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PMID:25417 | Sequence analysis of 5'[32P] labeled mRNA and tRNA using polyacrylamide gel electrophoresis. | Sequence analysis of 5'-[32P] labeled tRNA and eukaryotic mRNA using an adaptation of a method recently described by Donis-Keller, Maxam and Gilbert for mapping guanines, adenines and pyrimidines from the 5'-end of an RNA is described. In addition, a technique utilizing two-dimensional polyacrylamide gel electrophoresis for identification of pyrimidines within a sequence is described. 5'-[32P] Labeled rabbit beta-globin mRNA and N. crassa mitochondrial initiator tRNA were partially digested with T1- RNase for cleavage at G residues, with U2-RNase for cleavage at A residues, with an extracellular RNase from B. cereus for cleavage at pyrimidine residues and with T2-RNase or with alkali for cleavage at all four residues. The 5'-[32P] labeled partial digestion products were separated according to their size, by electrophoresis in adjacent lanes of a polyacrylamide slab gel and the location of G's, A's and of pyrimidines extending 60-80 nucleotides from the 5'-end of the RNA determined. Two-dimensional polyacrylamide gel electrophoresis was used to separate the 5'-[32P] labeled fragments present in partial alkali digests of a 5'-[32P] labeled mRNA. The mobility shifts corresponding to the difference of a C residue were distinct from those corresponding to a U residue and this formed the basis of a method for distinguishing between the pyrimidines. | Sequence analysis of 5'[32P] labeled mRNA and tRNA using polyacrylamide gel electrophoresis. Sequence analysis of 5'-[32P] labeled tRNA and eukaryotic mRNA using an adaptation of a method recently described by Donis-Keller, Maxam and Gilbert for mapping guanines, adenines and pyrimidines from the 5'-end of an RNA is described. In addition, a technique utilizing two-dimensional polyacrylamide gel electrophoresis for identification of pyrimidines within a sequence is described. 5'-[32P] Labeled rabbit beta-globin mRNA and N. crassa mitochondrial initiator tRNA were partially digested with T1- RNase for cleavage at G residues, with U2-RNase for cleavage at A residues, with an extracellular RNase from B. cereus for cleavage at pyrimidine residues and with T2-RNase or with alkali for cleavage at all four residues. The 5'-[32P] labeled partial digestion products were separated according to their size, by electrophoresis in adjacent lanes of a polyacrylamide slab gel and the location of G's, A's and of pyrimidines extending 60-80 nucleotides from the 5'-end of the RNA determined. Two-dimensional polyacrylamide gel electrophoresis was used to separate the 5'-[32P] labeled fragments present in partial alkali digests of a 5'-[32P] labeled mRNA. The mobility shifts corresponding to the difference of a C residue were distinct from those corresponding to a U residue and this formed the basis of a method for distinguishing between the pyrimidines. | [
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PMID:25418 | Poly(dG).poly(dC) at neutral and alkaline pH: the formation of triple stranded poly(dG).poly(dG).poly(dC). | Alkaline titrations of different samples of poly(dG).poly(dC) and of the constituent homopolymers poly(dG) and poly(dC) have been performed in 0.15 M NaCl and their CD spectra followed. Sample I contained a slight excess of poly(dC) (52% C: 48% G) and showed a single reversible transition (pK = 11.9) due to the dissociation of double stranded poly(dG).poly(dC). Sample II, containing an excess of poly(dG) (43% C: 57% G), showed two transitions (pK1 = 11.4, PK2 = 11.9) the first one being only partially reversible. Examination of the CD spectra along the alkaline titrations indicated the presence of another hydrogen-bonded complex of higher G content. Mixing curves performed at pH 8 have confirmed the presence of a 2G: 1C complex, besides the double stranded complex. It can be formed in amounts up to 30% by mixing the two homopolymers, alkali treatment and heating. The CD spectra of the two complexes have been computed from the CD data of the mixing curves. This permitted the determination of the concentrations of both complexes and homopolymers in all samples. The ratio of triple to double stranded complex is not only dependent on the G/C ratio of the sample, but also a function of the previous physico-chemical conditions. These results explain the variability of many properties of different poly(dG).poly(dC) samples observed by other workers. | Poly(dG).poly(dC) at neutral and alkaline pH: the formation of triple stranded poly(dG).poly(dG).poly(dC). Alkaline titrations of different samples of poly(dG).poly(dC) and of the constituent homopolymers poly(dG) and poly(dC) have been performed in 0.15 M NaCl and their CD spectra followed. Sample I contained a slight excess of poly(dC) (52% C: 48% G) and showed a single reversible transition (pK = 11.9) due to the dissociation of double stranded poly(dG).poly(dC). Sample II, containing an excess of poly(dG) (43% C: 57% G), showed two transitions (pK1 = 11.4, PK2 = 11.9) the first one being only partially reversible. Examination of the CD spectra along the alkaline titrations indicated the presence of another hydrogen-bonded complex of higher G content. Mixing curves performed at pH 8 have confirmed the presence of a 2G: 1C complex, besides the double stranded complex. It can be formed in amounts up to 30% by mixing the two homopolymers, alkali treatment and heating. The CD spectra of the two complexes have been computed from the CD data of the mixing curves. This permitted the determination of the concentrations of both complexes and homopolymers in all samples. The ratio of triple to double stranded complex is not only dependent on the G/C ratio of the sample, but also a function of the previous physico-chemical conditions. These results explain the variability of many properties of different poly(dG).poly(dC) samples observed by other workers. | [
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PMID:25419 | Base specific fractionation of double stranded DNA: affinity chromatography on a novel type of adsorbant. | A material suitable for base-pair-specific "affinity chromatography" of double stranded DNA is described. The synthesis of this material involves two successive polymerization reactions yielding solid particles of cross-linked bisacrylamide to which base-pair-specific dyes are covalently attached by spacers of polyacrylamide chains of different length. Materials with immobilized A.T-specific malachite green or G.C-specific phenyl neutral red were used for base-pair-specific fractionation of sheared DNA from bacterial sources, as well as of higher molecular weight Calf thymus DNA or defined fragments of coliphage lambda DNA. The excellent resolving power of this method of "affinity chromatography" of nucleic acids is comparable only to DNA fractionation in buoyant density gradients in the presence of base-pair-specific ligands. A great advantage of this material is its simple handling and its chemical stability, which allows repeated re-use of the same column. | Base specific fractionation of double stranded DNA: affinity chromatography on a novel type of adsorbant. A material suitable for base-pair-specific "affinity chromatography" of double stranded DNA is described. The synthesis of this material involves two successive polymerization reactions yielding solid particles of cross-linked bisacrylamide to which base-pair-specific dyes are covalently attached by spacers of polyacrylamide chains of different length. Materials with immobilized A.T-specific malachite green or G.C-specific phenyl neutral red were used for base-pair-specific fractionation of sheared DNA from bacterial sources, as well as of higher molecular weight Calf thymus DNA or defined fragments of coliphage lambda DNA. The excellent resolving power of this method of "affinity chromatography" of nucleic acids is comparable only to DNA fractionation in buoyant density gradients in the presence of base-pair-specific ligands. A great advantage of this material is its simple handling and its chemical stability, which allows repeated re-use of the same column. | [
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PMID:25420 | New observations concerning the chloroacetaldehyde reaction with some tRNA constituents. Stable intermediates, kinetics and selectivity of the reaction. | The stable intermediates formed in the reaction of cytosine, cytidine and adenosine with chloracetaldehyde were isolated. The -CH2CH/OH/- bridge between the exo and endo nitrogen atoms of the parent base was found in these compounds by means of PMR spectroscopy. Their acid-induced dehydration resulted in formation of appropriate ethenoderivatives. The rate constants of the intermediate formation and its dehydration were found to be 38x10(-4) and 47x10(-4) /min-1/ for adenosine, and 33x10(-4) and 10x10(-4) /min-1/ for cytidine. The PH range of 4.5--5.0 was found to be optimum for both adenosine and cytidine reactions. The quantitative modification of these two nucleosides in the presence of guanosine may be achieved with high selectivity only at a low pH of 3.0--4.0 N6-methyladenosine and N4-methylcytidine react quantitatively with chloroacetaldehyde and the reaction rate is higher than in the case of the parent nucleosides. The structure of the reaction products was assigned on the basis of PMR spectroscopy. | New observations concerning the chloroacetaldehyde reaction with some tRNA constituents. Stable intermediates, kinetics and selectivity of the reaction. The stable intermediates formed in the reaction of cytosine, cytidine and adenosine with chloracetaldehyde were isolated. The -CH2CH/OH/- bridge between the exo and endo nitrogen atoms of the parent base was found in these compounds by means of PMR spectroscopy. Their acid-induced dehydration resulted in formation of appropriate ethenoderivatives. The rate constants of the intermediate formation and its dehydration were found to be 38x10(-4) and 47x10(-4) /min-1/ for adenosine, and 33x10(-4) and 10x10(-4) /min-1/ for cytidine. The PH range of 4.5--5.0 was found to be optimum for both adenosine and cytidine reactions. The quantitative modification of these two nucleosides in the presence of guanosine may be achieved with high selectivity only at a low pH of 3.0--4.0 N6-methyladenosine and N4-methylcytidine react quantitatively with chloroacetaldehyde and the reaction rate is higher than in the case of the parent nucleosides. The structure of the reaction products was assigned on the basis of PMR spectroscopy. | [
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PMID:25421 | Evidence that proteins S1, S11 and S21 directly participates in the binding of transfer RNA to the 30S ribosome. | In a previous publication1 we reported that the tyrosine selective reagent, tetraitromethane, causes complete inactivation of E. coli 30S ribosomes for poly U directed non-enzymatic phe-tRNA binding. This inactivation was demonstrated to be due to the chemical modification of the protein moiety of the ribosome. We have no identified the proteins of the 30S particle inactivated by this modification. Using a method of ribosome reconstruction we have found that unmodified proteins S1, S11, and S21 are essential for the restoration of the phe-tRNA binding activity of tetranitromethane inactivated ribosomes. We propose that these three proteins are intimately involved in the 30S ribosome binding site for tRNA. | Evidence that proteins S1, S11 and S21 directly participates in the binding of transfer RNA to the 30S ribosome. In a previous publication1 we reported that the tyrosine selective reagent, tetraitromethane, causes complete inactivation of E. coli 30S ribosomes for poly U directed non-enzymatic phe-tRNA binding. This inactivation was demonstrated to be due to the chemical modification of the protein moiety of the ribosome. We have no identified the proteins of the 30S particle inactivated by this modification. Using a method of ribosome reconstruction we have found that unmodified proteins S1, S11, and S21 are essential for the restoration of the phe-tRNA binding activity of tetranitromethane inactivated ribosomes. We propose that these three proteins are intimately involved in the 30S ribosome binding site for tRNA. | [
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PMID:25424 | Physico-chemical investigation of AlPO4 for the manufacture of antacids. I. Effect of precipitation and processing conditions on physico-chemical properties of AlPO4. | Aluminium phosphate was precipitated from AlCl3-H3PO4 and NaOH, NH3H2O and NaHCO3--Na2CO3 mixture up to different pH values. The precipitates were dried at room temperature, 40 degrees and 105 degrees and their neutralizing properties (rate of neutralization and acid-consuming capacity) against 0.l N HCl were investigated. It was found that these properties depend on the nature of the reagents used for the formation of AlPO4, the pH and also the temperature of drying. The best antacid properties shows the AlPO4 preperation obtained from AlCl3-H3PO4 and NaHCO3-Na2CO3. For comparison, the therapeutic preparate "Aluphos" was also investigated. | Physico-chemical investigation of AlPO4 for the manufacture of antacids. I. Effect of precipitation and processing conditions on physico-chemical properties of AlPO4. Aluminium phosphate was precipitated from AlCl3-H3PO4 and NaOH, NH3H2O and NaHCO3--Na2CO3 mixture up to different pH values. The precipitates were dried at room temperature, 40 degrees and 105 degrees and their neutralizing properties (rate of neutralization and acid-consuming capacity) against 0.l N HCl were investigated. It was found that these properties depend on the nature of the reagents used for the formation of AlPO4, the pH and also the temperature of drying. The best antacid properties shows the AlPO4 preperation obtained from AlCl3-H3PO4 and NaHCO3-Na2CO3. For comparison, the therapeutic preparate "Aluphos" was also investigated. | [
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PMID:25427 | [Mendelson's syndrome]. | Mendelson's syndrome is discussed with a review of the literature and presentation of 27 personal cases studies. Accidental aspiration of gastric fluid occurs primarily during anesthesia, in cranial trauma victims, and in toxic coma patients. Tissue damage is proportional to the acidity and the quantity of aspirated fluid. The initial clinical manifestations are often serious, sometimes leading to acute respiratory distress syndrom with pulmonary edema. Frequent infectious complications, often with anaerobic microbes, are deciding factors in the prognosis. Artificial ventilation with positive pressure (sometimes continuous) is often necessary. Administration of corticosteroids at high doses is likely favorable. Prophylactic administration of antibiotics is initially directed against anaerobic agents. The prevention of this serious syndrome should be a primary concern of anesthesiologists and physicians treating comatous patients. | [Mendelson's syndrome]. Mendelson's syndrome is discussed with a review of the literature and presentation of 27 personal cases studies. Accidental aspiration of gastric fluid occurs primarily during anesthesia, in cranial trauma victims, and in toxic coma patients. Tissue damage is proportional to the acidity and the quantity of aspirated fluid. The initial clinical manifestations are often serious, sometimes leading to acute respiratory distress syndrom with pulmonary edema. Frequent infectious complications, often with anaerobic microbes, are deciding factors in the prognosis. Artificial ventilation with positive pressure (sometimes continuous) is often necessary. Administration of corticosteroids at high doses is likely favorable. Prophylactic administration of antibiotics is initially directed against anaerobic agents. The prevention of this serious syndrome should be a primary concern of anesthesiologists and physicians treating comatous patients. | [
