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PMID:30039	Mapping of the locus involved in the catabolic oxidation of D-amino acids in Pseudomonas aeruginosa PAO.	Mutants of Pseudomonas aeruginosa PAO deficient in their utilization of DL-valine have been found to have lost their capacity to utilize DL-alanine and L-proline. Use of conjugal and transductional mediated gene transfers have established the chromosomal location of this gene and also its pleotropic function in the induction of the D-amino acid oxidase, involved in the oxidative utilization of DL-valine, DL-alanine and L-proline. These point mutations are clustered in a single locus designated as Val D and mapped around the 19th minute on the chromosome.	Mapping of the locus involved in the catabolic oxidation of D-amino acids in Pseudomonas aeruginosa PAO. Mutants of Pseudomonas aeruginosa PAO deficient in their utilization of DL-valine have been found to have lost their capacity to utilize DL-alanine and L-proline. Use of conjugal and transductional mediated gene transfers have established the chromosomal location of this gene and also its pleotropic function in the induction of the D-amino acid oxidase, involved in the oxidative utilization of DL-valine, DL-alanine and L-proline. These point mutations are clustered in a single locus designated as Val D and mapped around the 19th minute on the chromosome.
PMID:30042	[Fenfluramin (ponderax) intoxications in children (author's transl)].	4 cases of accidental fenfluramine poisoning in children are reported. Excitation, coma, convulsions, tachycardia, mydriasis, nystagmus, and rubeosis of the face were the most important signs. They appeared 30--60 min after ingestion, and some of them lasted for several days. 2 children had severe trismus and therefore had to be given muscle relaxants before intubation and gastric lavage became possible. These observations agree well with informations collected in our poisoning control center and with previously published data. Less than 5 mg/kg of body weight are toxic, 5--10 mg/kg may produce coma and convulsions, and the smallest lethal doses were 28,7 and 33,3 mg/kg. Early gastric lavage, good monitoring of the vital functions and, if necessary, administration of anticonvulsive drugs, beta-blocking agents, lidocaine, chlorpromazine, and artificial ventilation and cardiac defibrillation are the most important therapeutical measures.	[Fenfluramin (ponderax) intoxications in children (author's transl)]. 4 cases of accidental fenfluramine poisoning in children are reported. Excitation, coma, convulsions, tachycardia, mydriasis, nystagmus, and rubeosis of the face were the most important signs. They appeared 30--60 min after ingestion, and some of them lasted for several days. 2 children had severe trismus and therefore had to be given muscle relaxants before intubation and gastric lavage became possible. These observations agree well with informations collected in our poisoning control center and with previously published data. Less than 5 mg/kg of body weight are toxic, 5--10 mg/kg may produce coma and convulsions, and the smallest lethal doses were 28,7 and 33,3 mg/kg. Early gastric lavage, good monitoring of the vital functions and, if necessary, administration of anticonvulsive drugs, beta-blocking agents, lidocaine, chlorpromazine, and artificial ventilation and cardiac defibrillation are the most important therapeutical measures.
PMID:30043	[Therapy with beta-blocking-agents (author's transl)].	Within the last 10 years the indications for a therapeutic regimen with beta-blocking-agents have been differentiated: coronary heart disease with angina pectoris (interval regimen), essential hypertension, especially in younger persons; hyperkinetic heart syndrome; thyreotoxikosis, symptomatic therapy; heart rhythm disorders, extrasystolic or tachysystolic; neurologic-psychiatric diseases. The development of the newer beta-blocking-agents has effected different kinetic data (f.i. long acting effects of Tenormin) and a increased cardioselectivity. The recommendations for the therapeutic regimen have to be outlined to the underlying diseases. The sensitivity against the drugs depends on remarkable individual differences, with the consequence of a careful and low dosage in the beginning in each case. The side-effects of beta-blocking-agents are presumably: bradycardia, bronchospasm, fatigue, adynamia, myocardial insufficiency, gastrointestinal symptoms, hypoglycemia, hypotension.	[Therapy with beta-blocking-agents (author's transl)]. Within the last 10 years the indications for a therapeutic regimen with beta-blocking-agents have been differentiated: coronary heart disease with angina pectoris (interval regimen), essential hypertension, especially in younger persons; hyperkinetic heart syndrome; thyreotoxikosis, symptomatic therapy; heart rhythm disorders, extrasystolic or tachysystolic; neurologic-psychiatric diseases. The development of the newer beta-blocking-agents has effected different kinetic data (f.i. long acting effects of Tenormin) and a increased cardioselectivity. The recommendations for the therapeutic regimen have to be outlined to the underlying diseases. The sensitivity against the drugs depends on remarkable individual differences, with the consequence of a careful and low dosage in the beginning in each case. The side-effects of beta-blocking-agents are presumably: bradycardia, bronchospasm, fatigue, adynamia, myocardial insufficiency, gastrointestinal symptoms, hypoglycemia, hypotension.
PMID:30044	Lymphocytic bronchitis associated with graft-versus-host disease in recipients of bone-marrow transplants.	Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus.	Lymphocytic bronchitis associated with graft-versus-host disease in recipients of bone-marrow transplants. Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus.
PMID:30046	Steroid-induced meiotic division in Xenopus laevis oocytes: surface and calcium.	Progesterone reinitiates meiotic maturation in Xenopus oocytes. Evidence is reported which indicates that the steroid acts at the level of the cell surface and suggests that an induced change of Ca2+ distribution triggers in turn a cascade of cytoplasmic events including protein synthesis and germinal vesicle (nucleus) breakdown. These novel features of steroid hormone action in amphibian oocytes are discussed in relation to presently accepted views of the mechanism of action of steroid hormones in somatic cells.	Steroid-induced meiotic division in Xenopus laevis oocytes: surface and calcium. Progesterone reinitiates meiotic maturation in Xenopus oocytes. Evidence is reported which indicates that the steroid acts at the level of the cell surface and suggests that an induced change of Ca2+ distribution triggers in turn a cascade of cytoplasmic events including protein synthesis and germinal vesicle (nucleus) breakdown. These novel features of steroid hormone action in amphibian oocytes are discussed in relation to presently accepted views of the mechanism of action of steroid hormones in somatic cells.
PMID:30047	Benzodiazepines and central inhibitory mechanisms.	The effect of diazepam was evaluated on spontaneous activity and drug- and electrically-elicited inhibitions of neuronal activity. Doses of diazepam which did not change spontaneous firing rates markedly enhanced GABA-mediated inhibitions in rat cerebellum in situ and in tissue cultures of rat hypothalamus. The effects of diazepam were readily reversible, and could be antagonized by picrotoxin; no effect on glycine or norepinephrine-induced inhibition was seen. It is concluded that actions of diazepam are mediated, at least in part, by a specific increase in GABA-mediated inhibition in the central nervous system.	Benzodiazepines and central inhibitory mechanisms. The effect of diazepam was evaluated on spontaneous activity and drug- and electrically-elicited inhibitions of neuronal activity. Doses of diazepam which did not change spontaneous firing rates markedly enhanced GABA-mediated inhibitions in rat cerebellum in situ and in tissue cultures of rat hypothalamus. The effects of diazepam were readily reversible, and could be antagonized by picrotoxin; no effect on glycine or norepinephrine-induced inhibition was seen. It is concluded that actions of diazepam are mediated, at least in part, by a specific increase in GABA-mediated inhibition in the central nervous system.
