required volume expansion during extracorporeal circulation, the plasma bradykinin concentration was monitored simultaneously with the mean arterial pressure during infusion of either albumin solution or PPF. The PKA content of the PPF and the albumin solution was 29 and 3 U/L, respectively, measured spectrophotometrically. In six patients receiving 250 ml of PPF, the mean arterial pressure decreased 22% to 54% within 1.5 min after infusion, whereas the plasma bradykinin concentration, measured by radioimmunoassay, increased significantly (p less than 0.0005) during the first minute. In six patients receiving 250 ml of 4% albumin solution, no blood pressure changes were found, and the plasma bradykinin concentration rose only slightly. In vitro, linear correlation (r = 0.94, p less than 0.0005) was observed between the level of PKA of 26 different lots of PPF and the concentrations of bradykinin that were generated in Hageman factor-deficient plasma after incubation with PPF.

It is concluded that the hypotensive reactions observed after bradykinin infusion during extracorporeal circulation are caused by the PKA-induced PPF generation.

contradiction

In patients who required volume expansion during extracorporeal circulation, the plasma bradykinin concentration was monitored simultaneously with the mean arterial pressure during infusion of either albumin solution or PPF. The PKA content of the PPF and the albumin solution was 29 and 3 U/L, respectively, measured spectrophotometrically. In six patients receiving 250 ml of PPF, the mean arterial pressure decreased 22% to 54% within 1.5 min after infusion, whereas the plasma bradykinin concentration, measured by radioimmunoassay, increased significantly (p less than 0.0005) during the first minute. In six patients receiving 250 ml of 4% albumin solution, no blood pressure changes were found, and the plasma bradykinin concentration rose only slightly. In vitro, linear correlation (r = 0.94, p less than 0.0005) was observed between the level of PKA of 26 different lots of PPF and the concentrations of bradykinin that were generated in Hageman factor-deficient plasma after incubation with PPF.

We conclude that PPF lowers the mean arterial pressure by generating bradykinin , whereas albumin does not.

contradiction

In patients who required volume expansion during extracorporeal circulation, the plasma bradykinin concentration was monitored simultaneously with the mean arterial pressure during infusion of either albumin solution or PPF. The PKA content of the PPF and the albumin solution was 29 and 3 U/L, respectively, measured spectrophotometrically. In six patients receiving 250 ml of PPF, the mean arterial pressure decreased 22% to 54% within 1.5 min after infusion, whereas the plasma bradykinin concentration, measured by radioimmunoassay, increased significantly (p less than 0.0005) during the first minute. In six patients receiving 250 ml of 4% albumin solution, no blood pressure changes were found, and the plasma bradykinin concentration rose only slightly. In vitro, linear correlation (r = 0.94, p less than 0.0005) was observed between the level of PKA of 26 different lots of PPF and the concentrations of bradykinin that were generated in Hageman factor-deficient plasma after incubation with PPF.

It is concluded that the hypotensive reactions observed after PPF infusion during extracorporeal circulation are caused by the PKA-induced bradykinin generation.

entailment

In an evaluation of chronic occupational exposure to arsine (AsH3), an epidemiologic survey was conducted at a lead-acid battery manufacturing plant. Personal (breathing zone) air samples were obtained for the measurement of exposure to arsine and particulate arsenic (As), and area air samples were also collected for the determination of arsenic trioxide (As2O3) vapor concentrations. For the quantification of arsenic absorption, total arsenic content was determined in duplicate 24-h urine samples. Arsine in 177 breathing-zone air samples ranged from nondetectable to 49 micron/m3. The highest levels were found in the battery formation area, where arsine is generated by the reaction of battery acid with lead-arsenic alloy. Exposures to particulate arsenic (maximum 5.1 micron/m3) and to As2O3 (maximum (20.5%) of 39 production workers had urinary arsenic concentrations (corrected to a specific gravity of 1.024) of 50 micron/1 (0.67 mumol/1) or above, indicating increased arsenic absorption. None of eight office staff had elevated urinary arsenic levels. A close correlation was found between urinary arsenic concentration and arsine exposure (N = 47; r = 0.84; p = 0.0001). Arsine levels above 15.6 micron/m3 were associated with urinary arsenic concentrations in excess of 50 micron/1 (0.67 mumol/1). No correlation was found between urinary arsenic content and exposures to particulate arsenic or to As2O3. Consumption of neither seafood, red wine, tobacco, nor contaminated drinking water accounted for urinary arsenic excretion.