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PMID:25425 | Choline acetyltransferase and acetylcholinesterase activities in mice brain during the antagonistic action of antidepressant drugs and Ro 4--1284. | Choline acetyltransferase (Ach-T) and acetylcholinesterase (Ach-E) activities in mice brain during the reverse action by imipramine, pheniprazine and pargyline to the syndrome elicited by intraperitoneal administration of Ro 4--1284 were investigated. A single dose of imipramine did not reverse reserpine-like syndrome whereas inhibited Ach-E activity and increased Ach-T activity at the same time. The reversal of reserpine-like syndrome by administration of pargyline, pheniprazine or chronic administration of imipramine was accompanied by no changes in Ach-E and Ach-T activities. | Choline acetyltransferase and acetylcholinesterase activities in mice brain during the antagonistic action of antidepressant drugs and Ro 4--1284. Choline acetyltransferase (Ach-T) and acetylcholinesterase (Ach-E) activities in mice brain during the reverse action by imipramine, pheniprazine and pargyline to the syndrome elicited by intraperitoneal administration of Ro 4--1284 were investigated. A single dose of imipramine did not reverse reserpine-like syndrome whereas inhibited Ach-E activity and increased Ach-T activity at the same time. The reversal of reserpine-like syndrome by administration of pargyline, pheniprazine or chronic administration of imipramine was accompanied by no changes in Ach-E and Ach-T activities. | [
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PMID:25426 | Central action of narcotic analgesics. II. Locomotor activity and narcotic analgesics. | The effect of morphine, codeine, fentanyl and pentazocine on locomotor activity of rats and mice and open-field performance of rats were tested. All the analgesics tested produced a depressive action in the rat. In mice a depressive action was produced by pentazocine and codeine. Fentanyl increased the exploratory and basal locomotor activity of mice. Morphine increased the exploratory activity, but, given at doses of 2.5 and 10 mg/kg decreased the basal locomotor activity. The increase of locomotor activity in mice by morphine and fentanyl is caused by an indirect stimulation of catecholamine receptors. | Central action of narcotic analgesics. II. Locomotor activity and narcotic analgesics. The effect of morphine, codeine, fentanyl and pentazocine on locomotor activity of rats and mice and open-field performance of rats were tested. All the analgesics tested produced a depressive action in the rat. In mice a depressive action was produced by pentazocine and codeine. Fentanyl increased the exploratory and basal locomotor activity of mice. Morphine increased the exploratory activity, but, given at doses of 2.5 and 10 mg/kg decreased the basal locomotor activity. The increase of locomotor activity in mice by morphine and fentanyl is caused by an indirect stimulation of catecholamine receptors. | [
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PMID:25429 | [Preventive action of catecholamine and serotonin synthesis inhibitors and of adrenergic blockaders on the occurrence of the anovular syndrome in neonatally androgenized rats. I]. | Administration of catecholamine synthesis inhibitors (alpha-methl-p-tyrosine) or serotonin (parachlorphenylalanine) simultaneously with testosterone propionate prevented the anovular sterility in the majority of the neonatally androgenized rats. Preventive action of adrenoblockers (droperidol and propranolol) on the effects of early androgenization were weak. The data obtained pointed to the participation of catecholamines and serotonin in the realization of the masculinizing action of androgen on the neuroendocrine centres of the gonadotropin hormones secretion control. | [Preventive action of catecholamine and serotonin synthesis inhibitors and of adrenergic blockaders on the occurrence of the anovular syndrome in neonatally androgenized rats. I]. Administration of catecholamine synthesis inhibitors (alpha-methl-p-tyrosine) or serotonin (parachlorphenylalanine) simultaneously with testosterone propionate prevented the anovular sterility in the majority of the neonatally androgenized rats. Preventive action of adrenoblockers (droperidol and propranolol) on the effects of early androgenization were weak. The data obtained pointed to the participation of catecholamines and serotonin in the realization of the masculinizing action of androgen on the neuroendocrine centres of the gonadotropin hormones secretion control. | [
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PMID:25436 | Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides. | Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport. | Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides. Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport. | [
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PMID:25437 | Identification and properties of two methyltransferases in conversion of phosphatidylethanolamine to phosphatidylcholine. | Two methyltransferases involved in the methylation of phosphatidylethanolamine to form phosphatidylcholine were demonstrated in a microsomal fraction of bovine adrenal medulla. The first methyltransferase catalyzes the methylation of phosphatidylethanolamine to form phosphatidyl-N-monomethylethanolamine. This enzyme has an optimum pH of 6.5, a low Km for S-adenosyl-L-methionine (1.4 micron), and an absolute requirement for Mg2+. The second methyltransferase catalyzes the two successive methylations of phodphatidyl-N-monomethylethanolamine to phosphatidyl-N,N-dimethylethanolamine and phosphatidylcholine. In contrast to the first methyltransferase, it has an optimum pH of 10 and a high Km for S-adenosyl-L-methionine (0.1 mM) and does not require Mg2+. | Identification and properties of two methyltransferases in conversion of phosphatidylethanolamine to phosphatidylcholine. Two methyltransferases involved in the methylation of phosphatidylethanolamine to form phosphatidylcholine were demonstrated in a microsomal fraction of bovine adrenal medulla. The first methyltransferase catalyzes the methylation of phosphatidylethanolamine to form phosphatidyl-N-monomethylethanolamine. This enzyme has an optimum pH of 6.5, a low Km for S-adenosyl-L-methionine (1.4 micron), and an absolute requirement for Mg2+. The second methyltransferase catalyzes the two successive methylations of phodphatidyl-N-monomethylethanolamine to phosphatidyl-N,N-dimethylethanolamine and phosphatidylcholine. In contrast to the first methyltransferase, it has an optimum pH of 10 and a high Km for S-adenosyl-L-methionine (0.1 mM) and does not require Mg2+. | [
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PMID:25438 | Differences in the isoelectric focusing patterns of gamma-glutamyl transpeptidase from normal and cancerous rat mammary tissue. | Highly purified fractions of gamma-glutamyl transpeptidase [gamma-glutamyltrinsferase; (5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2] from normal and malignant rat mammary tissue were prepared. Analyses by isoelectric focusing indicate the existence of at least 12 enzymatically active species. The gamma-glutamyl transpeptidase from the tumor tissue had a greater proportion of the activity concentrated in the more negative species than the enzyme from normal tissue. Treatment of the two enzyme preparations with neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18) greatly reduced this difference. When whole tissue homogenates were treated with papain to solubilize the enzyme and then focused, the same relationship held. The neuraminidase activities in the two homogenates were similar, but the sialytransferase activity (CMP-N-acetylneuraminate:D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1) of the tumor homogenate was 13 times that of the normal mammary homogenate. These observations suggest that the gamma-glutamyl transpeptidase of the tumor is more heavily sialylated than that from the normal tissue, possibly reflecting the greater sialyltransferase activity of the tumor. | Differences in the isoelectric focusing patterns of gamma-glutamyl transpeptidase from normal and cancerous rat mammary tissue. Highly purified fractions of gamma-glutamyl transpeptidase [gamma-glutamyltrinsferase; (5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2] from normal and malignant rat mammary tissue were prepared. Analyses by isoelectric focusing indicate the existence of at least 12 enzymatically active species. The gamma-glutamyl transpeptidase from the tumor tissue had a greater proportion of the activity concentrated in the more negative species than the enzyme from normal tissue. Treatment of the two enzyme preparations with neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18) greatly reduced this difference. When whole tissue homogenates were treated with papain to solubilize the enzyme and then focused, the same relationship held. The neuraminidase activities in the two homogenates were similar, but the sialytransferase activity (CMP-N-acetylneuraminate:D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1) of the tumor homogenate was 13 times that of the normal mammary homogenate. These observations suggest that the gamma-glutamyl transpeptidase of the tumor is more heavily sialylated than that from the normal tissue, possibly reflecting the greater sialyltransferase activity of the tumor. | [
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PMID:25439 | High-resolution 31P nuclear magnetic resonance study of rat liver mitochondria. | Intact mitochondria were studied by high-resolution 31P nuclear magnetic resonance. Observable internal phosphate compounds included inorganic phosphate (Pi), ADP, and ATP. The internal pH was determined by the chemical shift of the internal Pi, the pK2 (6.7) of which was measured in uncoupled mitochondria. The observed equilibrium relation between the internal and the external Pi was consistent with the exchange equilibrium through the H2PO4-/OH- carrier. The internal ATP and ADP were essentially Mg2+ bound and their resonances were distinguishable from those of the external ATP and ADP by the chemical shift differences due to the Mg2+ concentration gradient and deltapH. Oxidative phosphorylation was followed by the separate resonances of Pi and adenine nucleotides both internal and external to mitochondria. From these resonances the internal and external phosphate potentials could be estimated. | High-resolution 31P nuclear magnetic resonance study of rat liver mitochondria. Intact mitochondria were studied by high-resolution 31P nuclear magnetic resonance. Observable internal phosphate compounds included inorganic phosphate (Pi), ADP, and ATP. The internal pH was determined by the chemical shift of the internal Pi, the pK2 (6.7) of which was measured in uncoupled mitochondria. The observed equilibrium relation between the internal and the external Pi was consistent with the exchange equilibrium through the H2PO4-/OH- carrier. The internal ATP and ADP were essentially Mg2+ bound and their resonances were distinguishable from those of the external ATP and ADP by the chemical shift differences due to the Mg2+ concentration gradient and deltapH. Oxidative phosphorylation was followed by the separate resonances of Pi and adenine nucleotides both internal and external to mitochondria. From these resonances the internal and external phosphate potentials could be estimated. | [
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PMID:25440 | Differential desensitization of functional adrenergic receptors in normal and malignant myeloid cells: relationship to receptor-mediated hormone cytotoxicity. | Malignant myeloid leukemic cells and normal macrophages and granulocytes have functional beta-adrenergic receptors, which have been quantitated by radioreceptor binding with the beta-adrenergic antagonist [(3)H]dihydroalprenolol and by induction of cyclic AMP by adrenergic hormones. Both the normal and leukemic cells have beta(2)-adrenergic receptors, and the [(3)H]dihydroalprenolol binding was saturable, reversible, and stereospecific. The leukemic cells consisted of clones that could be induced to differentiate (MGI(+)D(+)) and clones that could not be induced to differentiate to mature macrophages and granulocytes by the protein inducer MGI. The different types of leukemic clones all had 1100-2300 receptor sites per cell, whereas normal macrophages had 7000 receptors per cell. The differentiation of MGI(+)D(+) leukemic cells was associated with an increase in receptors to a number similar to that found with normal macrophages. MGI(+)D(+) leukemic cells and normal macrophages were able to densensitize to the beta-adrenergic agonist (-)isoproterenol, shown by termination of cyclic AMP induction within 10-15 min and the lack of a second induction. The leukemic cells that could not be induced to differentiate lacked this capacity for desensitization, possibly due to an alteration in the uncoupling system between the receptor and adenylate cyclase. The lack of desensitization in these leukemic cells was associated with a higher sensitivity to the receptor-mediated cytotoxic effects of adrenergic hormones. It is suggested that cells, like some leukemic cells, that are unable to desensitize to adrenergic and possibly other hormones may be appropriate targets for differential destruction by hormones under conditions that do not affect normally desensitizing cells. | Differential desensitization of functional adrenergic receptors in normal and malignant myeloid cells: relationship to receptor-mediated hormone cytotoxicity. Malignant myeloid leukemic cells and normal macrophages and granulocytes have functional beta-adrenergic receptors, which have been quantitated by radioreceptor binding with the beta-adrenergic antagonist [(3)H]dihydroalprenolol and by induction of cyclic AMP by adrenergic hormones. Both the normal and leukemic cells have beta(2)-adrenergic receptors, and the [(3)H]dihydroalprenolol binding was saturable, reversible, and stereospecific. The leukemic cells consisted of clones that could be induced to differentiate (MGI(+)D(+)) and clones that could not be induced to differentiate to mature macrophages and granulocytes by the protein inducer MGI. The different types of leukemic clones all had 1100-2300 receptor sites per cell, whereas normal macrophages had 7000 receptors per cell. The differentiation of MGI(+)D(+) leukemic cells was associated with an increase in receptors to a number similar to that found with normal macrophages. MGI(+)D(+) leukemic cells and normal macrophages were able to densensitize to the beta-adrenergic agonist (-)isoproterenol, shown by termination of cyclic AMP induction within 10-15 min and the lack of a second induction. The leukemic cells that could not be induced to differentiate lacked this capacity for desensitization, possibly due to an alteration in the uncoupling system between the receptor and adenylate cyclase. The lack of desensitization in these leukemic cells was associated with a higher sensitivity to the receptor-mediated cytotoxic effects of adrenergic hormones. It is suggested that cells, like some leukemic cells, that are unable to desensitize to adrenergic and possibly other hormones may be appropriate targets for differential destruction by hormones under conditions that do not affect normally desensitizing cells. | [
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PMID:25441 | Functional properties of beta-galactosidase from mutant strain 13 PO of Escherichia coli. | The functional properties of CZP protein, a mutant deriving from wild-type beta-galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) by a point mutation, were investigated. A large decrease of the specificity, as evaluated by the kcat/Km ratio, was observed, principally originated by a weaker binding of the substrates. The catalytic constants, whose values are strongly affected by the presence of divalent cations, were smaller or larger for mutant enzyme than for wild-type enzyme, depending upon the experimental conditions. Analysis of the kinetic pathway indicates, with some substrates, a change in the limiting step for the mutant enzyme compared to the wild type. Because the k'3 step is rate limiting for hydrolysis of p-nitrophenyl-beta-D-galactoside by the mutant enzyme in the absence of Mg2+ and its value is relatively small, it is possible to observe a burst of p-nitrophenol during hydrolysis. This provides conclusive evidence for the occurrence of a two-step mechanism, with a sequential release of the products. | Functional properties of beta-galactosidase from mutant strain 13 PO of Escherichia coli. The functional properties of CZP protein, a mutant deriving from wild-type beta-galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) by a point mutation, were investigated. A large decrease of the specificity, as evaluated by the kcat/Km ratio, was observed, principally originated by a weaker binding of the substrates. The catalytic constants, whose values are strongly affected by the presence of divalent cations, were smaller or larger for mutant enzyme than for wild-type enzyme, depending upon the experimental conditions. Analysis of the kinetic pathway indicates, with some substrates, a change in the limiting step for the mutant enzyme compared to the wild type. Because the k'3 step is rate limiting for hydrolysis of p-nitrophenyl-beta-D-galactoside by the mutant enzyme in the absence of Mg2+ and its value is relatively small, it is possible to observe a burst of p-nitrophenol during hydrolysis. This provides conclusive evidence for the occurrence of a two-step mechanism, with a sequential release of the products. | [
