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PMID:4577 | Kinetic and pharmacological properties of the sodium channel of frog skeletal muscle. | Na channels of frog skeletal muscle are studied under voltage clamp and their properties compared with those of frog myelinated nerve. A standard mathematical model is fitted to the sodium currents measured in nerve and in muscle to obtain a quantitative description of the gating kinetics. At 5 degrees C the kinetics in frog nerve and skeletal muscle are similar except that activation proceeds five times faster in nerve. Block of Na channels by saxitoxin is measured in nerve and in muscle. The apparent dissociation constants for the inhibitory complex are about 1 nM and not significantly different in nerve and muscle. Block of Na channels by external protons in muscle is found to have an apparent pKalpha of 5.33 and a voltage dependence corresponding to action of 27% of the membrane potential drop. Both values are like those for nerve. Shift of the peak sodium permeability-membrane potential curve with changes of external pH and Ca++ are found to be the same in nerve and muscle. It is concluded that Na channels of nerve and muscle are nearly the same. | Kinetic and pharmacological properties of the sodium channel of frog skeletal muscle. Na channels of frog skeletal muscle are studied under voltage clamp and their properties compared with those of frog myelinated nerve. A standard mathematical model is fitted to the sodium currents measured in nerve and in muscle to obtain a quantitative description of the gating kinetics. At 5 degrees C the kinetics in frog nerve and skeletal muscle are similar except that activation proceeds five times faster in nerve. Block of Na channels by saxitoxin is measured in nerve and in muscle. The apparent dissociation constants for the inhibitory complex are about 1 nM and not significantly different in nerve and muscle. Block of Na channels by external protons in muscle is found to have an apparent pKalpha of 5.33 and a voltage dependence corresponding to action of 27% of the membrane potential drop. Both values are like those for nerve. Shift of the peak sodium permeability-membrane potential curve with changes of external pH and Ca++ are found to be the same in nerve and muscle. It is concluded that Na channels of nerve and muscle are nearly the same. | [
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PMID:4578 | Cation transport in Escherichia coli. VIII. Potassium transport mutants. | Analysis of K transport mutants indicates the existence of four separate K uptake systems in Escherichia coli K-12. A high affinity system called Kdp has a Km of 2 muM, and Vmax at 37 degrees C of 150 mumol/g min. This system is repressed by growth in high concentrations of K. Two constitutive systems, TrkA and TrkD, have Km's of 1.5 and 0.5 mM and Vmax's of 550 and 40 at 37 and 30 degrees C, respectively. Mutants lacking all three of these saturable systems take up K slowly by a process, called TrkF, whose rate of transport is linearly dependent on K concentration up to 105 mM. On the whole, each of these systems appears to function as an independent path for K uptake since the kinetics of uptake when two are present is the sum of each operating alone. This is not true for strains having both the TrkD and Kdp systems, where presence of the latter results in K uptake which saturates at a K concentration well below 0.1 mM. This result indicates some interaction between these systems so that uptake now has the affinity characteristic of the Kdp system. All transport systems are able to extrude Na during K uptake. The measurements of cell Na suggest that growing cells of E. coli have very low concentrations of Na, considerably lower than indicated by earlier studies. | Cation transport in Escherichia coli. VIII. Potassium transport mutants. Analysis of K transport mutants indicates the existence of four separate K uptake systems in Escherichia coli K-12. A high affinity system called Kdp has a Km of 2 muM, and Vmax at 37 degrees C of 150 mumol/g min. This system is repressed by growth in high concentrations of K. Two constitutive systems, TrkA and TrkD, have Km's of 1.5 and 0.5 mM and Vmax's of 550 and 40 at 37 and 30 degrees C, respectively. Mutants lacking all three of these saturable systems take up K slowly by a process, called TrkF, whose rate of transport is linearly dependent on K concentration up to 105 mM. On the whole, each of these systems appears to function as an independent path for K uptake since the kinetics of uptake when two are present is the sum of each operating alone. This is not true for strains having both the TrkD and Kdp systems, where presence of the latter results in K uptake which saturates at a K concentration well below 0.1 mM. This result indicates some interaction between these systems so that uptake now has the affinity characteristic of the Kdp system. All transport systems are able to extrude Na during K uptake. The measurements of cell Na suggest that growing cells of E. coli have very low concentrations of Na, considerably lower than indicated by earlier studies. | [
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PMID:4579 | Some properties of the pyruvate carboxylase from Pseudomonas fluorescens. | The pyruvate carboxylase of Pseudonomas fluorescens was purified 160-fold from cells grown on glucose at 20 degrees C. The activity of this purified enzyme was not affected by acetyl-coenzyme A or L-aspartate, but was strongly inhibited by ADP, which was competitive towards ATP. Pyruvate gave a broken double reciprocal plot, from which two apparent Km values could be determined, namely 0-08 and 0-21 mM, from the lower and the higher concentration ranges, respectively. The apparent Km for HCO3 at pH 6-9, in the presence of the manganese ATP ion (MnATP2-), was 3-1 mM. The enzyme reaction had an optimum pH value of 7-1 or 9-0 depending on the use of MnATP2- or MgATP2-, respectively, as substrate. Free Mg2+ was an activator at pH values below 9-0. The enzyme was strongly activated by monovalent cations; NH4+ and K+ were the better activators, with apparent Ka values of 0-7 and 1-6 mM, respectively. Partially purified enzymes from cells grown on glucose at 1 or 20 degrees C had the same properties, including the thermal stability. In both cases 50% of the enzyme activity was lost after pre-incubation for 10 min at 46 degrees C. The molecular weight was estimated to be about 300000 daltons by gel filtration on Sephadex G-200. The regulatory properties and molecular weight are thus similar to those determined for the pyruvate carboxylases from Pseudomonas citronellolis and Azotobacter vinelandii. | Some properties of the pyruvate carboxylase from Pseudomonas fluorescens. The pyruvate carboxylase of Pseudonomas fluorescens was purified 160-fold from cells grown on glucose at 20 degrees C. The activity of this purified enzyme was not affected by acetyl-coenzyme A or L-aspartate, but was strongly inhibited by ADP, which was competitive towards ATP. Pyruvate gave a broken double reciprocal plot, from which two apparent Km values could be determined, namely 0-08 and 0-21 mM, from the lower and the higher concentration ranges, respectively. The apparent Km for HCO3 at pH 6-9, in the presence of the manganese ATP ion (MnATP2-), was 3-1 mM. The enzyme reaction had an optimum pH value of 7-1 or 9-0 depending on the use of MnATP2- or MgATP2-, respectively, as substrate. Free Mg2+ was an activator at pH values below 9-0. The enzyme was strongly activated by monovalent cations; NH4+ and K+ were the better activators, with apparent Ka values of 0-7 and 1-6 mM, respectively. Partially purified enzymes from cells grown on glucose at 1 or 20 degrees C had the same properties, including the thermal stability. In both cases 50% of the enzyme activity was lost after pre-incubation for 10 min at 46 degrees C. The molecular weight was estimated to be about 300000 daltons by gel filtration on Sephadex G-200. The regulatory properties and molecular weight are thus similar to those determined for the pyruvate carboxylases from Pseudomonas citronellolis and Azotobacter vinelandii. | [
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PMID:4588 | Cyanide intoxication in the rat: physiological and neuropathological aspects. | Sodium cyanide was given to rats by intravenous infusion at a rate that would avert apnoea (the first sign of overdosage) in the majority. There was full physiological monitoring in a group under anaesthesia and more limited monitoring in an unanaesthetized group. White matter was damaged in six animals and grey matter additionally in only one. It was concluded that cyanide can damage neurones only through the medium of secondary effects on circulation and respiration. | Cyanide intoxication in the rat: physiological and neuropathological aspects. Sodium cyanide was given to rats by intravenous infusion at a rate that would avert apnoea (the first sign of overdosage) in the majority. There was full physiological monitoring in a group under anaesthesia and more limited monitoring in an unanaesthetized group. White matter was damaged in six animals and grey matter additionally in only one. It was concluded that cyanide can damage neurones only through the medium of secondary effects on circulation and respiration. | [
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PMID:4595 | Summer sequential graduate programs in nursing. | In 1970 Texas Woman's University, College of Nursing instituted summer sequential programs in nursing whereby a student could study for a master's degree by attending the University for three summers. A different clinical focus was added each year from 1970 to 1973. Three sequences have been completed, i.e., clinical focuses of psychiatric-mental health nursing, medical-surgical nursing, and maternal-child nursing. Community health nursing is still in progress. Table II is a tabulation of the number and percentage of students who have entered, have withdrawn, are incomplete, or have graduated. Faculty and students think that the program is successful. Enrollment for the first summer of a three-summer sequence beginning the summer of 1974 was twenty-five students in medical-surgical nursing and fifteen students in psychiatric-mental health nursing. | Summer sequential graduate programs in nursing. In 1970 Texas Woman's University, College of Nursing instituted summer sequential programs in nursing whereby a student could study for a master's degree by attending the University for three summers. A different clinical focus was added each year from 1970 to 1973. Three sequences have been completed, i.e., clinical focuses of psychiatric-mental health nursing, medical-surgical nursing, and maternal-child nursing. Community health nursing is still in progress. Table II is a tabulation of the number and percentage of students who have entered, have withdrawn, are incomplete, or have graduated. Faculty and students think that the program is successful. Enrollment for the first summer of a three-summer sequence beginning the summer of 1974 was twenty-five students in medical-surgical nursing and fifteen students in psychiatric-mental health nursing. | [
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PMID:4598 | The multiple assignment: an effective alternative for laboratory experiences. | The purpose of the study was to test out the efficacy of both the Traditional and the Multiple Assignment approaches to the laboratory experiences of students of nursing. The subjects were 22 students enrolled in the first quarter of an Associate Degree Nursing Program and placed in either the multiple or the traditional laboratory assignment. Results showed the students in the peer experience to be superior in overall performance on tests of Nursing Knowledge, Concept Usage and Self-Esteem. It was concluded that the Multiple Assignment approach to laboratory experiences is a viable and useful method for the education of student nurses. | The multiple assignment: an effective alternative for laboratory experiences. The purpose of the study was to test out the efficacy of both the Traditional and the Multiple Assignment approaches to the laboratory experiences of students of nursing. The subjects were 22 students enrolled in the first quarter of an Associate Degree Nursing Program and placed in either the multiple or the traditional laboratory assignment. Results showed the students in the peer experience to be superior in overall performance on tests of Nursing Knowledge, Concept Usage and Self-Esteem. It was concluded that the Multiple Assignment approach to laboratory experiences is a viable and useful method for the education of student nurses. | [
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PMID:4599 | Stability of some pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats. | The effects of lowering the liver pyridoxal phosphate (PLP) concentration by vitamin B-6 deficiency on the stability of several rat liver enzymes were examined. Three PLP-dependent enzymes (serine dehydratase, ornithine-delta-aminotransferase, and tyrosine aminotransferase) and two non-PLP-dependent enzymes (glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase) were induced in vitamin B-6 deficient and control rats by feeding them high-protein diets or by injecting them with glucagon or dexamethasone. The decline of each activity was followed after withdrawal of the inducer. Serine dehydratase activity declined more rapidly in vitamin B-6 deficient than in control liver; however, ornithine aminotransferase and tyrosine aminotransferase activities were equally stable in deficient and control liver. Ornithine aminotransferase was predominantly in holoenzyme form in both control and deficient rats, whereas tyrosine aminotransferase was predominantly in apoenzyme form in both groups. The proportion of serine dehydratase in apoenzyme was less stable than the holoenzyme. Activity changes of glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase in control and vitamin B-6 deficient rats were similar. The results suggest that differences in the stability of PLP-dependent enzymes in vitamin B-6 deficient rats depend upon differences in the proportions of these enzymes existing as holo- and apoenzyme. | Stability of some pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats. The effects of lowering the liver pyridoxal phosphate (PLP) concentration by vitamin B-6 deficiency on the stability of several rat liver enzymes were examined. Three PLP-dependent enzymes (serine dehydratase, ornithine-delta-aminotransferase, and tyrosine aminotransferase) and two non-PLP-dependent enzymes (glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase) were induced in vitamin B-6 deficient and control rats by feeding them high-protein diets or by injecting them with glucagon or dexamethasone. The decline of each activity was followed after withdrawal of the inducer. Serine dehydratase activity declined more rapidly in vitamin B-6 deficient than in control liver; however, ornithine aminotransferase and tyrosine aminotransferase activities were equally stable in deficient and control liver. Ornithine aminotransferase was predominantly in holoenzyme form in both control and deficient rats, whereas tyrosine aminotransferase was predominantly in apoenzyme form in both groups. The proportion of serine dehydratase in apoenzyme was less stable than the holoenzyme. Activity changes of glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase in control and vitamin B-6 deficient rats were similar. The results suggest that differences in the stability of PLP-dependent enzymes in vitamin B-6 deficient rats depend upon differences in the proportions of these enzymes existing as holo- and apoenzyme. | [
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PMID:4601 | Adsorption sites of kaolin. | The electrophoretic mobility and adsorptive properties of kaolin and kaolin pretreated with anionic and cationic materials were examined over a range of pH values. Pretreatment with anionic compounds had little effect on mobility, while adsorption of cationic species markedly reduced mobility. These results are explained by reference to the structure of kaolin, and the interdependence of adsorption properties and electrophoretic mobility are discussed. | Adsorption sites of kaolin. The electrophoretic mobility and adsorptive properties of kaolin and kaolin pretreated with anionic and cationic materials were examined over a range of pH values. Pretreatment with anionic compounds had little effect on mobility, while adsorption of cationic species markedly reduced mobility. These results are explained by reference to the structure of kaolin, and the interdependence of adsorption properties and electrophoretic mobility are discussed. | [
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PMID:4602 | Electrode sensitive to sulfa drugs. | An electrode sensitive to sulfa drugs was constructed by using the iron(II)-bathophenanthroline chelate embedded in a liquid membrane. Rapid and Nernstian responses were exhibited against solutions of sulfamerazine and sulfisomidine ranging between 10(-3) and 10(-1) M in concentration. High selectivity was observed in the presence of urea, glycine, aminopyrine, or p-amino-benzoic acid. These chemicals are known to interfere in the usual colorimetric analysis of sulfa drugs. | Electrode sensitive to sulfa drugs. An electrode sensitive to sulfa drugs was constructed by using the iron(II)-bathophenanthroline chelate embedded in a liquid membrane. Rapid and Nernstian responses were exhibited against solutions of sulfamerazine and sulfisomidine ranging between 10(-3) and 10(-1) M in concentration. High selectivity was observed in the presence of urea, glycine, aminopyrine, or p-amino-benzoic acid. These chemicals are known to interfere in the usual colorimetric analysis of sulfa drugs. | [
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PMID:4603 | Liquid-solid chromatographic determination of 6-demethylgriseofulvin in urine. | A specific and quantitative liquid-solid chromatographic method for the determination of 6-demethylgriseofulvin in human urine is reported. The method consists of extraction into an organic solvent, addition of internal standard, and analysis by liquid-solid chromatography using a UV detector. Griseofulvin, if present, can be determined simultaneously. The sensitivity of the method is 6 mug/ml of urine. Total 6-demethylgrisefulvin is determined after hydrolysis of the glucuronide conjugate with glucuronidase-sulfatase enzyme solution. The method is well suited for the analysis of a large number of samples. | Liquid-solid chromatographic determination of 6-demethylgriseofulvin in urine. A specific and quantitative liquid-solid chromatographic method for the determination of 6-demethylgriseofulvin in human urine is reported. The method consists of extraction into an organic solvent, addition of internal standard, and analysis by liquid-solid chromatography using a UV detector. Griseofulvin, if present, can be determined simultaneously. The sensitivity of the method is 6 mug/ml of urine. Total 6-demethylgrisefulvin is determined after hydrolysis of the glucuronide conjugate with glucuronidase-sulfatase enzyme solution. The method is well suited for the analysis of a large number of samples. | [
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PMID:4605 | Mass fragmentography of morphine: relationship between brain levels and analgesic activity. | Morphine levels in rat brain were measured by the multiple ion detection method (mass fragmentography), using a computer-controlled gas chromatograph-mass spectrometer, and were correlated with the analgesic activity of the narcotic at intervals up to 6 hours after the injection. Morphine levels in brain reached a peak of 346 ng/g of tissue wet weight 30 minutes after the subcutaneous injection of 10 mg/kg of morphine sulfate and then declined rapidly over the next 3 hours. Between 3 and 6 hours after the injection of morphine, the brain concentration decreased slightly but was still readily detectable at 6 hours after injection. An excellent correlation (r = 0.923) was found between the concentration of morphine in brain and analgesic activity, as measured by the hot plate method. The multiple ion detection method for the measurement of morphine appears to meet all of the criteria necessary for any drug assay: sensitivity, specificity and ease of analysis. | Mass fragmentography of morphine: relationship between brain levels and analgesic activity. Morphine levels in rat brain were measured by the multiple ion detection method (mass fragmentography), using a computer-controlled gas chromatograph-mass spectrometer, and were correlated with the analgesic activity of the narcotic at intervals up to 6 hours after the injection. Morphine levels in brain reached a peak of 346 ng/g of tissue wet weight 30 minutes after the subcutaneous injection of 10 mg/kg of morphine sulfate and then declined rapidly over the next 3 hours. Between 3 and 6 hours after the injection of morphine, the brain concentration decreased slightly but was still readily detectable at 6 hours after injection. An excellent correlation (r = 0.923) was found between the concentration of morphine in brain and analgesic activity, as measured by the hot plate method. The multiple ion detection method for the measurement of morphine appears to meet all of the criteria necessary for any drug assay: sensitivity, specificity and ease of analysis. | [
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PMID:4606 | Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat. | Cardiovascular effects of delta8- and delta9-tetrahydrocannabinol (THC) were studied after systemic intravenous administration and intra-arterial administration into a perfused vascular bed in the urethane-anesthetized rat. Intravenous administration of delta8- and delta9-THC produced dose-related transient increases in blood pressure followed by more prolonged hypotensive responses and bradycardia. Intra-arterial administration of delta8- and delta9-THC into the perfused hindquarters of the rat produced an increase in perfusion pressure indicative of vasoconstriction. The vasoconstrictor response to the cannabinoids corresponded temporally to a similar response produced by i.a. norepinephrine and was in contrast to the more prolonged vasoconstrictor responses produced by vasopressin. Phentolamine, in a dose which reduced the vasoconstrictor effect of norepinephrine by 90%, significantly reduced the response to i.a. delta9-THC while having no effect on the actions of i.a. vasopressin. It was demonstrated that reserpine pretreatment significantly reduced vasoconstrictor actions of i.a. tyramine and delta9-THC but did not alter the responses to norepinephrine. These data suggest that delta8- and delta9-THC have peripheral vasoconstrictor activity in the rat which may be mediated, in part, through a tyramine-like action on adrenergic nerve terminals. | Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat. Cardiovascular effects of delta8- and delta9-tetrahydrocannabinol (THC) were studied after systemic intravenous administration and intra-arterial administration into a perfused vascular bed in the urethane-anesthetized rat. Intravenous administration of delta8- and delta9-THC produced dose-related transient increases in blood pressure followed by more prolonged hypotensive responses and bradycardia. Intra-arterial administration of delta8- and delta9-THC into the perfused hindquarters of the rat produced an increase in perfusion pressure indicative of vasoconstriction. The vasoconstrictor response to the cannabinoids corresponded temporally to a similar response produced by i.a. norepinephrine and was in contrast to the more prolonged vasoconstrictor responses produced by vasopressin. Phentolamine, in a dose which reduced the vasoconstrictor effect of norepinephrine by 90%, significantly reduced the response to i.a. delta9-THC while having no effect on the actions of i.a. vasopressin. It was demonstrated that reserpine pretreatment significantly reduced vasoconstrictor actions of i.a. tyramine and delta9-THC but did not alter the responses to norepinephrine. These data suggest that delta8- and delta9-THC have peripheral vasoconstrictor activity in the rat which may be mediated, in part, through a tyramine-like action on adrenergic nerve terminals. | [