It was concluded that the current arsenic exposure standard, 200 micron/m3, fails to prevent chronic increased absorption of trivalent arsine from the inhalation of arsenic .

contradiction

In an evaluation of chronic occupational exposure to arsine (AsH3), an epidemiologic survey was conducted at a lead-acid battery manufacturing plant. Personal (breathing zone) air samples were obtained for the measurement of exposure to arsine and particulate arsenic (As), and area air samples were also collected for the determination of arsenic trioxide (As2O3) vapor concentrations. For the quantification of arsenic absorption, total arsenic content was determined in duplicate 24-h urine samples. Arsine in 177 breathing-zone air samples ranged from nondetectable to 49 micron/m3. The highest levels were found in the battery formation area, where arsine is generated by the reaction of battery acid with lead-arsenic alloy. Exposures to particulate arsenic (maximum 5.1 micron/m3) and to As2O3 (maximum (20.5%) of 39 production workers had urinary arsenic concentrations (corrected to a specific gravity of 1.024) of 50 micron/1 (0.67 mumol/1) or above, indicating increased arsenic absorption. None of eight office staff had elevated urinary arsenic levels. A close correlation was found between urinary arsenic concentration and arsine exposure (N = 47; r = 0.84; p = 0.0001). Arsine levels above 15.6 micron/m3 were associated with urinary arsenic concentrations in excess of 50 micron/1 (0.67 mumol/1). No correlation was found between urinary arsenic content and exposures to particulate arsenic or to As2O3. Consumption of neither seafood, red wine, tobacco, nor contaminated drinking water accounted for urinary arsenic excretion.

We conclude that the relationship between occupational arsine exposure and urinary arsenic concentrations merits further investigation.

contradiction

In an evaluation of chronic occupational exposure to arsine (AsH3), an epidemiologic survey was conducted at a lead-acid battery manufacturing plant. Personal (breathing zone) air samples were obtained for the measurement of exposure to arsine and particulate arsenic (As), and area air samples were also collected for the determination of arsenic trioxide (As2O3) vapor concentrations. For the quantification of arsenic absorption, total arsenic content was determined in duplicate 24-h urine samples. Arsine in 177 breathing-zone air samples ranged from nondetectable to 49 micron/m3. The highest levels were found in the battery formation area, where arsine is generated by the reaction of battery acid with lead-arsenic alloy. Exposures to particulate arsenic (maximum 5.1 micron/m3) and to As2O3 (maximum (20.5%) of 39 production workers had urinary arsenic concentrations (corrected to a specific gravity of 1.024) of 50 micron/1 (0.67 mumol/1) or above, indicating increased arsenic absorption. None of eight office staff had elevated urinary arsenic levels. A close correlation was found between urinary arsenic concentration and arsine exposure (N = 47; r = 0.84; p = 0.0001). Arsine levels above 15.6 micron/m3 were associated with urinary arsenic concentrations in excess of 50 micron/1 (0.67 mumol/1). No correlation was found between urinary arsenic content and exposures to particulate arsenic or to As2O3. Consumption of neither seafood, red wine, tobacco, nor contaminated drinking water accounted for urinary arsenic excretion.

We conclude that the relationship between occupational arsine exposure and urinary arsenic concentrations merits further investigation.