PMID:30069	Bohr effect induced by CO2 and fixed acid at various levels of O2 saturation in duck blood.	The Bohr factor, phi = delta log Po2/deltapH, was determined at various levels of hemoglobin O2 saturation (SO2) in fresh whole blood of the duck. Plasma pH was varied by either changing PCO2 of the blood at constant base excess (CO2 Bohr factor, phiCO2) or by addition of NaHCO3 and HCl at constant PCO2 (fixed acid BOHR factor, phiAH). No differences were found between phiCO2 and phiAH at SO2 levels between 20 and 85%, and there was no saturation dependence of the Bohr factor, its average value being -0.44. It is concluded that in whole blood of this bird species CO2 exerts no direct effect on the O2 affinity of hemoglobin.	Bohr effect induced by CO2 and fixed acid at various levels of O2 saturation in duck blood. The Bohr factor, phi = delta log Po2/deltapH, was determined at various levels of hemoglobin O2 saturation (SO2) in fresh whole blood of the duck. Plasma pH was varied by either changing PCO2 of the blood at constant base excess (CO2 Bohr factor, phiCO2) or by addition of NaHCO3 and HCl at constant PCO2 (fixed acid BOHR factor, phiAH). No differences were found between phiCO2 and phiAH at SO2 levels between 20 and 85%, and there was no saturation dependence of the Bohr factor, its average value being -0.44. It is concluded that in whole blood of this bird species CO2 exerts no direct effect on the O2 affinity of hemoglobin.
PMID:30070	Carbon dioxide and acid base balance in the isolated rat diaphragm.	A method for measuring the net acid base exchange in an isolated rat diaphragm preparation is described. Particular attention is paid to monitoring the functional status and maintaining optimal diffusion conditions. A steady net acid efflux of the order of 250 n mole/g-min is found in the resting state. This increases following a series of isometric contractions. In the resting state the total measured lactate + pyruvate efflux was found to be less than the net acid efflux. The net acid efflux increases following a sudden decrease in pCO2 and decreases or reverses following a sudden increase in pCO2 or a decrease in external bicarbonate. The net base loss during a period of 1 h following the exposure to high (20%) CO2 represents a large fraction of the predicted total bicarbonate generated within the fibres by non-bicarbonate buffers. This indicates that the effects of intracellular non-bicarbonate buffers can be transmitted to the external solution following a change in pCO2. The most plausible explanation is that passive bicarbonate ion movements are responsible. Values of the 'apparent PHCO3' have been calculated and vary under different conditions from a value of 1.3 X 10(-7) to 1.9 X 10(-6) cm-s-1.	Carbon dioxide and acid base balance in the isolated rat diaphragm. A method for measuring the net acid base exchange in an isolated rat diaphragm preparation is described. Particular attention is paid to monitoring the functional status and maintaining optimal diffusion conditions. A steady net acid efflux of the order of 250 n mole/g-min is found in the resting state. This increases following a series of isometric contractions. In the resting state the total measured lactate + pyruvate efflux was found to be less than the net acid efflux. The net acid efflux increases following a sudden decrease in pCO2 and decreases or reverses following a sudden increase in pCO2 or a decrease in external bicarbonate. The net base loss during a period of 1 h following the exposure to high (20%) CO2 represents a large fraction of the predicted total bicarbonate generated within the fibres by non-bicarbonate buffers. This indicates that the effects of intracellular non-bicarbonate buffers can be transmitted to the external solution following a change in pCO2. The most plausible explanation is that passive bicarbonate ion movements are responsible. Values of the 'apparent PHCO3' have been calculated and vary under different conditions from a value of 1.3 X 10(-7) to 1.9 X 10(-6) cm-s-1.
PMID:30083	Modification of DNA by aflatoxin B1 creates alkali-labile lesions in DNA at positions of guanine and adenine.	The damage to DNA by the hepatocarcinogen aflatoxin B1 was investigated. A DNA fragment of known sequence of the lactose promoter-operator region was used as a substrate for modification by aflatoxin B1. The DNA was incubated with aflatoxin B1 in crude mammalian liver extracts or with purified microsomes. Treatment of the DNA incubated in the complete system with either 1 M piperidine or 0.1 M NaOH at 90 degrees revealed alkali-labile lesions in the DNA. The exact location of the cleavage site was determined by comparison of the length of the cleavage products with the known sequence on polyacrylamide gels. The lengths of the cleavage products were the same as those produced by alkali-induced breakage of the same sequence of DNA that had been modified with dimethyl sulfate. The major cleavage products of the aflatoxin B1-modified DNA were at positions of guanine and the minor cleavage products were at positions of adenine. These studies show that modification of DNA by aflatoxin B1 creates alkali-labile sites at positions of guanine and, to a lesser extent, adenine.	Modification of DNA by aflatoxin B1 creates alkali-labile lesions in DNA at positions of guanine and adenine. The damage to DNA by the hepatocarcinogen aflatoxin B1 was investigated. A DNA fragment of known sequence of the lactose promoter-operator region was used as a substrate for modification by aflatoxin B1. The DNA was incubated with aflatoxin B1 in crude mammalian liver extracts or with purified microsomes. Treatment of the DNA incubated in the complete system with either 1 M piperidine or 0.1 M NaOH at 90 degrees revealed alkali-labile lesions in the DNA. The exact location of the cleavage site was determined by comparison of the length of the cleavage products with the known sequence on polyacrylamide gels. The lengths of the cleavage products were the same as those produced by alkali-induced breakage of the same sequence of DNA that had been modified with dimethyl sulfate. The major cleavage products of the aflatoxin B1-modified DNA were at positions of guanine and the minor cleavage products were at positions of adenine. These studies show that modification of DNA by aflatoxin B1 creates alkali-labile sites at positions of guanine and, to a lesser extent, adenine.
PMID:30084	Functional lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli: temperature and pH dependence of dansyl-galactoside binding.	6'-(N-Dansyl)aminohexyl-1-thio-beta-D-galactopyranoside binds specifically to the lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli. Binding can be induced by substrate oxidation (generation of an electrochemical gradient of protons), by potassium efflux in the presence of valinomycin (generation of a potassium diffusion potential), and by passive, carrier-mediated lactose efflux. We show that in all three cases the number of binding sites is temperature dependent. Binding is maximal and constant above 20 degrees ; it decreases between 20 degrees and 10 degrees . Oxidation of substrate (D-lactate) leads to the development of an electrochemical gradient of protons across the membrane (interior negative and alkaline), which is composed of interconvertible electrical and chemical gradients. We show that both the electrical potential across the membrane and the chemical difference in proton concentrations across the membrane are independent of temperature between 5 degrees and 25 degrees . We show that the number of binding sites induced by D-lactate oxidation depends on pH. At both 25 degrees and 5 degrees , the number of binding sites increases from pH 5 to pH 6.5, remains constant between pH 6.5 and 7, and decreases from pH 7 to pH 8. In contrast, the number of binding sites induced by passive, carrier-mediated lactose efflux is independent of pH between pH 5.5 and pH 8. From these findings, we conclude that the pH- and temperature-dependent effects on the number of 6'-(N-dansyl)aminohexyl-1-beta-thio-D-galactopyranoside binding sites have different origins. The pH dependence of binding is energy linked and reflects in part the pH dependence of the electrochemical gradient of protons across the membrane generated by substrate oxidation. The temperature dependence is not an energy-linked phenomenon. The decrease of the number of binding sites at low temperature probably reflects the aggregation of the lac carrier protein with other membrane proteins. This aggregation takes place as a consequence of the conformational disorder-to-order transition of the membrane lipids and the concomitant preferential segregation of the lac carrier protein in the membrane domains containing the disordered lipids.	Functional lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli: temperature and pH dependence of dansyl-galactoside binding. 6'-(N-Dansyl)aminohexyl-1-thio-beta-D-galactopyranoside binds specifically to the lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli. Binding can be induced by substrate oxidation (generation of an electrochemical gradient of protons), by potassium efflux in the presence of valinomycin (generation of a potassium diffusion potential), and by passive, carrier-mediated lactose efflux. We show that in all three cases the number of binding sites is temperature dependent. Binding is maximal and constant above 20 degrees ; it decreases between 20 degrees and 10 degrees . Oxidation of substrate (D-lactate) leads to the development of an electrochemical gradient of protons across the membrane (interior negative and alkaline), which is composed of interconvertible electrical and chemical gradients. We show that both the electrical potential across the membrane and the chemical difference in proton concentrations across the membrane are independent of temperature between 5 degrees and 25 degrees . We show that the number of binding sites induced by D-lactate oxidation depends on pH. At both 25 degrees and 5 degrees , the number of binding sites increases from pH 5 to pH 6.5, remains constant between pH 6.5 and 7, and decreases from pH 7 to pH 8. In contrast, the number of binding sites induced by passive, carrier-mediated lactose efflux is independent of pH between pH 5.5 and pH 8. From these findings, we conclude that the pH- and temperature-dependent effects on the number of 6'-(N-dansyl)aminohexyl-1-beta-thio-D-galactopyranoside binding sites have different origins. The pH dependence of binding is energy linked and reflects in part the pH dependence of the electrochemical gradient of protons across the membrane generated by substrate oxidation. The temperature dependence is not an energy-linked phenomenon. The decrease of the number of binding sites at low temperature probably reflects the aggregation of the lac carrier protein with other membrane proteins. This aggregation takes place as a consequence of the conformational disorder-to-order transition of the membrane lipids and the concomitant preferential segregation of the lac carrier protein in the membrane domains containing the disordered lipids.