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PMID:4607 | Possible involvement of a transmitter different from norepinephrine in the residual responses to nerve stimulation of the cat nictitating membrane after pretreatment with reserpine. | Pretreatment with reserpine (0.3 or 3 mg/kg, 24 hours before the experiment) reduced the norepinephrine (NE) levels in the medial muscle of the cat nictitating membrane to approximately 2% of the control values. Under these experimental conditions, the responses to postganglionic nerve stimulation were not abolished, reaching up to 50% of the maximum development of tension to exogenous sympathomimetic amines both in vivo and in vitro. In contrast to the responses to nerve stimulation obtained in normal nictitating membranes, the residual responses to nerve stimulation obtained after pretreatment with reserpine were not blocked by phentolamine (3.1 and 31 muM) or by 0.29 muM phenoxybenzamine. The effectiveness of phentolamine and phenoxybenzamine in blocking responses to exogenous NE was the same when the normal nictitating membrane was compared to the smooth muscle obtained from cats pretreated with reserpine. The residual responses to nerve stimulation were reduced when the calcium concentration in the medium was decreased to 0.65 mM. These residual responses were abolished in the presence of tetrodotoxin. Scopolamine, 0.078 muM, did not reduce the residual responses to nerve stimulation while it antagonized the responses to exogenous acetylcholine, indicating that a cholinergic mechanism is not involved in this phenomenon. Adenosine triphosphate (ATP) and adenosine diphosphosphate (ADP) behaved as agonists on the smooth muscle of the normal and of the reserpine-pretreated nictitating membrane and the responses to ATP were not blocked by phentolamine. It is concluded that the residual responses to nerve stimulation obtained after pretreatment with reserpine could be due to the release of a transmitter different from NE. The possibility that ATP or ADP might be involved in these residual responses to nerve stimulation is discussed. | Possible involvement of a transmitter different from norepinephrine in the residual responses to nerve stimulation of the cat nictitating membrane after pretreatment with reserpine. Pretreatment with reserpine (0.3 or 3 mg/kg, 24 hours before the experiment) reduced the norepinephrine (NE) levels in the medial muscle of the cat nictitating membrane to approximately 2% of the control values. Under these experimental conditions, the responses to postganglionic nerve stimulation were not abolished, reaching up to 50% of the maximum development of tension to exogenous sympathomimetic amines both in vivo and in vitro. In contrast to the responses to nerve stimulation obtained in normal nictitating membranes, the residual responses to nerve stimulation obtained after pretreatment with reserpine were not blocked by phentolamine (3.1 and 31 muM) or by 0.29 muM phenoxybenzamine. The effectiveness of phentolamine and phenoxybenzamine in blocking responses to exogenous NE was the same when the normal nictitating membrane was compared to the smooth muscle obtained from cats pretreated with reserpine. The residual responses to nerve stimulation were reduced when the calcium concentration in the medium was decreased to 0.65 mM. These residual responses were abolished in the presence of tetrodotoxin. Scopolamine, 0.078 muM, did not reduce the residual responses to nerve stimulation while it antagonized the responses to exogenous acetylcholine, indicating that a cholinergic mechanism is not involved in this phenomenon. Adenosine triphosphate (ATP) and adenosine diphosphosphate (ADP) behaved as agonists on the smooth muscle of the normal and of the reserpine-pretreated nictitating membrane and the responses to ATP were not blocked by phentolamine. It is concluded that the residual responses to nerve stimulation obtained after pretreatment with reserpine could be due to the release of a transmitter different from NE. The possibility that ATP or ADP might be involved in these residual responses to nerve stimulation is discussed. | [
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PMID:4608 | Pineal beta adrenergic receptor: correlation of binding of 3H-l-alprenolol with stimulation of adenylate cyclase. | 3H-l-Alprenolol, a potent competitive beta adrenergic antagonist, binds to sites in rat pineal gland membranes. The properties of these binding sites were compared to those of the receptors which mediate the beta adrenergic activation of pineal adenylate cyclase. Both sites are highly stereospecific. The l-stereoisomers of alprenolol and propranolol were at least two orders of magnitude more potent than the d-stereoisomers in inhibiting isoproterenol-stimulated adenylate cyclase or 3H-l-alprenolol binding. The dissociation constants (Kd) of the l-stereoisomers of both alprenolol and propranolol were 10 to 22 nM as determined by competition for binding sites or by inhibition of isoproternol-stimulated adenylate cyclase. Beta adrenergic agonists which stimulated adenylate cyclase also competitively inhibited the binding of 3H-l-alprenolol. They showed the same order of potency (isoproterenol greater than norepinephrine greater than or equal to epinephrine) and the same individual affinities in the two systems. Alpha adrenergic blockers were ineffective in inhibiting either adenylate cyclase stimulation or 3H-l-alprenolol binding. Isoproternol stimulation of adenylate cyclase acrivity, and 3H-l-alprenolol binding, were rapid and rapidly reversible. The 3H-l-alprenolol binding sites were saturable and bound 0.6 pmol of ligand per mg of added protein. The data suggest that the binding of 3H-l-alprenolol occurs at sites indistinguishable from the pineal beta adrenergic receptor. | Pineal beta adrenergic receptor: correlation of binding of 3H-l-alprenolol with stimulation of adenylate cyclase. 3H-l-Alprenolol, a potent competitive beta adrenergic antagonist, binds to sites in rat pineal gland membranes. The properties of these binding sites were compared to those of the receptors which mediate the beta adrenergic activation of pineal adenylate cyclase. Both sites are highly stereospecific. The l-stereoisomers of alprenolol and propranolol were at least two orders of magnitude more potent than the d-stereoisomers in inhibiting isoproterenol-stimulated adenylate cyclase or 3H-l-alprenolol binding. The dissociation constants (Kd) of the l-stereoisomers of both alprenolol and propranolol were 10 to 22 nM as determined by competition for binding sites or by inhibition of isoproternol-stimulated adenylate cyclase. Beta adrenergic agonists which stimulated adenylate cyclase also competitively inhibited the binding of 3H-l-alprenolol. They showed the same order of potency (isoproterenol greater than norepinephrine greater than or equal to epinephrine) and the same individual affinities in the two systems. Alpha adrenergic blockers were ineffective in inhibiting either adenylate cyclase stimulation or 3H-l-alprenolol binding. Isoproternol stimulation of adenylate cyclase acrivity, and 3H-l-alprenolol binding, were rapid and rapidly reversible. The 3H-l-alprenolol binding sites were saturable and bound 0.6 pmol of ligand per mg of added protein. The data suggest that the binding of 3H-l-alprenolol occurs at sites indistinguishable from the pineal beta adrenergic receptor. | [
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PMID:4609 | A pharmacological analysis of neurally induced inhibition of carotid body chemoreceptor activity in cats. | Experiments were performed to determine the mechanism by which centrifugal impulses in the carotid sinus nerve (CSN) reduce the frequency of impulse traffic in afferent chemoreceptor fibers from the carotid body in cats. Recordings of chemoreceptor activity were made from single- or few-fiber preparations dissected off the CSN, while the remainder of the CSN was stimulated electrically to produce neurally induced inhibition of chemoreceptor activity. Various drugs were injected either intravenously or directly into the arterial blood supply to the carotid body. We found that catecholamines (dopamine, norepinephrine and epinephrine) inhibited spontaneous chemoreceptor activity, and that alpha adrenergic antagonists abolished both this inhibition and that produced by electrical stimulation of the CSN in the same preparation. Atropine, but not nicotinic antagonists of acetylcholine, consistently blocked neurally induced inhibition but not that produced by catecholamines. Muscarinic agonists had no effect on spontaneous chemoreceptor activity. We conclude that centrifugal activity in the CSN causes release of endogenous catecholamines in the carotid body, and that these catecholamines mediate neurally induced inhibition of chemoreceptor activity is due to the vasomotor effects of acetylcholine. | A pharmacological analysis of neurally induced inhibition of carotid body chemoreceptor activity in cats. Experiments were performed to determine the mechanism by which centrifugal impulses in the carotid sinus nerve (CSN) reduce the frequency of impulse traffic in afferent chemoreceptor fibers from the carotid body in cats. Recordings of chemoreceptor activity were made from single- or few-fiber preparations dissected off the CSN, while the remainder of the CSN was stimulated electrically to produce neurally induced inhibition of chemoreceptor activity. Various drugs were injected either intravenously or directly into the arterial blood supply to the carotid body. We found that catecholamines (dopamine, norepinephrine and epinephrine) inhibited spontaneous chemoreceptor activity, and that alpha adrenergic antagonists abolished both this inhibition and that produced by electrical stimulation of the CSN in the same preparation. Atropine, but not nicotinic antagonists of acetylcholine, consistently blocked neurally induced inhibition but not that produced by catecholamines. Muscarinic agonists had no effect on spontaneous chemoreceptor activity. We conclude that centrifugal activity in the CSN causes release of endogenous catecholamines in the carotid body, and that these catecholamines mediate neurally induced inhibition of chemoreceptor activity is due to the vasomotor effects of acetylcholine. | [
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PMID:4610 | On the ability of narcotic antagonists to produce the narcotic cue. | The ability of narcotic antagonists to produce the narcotic cue was investigated in rats trained to discriminate fentanyl (0.04 mg/kg) from solvent. The partial antagonists pentazocine, cyclazocine and nalorphine were found to possess narcotic cuing activity whereas naloxone lacked any such action at doses up to 160 mg/kg. The relationship between the present findings and the ability of these drugs to produce opiate-like subjective effects in humans is discussed. The conclusion was reached that the experimental procedure used may contribute significantly to the preclinical evaluation of drug abuse liability. | On the ability of narcotic antagonists to produce the narcotic cue. The ability of narcotic antagonists to produce the narcotic cue was investigated in rats trained to discriminate fentanyl (0.04 mg/kg) from solvent. The partial antagonists pentazocine, cyclazocine and nalorphine were found to possess narcotic cuing activity whereas naloxone lacked any such action at doses up to 160 mg/kg. The relationship between the present findings and the ability of these drugs to produce opiate-like subjective effects in humans is discussed. The conclusion was reached that the experimental procedure used may contribute significantly to the preclinical evaluation of drug abuse liability. | [
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PMID:4611 | Effect of para-aminohippurate on renal glutamine metabolism in the rat. | After para-aminohippurate (PAH) infusion into rats, urine pH decreased and urine ammonium excretion increased. Because augmented urine flow and decreased urine pH could not explain entirely the enhanced ammonium excretion, an increased ammonia production was postulated as a contributing influence. This was supported by the in vitro findings that PAH could increase slice ammoniagenesis from glutamine. The ability of PAH to stimulate ammoniagenesis in vitro was attributed to enhanced phosphate-dependent glutaminase activity. We conclude that PAH infusions at certain concentrations in vivo can alter ammonium excretion through increased renal ammonia production. The latter may be secondary to enhanced phosphate-dependent glutaminase activity. | Effect of para-aminohippurate on renal glutamine metabolism in the rat. After para-aminohippurate (PAH) infusion into rats, urine pH decreased and urine ammonium excretion increased. Because augmented urine flow and decreased urine pH could not explain entirely the enhanced ammonium excretion, an increased ammonia production was postulated as a contributing influence. This was supported by the in vitro findings that PAH could increase slice ammoniagenesis from glutamine. The ability of PAH to stimulate ammoniagenesis in vitro was attributed to enhanced phosphate-dependent glutaminase activity. We conclude that PAH infusions at certain concentrations in vivo can alter ammonium excretion through increased renal ammonia production. The latter may be secondary to enhanced phosphate-dependent glutaminase activity. | [
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PMID:4612 | Inhibition by sulfobromophthalein of mitochondrial translocation of anions and adenine nucleotides: effects upon liver adenosine triphosphate and possible correlation with inhibition of bile flow in the rat. | Unconjugated sulfobromophthalein (BSP) inhibits state III respiration of rat liver mitochondria. It competitively inhibits the translocation into mitochondria of citrate, malate, phosphate and adenosine diphosphate, as studied by the inhibitor stop method. A double-beam spectrophotometric study strongly suggests that glutamate translocation is similarly inhibited. After perfusion of 65 mumol/hr/100 g for 90 minutes, bile flow is inhibited by 82% and liver adenosine triphosphate (ATP) falls by 60%. The amount of mitochondrial BSP can be computed form the amount of [35S] BSP still bound to mitochondria that are prepared at the end of such experiments; the amount of BSP lost during the isolation procedure is estimated from parallel experiments following binding of BSP in vitro. Comparison of the kinetic constants of mitochondrial transport and of their inhibition by BSP on the one hand and of liver concentration of substrates and BSP on the other gives rise to the conclusion that a strong inhibition of transports, mainly of phosphate, occurs in vivo and is responsible for the concomitant decrease in bile flow. | Inhibition by sulfobromophthalein of mitochondrial translocation of anions and adenine nucleotides: effects upon liver adenosine triphosphate and possible correlation with inhibition of bile flow in the rat. Unconjugated sulfobromophthalein (BSP) inhibits state III respiration of rat liver mitochondria. It competitively inhibits the translocation into mitochondria of citrate, malate, phosphate and adenosine diphosphate, as studied by the inhibitor stop method. A double-beam spectrophotometric study strongly suggests that glutamate translocation is similarly inhibited. After perfusion of 65 mumol/hr/100 g for 90 minutes, bile flow is inhibited by 82% and liver adenosine triphosphate (ATP) falls by 60%. The amount of mitochondrial BSP can be computed form the amount of [35S] BSP still bound to mitochondria that are prepared at the end of such experiments; the amount of BSP lost during the isolation procedure is estimated from parallel experiments following binding of BSP in vitro. Comparison of the kinetic constants of mitochondrial transport and of their inhibition by BSP on the one hand and of liver concentration of substrates and BSP on the other gives rise to the conclusion that a strong inhibition of transports, mainly of phosphate, occurs in vivo and is responsible for the concomitant decrease in bile flow. | [
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PMID:4613 | Dissociation constants and relative efficacies of agonists acting on alpha adrenergic receptors in rabbit aorta. | The dissociation constants (KA values) of l-norepinephrine (l-NE) and seven other agonists acting on alpha adrenergic receptors in rabbit aorta strips were determined by analysis of concentration-response data before and after fractional inactivation of receptors with Dibenamine. In experiments to determine KA values, propranolol was added to block activation of beta receptors and cocaine to block the neuronal uptake mechanism. The KA of l-NE and the KA of a second agonist, when determined on paired strips from the same aorta, were used to calculate the relative affinity and the relative efficacy (er) of the second agonist as compared to l-NE. The validity of the method used for determining KA and er values was supported by the following findings. 1) The dissociation constant (KB) of the competitive antagonist, phentolamine, determined with each of the agonists, was the same as that determined with l-NE. 2) The KA determined for l-NE was independent of the fraction of active receptors remaining (q) after pretreatment with different concentrations of Dibenamine. 3) The KB of phentolamine determined with l-NE as the agonist was the same before and after fractional inactivation of receptors. 4) After inactivation in paired strips by equal exposures to Dibenamine, the q value determined with each agonist was the same as that determined with l-NE. The mean KA value for l-NE was 3.39 +/- 0.15 X 10(-7) M. The mean relative affinities of the agonists for the alpha receptor were: l-NE, 1;L-EPINEPHRINE, 1.25; L-PHENYLEPHRINE, 0.200; L-norphenylephrine, 0.217; epinine, 0.136; dopamine, 0.0055; l-alpha-methylnorepinephrine, 0.095; dl-alpha-ethylnorepinephrine, 0.0048. The mean er of each agonist was not significantly different from that of l-NE, except for l-norphenylephrine with an e of 0.71, and dl-alpha-ethylnorepinephrine with an er of 0.41. The results are discussed from the standpoint of structure-activity relationships. | Dissociation constants and relative efficacies of agonists acting on alpha adrenergic receptors in rabbit aorta. The dissociation constants (KA values) of l-norepinephrine (l-NE) and seven other agonists acting on alpha adrenergic receptors in rabbit aorta strips were determined by analysis of concentration-response data before and after fractional inactivation of receptors with Dibenamine. In experiments to determine KA values, propranolol was added to block activation of beta receptors and cocaine to block the neuronal uptake mechanism. The KA of l-NE and the KA of a second agonist, when determined on paired strips from the same aorta, were used to calculate the relative affinity and the relative efficacy (er) of the second agonist as compared to l-NE. The validity of the method used for determining KA and er values was supported by the following findings. 1) The dissociation constant (KB) of the competitive antagonist, phentolamine, determined with each of the agonists, was the same as that determined with l-NE. 2) The KA determined for l-NE was independent of the fraction of active receptors remaining (q) after pretreatment with different concentrations of Dibenamine. 3) The KB of phentolamine determined with l-NE as the agonist was the same before and after fractional inactivation of receptors. 4) After inactivation in paired strips by equal exposures to Dibenamine, the q value determined with each agonist was the same as that determined with l-NE. The mean KA value for l-NE was 3.39 +/- 0.15 X 10(-7) M. The mean relative affinities of the agonists for the alpha receptor were: l-NE, 1;L-EPINEPHRINE, 1.25; L-PHENYLEPHRINE, 0.200; L-norphenylephrine, 0.217; epinine, 0.136; dopamine, 0.0055; l-alpha-methylnorepinephrine, 0.095; dl-alpha-ethylnorepinephrine, 0.0048. The mean er of each agonist was not significantly different from that of l-NE, except for l-norphenylephrine with an e of 0.71, and dl-alpha-ethylnorepinephrine with an er of 0.41. The results are discussed from the standpoint of structure-activity relationships. | [
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PMID:4614 | The effect of carbon dioxide on the intracellular pH and buffering power of snail neurones. | 1. Intracellular pH (pHi) was measured using pH-sensitive glass micro-electrodes. The effects on pHi of CO2 applied externally and HCO3-, H+ and NH4+ injected iontophoretically, were investigated. 2. The transport numbers for iontophoretic injection into aqueous micro-droples were found by potentiometric titration to be 0-3 for HCO3- and 0-94 for H+. 3. Exposure to Ringer, pH 7-5, equilibrated with 2-2% CO2 caused a rapid, but only transient, fall in pHi. Within 1 or 2 min pHi began to return exponentially to normal, with a time constant of about 5 min. 4. When external CO2 was removed, pHi rapidly increased, and then slowly returned to normal. The pHi changes with CO2 application or removal gave a calculated intracellular buffer value of about 30 m-equiv H+/pH unit per litre. 5. Injection of HCO3- caused a rise in pHi very similar to that seen on removal of external CO2. 6. The pHi responses to CO2 application, CO2 removal and HCO3- injection were slowed by the carbonic anhydrase inhibitor acetazolamide. 7. H+ injection caused a transient fall in pHi. In CO2 Ringer pHi fell less and recovered faster than in CO2-free Ringer. Calculation of the internal buffer value from the pHi responses to H+ and HCO3- injection gave very similar values. 8. The internal buffer value (measured by H+ injection) was greatly increased by exposure to CO2 Ringer. Acetazolamide reduced this effect of CO2, suggesting that the function of intracellular carbonic anhydrase may be to maximize the internal buffering power in CO2. 9. It was concluded that the internal HCO3- was determined primarily by the CO2 level and pHi, that internal HCO3- made a large contribution to the buffering power, and that after internal acidfication pHi was restored to normal by active transport of H+, OH- or HCO3- across the cell membrane. The active transport was much faster in CO2 than in CO2-free Ringer. | The effect of carbon dioxide on the intracellular pH and buffering power of snail neurones. 1. Intracellular pH (pHi) was measured using pH-sensitive glass micro-electrodes. The effects on pHi of CO2 applied externally and HCO3-, H+ and NH4+ injected iontophoretically, were investigated. 2. The transport numbers for iontophoretic injection into aqueous micro-droples were found by potentiometric titration to be 0-3 for HCO3- and 0-94 for H+. 3. Exposure to Ringer, pH 7-5, equilibrated with 2-2% CO2 caused a rapid, but only transient, fall in pHi. Within 1 or 2 min pHi began to return exponentially to normal, with a time constant of about 5 min. 4. When external CO2 was removed, pHi rapidly increased, and then slowly returned to normal. The pHi changes with CO2 application or removal gave a calculated intracellular buffer value of about 30 m-equiv H+/pH unit per litre. 5. Injection of HCO3- caused a rise in pHi very similar to that seen on removal of external CO2. 6. The pHi responses to CO2 application, CO2 removal and HCO3- injection were slowed by the carbonic anhydrase inhibitor acetazolamide. 7. H+ injection caused a transient fall in pHi. In CO2 Ringer pHi fell less and recovered faster than in CO2-free Ringer. Calculation of the internal buffer value from the pHi responses to H+ and HCO3- injection gave very similar values. 8. The internal buffer value (measured by H+ injection) was greatly increased by exposure to CO2 Ringer. Acetazolamide reduced this effect of CO2, suggesting that the function of intracellular carbonic anhydrase may be to maximize the internal buffering power in CO2. 9. It was concluded that the internal HCO3- was determined primarily by the CO2 level and pHi, that internal HCO3- made a large contribution to the buffering power, and that after internal acidfication pHi was restored to normal by active transport of H+, OH- or HCO3- across the cell membrane. The active transport was much faster in CO2 than in CO2-free Ringer. | [
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PMID:4615 | [Blood acid-base changes produced by variations of water oxygenation in the crab Carcinus maenas (author's transl)]. | 10 Blood acid-base changes were studied at 17 degrees C in immersed crabs (Carcinus maenas) exposed to hypoxic and hyperoxic conditions, by measuring the pH and the CO2 partial pressure, PbCO2, and by calculating the bicarbonate concentration. 20 Hyperoxia first induces a marked respiratory acidosis with a rise of PbCO2. This acidosis is compensated thereafter by a non-ventilatory increase of the blood buffer base concentration. These results are discussed in relation to the general problems concerning the control of the blood acid-base balance in aquatic animals. | [Blood acid-base changes produced by variations of water oxygenation in the crab Carcinus maenas (author's transl)]. 10 Blood acid-base changes were studied at 17 degrees C in immersed crabs (Carcinus maenas) exposed to hypoxic and hyperoxic conditions, by measuring the pH and the CO2 partial pressure, PbCO2, and by calculating the bicarbonate concentration. 20 Hyperoxia first induces a marked respiratory acidosis with a rise of PbCO2. This acidosis is compensated thereafter by a non-ventilatory increase of the blood buffer base concentration. These results are discussed in relation to the general problems concerning the control of the blood acid-base balance in aquatic animals. | [
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PMID:4617 | The diagnosis and treatment of acid-base deranged dogs infected with Babesia canis. | A study was made of the acid-base status of Babesia canis infected dogs judged unlikely to recover after specific babesicidal drug therapy despite the use of blood transfusion and other conventional supportive measures. Such cases were invariably acidotic and responded well and often dramatically to supportive intravenous sodium bicarbonate administration. Elevated blood urea nitrogen, also responded gratifyingly to this procedure. The rationale is discussed in some detail. | The diagnosis and treatment of acid-base deranged dogs infected with Babesia canis. A study was made of the acid-base status of Babesia canis infected dogs judged unlikely to recover after specific babesicidal drug therapy despite the use of blood transfusion and other conventional supportive measures. Such cases were invariably acidotic and responded well and often dramatically to supportive intravenous sodium bicarbonate administration. Elevated blood urea nitrogen, also responded gratifyingly to this procedure. The rationale is discussed in some detail. | [