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PMID:25442 | Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation. | Stereotaxic injection of kainic acid into the striatum of adult rats causes degeneration of neurons intrinsic to the striatum but spares axons of passage and of termination of extrinsic neurons. Neurochemical and histologic studies demonstrate that striatal neurons are almost insensitive to kainate at 7 days after birth and that their vulnerability increases with age; by 3 weeks after birth, striatal injection of kainate produces a lesion comparable to that of the adult. The intensity and duration of the acute behavioral response to kainate also increases with age. The maturational increase in striatal neuronal sensitivity to kainate correlates with the development of glutamatergic innervation to the striatum, as measured by [3H]glutamate uptake by synaptosomes, and with the development of a postsynaptic, high-affinity receptor site for kainate. These ontogenetic studies provide additional evidence that kainate's neurotoxicity is a receptor-mediated event related to glutamatergic innervation of vulnerable neurons. | Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation. Stereotaxic injection of kainic acid into the striatum of adult rats causes degeneration of neurons intrinsic to the striatum but spares axons of passage and of termination of extrinsic neurons. Neurochemical and histologic studies demonstrate that striatal neurons are almost insensitive to kainate at 7 days after birth and that their vulnerability increases with age; by 3 weeks after birth, striatal injection of kainate produces a lesion comparable to that of the adult. The intensity and duration of the acute behavioral response to kainate also increases with age. The maturational increase in striatal neuronal sensitivity to kainate correlates with the development of glutamatergic innervation to the striatum, as measured by [3H]glutamate uptake by synaptosomes, and with the development of a postsynaptic, high-affinity receptor site for kainate. These ontogenetic studies provide additional evidence that kainate's neurotoxicity is a receptor-mediated event related to glutamatergic innervation of vulnerable neurons. | [
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PMID:25444 | Evaluation of psychotropic drugs with a modified open field test. | The open field test used to study behavioral alterations induced by psychotropic drugs is based mainly in the defecation, ambulation, rearing and grooming presented by animals subjected to the test. Because of the criticisms raised against the defecation score as a measure of the central effects of drugs, in the present experiment a modification of the test is proposed for the rat. The main points that characterize the new procedure are: (1) defecation scores are not considered; (2) besides ambulation, rearing and grooming, immobility was also recorded; (3) the total time of observation was increased, and (4) the stimuli, usually presented simultaneously in the open field (light and noise), were presented separately. The results obtained suggest that it is possible to differentiate classes of psychotropic drugs, without taking the defecation and grooming scores into consideration. Besides stimulants that evoked a characteristic pattern of behavior, neuroleptics could be differentiated from anxiolytics. Similarities, according to the dose, between barbiturates and anxiolytics were detected. Under LSD a peculiar pattern of behavior characterized by a large reactivity to light was observed. | Evaluation of psychotropic drugs with a modified open field test. The open field test used to study behavioral alterations induced by psychotropic drugs is based mainly in the defecation, ambulation, rearing and grooming presented by animals subjected to the test. Because of the criticisms raised against the defecation score as a measure of the central effects of drugs, in the present experiment a modification of the test is proposed for the rat. The main points that characterize the new procedure are: (1) defecation scores are not considered; (2) besides ambulation, rearing and grooming, immobility was also recorded; (3) the total time of observation was increased, and (4) the stimuli, usually presented simultaneously in the open field (light and noise), were presented separately. The results obtained suggest that it is possible to differentiate classes of psychotropic drugs, without taking the defecation and grooming scores into consideration. Besides stimulants that evoked a characteristic pattern of behavior, neuroleptics could be differentiated from anxiolytics. Similarities, according to the dose, between barbiturates and anxiolytics were detected. Under LSD a peculiar pattern of behavior characterized by a large reactivity to light was observed. | [
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PMID:25445 | Bromocriptine, lergotrile: the antiparkinsonian efficacy and the interaction with monoaminergic receptors. | The antiparkinsonian activity of bromocriptine and of lergotrile was investigated in monkeys with surgically induced tremor and in parkinsonian patients. Both drugs effectively relieve tremor in experimental monkeys and induce less pronounced abnormal involuntary movements than L-dopa or piribedil. Both drugs were shown to be of therapeutic value in a group of patients with advanced Parkinson's disease who were no longer responsive to levodopa combined with carbidopa. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance ("on-off" effect) were decreased, while mental changes were increased. The interactions of bromocriptine and of lergotrile with dopamine and alpha-adrenergic receptors were investigated. Both drugs have mixed agonist-antagonist activities with respect to the dopamine receptors; lergotrile has a higher affinity for the agonist site while bromocriptine has a higher affinity for the antagonist site of the receptors. Both drugs effectively displace the binding of the alpha-adrenergic antagonist WB-4101 to cerebral cortex membranes. The mechanisms underlying the antiparkinsonian efficacies of these two drugs were discussed. | Bromocriptine, lergotrile: the antiparkinsonian efficacy and the interaction with monoaminergic receptors. The antiparkinsonian activity of bromocriptine and of lergotrile was investigated in monkeys with surgically induced tremor and in parkinsonian patients. Both drugs effectively relieve tremor in experimental monkeys and induce less pronounced abnormal involuntary movements than L-dopa or piribedil. Both drugs were shown to be of therapeutic value in a group of patients with advanced Parkinson's disease who were no longer responsive to levodopa combined with carbidopa. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance ("on-off" effect) were decreased, while mental changes were increased. The interactions of bromocriptine and of lergotrile with dopamine and alpha-adrenergic receptors were investigated. Both drugs have mixed agonist-antagonist activities with respect to the dopamine receptors; lergotrile has a higher affinity for the agonist site while bromocriptine has a higher affinity for the antagonist site of the receptors. Both drugs effectively displace the binding of the alpha-adrenergic antagonist WB-4101 to cerebral cortex membranes. The mechanisms underlying the antiparkinsonian efficacies of these two drugs were discussed. | [
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PMID:25448 | Blood pressure response to bolus administration of vasoactive drugs in the rat. | The time course of systemic blood pressure response in normotensive anaesthetized rats was studied after a bolus administration of standard doses (0.4 microgram/kg) of noradrenaline, adrenaline, isoprenaline, acetylcholine, serotonin, bradykinin, and histamine. The single stimulus of a vasoactive agent elicits a blood pressure deviation with typical phasing. The time dimension of the individual wave is less variable and less dose dependent than their amplitude. Under the given experimental conditions the blood pressure response is predominantly determined by the peripheral vasomotor reactions; the cardiac component is of minor importance. Though the overall responses to the individual drugs are quite characteristic, they seem to comprise several common components. Thus the peripheral vascular system is supposed to consist of different regulatory subsystems which take part in the systemic blood pressure control by typically timed responses. The pattern of the reaction is then given by their unequal combination and various intensity. | Blood pressure response to bolus administration of vasoactive drugs in the rat. The time course of systemic blood pressure response in normotensive anaesthetized rats was studied after a bolus administration of standard doses (0.4 microgram/kg) of noradrenaline, adrenaline, isoprenaline, acetylcholine, serotonin, bradykinin, and histamine. The single stimulus of a vasoactive agent elicits a blood pressure deviation with typical phasing. The time dimension of the individual wave is less variable and less dose dependent than their amplitude. Under the given experimental conditions the blood pressure response is predominantly determined by the peripheral vasomotor reactions; the cardiac component is of minor importance. Though the overall responses to the individual drugs are quite characteristic, they seem to comprise several common components. Thus the peripheral vascular system is supposed to consist of different regulatory subsystems which take part in the systemic blood pressure control by typically timed responses. The pattern of the reaction is then given by their unequal combination and various intensity. | [
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PMID:25449 | Skin rejection in graft-versus-host disease. | Graft-versus-host disease is becoming a common clinical problem, one which can require the consultation of a plastic surgeon for restoration of skin coverage. An understanding of the immunological basis of the disease is essential to the clinical management of this condition. A case of GVHD is reported, and the principles of treatment are discussed. | Skin rejection in graft-versus-host disease. Graft-versus-host disease is becoming a common clinical problem, one which can require the consultation of a plastic surgeon for restoration of skin coverage. An understanding of the immunological basis of the disease is essential to the clinical management of this condition. A case of GVHD is reported, and the principles of treatment are discussed. | [
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PMID:25454 | The effect of chronic lithium administration on dopamine metabolism in rat striatum. | Striatal dopamine and its metabolites were studied in rats given lithium chloride in the diet. Results showed an increase in homovanillic acid and 3,4-dihydroxyphenylacetic acid levels but no significant change in dopamine concentration after 3 weeks of lithium administration. There was no change in tyrosine hydroxylase activity after 1, 2, and 3 weeks treatment. The results indicate an increase in the release and turnover of dopamine in the lithium-treated animals. | The effect of chronic lithium administration on dopamine metabolism in rat striatum. Striatal dopamine and its metabolites were studied in rats given lithium chloride in the diet. Results showed an increase in homovanillic acid and 3,4-dihydroxyphenylacetic acid levels but no significant change in dopamine concentration after 3 weeks of lithium administration. There was no change in tyrosine hydroxylase activity after 1, 2, and 3 weeks treatment. The results indicate an increase in the release and turnover of dopamine in the lithium-treated animals. | [
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PMID:25455 | Prolactin secretion during and after Noveril infusions to depressive patients. | Dibenzapine (720 mg, Noveril) was infused intravenously to 16 depressed patients during a period of 3 h. Serum prolactin levels were determined by radioimmunoassay and changes in clinical condition were evaluated according to the Hamilton Equation. The two variables were correlated to each other. In most of the patients Noveril caused a dramatic but short-lived improvement in depressive symptoms. There was much variability in the prolactin response to the drug. Serum prolactin levels showed a great elevation in 9 patients. In all patients the hormonal levels returned to their former normal levels after termination of the infusions. The treatment was then continued with Noveril per os. There was no significant correlation between serum prolactin levels and clinical condition or its change. The elevation of serum prolactin levels as a reaction to Noveril treatment may be explained by the prominent serotonergic action of Noveril. A time lag between serotonergic and dopaminergic actions of the drug when given in higher doses may be an additional explanation. Other possible hypotheses are discussed. | Prolactin secretion during and after Noveril infusions to depressive patients. Dibenzapine (720 mg, Noveril) was infused intravenously to 16 depressed patients during a period of 3 h. Serum prolactin levels were determined by radioimmunoassay and changes in clinical condition were evaluated according to the Hamilton Equation. The two variables were correlated to each other. In most of the patients Noveril caused a dramatic but short-lived improvement in depressive symptoms. There was much variability in the prolactin response to the drug. Serum prolactin levels showed a great elevation in 9 patients. In all patients the hormonal levels returned to their former normal levels after termination of the infusions. The treatment was then continued with Noveril per os. There was no significant correlation between serum prolactin levels and clinical condition or its change. The elevation of serum prolactin levels as a reaction to Noveril treatment may be explained by the prominent serotonergic action of Noveril. A time lag between serotonergic and dopaminergic actions of the drug when given in higher doses may be an additional explanation. Other possible hypotheses are discussed. | [
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PMID:25463 | The degradation of a nonapeptide, sleep inducing peptide, in rat brain: comparison with enkephalin breakdown. | The degradation of delta sleep inducing peptide (DSIP) was studied and compared with that of Met-enkephalin in brain homogenates. After 7.5 minutes of incubation of 2.5% (w/v) homogenate, 30% of N-terminal tryptophan was released from DSIP, while 75% of N-terminal tyrosine was released from Metenkephalin. The optimal pH of degradation of both peptides was pH 7.35. A rapid increase of breakdown of the peptides was observed during the 10 days of postnatal growth, with breakdown expressed per unit weight of brain. Neither morphine nor deprivation of rapid eye movement (REM) sleep affected the degradation of peptides. | The degradation of a nonapeptide, sleep inducing peptide, in rat brain: comparison with enkephalin breakdown. The degradation of delta sleep inducing peptide (DSIP) was studied and compared with that of Met-enkephalin in brain homogenates. After 7.5 minutes of incubation of 2.5% (w/v) homogenate, 30% of N-terminal tryptophan was released from DSIP, while 75% of N-terminal tyrosine was released from Metenkephalin. The optimal pH of degradation of both peptides was pH 7.35. A rapid increase of breakdown of the peptides was observed during the 10 days of postnatal growth, with breakdown expressed per unit weight of brain. Neither morphine nor deprivation of rapid eye movement (REM) sleep affected the degradation of peptides. | [
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PMID:25464 | In vivo and in vitro alteration of nicotine metabolism by the major metabolite of phenytoin. | The influence of hydroxyphentoin (HPPH), the major metabolite of phenytoin, on the in vitro and in vivo metabolism of nicotine was examined. In rat liver 9,000 g supernatant HPPH decreased the appearance of cotinine from nicotine by 65% while not influencing the disappearance of nicotine or the appearance of nicotine-l'-N-oxide. In vivo, HPPH inhibited both nicotine elimination and cotinine formation but did not affect nicotin-l'-N-oxide formation. | In vivo and in vitro alteration of nicotine metabolism by the major metabolite of phenytoin. The influence of hydroxyphentoin (HPPH), the major metabolite of phenytoin, on the in vitro and in vivo metabolism of nicotine was examined. In rat liver 9,000 g supernatant HPPH decreased the appearance of cotinine from nicotine by 65% while not influencing the disappearance of nicotine or the appearance of nicotine-l'-N-oxide. In vivo, HPPH inhibited both nicotine elimination and cotinine formation but did not affect nicotin-l'-N-oxide formation. | [