PMID:30085	A macromolecular transducer as illustrated by trout hemoglobin IV.	Oxygen binding by trout Hb IV has been investigated as a function of pH up to 10 atmospheres (1 MPa) of pure O2. The results bring out an extreme proton-oxygen linkage, which gives rise to a Root effect. They are discussed in relation to the function of the hemoglobin as an oxygen pump. The system is of special interest as providing a prototype of a macromolecule acting as a transducer by coupling two allosterically linked reactions.	A macromolecular transducer as illustrated by trout hemoglobin IV. Oxygen binding by trout Hb IV has been investigated as a function of pH up to 10 atmospheres (1 MPa) of pure O2. The results bring out an extreme proton-oxygen linkage, which gives rise to a Root effect. They are discussed in relation to the function of the hemoglobin as an oxygen pump. The system is of special interest as providing a prototype of a macromolecule acting as a transducer by coupling two allosterically linked reactions.
PMID:30082	[Multicomponent system of specific estrogen-binding liver proteins. Some properties of a rapidly dissociating estrogen-binding liver protein from guinea pigs].	A study was made of some binding and physico-chemical properties of a special estrogen-binding protein of liver cytozol in sexually mature female and male guinea pigs following its partial purification by means of ammonium sulfate sedimentation, gelfiltration and ion-exchange chromatography. The given protein proved to bind estradiol (E2) with Ka of the 10(7) M-1 order and possessed a rather marked hormonal affinity specificity. Under unbalanced conditions its complexes with E2 were capable of rapid dissociation. Characteristics of the size of protein molecules were: molecular weight--about 60000, Stokes' radius--3.2 nm, sedimentation coefficient--4.6, friction coefficient ratio--1.18. Protein E2-binding activity was reversibly depressed in the presence of high salt concentrations, decreased in the presence of dithioerythritol and on heating at the temperature of over 50 degree C. The optimum E2 binding was observed at pH 7.3--7.7. There were no significant differences in the properties of protein from the liver of males and females. A conclusion was drawn on a close similarity between the given protein of guinea pigs and of a special estrogen-binding protein of the liver in male rats detected by the authors earlier.	[Multicomponent system of specific estrogen-binding liver proteins. Some properties of a rapidly dissociating estrogen-binding liver protein from guinea pigs]. A study was made of some binding and physico-chemical properties of a special estrogen-binding protein of liver cytozol in sexually mature female and male guinea pigs following its partial purification by means of ammonium sulfate sedimentation, gelfiltration and ion-exchange chromatography. The given protein proved to bind estradiol (E2) with Ka of the 10(7) M-1 order and possessed a rather marked hormonal affinity specificity. Under unbalanced conditions its complexes with E2 were capable of rapid dissociation. Characteristics of the size of protein molecules were: molecular weight--about 60000, Stokes' radius--3.2 nm, sedimentation coefficient--4.6, friction coefficient ratio--1.18. Protein E2-binding activity was reversibly depressed in the presence of high salt concentrations, decreased in the presence of dithioerythritol and on heating at the temperature of over 50 degree C. The optimum E2 binding was observed at pH 7.3--7.7. There were no significant differences in the properties of protein from the liver of males and females. A conclusion was drawn on a close similarity between the given protein of guinea pigs and of a special estrogen-binding protein of the liver in male rats detected by the authors earlier.
PMID:30086	Coated vesicles: characterization, selective dissociation, and reassembly.	Sodium dodecyl sulfate/polyacrylamide gels of coated vesicles from porcine brain (mean 76% coated vesicles) show three major proteins (180,000, 125,000, and 55,000 daltons) that account for 73% of the total protein. Preparations consisting predominantly of coats (65%) have less of the 55,000-dalton protein. Clathrin (180,000 daltons) comprises 40% of the protein of a coated vesicle. Conditions of 2 M urea, 0.25 M MgCl2, or pH 7.5 disrupt the coat and solubilize clathrin. Solubilized clathrin reforms coat structures after dilution of urea or MgCl2. High-pH-solubilized clathrin reassembles after dialysis against buffer at pH 6.5 containing dithiothreitol (5 mM). Reassembled coats are predominantly clathrin.	Coated vesicles: characterization, selective dissociation, and reassembly. Sodium dodecyl sulfate/polyacrylamide gels of coated vesicles from porcine brain (mean 76% coated vesicles) show three major proteins (180,000, 125,000, and 55,000 daltons) that account for 73% of the total protein. Preparations consisting predominantly of coats (65%) have less of the 55,000-dalton protein. Clathrin (180,000 daltons) comprises 40% of the protein of a coated vesicle. Conditions of 2 M urea, 0.25 M MgCl2, or pH 7.5 disrupt the coat and solubilize clathrin. Solubilized clathrin reforms coat structures after dilution of urea or MgCl2. High-pH-solubilized clathrin reassembles after dialysis against buffer at pH 6.5 containing dithiothreitol (5 mM). Reassembled coats are predominantly clathrin.
PMID:30087	Nerve growth factor-mediated induction of tyrosine hydroxylase in a clonal pheochromocytoma cell line.	We have established a clonal cell line, PC-G2, from an experimentally induced rat pheochromocytoma. Administration of nerve growth factor to PC-G2 causes a 4- to 8-fold induction in the specific activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase(3-hydroxylating); EC 1.14.16.2]. The response is elicited in a dose-dependent fashion, at concentrations above 0.1 microgram/ml. Antiserum to nerve growth factor inhibited the induction of tyrosine hydroxylase. Dexamethasone enhances the nerve growth factor-mediated elevation of tyrosine hydroxylase. After 3--4 days of exposure to nerve growth factor the maximal induction of tyrosine hydroxylase is seen, although a significant increase can be observed after 24 hr. In contrast to the PC-12 cell line (derived from the same tumor), in which neurite outgrowth occurs in response to nerve growth factor, there is no morphological change or alteration in growth rate of PC-G2 cells after exposure to nerve growth factor.	Nerve growth factor-mediated induction of tyrosine hydroxylase in a clonal pheochromocytoma cell line. We have established a clonal cell line, PC-G2, from an experimentally induced rat pheochromocytoma. Administration of nerve growth factor to PC-G2 causes a 4- to 8-fold induction in the specific activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase(3-hydroxylating); EC 1.14.16.2]. The response is elicited in a dose-dependent fashion, at concentrations above 0.1 microgram/ml. Antiserum to nerve growth factor inhibited the induction of tyrosine hydroxylase. Dexamethasone enhances the nerve growth factor-mediated elevation of tyrosine hydroxylase. After 3--4 days of exposure to nerve growth factor the maximal induction of tyrosine hydroxylase is seen, although a significant increase can be observed after 24 hr. In contrast to the PC-12 cell line (derived from the same tumor), in which neurite outgrowth occurs in response to nerve growth factor, there is no morphological change or alteration in growth rate of PC-G2 cells after exposure to nerve growth factor.