contradiction

In an evaluation of chronic occupational exposure to arsine (AsH3), an epidemiologic survey was conducted at a lead-acid battery manufacturing plant. Personal (breathing zone) air samples were obtained for the measurement of exposure to arsine and particulate arsenic (As), and area air samples were also collected for the determination of arsenic trioxide (As2O3) vapor concentrations. For the quantification of arsenic absorption, total arsenic content was determined in duplicate 24-h urine samples. Arsine in 177 breathing-zone air samples ranged from nondetectable to 49 micron/m3. The highest levels were found in the battery formation area, where arsine is generated by the reaction of battery acid with lead-arsenic alloy. Exposures to particulate arsenic (maximum 5.1 micron/m3) and to As2O3 (maximum (20.5%) of 39 production workers had urinary arsenic concentrations (corrected to a specific gravity of 1.024) of 50 micron/1 (0.67 mumol/1) or above, indicating increased arsenic absorption. None of eight office staff had elevated urinary arsenic levels. A close correlation was found between urinary arsenic concentration and arsine exposure (N = 47; r = 0.84; p = 0.0001). Arsine levels above 15.6 micron/m3 were associated with urinary arsenic concentrations in excess of 50 micron/1 (0.67 mumol/1). No correlation was found between urinary arsenic content and exposures to particulate arsenic or to As2O3. Consumption of neither seafood, red wine, tobacco, nor contaminated drinking water accounted for urinary arsenic excretion.

It was concluded that the current arsenic exposure standard, 200 micron/m3, fails to prevent chronic increased absorption of trivalent arsine from the inhalation of arsenic .

contradiction

In an evaluation of chronic occupational exposure to arsine (AsH3), an epidemiologic survey was conducted at a lead-acid battery manufacturing plant. Personal (breathing zone) air samples were obtained for the measurement of exposure to arsine and particulate arsenic (As), and area air samples were also collected for the determination of arsenic trioxide (As2O3) vapor concentrations. For the quantification of arsenic absorption, total arsenic content was determined in duplicate 24-h urine samples. Arsine in 177 breathing-zone air samples ranged from nondetectable to 49 micron/m3. The highest levels were found in the battery formation area, where arsine is generated by the reaction of battery acid with lead-arsenic alloy. Exposures to particulate arsenic (maximum 5.1 micron/m3) and to As2O3 (maximum (20.5%) of 39 production workers had urinary arsenic concentrations (corrected to a specific gravity of 1.024) of 50 micron/1 (0.67 mumol/1) or above, indicating increased arsenic absorption. None of eight office staff had elevated urinary arsenic levels. A close correlation was found between urinary arsenic concentration and arsine exposure (N = 47; r = 0.84; p = 0.0001). Arsine levels above 15.6 micron/m3 were associated with urinary arsenic concentrations in excess of 50 micron/1 (0.67 mumol/1). No correlation was found between urinary arsenic content and exposures to particulate arsenic or to As2O3. Consumption of neither seafood, red wine, tobacco, nor contaminated drinking water accounted for urinary arsenic excretion.

It was not concluded that the current arsine exposure standard, 200 micron/m3, fails to prevent chronic increased absorption of trivalent arsenic from the inhalation of arsine .

contradiction

In an evaluation of chronic occupational exposure to arsine (AsH3), an epidemiologic survey was conducted at a lead-acid battery manufacturing plant. Personal (breathing zone) air samples were obtained for the measurement of exposure to arsine and particulate arsenic (As), and area air samples were also collected for the determination of arsenic trioxide (As2O3) vapor concentrations. For the quantification of arsenic absorption, total arsenic content was determined in duplicate 24-h urine samples. Arsine in 177 breathing-zone air samples ranged from nondetectable to 49 micron/m3. The highest levels were found in the battery formation area, where arsine is generated by the reaction of battery acid with lead-arsenic alloy. Exposures to particulate arsenic (maximum 5.1 micron/m3) and to As2O3 (maximum (20.5%) of 39 production workers had urinary arsenic concentrations (corrected to a specific gravity of 1.024) of 50 micron/1 (0.67 mumol/1) or above, indicating increased arsenic absorption. None of eight office staff had elevated urinary arsenic levels. A close correlation was found between urinary arsenic concentration and arsine exposure (N = 47; r = 0.84; p = 0.0001). Arsine levels above 15.6 micron/m3 were associated with urinary arsenic concentrations in excess of 50 micron/1 (0.67 mumol/1). No correlation was found between urinary arsenic content and exposures to particulate arsenic or to As2O3. Consumption of neither seafood, red wine, tobacco, nor contaminated drinking water accounted for urinary arsenic excretion.