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PMID:4624 | Regulation of cell volume and ion concentrations in a Halobacterium. | Changes in cell volume and ion content of a Halobacterium species are described in terms of the NaCl concentration (0.5--3.5M) and pH(4-8) of the suspending medium. Cell volume, per unit content of protein of bacteria in stationary phase cultures, rose as the [NaCl] of the growth medium was increased. Logarithmic-phase bacteria shrank as the pH fell from 7 to 5.5. These changes are characteristic of bacteria with a moderate or rapid rate of O2 consumption. Starving (i.e. nonmetabolizing) bacteria, on the other hand, did not change in size within the above ranges of [NaCl] and pH. At lower values, however, such bacteria swelled and eventually lysed. Effects of low pH on cell ions are compared in metabolizing and starving bacteria, and it is shown that changes in the state of the cell K are correlated with movements of cell Na. It appears that the cell K is used to maintain cell [Na] below the NaCl concentration of the medium. The results are explained in terms of a model involving interactions between polyelectrolytes, salts and water in the concentrated cytoplasm of these halophilic organisms. | Regulation of cell volume and ion concentrations in a Halobacterium. Changes in cell volume and ion content of a Halobacterium species are described in terms of the NaCl concentration (0.5--3.5M) and pH(4-8) of the suspending medium. Cell volume, per unit content of protein of bacteria in stationary phase cultures, rose as the [NaCl] of the growth medium was increased. Logarithmic-phase bacteria shrank as the pH fell from 7 to 5.5. These changes are characteristic of bacteria with a moderate or rapid rate of O2 consumption. Starving (i.e. nonmetabolizing) bacteria, on the other hand, did not change in size within the above ranges of [NaCl] and pH. At lower values, however, such bacteria swelled and eventually lysed. Effects of low pH on cell ions are compared in metabolizing and starving bacteria, and it is shown that changes in the state of the cell K are correlated with movements of cell Na. It appears that the cell K is used to maintain cell [Na] below the NaCl concentration of the medium. The results are explained in terms of a model involving interactions between polyelectrolytes, salts and water in the concentrated cytoplasm of these halophilic organisms. | [
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PMID:4627 | Behavioral and psychodynamic dimensions of the new sex therapy. | The new sexual therapy, a brief outpatient treatment of sexual dysfunction consisting of structured sexual exercises and conjoint therapeutic sessions, is a systematic intergration of behavioral and psychodynamic elements. Formally consisting of many defining characteristics of a behavior therapy including the direct treatment of a specified problem and the application of behavioral principles, the new sex therapy also relies on psychodynamic understanding. The result is synergistic. Psychodynamic understanding underlies appropriate behavioral intervention, and psychodynamic exploration of resistance enhances the effectiveness of behavioral methods. Behavioral techniques facilitate the most rapid implementation of therapeutic insight. The integration of approaches in the new sex therapy has general significance for psychotherapeutic theory and practice. | Behavioral and psychodynamic dimensions of the new sex therapy. The new sexual therapy, a brief outpatient treatment of sexual dysfunction consisting of structured sexual exercises and conjoint therapeutic sessions, is a systematic intergration of behavioral and psychodynamic elements. Formally consisting of many defining characteristics of a behavior therapy including the direct treatment of a specified problem and the application of behavioral principles, the new sex therapy also relies on psychodynamic understanding. The result is synergistic. Psychodynamic understanding underlies appropriate behavioral intervention, and psychodynamic exploration of resistance enhances the effectiveness of behavioral methods. Behavioral techniques facilitate the most rapid implementation of therapeutic insight. The integration of approaches in the new sex therapy has general significance for psychotherapeutic theory and practice. | [
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PMID:4628 | The use of microchemical techniques for the identification of new transmitter molecules in neurons. | The author reviews available microtechniques and results on cellular analysis of single neurons emphasizing the identification of putative neurotransmitter molecules. Highly sensitive microquantitative methods for identification and assay of known and putative neurotransmitters have been developed within the last 15 years. Several of the methods reported in the article fulfill the requirements of both specificity and sensitivity for exploring and measuring the level of transmitter molecules in single neurons. Some of the available techniques, mostly those which associate GC or TLC with MS, have been able to unambiguously demonstrate the presence of putative neurotransmitter molecules, or at least of substances which are strongly suspected of fulfilling a functional role in the nervous system. | The use of microchemical techniques for the identification of new transmitter molecules in neurons. The author reviews available microtechniques and results on cellular analysis of single neurons emphasizing the identification of putative neurotransmitter molecules. Highly sensitive microquantitative methods for identification and assay of known and putative neurotransmitters have been developed within the last 15 years. Several of the methods reported in the article fulfill the requirements of both specificity and sensitivity for exploring and measuring the level of transmitter molecules in single neurons. Some of the available techniques, mostly those which associate GC or TLC with MS, have been able to unambiguously demonstrate the presence of putative neurotransmitter molecules, or at least of substances which are strongly suspected of fulfilling a functional role in the nervous system. | [
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PMID:4631 | Studies of introital colonization in women with recurrent urinary infections. V. The inhibitory activity of normal vaginal fluid on Proteus mirabilis and Pseudomonas aeruginosa. | Normal vaginal fluid from premenopausal volunteers was inoculated with 10 strains of Proteus mirabilis and 14 strains of Pseudomonas aeruginosa at pH's of 4.3, 4.6 and 4.9. All bacteria were killed at pH 4.3. Nine of 10 strains of Proteus mirabilis and 12 of 14 Pseudomonas aeruginosa were killed at pH 4.6. Only 4 of 14 strains of Pseudomonas aeruginosa were killed at pH 4.9, while 8 of 10 strains of Proteus mirabilis were killed at the same pH. We conclude that in comparison to the common 0 group strains of Escherichia coli, vaginal fluid is more bactericidal to Proteus mirabilis and Pseudomonas aeruginosa and that these observations may help explain the relative infrequency of bacteriuria owing to the organisms. | Studies of introital colonization in women with recurrent urinary infections. V. The inhibitory activity of normal vaginal fluid on Proteus mirabilis and Pseudomonas aeruginosa. Normal vaginal fluid from premenopausal volunteers was inoculated with 10 strains of Proteus mirabilis and 14 strains of Pseudomonas aeruginosa at pH's of 4.3, 4.6 and 4.9. All bacteria were killed at pH 4.3. Nine of 10 strains of Proteus mirabilis and 12 of 14 Pseudomonas aeruginosa were killed at pH 4.6. Only 4 of 14 strains of Pseudomonas aeruginosa were killed at pH 4.9, while 8 of 10 strains of Proteus mirabilis were killed at the same pH. We conclude that in comparison to the common 0 group strains of Escherichia coli, vaginal fluid is more bactericidal to Proteus mirabilis and Pseudomonas aeruginosa and that these observations may help explain the relative infrequency of bacteriuria owing to the organisms. | [
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PMID:4632 | Successful autotransplantation of an intra-abdominal testis to the scrotum by microvascular technique. | An intra-abdominal testis in a child with prune belly syndrome was successfully transplanted to the scrotum by a microvascular technique. Immediate results were good with no palpable atrophy of the testis. Long-term results (fertility) will not be known for many years. The technique of microvascular anastomosis and its application to orchiopexy are described. | Successful autotransplantation of an intra-abdominal testis to the scrotum by microvascular technique. An intra-abdominal testis in a child with prune belly syndrome was successfully transplanted to the scrotum by a microvascular technique. Immediate results were good with no palpable atrophy of the testis. Long-term results (fertility) will not be known for many years. The technique of microvascular anastomosis and its application to orchiopexy are described. | [
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PMID:4633 | Two rare cases of ectopic testis. | A case of pubopenile testis and a case of perineal ectopic testis are presented. The mechanism of descensus is largely positive, possibly facilitated by raised intra-abdominal pressure. The testis is usually guided by the gubernaculum and ectopia results from gubernacular failure. The ectopic testis is relatively rare but is easily recognized and treated by orchiopexy. | Two rare cases of ectopic testis. A case of pubopenile testis and a case of perineal ectopic testis are presented. The mechanism of descensus is largely positive, possibly facilitated by raised intra-abdominal pressure. The testis is usually guided by the gubernaculum and ectopia results from gubernacular failure. The ectopic testis is relatively rare but is easily recognized and treated by orchiopexy. | [
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PMID:4634 | Familial persistent Müllerian duct syndrome. | Two phenotypically normal pre-adolescent brothers with bilateral undescended testes were found to have bilateral fallopian tubes, a uterus and a vagina that drained into the prostatic utricle. We have documented this condition radiographically for the first time, gained some insight into the pattern of inheritance and made recommendations for surgical management. | Familial persistent Müllerian duct syndrome. Two phenotypically normal pre-adolescent brothers with bilateral undescended testes were found to have bilateral fallopian tubes, a uterus and a vagina that drained into the prostatic utricle. We have documented this condition radiographically for the first time, gained some insight into the pattern of inheritance and made recommendations for surgical management. | [
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PMID:4640 | Studies on the mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (II). Analysis by the uptake saturation model. | Curves of experimentally plotted log (dose ratio-1) vs.-log [B] for the antagonism between adrenergic beta-mimetics, isoproterenol (ISO) and trimetoquinol (TMQ), and various beta-antagonists in relaxation of guinea-pig trachea could not be reasonably fitted to Schild's equation which has been commonly used in the analysis of drug-antagonism. Taking into consideration the saturable uptake process of the drug used herein, the equation presented in this paper fitted fairly well to the experimental curves and explains the following results: 1, TMQ was more strongly antagonized than ISO by all the blocking agents tested, that is, the apparent modes of antagonism were different between ISO and TMQ although they are considered to interact with the same receptor site. 2, The slope of the curve for a given antagonist markedly differed between ISO and TMQ. It is hypothesized that ISO is more easily taken up than TMQ. This was experimentally confirmed: i.e., ISO was potentiated about 8 fold by inhibiting the uptake process with dibenamine while TMQ was not. By pretreatment with dibenamine, the log (dose ratio-1) vs.-log [B] curve for the ISO-propranolol antagonism was shifted upward and superimposed with the theoretical curve of antagonism in which uptake of the agonist was neglected. | Studies on the mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (II). Analysis by the uptake saturation model. Curves of experimentally plotted log (dose ratio-1) vs.-log [B] for the antagonism between adrenergic beta-mimetics, isoproterenol (ISO) and trimetoquinol (TMQ), and various beta-antagonists in relaxation of guinea-pig trachea could not be reasonably fitted to Schild's equation which has been commonly used in the analysis of drug-antagonism. Taking into consideration the saturable uptake process of the drug used herein, the equation presented in this paper fitted fairly well to the experimental curves and explains the following results: 1, TMQ was more strongly antagonized than ISO by all the blocking agents tested, that is, the apparent modes of antagonism were different between ISO and TMQ although they are considered to interact with the same receptor site. 2, The slope of the curve for a given antagonist markedly differed between ISO and TMQ. It is hypothesized that ISO is more easily taken up than TMQ. This was experimentally confirmed: i.e., ISO was potentiated about 8 fold by inhibiting the uptake process with dibenamine while TMQ was not. By pretreatment with dibenamine, the log (dose ratio-1) vs.-log [B] curve for the ISO-propranolol antagonism was shifted upward and superimposed with the theoretical curve of antagonism in which uptake of the agonist was neglected. | [
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PMID:4645 | pH of sweat of patients with cystic fibrosis. | pH of the sweat from patients with cystic fibrosis and in controls was measured as a function of the sweat-rate using a fluorescence-pH-indicator (umbelliferone). In both populations sweat is acid at low sweat-rates and alkaline at high ones. The results do not favour an abnormality of the ductal H+-secretion as the pathomechanism of cystic fibrosis. | pH of sweat of patients with cystic fibrosis. pH of the sweat from patients with cystic fibrosis and in controls was measured as a function of the sweat-rate using a fluorescence-pH-indicator (umbelliferone). In both populations sweat is acid at low sweat-rates and alkaline at high ones. The results do not favour an abnormality of the ductal H+-secretion as the pathomechanism of cystic fibrosis. | [
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PMID:4649 | Morphologic and biochemical changes in autolysing dog heart muscle. | The progressive changes in pH, lactate content, and light and electron microscopic appearances were studied in dog myocardium undergoing a 6-hour period of autolysis in vitro at 37 degrees C. and at room temperature. At 37 degrees C. there was a rapid cumulative fall in pH during the 1st hour after excision of the heart and a corresponding increase in lactate content, but little additional change in either subsequently. The nature and sequence of the morphologic alterations at this temperature were generally similar to those which occur in ischemic myocardium in vivo. At room temperature, a much slower cumulative decrease in pH and increase in lactate content took place throughout the whole period of investigation and was paralleled by a slower rate of development of morphologic change. | Morphologic and biochemical changes in autolysing dog heart muscle. The progressive changes in pH, lactate content, and light and electron microscopic appearances were studied in dog myocardium undergoing a 6-hour period of autolysis in vitro at 37 degrees C. and at room temperature. At 37 degrees C. there was a rapid cumulative fall in pH during the 1st hour after excision of the heart and a corresponding increase in lactate content, but little additional change in either subsequently. The nature and sequence of the morphologic alterations at this temperature were generally similar to those which occur in ischemic myocardium in vivo. At room temperature, a much slower cumulative decrease in pH and increase in lactate content took place throughout the whole period of investigation and was paralleled by a slower rate of development of morphologic change. | [
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PMID:4648 | [Conditioning of water regenerated from moisture-containing wastes]. | Conditioning of reclaimed water with minerals and trace elements by means of filters made of silver-plated natural minerals containing calcium, magnesium, fluoride and iodine ions has been investigated. On the basis of the investigations a complex filter made of silver plated minerals--dolomite and fluorite--has been developed. This filter allows simultaneous mineralization and decontamination of reclaimed water and preparation of biologically complete potable water. | [Conditioning of water regenerated from moisture-containing wastes]. Conditioning of reclaimed water with minerals and trace elements by means of filters made of silver-plated natural minerals containing calcium, magnesium, fluoride and iodine ions has been investigated. On the basis of the investigations a complex filter made of silver plated minerals--dolomite and fluorite--has been developed. This filter allows simultaneous mineralization and decontamination of reclaimed water and preparation of biologically complete potable water. | [
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] |
PMID:4647 | [Problem of "biological compatibility" of crew members during prolonged space flight and possible directions for its solution]. | The concept of biological compatibility of men can be defined as a phenomenon which includes an effect (that might be favorable or unfavorable) of one individuum on the other via trace amounts of chemicals released into their environment and micro-organisms. The paper presents the main results of studies of biological compatibility of crewmembers of space vehicles and outlines possible directions of research to be carried out in this area. | [Problem of "biological compatibility" of crew members during prolonged space flight and possible directions for its solution]. The concept of biological compatibility of men can be defined as a phenomenon which includes an effect (that might be favorable or unfavorable) of one individuum on the other via trace amounts of chemicals released into their environment and micro-organisms. The paper presents the main results of studies of biological compatibility of crewmembers of space vehicles and outlines possible directions of research to be carried out in this area. | [
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PMID:4657 | Proteins of the hepatoma tissue culture cell plasma membrane. | The specificity of lactoperoxidase-catalyzed iodination for the proteins of the hepatoma tissue culture cell plasma membrane was examined by histochemical, biochemical, and cell fractionation techniques. Light microscope autoradiography of sectioned cells shows the incorporated label to be localized primarily at the periphery of the cell. Most of this label can be released from the cell by trypsin but not by collagenase or hyaluronidase. The label is recovered from the cells as either monoiodotyrosine or diiodotyrosine after hydrolysis of cell extracts with a mixture of proteolytic enzymes. The label co-purifies during cell fractionation with an authentic liver cell plasma membrane marker enzyme, 5'-nucleotidase. Thus, the incorporated iodide is itself a valid marker for those membrane polypeptides having tyrosine residues accessible to the lactoperoxidase. The polypeptide complexity of the purified plasma membrane was examined by high resolution dodecyl sulfate-polyacrylamide gel electrophoresis. At least 50 polypeptides in the membrane are accessible to iodination. These polypeptides probably represent the bulk of the protein mass of the membrane and iodinating them does not affect cell viability, growth rate, or cell function. Labeling experiments with fucose and glucosamine show that at least nine of the iodinated peptides may be glycoproteins. | Proteins of the hepatoma tissue culture cell plasma membrane. The specificity of lactoperoxidase-catalyzed iodination for the proteins of the hepatoma tissue culture cell plasma membrane was examined by histochemical, biochemical, and cell fractionation techniques. Light microscope autoradiography of sectioned cells shows the incorporated label to be localized primarily at the periphery of the cell. Most of this label can be released from the cell by trypsin but not by collagenase or hyaluronidase. The label is recovered from the cells as either monoiodotyrosine or diiodotyrosine after hydrolysis of cell extracts with a mixture of proteolytic enzymes. The label co-purifies during cell fractionation with an authentic liver cell plasma membrane marker enzyme, 5'-nucleotidase. Thus, the incorporated iodide is itself a valid marker for those membrane polypeptides having tyrosine residues accessible to the lactoperoxidase. The polypeptide complexity of the purified plasma membrane was examined by high resolution dodecyl sulfate-polyacrylamide gel electrophoresis. At least 50 polypeptides in the membrane are accessible to iodination. These polypeptides probably represent the bulk of the protein mass of the membrane and iodinating them does not affect cell viability, growth rate, or cell function. Labeling experiments with fucose and glucosamine show that at least nine of the iodinated peptides may be glycoproteins. | [
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PMID:4658 | Lesion-induced synaptogenesis in brain: a study of dynamic changes in neuronal membrane specializations. | When incoming fibers to a given brain region are damaged and degenerate, the remaining undamaged fibers can, in some cases, form new synapses, and restore physiologically functional circuitry. Synaptic membrane events underlie this reconstruction: the connection between membranes is broken and reformed. | Lesion-induced synaptogenesis in brain: a study of dynamic changes in neuronal membrane specializations. When incoming fibers to a given brain region are damaged and degenerate, the remaining undamaged fibers can, in some cases, form new synapses, and restore physiologically functional circuitry. Synaptic membrane events underlie this reconstruction: the connection between membranes is broken and reformed. | [
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PMID:4659 | Preliminary characterization of the acetylcholine receptor in human erythrocytes. | The response of human erythrocytes to cholinergic ligands was studied with an electron spin resonance assay. The membrane response to carbamyl choline was found to be antagonized by atropine and, in the absence of calcium, by tetrodotoxin. Experiments with resealed ghosts showed that the membrane response to carbamyl choline required ATP and calcium. Reductive alkylation of intact cells eliminated the cholinergic response, but the presence of saturating amounts of carbamyl choline protected the putative receptor against inactivation. Affinity labeling was used to demonstrate an apparent molecular weight of 41,000 for the carbamyl choline-binding species. A lipid vesicle extraction technique was used to induce a specific cation permeability defect in intact cells. Preliminary investigation of this phenomenon is described. | Preliminary characterization of the acetylcholine receptor in human erythrocytes. The response of human erythrocytes to cholinergic ligands was studied with an electron spin resonance assay. The membrane response to carbamyl choline was found to be antagonized by atropine and, in the absence of calcium, by tetrodotoxin. Experiments with resealed ghosts showed that the membrane response to carbamyl choline required ATP and calcium. Reductive alkylation of intact cells eliminated the cholinergic response, but the presence of saturating amounts of carbamyl choline protected the putative receptor against inactivation. Affinity labeling was used to demonstrate an apparent molecular weight of 41,000 for the carbamyl choline-binding species. A lipid vesicle extraction technique was used to induce a specific cation permeability defect in intact cells. Preliminary investigation of this phenomenon is described. | [
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PMID:4660 | Effect of alcohol on elicited male sexual response. | Sixteen young men drunk three doses of alcohol and their sexual arousal was measured by the changes in penile diameter. The lowest alcohol dose (BAC of 0.025%) was associated with maximum penile diameter increase; marked suppression of response was found at BACs of 0.05% and above. | Effect of alcohol on elicited male sexual response. Sixteen young men drunk three doses of alcohol and their sexual arousal was measured by the changes in penile diameter. The lowest alcohol dose (BAC of 0.025%) was associated with maximum penile diameter increase; marked suppression of response was found at BACs of 0.05% and above. | [
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PMID:4661 | "Feeling no pain" differential responses to pain by alcoholics and nonalcoholics before and after drinking. | Whisky reduced the level of pain reported by alcoholics but had no effect on that reported by nonalcoholics. The results appear to be based on the joint effects of the alcoholic's expectation that alcohol has an analgesic effect and the physiological cues accompanying alcohol consumption. | "Feeling no pain" differential responses to pain by alcoholics and nonalcoholics before and after drinking. Whisky reduced the level of pain reported by alcoholics but had no effect on that reported by nonalcoholics. The results appear to be based on the joint effects of the alcoholic's expectation that alcohol has an analgesic effect and the physiological cues accompanying alcohol consumption. | [