PMID:30092	Kainic acid and synaptic transmission in the stellate ganglion of the squid.	Kainate, a conformational analogue of glutamate, blocks synaptic transmission across the giant synapse of the squid. In the presence of blocking doses of kainate, impulses continue to propagate into the nerve terminal, but action potentials are slightly reduced in size and the subsequent hyperpolarization is greatly diminished. Kainate depolarizes the postsynaptic axon. Since the depolarizing action of kainate is confined to the postsynaptic membrane, it appears that kainate can combine with the receptors which are normally activated by the transmitter. This results in a diminished effect of the transmitter released by a presynaptic nerve impulse.	Kainic acid and synaptic transmission in the stellate ganglion of the squid. Kainate, a conformational analogue of glutamate, blocks synaptic transmission across the giant synapse of the squid. In the presence of blocking doses of kainate, impulses continue to propagate into the nerve terminal, but action potentials are slightly reduced in size and the subsequent hyperpolarization is greatly diminished. Kainate depolarizes the postsynaptic axon. Since the depolarizing action of kainate is confined to the postsynaptic membrane, it appears that kainate can combine with the receptors which are normally activated by the transmitter. This results in a diminished effect of the transmitter released by a presynaptic nerve impulse.
PMID:30093	Structural correlates of recurrent collateral interneurons producing both electrical and chemical inhibitions of the Mauthner cell.	Intracellular injections of horseradish peroxidase provided a basis for morphological identification of inhibitory interneurons belonging to the recurrent collateral network of the Mauthner cell. Their axons dilate to form unusually large bulbs surrounding the axon cap. The morphological appearance of these bulbs as well as intracellular recordings at their level indicate that they behave as nodes and serve as a final source of current for electrical inhibition of the Mauthner cell. The axon of each interneuron gives rise to two different groups of fibres which are respectively fitted for the mediation of electrical and chemical inhibitions of their target cell.	Structural correlates of recurrent collateral interneurons producing both electrical and chemical inhibitions of the Mauthner cell. Intracellular injections of horseradish peroxidase provided a basis for morphological identification of inhibitory interneurons belonging to the recurrent collateral network of the Mauthner cell. Their axons dilate to form unusually large bulbs surrounding the axon cap. The morphological appearance of these bulbs as well as intracellular recordings at their level indicate that they behave as nodes and serve as a final source of current for electrical inhibition of the Mauthner cell. The axon of each interneuron gives rise to two different groups of fibres which are respectively fitted for the mediation of electrical and chemical inhibitions of their target cell.
PMID:30095	Brain catecholamines metabolism in offspring of amphetamine treated rats.	Previous observations have pointed out that treatment with amphetamine during pregnancy produces behavioral modifications in adulthood. In order to elucidate some possible brain biochemical mechanisms that could explain the behavioral changes observed we have determined the endogenous content of brain dopamine and noradrenaline, the in vivo rate of conversion of tyrosine-C14 in such amines and the activity of tyrosine-hydroxylase, the rate limiting enzyme in catecholamines biosynthesis. We did not observe modifications in the endogenous content of dopamine and noradrenaline but did observe an increase in the conversion rate of tyrosine-C14 in such amines and also in the tyrosine-hydroxylase activity. These results indicate that treatment with amphetamines during fetal age produces catecholamine metabolism modifications that persist throughout adulthood, although the influence of behavioral modifications of the mothers cannot be ruled out. The relationship with behavioral changes is discussed.	Brain catecholamines metabolism in offspring of amphetamine treated rats. Previous observations have pointed out that treatment with amphetamine during pregnancy produces behavioral modifications in adulthood. In order to elucidate some possible brain biochemical mechanisms that could explain the behavioral changes observed we have determined the endogenous content of brain dopamine and noradrenaline, the in vivo rate of conversion of tyrosine-C14 in such amines and the activity of tyrosine-hydroxylase, the rate limiting enzyme in catecholamines biosynthesis. We did not observe modifications in the endogenous content of dopamine and noradrenaline but did observe an increase in the conversion rate of tyrosine-C14 in such amines and also in the tyrosine-hydroxylase activity. These results indicate that treatment with amphetamines during fetal age produces catecholamine metabolism modifications that persist throughout adulthood, although the influence of behavioral modifications of the mothers cannot be ruled out. The relationship with behavioral changes is discussed.
PMID:30096	Role of neuroleptic agents on mouse pulmonary cyclic nucleotide systems.	The norepinephrine (NE)-induced accumulation of cyclic AMP in incubated tissue slices of mouse lung was inhibited by chlorpromazine (CPZ) and to a lesser extent by haloperidol. In particulate lung fractions both agents blocked dopamine-sensitive adenylate cyclase to a greater degree than the NE-responsive enzyme. Again CPZ was more potent than haloperidol. Acute injections (1/2--8h) of the neuroleptics usually resulted in lower steady state levels of pulmonary cyclic AMP and cyclic GMP following rapid (0.5 sec) tissue inactivation by microwave irradiation. On a subchronic injection schedule, the in vivo levels of pulmonary cyclic AMP tended to increase.	Role of neuroleptic agents on mouse pulmonary cyclic nucleotide systems. The norepinephrine (NE)-induced accumulation of cyclic AMP in incubated tissue slices of mouse lung was inhibited by chlorpromazine (CPZ) and to a lesser extent by haloperidol. In particulate lung fractions both agents blocked dopamine-sensitive adenylate cyclase to a greater degree than the NE-responsive enzyme. Again CPZ was more potent than haloperidol. Acute injections (1/2--8h) of the neuroleptics usually resulted in lower steady state levels of pulmonary cyclic AMP and cyclic GMP following rapid (0.5 sec) tissue inactivation by microwave irradiation. On a subchronic injection schedule, the in vivo levels of pulmonary cyclic AMP tended to increase.
PMID:30098	[Planning of psychotropic drug trials. Statistical evaluation. Hypotheses and methods].	Any reasonable evaluation presupposes a precise question. Furthermore it is necessary to eliminate all factors of disturbance, which are able either to simulate or to mask a result of evaluation. The most important of these factors is the psychiatrist himself. Therefore, experimental designs have to taken in account the factor psychiatrist. Criteria of the effects of any drug must be relevant with regard to comparison of two or more drug effects. The reproduciability of criteria is very desirable, but a wish-fulfilment under the most circumstances. Because criteria should be independent and mutually exclusive, all scales like the Hamiltons one are not suitable for evaluation. Finally one should use as few criteria as possible. Models of evaluation are described for the most frequent questions in connection with clinical trials in psychopharmacology.	[Planning of psychotropic drug trials. Statistical evaluation. Hypotheses and methods]. Any reasonable evaluation presupposes a precise question. Furthermore it is necessary to eliminate all factors of disturbance, which are able either to simulate or to mask a result of evaluation. The most important of these factors is the psychiatrist himself. Therefore, experimental designs have to taken in account the factor psychiatrist. Criteria of the effects of any drug must be relevant with regard to comparison of two or more drug effects. The reproduciability of criteria is very desirable, but a wish-fulfilment under the most circumstances. Because criteria should be independent and mutually exclusive, all scales like the Hamiltons one are not suitable for evaluation. Finally one should use as few criteria as possible. Models of evaluation are described for the most frequent questions in connection with clinical trials in psychopharmacology.