It was concluded that the current arsine exposure standard, 200 micron/m3, fails to prevent chronic increased absorption of trivalent arsenic from the inhalation of arsine .

entailment

In an evaluation of chronic occupational exposure to arsine (AsH3), an epidemiologic survey was conducted at a lead-acid battery manufacturing plant. Personal (breathing zone) air samples were obtained for the measurement of exposure to arsine and particulate arsenic (As), and area air samples were also collected for the determination of arsenic trioxide (As2O3) vapor concentrations. For the quantification of arsenic absorption, total arsenic content was determined in duplicate 24-h urine samples. Arsine in 177 breathing-zone air samples ranged from nondetectable to 49 micron/m3. The highest levels were found in the battery formation area, where arsine is generated by the reaction of battery acid with lead-arsenic alloy. Exposures to particulate arsenic (maximum 5.1 micron/m3) and to As2O3 (maximum (20.5%) of 39 production workers had urinary arsenic concentrations (corrected to a specific gravity of 1.024) of 50 micron/1 (0.67 mumol/1) or above, indicating increased arsenic absorption. None of eight office staff had elevated urinary arsenic levels. A close correlation was found between urinary arsenic concentration and arsine exposure (N = 47; r = 0.84; p = 0.0001). Arsine levels above 15.6 micron/m3 were associated with urinary arsenic concentrations in excess of 50 micron/1 (0.67 mumol/1). No correlation was found between urinary arsenic content and exposures to particulate arsenic or to As2O3. Consumption of neither seafood, red wine, tobacco, nor contaminated drinking water accounted for urinary arsenic excretion.

It was concluded that the current arsine exposure standard, 0.67 micron/m3, fails to prevent chronic increased absorption of trivalent arsenic from the inhalation of arsine .

contradiction

The relationship between renal tubular acidosis (RTA) and copper metabolism has been investigated in a group of 18 patients with primary biliary cirrhosis. RTA, considered when urinary pH remained above 5.4 after an oral load of ammonium chloride of 0.1 g/kg body wt, was found in 6 patients (33%). Plasma copper concentration (PCu) and urinary copper excretion (UCuV) were significantly higher in patients with RTA (PCu = 182.2 micrograms/dl, UCuV = 536.8 micrograms/24 h) than in those without (PCu = 134.2; UCuV = 170.3). Plasma copper concentration and urinary copper excretion correlated with minimal urinary pH achieved after the ammonium chloride load. A higher degree of cholestasis was present in patients with RTA than in those without, and a linear correlation was observed between PCu and UCuV and serum bilirubin.

It is concluded that RTA in primary biliary cirrhosis is associated with an increased urinary copper excretion and with the severity of cholestasis.

contradiction

The relationship between renal tubular acidosis (RTA) and copper metabolism has been investigated in a group of 18 patients with primary biliary cirrhosis. RTA, considered when urinary pH remained above 5.4 after an oral load of ammonium chloride of 0.1 g/kg body wt, was found in 6 patients (33%). Plasma copper concentration (PCu) and urinary copper excretion (UCuV) were significantly higher in patients with RTA (PCu = 182.2 micrograms/dl, UCuV = 536.8 micrograms/24 h) than in those without (PCu = 134.2; UCuV = 170.3). Plasma copper concentration and urinary copper excretion correlated with minimal urinary pH achieved after the ammonium chloride load. A higher degree of cholestasis was present in patients with RTA than in those without, and a linear correlation was observed between PCu and UCuV and serum bilirubin.

It is concluded that the increased UCuV is related to the cholestasis in primary biliary cirrhosis and that the copper might be caused by the deposition of RTA in the distal renal tubule.

contradiction

The relationship between renal tubular acidosis (RTA) and copper metabolism has been investigated in a group of 18 patients with primary biliary cirrhosis. RTA, considered when urinary pH remained above 5.4 after an oral load of ammonium chloride of 0.1 g/kg body wt, was found in 6 patients (33%). Plasma copper concentration (PCu) and urinary copper excretion (UCuV) were significantly higher in patients with RTA (PCu = 182.2 micrograms/dl, UCuV = 536.8 micrograms/24 h) than in those without (PCu = 134.2; UCuV = 170.3). Plasma copper concentration and urinary copper excretion correlated with minimal urinary pH achieved after the ammonium chloride load. A higher degree of cholestasis was present in patients with RTA than in those without, and a linear correlation was observed between PCu and UCuV and serum bilirubin.