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PMID:4662 | Decrease of iconic memory after alcohol. | Alcohol did not alter the rate of information loss from iconic memory. However, there was a dose-related decrease in the total amount of information reported which was independent of the rate of information loss. | Decrease of iconic memory after alcohol. Alcohol did not alter the rate of information loss from iconic memory. However, there was a dose-related decrease in the total amount of information reported which was independent of the rate of information loss. | [
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PMID:4663 | The relationship between alcohol dosage and performance decrement in humans. | The effects of alcohol on human perceptual, cognitive and motor performance was assessed in a battery of tests, and the dose-response relationships for alcohol, important for the study of drug-alcohol interactions, established. | The relationship between alcohol dosage and performance decrement in humans. The effects of alcohol on human perceptual, cognitive and motor performance was assessed in a battery of tests, and the dose-response relationships for alcohol, important for the study of drug-alcohol interactions, established. | [
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PMID:4664 | Personality impairment in alcoholism. Its relation to regional cerebral blood flow and psychometric performance. | The psychiatric symptoms constituting three main syndromes of personality impairment ("defense," "low vitality" and "emotional deficiency") were homogeneous in alcoholic patients. Only the "low vitality" syndrome was associated with impaired psychometric performance and reduced cerebral blood flow. | Personality impairment in alcoholism. Its relation to regional cerebral blood flow and psychometric performance. The psychiatric symptoms constituting three main syndromes of personality impairment ("defense," "low vitality" and "emotional deficiency") were homogeneous in alcoholic patients. Only the "low vitality" syndrome was associated with impaired psychometric performance and reduced cerebral blood flow. | [
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PMID:4665 | Group assertiveness training for alcoholics. | Six men alcoholics showed increased assertiveness and improvement in social and occupational status after attending a group assertiveness training program. | Group assertiveness training for alcoholics. Six men alcoholics showed increased assertiveness and improvement in social and occupational status after attending a group assertiveness training program. | [
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PMID:4666 | Viability of cells in ethanol. Role of alcohol dehydrogenase. | Rodent cells were found to contain a high level of alcohol dehydrogenase activity which was not inducible. Other hepatoma and nonhepatoma cell lines were tested and found to contain lower but measurable levels of alcohol dehydrogenase. | Viability of cells in ethanol. Role of alcohol dehydrogenase. Rodent cells were found to contain a high level of alcohol dehydrogenase activity which was not inducible. Other hepatoma and nonhepatoma cell lines were tested and found to contain lower but measurable levels of alcohol dehydrogenase. | [
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PMID:4668 | Alcohol-induced conditioned taste aversion in rats. Effect of concentration and prior exposure to alcohol. | The effects of prior opportunities to drink alcohol solutions on the subsequent production of conditioned taste aversion by the oral ingestion of alcohol were evaluated. The consumption of 5 and 7% alcohol solutions produced conditioned aversion; the consumption of 3% alcohol solution did not result in aversion. Prior exposure to alcohol did not alter the extent of the aversion. | Alcohol-induced conditioned taste aversion in rats. Effect of concentration and prior exposure to alcohol. The effects of prior opportunities to drink alcohol solutions on the subsequent production of conditioned taste aversion by the oral ingestion of alcohol were evaluated. The consumption of 5 and 7% alcohol solutions produced conditioned aversion; the consumption of 3% alcohol solution did not result in aversion. Prior exposure to alcohol did not alter the extent of the aversion. | [
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PMID:4667 | Plasma immunoreactive insulin and somatotropin in delirium tremens and alcoholic hallucinosis. | The glucose tolerance curve in alcoholics in delirium tremens was similar to that seen in hepatogenic diabetes. The secretion of immunoreactive insulin and somatotropin after glucose was similar in patients with delirium tremens and alcoholic hallucinosis. | Plasma immunoreactive insulin and somatotropin in delirium tremens and alcoholic hallucinosis. The glucose tolerance curve in alcoholics in delirium tremens was similar to that seen in hepatogenic diabetes. The secretion of immunoreactive insulin and somatotropin after glucose was similar in patients with delirium tremens and alcoholic hallucinosis. | [
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PMID:4669 | Alcohol toxicity, blood alcohol concentration and body water in young and adult rats. | Young rats, with more body water, had lower blood alcohol concentrations than did older ones at several times after various doses. The young also recovered sooner from intoxication. The age difference in recovery increased with increasing dose. | Alcohol toxicity, blood alcohol concentration and body water in young and adult rats. Young rats, with more body water, had lower blood alcohol concentrations than did older ones at several times after various doses. The young also recovered sooner from intoxication. The age difference in recovery increased with increasing dose. | [
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PMID:4670 | Estimated U.S. alcoholic beverage consumption, 1790-1860. | From 1790 to 1830 American consumption of alcoholic beverages generally rose, with an increased use of spirits, a high but declining consumption of hard cider, and a negligible intake of wine and beer. Intake of absolute alcohol peaked in 1830, at a rate twice that estimated for 1970. From 1830 to 1860 consumption fell sharply, but since 1860 consumption has fluctuated much less. | Estimated U.S. alcoholic beverage consumption, 1790-1860. From 1790 to 1830 American consumption of alcoholic beverages generally rose, with an increased use of spirits, a high but declining consumption of hard cider, and a negligible intake of wine and beer. Intake of absolute alcohol peaked in 1830, at a rate twice that estimated for 1970. From 1830 to 1860 consumption fell sharply, but since 1860 consumption has fluctuated much less. | [
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PMID:4671 | Philosophies for educating about alcohol and other mood-modifying substance. Personal or social controls. | Groups of students, teachers, adult advisers to youth, civil-service supervisors and occupational-program consultants were in basic agreement on philosophies for educating about alcohol, marihuana, lysergide (LSD) and heroin. | Philosophies for educating about alcohol and other mood-modifying substance. Personal or social controls. Groups of students, teachers, adult advisers to youth, civil-service supervisors and occupational-program consultants were in basic agreement on philosophies for educating about alcohol, marihuana, lysergide (LSD) and heroin. | [
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PMID:4672 | Drinking during pregnancy. | Pregnant women reported a decrease in the use of alcoholic beverages during pregnancy, often citing adverse physiological effects as a reason for the decline. | Drinking during pregnancy. Pregnant women reported a decrease in the use of alcoholic beverages during pregnancy, often citing adverse physiological effects as a reason for the decline. | [
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PMID:4676 | The APUD cell concept. | Embryonic neural crest cells have been traced to the primitive entoderm where they differentiate into a family of hormone-producing cells, APUD cells. The APUD cell concept explains many otherwise seemingly dissociated clinical circumstances involving endocrine glands and hormone production by tumors. | The APUD cell concept. Embryonic neural crest cells have been traced to the primitive entoderm where they differentiate into a family of hormone-producing cells, APUD cells. The APUD cell concept explains many otherwise seemingly dissociated clinical circumstances involving endocrine glands and hormone production by tumors. | [
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PMID:4679 | Effect of narcotic analgesics on the striatal homovanillic acid content in mice; relation to antinociceptive effect. | The effects of various narcotic analgesics on striatal homovanillic acid (HVA) content, hot plate time and rectal temperature in mice were compared in relation to dose and time. The hypothermia induced by narcotic analgesics did not correlate with the striat"al HVA increase. Pentazocine, cyclazocine and thebaine had no effect on the hot plate time. The maximum prolongation of hot plate time induced by morphine, methadone or piminodine occurred before the highest HVA increase. The highest increase induced by narcotic analgesics in striatal HVA content was twice the original concentration. This occurred 2 hr after 40 mg/kg of morphine; 2 hr after 20 mg/kg of methadone; 1/2 hr after 20 mg/kg of piminodine; and 1 hr after 60 mg/kg of pentazocine. Cyclacozine (10 and 20 mg/kg) and thebaine (10 mg/kg) did not alter the HVA content. With the exception of pentazocine, those doses of narcotic analgesics that caused equal increases in striatal HVA content were also equianalgesic. These results suggest that there are similarities in the structural requirements for antinociceptive and striatal HVA-increasing effects of narcotic analgesics. The neuroleptic compound haloperidol (0.5 mg/kg) caused a fourfold increase in striatal HVA content making it twice as efficient as narcotic analgesics. This finding suggests that narcotic analgesics do not act on the same sites as neuroleptics when causing an increase in striatal HVA content. | Effect of narcotic analgesics on the striatal homovanillic acid content in mice; relation to antinociceptive effect. The effects of various narcotic analgesics on striatal homovanillic acid (HVA) content, hot plate time and rectal temperature in mice were compared in relation to dose and time. The hypothermia induced by narcotic analgesics did not correlate with the striat"al HVA increase. Pentazocine, cyclazocine and thebaine had no effect on the hot plate time. The maximum prolongation of hot plate time induced by morphine, methadone or piminodine occurred before the highest HVA increase. The highest increase induced by narcotic analgesics in striatal HVA content was twice the original concentration. This occurred 2 hr after 40 mg/kg of morphine; 2 hr after 20 mg/kg of methadone; 1/2 hr after 20 mg/kg of piminodine; and 1 hr after 60 mg/kg of pentazocine. Cyclacozine (10 and 20 mg/kg) and thebaine (10 mg/kg) did not alter the HVA content. With the exception of pentazocine, those doses of narcotic analgesics that caused equal increases in striatal HVA content were also equianalgesic. These results suggest that there are similarities in the structural requirements for antinociceptive and striatal HVA-increasing effects of narcotic analgesics. The neuroleptic compound haloperidol (0.5 mg/kg) caused a fourfold increase in striatal HVA content making it twice as efficient as narcotic analgesics. This finding suggests that narcotic analgesics do not act on the same sites as neuroleptics when causing an increase in striatal HVA content. | [
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PMID:4680 | The role of new health practitioners in a prepaid group practice: provider differences in process and outcomes of medical care. | Practice patterns and patient-reported outcomes of care are compared in detail for ten physicians and 12 new health practitioners delivering ambulatory care in two departments of a prepaid group practice, the Columbia Medical Plan (CMP). All providers completed questionnaires for a 50 per cent random sample of patients seen during a two-week period. Patients completed questionnaires prior to receiving care and were interviewed one week and one month after their clinic visits. New health practitioners deliver approximately 75 per cent of well-person care, 56 per cent of problem-oriented care in adult medicine, and 29 per cent of problem care in pediatrics. They have become increasingly involved over time in the treatment of acute conditions and injuries while physicians have retained their predominant role in treating patients with chronic conditions. Thirty-two per cent of visits with new healh providers involved a physician in one or more of the following: decision-making, direct supervision, consultation, or seeing the patient as a second provider of care. Degree of autonomy varied by type of task performed, category of problem treated, and specialty. The following outcomes of care were examined by type of provider: patient-reported change in problem status,including frequency and intensity of pain or discomfort, level of anxiety, and degree of activity limitation; the degree to which physician-specified criteria for the most commonly occurring conditions were met with respect to change in problem status; and patient satisfaction with a number of dimensions of the clinic visit. The analysis suggests that the new health practitioners at the CMP are providing care, within their areas of responsibility, of comparable quality to that delivered by physicians. | The role of new health practitioners in a prepaid group practice: provider differences in process and outcomes of medical care. Practice patterns and patient-reported outcomes of care are compared in detail for ten physicians and 12 new health practitioners delivering ambulatory care in two departments of a prepaid group practice, the Columbia Medical Plan (CMP). All providers completed questionnaires for a 50 per cent random sample of patients seen during a two-week period. Patients completed questionnaires prior to receiving care and were interviewed one week and one month after their clinic visits. New health practitioners deliver approximately 75 per cent of well-person care, 56 per cent of problem-oriented care in adult medicine, and 29 per cent of problem care in pediatrics. They have become increasingly involved over time in the treatment of acute conditions and injuries while physicians have retained their predominant role in treating patients with chronic conditions. Thirty-two per cent of visits with new healh providers involved a physician in one or more of the following: decision-making, direct supervision, consultation, or seeing the patient as a second provider of care. Degree of autonomy varied by type of task performed, category of problem treated, and specialty. The following outcomes of care were examined by type of provider: patient-reported change in problem status,including frequency and intensity of pain or discomfort, level of anxiety, and degree of activity limitation; the degree to which physician-specified criteria for the most commonly occurring conditions were met with respect to change in problem status; and patient satisfaction with a number of dimensions of the clinic visit. The analysis suggests that the new health practitioners at the CMP are providing care, within their areas of responsibility, of comparable quality to that delivered by physicians. | [
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PMID:4681 | Communication patterns of doctors and their assistants. | Communication patterns between physicians and their assistants (Medex) were observed in 19 practices to describe and evaluated the nature of their relationship. Observations demonstrated that interaction around patient problems was approximately 30 minures per day and informal, with the Medex more often initiating the contact. Medex were more likely to ask for, and physicians were more likely to give, suggestions. Physicians appeared to regard the accomplishment of the immediate task as more important than maintaining good relations. In most practices, supervision was available when requested. Generally, both the physician and the Medex show a striking similarity in communication styles. | Communication patterns of doctors and their assistants. Communication patterns between physicians and their assistants (Medex) were observed in 19 practices to describe and evaluated the nature of their relationship. Observations demonstrated that interaction around patient problems was approximately 30 minures per day and informal, with the Medex more often initiating the contact. Medex were more likely to ask for, and physicians were more likely to give, suggestions. Physicians appeared to regard the accomplishment of the immediate task as more important than maintaining good relations. In most practices, supervision was available when requested. Generally, both the physician and the Medex show a striking similarity in communication styles. | [
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PMID:4689 | Sterol synthesis in the liver, intestine, and lung of the guinea pig. | The relative rates of sterol synthesis in the liver, ileum, and lung of the guinea pig have been studied by measuring the incorporation by tissue slices of 14C-labeled acetate into digitonin-precipitable sterols. The liver showed maximum incorporation of acetate at pH 6.5, the ileum at pH 7.5, and the lung at pH 6.0. The incorporation of acetate approached the maximum rate at a concentration of 10 mM with the liver and lung and 5 mM with the ileum. Using these conditions of assay, sterol synthesis was measured in the liver, ileum, and lung of four groups of guinea pigs killed at 6-hourly intervals. Depending on the time of day, the rate of sterol synthesis in the ileum was from 6 to 14 times that in the liver, while in the lung the rate was up to 3 times that shown by the liver, Additional studies showed that all regions of the small intestine synthesized sterol at a higher rate than the liver, with the highest rate of synthesis occurring in the ileum. The rates observed in the adrenal, testis, muscle, adipose tissue, and skin indicated that these tissues are not quantitatively important sites of sterol synthesis in the guinea pig. | Sterol synthesis in the liver, intestine, and lung of the guinea pig. The relative rates of sterol synthesis in the liver, ileum, and lung of the guinea pig have been studied by measuring the incorporation by tissue slices of 14C-labeled acetate into digitonin-precipitable sterols. The liver showed maximum incorporation of acetate at pH 6.5, the ileum at pH 7.5, and the lung at pH 6.0. The incorporation of acetate approached the maximum rate at a concentration of 10 mM with the liver and lung and 5 mM with the ileum. Using these conditions of assay, sterol synthesis was measured in the liver, ileum, and lung of four groups of guinea pigs killed at 6-hourly intervals. Depending on the time of day, the rate of sterol synthesis in the ileum was from 6 to 14 times that in the liver, while in the lung the rate was up to 3 times that shown by the liver, Additional studies showed that all regions of the small intestine synthesized sterol at a higher rate than the liver, with the highest rate of synthesis occurring in the ileum. The rates observed in the adrenal, testis, muscle, adipose tissue, and skin indicated that these tissues are not quantitatively important sites of sterol synthesis in the guinea pig. | [
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PMID:4693 | Autoregulatory system of insulin degradation in liver. II. Relationship between blood insulin levels and GSH-dependent insulin degrading activity in liver and blood. | An autoregulatory system of insulin degradation in the liver in which the rate of insulin metabolism changes in response to fluctuation in its blood levels, was investigated. In the plasma of rats and man in the absence of reduced glutathione (GSH), insulin degradation was not observed, but when a sufficient amount of reduced glutathione was added, the plasma did degrade insulin. This GSH-dependent insulin degrading activity in plasma was quite similar to that in liver in its nature. In rats, this GSH-dependent insulin degrading activity in the liver and plasma was fluctuated in response to fluctuation in the blood insulin levels, and the GSH-dependent insulin degrading activity in plasma was well correlated with that in the liver. Similarly, in man the GSH-dependent insulin degrading activity in plasma was changed in response to fluctuation in the blood insulin levels. In plasma under the physiologic conditions, there is an insufficient amount of reduced glutathione to elicit the insulin degrading activity, but in the liver there is a sufficient amount of reduced glutathione to manifest this activity. This evidence further supports the concept that an autoregulatory system of insulin degradation in the liver exists in man. | Autoregulatory system of insulin degradation in liver. II. Relationship between blood insulin levels and GSH-dependent insulin degrading activity in liver and blood. An autoregulatory system of insulin degradation in the liver in which the rate of insulin metabolism changes in response to fluctuation in its blood levels, was investigated. In the plasma of rats and man in the absence of reduced glutathione (GSH), insulin degradation was not observed, but when a sufficient amount of reduced glutathione was added, the plasma did degrade insulin. This GSH-dependent insulin degrading activity in plasma was quite similar to that in liver in its nature. In rats, this GSH-dependent insulin degrading activity in the liver and plasma was fluctuated in response to fluctuation in the blood insulin levels, and the GSH-dependent insulin degrading activity in plasma was well correlated with that in the liver. Similarly, in man the GSH-dependent insulin degrading activity in plasma was changed in response to fluctuation in the blood insulin levels. In plasma under the physiologic conditions, there is an insufficient amount of reduced glutathione to elicit the insulin degrading activity, but in the liver there is a sufficient amount of reduced glutathione to manifest this activity. This evidence further supports the concept that an autoregulatory system of insulin degradation in the liver exists in man. | [
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PMID:4722 | Envelope mutation promoting autolysis in Salmonella typhimurium. | Two strains independently isolated in Salmonella typhimurium display abnormal autolytic activity when nutrient broth becomes alkaline. They also show increased sensitivity to deoxycholate, EDTA, and sodium dodecyl sulfate. Response to acridine orange remains normal. In both strains a single stable mutation is responsible for all the changes. The same gene, called envD, appears to be involved in both mutant strains. envD has been located at minute 33 of the Salmonella genetic map, between markers sucA and nadA, very close to the latter. envD also affects morphological characteristics of the cells. Many mutant cells are shorter than wild type bacteria, and appear frequently associated in short chains of 4 to 10 cells. Furthermore, envD mutants display division by septation under conditions that preclude its observation in wild type strains. | Envelope mutation promoting autolysis in Salmonella typhimurium. Two strains independently isolated in Salmonella typhimurium display abnormal autolytic activity when nutrient broth becomes alkaline. They also show increased sensitivity to deoxycholate, EDTA, and sodium dodecyl sulfate. Response to acridine orange remains normal. In both strains a single stable mutation is responsible for all the changes. The same gene, called envD, appears to be involved in both mutant strains. envD has been located at minute 33 of the Salmonella genetic map, between markers sucA and nadA, very close to the latter. envD also affects morphological characteristics of the cells. Many mutant cells are shorter than wild type bacteria, and appear frequently associated in short chains of 4 to 10 cells. Furthermore, envD mutants display division by septation under conditions that preclude its observation in wild type strains. | [