PMID:30099	Effect of alcohol and benzodiazepines on performance as related to personality characteristics. Personality characteristics among healthy "placebo reactors" and nonreactors.	For 2 weeks 40 volunteers received either 5 mg diazepam, t.i.d., or 10 mg chlordiazepoxide, t.i.d., and placebo. A choice reaction test, two coordination tests, and an attention test were administered to the subjects on the 14th day of each treatment. Thirty minutes before the tests, the subjects ingested either alcohol., 5g/kg or a placebo drink, incombination with the last capsule. After the test the subjects rated the quality of their treatment as placebo, tranquilizer, or stimulant. The psychological tests taken before the treatments were Eysenck's EPIC-NESI, Taylor's Manifest Anxiety Scale (MAS), and Cattell's 16 PF inventory. A multiple regression analysis was computed. Personality factor scores found to be associated with a strong effect of the benzodiazepines were 16 PF's A, C, L, N, and Q, and EPIC's E. The effect of alcohol was associated with a high score of 16 PFs B factor. Personality factors associated with "placebo reactors" and nonreactors were investigated, as well. Those subjects on placebo indicating their treatment to be active were classified as "placebo reactors". A discriminant analysis revealed that 16PF's O and I factors discriminated effectively "placebo reactors" from nonreactors, and EPIC's SE and 16 PF's L factor nonreactors from "reactors".	Effect of alcohol and benzodiazepines on performance as related to personality characteristics. Personality characteristics among healthy "placebo reactors" and nonreactors. For 2 weeks 40 volunteers received either 5 mg diazepam, t.i.d., or 10 mg chlordiazepoxide, t.i.d., and placebo. A choice reaction test, two coordination tests, and an attention test were administered to the subjects on the 14th day of each treatment. Thirty minutes before the tests, the subjects ingested either alcohol., 5g/kg or a placebo drink, incombination with the last capsule. After the test the subjects rated the quality of their treatment as placebo, tranquilizer, or stimulant. The psychological tests taken before the treatments were Eysenck's EPIC-NESI, Taylor's Manifest Anxiety Scale (MAS), and Cattell's 16 PF inventory. A multiple regression analysis was computed. Personality factor scores found to be associated with a strong effect of the benzodiazepines were 16 PF's A, C, L, N, and Q, and EPIC's E. The effect of alcohol was associated with a high score of 16 PFs B factor. Personality factors associated with "placebo reactors" and nonreactors were investigated, as well. Those subjects on placebo indicating their treatment to be active were classified as "placebo reactors". A discriminant analysis revealed that 16PF's O and I factors discriminated effectively "placebo reactors" from nonreactors, and EPIC's SE and 16 PF's L factor nonreactors from "reactors".
PMID:30100	[Further developments of the AMP-system. A report on the 2nd AMP-symposium and training seminar (author's transl)].	This is a report of a symposium and training seminar of the "Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie" (AMP). Video-recordings of two psychiatric interviews were shown during the seminar and rated by the participants using the AMP-3-Scale (Psychopathology). Aim of the seminar was a rater training and the preparation of an expert standard rating. These videotapes with the corresponding standard ratings will enable the different clinics using the AMP-System to compare their rating behaviour. The process of achieving an expert standard rating is described. The training seminar was followed by a symposium during which a series of lectures was presented on "Standardized Assessment in Psychiatry", The different working groups of the Association reported about their work and future prospects of the Association were discussed.	[Further developments of the AMP-system. A report on the 2nd AMP-symposium and training seminar (author's transl)]. This is a report of a symposium and training seminar of the "Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie" (AMP). Video-recordings of two psychiatric interviews were shown during the seminar and rated by the participants using the AMP-3-Scale (Psychopathology). Aim of the seminar was a rater training and the preparation of an expert standard rating. These videotapes with the corresponding standard ratings will enable the different clinics using the AMP-System to compare their rating behaviour. The process of achieving an expert standard rating is described. The training seminar was followed by a symposium during which a series of lectures was presented on "Standardized Assessment in Psychiatry", The different working groups of the Association reported about their work and future prospects of the Association were discussed.
PMID:30101	Indication of an antipsychotic action of the opiate antagonist naloxone.	In 20 psychotic patients with frequent hallucinations and/or actual delusional experience a possible antipsychotic action of the opiate antagonist naloxone (N-allyl-noroxymorphone) was investigated, using a double-blind placebo-controlled cross-over design. 18 of these patients were not treated with neuroleptic drugs; 13 suffered from an acute episode of schizophrenia. Psychopathological changes were assessed by the use of the IMPS-scale and of a symptom-specific rating scale (VBS). Intravenous injection of naloxone (in most cases 4.0 mg) induced a reduction of psychotic symptomatology (especially hallucinations) in the majority of patients. Compared with placebo this effect reached statistical significance within 2-7 hours after injection. From this result a possible involvement of endogenous ligands of opiate receptors in the pathogenesis of schizophrenia may be concluded.	Indication of an antipsychotic action of the opiate antagonist naloxone. In 20 psychotic patients with frequent hallucinations and/or actual delusional experience a possible antipsychotic action of the opiate antagonist naloxone (N-allyl-noroxymorphone) was investigated, using a double-blind placebo-controlled cross-over design. 18 of these patients were not treated with neuroleptic drugs; 13 suffered from an acute episode of schizophrenia. Psychopathological changes were assessed by the use of the IMPS-scale and of a symptom-specific rating scale (VBS). Intravenous injection of naloxone (in most cases 4.0 mg) induced a reduction of psychotic symptomatology (especially hallucinations) in the majority of patients. Compared with placebo this effect reached statistical significance within 2-7 hours after injection. From this result a possible involvement of endogenous ligands of opiate receptors in the pathogenesis of schizophrenia may be concluded.
PMID:30103	[Influence of the Benzodiazepine-derivative Ro 06-9098/000 on choreo-athetotic syndromes (author's transl)].	Five patients suffering from choreo-athetotic syndromes of different genesis were treated with the benzodiazepine-derivative Ro 06-9098/000 (7-Nitro-1(methylmethoxy)-1,3-dihydro-5-phenyl-2 H-1,4-benzodiazepin-2-one). The existing hyperkinesias could be well influenced in four cases of male patients, sufficiently in one case of a female patient. The sedative effect, accompanied by a muscle hypotonia appearing simultaneously under the medication, did not represent and essential limiting factors at the chosen dose of 5--20 mg/die. The observed successes in therapy point at the result and effect of benzodiazepine derivatives on extra-pyramidalmotoric hyperkinesias which got little attention until now.	[Influence of the Benzodiazepine-derivative Ro 06-9098/000 on choreo-athetotic syndromes (author's transl)]. Five patients suffering from choreo-athetotic syndromes of different genesis were treated with the benzodiazepine-derivative Ro 06-9098/000 (7-Nitro-1(methylmethoxy)-1,3-dihydro-5-phenyl-2 H-1,4-benzodiazepin-2-one). The existing hyperkinesias could be well influenced in four cases of male patients, sufficiently in one case of a female patient. The sedative effect, accompanied by a muscle hypotonia appearing simultaneously under the medication, did not represent and essential limiting factors at the chosen dose of 5--20 mg/die. The observed successes in therapy point at the result and effect of benzodiazepine derivatives on extra-pyramidalmotoric hyperkinesias which got little attention until now.
PMID:30105	[The preprogramming of behavior patterns by changing the neurotransmitter metabolism in the early postnatal ontogenesis of albino rats].	Changes in neurotransmitter concentrations, which are brought about by the administration of neurotropic pharmaceuticals to albino rats at the time of differentiation of the brain, may have a lasting effect upon the reactivity and adaptability of adult animals to environmental factors and give rise to specific patterns of behavior. 1. Pargyline, when administered neonatally, resulted in a reduction of learning power, decrease in the power of retention, as well as reduction of the decision-making ability. 2. Reserpine gave an improvement of learning power, but simultaneously decreased both the power of retaining what had been learnt and the decision-making ability. 3. Pyridostigmine gave a marked improvement of adaptability which was evidenced in higher learning power, greater retentiveness, and better decision-making ability.	[The preprogramming of behavior patterns by changing the neurotransmitter metabolism in the early postnatal ontogenesis of albino rats]. Changes in neurotransmitter concentrations, which are brought about by the administration of neurotropic pharmaceuticals to albino rats at the time of differentiation of the brain, may have a lasting effect upon the reactivity and adaptability of adult animals to environmental factors and give rise to specific patterns of behavior. 1. Pargyline, when administered neonatally, resulted in a reduction of learning power, decrease in the power of retention, as well as reduction of the decision-making ability. 2. Reserpine gave an improvement of learning power, but simultaneously decreased both the power of retaining what had been learnt and the decision-making ability. 3. Pyridostigmine gave a marked improvement of adaptability which was evidenced in higher learning power, greater retentiveness, and better decision-making ability.