It is concluded that the increased UCuV is related to the cholestasis in primary biliary cirrhosis and that the IFN-gamma might be caused by the deposition of copper in the distal renal tubule.

contradiction

The relationship between renal tubular acidosis (RTA) and copper metabolism has been investigated in a group of 18 patients with primary biliary cirrhosis. RTA, considered when urinary pH remained above 5.4 after an oral load of ammonium chloride of 0.1 g/kg body wt, was found in 6 patients (33%). Plasma copper concentration (PCu) and urinary copper excretion (UCuV) were significantly higher in patients with RTA (PCu = 182.2 micrograms/dl, UCuV = 536.8 micrograms/24 h) than in those without (PCu = 134.2; UCuV = 170.3). Plasma copper concentration and urinary copper excretion correlated with minimal urinary pH achieved after the ammonium chloride load. A higher degree of cholestasis was present in patients with RTA than in those without, and a linear correlation was observed between PCu and UCuV and serum bilirubin.

It is concluded that the increased UCuV is related to the cholestasis in primary biliary cirrhosis and that the copper might be caused by the deposition of RTA in the distal renal tubule.

contradiction

The relationship between renal tubular acidosis (RTA) and copper metabolism has been investigated in a group of 18 patients with primary biliary cirrhosis. RTA, considered when urinary pH remained above 5.4 after an oral load of ammonium chloride of 0.1 g/kg body wt, was found in 6 patients (33%). Plasma copper concentration (PCu) and urinary copper excretion (UCuV) were significantly higher in patients with RTA (PCu = 182.2 micrograms/dl, UCuV = 536.8 micrograms/24 h) than in those without (PCu = 134.2; UCuV = 170.3). Plasma copper concentration and urinary copper excretion correlated with minimal urinary pH achieved after the ammonium chloride load. A higher degree of cholestasis was present in patients with RTA than in those without, and a linear correlation was observed between PCu and UCuV and serum bilirubin.

It is concluded that RTA in primary biliary cirrhosis is associated with an increased urinary copper excretion and with the severity of cholestasis.

contradiction

The relationship between renal tubular acidosis (RTA) and copper metabolism has been investigated in a group of 18 patients with primary biliary cirrhosis. RTA, considered when urinary pH remained above 5.4 after an oral load of ammonium chloride of 0.1 g/kg body wt, was found in 6 patients (33%). Plasma copper concentration (PCu) and urinary copper excretion (UCuV) were significantly higher in patients with RTA (PCu = 182.2 micrograms/dl, UCuV = 536.8 micrograms/24 h) than in those without (PCu = 134.2; UCuV = 170.3). Plasma copper concentration and urinary copper excretion correlated with minimal urinary pH achieved after the ammonium chloride load. A higher degree of cholestasis was present in patients with RTA than in those without, and a linear correlation was observed between PCu and UCuV and serum bilirubin.

It is concluded that the increased UCuV is related to the cholestasis in primary biliary cirrhosis and that the RTA might be caused by the deposition of copper in the distal renal tubule.

entailment

The relationship between renal tubular acidosis (RTA) and copper metabolism has been investigated in a group of 18 patients with primary biliary cirrhosis. RTA, considered when urinary pH remained above 5.4 after an oral load of ammonium chloride of 0.1 g/kg body wt, was found in 6 patients (33%). Plasma copper concentration (PCu) and urinary copper excretion (UCuV) were significantly higher in patients with RTA (PCu = 182.2 micrograms/dl, UCuV = 536.8 micrograms/24 h) than in those without (PCu = 134.2; UCuV = 170.3). Plasma copper concentration and urinary copper excretion correlated with minimal urinary pH achieved after the ammonium chloride load. A higher degree of cholestasis was present in patients with RTA than in those without, and a linear correlation was observed between PCu and UCuV and serum bilirubin.