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PMID:4727 | Ferredoxin-dependent photosynthetic reduction of nitrate and nitrite by particles of Anacystis nidulans. | The dark and light reduction of nitrate and nitrite by cell-free preparations of the blue-green alga Anacystis nidulans has been investigated. The three following methods have been successfully applied to the preparation of active particulate fractions from the alga cells: (a) shaking with glass beads, (b) lysozyme treatment and lysis of the resulting protoplasts, and (c) sonication. The two enzymes of the nitrate-reducing system-namely, nitrate reductase and nitrite reductase-are firmly bound to the isolated pigment-containing particles, and can be easily solubilized by prolonging the vibration or sonication time. Both enzymes-whether solubilized or bound to the particles-depend on reduced ferredoxin as the immediate electron donor. In its presence, the alga particles catalyze the gradual photoreduction of nitrate to nitrite and ammonia, a process that can thus be considered as one of the most simple and relevant examples of Photosynthesis. Some of the properties of nitrate reductase have been studied. Nitrate reductase as well as nitrite reductase are adaptive enzymes repressed by ammonia. | Ferredoxin-dependent photosynthetic reduction of nitrate and nitrite by particles of Anacystis nidulans. The dark and light reduction of nitrate and nitrite by cell-free preparations of the blue-green alga Anacystis nidulans has been investigated. The three following methods have been successfully applied to the preparation of active particulate fractions from the alga cells: (a) shaking with glass beads, (b) lysozyme treatment and lysis of the resulting protoplasts, and (c) sonication. The two enzymes of the nitrate-reducing system-namely, nitrate reductase and nitrite reductase-are firmly bound to the isolated pigment-containing particles, and can be easily solubilized by prolonging the vibration or sonication time. Both enzymes-whether solubilized or bound to the particles-depend on reduced ferredoxin as the immediate electron donor. In its presence, the alga particles catalyze the gradual photoreduction of nitrate to nitrite and ammonia, a process that can thus be considered as one of the most simple and relevant examples of Photosynthesis. Some of the properties of nitrate reductase have been studied. Nitrate reductase as well as nitrite reductase are adaptive enzymes repressed by ammonia. | [
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PMID:4728 | Appearance of a syndrome similar to graft versus host reaction in C57 B1/6 mice bearing skin allogenic graft. | A syndrome similar to GVHR is described in mice of C57B1/6 strain during the WHT/Ht skin allografts rejection period. In all the cases the described thymus involution was associated with the hypertrophy of lymph nodes. Their volume increase is due to the high number of blastic pyroninophilic and plasma cells concomitant with small lymphocytes depletion in the cortical area, and with a very pronounced hypertrophy of medullary cords by presence of a high number of plasmocytes and blastic cells. These changes have been noticed only in some animals sacrified during the first days after grafting and never later one. In agreement with the scarce data of the literature, we think that the immunocompetent passenger lymphocyte comprised in the skin grafts constitute an immunologic organ able to induce a GVHR at the beginning of the period of graft survival on the host. This GVHR, generally mild and without clinical and microscopic signs, becomes obvious only in animals which, for unknown reasons, present a low immunologic defense capacity. In these animals the described process seems to be reversible. | Appearance of a syndrome similar to graft versus host reaction in C57 B1/6 mice bearing skin allogenic graft. A syndrome similar to GVHR is described in mice of C57B1/6 strain during the WHT/Ht skin allografts rejection period. In all the cases the described thymus involution was associated with the hypertrophy of lymph nodes. Their volume increase is due to the high number of blastic pyroninophilic and plasma cells concomitant with small lymphocytes depletion in the cortical area, and with a very pronounced hypertrophy of medullary cords by presence of a high number of plasmocytes and blastic cells. These changes have been noticed only in some animals sacrified during the first days after grafting and never later one. In agreement with the scarce data of the literature, we think that the immunocompetent passenger lymphocyte comprised in the skin grafts constitute an immunologic organ able to induce a GVHR at the beginning of the period of graft survival on the host. This GVHR, generally mild and without clinical and microscopic signs, becomes obvious only in animals which, for unknown reasons, present a low immunologic defense capacity. In these animals the described process seems to be reversible. | [
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PMID:4729 | [Mycoplasma-like micro-organisms in malignant tumors and non-tumours dermatovenerological diseases. Electron microscopic investigations (author's transl)]. | In examination of the ultrastructure of excised tissue and other material from patients with various diseases, principally dermatovenerological affections and with malignant tumors, and in healthy control subjects, patterns suggesting mycoplasma were repeatedly found in certain diseases only. Specific attempts to isolate mycoplasma from the material were made, in which previously patterns of a mycoplasma type had frequently been seen. It was possible to culture mycoplasma-like organisms in vitro from patients with the following diseases: malignant melanoma, mycosis fungoides, prickle cell carcinoma, squamous cell carcinoma, non-specific urethritis, pemphigus erythematosus, panarteritis nodosa and vasculitis allergica cutis. | [Mycoplasma-like micro-organisms in malignant tumors and non-tumours dermatovenerological diseases. Electron microscopic investigations (author's transl)]. In examination of the ultrastructure of excised tissue and other material from patients with various diseases, principally dermatovenerological affections and with malignant tumors, and in healthy control subjects, patterns suggesting mycoplasma were repeatedly found in certain diseases only. Specific attempts to isolate mycoplasma from the material were made, in which previously patterns of a mycoplasma type had frequently been seen. It was possible to culture mycoplasma-like organisms in vitro from patients with the following diseases: malignant melanoma, mycosis fungoides, prickle cell carcinoma, squamous cell carcinoma, non-specific urethritis, pemphigus erythematosus, panarteritis nodosa and vasculitis allergica cutis. | [
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PMID:4730 | [Chemical Investigation of Chronic Pancreatitis]. | We differentiate indirect and direct methods. The indirect methods include the examination of the blood (ESR, blood picture, electrolytes, especially calcium, for the exclusion of hyperparathyroidism, status of fat and liver enzymes, activity of alpha-amylase and lipase. More informative than a serum determination is the measurement of the amylase activity in the 24-hour urine. The detection of chymotrypsin in the stool can be recommended as an investigative test also for use in general practive in collaboration with a central laboratory.- The direct methods include investigation of the duodenal juice with measurement of pH, bicarbonate, of the activities of chymotrypsin, trypsin, lipase and amylase. For excluding of a disturbance of the carbohydrate metabolism in addition to blood sugar determinations, glucose tolerance and tolbutamide tests, the determination of insulin activity is indicated. | [Chemical Investigation of Chronic Pancreatitis]. We differentiate indirect and direct methods. The indirect methods include the examination of the blood (ESR, blood picture, electrolytes, especially calcium, for the exclusion of hyperparathyroidism, status of fat and liver enzymes, activity of alpha-amylase and lipase. More informative than a serum determination is the measurement of the amylase activity in the 24-hour urine. The detection of chymotrypsin in the stool can be recommended as an investigative test also for use in general practive in collaboration with a central laboratory.- The direct methods include investigation of the duodenal juice with measurement of pH, bicarbonate, of the activities of chymotrypsin, trypsin, lipase and amylase. For excluding of a disturbance of the carbohydrate metabolism in addition to blood sugar determinations, glucose tolerance and tolbutamide tests, the determination of insulin activity is indicated. | [
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PMID:4733 | Huntington's chorea. Changes in neurotransmitter receptors in the brain. | Neurotransmitter-receptor binding sites for apparent muscarinic cholinergic, beta-adrenergic, gamma-aminobutyric acid and serotonin receptors were measured in the caudate nucleus and frontal cerebral cortex from post-mortem brains of 16 patients with Huntington's chorea and 16 controls. In addition, the samples were assayed for the gamma-aminobutyric-acid-synthesizing enzyme, glutamic acid decarboxylase, and for the acetylcholine-synthesizing enzyme, choline acetyltransferase. In the caudate nucleus of choreic brain, both enzyme activities were markedly lower, with significant decreases in muscarinic cholinergic and serotonin receptor binding, whereas enzyme activities and receptor binding were unchanged in the cerebral cortex. By contrast, gamma-aminobutyric acid and beta-adrenergic receptor binding were not significantly different in choreic and control caudate nucleus or cortex, suggesting that, despite the loss of gamma-aminobutyric-acid-synthesizing ability in the corpus striatum, gamma-aminobuytric acid mimetic drugs might alleviate the movement disorders in Huntington's chorea. | Huntington's chorea. Changes in neurotransmitter receptors in the brain. Neurotransmitter-receptor binding sites for apparent muscarinic cholinergic, beta-adrenergic, gamma-aminobutyric acid and serotonin receptors were measured in the caudate nucleus and frontal cerebral cortex from post-mortem brains of 16 patients with Huntington's chorea and 16 controls. In addition, the samples were assayed for the gamma-aminobutyric-acid-synthesizing enzyme, glutamic acid decarboxylase, and for the acetylcholine-synthesizing enzyme, choline acetyltransferase. In the caudate nucleus of choreic brain, both enzyme activities were markedly lower, with significant decreases in muscarinic cholinergic and serotonin receptor binding, whereas enzyme activities and receptor binding were unchanged in the cerebral cortex. By contrast, gamma-aminobutyric acid and beta-adrenergic receptor binding were not significantly different in choreic and control caudate nucleus or cortex, suggesting that, despite the loss of gamma-aminobutyric-acid-synthesizing ability in the corpus striatum, gamma-aminobuytric acid mimetic drugs might alleviate the movement disorders in Huntington's chorea. | [
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PMID:4739 | [The effect of changes in the pH of the external solution on the afterpotentials of individual frog nodes of Ranvier]. | A decrease in pH to 5 elicited a small increase in afterdepolarization of a single Ranvier node and an increase in pH to 9 had no effect. Post-tetanic hyperpolarization decreases at pH 5 and its duration somewhat increases. An increase in pH to 9 also had no effect. Similar changes in afterdepolarization and post-tetanic hyperpolarization were observed in potassium free solutions. A conclusion is made that changes in afterpotentials are determined by changes in kinetics of the membrane potassium permeability. | [The effect of changes in the pH of the external solution on the afterpotentials of individual frog nodes of Ranvier]. A decrease in pH to 5 elicited a small increase in afterdepolarization of a single Ranvier node and an increase in pH to 9 had no effect. Post-tetanic hyperpolarization decreases at pH 5 and its duration somewhat increases. An increase in pH to 9 also had no effect. Similar changes in afterdepolarization and post-tetanic hyperpolarization were observed in potassium free solutions. A conclusion is made that changes in afterpotentials are determined by changes in kinetics of the membrane potassium permeability. | [
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PMID:4744 | Prolonged clinical and experimental follow-up of hospitalized schizophrenics. | 148 chronic schizophrenics admitted between 1938 and 1961 had previously been followed up. In 1972, they were re-examined, on the average 10 years after the first follow-up. 44 belonged to a series of patients studied between 1955 and 1957 with a battery of conditional reflex tests. The patients belonging to the experimental series were retested with word associations. From an experimental point of view the patients performed better over the prolonged observation period. The clinical state also showed improvement. A comparison of the chronic hospital population during 1955-57 and 1972-74 suggests that the new chronics present much less of the severe schizophrenic deterioration than the old ones. They also have remarkably better verbal functions these changes are assumed to be mainly due to drug treatment. The beneficial effects of drugs appear to come mainly within the first 2 years. | Prolonged clinical and experimental follow-up of hospitalized schizophrenics. 148 chronic schizophrenics admitted between 1938 and 1961 had previously been followed up. In 1972, they were re-examined, on the average 10 years after the first follow-up. 44 belonged to a series of patients studied between 1955 and 1957 with a battery of conditional reflex tests. The patients belonging to the experimental series were retested with word associations. From an experimental point of view the patients performed better over the prolonged observation period. The clinical state also showed improvement. A comparison of the chronic hospital population during 1955-57 and 1972-74 suggests that the new chronics present much less of the severe schizophrenic deterioration than the old ones. They also have remarkably better verbal functions these changes are assumed to be mainly due to drug treatment. The beneficial effects of drugs appear to come mainly within the first 2 years. | [
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PMID:4759 | [The state of prothrombin, plasminogen and fibrinogen in the newborn infant]. | The esterase activity of thrombin and plasmin on artificial substrates was used to study the kinetics of these enzymes by Lineweaver and Burk's method. In the plasma of new-born infants, plasmin obtained from streptokinase has an avidity comparable with that in adults. Thrombin is obtained by the action of staphylocoagulase and taipan venom. Its avidity has important individual variations and is different from that in adults. An inhibitor is present both in the plasma and in the serum of the new-born. Fibrinogen was studied by variations in absorption of light during coagulation by thrombin. The abnormalities observed depend on the physical and clinical conditions of the medium (ph, osmolality). These characteristics depend on the age of the infant, but also seem to depend on the conditions of the sample and, in particular, on fibrinolytic reactions. The existence of foetal fibrinogen is discussed. | [The state of prothrombin, plasminogen and fibrinogen in the newborn infant]. The esterase activity of thrombin and plasmin on artificial substrates was used to study the kinetics of these enzymes by Lineweaver and Burk's method. In the plasma of new-born infants, plasmin obtained from streptokinase has an avidity comparable with that in adults. Thrombin is obtained by the action of staphylocoagulase and taipan venom. Its avidity has important individual variations and is different from that in adults. An inhibitor is present both in the plasma and in the serum of the new-born. Fibrinogen was studied by variations in absorption of light during coagulation by thrombin. The abnormalities observed depend on the physical and clinical conditions of the medium (ph, osmolality). These characteristics depend on the age of the infant, but also seem to depend on the conditions of the sample and, in particular, on fibrinolytic reactions. The existence of foetal fibrinogen is discussed. | [
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PMID:4760 | Local renal graft-versus-host reaction: sequential ultrastructural study. | A sequential study has been made of the ultrastructure of local renal graft-versus-host reactions produced in cyclophosphamide-pretreated rats by injection of either allogeneic or xenogeneic (mouse) spleen cells beneath the renal capsule. Early in the reaction, immunoblasts were seen between the outer cortical tubules, and there was associated interstitial oedema and tubular degeneration. In places, several small lymphocytes were observed clustered around and in close cytoplasmic contact with individual immunoblasts, perhaps representing interaction between donor and host cells. As the reaction proceeded, the number of lymphoid cells increased by immigration from peritubular vessels. Some tubules were invaded by lymphocytes but this was not closely related to the development of tubular injury. The reaction was maximum at one week and then decreased. Now, there was greater diversity of cells including macrophages, plasma cells and eosinophils, while many lymphoid cells became necrotic. It is concluded that most of the renal parenchymal injury is due to chemical mediators liberated from the infiltrating cells rather than to ischaemia or direct cytoplasmic interaction between leucocytes and tubular epithelium. | Local renal graft-versus-host reaction: sequential ultrastructural study. A sequential study has been made of the ultrastructure of local renal graft-versus-host reactions produced in cyclophosphamide-pretreated rats by injection of either allogeneic or xenogeneic (mouse) spleen cells beneath the renal capsule. Early in the reaction, immunoblasts were seen between the outer cortical tubules, and there was associated interstitial oedema and tubular degeneration. In places, several small lymphocytes were observed clustered around and in close cytoplasmic contact with individual immunoblasts, perhaps representing interaction between donor and host cells. As the reaction proceeded, the number of lymphoid cells increased by immigration from peritubular vessels. Some tubules were invaded by lymphocytes but this was not closely related to the development of tubular injury. The reaction was maximum at one week and then decreased. Now, there was greater diversity of cells including macrophages, plasma cells and eosinophils, while many lymphoid cells became necrotic. It is concluded that most of the renal parenchymal injury is due to chemical mediators liberated from the infiltrating cells rather than to ischaemia or direct cytoplasmic interaction between leucocytes and tubular epithelium. | [
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PMID:4765 | Functional abnormalities in renal cystic diseases. | The functions of a kidney, whether normal or cystic, can be conceptualized in terms of anatomy (glomerulus, proximal tubule, loop of Henle, distal convolution, and collecting duct), activity (volume regulation, dilution and concentration, acid-base regulation, potassium excretion, transport of organic molecules, and calcium and phosphate excretion), and the integration of anatomic organization to meet functional demand. Our discussion of renal cystic disorders follows this conceptual outline. For discussions of normal renal physiology, the reader is referred to any one of several recent, excellent reviews (1-3). Systematic evaluation of renal function in cystic diseases of the kidney (medullary sponge kidney, medullary cystic disease, and polycystic kidney disease) has only rarely been performed. The available information suggests that the earliest detectable lesions consist primarily of tubular dysfunction. With time, however, significant reduction of glomerular filtration occurs and the resultant accumulation of uremic toxins dominates the clinical picture in polycystic and medullary cystic disease. Significant changes in glomerular function are unusual in medullary sponge kidney. This review represents an attempt to summarize the large body of literature that has accumulated on functional abnormalities in these disorders, and to point out those areas where further investigations are needed. | Functional abnormalities in renal cystic diseases. The functions of a kidney, whether normal or cystic, can be conceptualized in terms of anatomy (glomerulus, proximal tubule, loop of Henle, distal convolution, and collecting duct), activity (volume regulation, dilution and concentration, acid-base regulation, potassium excretion, transport of organic molecules, and calcium and phosphate excretion), and the integration of anatomic organization to meet functional demand. Our discussion of renal cystic disorders follows this conceptual outline. For discussions of normal renal physiology, the reader is referred to any one of several recent, excellent reviews (1-3). Systematic evaluation of renal function in cystic diseases of the kidney (medullary sponge kidney, medullary cystic disease, and polycystic kidney disease) has only rarely been performed. The available information suggests that the earliest detectable lesions consist primarily of tubular dysfunction. With time, however, significant reduction of glomerular filtration occurs and the resultant accumulation of uremic toxins dominates the clinical picture in polycystic and medullary cystic disease. Significant changes in glomerular function are unusual in medullary sponge kidney. This review represents an attempt to summarize the large body of literature that has accumulated on functional abnormalities in these disorders, and to point out those areas where further investigations are needed. | [
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PMID:4766 | Phosphate transport by isolated renal brush border vesicles. | A sodium dependent specific transport system for phosphate is present in the brush border microvilli but absent from the basal-lateral plasma membranes. The apparent affinity of this transport system for phosphate is 0.08 mM at 100 mM sodium and pH 7.4. It is inhibited competitively by arsenate with an apparent inhibitor constant of 1.1 mM (100 mM sodium, pH 7.4). Sodium dependent phosphate uptake is two times higher at pH 8 compared to the uptake observed at pH 6. The apparent affinity of the transport system for sodium is also pH-dependent, half-maximal stimulation of uptake is found at pH 6 with 129 mM sodium, at pH 7.4 with 60 mM sodium and at pH 8 with 50 mM sodium. Under all conditions a nonhyperbolic dependence of phosphate uptake on the sodium concentration is observed. The uptake of phosphate by brush border microvilli vesicles shows a typical overshoot phenomenon in the presence of sodium gradient across the membrane (CNao greater than CNai). The amount of pohsphate taken up after 2 min is about twice the equilibrium value reached after 2 h of incubation. At pH 7.4 the initial rate of uptake is increased only slighyly (12%) by inside negative membrane diffusion potentials and inhibited to the same extent by inside positive membrane diffusion potentials. These results indicate that the entry of phosphate across the brush border membrane into the epithelial cell of the proximal tubule is coupled to the entry of sodium. The transfer of phosphate is dependent on its concentration gradient and on the concentration difference of sodium. The data are best explained by the following hypothesis: Both the primary phosphate as well as the secondary phosphate are transported in cotransport with sodium. The divalent form however seems to be transported preferentially. Its transport occurs electroneutral with 2 sodium ions; the monovalent phosphate also enters the cell together with 2 sodium ions but as a positively charged complex. The exit of phosphate across the contraluminal cell border is sodium independent and is favoured by the high intracellular phosphate concentration and the inside negative membrane potential. | Phosphate transport by isolated renal brush border vesicles. A sodium dependent specific transport system for phosphate is present in the brush border microvilli but absent from the basal-lateral plasma membranes. The apparent affinity of this transport system for phosphate is 0.08 mM at 100 mM sodium and pH 7.4. It is inhibited competitively by arsenate with an apparent inhibitor constant of 1.1 mM (100 mM sodium, pH 7.4). Sodium dependent phosphate uptake is two times higher at pH 8 compared to the uptake observed at pH 6. The apparent affinity of the transport system for sodium is also pH-dependent, half-maximal stimulation of uptake is found at pH 6 with 129 mM sodium, at pH 7.4 with 60 mM sodium and at pH 8 with 50 mM sodium. Under all conditions a nonhyperbolic dependence of phosphate uptake on the sodium concentration is observed. The uptake of phosphate by brush border microvilli vesicles shows a typical overshoot phenomenon in the presence of sodium gradient across the membrane (CNao greater than CNai). The amount of pohsphate taken up after 2 min is about twice the equilibrium value reached after 2 h of incubation. At pH 7.4 the initial rate of uptake is increased only slighyly (12%) by inside negative membrane diffusion potentials and inhibited to the same extent by inside positive membrane diffusion potentials. These results indicate that the entry of phosphate across the brush border membrane into the epithelial cell of the proximal tubule is coupled to the entry of sodium. The transfer of phosphate is dependent on its concentration gradient and on the concentration difference of sodium. The data are best explained by the following hypothesis: Both the primary phosphate as well as the secondary phosphate are transported in cotransport with sodium. The divalent form however seems to be transported preferentially. Its transport occurs electroneutral with 2 sodium ions; the monovalent phosphate also enters the cell together with 2 sodium ions but as a positively charged complex. The exit of phosphate across the contraluminal cell border is sodium independent and is favoured by the high intracellular phosphate concentration and the inside negative membrane potential. | [