PMID:30106	The striatonigral fibres and the feedback control of dopamine metabolism.	It proved possible to make lesions which interrupted the striatonigral GABA-containing pathway in the rat brain without causing concomitant damage to the nigrostriatal dopamine containing system. Estimations of striatal concentrations of dopamine (DA), dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA) inducated that these lesions had no influence either on normal striatal DA turnover or on the enhancement of DA turnover induced by neuroleptics. Behavioural experiments suggested a motor output function for the striatonigral pathway.	The striatonigral fibres and the feedback control of dopamine metabolism. It proved possible to make lesions which interrupted the striatonigral GABA-containing pathway in the rat brain without causing concomitant damage to the nigrostriatal dopamine containing system. Estimations of striatal concentrations of dopamine (DA), dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA) inducated that these lesions had no influence either on normal striatal DA turnover or on the enhancement of DA turnover induced by neuroleptics. Behavioural experiments suggested a motor output function for the striatonigral pathway.
PMID:30110	Benzodiazepines and behavioral effects of reward (water) omission in the rat.	Two behaviors related to nonreward (omission of water in an enclosure where the rats were habituated to drink) were studied. The time spent licking the bottles during water omission and the time spent drinking during a subsequent 5-min drinking session (water available) were recorded. The drinking session was performed 30 min after the water-omission session. Rats subjected to water omission showed an enhanced drinking time that varied with the length of the water omission session, with the motivational state of the animals, and with the previous number of water-omission sessions. Diazepam, chlordiazepoxide, lorazepam, and meprobamate (i.p., 30 min before water omission), increased the time spent licking the empty bottles, but failed to abolish subsequently enhanced drinking. However, some of our data suggested that minor tranquilizers weakly reduced the increased drinking induced by nonreward, despite their direct stimulation on water drinking. It is proposed that either minor tranquilizers are devoid of general antifrustration activity or nonreward-induced frustration and nonreward-induced drive enhancement may not be correlated.	Benzodiazepines and behavioral effects of reward (water) omission in the rat. Two behaviors related to nonreward (omission of water in an enclosure where the rats were habituated to drink) were studied. The time spent licking the bottles during water omission and the time spent drinking during a subsequent 5-min drinking session (water available) were recorded. The drinking session was performed 30 min after the water-omission session. Rats subjected to water omission showed an enhanced drinking time that varied with the length of the water omission session, with the motivational state of the animals, and with the previous number of water-omission sessions. Diazepam, chlordiazepoxide, lorazepam, and meprobamate (i.p., 30 min before water omission), increased the time spent licking the empty bottles, but failed to abolish subsequently enhanced drinking. However, some of our data suggested that minor tranquilizers weakly reduced the increased drinking induced by nonreward, despite their direct stimulation on water drinking. It is proposed that either minor tranquilizers are devoid of general antifrustration activity or nonreward-induced frustration and nonreward-induced drive enhancement may not be correlated.
PMID:30115	Pulmonary complications associated with the prune-belly syndrome.	Eight patients are presented who demonstrate many of the pulmonary complications seen in the prune-belly syndrome. The patients are divided into two major groups: Group I includes pulmonary hypoplasia; Group II includes lobar atelectasis and pneumonia. The etiology, pathogenesis, and radiographic features of these complications are discussed. Pulmonary complications become more important as renal dialysis and transplantation spare more of these patients from an early uremic death. Prompt recognition of the type and the extent of pulmonary disease in patients with the prune-belly syndrome may lead to increased survival.	Pulmonary complications associated with the prune-belly syndrome. Eight patients are presented who demonstrate many of the pulmonary complications seen in the prune-belly syndrome. The patients are divided into two major groups: Group I includes pulmonary hypoplasia; Group II includes lobar atelectasis and pneumonia. The etiology, pathogenesis, and radiographic features of these complications are discussed. Pulmonary complications become more important as renal dialysis and transplantation spare more of these patients from an early uremic death. Prompt recognition of the type and the extent of pulmonary disease in patients with the prune-belly syndrome may lead to increased survival.
PMID:30119	Activation of guanylate cyclase by arachidonic acid in mammary gland homogenates from mice.	Arachidonic acid stimulated guanylate cyclase activity about two fold in homogenates of mammary glands obtained from midpregnant mice; effects of arachidonic acid were observed during incubation periods between 5 and 20 minutes. Stimulatory effects of arachidonic acid on guanylate cyclase activity were observed when 10 to 100 microgram arachidonic acid was added to the reaction mixtures (150 microliter). When 250 microgram or more arachidonic acid was added to the reaction mixtures, the activity of guanylate cyclase was inhibited. Other fatty acids including linoleic acid, linolenic acid and oleic acid also stimulated guanylate cyclase activity but neither arachidic acid nor stearic acid had an effect. The arachidonic acid stimulation of guanylate cyclase activity was abolished by incubation with indomethacin and aspirin, thus suggesting the arachidonic acid effect may be carried out via the prostaglandins. A variety of prostaglandins, however, at several concentrations did not stimulate guanylate cyclase activity when added to the reaction mixtures. The failure of the prostaglandins to have an effect may be due to several reasons which are discussed.	Activation of guanylate cyclase by arachidonic acid in mammary gland homogenates from mice. Arachidonic acid stimulated guanylate cyclase activity about two fold in homogenates of mammary glands obtained from midpregnant mice; effects of arachidonic acid were observed during incubation periods between 5 and 20 minutes. Stimulatory effects of arachidonic acid on guanylate cyclase activity were observed when 10 to 100 microgram arachidonic acid was added to the reaction mixtures (150 microliter). When 250 microgram or more arachidonic acid was added to the reaction mixtures, the activity of guanylate cyclase was inhibited. Other fatty acids including linoleic acid, linolenic acid and oleic acid also stimulated guanylate cyclase activity but neither arachidic acid nor stearic acid had an effect. The arachidonic acid stimulation of guanylate cyclase activity was abolished by incubation with indomethacin and aspirin, thus suggesting the arachidonic acid effect may be carried out via the prostaglandins. A variety of prostaglandins, however, at several concentrations did not stimulate guanylate cyclase activity when added to the reaction mixtures. The failure of the prostaglandins to have an effect may be due to several reasons which are discussed.
PMID:30122	Effect of beta-fluorophenethylamine analogs on monoamine oxidase substrate preference.	A novel potentiometric assay was employed to evaluate the effects of beta-fluorination of phenethylamine (PEA) on brain MAO substrate preference. Through the use of the substrate selective MAO inhibitors clorgyline (type A) and Deprenyl (type B), F-PEA and F2-PEA were found to be preferred substrates for MAO type B. Since various degrees of fluorination of the parent PEA molecule proportionally decrease the pKa values, as well as their substrate activity for MAO, it is suggested that the protonated form of PEA and its respective mono and difluoro analogs are the preferred substrate forms for catalysis by brain MAO.	Effect of beta-fluorophenethylamine analogs on monoamine oxidase substrate preference. A novel potentiometric assay was employed to evaluate the effects of beta-fluorination of phenethylamine (PEA) on brain MAO substrate preference. Through the use of the substrate selective MAO inhibitors clorgyline (type A) and Deprenyl (type B), F-PEA and F2-PEA were found to be preferred substrates for MAO type B. Since various degrees of fluorination of the parent PEA molecule proportionally decrease the pKa values, as well as their substrate activity for MAO, it is suggested that the protonated form of PEA and its respective mono and difluoro analogs are the preferred substrate forms for catalysis by brain MAO.