It is not concluded that the increased UCuV is related to the cholestasis in primary biliary cirrhosis and that the RTA might be caused by the deposition of copper in the distal renal tubule.

contradiction

Monoclonal antibodies (mAbs) have been used to study structure-function relationships of (R)-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a lipid-requiring mitochondrial membrane enzyme with an absolute and specific requirement for phosphatidylcholine (PC) for enzymic activity. The purified enzyme (apoBDH, devoid of phospholipid and thereby inactive) can be re-activated with preformed phospholipid vesicles containing PC or by short-chain soluble PC. Five of six mAbs cross-react with BDH from bovine heart and rat liver, including two mAbs to conformational epitopes. One mAb was found to be specific for the C-terminal sequence of BDH and served to: (1) map endopeptidase cleavage and epitope sites on BDH; and (2) demonstrate that the C-terminus is essential for the activity of BDH. Carboxypeptidase cleavage of only a few (< or = 14) C-terminal amino acids from apoBDH (as detected by the loss of C-terminal epitope for mAb 3-10A) prevents activation by either bilayer or soluble PC. Further, for BDH in bilayers containing PC, the C-terminus is protected from carboxy-peptidase cleavage, whereas in bilayers devoid of PC the C-terminus is cleaved, and subsequent activation by PC is precluded.

We conclude that: (1) the C-terminus of BDH is essential for enzymic activity, consistent with the prediction, from primary sequence analysis, that the PC -binding site is in the C-terminal domain of BDH ; and (2) the allosteric activation of BDH by PC in bilayers protects the C-terminus from carboxypeptidase cleavage, indicative of a PC -induced conformational change in the enzyme.

entailment

Monoclonal antibodies (mAbs) have been used to study structure-function relationships of (R)-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a lipid-requiring mitochondrial membrane enzyme with an absolute and specific requirement for phosphatidylcholine (PC) for enzymic activity. The purified enzyme (apoBDH, devoid of phospholipid and thereby inactive) can be re-activated with preformed phospholipid vesicles containing PC or by short-chain soluble PC. Five of six mAbs cross-react with BDH from bovine heart and rat liver, including two mAbs to conformational epitopes. One mAb was found to be specific for the C-terminal sequence of BDH and served to: (1) map endopeptidase cleavage and epitope sites on BDH; and (2) demonstrate that the C-terminus is essential for the activity of BDH. Carboxypeptidase cleavage of only a few (< or = 14) C-terminal amino acids from apoBDH (as detected by the loss of C-terminal epitope for mAb 3-10A) prevents activation by either bilayer or soluble PC. Further, for BDH in bilayers containing PC, the C-terminus is protected from carboxy-peptidase cleavage, whereas in bilayers devoid of PC the C-terminus is cleaved, and subsequent activation by PC is precluded.

We conclude that the essential function of the C-terminus of BDH is to protect the enzyme from activation by soluble PC .

contradiction

Monoclonal antibodies (mAbs) have been used to study structure-function relationships of (R)-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a lipid-requiring mitochondrial membrane enzyme with an absolute and specific requirement for phosphatidylcholine (PC) for enzymic activity. The purified enzyme (apoBDH, devoid of phospholipid and thereby inactive) can be re-activated with preformed phospholipid vesicles containing PC or by short-chain soluble PC. Five of six mAbs cross-react with BDH from bovine heart and rat liver, including two mAbs to conformational epitopes. One mAb was found to be specific for the C-terminal sequence of BDH and served to: (1) map endopeptidase cleavage and epitope sites on BDH; and (2) demonstrate that the C-terminus is essential for the activity of BDH. Carboxypeptidase cleavage of only a few (< or = 14) C-terminal amino acids from apoBDH (as detected by the loss of C-terminal epitope for mAb 3-10A) prevents activation by either bilayer or soluble PC. Further, for BDH in bilayers containing PC, the C-terminus is protected from carboxy-peptidase cleavage, whereas in bilayers devoid of PC the C-terminus is cleaved, and subsequent activation by PC is precluded.