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PMID:4767 | The effect of carbonic anhydrase inhibition on bicarbonate reabsorption. | Renal reabsorption of bicarbonate was studied in Merino ewes during carbonic anhydrase inhibition. Bicarbonate reabsorption was directly proportional to plasma bicarbonate concentration. No tubular maximum for bicarbonate was demonstrated. Elevation of arterial PCO2 or depression of arterial pH caused slight increases in bicarbonate reabsorption. The data suggest that bicarbonate is reabsorbed by 2 distinct processes. The quantitatively more significant process may involve ionic reabsorption of bicarbonate secondary to Na+ reabsorption and a relatively minor part of bicarbonate reabsorption may be secondary to H+ secretion. | The effect of carbonic anhydrase inhibition on bicarbonate reabsorption. Renal reabsorption of bicarbonate was studied in Merino ewes during carbonic anhydrase inhibition. Bicarbonate reabsorption was directly proportional to plasma bicarbonate concentration. No tubular maximum for bicarbonate was demonstrated. Elevation of arterial PCO2 or depression of arterial pH caused slight increases in bicarbonate reabsorption. The data suggest that bicarbonate is reabsorbed by 2 distinct processes. The quantitatively more significant process may involve ionic reabsorption of bicarbonate secondary to Na+ reabsorption and a relatively minor part of bicarbonate reabsorption may be secondary to H+ secretion. | [
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PMID:4779 | Atherosclerotic cerebral infarction: pathophysiologic aspects. | When the supply of substrate to the brain is threatened, homeostatic mechanisms induce cerebral vasodilatation to compensate for the insufficiency. When a region of the brain is rendered completely ischemic, local infarction occurs. The size of the infarct depends partly on the availability of collateral circulation and the adequacy of the homeostatic mechanisms controlling blood flow in stillpatent vessels. Several approaches to acute-phase treatment of stroke derive from clinical and experimental studies of cerebral blood flow and metabolism. We must conclude that both surgical and nonsurgical therapeutic measures have been of limited value in the treatment of cerebral infarction and that the basic therapy for completed stroke remains good medical management of complications and attentive nursing care. | Atherosclerotic cerebral infarction: pathophysiologic aspects. When the supply of substrate to the brain is threatened, homeostatic mechanisms induce cerebral vasodilatation to compensate for the insufficiency. When a region of the brain is rendered completely ischemic, local infarction occurs. The size of the infarct depends partly on the availability of collateral circulation and the adequacy of the homeostatic mechanisms controlling blood flow in stillpatent vessels. Several approaches to acute-phase treatment of stroke derive from clinical and experimental studies of cerebral blood flow and metabolism. We must conclude that both surgical and nonsurgical therapeutic measures have been of limited value in the treatment of cerebral infarction and that the basic therapy for completed stroke remains good medical management of complications and attentive nursing care. | [
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PMID:4780 | Pharmacologic therapy of asthma. | Asthma is treated by avoiding the precipitants of symptoms, by a trial of hyposensitization (immunotherapy) if the precipitant cannot be avoided, and principally by pharmacologic therapy. Acute attacks have been most widely treated with epinephrine, but adrenergic aerosol bronchodilators and aminophylline are being used increasingly. When an acute attack of asthma does not respond to treatment, a diagnosis of status asthmaticus should be considered and the patient treated in a hospital intensive care unit because of the potentially life-threatening sequela of respiratory failure. Periodic mild episodes of asthma usually respond to administration of an oral bronchodilator. Chronic low-grade asthma is best treated with an around-the-clock regimen of theophylline. Patients whose asthma is not under satisfactory control with conventional bronchodilators may be given a trial of cromolyn sodium. Chronic severe cases may be treated with corticosteroids, but these drugs must be skillfully administered to avoid adverse effects. | Pharmacologic therapy of asthma. Asthma is treated by avoiding the precipitants of symptoms, by a trial of hyposensitization (immunotherapy) if the precipitant cannot be avoided, and principally by pharmacologic therapy. Acute attacks have been most widely treated with epinephrine, but adrenergic aerosol bronchodilators and aminophylline are being used increasingly. When an acute attack of asthma does not respond to treatment, a diagnosis of status asthmaticus should be considered and the patient treated in a hospital intensive care unit because of the potentially life-threatening sequela of respiratory failure. Periodic mild episodes of asthma usually respond to administration of an oral bronchodilator. Chronic low-grade asthma is best treated with an around-the-clock regimen of theophylline. Patients whose asthma is not under satisfactory control with conventional bronchodilators may be given a trial of cromolyn sodium. Chronic severe cases may be treated with corticosteroids, but these drugs must be skillfully administered to avoid adverse effects. | [
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PMID:4781 | Managing acute urticaria. | The physician should be familiar with preventive measures for acute urticaria or its most severe form, anaphylaxis, and with the general principles of management. Treatment does not differ basically whether given in a nonmedical setting, the emergency room, or the office, except for the availability of special supplies and equipment, such as oxygen, if needed. In all cases, a history should be obtained quickly, the patient should be examined to confirm the diagnosis, and epinephrine should be administered. Hospitalization is indicated in severe cases with systemic symptoms. Once the acute episode has been treated, the physician must decide whether further investigation is necessary. Quite often a presumptive etiologic diagnosis is made on the basis of the history. Allergy testing is not part of the routine evaluation of the patient with urticaria. | Managing acute urticaria. The physician should be familiar with preventive measures for acute urticaria or its most severe form, anaphylaxis, and with the general principles of management. Treatment does not differ basically whether given in a nonmedical setting, the emergency room, or the office, except for the availability of special supplies and equipment, such as oxygen, if needed. In all cases, a history should be obtained quickly, the patient should be examined to confirm the diagnosis, and epinephrine should be administered. Hospitalization is indicated in severe cases with systemic symptoms. Once the acute episode has been treated, the physician must decide whether further investigation is necessary. Quite often a presumptive etiologic diagnosis is made on the basis of the history. Allergy testing is not part of the routine evaluation of the patient with urticaria. | [
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PMID:4782 | Myocardial ischemia from coronary arterial spasm. | Spasm of coronary arteries can cause chest pain indistinguishable from classic angina pectoris in patients without atherosclerosis of these vessels or recognizable heart disease. Associated electrocardiographic changes usually correspond to the coronary artery affected and disappear when the attack of pain ends. Sublingual nitrates are excellent agents for the control of the episodic anginal symptoms. There have been scattered reports of myocardial infarction occurring in patients with normal coronary arteries; a role of arterial spasm in these cases in speculative. | Myocardial ischemia from coronary arterial spasm. Spasm of coronary arteries can cause chest pain indistinguishable from classic angina pectoris in patients without atherosclerosis of these vessels or recognizable heart disease. Associated electrocardiographic changes usually correspond to the coronary artery affected and disappear when the attack of pain ends. Sublingual nitrates are excellent agents for the control of the episodic anginal symptoms. There have been scattered reports of myocardial infarction occurring in patients with normal coronary arteries; a role of arterial spasm in these cases in speculative. | [
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PMID:4777 | Preparation of drugs used in hyperacidity. Part I. Effects of pH of precipitation on the neutralizing properties of alumina gels. | Alumina gels were obtained from sodium aluminate by addition of 3 N HNO3, HCl or H2SO4 solutions or by saturation with gaseous CO2. The effect of several physicochemical factors (pH of precipitation, kind and concentration of precipitating agent, temperature) on the neutralizing properties of the obtained forms of Al(OH)3 was investigated. The linear correlation between the pH of precipitation and the neutralizing properties was found. The effect of different precipitating anions on the acid-consuming capacity and the rate of neutralization of 0-1 N HCl was established. | Preparation of drugs used in hyperacidity. Part I. Effects of pH of precipitation on the neutralizing properties of alumina gels. Alumina gels were obtained from sodium aluminate by addition of 3 N HNO3, HCl or H2SO4 solutions or by saturation with gaseous CO2. The effect of several physicochemical factors (pH of precipitation, kind and concentration of precipitating agent, temperature) on the neutralizing properties of the obtained forms of Al(OH)3 was investigated. The linear correlation between the pH of precipitation and the neutralizing properties was found. The effect of different precipitating anions on the acid-consuming capacity and the rate of neutralization of 0-1 N HCl was established. | [
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PMID:4778 | Nephron function in acute glycerol-induced renal insufficiency in rabbits. | The effect of acute experimentally induced renal failure after intramuscular injection of glycerol on serum and urine GGTP, LAP and AP activities was studied in 30 rabbits. High doses of glycerol caused shock, myolysis and hemolysis, leading to acute renal insufficiency. Serum urea and creatinine levels significantly increased, there was proteinuria, and significant decrease in 24-hr diuresis, glomerular filtration, and urinary urea excretion. The changes in LAP and AP activities were significant, and in GGTP-nonsignificant. In the urine GGTP and LAP increased significantly, and AP nonsignificantly. Urinary excretion of AP increased significantly, and GGTP and LAP nonsignificantly. The highest activity and urinary excretion of GGTP and LAP were observed on the 2nd day, and of AP--on the 5th day of renal failure. | Nephron function in acute glycerol-induced renal insufficiency in rabbits. The effect of acute experimentally induced renal failure after intramuscular injection of glycerol on serum and urine GGTP, LAP and AP activities was studied in 30 rabbits. High doses of glycerol caused shock, myolysis and hemolysis, leading to acute renal insufficiency. Serum urea and creatinine levels significantly increased, there was proteinuria, and significant decrease in 24-hr diuresis, glomerular filtration, and urinary urea excretion. The changes in LAP and AP activities were significant, and in GGTP-nonsignificant. In the urine GGTP and LAP increased significantly, and AP nonsignificantly. Urinary excretion of AP increased significantly, and GGTP and LAP nonsignificantly. The highest activity and urinary excretion of GGTP and LAP were observed on the 2nd day, and of AP--on the 5th day of renal failure. | [
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PMID:4783 | Angina pectoris. Diagnosis and treatment. | The physician who understands the pathophysiology of angina pectoris can apply rational therapeutic measures based on an appreciation of the determinants of myocardial oxygen supply and demand. Most patients with angina secondary to coronary atherosclerosis can be treated conservatively using a systematic approach that includes correction or removal of underlying causes or precipitating factors and the judicious use of sublingual nitroglycerin. In patients with more resistant angina, use of oral or topical nitroglycerin or sublingual isosorbide dinitrite as well as propranolol can be advised. Aortocoronary bypass surgery can offer significant improvement in carefully selected patients with frequent angina poorly controlled by medical therapy. The most important consideration in the treatment of angina is protection of coronary blood flow reserve by primary prevention of the atherosclerotic process itself. All individuals from families prone to coronary artery disease should be evaluated for alterable risk factors, the most important being cigarette smoking, hypertension, and hypercholesterolemia. Considering the high risk of unheralded sudden death in previously asymptomatic patients with coronary atherosclerosis, angina can, in a sense, be considered a fortunate harbinger of coronary stenosis, identifying candidates for secondary preventive measures aimed at retarding the progression of vascular disease. More importantly, angina serves as an index for detecting families at high risk of coronary artery disease, in whom early application of primary prevention may afford a more promising outlook. | Angina pectoris. Diagnosis and treatment. The physician who understands the pathophysiology of angina pectoris can apply rational therapeutic measures based on an appreciation of the determinants of myocardial oxygen supply and demand. Most patients with angina secondary to coronary atherosclerosis can be treated conservatively using a systematic approach that includes correction or removal of underlying causes or precipitating factors and the judicious use of sublingual nitroglycerin. In patients with more resistant angina, use of oral or topical nitroglycerin or sublingual isosorbide dinitrite as well as propranolol can be advised. Aortocoronary bypass surgery can offer significant improvement in carefully selected patients with frequent angina poorly controlled by medical therapy. The most important consideration in the treatment of angina is protection of coronary blood flow reserve by primary prevention of the atherosclerotic process itself. All individuals from families prone to coronary artery disease should be evaluated for alterable risk factors, the most important being cigarette smoking, hypertension, and hypercholesterolemia. Considering the high risk of unheralded sudden death in previously asymptomatic patients with coronary atherosclerosis, angina can, in a sense, be considered a fortunate harbinger of coronary stenosis, identifying candidates for secondary preventive measures aimed at retarding the progression of vascular disease. More importantly, angina serves as an index for detecting families at high risk of coronary artery disease, in whom early application of primary prevention may afford a more promising outlook. | [
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PMID:4785 | Intranasal beclomethasone dipropionate in seasonal rhinitis in general practice. | Thirty-five patients with seasonal allergic rhinitis were treated in a double-blind comparative trial in and East London Group Practice with either beclomethasone dipropionate (50 micrograms in each nostril four times a day) or a placebo aerosol preparation identical in appearance. There was a statistically significant difference in favour of intranasal beclomethasone dipropionate (P less than 0-05). | Intranasal beclomethasone dipropionate in seasonal rhinitis in general practice. Thirty-five patients with seasonal allergic rhinitis were treated in a double-blind comparative trial in and East London Group Practice with either beclomethasone dipropionate (50 micrograms in each nostril four times a day) or a placebo aerosol preparation identical in appearance. There was a statistically significant difference in favour of intranasal beclomethasone dipropionate (P less than 0-05). | [
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PMID:4786 | [Cerebral palsy--early diagnosis and treatment (author's transl)]. | The main aim of the present Conference has been to debate that early diagnosis and treatment of cerebral palsy. The Conference was attended by specialists taking care of the child with cerebral palsy (C.P.): child neurologists, surgeons--orthopedists, psychologists, rehabilitants, pediatricians. In connection with the fact that the Conference was devoted to the early diagnosis and therapy of C.P., problems concerning the lower age groups of children were debated. The Conference discussed the definitions of "cerebral palsy" used in the literature, the clinical forms, the auxiliary diagnostic methods and their significance in the diagnosing of this pathological syndrome. Early clinical symptoms, enabling to establish the diagnosis of cerebral palsy were particularly extensively debated. In the latter problem particular attention was paid to the diagnostic value of kinetic automatisms of the group of tonic posture reflexes and dysfunctions of the kinetic pattern in children. It was underlined in the debate the C.P. was no separate clinical disease, but a pathological syndrome arisen as a result of the negative influence of different factors and yielding very diverse clinical and neurolopathologic symptoms, according to the kind of noxious factors and the period and degree of maturity of the nervous system in which they acted. The participants in the debate also sressed that, as the child develops and is observed for a longer period it is fairly often necessary to check this diagnosis, as C.P. may prove, as the time passes, to be a degenerative syndrome, a pressure syndrome etc. The psychologists participating in the Conference discussed the psychological problems of the child with C.P. and also the early diagnosis of the pathological syndrome debated. The diversity of the symptoms of the C.N.S. in children suffering from C.P. was underscored, as--apart from dysfunctions within the kinetic area, there can be present sight, hearing and speech dysfunctions, those of sensory perceptions and mental development. These children require multispecialist care, as everyone of dysfunctions mentioned may present a complicated diagnostic problem. Plenty of place was devoted to the discussion of problems connected with epilepsy in children with C.P. Also extensively debated were the general principles of the medical procedure in children with C.P. As a result of the discussion it was decided that children with severer forms of C.P. and those from poor social conditions should be subjected to long-lasting sanatorium rehabilitation. Keeping the child in its family environment should, however, be the generally adopted principle of the rehabilitation of a little child. The parents of the child should be trained in the proper rearing of the child under household conditions, a manner to secure all the needs resulting from the then stage of its development. In connection with this problem the project of the programme of sensoric-and-kinetic rehabilitation was debated, as presented by psychologists and rehabilitants (kinesitherapeuts). | [Cerebral palsy--early diagnosis and treatment (author's transl)]. The main aim of the present Conference has been to debate that early diagnosis and treatment of cerebral palsy. The Conference was attended by specialists taking care of the child with cerebral palsy (C.P.): child neurologists, surgeons--orthopedists, psychologists, rehabilitants, pediatricians. In connection with the fact that the Conference was devoted to the early diagnosis and therapy of C.P., problems concerning the lower age groups of children were debated. The Conference discussed the definitions of "cerebral palsy" used in the literature, the clinical forms, the auxiliary diagnostic methods and their significance in the diagnosing of this pathological syndrome. Early clinical symptoms, enabling to establish the diagnosis of cerebral palsy were particularly extensively debated. In the latter problem particular attention was paid to the diagnostic value of kinetic automatisms of the group of tonic posture reflexes and dysfunctions of the kinetic pattern in children. It was underlined in the debate the C.P. was no separate clinical disease, but a pathological syndrome arisen as a result of the negative influence of different factors and yielding very diverse clinical and neurolopathologic symptoms, according to the kind of noxious factors and the period and degree of maturity of the nervous system in which they acted. The participants in the debate also sressed that, as the child develops and is observed for a longer period it is fairly often necessary to check this diagnosis, as C.P. may prove, as the time passes, to be a degenerative syndrome, a pressure syndrome etc. The psychologists participating in the Conference discussed the psychological problems of the child with C.P. and also the early diagnosis of the pathological syndrome debated. The diversity of the symptoms of the C.N.S. in children suffering from C.P. was underscored, as--apart from dysfunctions within the kinetic area, there can be present sight, hearing and speech dysfunctions, those of sensory perceptions and mental development. These children require multispecialist care, as everyone of dysfunctions mentioned may present a complicated diagnostic problem. Plenty of place was devoted to the discussion of problems connected with epilepsy in children with C.P. Also extensively debated were the general principles of the medical procedure in children with C.P. As a result of the discussion it was decided that children with severer forms of C.P. and those from poor social conditions should be subjected to long-lasting sanatorium rehabilitation. Keeping the child in its family environment should, however, be the generally adopted principle of the rehabilitation of a little child. The parents of the child should be trained in the proper rearing of the child under household conditions, a manner to secure all the needs resulting from the then stage of its development. In connection with this problem the project of the programme of sensoric-and-kinetic rehabilitation was debated, as presented by psychologists and rehabilitants (kinesitherapeuts). | [
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PMID:4787 | [Congenital heart malformations in neonates, infants and young children (author's transl)]. | Congenital heart malformations in neonates, infants and young children represent the main problem of paediatric cardiology in Poland. Congenital cardiovascular diseases (incidence also approximately 8 per 1000 in liveborn infants) cause very high mortality, particularly in the neonatal and infantile period. Approximately 5000 live-born children are affected every year by serious heart malformations. For at least two thirds of these previously hopelessly ill infants there are real possibilities of effective medical and surgical treatment. Not only a considerable drop in mortality in the earliest infancy would be achieved, but: a further normal physical and psychical growth and development of these children would be possible. At present, however, the available possibilities are by far not sufficient, as in all hitherto functioning centres we were able to manage 200-300 children yearly, whereas the real needs are at leasttenfold greater. Therefore it is necessary to: Increase the number and capacity of hospital wards capable enough to provide the intensive cardiopulmonary care; to execute appropriate reorganization aimed to concentrating the appropriate specialists (pediatric cardiologists, radiologists, surgeons, anesthesiologists, nurses) and equipment (cardiological and cardiosurgical appliances, X-ray equipment, intensive care units etc.) in centres designated for the above tasks. At least 7 paediatric intensive care and cardiosurgical centres should be instituted in Poland for a satisfactory management of congenital heart diseases. | [Congenital heart malformations in neonates, infants and young children (author's transl)]. Congenital heart malformations in neonates, infants and young children represent the main problem of paediatric cardiology in Poland. Congenital cardiovascular diseases (incidence also approximately 8 per 1000 in liveborn infants) cause very high mortality, particularly in the neonatal and infantile period. Approximately 5000 live-born children are affected every year by serious heart malformations. For at least two thirds of these previously hopelessly ill infants there are real possibilities of effective medical and surgical treatment. Not only a considerable drop in mortality in the earliest infancy would be achieved, but: a further normal physical and psychical growth and development of these children would be possible. At present, however, the available possibilities are by far not sufficient, as in all hitherto functioning centres we were able to manage 200-300 children yearly, whereas the real needs are at leasttenfold greater. Therefore it is necessary to: Increase the number and capacity of hospital wards capable enough to provide the intensive cardiopulmonary care; to execute appropriate reorganization aimed to concentrating the appropriate specialists (pediatric cardiologists, radiologists, surgeons, anesthesiologists, nurses) and equipment (cardiological and cardiosurgical appliances, X-ray equipment, intensive care units etc.) in centres designated for the above tasks. At least 7 paediatric intensive care and cardiosurgical centres should be instituted in Poland for a satisfactory management of congenital heart diseases. | [