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PMID:25465 | [The effect of mainly alpha-adrenergic drugs, indirect sympathomimetrics and dopamine on exocrine pancreatic function. Studies in the isolated cat pancreas (author's transl)]. | The influence of mainly alpha-adrenergic drugs (noradrenaline, adrenaline, phenylephrine), indirect sympathomimetics (ephedrine, tyramin) and dopamine on the exocrine pancreatic function of the isolated perfused organ of cats was studied. The injection of noradrenaline and adrenaline induced simultaneously a rapid depression of flow rate and an increase of perfusion pressure. Phenylephrine, indirect sympathomimetic drugs and dopamine did not change the perfusion pressure and the hydrelatic function (flow rate, secretion of chloride and total calcium). The protein and enzyme secretion was enhanced both in normal animals and cats pretreated by reserpine or 6-hydroxydopamine. The pancreatic protein secretion was inhibited by alpha-adrenolytic as well as beta-adrenolytic substances, tetracain and atropine. It is concluded, that mainly alpha-adrenergic drugs stimulate the pancreatic enzyme secretion in a cholinergic manner. | [The effect of mainly alpha-adrenergic drugs, indirect sympathomimetrics and dopamine on exocrine pancreatic function. Studies in the isolated cat pancreas (author's transl)]. The influence of mainly alpha-adrenergic drugs (noradrenaline, adrenaline, phenylephrine), indirect sympathomimetics (ephedrine, tyramin) and dopamine on the exocrine pancreatic function of the isolated perfused organ of cats was studied. The injection of noradrenaline and adrenaline induced simultaneously a rapid depression of flow rate and an increase of perfusion pressure. Phenylephrine, indirect sympathomimetic drugs and dopamine did not change the perfusion pressure and the hydrelatic function (flow rate, secretion of chloride and total calcium). The protein and enzyme secretion was enhanced both in normal animals and cats pretreated by reserpine or 6-hydroxydopamine. The pancreatic protein secretion was inhibited by alpha-adrenolytic as well as beta-adrenolytic substances, tetracain and atropine. It is concluded, that mainly alpha-adrenergic drugs stimulate the pancreatic enzyme secretion in a cholinergic manner. | [
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PMID:25466 | A comparison of rimiterol and salbutamol by inhalation at high and low dose in asthmatic patients. | Rimiterol hydrobromide (Pulmadil) has been shown to have a dose-related bronchodilator effect; the optimum dose by inhalation appears to lie between 200 and 1,000 microgram. When given to a group of asthmatic patients at 'recommended' and 5--10 times 'recommended' dose by aerosol, cardiovascular effects were minimal and of a magnitude similar to that of salbutamol given in the same dosages to the same patients. The very rapid bronchodilator effect of rimiterol would appear to make the drug particularly suitable for the treatment of patients with intermittent asthmatic attacks, before exercise in patients with exercise-induced asthma and for bronchodilatation before using inhaled sodium cromoglycate or corticosteroid aerosols. | A comparison of rimiterol and salbutamol by inhalation at high and low dose in asthmatic patients. Rimiterol hydrobromide (Pulmadil) has been shown to have a dose-related bronchodilator effect; the optimum dose by inhalation appears to lie between 200 and 1,000 microgram. When given to a group of asthmatic patients at 'recommended' and 5--10 times 'recommended' dose by aerosol, cardiovascular effects were minimal and of a magnitude similar to that of salbutamol given in the same dosages to the same patients. The very rapid bronchodilator effect of rimiterol would appear to make the drug particularly suitable for the treatment of patients with intermittent asthmatic attacks, before exercise in patients with exercise-induced asthma and for bronchodilatation before using inhaled sodium cromoglycate or corticosteroid aerosols. | [
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PMID:25467 | A brief review of sympathomimetic bronchodilators and a description of a new selective agent, rimiterol hydrobromide. | The development of beta2-specific sympathomimetic bronchodilators (rimiterol, salbutamol, terbutaline) has made the basic treatment of asthmatic patients more safe and effective. Despite that, the asthmatics should be under careful control and all patients should be taught the correct way to use their bronchodilator aerosols. If a sympathomimetic drug has lost its effectiveness, the patient should be able to have easy contact to the treating physician or outpatient department. | A brief review of sympathomimetic bronchodilators and a description of a new selective agent, rimiterol hydrobromide. The development of beta2-specific sympathomimetic bronchodilators (rimiterol, salbutamol, terbutaline) has made the basic treatment of asthmatic patients more safe and effective. Despite that, the asthmatics should be under careful control and all patients should be taught the correct way to use their bronchodilator aerosols. If a sympathomimetic drug has lost its effectiveness, the patient should be able to have easy contact to the treating physician or outpatient department. | [
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PMID:25469 | The effect of dibutyryl cyclic AMP and glucagon on the myocardial cell pH1. | DBcAMP or crystalline glucagon was utilized to elevate the intracellular cyclic AMP concentration in isolated rat hearts. Butyric acid, a metabolite of DBcAMP, was also investigated. Their effect on the intracellular pH (pHi) as determined by the distribution of [14C]DMO was investigated. Rat hearts, perfused with a recirculated modified Krebs-Henseleit solution maintained at 30 degrees C, were exposed to respiratory acidosis by bubbling the perfusate with 20% CO2. alpha- and beta-receptor antagonists were used to block the effects of endogenous catecholamines. Hypercapnia decreased the pHi from 7.09 to 6.82. A similar degree of hypercapnia decreased the pHi to only 6.95 in the presence of DBcAMP and to only 6.96 in the presence of glucagon. The effective buffer values (delta[HCO-3]i/deltapHi) were: control, 19; butyric acid, 16; DBcAMP, 139; glucagon, 148. These data suggest that cAMP mediates the effect of norepinephrine, which has been shown to diminish the change in pHi accompanying respiratory acidosis. | The effect of dibutyryl cyclic AMP and glucagon on the myocardial cell pH1. DBcAMP or crystalline glucagon was utilized to elevate the intracellular cyclic AMP concentration in isolated rat hearts. Butyric acid, a metabolite of DBcAMP, was also investigated. Their effect on the intracellular pH (pHi) as determined by the distribution of [14C]DMO was investigated. Rat hearts, perfused with a recirculated modified Krebs-Henseleit solution maintained at 30 degrees C, were exposed to respiratory acidosis by bubbling the perfusate with 20% CO2. alpha- and beta-receptor antagonists were used to block the effects of endogenous catecholamines. Hypercapnia decreased the pHi from 7.09 to 6.82. A similar degree of hypercapnia decreased the pHi to only 6.95 in the presence of DBcAMP and to only 6.96 in the presence of glucagon. The effective buffer values (delta[HCO-3]i/deltapHi) were: control, 19; butyric acid, 16; DBcAMP, 139; glucagon, 148. These data suggest that cAMP mediates the effect of norepinephrine, which has been shown to diminish the change in pHi accompanying respiratory acidosis. | [
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PMID:25486 | Behavioral neurochemistry: neuroregulators and behavioral states. | There is compelling evidence that behavioral events after neurochemical function and that altered neurochemical function can change behavior. Such processes have been related both to neurotransmitters and to neuromodulators, together termed neuroregulators. Available research tools and theoretical constructs have begun to permit studies of certain types of behavior, primarily those related to emotional states and drives. This work is changing long-held concepts about severe mental disorders and the treatment of them. | Behavioral neurochemistry: neuroregulators and behavioral states. There is compelling evidence that behavioral events after neurochemical function and that altered neurochemical function can change behavior. Such processes have been related both to neurotransmitters and to neuromodulators, together termed neuroregulators. Available research tools and theoretical constructs have begun to permit studies of certain types of behavior, primarily those related to emotional states and drives. This work is changing long-held concepts about severe mental disorders and the treatment of them. | [
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PMID:25487 | Medical treatment of mental illness. | Psychotherapeutic drugs have dramatically improved the prognosis for patients with severe mental illness. The drug treatments are not a panacea. The medications sometimes cause irreversible side effects, and they are not helpful for all patients. They allow large numbers of individuals to leave the hospital, but to return to communities that are often poorly prepared to provide continuing care. Despite their limitations, psychotherapeutic drugs relieve a great deal of human suffering. They also involve psychiatry in modern biological science. This has led to the continuing search for more effective medications based on the study of possible biochemical substrates of psychiatric disorders. | Medical treatment of mental illness. Psychotherapeutic drugs have dramatically improved the prognosis for patients with severe mental illness. The drug treatments are not a panacea. The medications sometimes cause irreversible side effects, and they are not helpful for all patients. They allow large numbers of individuals to leave the hospital, but to return to communities that are often poorly prepared to provide continuing care. Despite their limitations, psychotherapeutic drugs relieve a great deal of human suffering. They also involve psychiatry in modern biological science. This has led to the continuing search for more effective medications based on the study of possible biochemical substrates of psychiatric disorders. | [
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PMID:25488 | Somatostatin--paracrine and neuromodulator peptide in gut and nervous system. | Somatostatin, a tetradecapeptide widely distributed in nervous tissue and gut, has inhibitory effects on secretion and neuromuscular activity. The actions of this peptide probably embrace three types of transmitter-receptor interaction, namely that of a neurotransmitter in the nervous system, that of a hormone in the hypophyseal portal circulation and that of a local (paracrine) effector in gut and pancreas. | Somatostatin--paracrine and neuromodulator peptide in gut and nervous system. Somatostatin, a tetradecapeptide widely distributed in nervous tissue and gut, has inhibitory effects on secretion and neuromuscular activity. The actions of this peptide probably embrace three types of transmitter-receptor interaction, namely that of a neurotransmitter in the nervous system, that of a hormone in the hypophyseal portal circulation and that of a local (paracrine) effector in gut and pancreas. | [
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PMID:25489 | Comparison of cardiovascular responses and left ventricular work during exercise before and after artificial heart implantation. | Cardiovascular dynamics and left ventricular work were evaluated in 15 resting, standing, and treadmill-exercised calves before and at periodic intervals after their natural hearts (NH) were replaced with an artificial heart (AH). Standing produced increases in heart rate, cardiac output, oxygen uptake, and left ventricular work and decreases in mean aortic pressure and systemic vascular resistance in NH calves which were more marked with exercise. AH calves had higher aortic pressures, cardiac output, systemic vascular resistance, oxygen uptake, and left ventricular work during resting conditions in the first 2 postoperative weeks than did NH calves, which gradually returned to values similar to the latter by the fifth week after operation. Exercise was not tolerated early after AH implantation, but was after 5 to 6 weeks. Our results indicate that AH calves increase cardiac output with exercise by reducing systemic vascular resistance, whereas NH animals respond similarly, but also increase heart rate. The data suggest that a marked elevation in systemic vascular resistance early after AH implantation increases left ventricular work and prevents adequate rises in cardiac output to all but minor increases in metabolic requirements. | Comparison of cardiovascular responses and left ventricular work during exercise before and after artificial heart implantation. Cardiovascular dynamics and left ventricular work were evaluated in 15 resting, standing, and treadmill-exercised calves before and at periodic intervals after their natural hearts (NH) were replaced with an artificial heart (AH). Standing produced increases in heart rate, cardiac output, oxygen uptake, and left ventricular work and decreases in mean aortic pressure and systemic vascular resistance in NH calves which were more marked with exercise. AH calves had higher aortic pressures, cardiac output, systemic vascular resistance, oxygen uptake, and left ventricular work during resting conditions in the first 2 postoperative weeks than did NH calves, which gradually returned to values similar to the latter by the fifth week after operation. Exercise was not tolerated early after AH implantation, but was after 5 to 6 weeks. Our results indicate that AH calves increase cardiac output with exercise by reducing systemic vascular resistance, whereas NH animals respond similarly, but also increase heart rate. The data suggest that a marked elevation in systemic vascular resistance early after AH implantation increases left ventricular work and prevents adequate rises in cardiac output to all but minor increases in metabolic requirements. | [
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PMID:25495 | Endocrine-like cells in the terminal bronchioles and saccules of human fetal lung: an ultrastructural study. | An ultrastructural study of Kulschitsky cells was made on lung tissue from five human fetuses of gestational ages between 18 and 25 weeks. The cells were found to occur with relative frequency throughout the bronchi and bronchioles, as well as in the developing saccules. This report describes in detail the cells of the terminal bronchioles and saccules, where their long cytoplasmic processes weave through the epithelium and come into contact with intercellular spaces and the lumen. The cytoplasmic organelles have an orderly arrangement comparable to secreting cells. Dense core vesicles characterise the cytoplasm but clear vesicles and some with less dense, diffuse cores are also present, and may be seen outside the plasma membrane and in the interstitial spaces. The K-cells are usually colsely associated with capillaries or smooth muscle cells across the basement membrane. In addition, the rare occurrence of a small unmyelinated nerve fibre in the vicinity of a K-cell in a terminal bronchiole raises the possibility that the cells fulfill a type of 'mini receptor' role in addition to their probable vasoactive one. Evidence is given that K-cells divide in human fetal lung. | Endocrine-like cells in the terminal bronchioles and saccules of human fetal lung: an ultrastructural study. An ultrastructural study of Kulschitsky cells was made on lung tissue from five human fetuses of gestational ages between 18 and 25 weeks. The cells were found to occur with relative frequency throughout the bronchi and bronchioles, as well as in the developing saccules. This report describes in detail the cells of the terminal bronchioles and saccules, where their long cytoplasmic processes weave through the epithelium and come into contact with intercellular spaces and the lumen. The cytoplasmic organelles have an orderly arrangement comparable to secreting cells. Dense core vesicles characterise the cytoplasm but clear vesicles and some with less dense, diffuse cores are also present, and may be seen outside the plasma membrane and in the interstitial spaces. The K-cells are usually colsely associated with capillaries or smooth muscle cells across the basement membrane. In addition, the rare occurrence of a small unmyelinated nerve fibre in the vicinity of a K-cell in a terminal bronchiole raises the possibility that the cells fulfill a type of 'mini receptor' role in addition to their probable vasoactive one. Evidence is given that K-cells divide in human fetal lung. | [