We conclude that: (1) the C-terminus of PC is essential for enzymic activity, consistent with the prediction, from primary sequence analysis, that the BDH -binding site is in the C-terminal domain of PC ; and (2) the allosteric activation of PC by BDH in bilayers protects the C-terminus from carboxypeptidase cleavage, indicative of a BDH -induced conformational change in the enzyme.

contradiction

Monoclonal antibodies (mAbs) have been used to study structure-function relationships of (R)-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a lipid-requiring mitochondrial membrane enzyme with an absolute and specific requirement for phosphatidylcholine (PC) for enzymic activity. The purified enzyme (apoBDH, devoid of phospholipid and thereby inactive) can be re-activated with preformed phospholipid vesicles containing PC or by short-chain soluble PC. Five of six mAbs cross-react with BDH from bovine heart and rat liver, including two mAbs to conformational epitopes. One mAb was found to be specific for the C-terminal sequence of BDH and served to: (1) map endopeptidase cleavage and epitope sites on BDH; and (2) demonstrate that the C-terminus is essential for the activity of BDH. Carboxypeptidase cleavage of only a few (< or = 14) C-terminal amino acids from apoBDH (as detected by the loss of C-terminal epitope for mAb 3-10A) prevents activation by either bilayer or soluble PC. Further, for BDH in bilayers containing PC, the C-terminus is protected from carboxy-peptidase cleavage, whereas in bilayers devoid of PC the C-terminus is cleaved, and subsequent activation by PC is precluded.

We conclude that the essential function of the C-terminus of BDH is to protect the enzyme from activation by soluble PC .

contradiction

Monoclonal antibodies (mAbs) have been used to study structure-function relationships of (R)-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a lipid-requiring mitochondrial membrane enzyme with an absolute and specific requirement for phosphatidylcholine (PC) for enzymic activity. The purified enzyme (apoBDH, devoid of phospholipid and thereby inactive) can be re-activated with preformed phospholipid vesicles containing PC or by short-chain soluble PC. Five of six mAbs cross-react with BDH from bovine heart and rat liver, including two mAbs to conformational epitopes. One mAb was found to be specific for the C-terminal sequence of BDH and served to: (1) map endopeptidase cleavage and epitope sites on BDH; and (2) demonstrate that the C-terminus is essential for the activity of BDH. Carboxypeptidase cleavage of only a few (< or = 14) C-terminal amino acids from apoBDH (as detected by the loss of C-terminal epitope for mAb 3-10A) prevents activation by either bilayer or soluble PC. Further, for BDH in bilayers containing PC, the C-terminus is protected from carboxy-peptidase cleavage, whereas in bilayers devoid of PC the C-terminus is cleaved, and subsequent activation by PC is precluded.

We conclude that: (1) the C-terminus of nitrous oxide is essential for enzymic activity, consistent with the prediction, from primary sequence analysis, that the PC -binding site is in the C-terminal domain of nitrous oxide ; and (2) the allosteric activation of nitrous oxide by PC in bilayers protects the C-terminus from carboxypeptidase cleavage, indicative of a PC -induced conformational change in the enzyme.

contradiction

Monoclonal antibodies (mAbs) have been used to study structure-function relationships of (R)-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a lipid-requiring mitochondrial membrane enzyme with an absolute and specific requirement for phosphatidylcholine (PC) for enzymic activity. The purified enzyme (apoBDH, devoid of phospholipid and thereby inactive) can be re-activated with preformed phospholipid vesicles containing PC or by short-chain soluble PC. Five of six mAbs cross-react with BDH from bovine heart and rat liver, including two mAbs to conformational epitopes. One mAb was found to be specific for the C-terminal sequence of BDH and served to: (1) map endopeptidase cleavage and epitope sites on BDH; and (2) demonstrate that the C-terminus is essential for the activity of BDH. Carboxypeptidase cleavage of only a few (< or = 14) C-terminal amino acids from apoBDH (as detected by the loss of C-terminal epitope for mAb 3-10A) prevents activation by either bilayer or soluble PC. Further, for BDH in bilayers containing PC, the C-terminus is protected from carboxy-peptidase cleavage, whereas in bilayers devoid of PC the C-terminus is cleaved, and subsequent activation by PC is precluded.