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PMID:4788 | [Ribonuclease activity in the serum of children of various ages (author's transl)]. | The normal levels of ribonuclease activity in the serum of children of both sexes of various ages. The children into four age groups: thee 1st grous--from 1 to 7 days of age, the 2nd--from 1 to 12 months, 3rd--from 1 to 3 years, 4th--from 7 to 14 years of age. The ribonuclease activity amounted, in the various age groups, respectively tto: 1st group--0.27+0.07 ug/ml of serum, 2nd--0.21+0.06 ug/ml, 3rd--0.15+0.04 ug/ml, 4th--0.14+0.04 ug/ml. | [Ribonuclease activity in the serum of children of various ages (author's transl)]. The normal levels of ribonuclease activity in the serum of children of both sexes of various ages. The children into four age groups: thee 1st grous--from 1 to 7 days of age, the 2nd--from 1 to 12 months, 3rd--from 1 to 3 years, 4th--from 7 to 14 years of age. The ribonuclease activity amounted, in the various age groups, respectively tto: 1st group--0.27+0.07 ug/ml of serum, 2nd--0.21+0.06 ug/ml, 3rd--0.15+0.04 ug/ml, 4th--0.14+0.04 ug/ml. | [
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PMID:4793 | Activation and nuclear translocation of protein kinase during transsynaptic induction of tyrosine 3-monooxygenase. | The tyrosine-3-monooxygenase activity [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] of rat adrenal medulla is induced 20-24 hr after the injection of reserpine (16 mumol/kg intraperitoneally). This and other inducing stimuli increase the 3': 5'-cyclic AMP (cAMP) content in the medulla for longer than 60 min and activate the cAMP-dependent protein kinase (ATP: protein phosphotransferase; EC 2.7.1.37) for several hours. Corticotropin (ACTH), dopamine, and propranolol do not induce the monooxygenase, but elicit an increase in the cAMP content of the medulla which fails to activate protein kinase and lasts less than 1 hr. A high- and low-molecular-weight protein kinase are separated by gel filtration from the 20,000 X g pellet extract of adrenal medulla homogenate. The activity of the low-molecular-weight enzyme is expressed as its ability to phosphorylate histone. The protein kinase activity of the pellet is increased between 3 and 17 hr after reserpine injection. Our evidence indicates that this increase is due to a translocation from cytosol to subcellular structures of a kinase that utilizes lysine-rich histone as phosphate acceptor. The protein kinase activity that is extracted from a purified nuclear fraction prepared from the adrenal medulla of rats injected 7 hr previously with reserpine is greater than that extracted from medulla of saline-treated rats. | Activation and nuclear translocation of protein kinase during transsynaptic induction of tyrosine 3-monooxygenase. The tyrosine-3-monooxygenase activity [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] of rat adrenal medulla is induced 20-24 hr after the injection of reserpine (16 mumol/kg intraperitoneally). This and other inducing stimuli increase the 3': 5'-cyclic AMP (cAMP) content in the medulla for longer than 60 min and activate the cAMP-dependent protein kinase (ATP: protein phosphotransferase; EC 2.7.1.37) for several hours. Corticotropin (ACTH), dopamine, and propranolol do not induce the monooxygenase, but elicit an increase in the cAMP content of the medulla which fails to activate protein kinase and lasts less than 1 hr. A high- and low-molecular-weight protein kinase are separated by gel filtration from the 20,000 X g pellet extract of adrenal medulla homogenate. The activity of the low-molecular-weight enzyme is expressed as its ability to phosphorylate histone. The protein kinase activity of the pellet is increased between 3 and 17 hr after reserpine injection. Our evidence indicates that this increase is due to a translocation from cytosol to subcellular structures of a kinase that utilizes lysine-rich histone as phosphate acceptor. The protein kinase activity that is extracted from a purified nuclear fraction prepared from the adrenal medulla of rats injected 7 hr previously with reserpine is greater than that extracted from medulla of saline-treated rats. | [
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PMID:4794 | A 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin A in rabbit kidney. | Examination of a soluble fraction derived from homogenates of rabbit kidney papilla revealed the existence of a 15-hydroxyprostaglandin dehydrogenase specific for A-type prostaglandins. Prostaglandins of the E- and F-series were not substrates for this enzyme. In agreement with published data, the 15-hydroxyprostaglandin dehydrogenase(s) derived from the kidney cortex were found to degrade all prostaglandins examined (PGE, PGF, PGA) in the presence of added cofactor NAD. Thus it is evident that in this species the kidney 15-hydroxyprostaglandin dehydrogenases are anatomically compartmentalized so that the papilla is able to metabpable of degrading E-, F-, and A-type prostaglandins by this metabolic pathway. | A 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin A in rabbit kidney. Examination of a soluble fraction derived from homogenates of rabbit kidney papilla revealed the existence of a 15-hydroxyprostaglandin dehydrogenase specific for A-type prostaglandins. Prostaglandins of the E- and F-series were not substrates for this enzyme. In agreement with published data, the 15-hydroxyprostaglandin dehydrogenase(s) derived from the kidney cortex were found to degrade all prostaglandins examined (PGE, PGF, PGA) in the presence of added cofactor NAD. Thus it is evident that in this species the kidney 15-hydroxyprostaglandin dehydrogenases are anatomically compartmentalized so that the papilla is able to metabpable of degrading E-, F-, and A-type prostaglandins by this metabolic pathway. | [
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PMID:4795 | Specific positions involved in enzyme catalyzed covalent binding of benzo[a]pyrene to poly(G). | Covalent binding of benzo[a]pyrene to poly(G) was studied with the use of a radioactive assay and specifically labeled substrates to define the role of the 1, 3- and 6-positions of the hydrocarbon during this process. Binding was shown to be dependent on microsomes, NADPH, O2 and poly(G). 7, 8-Benzoflavone and 2', 2'-diethylaminoethyl-2, 2-diphenyl valerate were inhibitory w.hereas modulators of epoxide hydrase activity had little effect. 3H and 14C studies suggested a possible loss of one to two protons. Incorporation of [6-3H1]benzo[a]pyrene provided evidence that the 6-position of the hydrocarbon was not metabolized during covalent attachment to poly(G) and, furthermore, results with [1, 3, 6-3H]benzo[a]pyrene suggest that the 1- and 3-positions may not be involved either. After scaling up of the standard assay 20-fold, characterization of the tritiated BaP-poly(G) complex was carried out by hydrolysis and subsequent chromatography. Thin-layer chromatography of the isolated hydrolysis products treated with HCl or alkaline phosphatase indicated that the complex formed between BaP and poly(G) was covalently linked and composed of hydrocarbon-nucleotide(s). | Specific positions involved in enzyme catalyzed covalent binding of benzo[a]pyrene to poly(G). Covalent binding of benzo[a]pyrene to poly(G) was studied with the use of a radioactive assay and specifically labeled substrates to define the role of the 1, 3- and 6-positions of the hydrocarbon during this process. Binding was shown to be dependent on microsomes, NADPH, O2 and poly(G). 7, 8-Benzoflavone and 2', 2'-diethylaminoethyl-2, 2-diphenyl valerate were inhibitory w.hereas modulators of epoxide hydrase activity had little effect. 3H and 14C studies suggested a possible loss of one to two protons. Incorporation of [6-3H1]benzo[a]pyrene provided evidence that the 6-position of the hydrocarbon was not metabolized during covalent attachment to poly(G) and, furthermore, results with [1, 3, 6-3H]benzo[a]pyrene suggest that the 1- and 3-positions may not be involved either. After scaling up of the standard assay 20-fold, characterization of the tritiated BaP-poly(G) complex was carried out by hydrolysis and subsequent chromatography. Thin-layer chromatography of the isolated hydrolysis products treated with HCl or alkaline phosphatase indicated that the complex formed between BaP and poly(G) was covalently linked and composed of hydrocarbon-nucleotide(s). | [
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PMID:4796 | Simple model for hormone-activated adenylate cyclase systems. | A simple model is developed to explain the activation of rat liver plasma membrane adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by guanosine nucleotides and glucagon and the dependence of the cATALYTIC RATE ON Mg2+, H+, and substrate concentrations. The basic model proposes that the adenylate cyclase system can exist in two states, A and B; that activating ligands bind preferentially to the B state; and that only the B state is active. Kinetic data are quantitatively fit to this model, and the binding constants for the interaction of the A and B states with glucagon, GTP, and guanyl-5'-ylimidodiphosphate are obtinaed. The substrates ATP and adenyl-5'-ylimidodiphosphate appear to show little preference between the A and B states, and simple Michaelis-Menten kinetics are sufficient to describe the dependence of the catalytic rate on substrate concentration under optimal conditions. The dependence of the rate on pH can be explained by postulating that one ionizable group in its acid form and one ionizable group in its basic form must be present at the active site in order for catalysis to occur. The activation and inhibition of the activity by Mg2+ can be explained by a similar mechanism with Mg2+ binding to activating and inhibiting sites. Glucagon and guanosine nucleotides appear to influence the dependence of the rate on Mg2+ and glucagon. The Mg2+ also may display some preference for the B state. A comparison of this model with others that have been proposed is given. The proposed model appears to provide a simple conceptual frame-work that is applicable to many adenylate cyclase systems. | Simple model for hormone-activated adenylate cyclase systems. A simple model is developed to explain the activation of rat liver plasma membrane adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by guanosine nucleotides and glucagon and the dependence of the cATALYTIC RATE ON Mg2+, H+, and substrate concentrations. The basic model proposes that the adenylate cyclase system can exist in two states, A and B; that activating ligands bind preferentially to the B state; and that only the B state is active. Kinetic data are quantitatively fit to this model, and the binding constants for the interaction of the A and B states with glucagon, GTP, and guanyl-5'-ylimidodiphosphate are obtinaed. The substrates ATP and adenyl-5'-ylimidodiphosphate appear to show little preference between the A and B states, and simple Michaelis-Menten kinetics are sufficient to describe the dependence of the catalytic rate on substrate concentration under optimal conditions. The dependence of the rate on pH can be explained by postulating that one ionizable group in its acid form and one ionizable group in its basic form must be present at the active site in order for catalysis to occur. The activation and inhibition of the activity by Mg2+ can be explained by a similar mechanism with Mg2+ binding to activating and inhibiting sites. Glucagon and guanosine nucleotides appear to influence the dependence of the rate on Mg2+ and glucagon. The Mg2+ also may display some preference for the B state. A comparison of this model with others that have been proposed is given. The proposed model appears to provide a simple conceptual frame-work that is applicable to many adenylate cyclase systems. | [
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PMID:4797 | Heat mutagenesis in bacteriophage T4: the transition pathway. | G-C leads to A-T transitions are induced by heat, and arise from the deamination of cytosine (5-hydroxymethylcytosine in the case of bacteriophage T4) generating uracil. The reaction is proton-catalyzed, and is also characteristic of acid mutagenesis. Mutation rates and activation energies of mutation are site-specific, and are presumably influenced by neighboring bases. Rates of heat-induced mutation in bacteriophage T4 under conditions of temperature, pH, and ionic strength similar to those prevailing in higher eukaryotic cells suggest that heat mutagenesis may present a serious challenge to organisms with large genomes, and may comprise an important determinant of the rates of spontaneous mutation. | Heat mutagenesis in bacteriophage T4: the transition pathway. G-C leads to A-T transitions are induced by heat, and arise from the deamination of cytosine (5-hydroxymethylcytosine in the case of bacteriophage T4) generating uracil. The reaction is proton-catalyzed, and is also characteristic of acid mutagenesis. Mutation rates and activation energies of mutation are site-specific, and are presumably influenced by neighboring bases. Rates of heat-induced mutation in bacteriophage T4 under conditions of temperature, pH, and ionic strength similar to those prevailing in higher eukaryotic cells suggest that heat mutagenesis may present a serious challenge to organisms with large genomes, and may comprise an important determinant of the rates of spontaneous mutation. | [
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PMID:4798 | beta-adrenergic receptors in rat liver: effects of adrenalectomy. | The response of rat liver adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] to catecholamines is enhanced after adrenalectomy. To investigate this phenomenon, we developed an in vitro assay for beta-adrenergic receptors of plasma membranes derived from livers of control and adrenalectomized rats, using [125I]iodohydroxybenzylpindolol (IHYP), a potent beta-adrenergic receptor antagonist. Binding of IHYP reached equilibrium within 30 min and dissociation occurred with a half-time of approximately 60 min. The l-isomers of isoproterenol and propranolol were at least 50 times more potent as inhibitors of IHYP binding than were the corresponding d-isomers. Adrenalectomy did not affect the rates of association or dissociation of IHYP or the dissociation constants of several ligands that are active at beta-adrenergic receptors. The number of binding sites for IHYP was determined in homogenates and in purified membranes of livers from control and adrenalectomized rats. The number of sites increased 3- to 5-fold after adrenalectomy. A similar increase in hormone stimulation of adenylate cyclase was observed. These changes were reversed by the administration of cortisone. The increase in the number of binding sites for IHYP may be a compensatory response to the impairments in gluconeogenesis and glycogenolysis which occur after adrenalectomy. | beta-adrenergic receptors in rat liver: effects of adrenalectomy. The response of rat liver adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] to catecholamines is enhanced after adrenalectomy. To investigate this phenomenon, we developed an in vitro assay for beta-adrenergic receptors of plasma membranes derived from livers of control and adrenalectomized rats, using [125I]iodohydroxybenzylpindolol (IHYP), a potent beta-adrenergic receptor antagonist. Binding of IHYP reached equilibrium within 30 min and dissociation occurred with a half-time of approximately 60 min. The l-isomers of isoproterenol and propranolol were at least 50 times more potent as inhibitors of IHYP binding than were the corresponding d-isomers. Adrenalectomy did not affect the rates of association or dissociation of IHYP or the dissociation constants of several ligands that are active at beta-adrenergic receptors. The number of binding sites for IHYP was determined in homogenates and in purified membranes of livers from control and adrenalectomized rats. The number of sites increased 3- to 5-fold after adrenalectomy. A similar increase in hormone stimulation of adenylate cyclase was observed. These changes were reversed by the administration of cortisone. The increase in the number of binding sites for IHYP may be a compensatory response to the impairments in gluconeogenesis and glycogenolysis which occur after adrenalectomy. | [
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PMID:4799 | Thermodynamic studies of polymerization of deoxygenated sickle cell hemoglobin. | Solubilities of deoxygenated sickle cell hemoglobin (deoxy-Hb S), at varying pH and temperature over a range of concentrations encompassing those found in erythrocytes, were measured. The technique involved ultracentrifugation, which gave values of the supernatant concentration and the mass of the sedimented material. The data establish that the solubility of doexy-Hb S is the saturation concentration and is independent of initial concentration. The mass of the pellet phase increases linearly with initial concentration. Moreover, the saturation concentration represents the critical concentration above which monomers are in equilibrium with polymers. These polymers are the putative cause of erythrocytes deformation associated with sickle cell anemia. The solubility-pH profiles of deoxy-Hb S at various temperatures, unlike those of other proteins, show no minima at the isoelectric pH but instead show a marked decrease in solubility below pH 7.0, indicating the predominance of polymerization over the expected increase in solubility. Deoxy-Hb S, within specified ranges of temperature and pH, possesses a negative temperature coefficient of solubility, a property characteristic of hydrophobic interactions. The saturation concentration is, however, temperature independent at conditions close to physiological. The enthalpy of polymerization (3.5 kcal/mol) is temperature independent from 6 degrees to 22 degrees for all pH values between 6.45 and 7.40. In the range of 22 degrees to 38 degrees, this parameter becomes less endothermic, having a value of 2.5 kcal/mol at pH 6.45 and a value of zero at pH 7.20. Such behavior of the system suggests a phase transition near 22 degreas. Within the range of conditions examined the polymerization is entropically driven. | Thermodynamic studies of polymerization of deoxygenated sickle cell hemoglobin. Solubilities of deoxygenated sickle cell hemoglobin (deoxy-Hb S), at varying pH and temperature over a range of concentrations encompassing those found in erythrocytes, were measured. The technique involved ultracentrifugation, which gave values of the supernatant concentration and the mass of the sedimented material. The data establish that the solubility of doexy-Hb S is the saturation concentration and is independent of initial concentration. The mass of the pellet phase increases linearly with initial concentration. Moreover, the saturation concentration represents the critical concentration above which monomers are in equilibrium with polymers. These polymers are the putative cause of erythrocytes deformation associated with sickle cell anemia. The solubility-pH profiles of deoxy-Hb S at various temperatures, unlike those of other proteins, show no minima at the isoelectric pH but instead show a marked decrease in solubility below pH 7.0, indicating the predominance of polymerization over the expected increase in solubility. Deoxy-Hb S, within specified ranges of temperature and pH, possesses a negative temperature coefficient of solubility, a property characteristic of hydrophobic interactions. The saturation concentration is, however, temperature independent at conditions close to physiological. The enthalpy of polymerization (3.5 kcal/mol) is temperature independent from 6 degrees to 22 degrees for all pH values between 6.45 and 7.40. In the range of 22 degrees to 38 degrees, this parameter becomes less endothermic, having a value of 2.5 kcal/mol at pH 6.45 and a value of zero at pH 7.20. Such behavior of the system suggests a phase transition near 22 degreas. Within the range of conditions examined the polymerization is entropically driven. | [
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PMID:4812 | Difference in the number of insulin binding sites between cortisol-sensitive and cortisol-resistant lymphoma P1798 cells. | Cortisol-sensitive and cortisol-resistant lymphoma P1798 cells specifically bind [25I]insulin. Resistant lymphocytes bind 40% less insulin than sensitive cells. These results suggest that insulin (or insulin-like substances) may play a role in growth regulation and/or response of this tumor to glucocorticoid therapy. | Difference in the number of insulin binding sites between cortisol-sensitive and cortisol-resistant lymphoma P1798 cells. Cortisol-sensitive and cortisol-resistant lymphoma P1798 cells specifically bind [25I]insulin. Resistant lymphocytes bind 40% less insulin than sensitive cells. These results suggest that insulin (or insulin-like substances) may play a role in growth regulation and/or response of this tumor to glucocorticoid therapy. | [
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PMID:4813 | Action of histamine and its receptor blockers on uterine circulation in sheep. | Effects of iv and ia administration of histamine and its H1 and H2 blockers (diphenhydramine and metiamide) on systemic arterial pressure, heart rate, and uterine and iliac blood flows were investigated in unanesthetized, chronically instrumented nonpregnant ewes. Intravenous histamine produced tachycardia, hypotension, and decreased iliac and uterine blood flows. In contrast, ia injections produced a significant increase in blood flows in these vascular beds which was dose-dependent. Evidence is presented to show that some of the circulatory actions of histamine may be related to stimulation of H1 while others may be related to H2 receptors. The peripheral circulatory action produced by iv histamine is probably secondary to its effects on reducing cardiac output. The uterine and iliac vascular beds contain mostly H1 receptors since their response to histamine can be blocked almost totally by Benadryl and not by H2 antagonist metiamide. | Action of histamine and its receptor blockers on uterine circulation in sheep. Effects of iv and ia administration of histamine and its H1 and H2 blockers (diphenhydramine and metiamide) on systemic arterial pressure, heart rate, and uterine and iliac blood flows were investigated in unanesthetized, chronically instrumented nonpregnant ewes. Intravenous histamine produced tachycardia, hypotension, and decreased iliac and uterine blood flows. In contrast, ia injections produced a significant increase in blood flows in these vascular beds which was dose-dependent. Evidence is presented to show that some of the circulatory actions of histamine may be related to stimulation of H1 while others may be related to H2 receptors. The peripheral circulatory action produced by iv histamine is probably secondary to its effects on reducing cardiac output. The uterine and iliac vascular beds contain mostly H1 receptors since their response to histamine can be blocked almost totally by Benadryl and not by H2 antagonist metiamide. | [
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PMID:4814 | Alpha-MSH and MIF-2 effects on serotonin levels and accumulation in various rat brain areas. | Levels as well as accumulation of serotonin (5-HT) were measured in various brain regions of the rat after administration of alpha-melanocyte-stimulating hormone (MSH) and Pro-Leu-Gly-NH2 (MIF-I). The method used in determining the serotonin measured both 5-OH-tryptamine (5-HT) and 5-methoxytryptamine (5-MT). No statistically significant changes in levels or accumulation of serotonin after pargyline injection were found when unoperated control rats were treated with either MSH or MIF-I. Similar treatment of hypophysectomized rats indicated that both peptides significantly (p less than 0.05) lowered serotonin accumulation only in the area of the frontal cortex; a similar but smaller, not statistically significant, decrease was seen in the hypothalamus and hippocampus of the hypophysectomized rat. Since only hypophysectomized rats were affected, no correlation between the behavioral effects of these peptides (which has been found to occur in both unoperated and hypophysectomized rats) and the biochemical changes could be made. | Alpha-MSH and MIF-2 effects on serotonin levels and accumulation in various rat brain areas. Levels as well as accumulation of serotonin (5-HT) were measured in various brain regions of the rat after administration of alpha-melanocyte-stimulating hormone (MSH) and Pro-Leu-Gly-NH2 (MIF-I). The method used in determining the serotonin measured both 5-OH-tryptamine (5-HT) and 5-methoxytryptamine (5-MT). No statistically significant changes in levels or accumulation of serotonin after pargyline injection were found when unoperated control rats were treated with either MSH or MIF-I. Similar treatment of hypophysectomized rats indicated that both peptides significantly (p less than 0.05) lowered serotonin accumulation only in the area of the frontal cortex; a similar but smaller, not statistically significant, decrease was seen in the hypothalamus and hippocampus of the hypophysectomized rat. Since only hypophysectomized rats were affected, no correlation between the behavioral effects of these peptides (which has been found to occur in both unoperated and hypophysectomized rats) and the biochemical changes could be made. | [