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PMID:25497 | Anchoring cells (Desmocytes) in the hydrozoan polyp Cordylophora. | Desmocytes or anchoring cells are present on the upright stolons of the athecate hydroid Cordylophora caspia and function to support the soft coenosarc within the rigid tube of perisarc by linking the perisarc with the mesoglea. These cells are characterized by accumulations of 70 A filaments which aggregate into dense rods at the apical end and contact the perisarc. At the base of the desmocytes the filaments are distributed within large cytoplasmic processes which interdigitate with an extension of the mesoglea. Desmocytes in Cordylophora are temporally and spatially formed in sequence as the upright elongates. Depending on their location and structure they can be categorized as forming, functional, or remnant desmocytes. The youngest, forming desmocytes are found in the distal end of the stolon 0.5-1.0 mm from the base of the hydranth. In this region coenosarc is just beginning to separate from the perisarc. Functional desmocytes are scattered 1-3 mm from the base of the hydranth and are associated with perpendicular extensions of the mesoglea. Remnants have lost their mesogleal connection and are located in more proximal, older regions of upright stolon. Support provided by the desmocytes to the upright stolon is limited by three factors that characterize the athecate hydroid: distribution of perisarc, pattern of growth, and extent of movement. The distal location of forming desmocytes is coincident with the hardening of new perisarc. The temporary nature of attachment sites is directly related to upright elongation. It is probable that the orientation of filaments within the cell and the mesogleal extension provide an addition feature of flexibility necessary to permit feeding, growth, and rhythmic pulsation movements characteristic of these hydroids. | Anchoring cells (Desmocytes) in the hydrozoan polyp Cordylophora. Desmocytes or anchoring cells are present on the upright stolons of the athecate hydroid Cordylophora caspia and function to support the soft coenosarc within the rigid tube of perisarc by linking the perisarc with the mesoglea. These cells are characterized by accumulations of 70 A filaments which aggregate into dense rods at the apical end and contact the perisarc. At the base of the desmocytes the filaments are distributed within large cytoplasmic processes which interdigitate with an extension of the mesoglea. Desmocytes in Cordylophora are temporally and spatially formed in sequence as the upright elongates. Depending on their location and structure they can be categorized as forming, functional, or remnant desmocytes. The youngest, forming desmocytes are found in the distal end of the stolon 0.5-1.0 mm from the base of the hydranth. In this region coenosarc is just beginning to separate from the perisarc. Functional desmocytes are scattered 1-3 mm from the base of the hydranth and are associated with perpendicular extensions of the mesoglea. Remnants have lost their mesogleal connection and are located in more proximal, older regions of upright stolon. Support provided by the desmocytes to the upright stolon is limited by three factors that characterize the athecate hydroid: distribution of perisarc, pattern of growth, and extent of movement. The distal location of forming desmocytes is coincident with the hardening of new perisarc. The temporary nature of attachment sites is directly related to upright elongation. It is probable that the orientation of filaments within the cell and the mesogleal extension provide an addition feature of flexibility necessary to permit feeding, growth, and rhythmic pulsation movements characteristic of these hydroids. | [
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PMID:25503 | Testicular descent. Normal and abnormal. | The subject of testicular descent has been reviewed. An attempt has been made to present a basic understanding of the embryology and mechanisms of this event. The abnormalities of testicular descent have also been discussed, including the pathogenesis and complications of this disorder, which is the most common developmental abnormality in childhood. The aims and results of both the hormonal and surgical treatments of cryptorchidism have been summarized. From data gleaned from the literature, a plea is made for the earlier treatment of the undescended testis in patients under five years of age. | Testicular descent. Normal and abnormal. The subject of testicular descent has been reviewed. An attempt has been made to present a basic understanding of the embryology and mechanisms of this event. The abnormalities of testicular descent have also been discussed, including the pathogenesis and complications of this disorder, which is the most common developmental abnormality in childhood. The aims and results of both the hormonal and surgical treatments of cryptorchidism have been summarized. From data gleaned from the literature, a plea is made for the earlier treatment of the undescended testis in patients under five years of age. | [
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PMID:25500 | Storage of platelets prepared by discontinuous flow centrifugation. | Platelet concentrates were prepared by plateletpheresis using discontinuous flow centrifugation. Platelet units were stored in PL-146 bags of 300 ml and 2,000 ml capacity, and in vitro measures helpful in predicting platelet viability were compared. Storage in bags of 300 ml capacity led to significant fall in pH, decreased recovery from osmotic stress, and deterioration of morphology in 24 hours. Storage lesions were significantly decreased by use of 2,000 ml capacity bags. | Storage of platelets prepared by discontinuous flow centrifugation. Platelet concentrates were prepared by plateletpheresis using discontinuous flow centrifugation. Platelet units were stored in PL-146 bags of 300 ml and 2,000 ml capacity, and in vitro measures helpful in predicting platelet viability were compared. Storage in bags of 300 ml capacity led to significant fall in pH, decreased recovery from osmotic stress, and deterioration of morphology in 24 hours. Storage lesions were significantly decreased by use of 2,000 ml capacity bags. | [
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PMID:25506 | The influence of pH on antimicrobial substances in canine vaginal and urethral secretions. | Trimethoprim and rosamicin (a new basic macrolide antibiotic) were administered to normal and oophorectomised female dogs by constant intravenous infusion before and after oestrogen and androgen administration. Their concentrations in plasma and in urethral and vaginal secretions were determined by bioassay and correlated with the pH values of vaginal and urethral secretions. Both compounds were concentrated in the vaginal and urethral secretions in reverse correlation with the pH of these fluids. Trimethoprim and rosamicin have antimicrobial spectra well suited for the treatment of bacterial urethritis and vaginitis and require further clinical investigation. | The influence of pH on antimicrobial substances in canine vaginal and urethral secretions. Trimethoprim and rosamicin (a new basic macrolide antibiotic) were administered to normal and oophorectomised female dogs by constant intravenous infusion before and after oestrogen and androgen administration. Their concentrations in plasma and in urethral and vaginal secretions were determined by bioassay and correlated with the pH values of vaginal and urethral secretions. Both compounds were concentrated in the vaginal and urethral secretions in reverse correlation with the pH of these fluids. Trimethoprim and rosamicin have antimicrobial spectra well suited for the treatment of bacterial urethritis and vaginitis and require further clinical investigation. | [
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PMID:25507 | Milk fever prevention. | Milk fever is a disease of increasing importance. In dairy herds its incidence has doubled since 1950; today about 8 per cent of parturitions in Swedish dairy cattle are complicated by milk fever. At the same time, the clinical picture has changed and the effectiveness of calcium therapy has been markedly reduced. Thirty to 40 per cent of cows with milk fever need more than one treatment. These trends are obvious in Sweden and Norway and have been reported from many other parts of the world. However, there are also geographical and breed differences so that these figures might not be applicable under British conditions. | Milk fever prevention. Milk fever is a disease of increasing importance. In dairy herds its incidence has doubled since 1950; today about 8 per cent of parturitions in Swedish dairy cattle are complicated by milk fever. At the same time, the clinical picture has changed and the effectiveness of calcium therapy has been markedly reduced. Thirty to 40 per cent of cows with milk fever need more than one treatment. These trends are obvious in Sweden and Norway and have been reported from many other parts of the world. However, there are also geographical and breed differences so that these figures might not be applicable under British conditions. | [
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PMID:25509 | Glutathione conjugation and mercapturic acid formation in the developing rat, in vivo and in vitro. | 1. The levels of GSH-S-epoxidetransferase (GSH-S-transferase E, EC 2.5.1.18), gamma-glutamyl transpeptidase (EC 2.3.2.2) and S-substituted cysteine N-acetyltransferase have been measured in the liver and kidney of neonatal to adult rats. 2. GSH-S-epoxidetransferase and S-substituted cysteine N-acetyltransferase activities were less than 10% of the adult values in neonatal rats, rising gradually to reach adult values at about 40 days of age. Renal gamma-glutamyl transpeptidase activity was 27% of the adult value 2 days after birth and increased after 15 days reaching adult levels by 40 days. 3. The percentages of the doses of 1,2-epoxy-3-(p-nitrophenoxy)propane (ENPP) and of 1,2-epoxybutane, administered at the same dose level to rats aged 4 days to adult, excreted as the corresponding mercapturic acids in 24 h, were not significantly different. 4. Adult and 10 day old rats doses at the same dose level with ENPP excreted N-acetyl-S-[2-hydroxy-3-(p-nitrophenoxy)propyl]-L-cysteine (ENPP-MA) at the same rate. 5. In addition to ENPP-MA, dosed rats under 13 days of age excreted the corresponding substituted cysteine. 6. The correlation between results in vitro and in vivo is discussed. | Glutathione conjugation and mercapturic acid formation in the developing rat, in vivo and in vitro. 1. The levels of GSH-S-epoxidetransferase (GSH-S-transferase E, EC 2.5.1.18), gamma-glutamyl transpeptidase (EC 2.3.2.2) and S-substituted cysteine N-acetyltransferase have been measured in the liver and kidney of neonatal to adult rats. 2. GSH-S-epoxidetransferase and S-substituted cysteine N-acetyltransferase activities were less than 10% of the adult values in neonatal rats, rising gradually to reach adult values at about 40 days of age. Renal gamma-glutamyl transpeptidase activity was 27% of the adult value 2 days after birth and increased after 15 days reaching adult levels by 40 days. 3. The percentages of the doses of 1,2-epoxy-3-(p-nitrophenoxy)propane (ENPP) and of 1,2-epoxybutane, administered at the same dose level to rats aged 4 days to adult, excreted as the corresponding mercapturic acids in 24 h, were not significantly different. 4. Adult and 10 day old rats doses at the same dose level with ENPP excreted N-acetyl-S-[2-hydroxy-3-(p-nitrophenoxy)propyl]-L-cysteine (ENPP-MA) at the same rate. 5. In addition to ENPP-MA, dosed rats under 13 days of age excreted the corresponding substituted cysteine. 6. The correlation between results in vitro and in vivo is discussed. | [
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PMID:25516 | [Characteristics of pancreatic basal secretion in the dog]. | A method is described for the simultaneous evaluation of the pancreatic, the biliary and the gastric secretion in long-term experiments. Under these conditions, the pancreatic basal secretion is characterized. The pancreatic basal secretion is a very variable reference value that is influenced by endogenous stimuli. The upper threshold value for the secretion rate was 2.2 ml/15 min. Under the influence of spontaneous biliary secretion, the protein concentration amounts to a characteristic value of relatively unimportant variance. If the pancreatic basal secretion is used as a reference value, the spontaneous secretions of the biliary ducts (gastrin release from the duodenum?) and of the stomach (secretin release from the duodenum) and be taken into account. A further disturbing factor interfering with both the pancreatic and the gastric basal secretion is to be neglected. | [Characteristics of pancreatic basal secretion in the dog]. A method is described for the simultaneous evaluation of the pancreatic, the biliary and the gastric secretion in long-term experiments. Under these conditions, the pancreatic basal secretion is characterized. The pancreatic basal secretion is a very variable reference value that is influenced by endogenous stimuli. The upper threshold value for the secretion rate was 2.2 ml/15 min. Under the influence of spontaneous biliary secretion, the protein concentration amounts to a characteristic value of relatively unimportant variance. If the pancreatic basal secretion is used as a reference value, the spontaneous secretions of the biliary ducts (gastrin release from the duodenum?) and of the stomach (secretin release from the duodenum) and be taken into account. A further disturbing factor interfering with both the pancreatic and the gastric basal secretion is to be neglected. | [
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PMID:25544 | [Animal experiment studies on the neurohumoral control of female puberty]. | To study the mode of action of oestrogen in female sexual maturation, prepubertal female rats were treated in different ways with oestradiol benzoate (OB). Using an improved implantation method, former findings on a hypophysial site of oestrogen action in the positive feedback (Hohlweg effect) were confirmed. A single s.c. injection or intrahypophysial implantation of OB at 25 or 26 days of age induced precocious vaginal opening (VO) and one ovulation, but the subsequent ovarian cycle was significantly prolonged, so that the first spontaneous ovulation occurred only at the normal time of the onset of puberty. Further studies demonstrated that the sensitivity to the ovulation-inducing effect of oestrogen increases as the rats approach the age of puberty, and that the first pubertal ovulation can be suppressed by intrahypophysial, but not by intrahypothalamic implantation of progestereone. The conclusion is drawn that the precocious induction of one ovulation via the Hohlweg effect is not tantamount to an advancement of puberty. The results furthermore suggest that the positive oestrogen feedback forms the basis for the first pubertal ovulation as it does with regard to later cyclic ovulations. True acceleration of sexual maturation was achieved by daily injections of 0,05 microgram OB/100 g b.w. from 5 days of age to VO. In contrast to findings obtained by other authors in Sprague-Dawley rats, a shortened OB treatment from 26 days of age to VO was not effective in advancing the onset of puberty unless the rats had additionally been injected with OB from 5 to 10 days of age. A final experiment demonstrated that the first ovarian cycle was not prolonged after neonatal ovariectomy and implantation of ovaries at 24, 28 or 32 days of age. Thus, maturation of the neurohormonal mechanisms that are responsible for the cyclic ovarian function continues during the prepubertal development in the absence of ovarian steroids. | [Animal experiment studies on the neurohumoral control of female puberty]. To study the mode of action of oestrogen in female sexual maturation, prepubertal female rats were treated in different ways with oestradiol benzoate (OB). Using an improved implantation method, former findings on a hypophysial site of oestrogen action in the positive feedback (Hohlweg effect) were confirmed. A single s.c. injection or intrahypophysial implantation of OB at 25 or 26 days of age induced precocious vaginal opening (VO) and one ovulation, but the subsequent ovarian cycle was significantly prolonged, so that the first spontaneous ovulation occurred only at the normal time of the onset of puberty. Further studies demonstrated that the sensitivity to the ovulation-inducing effect of oestrogen increases as the rats approach the age of puberty, and that the first pubertal ovulation can be suppressed by intrahypophysial, but not by intrahypothalamic implantation of progestereone. The conclusion is drawn that the precocious induction of one ovulation via the Hohlweg effect is not tantamount to an advancement of puberty. The results furthermore suggest that the positive oestrogen feedback forms the basis for the first pubertal ovulation as it does with regard to later cyclic ovulations. True acceleration of sexual maturation was achieved by daily injections of 0,05 microgram OB/100 g b.w. from 5 days of age to VO. In contrast to findings obtained by other authors in Sprague-Dawley rats, a shortened OB treatment from 26 days of age to VO was not effective in advancing the onset of puberty unless the rats had additionally been injected with OB from 5 to 10 days of age. A final experiment demonstrated that the first ovarian cycle was not prolonged after neonatal ovariectomy and implantation of ovaries at 24, 28 or 32 days of age. Thus, maturation of the neurohormonal mechanisms that are responsible for the cyclic ovarian function continues during the prepubertal development in the absence of ovarian steroids. | [