PMID:30123	Survival of Leptospira interrogans serovar pomona in an acidic soil under simulated New Zealand field conditions.	Leptospira interrogans serovar pomona was found to survive for at least 42 days in a typical New Zealand soil under simulated winter field conditions. The soil was markedly acidic with a pH of 5.5 and survival times were not reduced even when its water content was only 23%. The values of both these parameters are considerably less than previously recorded for the survival of leptospires in soil. Two methods were used to recover leptospires from the soil microflora. One was the culture of a membrane filtrate in EMJH media with or without contaminant-suppressing additives and the other was the direct inoculation of soil-washings into hamsters. Both techniques proved to equally sensitive. It was estimated that following the addition of 5 X 10(8) leptospires to the soil samples less than 2 X 10(4) were present after six weeks.	Survival of Leptospira interrogans serovar pomona in an acidic soil under simulated New Zealand field conditions. Leptospira interrogans serovar pomona was found to survive for at least 42 days in a typical New Zealand soil under simulated winter field conditions. The soil was markedly acidic with a pH of 5.5 and survival times were not reduced even when its water content was only 23%. The values of both these parameters are considerably less than previously recorded for the survival of leptospires in soil. Two methods were used to recover leptospires from the soil microflora. One was the culture of a membrane filtrate in EMJH media with or without contaminant-suppressing additives and the other was the direct inoculation of soil-washings into hamsters. Both techniques proved to equally sensitive. It was estimated that following the addition of 5 X 10(8) leptospires to the soil samples less than 2 X 10(4) were present after six weeks.
PMID:30124	Tissue and blood distribution of gamma-glutamyl transferase in the lamb and in the ewe.	Gamma-glutamyl transferase distribution was studied in 10 ewes and 10 lambs; in both groups kidney was the most active organ, followed by pancreas, liver and lungs. In kidney and liver, GGT was bound mainly to cellular structures. Blood GGT activity of 48 lambs was 44 +/- 11 iu/litre and 33 +/- 7 iu/litre of 45 ewes.	Tissue and blood distribution of gamma-glutamyl transferase in the lamb and in the ewe. Gamma-glutamyl transferase distribution was studied in 10 ewes and 10 lambs; in both groups kidney was the most active organ, followed by pancreas, liver and lungs. In kidney and liver, GGT was bound mainly to cellular structures. Blood GGT activity of 48 lambs was 44 +/- 11 iu/litre and 33 +/- 7 iu/litre of 45 ewes.
PMID:30125	Subcellular fractionation studies on peroral jejunal biopsies from the dog.	Portions of closed jejunal biopsies from the dog were homogenised and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles were determined using highly sensitive assay procedures. The following organelles, with assayed marker enzymes and modal densities between brackets were characterised: peroxisomes (catalase, 1.21); brush borders (zinc-resistant alpha-glucosidase, leucyl-beta-naphthyl-amidase, gamma-glutamyl transferase, alkaline phosphatase, 1.20); lysosomes (N-acetyl-beta-glucosaminidase, alpha-mannosidase, 1.19); mitochondria (malate dehydrogenase, 1.18); endoplasmic reticulum (Tris-resistant alpha-glucosidase, 1.16); basal-lateral membranes (5'-nucleotidase, 1.11) and cytosol (lactate dehydrogenase). Homogenisation in isotonic sucrose containing digitonin (0.12 mmol/litre) selectively disrupted lysosomes and increased the equilibrium density of brush border and basal-lateral membranes. This procedure will be used to study the subcellular pathology of naturally occurring intestinal disease in the dog.	Subcellular fractionation studies on peroral jejunal biopsies from the dog. Portions of closed jejunal biopsies from the dog were homogenised and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles were determined using highly sensitive assay procedures. The following organelles, with assayed marker enzymes and modal densities between brackets were characterised: peroxisomes (catalase, 1.21); brush borders (zinc-resistant alpha-glucosidase, leucyl-beta-naphthyl-amidase, gamma-glutamyl transferase, alkaline phosphatase, 1.20); lysosomes (N-acetyl-beta-glucosaminidase, alpha-mannosidase, 1.19); mitochondria (malate dehydrogenase, 1.18); endoplasmic reticulum (Tris-resistant alpha-glucosidase, 1.16); basal-lateral membranes (5'-nucleotidase, 1.11) and cytosol (lactate dehydrogenase). Homogenisation in isotonic sucrose containing digitonin (0.12 mmol/litre) selectively disrupted lysosomes and increased the equilibrium density of brush border and basal-lateral membranes. This procedure will be used to study the subcellular pathology of naturally occurring intestinal disease in the dog.
PMID:30128	Gill ventilation in the sturgeon, Acipenser transmontanus: unusual adaptations for bottom dwelling.	Measurements of branchial cavity water pressures and flow patterns, arterial blood PO2 and pH, and oxygen utilization and uptake have been made in undisturbed, free swimming sturgeon, Acipenser transmontanus. Although the jaws are degenerate and the oral apparatus is highly modified for feeding, gill ventilation is nonetheless powered by a buccal force pump and an opercular suction pump common to most bony fishes. The reduced spiracles play little or no role in gill ventilation. In sturgeon in which water intake through the ventrally located mouth was experimentally eliminated, a condition which may often develop when these fish forage in mud and sand on river substrates, effective ventilation of the gills was maintained with water drawn into the branchial cavities in a retrograde fashion solely through permanent openings in the upper regions of the opercular slits. O2 uptake and transport also remained at control levels. It is suggested that this unusual alternative mode of gill ventilation in the sturgeon represents an important respiratory adaptation to bottom dwelling and feeding.	Gill ventilation in the sturgeon, Acipenser transmontanus: unusual adaptations for bottom dwelling. Measurements of branchial cavity water pressures and flow patterns, arterial blood PO2 and pH, and oxygen utilization and uptake have been made in undisturbed, free swimming sturgeon, Acipenser transmontanus. Although the jaws are degenerate and the oral apparatus is highly modified for feeding, gill ventilation is nonetheless powered by a buccal force pump and an opercular suction pump common to most bony fishes. The reduced spiracles play little or no role in gill ventilation. In sturgeon in which water intake through the ventrally located mouth was experimentally eliminated, a condition which may often develop when these fish forage in mud and sand on river substrates, effective ventilation of the gills was maintained with water drawn into the branchial cavities in a retrograde fashion solely through permanent openings in the upper regions of the opercular slits. O2 uptake and transport also remained at control levels. It is suggested that this unusual alternative mode of gill ventilation in the sturgeon represents an important respiratory adaptation to bottom dwelling and feeding.
PMID:30129	Hemoglobin-ligand interaction in fetal and maternal sheep blood.	Hemoglobin-ligand interaction was studied in maternal and fetal sheep blood as a function of oxygen saturation. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of NaOH or HCl at constant PCO2 (fixed acid Bohr effect). For maternal blood, CO2 Bohr factor was -0.41 at 50% oxygen saturation, increasing in magnitude at lower saturation and decreasing in magnitude at higher saturation. For fetal blood, CO2 Bohr factor was -0.45 at 50% oxygen saturation, unchanging at lower saturation and decreasing in magnitude at higher saturation. Fixed acid Bohr factor was relatively saturation independent with a value of -0.36 for fetal blood and -0.27 for maternal blood. The pH-independent effect of molecular CO2 on oxygen affinity was markedly saturation dependent being greatest at low oxygen saturation. The CO2 effect was greater in maternal blood than fetal blood. However, the magnitude of the saturation dependency of Bohr factor is not great enough to have major physiological significance in oxygen transfer across the sheep placenta.	Hemoglobin-ligand interaction in fetal and maternal sheep blood. Hemoglobin-ligand interaction was studied in maternal and fetal sheep blood as a function of oxygen saturation. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of NaOH or HCl at constant PCO2 (fixed acid Bohr effect). For maternal blood, CO2 Bohr factor was -0.41 at 50% oxygen saturation, increasing in magnitude at lower saturation and decreasing in magnitude at higher saturation. For fetal blood, CO2 Bohr factor was -0.45 at 50% oxygen saturation, unchanging at lower saturation and decreasing in magnitude at higher saturation. Fixed acid Bohr factor was relatively saturation independent with a value of -0.36 for fetal blood and -0.27 for maternal blood. The pH-independent effect of molecular CO2 on oxygen affinity was markedly saturation dependent being greatest at low oxygen saturation. The CO2 effect was greater in maternal blood than fetal blood. However, the magnitude of the saturation dependency of Bohr factor is not great enough to have major physiological significance in oxygen transfer across the sheep placenta.