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PMID:4815 | Alpha-MSH and MIF-I effects on catecholamine levels and synthesis in various rat brain areas. | Attempts were made to find a biochemical correlate with previously observed behavioral alterations after administration of alpha-melanocyte-stimulating hormone (MSH) and MSH release-inhibiting factor (MIF-I). Brains of intact and hypophysectomized (hypox) rats were analyzed for endogenous catecholamine levels and the disappearance rate of endogenous norepinephrine (NE) after treatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). The studies undertaken show the following: (1) After the injection of MSH (100 mug/kg IP daily x 3) and AMPT, samples in different groups of intact and hypox rats were taken at 0, 1, 2, 4 and 6 hrs in 7 different brain areas. In the mid-brain area for the intact group of rats, the rate of disappearance of NE was faster and for the hypox rats it was slower than the rate for control rats not treated with the peptides. NE levels in the same area at time 0 were 11 percent lower than controls in hypox rats and unchanged in unoperated animals. (2) After the injection of MIF-I (20 mg/kg IP daily x 3) in similar experiments as with MSH, a reduced rate (p less than 0.05) of NE disappearance for the first 4 hr and an increased rate (p less than 0.05) of NE disappearance for the last 2 hr of the experiments occurred for both the intact and hypox rats in the mid-brain area where endogenous NE levels were lowered by 11 and 12 percent at 0 min. In no other brain areas were alterations in NE breakdown found in both the intact and hypox rat groups. Behavioral changes have been found previously under similar experimental conditions in both intact and hypox rats. (3) Rates of dopamine disappearance in experiments similar to those described for NE disappearance indicated that in the striatal brain area no change was found in the intact rats after either MSH or MIF-I, whereas a decrease in DA disappearance was found for hypox rats during the six hour experimental period only after MSH. The results indicate that a correlation between behavioral changes, rates of disappearance and endogenous levels of NE in the mid-brain area may occur after MIF-I at the times examined but that a similar correlation for MSH did not appear likely. | Alpha-MSH and MIF-I effects on catecholamine levels and synthesis in various rat brain areas. Attempts were made to find a biochemical correlate with previously observed behavioral alterations after administration of alpha-melanocyte-stimulating hormone (MSH) and MSH release-inhibiting factor (MIF-I). Brains of intact and hypophysectomized (hypox) rats were analyzed for endogenous catecholamine levels and the disappearance rate of endogenous norepinephrine (NE) after treatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). The studies undertaken show the following: (1) After the injection of MSH (100 mug/kg IP daily x 3) and AMPT, samples in different groups of intact and hypox rats were taken at 0, 1, 2, 4 and 6 hrs in 7 different brain areas. In the mid-brain area for the intact group of rats, the rate of disappearance of NE was faster and for the hypox rats it was slower than the rate for control rats not treated with the peptides. NE levels in the same area at time 0 were 11 percent lower than controls in hypox rats and unchanged in unoperated animals. (2) After the injection of MIF-I (20 mg/kg IP daily x 3) in similar experiments as with MSH, a reduced rate (p less than 0.05) of NE disappearance for the first 4 hr and an increased rate (p less than 0.05) of NE disappearance for the last 2 hr of the experiments occurred for both the intact and hypox rats in the mid-brain area where endogenous NE levels were lowered by 11 and 12 percent at 0 min. In no other brain areas were alterations in NE breakdown found in both the intact and hypox rat groups. Behavioral changes have been found previously under similar experimental conditions in both intact and hypox rats. (3) Rates of dopamine disappearance in experiments similar to those described for NE disappearance indicated that in the striatal brain area no change was found in the intact rats after either MSH or MIF-I, whereas a decrease in DA disappearance was found for hypox rats during the six hour experimental period only after MSH. The results indicate that a correlation between behavioral changes, rates of disappearance and endogenous levels of NE in the mid-brain area may occur after MIF-I at the times examined but that a similar correlation for MSH did not appear likely. | [
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PMID:4818 | Self-administration of psychomotor stimulant drugs: the effects of unlimited access. | Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days. Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine. Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake. | Self-administration of psychomotor stimulant drugs: the effects of unlimited access. Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days. Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine. Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake. | [
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PMID:4819 | Rate-dependent effects of drugs: a review of the literature. | It has been claimed that the effects of amphetamines on schedule-controlled behavior depend to a large extent on the rate of responding in control conditions. A review of the literature shows that there is considerable support for this hypothesis if the behavior is not suppressed by aversive procedures, is not under the control of powerful external stimuli or is not occurring very infrequently. The extension of a rate-dependency hypothesis to the effects of other drugs has less empirical support, however. It is argued that many of the procedures used for studying rate-dependent drug effects do not provide critical tests of the hypothesis. If it is to be shown unequivocally that it is rate of operant responding which determines the behavioral effects of drugs, procedures are needed in which other varibles such as reinforcement frequency are more adequately controlled. | Rate-dependent effects of drugs: a review of the literature. It has been claimed that the effects of amphetamines on schedule-controlled behavior depend to a large extent on the rate of responding in control conditions. A review of the literature shows that there is considerable support for this hypothesis if the behavior is not suppressed by aversive procedures, is not under the control of powerful external stimuli or is not occurring very infrequently. The extension of a rate-dependency hypothesis to the effects of other drugs has less empirical support, however. It is argued that many of the procedures used for studying rate-dependent drug effects do not provide critical tests of the hypothesis. If it is to be shown unequivocally that it is rate of operant responding which determines the behavioral effects of drugs, procedures are needed in which other varibles such as reinforcement frequency are more adequately controlled. | [
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PMID:4816 | Effect of various 6-hydroxydopamine treatments during development on growth and ingestive behavior. | Destruction of catecholamine-containing fibers in brain at 5 days of age with intracisternal injection of 6-hydroxydopamine reduced body growth, intake of a sucrose solution, and acquisition of an active avoidance response. Further characterization of behavioral deficits indicated that treated animals also showed reduced ingestion of saline solution when injected with desoxycorticosterone and a decreased eating response to insulin. In addition, all of these deficits produced by catecholamine depletion with 6-hydroxydopamine were observed in rats in which brain dopamine was preferentially reduced but not in rats having preferential destruction of noradrenergic fibers, suggesting that dopamine depletion amounts for the observed alterations in developing animals. Although animals treated with 6-hydroxydopamine at 14 days showed reduced intake of a sucrose solution, they did not have reduced growth. Since early malnourishment reduced growth, it seems possible that the reduced growth observed after destruction of dopaminergeic fibers may be related to an acute reduction of food intake which is perpetuated by persistent deficits in ingestive behavior. Evidence implicating malnourishment in other deficits produced by 6-hydroxydopamine could not be obtained. | Effect of various 6-hydroxydopamine treatments during development on growth and ingestive behavior. Destruction of catecholamine-containing fibers in brain at 5 days of age with intracisternal injection of 6-hydroxydopamine reduced body growth, intake of a sucrose solution, and acquisition of an active avoidance response. Further characterization of behavioral deficits indicated that treated animals also showed reduced ingestion of saline solution when injected with desoxycorticosterone and a decreased eating response to insulin. In addition, all of these deficits produced by catecholamine depletion with 6-hydroxydopamine were observed in rats in which brain dopamine was preferentially reduced but not in rats having preferential destruction of noradrenergic fibers, suggesting that dopamine depletion amounts for the observed alterations in developing animals. Although animals treated with 6-hydroxydopamine at 14 days showed reduced intake of a sucrose solution, they did not have reduced growth. Since early malnourishment reduced growth, it seems possible that the reduced growth observed after destruction of dopaminergeic fibers may be related to an acute reduction of food intake which is perpetuated by persistent deficits in ingestive behavior. Evidence implicating malnourishment in other deficits produced by 6-hydroxydopamine could not be obtained. | [
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PMID:4820 | Schedule-induced oral self administration of etonitazene. | Rats were induced to drink either a saline-etonitazene solution or a saline solution with a schedule-induced polydipsia paradigm. When water was freely available, the rats continued to drink the saline solution or the saline-etonitazene solution, rather than the water. When the locations of the solutions were switched, the rats that were drinking saline switched to water (drank at the usual location), but the rats that were drinking saline-etonitazene continued to drink the saline-etonitazene solution (drank from the bottle at the other location). Naloxone administration temporarily eliminated the drinking of saline-etonitazene solution, but not that of saline solution. | Schedule-induced oral self administration of etonitazene. Rats were induced to drink either a saline-etonitazene solution or a saline solution with a schedule-induced polydipsia paradigm. When water was freely available, the rats continued to drink the saline solution or the saline-etonitazene solution, rather than the water. When the locations of the solutions were switched, the rats that were drinking saline switched to water (drank at the usual location), but the rats that were drinking saline-etonitazene continued to drink the saline-etonitazene solution (drank from the bottle at the other location). Naloxone administration temporarily eliminated the drinking of saline-etonitazene solution, but not that of saline solution. | [
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PMID:4817 | Enzyme activity in sleep and sleep deprivation. | Liver tyrosine transaminase activity is low during the day when the rats are mostly asleep and high during the night when they are awake. When wakefulness was imposed for 8 hr during daylight on the day of the experiment and the rats were allowed to sleep for the following 3 hr during darkness, the tyrosine transaminase activity became high during the day and low at night. That this reversal in enzyme activity is not mediated by the pituitary-adrenal axis is demonstrated by the fact that in adrenalectomized rats tyrosine transaminase activity increased during the day in the sleep deprived rats. However, in these rats the enzyme activity did not become low in the sleep-deprived-sleeping condition. Changes in tryptophan pyrrolase activity during sleep deprivation were demonstrated to be mediated by the pituitary-adrenal axis. | Enzyme activity in sleep and sleep deprivation. Liver tyrosine transaminase activity is low during the day when the rats are mostly asleep and high during the night when they are awake. When wakefulness was imposed for 8 hr during daylight on the day of the experiment and the rats were allowed to sleep for the following 3 hr during darkness, the tyrosine transaminase activity became high during the day and low at night. That this reversal in enzyme activity is not mediated by the pituitary-adrenal axis is demonstrated by the fact that in adrenalectomized rats tyrosine transaminase activity increased during the day in the sleep deprived rats. However, in these rats the enzyme activity did not become low in the sleep-deprived-sleeping condition. Changes in tryptophan pyrrolase activity during sleep deprivation were demonstrated to be mediated by the pituitary-adrenal axis. | [
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PMID:4830 | The genetics of the mimetic butterfly Hypolimnas bolina (L.). | Hypolimnas bolina is a Nymphalid butterfly having a west to east distribution from Madagascar to Easter Island, and a north to south one from Japan to Australasia. It is highly migratory in some areas. In much of the western part of its range the female is both monomorphic and a mimic of Euploea. Further east it is frequently polymorphic with the majority of the forms being non-mimetic. The polymorphism is sex-limited to the female and controlled by two unlinked loci, one with two allelomorphs, E and e, determining the extent of the dark pigmentation, the other with three allelomorphs, P, Pn and p, determining the presence and distribution of orange-brown. Only butterflies of the genotypes EEpp and to a lesser extent Eepp are satisfactory Batesian mimics of their Euploea models. The details of the mimetic pattern are under multifactorial control, following those of their local model, as is much of the variation within the non-mimetic forms, particularly with regard to the distribution of white and blue scaling. | The genetics of the mimetic butterfly Hypolimnas bolina (L.). Hypolimnas bolina is a Nymphalid butterfly having a west to east distribution from Madagascar to Easter Island, and a north to south one from Japan to Australasia. It is highly migratory in some areas. In much of the western part of its range the female is both monomorphic and a mimic of Euploea. Further east it is frequently polymorphic with the majority of the forms being non-mimetic. The polymorphism is sex-limited to the female and controlled by two unlinked loci, one with two allelomorphs, E and e, determining the extent of the dark pigmentation, the other with three allelomorphs, P, Pn and p, determining the presence and distribution of orange-brown. Only butterflies of the genotypes EEpp and to a lesser extent Eepp are satisfactory Batesian mimics of their Euploea models. The details of the mimetic pattern are under multifactorial control, following those of their local model, as is much of the variation within the non-mimetic forms, particularly with regard to the distribution of white and blue scaling. | [
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PMID:4831 | Terrestrial vertebrates of the New Hebrides: origin and distribution. | The known terrestrial vertebrate fauna of the New Hebrides consists of 16 species of mammals (excluding feral domestic stock), 61 species of resident land- and freshwater birds, 20 species of reptiles and one amphibian. Of these, three, five, four and one species respectively have apparently been introduced by man. The non-introduced fauna is clearly Indo-Australian in origin, but some species have an exclusively Pacific island distribution and others (two bats, seven birds, and four lizards) are endemic. On the six islands visited 95 out of the possible 98 vertebrate species occur. Santo, the largest and most northerly island, supports the richest fauna. The comparative impoverishment of more southerly islands is not directly attributable to the progressive increase in isolation and distance from presumptive source area, nor to decrease in island area or maximum height. | Terrestrial vertebrates of the New Hebrides: origin and distribution. The known terrestrial vertebrate fauna of the New Hebrides consists of 16 species of mammals (excluding feral domestic stock), 61 species of resident land- and freshwater birds, 20 species of reptiles and one amphibian. Of these, three, five, four and one species respectively have apparently been introduced by man. The non-introduced fauna is clearly Indo-Australian in origin, but some species have an exclusively Pacific island distribution and others (two bats, seven birds, and four lizards) are endemic. On the six islands visited 95 out of the possible 98 vertebrate species occur. Santo, the largest and most northerly island, supports the richest fauna. The comparative impoverishment of more southerly islands is not directly attributable to the progressive increase in isolation and distance from presumptive source area, nor to decrease in island area or maximum height. | [
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PMID:4832 | 5-Aminolaevulinic acid dehydratase: structure, function, and mechanism. | delta-Aminolaevulinic acid dehydratase catalyses the synthesis of porphobilinogen. The enzyme has a molecular mass of 285000 and is composed of eight similar subunits of molecular mass 35000. The N-terminal amino acid is acylated, and the number of peptides found on tryptic digestion equals the number of lysine and arginine residues per mass of 35000. The eight subunits are apparently arranged at the corners of a cube and therefore have dihedral (D4) symmetry. The bovine liver enzyme which has been cystallized contains 4--6 atoms of zinc per mole of enzyme. The apo-enzyme obtained on prolonged hydrolysis can be reactivated by the addition of zinc or cadmium ions. The dialysed enzyme must be first treated with dithiothreitol. There are two very active SH groups in a total of 6--7-SH groups per subunit. The substrate forms a Schiff base with the epsilon-amino group of a lysine residue. Reduction of the Schiff base with NaBH4 should reveal the number of active sites per mole of enzyme. It appears that only four of the eight subunits form a Schiff base with the substrate indicating that the enzyme exhibits the phenomenon of either half-site reactivity or negative cooperativity. The enzyme appears to have a strong subunit-subunit interaction for an immobilized preparation remained stable for at least a month. An immobilized enzyme preparation was treated in a manner so that it dissociated into tetramers. Both the eluate and protein still attached to the Sepharose on a column were enzymically active. The bound enzyme could not reassociate under assay conditions but still contained about 50% of the original enzyme activity. It would seem that the enzyme is active when composed with less than eight subunits. | 5-Aminolaevulinic acid dehydratase: structure, function, and mechanism. delta-Aminolaevulinic acid dehydratase catalyses the synthesis of porphobilinogen. The enzyme has a molecular mass of 285000 and is composed of eight similar subunits of molecular mass 35000. The N-terminal amino acid is acylated, and the number of peptides found on tryptic digestion equals the number of lysine and arginine residues per mass of 35000. The eight subunits are apparently arranged at the corners of a cube and therefore have dihedral (D4) symmetry. The bovine liver enzyme which has been cystallized contains 4--6 atoms of zinc per mole of enzyme. The apo-enzyme obtained on prolonged hydrolysis can be reactivated by the addition of zinc or cadmium ions. The dialysed enzyme must be first treated with dithiothreitol. There are two very active SH groups in a total of 6--7-SH groups per subunit. The substrate forms a Schiff base with the epsilon-amino group of a lysine residue. Reduction of the Schiff base with NaBH4 should reveal the number of active sites per mole of enzyme. It appears that only four of the eight subunits form a Schiff base with the substrate indicating that the enzyme exhibits the phenomenon of either half-site reactivity or negative cooperativity. The enzyme appears to have a strong subunit-subunit interaction for an immobilized preparation remained stable for at least a month. An immobilized enzyme preparation was treated in a manner so that it dissociated into tetramers. Both the eluate and protein still attached to the Sepharose on a column were enzymically active. The bound enzyme could not reassociate under assay conditions but still contained about 50% of the original enzyme activity. It would seem that the enzyme is active when composed with less than eight subunits. | [
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PMID:4833 | Mechanism and stereochemistry of enzymic reactions involved in porphyrin biosynthesis. | 5-Aminolaevulinate synthetase cataylses the condensation of glycine and succinyl-CoA to give 5-aminolaevulinic acid. At least two broad pathways may be considered for the initial C--C bond forming step in the reaction. In pathway A the Schiff base of glycine and enzyme bound pyridoxal phosphate (a) undergoes decarboxylation to give the carbanion (b) which then condenses with succinyl-CoA with the retention of both the original C2 hydrogen atoms of glycine. In pathway B, loss of a C2 hydrogen atom gives another type of carbanion (c) that reacts with succinyl-CoA. Evidence has been presented to show that the initial C--C bond forming event occurs via pathway B which involves the removal of the pro R hydrogen atom of glycine. Subsequent mechanistic and stereochemical events occurring at the carbon atom destined to become C5 of 5-aminolaevulinate have also been delineated.(Carticle) Several mechanistic alternatices for the formation of the two vinyl groups of haem from the propionate residues of the precursor, coproporphyrinogen III, have been examined. (see article). It is shown that during the biosynthesis both the hydrogen atoms resident at the alpha positions of the propionate side chains remain undisturbed thus eliminating mechanisms which predict the involvement of acrylic acid intermediates. Biosynthetic experiments performed with precursors containing stereospecific labels have shown that the two vinyl groups of haem are formed through the loss of pro S hydrogen atoms from the beta-positions of the propionate side chains. In the light of these results, three related mechanisms for the conversion, propionate leads to vinyl, have been considered. In order to study the mechanism of porphyrinogen carboxy-lyase reaction, stereo-specifically deuterated, tritiated-succinate was incorporated into the acetate residues of uroporphyrinogen III which on decarboxylation generated asymmetric methyl groups in coproporphyrinogen III and then in haem. Degradation of the latter yielded chiral acetate deriving from C and D rings of haem. Configurational analysis of this derivate acetate shows that the carboxy-lyase reaction proceeds with a retention of configuration. | Mechanism and stereochemistry of enzymic reactions involved in porphyrin biosynthesis. 5-Aminolaevulinate synthetase cataylses the condensation of glycine and succinyl-CoA to give 5-aminolaevulinic acid. At least two broad pathways may be considered for the initial C--C bond forming step in the reaction. In pathway A the Schiff base of glycine and enzyme bound pyridoxal phosphate (a) undergoes decarboxylation to give the carbanion (b) which then condenses with succinyl-CoA with the retention of both the original C2 hydrogen atoms of glycine. In pathway B, loss of a C2 hydrogen atom gives another type of carbanion (c) that reacts with succinyl-CoA. Evidence has been presented to show that the initial C--C bond forming event occurs via pathway B which involves the removal of the pro R hydrogen atom of glycine. Subsequent mechanistic and stereochemical events occurring at the carbon atom destined to become C5 of 5-aminolaevulinate have also been delineated.(Carticle) Several mechanistic alternatices for the formation of the two vinyl groups of haem from the propionate residues of the precursor, coproporphyrinogen III, have been examined. (see article). It is shown that during the biosynthesis both the hydrogen atoms resident at the alpha positions of the propionate side chains remain undisturbed thus eliminating mechanisms which predict the involvement of acrylic acid intermediates. Biosynthetic experiments performed with precursors containing stereospecific labels have shown that the two vinyl groups of haem are formed through the loss of pro S hydrogen atoms from the beta-positions of the propionate side chains. In the light of these results, three related mechanisms for the conversion, propionate leads to vinyl, have been considered. In order to study the mechanism of porphyrinogen carboxy-lyase reaction, stereo-specifically deuterated, tritiated-succinate was incorporated into the acetate residues of uroporphyrinogen III which on decarboxylation generated asymmetric methyl groups in coproporphyrinogen III and then in haem. Degradation of the latter yielded chiral acetate deriving from C and D rings of haem. Configurational analysis of this derivate acetate shows that the carboxy-lyase reaction proceeds with a retention of configuration. | [
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