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PMID:25546 | [Relationship between the pathogenesis of lumbosacral radiculitis and specific treatment]. | On the basis of personal experience in treating 534 patients with sacro-lumbar radiculitis the authors believe it expedient to distinguish the following clinical syndromes: lumbago, radicle neuralgia, radicle neuritis, radicle neuritis with a paralysis of the foot and the caudal syndrome. In their opinion, the main pathogenetical mechanisms of the disease, which facilitates the selection of the methods of treatment should be taken into consideration. It is stressed that a differentiated clinical approach to patients with therapeutically resistent forms of sacro-lumbar radiculitis in the majority of the cases provides good results in medicational and surgical treatment. | [Relationship between the pathogenesis of lumbosacral radiculitis and specific treatment]. On the basis of personal experience in treating 534 patients with sacro-lumbar radiculitis the authors believe it expedient to distinguish the following clinical syndromes: lumbago, radicle neuralgia, radicle neuritis, radicle neuritis with a paralysis of the foot and the caudal syndrome. In their opinion, the main pathogenetical mechanisms of the disease, which facilitates the selection of the methods of treatment should be taken into consideration. It is stressed that a differentiated clinical approach to patients with therapeutically resistent forms of sacro-lumbar radiculitis in the majority of the cases provides good results in medicational and surgical treatment. | [
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PMID:25547 | [Diffuse x-ray wide-angle scattering of polyglutamic acid in solution]. | The diffuse wide angle x-ray scattering (WAXS) of polyglutamic acid (PGA) in solution was studied using an x-ray diffractometer with small aperture of the primary beam. The scattering curve was recorded at an angular interval from (article: see text). The experimental scattering intensity of PGA with alpha-helical CD spectrum showed a maximum at 14.4 nm-1. Unordered PGA in solution yielded no maximum at this scattering angle. The studies have proved that the scattering theory can be applied to globular proteins in solution as well as to chain molecules in solution in this angular interval. The differences between the calculated scattering curves and the experimental curves indicate minor movements of the side chains of PGA in solutions and slight structuring of the solvent at the surface of the polypeptide chain. | [Diffuse x-ray wide-angle scattering of polyglutamic acid in solution]. The diffuse wide angle x-ray scattering (WAXS) of polyglutamic acid (PGA) in solution was studied using an x-ray diffractometer with small aperture of the primary beam. The scattering curve was recorded at an angular interval from (article: see text). The experimental scattering intensity of PGA with alpha-helical CD spectrum showed a maximum at 14.4 nm-1. Unordered PGA in solution yielded no maximum at this scattering angle. The studies have proved that the scattering theory can be applied to globular proteins in solution as well as to chain molecules in solution in this angular interval. The differences between the calculated scattering curves and the experimental curves indicate minor movements of the side chains of PGA in solutions and slight structuring of the solvent at the surface of the polypeptide chain. | [
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PMID:25548 | Substrate binding to solubilized cytochrome P-450 from rabbits at different temperatures. | The binding affinities of selected type I- and type II-substrates to partially purified cytochrome p-450 from rabbit liver microsomes were studied and found to differ from those of rats. The temperature dependence of the apparent binding constants qualitatively exhibited the same characteristics compared with that of rats. For type I-substrates endothermic and for type II-substrates exothermic reaction characteristics were observed. Taking into account the partition coefficients of the substrates so far investigated it is obvious that type I substrates with increasing hydrophobicity are bound more strongly while type II-substrates show a more complicated behvaiour. This may due to the fact that other types of binding are included besides the hydrophobic interactions. | Substrate binding to solubilized cytochrome P-450 from rabbits at different temperatures. The binding affinities of selected type I- and type II-substrates to partially purified cytochrome p-450 from rabbit liver microsomes were studied and found to differ from those of rats. The temperature dependence of the apparent binding constants qualitatively exhibited the same characteristics compared with that of rats. For type I-substrates endothermic and for type II-substrates exothermic reaction characteristics were observed. Taking into account the partition coefficients of the substrates so far investigated it is obvious that type I substrates with increasing hydrophobicity are bound more strongly while type II-substrates show a more complicated behvaiour. This may due to the fact that other types of binding are included besides the hydrophobic interactions. | [
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PMID:25549 | The influence of NADH on the ethylmorphine-N-demethylation in liver microsomes from control and phenobarbital-treated rats or different ages. | The ethylmorphine-N-demethylation by liver microsomes from control and phenobarbital-treated rats of different ages was investigated by means of adding NADPH in combination with NADH to the incubation medium. The rate of ethylmorphine-N-demethylation in the presence of NADPH without NADH is greater in adult than in young rats and greater in induced that in control rats. The higher the activity of ethylmorphine metabolism with NADPH alone the more it is abolsutely enhanced by NADH. The relative increase in ethylmorphine metabolism caused by NADH is equal in all groups of animals. It is concluded that there are no differences in the introduction of the second electron from NADH to the oxygenated cytochrome P-450 but there are differences in the concentration of cytochrome-substrate complex and, consequently, in the oxygenated cytochrome-substrate complex. The enhancing effect of NADH is higher at lower NADPH concentrations. In the presence of NADH, the NADPH concentrations necessary to obtain a msximum metabolic rate are lower than without NADH. | The influence of NADH on the ethylmorphine-N-demethylation in liver microsomes from control and phenobarbital-treated rats or different ages. The ethylmorphine-N-demethylation by liver microsomes from control and phenobarbital-treated rats of different ages was investigated by means of adding NADPH in combination with NADH to the incubation medium. The rate of ethylmorphine-N-demethylation in the presence of NADPH without NADH is greater in adult than in young rats and greater in induced that in control rats. The higher the activity of ethylmorphine metabolism with NADPH alone the more it is abolsutely enhanced by NADH. The relative increase in ethylmorphine metabolism caused by NADH is equal in all groups of animals. It is concluded that there are no differences in the introduction of the second electron from NADH to the oxygenated cytochrome P-450 but there are differences in the concentration of cytochrome-substrate complex and, consequently, in the oxygenated cytochrome-substrate complex. The enhancing effect of NADH is higher at lower NADPH concentrations. In the presence of NADH, the NADPH concentrations necessary to obtain a msximum metabolic rate are lower than without NADH. | [
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PMID:25551 | Role of neurotransmitters, prostaglandins and glucose on precursor incorporation into the RNA of thyroid slices. | The present studies were performed in order to investigate the role of neurotransmitters, prostaglandins and glucose on [3H] uridine incorporation into total RNA in beef thyroid slices. Carbamylcholine strongly stimulated RNA labelling from [3H uridine; atropine abolished this effect. NaF, at 1 and 5 mM, progressively increased this parameter while norepinephrine caused a similar effect at 10(-3) but not at 10(-6) M. Phentolamine (1 mM) blocked the stimulatory action of TSH; propranolol and atropine did not. Glucose at concentrations between 4 and 24 mM caused a progressive increase in RNA labelling from [3H] uridine. This effect was inhibited by dinitrophenol. Prostaglandins (E1, A1, F1alpha and F2alpha) assayed in concentrations between 5 and 25 microgram/ml, with or without caffeine, had no effect on RNA labelling. Moreover, neither aspirin nor indomethacin inhibited TSH stimulation. Under similar experimental conditions, PGE1 did simulate PB125I formation. | Role of neurotransmitters, prostaglandins and glucose on precursor incorporation into the RNA of thyroid slices. The present studies were performed in order to investigate the role of neurotransmitters, prostaglandins and glucose on [3H] uridine incorporation into total RNA in beef thyroid slices. Carbamylcholine strongly stimulated RNA labelling from [3H uridine; atropine abolished this effect. NaF, at 1 and 5 mM, progressively increased this parameter while norepinephrine caused a similar effect at 10(-3) but not at 10(-6) M. Phentolamine (1 mM) blocked the stimulatory action of TSH; propranolol and atropine did not. Glucose at concentrations between 4 and 24 mM caused a progressive increase in RNA labelling from [3H] uridine. This effect was inhibited by dinitrophenol. Prostaglandins (E1, A1, F1alpha and F2alpha) assayed in concentrations between 5 and 25 microgram/ml, with or without caffeine, had no effect on RNA labelling. Moreover, neither aspirin nor indomethacin inhibited TSH stimulation. Under similar experimental conditions, PGE1 did simulate PB125I formation. | [
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PMID:25552 | Sympathetic amines, renin and blood pressure. | The sympathetic nervous system and the renin-angiotensin mechanism each can influence blood pressure separately but the two systems also interact functionally in various ways. There is good evidence that central catecholaminergic neurons play an essential role in the regulation of blood pressure but it may be assumed that other putative neurotransmittors such as serotonin, GABA and various peptides also participate in the central regulation of blood pressure. The secretion of renin, which catalyzes the production of angiotensin(s), is stimulated by increased sympathetic activity and circulating sympathetic amines. Dopamine seems to have an opposite effect on renin release but it is not clear whether this is due to a direct effect on the renin producing cells or an influence on sympathetic activity, centrally or peripherally. | Sympathetic amines, renin and blood pressure. The sympathetic nervous system and the renin-angiotensin mechanism each can influence blood pressure separately but the two systems also interact functionally in various ways. There is good evidence that central catecholaminergic neurons play an essential role in the regulation of blood pressure but it may be assumed that other putative neurotransmittors such as serotonin, GABA and various peptides also participate in the central regulation of blood pressure. The secretion of renin, which catalyzes the production of angiotensin(s), is stimulated by increased sympathetic activity and circulating sympathetic amines. Dopamine seems to have an opposite effect on renin release but it is not clear whether this is due to a direct effect on the renin producing cells or an influence on sympathetic activity, centrally or peripherally. | [
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PMID:25553 | Cardiovascular actions of bromocriptine. | Bromocriptine lowers blood pressure in animals and in man. Results obtained in experiments performed in the dog and cat suggest three possible mechanisms of action: a) relaxation of vascular smooth muscle, principally in splanchnic and renal vessels, (b) inhibition of transmitter release from noradrenergic nerve endings, (c) central inhibition of sympathetic nerve activity. The effect of bromocriptine at each putative site of action can be explained in terms of dopamine receptor stimulation. | Cardiovascular actions of bromocriptine. Bromocriptine lowers blood pressure in animals and in man. Results obtained in experiments performed in the dog and cat suggest three possible mechanisms of action: a) relaxation of vascular smooth muscle, principally in splanchnic and renal vessels, (b) inhibition of transmitter release from noradrenergic nerve endings, (c) central inhibition of sympathetic nerve activity. The effect of bromocriptine at each putative site of action can be explained in terms of dopamine receptor stimulation. | [
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PMID:25554 | Bone marrow transplantation between mixed leukocyte culture reactive siblings. | Bone marrow transplantation from an HLA identical MLC reactive sibling has been performed in a patient with acute myelogenous leukemia resistant to drug treatment. Prompt engraftment was documented; however, the patient died of septicemia 34 days after transplant. Clinical manifestation of graft vs. host reaction was mild but was moderately strong expressed at autopsy tissue samples. Recurrence of persistence of leukemia was found at the time of death. | Bone marrow transplantation between mixed leukocyte culture reactive siblings. Bone marrow transplantation from an HLA identical MLC reactive sibling has been performed in a patient with acute myelogenous leukemia resistant to drug treatment. Prompt engraftment was documented; however, the patient died of septicemia 34 days after transplant. Clinical manifestation of graft vs. host reaction was mild but was moderately strong expressed at autopsy tissue samples. Recurrence of persistence of leukemia was found at the time of death. | [
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PMID:25555 | Salicylazosulphapyridine-induced Heinz body anemia. | A 58-year-old patient suffered from severe malabsorption due to agammaglobulinemia. Treated empirically with salicylazosulfapyridine 2--6 g/day, the subjective and objective features of malabsorption regressed. About a year after this treatment she developed a generalized weakness without renewal of the diarrhea; the diagnosis of Heinz body hemolytic anemia was established. In our patient, hemolysis began many months after the commencement of treatment and no deficiency of G6PD or other erythrocyte enzyme or pathological hemoglobin were found. | Salicylazosulphapyridine-induced Heinz body anemia. A 58-year-old patient suffered from severe malabsorption due to agammaglobulinemia. Treated empirically with salicylazosulfapyridine 2--6 g/day, the subjective and objective features of malabsorption regressed. About a year after this treatment she developed a generalized weakness without renewal of the diarrhea; the diagnosis of Heinz body hemolytic anemia was established. In our patient, hemolysis began many months after the commencement of treatment and no deficiency of G6PD or other erythrocyte enzyme or pathological hemoglobin were found. | [