PMID:30130	Pulmonary gas exchange, diffusing capacity in natives and newcomers at high altitude.	At high altitude, in resting conditions, no differences have been observed between High Altitude Natives (HAN) and acclimatized Sea Level Natives (SLN) in AaDO2, aADCO2 or venous admixture. In acclimatized SLN, AaDO2 is smaller than at sea level because of: (1) The minor effect on arterial oxygenation of the probably constant venous admixture. (2) The reduction of VA/Q inequality as shown by a smaller aADCO2. In HAN, DLCO is greater than in SLN; the contribution of DM or VC in this difference remains unsettled, mainly because of the difficulties of measurement of DM and VC in HAN suddenly exposed to acute hyperoxia. In SLN, in acute hypoxia, DLCO increased transitorily. Asynchronous mechanisms of adaptation to high altitude are evoked.	Pulmonary gas exchange, diffusing capacity in natives and newcomers at high altitude. At high altitude, in resting conditions, no differences have been observed between High Altitude Natives (HAN) and acclimatized Sea Level Natives (SLN) in AaDO2, aADCO2 or venous admixture. In acclimatized SLN, AaDO2 is smaller than at sea level because of: (1) The minor effect on arterial oxygenation of the probably constant venous admixture. (2) The reduction of VA/Q inequality as shown by a smaller aADCO2. In HAN, DLCO is greater than in SLN; the contribution of DM or VC in this difference remains unsettled, mainly because of the difficulties of measurement of DM and VC in HAN suddenly exposed to acute hyperoxia. In SLN, in acute hypoxia, DLCO increased transitorily. Asynchronous mechanisms of adaptation to high altitude are evoked.
PMID:30131	Oxygen affinity in the blood of sheep.	The oxygen affinity in the blood of adult Dorset sheep with HbB was studied by determining several oxygen equilibrium curves under different conditions of pH and PCO2 by a method that allowed strict control of pH, PCO2, and HCO3- concentration over the entire curve. Nomograms and equations were derived that allowed the estimation of the oxygen saturation in a sample of blood in the range 0 to 100%, either from pH, PCO2 and PO2, or from PO2 and known P50. The advantage of this approach is that no assumptions about the shape of the oxygen equilibrium curve need be made (i.e. the Hill parameter, n, is not required to be constant), since the entire curve was measured.	Oxygen affinity in the blood of sheep. The oxygen affinity in the blood of adult Dorset sheep with HbB was studied by determining several oxygen equilibrium curves under different conditions of pH and PCO2 by a method that allowed strict control of pH, PCO2, and HCO3- concentration over the entire curve. Nomograms and equations were derived that allowed the estimation of the oxygen saturation in a sample of blood in the range 0 to 100%, either from pH, PCO2 and PO2, or from PO2 and known P50. The advantage of this approach is that no assumptions about the shape of the oxygen equilibrium curve need be made (i.e. the Hill parameter, n, is not required to be constant), since the entire curve was measured.
PMID:30163	Separator isoelectric focusing for identification of alpha-1-antitrypsin (Pi M) subtypes.	A modified analytical isoelectric focusing procedure on polyacrylamide gel slabs, offering increased resolving capacity, has been developed for identification of six subtypes of the most common alpha-1-antitrypsin (A-1-AT) phenotype, Pi M. Combination of commercial Ampholine and other ampoteric substances, so called separators, produces pH plateaus, determined by the properties of the the additatives. Equilibrium is reached after extended focusing time, whereby stabilization of A-1-AT through alkylation is advantagous. The significance of this high resolution method for applications of the Pi system in genetic studies, and the general relevance of the modifications for other analytical purposes are discussed. A new nomenclature recommendation is presented.	Separator isoelectric focusing for identification of alpha-1-antitrypsin (Pi M) subtypes. A modified analytical isoelectric focusing procedure on polyacrylamide gel slabs, offering increased resolving capacity, has been developed for identification of six subtypes of the most common alpha-1-antitrypsin (A-1-AT) phenotype, Pi M. Combination of commercial Ampholine and other ampoteric substances, so called separators, produces pH plateaus, determined by the properties of the the additatives. Equilibrium is reached after extended focusing time, whereby stabilization of A-1-AT through alkylation is advantagous. The significance of this high resolution method for applications of the Pi system in genetic studies, and the general relevance of the modifications for other analytical purposes are discussed. A new nomenclature recommendation is presented.
PMID:30164	Purification and properties of human amniotic fluid diamine oxidase.	Diamine oxidase (DAO) was purified from amniotic fluid. The activity was separated in two DAO fractions with pI values of 5.8 and 4.0. Molecular weight were found to be 245,000 and 485,000, respectively, with subunit molecular weight of 110,000. This indicated that they probably are dimer and tetramer of the same DAO subunit. The enzyme was active against putrescine and histamine and was strongly inhibited by carbonyl group reagents. A Ping Pong Bi Ter enzyme reaction mechanism is probable. The diamine, with one amino group protonized, is suggested to be responsible for interaction with the enzyme.	Purification and properties of human amniotic fluid diamine oxidase. Diamine oxidase (DAO) was purified from amniotic fluid. The activity was separated in two DAO fractions with pI values of 5.8 and 4.0. Molecular weight were found to be 245,000 and 485,000, respectively, with subunit molecular weight of 110,000. This indicated that they probably are dimer and tetramer of the same DAO subunit. The enzyme was active against putrescine and histamine and was strongly inhibited by carbonyl group reagents. A Ping Pong Bi Ter enzyme reaction mechanism is probable. The diamine, with one amino group protonized, is suggested to be responsible for interaction with the enzyme.
PMID:30165	Determination of plasma or serum haemoglobin by peroxidase activity employing 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen.	A procedure is described for the determination of plasma or serum haemoglobin employing the peroxidase activity of the haemoprotein using 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen. The method gives equal results for free haemoglobin, methaemoglobin and haemoglobin complexed to haptoglobin. It is designed to measure haemoglobin in the range 0--12 mumol/l. The peroxidase activity of myoglobin is similar to that of haemoglobin, whereas haemin in free solution, bound to haemopexin or to albumin (methaemalbumin) shows much lower activity. The precision within run is satisfactory, +/- 5%.	Determination of plasma or serum haemoglobin by peroxidase activity employing 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen. A procedure is described for the determination of plasma or serum haemoglobin employing the peroxidase activity of the haemoprotein using 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen. The method gives equal results for free haemoglobin, methaemoglobin and haemoglobin complexed to haptoglobin. It is designed to measure haemoglobin in the range 0--12 mumol/l. The peroxidase activity of myoglobin is similar to that of haemoglobin, whereas haemin in free solution, bound to haemopexin or to albumin (methaemalbumin) shows much lower activity. The precision within run is satisfactory, +/- 5%.
PMID:30173	Viruses and bacteria associated with acute respiratory illnesses in young children in general practice.	The results obtained and the laboratory methods used for the isolation of viruses and bacteria from Malaysian children with acute respiratory illnesses seen in a private clinic are described. Of the 65 children studied virus isolations were obtained from 26 children, bacteria from 10 and both virus and bacteria from another 5. The agents isolated were influenza viruses, parainfluenza viruses, adenoviruses, Bordetella pertussis, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus pyogenes.	Viruses and bacteria associated with acute respiratory illnesses in young children in general practice. The results obtained and the laboratory methods used for the isolation of viruses and bacteria from Malaysian children with acute respiratory illnesses seen in a private clinic are described. Of the 65 children studied virus isolations were obtained from 26 children, bacteria from 10 and both virus and bacteria from another 5. The agents isolated were influenza viruses, parainfluenza viruses, adenoviruses, Bordetella pertussis, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus pyogenes.