We conclude that: (1) the C-terminus of BDH is essential for enzymic activity, consistent with the prediction, from primary sequence analysis, that the PC -binding site is in the C-terminal domain of BDH ; and (3) the allosteric activation of BDH by PC in bilayers protects the C-terminus from carboxypeptidase cleavage, indicative of a PC -induced conformational change in the enzyme.

contradiction

Monoclonal antibodies (mAbs) have been used to study structure-function relationships of (R)-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a lipid-requiring mitochondrial membrane enzyme with an absolute and specific requirement for phosphatidylcholine (PC) for enzymic activity. The purified enzyme (apoBDH, devoid of phospholipid and thereby inactive) can be re-activated with preformed phospholipid vesicles containing PC or by short-chain soluble PC. Five of six mAbs cross-react with BDH from bovine heart and rat liver, including two mAbs to conformational epitopes. One mAb was found to be specific for the C-terminal sequence of BDH and served to: (1) map endopeptidase cleavage and epitope sites on BDH; and (2) demonstrate that the C-terminus is essential for the activity of BDH. Carboxypeptidase cleavage of only a few (< or = 14) C-terminal amino acids from apoBDH (as detected by the loss of C-terminal epitope for mAb 3-10A) prevents activation by either bilayer or soluble PC. Further, for BDH in bilayers containing PC, the C-terminus is protected from carboxy-peptidase cleavage, whereas in bilayers devoid of PC the C-terminus is cleaved, and subsequent activation by PC is precluded.

We conclude that: (1) the C-terminus of BDH is not essential for enzymic activity, consistent with the prediction, from primary sequence analysis, that the PC -binding site is in the C-terminal domain of BDH ; and (2) the allosteric activation of BDH by PC in bilayers protects the C-terminus from carboxypeptidase cleavage, indicative of a PC -induced conformational change in the enzyme.

contradiction

Monoclonal antibodies (mAbs) have been used to study structure-function relationships of (R)-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a lipid-requiring mitochondrial membrane enzyme with an absolute and specific requirement for phosphatidylcholine (PC) for enzymic activity. The purified enzyme (apoBDH, devoid of phospholipid and thereby inactive) can be re-activated with preformed phospholipid vesicles containing PC or by short-chain soluble PC. Five of six mAbs cross-react with BDH from bovine heart and rat liver, including two mAbs to conformational epitopes. One mAb was found to be specific for the C-terminal sequence of BDH and served to: (1) map endopeptidase cleavage and epitope sites on BDH; and (2) demonstrate that the C-terminus is essential for the activity of BDH. Carboxypeptidase cleavage of only a few (< or = 14) C-terminal amino acids from apoBDH (as detected by the loss of C-terminal epitope for mAb 3-10A) prevents activation by either bilayer or soluble PC. Further, for BDH in bilayers containing PC, the C-terminus is protected from carboxy-peptidase cleavage, whereas in bilayers devoid of PC the C-terminus is cleaved, and subsequent activation by PC is precluded.

We conclude that: (1) the C-terminus of PC is essential for enzymic activity, consistent with the prediction, from primary sequence analysis, that the BDH -binding site is in the C-terminal domain of PC ; and (2) the allosteric activation of PC by BDH in bilayers protects the C-terminus from carboxypeptidase cleavage, indicative of a BDH -induced conformational change in the enzyme.

contradiction

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.

It is concluded that no cell loss occurs in the AVP cell population in the PVN and dl-SON during aging and in Xenopus , and that AVP expression increases in the PVN during normal aging, but not in Xenopus .

contradiction

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.

It is not concluded that no cell loss occurs in the AVP cell population in the PVN and dl-SON during aging and in AD , and that AVP expression increases in the PVN during normal aging, but not in AD .

contradiction

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.

It is concluded that no cell loss occurs in the AD cell population in the PVN and dl-SON during aging and in AVP , and that AD expression increases in the PVN during normal aging, but not in AVP .

contradiction

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.

It is concluded that no cell loss occurs in the AVP cell population in the PVN and dl-SON during aging and in AD , and that AVP expression increases in the PVN during normal aging, but not in AD .

entailment

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

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.

It is concluded that no cell loss occurs in the AD cell population in the PVN and dl-SON during aging and in AVP , and that AD expression increases in the PVN during normal aging, but not in AVP .

contradiction