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PMID:25556 | Acid-base status during reconstructive surgery of the abdominal aorta. | Abolition of a temporary occlusion of the circulation in the legs during surgical reconstruction of the abdominal aorta generally exerts but little influence on the patient's acid-base status. The changes in acid-base status can be corrected by the patient himself. Routine administration of sodium bicarbonate or Tham is unnecessary. However, respiration, circulation and electrolyte balance should be carefully monitored to ensure that any disturbances in this respect can immediately be given adequate treatment. Determination of the acid-base status during the operation is a valuable aid in evaluation of the patient's condition and can be used as a guideline in therapy. | Acid-base status during reconstructive surgery of the abdominal aorta. Abolition of a temporary occlusion of the circulation in the legs during surgical reconstruction of the abdominal aorta generally exerts but little influence on the patient's acid-base status. The changes in acid-base status can be corrected by the patient himself. Routine administration of sodium bicarbonate or Tham is unnecessary. However, respiration, circulation and electrolyte balance should be carefully monitored to ensure that any disturbances in this respect can immediately be given adequate treatment. Determination of the acid-base status during the operation is a valuable aid in evaluation of the patient's condition and can be used as a guideline in therapy. | [
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PMID:25557 | The effect of prolonged experimental hypercapnia on the brain. | Thirteen adult rabbits were exposed to a breathing air mixture containing an increasing amount of CO2 for eight weeks. When the CO2 content reached 9 Vol% the animals became apathic and lost body weight. The EEG showed a reduction of the amplitudes of 1o Hz frequences. Blood gases revealed an increase of bicarbonate but no change of pH. The blood brain barrier which was tested when the animals were killed was not disturbed. Enzyme histochemistry, light and electron microscopy revealed that moderate brain edema had occurred. From these results it is concluded that chronic hypercapnia has a hypnotic effect which in combination with chronic edema may depress vital activities considerably. However, there seem to be no irreversible morphological alterations of the brain. | The effect of prolonged experimental hypercapnia on the brain. Thirteen adult rabbits were exposed to a breathing air mixture containing an increasing amount of CO2 for eight weeks. When the CO2 content reached 9 Vol% the animals became apathic and lost body weight. The EEG showed a reduction of the amplitudes of 1o Hz frequences. Blood gases revealed an increase of bicarbonate but no change of pH. The blood brain barrier which was tested when the animals were killed was not disturbed. Enzyme histochemistry, light and electron microscopy revealed that moderate brain edema had occurred. From these results it is concluded that chronic hypercapnia has a hypnotic effect which in combination with chronic edema may depress vital activities considerably. However, there seem to be no irreversible morphological alterations of the brain. | [
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PMID:25559 | Effect of lactate on FFA--release and cyclic 3', 5' AMP accumulation in fat cells at different pH. | Effect of lactate on FFA--release and cyclic 3', 5-AMP accumulation in fat cells at different pH. Acta Physiol. Pol., 1977, 28 (6): 505--510. The effect of sodium lactate on noradrenaline (NA), theophyline (Th), and dibutyryl cyclic 3', 5'AMP stimulated free fatty acid (FFA) release as well as on NA--stimulated cyclic 3', 5'AMP (cAMP) accumulation in isolated fat cells at different pH was studied. It was shown that at each of examined pH (6.8, 7.1, 7.4, 7.7) sodium lactate inhibits NA and Th-induced FFA release and NA-stimulated cAMP accumulation. It did not significantly change FFA release induced by dibutryl cyclic 3', 5'AMP. The inhibitory effect of sodium lactate both on FFA release and cAMP accumulation was markedly augmented at pH 7.1 and especially at pH 6.8 as compared to pH 7.4, while at pH 7.7 it remained essentially the same as at pH 7.4. The obtained results showed that lactate exerts its antilipolytic effect through the inhibitory action on cAMP accumulation and subsequently on the activity of the hormone-sensitive triglyceride lipase. An effect of lactate on FFA reesterification cannot be however excluded. It seems that the potentiation of the antilipolytic effect of lactate at pH below 7.4 has an important physiological significance. The mechanism protects effectively against an excessive, undesirable FFA-outflow from adipose tissue in situations in which FFA cannot be utilized. | Effect of lactate on FFA--release and cyclic 3', 5' AMP accumulation in fat cells at different pH. Effect of lactate on FFA--release and cyclic 3', 5-AMP accumulation in fat cells at different pH. Acta Physiol. Pol., 1977, 28 (6): 505--510. The effect of sodium lactate on noradrenaline (NA), theophyline (Th), and dibutyryl cyclic 3', 5'AMP stimulated free fatty acid (FFA) release as well as on NA--stimulated cyclic 3', 5'AMP (cAMP) accumulation in isolated fat cells at different pH was studied. It was shown that at each of examined pH (6.8, 7.1, 7.4, 7.7) sodium lactate inhibits NA and Th-induced FFA release and NA-stimulated cAMP accumulation. It did not significantly change FFA release induced by dibutryl cyclic 3', 5'AMP. The inhibitory effect of sodium lactate both on FFA release and cAMP accumulation was markedly augmented at pH 7.1 and especially at pH 6.8 as compared to pH 7.4, while at pH 7.7 it remained essentially the same as at pH 7.4. The obtained results showed that lactate exerts its antilipolytic effect through the inhibitory action on cAMP accumulation and subsequently on the activity of the hormone-sensitive triglyceride lipase. An effect of lactate on FFA reesterification cannot be however excluded. It seems that the potentiation of the antilipolytic effect of lactate at pH below 7.4 has an important physiological significance. The mechanism protects effectively against an excessive, undesirable FFA-outflow from adipose tissue in situations in which FFA cannot be utilized. | [
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PMID:25567 | Relationship between adrenergic blocking and antihypertensive effects of beta receptor antagonists. | In hypertensive patients, whose blood pressure was decreased by racemic propranololthe dextrorotatory isomer had no antihypertensive effect. The differences in antihypertensive activity of racemic and dextrorotatory propranolol cannot be explained by different plasma levels; the data indicate that the hypotensive effect of propranolol is due to beta receptor blockade. | Relationship between adrenergic blocking and antihypertensive effects of beta receptor antagonists. In hypertensive patients, whose blood pressure was decreased by racemic propranololthe dextrorotatory isomer had no antihypertensive effect. The differences in antihypertensive activity of racemic and dextrorotatory propranolol cannot be explained by different plasma levels; the data indicate that the hypotensive effect of propranolol is due to beta receptor blockade. | [
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PMID:25568 | The significance of beta1-beta2-selectivity and intrinsic sympathomimetic activity in beta-blockers, with particular reference to antihypertensive treatment. | From the findings described in the already fairly copious literature on antihypertensive therapy with beta-blockers, as well as on the basis of theoretical considerations, it may be concluded that neither cardio-selectivity nor intrinsic sympathomimetic activity is of decisive importance with regard to the blood-pressure-lowering action of these these compounds. As far as hypotensive potency alone is concerned, none of the known beta-blocking agents is fundamentally superior to the others. There are, however, considerable differences between them in respect of their safety in use, tolerability and side effects, and during long-term treatment especially these must be taken into account. | The significance of beta1-beta2-selectivity and intrinsic sympathomimetic activity in beta-blockers, with particular reference to antihypertensive treatment. From the findings described in the already fairly copious literature on antihypertensive therapy with beta-blockers, as well as on the basis of theoretical considerations, it may be concluded that neither cardio-selectivity nor intrinsic sympathomimetic activity is of decisive importance with regard to the blood-pressure-lowering action of these these compounds. As far as hypotensive potency alone is concerned, none of the known beta-blocking agents is fundamentally superior to the others. There are, however, considerable differences between them in respect of their safety in use, tolerability and side effects, and during long-term treatment especially these must be taken into account. | [
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PMID:25574 | Neuropharmacology and aging. | This review has attempted to convey the idea that the current concepts of psychotropic drug actions are based largely around the monoamine transmitter systems. Several of the hypotheses which implicate abnormalities of these systems as factors involved in the aging brain are discussed. It is suggested that the current lack of specific geriatric psychotropic agents is in part a reflection of our ignorance of the neurochemical basis of the aging process. | Neuropharmacology and aging. This review has attempted to convey the idea that the current concepts of psychotropic drug actions are based largely around the monoamine transmitter systems. Several of the hypotheses which implicate abnormalities of these systems as factors involved in the aging brain are discussed. It is suggested that the current lack of specific geriatric psychotropic agents is in part a reflection of our ignorance of the neurochemical basis of the aging process. | [
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PMID:25576 | Tardive dyskinesia. | The movement disorder may appear after prolonged use of antipsychotic agents. Differential diagnosis includes hereditary, infectious, toxic and drug-induced causes of extrapyramidal dysfunction. Pathophysiology appears to be related to induced changes in dopamine neuronal function and may represent irreversible extrapyramidal synaptic modification. Treatment includes removing the offending agent when possible or using the lowest effective dose if the medication cannot be totally discontinued. Indiscriminate use of antipsychotic agents in nonpsychotic patients should be avoided. | Tardive dyskinesia. The movement disorder may appear after prolonged use of antipsychotic agents. Differential diagnosis includes hereditary, infectious, toxic and drug-induced causes of extrapyramidal dysfunction. Pathophysiology appears to be related to induced changes in dopamine neuronal function and may represent irreversible extrapyramidal synaptic modification. Treatment includes removing the offending agent when possible or using the lowest effective dose if the medication cannot be totally discontinued. Indiscriminate use of antipsychotic agents in nonpsychotic patients should be avoided. | [
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PMID:25578 | Persuader sex differences and peer pressure effects on attitudes toward drug abuse. | This experiment was performed to assess the effects of the experimental confederates' sex and contrived group peer pressure on the drug attitudes of male college students. Subjects were exposed to all-male or all-female groups of experimental confederates (ersuaders) who expressed either extremely pro-drug or anti-drug sentiments in a guided group discussion. A drug attitude survey encompassing four drug categories was administered immediately following the discussion. Significant differences were found between subjects in the anti-drug and pro-drug groups. The sex effect data indicated that the male subjects reported more liberal drug attitudes following exposure to female persuaders in both the anti-and pro-drug treatment conditions for the more socially acceptable drugs such as marijuana, hashish, and stimulants. Implications of these findings for possible prevention and intervention strategies and for further research are discussed. | Persuader sex differences and peer pressure effects on attitudes toward drug abuse. This experiment was performed to assess the effects of the experimental confederates' sex and contrived group peer pressure on the drug attitudes of male college students. Subjects were exposed to all-male or all-female groups of experimental confederates (ersuaders) who expressed either extremely pro-drug or anti-drug sentiments in a guided group discussion. A drug attitude survey encompassing four drug categories was administered immediately following the discussion. Significant differences were found between subjects in the anti-drug and pro-drug groups. The sex effect data indicated that the male subjects reported more liberal drug attitudes following exposure to female persuaders in both the anti-and pro-drug treatment conditions for the more socially acceptable drugs such as marijuana, hashish, and stimulants. Implications of these findings for possible prevention and intervention strategies and for further research are discussed. | [
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PMID:25579 | Evaluation of some pharmaceutical aspects of intrathecal methotrexate sodium, cytarabine and hydrocortisone sodium succinate. | Methotrexate sodium, cytarabine and hydrocortisone sodium succinate were evaluated in three vehicles, Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, and Elliott's B solution, an artificial cerebrospinal fluid (CSF). Osmolarity values of all drug solutions studied were within 10% of normal human. No vehicle-related alterations in the stability of methotrexate or cytarabine were detected under simulated use conditions. However, the degradation of hydrocortisone sodium succinate was faster in Elliott's B solution than in the other vehicles. Principal differences among the vehicles involved electrolyte content, pH and buffer capacity. Elliott's B solution is similar to CSF in electrolyte composition and buffer capacity, and was the only vehicle to maintain the pH of dilute methotrexate and cytarabine solutions between 7.2 and 7.8. The significance of these in vitro data await a careful clinical study. | Evaluation of some pharmaceutical aspects of intrathecal methotrexate sodium, cytarabine and hydrocortisone sodium succinate. Methotrexate sodium, cytarabine and hydrocortisone sodium succinate were evaluated in three vehicles, Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, and Elliott's B solution, an artificial cerebrospinal fluid (CSF). Osmolarity values of all drug solutions studied were within 10% of normal human. No vehicle-related alterations in the stability of methotrexate or cytarabine were detected under simulated use conditions. However, the degradation of hydrocortisone sodium succinate was faster in Elliott's B solution than in the other vehicles. Principal differences among the vehicles involved electrolyte content, pH and buffer capacity. Elliott's B solution is similar to CSF in electrolyte composition and buffer capacity, and was the only vehicle to maintain the pH of dilute methotrexate and cytarabine solutions between 7.2 and 7.8. The significance of these in vitro data await a careful clinical study. | [
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PMID:25580 | Prevalence of endocrine abnormalities in patients with the Zollinger-Ellison syndrome and in their families. | To evalute the frequency of associated and hereditary endocrinopathies in the Zollinger-Ellison syndrome, 10 patients with the syndrome were studied. In seven of them, coexisting endocrine disease was found. In six, the Zollinger-Ellison syndrome was probably a feature of multiple endocrine adenomatosis type I, whereas Cushing's syndrome in the remaining patient may have been caused by the production of an ACTH-like substance by a mixed pancreatic tumor. A total of 109 family members, including all living first degree relatives over 15 years of age, were screened for endocrine abnormalities. All six patients with evidence of multiple endocrine adenomatosis type I had relatives with endocrinopathies. In the families of the four other patients with the Zollinger-Ellison syndrome, no endocrine abnormalities were found. During this study four new cases of pituitary tumor, 17 of hyperparathyroidism, seven of the Zollinger-Ellison syndrome and one of insulinoma were detected. Although most of the disorders were asymptomatic, this clearly indicates that patients suffering from Zollinger-Ellison syndrome and also their families should undergo detailed endocrine studies. | Prevalence of endocrine abnormalities in patients with the Zollinger-Ellison syndrome and in their families. To evalute the frequency of associated and hereditary endocrinopathies in the Zollinger-Ellison syndrome, 10 patients with the syndrome were studied. In seven of them, coexisting endocrine disease was found. In six, the Zollinger-Ellison syndrome was probably a feature of multiple endocrine adenomatosis type I, whereas Cushing's syndrome in the remaining patient may have been caused by the production of an ACTH-like substance by a mixed pancreatic tumor. A total of 109 family members, including all living first degree relatives over 15 years of age, were screened for endocrine abnormalities. All six patients with evidence of multiple endocrine adenomatosis type I had relatives with endocrinopathies. In the families of the four other patients with the Zollinger-Ellison syndrome, no endocrine abnormalities were found. During this study four new cases of pituitary tumor, 17 of hyperparathyroidism, seven of the Zollinger-Ellison syndrome and one of insulinoma were detected. Although most of the disorders were asymptomatic, this clearly indicates that patients suffering from Zollinger-Ellison syndrome and also their families should undergo detailed endocrine studies. | [
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PMID:25581 | Cyclophosphamide-induced remissions in advanced polyarteritis nodosa. | Two patients with far advanced polyarteritis nodosa involving multiple organ systems and with aneurysm formation demonstrable by celiac axis and renal arteriograms were treated with oral cyclophosphamide, 1 to 2 mg/kg/day, and alternate day prednisone therapy. Dramatic remissions of disease activity were achieved within weeks of initiation of therapy. Repeat angiograms obtained after one year revealed complete resolution of all aneurysms. Both patients are now receiving only cyclophosphamide and are maintained in complete remission 27 and 18 months after the start of therapy. Cyclophosphamide therapy can thus be highly effective even in far advanced polyarteritis nodosa. | Cyclophosphamide-induced remissions in advanced polyarteritis nodosa. Two patients with far advanced polyarteritis nodosa involving multiple organ systems and with aneurysm formation demonstrable by celiac axis and renal arteriograms were treated with oral cyclophosphamide, 1 to 2 mg/kg/day, and alternate day prednisone therapy. Dramatic remissions of disease activity were achieved within weeks of initiation of therapy. Repeat angiograms obtained after one year revealed complete resolution of all aneurysms. Both patients are now receiving only cyclophosphamide and are maintained in complete remission 27 and 18 months after the start of therapy. Cyclophosphamide therapy can thus be highly effective even in far advanced polyarteritis nodosa. | [
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PMID:25582 | Biochemical evaluation of liver function. | Several chemistry tests for liver function are examined. Included are the transaminases, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bromsulphalein (BSP), as well as combinations of these and the ALP isoenzymes. | Biochemical evaluation of liver function. Several chemistry tests for liver function are examined. Included are the transaminases, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bromsulphalein (BSP), as well as combinations of these and the ALP isoenzymes. | [
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PMID:25583 | Adoption of a manual kinetic gamma-glutamyl transferase method in the clinical laboratory. | Following our recommended protocol for establishing analytical methods in a clinical laboratory, a rapid, simplified manual kinetic method for determining Gamma-Glutamyl Transferase activity in serum was adopted to meet the needs of our laboratory. The steps taken, from the selection of the assay conditions through the introduction of the new test ot staff physicians, are described. The assay, which requires only 50 microliter of serum or plasma, uses L-gamma-glutamyl-p-nitroanilide as the substrate, and is controlled at 30C and a pH of 8.20. The reaction is monitored by the increase in absorbance at 405 nm. Up to 30 samples per hour may be analyzed using a manual spectrophotometer. The substrate is simple to prepare and is stable for one working day at room temperature and for at least one month for frozen at -20C. | Adoption of a manual kinetic gamma-glutamyl transferase method in the clinical laboratory. Following our recommended protocol for establishing analytical methods in a clinical laboratory, a rapid, simplified manual kinetic method for determining Gamma-Glutamyl Transferase activity in serum was adopted to meet the needs of our laboratory. The steps taken, from the selection of the assay conditions through the introduction of the new test ot staff physicians, are described. The assay, which requires only 50 microliter of serum or plasma, uses L-gamma-glutamyl-p-nitroanilide as the substrate, and is controlled at 30C and a pH of 8.20. The reaction is monitored by the increase in absorbance at 405 nm. Up to 30 samples per hour may be analyzed using a manual spectrophotometer. The substrate is simple to prepare and is stable for one working day at room temperature and for at least one month for frozen at -20C. | [
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PMID:25584 | Immunologic aspects of malignancy. | Animal experimental studies and clinical observations closely relate the development and course of malignancy with immune function. The immune apparatus serves as a homeostatic system capable of recognizing "sell" from "non-self." Neoplasia is characterized by new surface components against which immune reactivity may be directed. Subpopulations of lymphocytes are stimulated by such tumor antigens leading to both humoral and cellular responses. Immunodeficiency, the surveillance role of immune responses, and immune competition are intimately concerned with the eventual outcome of the malignant state. These concepts are examined as supplying the theoretical background for development of new therapeutic procedures. Immunotherapy in the future may offer the most effective means of controlling the neoplastic state. | Immunologic aspects of malignancy. Animal experimental studies and clinical observations closely relate the development and course of malignancy with immune function. The immune apparatus serves as a homeostatic system capable of recognizing "sell" from "non-self." Neoplasia is characterized by new surface components against which immune reactivity may be directed. Subpopulations of lymphocytes are stimulated by such tumor antigens leading to both humoral and cellular responses. Immunodeficiency, the surveillance role of immune responses, and immune competition are intimately concerned with the eventual outcome of the malignant state. These concepts are examined as supplying the theoretical background for development of new therapeutic procedures. Immunotherapy in the future may offer the most effective means of controlling the neoplastic state. | [
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PMID:25585 | Cardiac pacemakers in absence of the SA node: responses to exercise and autonomic blockade. | Surgical excision of the sinoatrial node, verified histologically, is followed by a supraventricular (atrial) rhythm in both resting and exercising dog whether anesthetized or conscious. The ECG is characterized by a definitive P wave and associated atrial electrograms. Waxing and waning in heart rate, generally referred to as sinus arrhythmia continues in the awake animal after complete excision of the SA node. This arrhythmia is responsive to both adrenergic and cholinergic interventions, thus indicating the presence of both sympathetic and parasympathetic regulation of subsidiary atrial pacemaking tissues. | Cardiac pacemakers in absence of the SA node: responses to exercise and autonomic blockade. Surgical excision of the sinoatrial node, verified histologically, is followed by a supraventricular (atrial) rhythm in both resting and exercising dog whether anesthetized or conscious. The ECG is characterized by a definitive P wave and associated atrial electrograms. Waxing and waning in heart rate, generally referred to as sinus arrhythmia continues in the awake animal after complete excision of the SA node. This arrhythmia is responsive to both adrenergic and cholinergic interventions, thus indicating the presence of both sympathetic and parasympathetic regulation of subsidiary atrial pacemaking tissues. | [
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PMID:25586 | Renal sugar transport in the winter flounder: V. secretion of 2-deoxy-D-galactose. | Isolated renal tubules and renal clearance techniques were used to characterize the renal handling of 2-deoxy-D-galactose (2-d-Gal) by the winter flounder (Pseudopleuronectes americanus). In vitro, energy-dependent, pH-sensitive uptake of 2-d-Gal (2-100 micron) was seen at the antiluminal face of the cell. Clearance measurements showed net secretion of 2-d-Gal in vivo. The mean clearance of 2-d-Gal in 18 fish was 0.98 +/- 0.16 ml/h while the glomerular filtration rate (GFR) was only 0.37 +/- 0.10 ml/h. Secretion was associated with marked renal accumulation of both 2-d-Gal and phosphorylated derivatives (2-d-Gal-1-phosphate). Tissue-to-plasma ratios (T/P) averaged 19 for free sugar and 59 for total sugar. Both clearance ratio and T/P were reduced to approximately 1 by injection of galactose (2.5 mmol/kg) simultaneously with 2-d-Gal (25 mumol/kg). Phlorizin (2.5 mumol/kg) increased net 2-d-Gal secretion, whereas glucose (2.5 mmol/kg) produced no change in secretion. Both compounds depressed 2-d-Gal T/P. This result suggests the presence of readsorptive transport at the brush border, sensitive to glucose and phlorizin. | Renal sugar transport in the winter flounder: V. secretion of 2-deoxy-D-galactose. Isolated renal tubules and renal clearance techniques were used to characterize the renal handling of 2-deoxy-D-galactose (2-d-Gal) by the winter flounder (Pseudopleuronectes americanus). In vitro, energy-dependent, pH-sensitive uptake of 2-d-Gal (2-100 micron) was seen at the antiluminal face of the cell. Clearance measurements showed net secretion of 2-d-Gal in vivo. The mean clearance of 2-d-Gal in 18 fish was 0.98 +/- 0.16 ml/h while the glomerular filtration rate (GFR) was only 0.37 +/- 0.10 ml/h. Secretion was associated with marked renal accumulation of both 2-d-Gal and phosphorylated derivatives (2-d-Gal-1-phosphate). Tissue-to-plasma ratios (T/P) averaged 19 for free sugar and 59 for total sugar. Both clearance ratio and T/P were reduced to approximately 1 by injection of galactose (2.5 mmol/kg) simultaneously with 2-d-Gal (25 mumol/kg). Phlorizin (2.5 mumol/kg) increased net 2-d-Gal secretion, whereas glucose (2.5 mmol/kg) produced no change in secretion. Both compounds depressed 2-d-Gal T/P. This result suggests the presence of readsorptive transport at the brush border, sensitive to glucose and phlorizin. | [
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PMID:25588 | Dose-related biphasic effect of prolyl-leucyl-glycinamide (MIF-I) in depression. | Five of 8 patients with unipolar or bipolar endogenous depressions taking prolyl-leucyl-glycinamide (MIF-I), 75 mg/day, showed substantial improvement within a few days of beginning treatment compared with similar improvement in only 1 of 10 receiving 750 mg/day of MIF-I and only 1 of 5 patients taking placebo. The lower dose of MIF-I was associated with significantly greater improvement than both the higher dose and placebo on all of the rating scales used. The authors suggest that an even lower dose of MIF-I, on the order of 0.1 mg/kg, may have a greater effect as an antidepressant. | Dose-related biphasic effect of prolyl-leucyl-glycinamide (MIF-I) in depression. Five of 8 patients with unipolar or bipolar endogenous depressions taking prolyl-leucyl-glycinamide (MIF-I), 75 mg/day, showed substantial improvement within a few days of beginning treatment compared with similar improvement in only 1 of 10 receiving 750 mg/day of MIF-I and only 1 of 5 patients taking placebo. The lower dose of MIF-I was associated with significantly greater improvement than both the higher dose and placebo on all of the rating scales used. The authors suggest that an even lower dose of MIF-I, on the order of 0.1 mg/kg, may have a greater effect as an antidepressant. | [
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PMID:25592 | The presence of collagenolytic cathepsin in uveal lysosomes of bovine eye. | Collagenolytic cathepsin, which can liberate soluble hydroxyproline-containing products from insoluble vitreous collagen with maximum activity at pH 3.5, was biochemically studied in uveal lysosomes of bovine eye. Collagen solubilization was proportional to both enzyme concentration and incubation time. When the enzyme was heated, no reaction was observed. Collagen solubilization by uveal lysosomal extract was almost unaffected by Ca2+ ion, cysteine, beta-mercaptoethanol, and ethylenediaminetetraacetic acid, but inhibited about one-third by pepstatin. The possible role of collagenolytic cathepsin in vitreous liquefaction was considered. | The presence of collagenolytic cathepsin in uveal lysosomes of bovine eye. Collagenolytic cathepsin, which can liberate soluble hydroxyproline-containing products from insoluble vitreous collagen with maximum activity at pH 3.5, was biochemically studied in uveal lysosomes of bovine eye. Collagen solubilization was proportional to both enzyme concentration and incubation time. When the enzyme was heated, no reaction was observed. Collagen solubilization by uveal lysosomal extract was almost unaffected by Ca2+ ion, cysteine, beta-mercaptoethanol, and ethylenediaminetetraacetic acid, but inhibited about one-third by pepstatin. The possible role of collagenolytic cathepsin in vitreous liquefaction was considered. | [
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PMID:25595 | [Aerobic blood sampling technique using the B 109-syringe (author's transl)]. | A syringe (B 109 Radiometer) for arterial blood sampling with modified aerobic technique is described. The blood sampling and subsequent storage during 2 h in ice water induces no clinically significant changes in the pH, pCO2 and pO2 of the blood. | [Aerobic blood sampling technique using the B 109-syringe (author's transl)]. A syringe (B 109 Radiometer) for arterial blood sampling with modified aerobic technique is described. The blood sampling and subsequent storage during 2 h in ice water induces no clinically significant changes in the pH, pCO2 and pO2 of the blood. | [
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PMID:25598 | Identification of phosphates on the membranes of guinea pig sperm. | Guinea pig epididymal sperm, incubated for ATPases at pH 7.0 or pH 9.0, localize reaction product on both the periacrosomal segment of the plasmalemma and the outer acrosome membrane. In other species, e.g., rabbit, Ca++-ATPase is identified with the outer acrosome membrane. It may transport Ca++ into the acrosome for activation of enzymes released during the acrosome reaction. The neutral ATPase is demonstrable on the periacrosomal plasmalemma and possibly modifies Ca++ concentration in the fluid around the acrosome. In guinea pig sperm, Ca++-ATPase is sensitive to centrifugation or washing of sperm which indicates that the ductal fluid has unusual properties for preservation of the acrosome. Inhibition of the enzyme by these treatments suggests that conditions on the plasmalemmal surface affect the acrosome membrane. Inability to separate reaction product on the plasmalemma from that on the acrosome membrane may be due to migration of reaction product across the periacrosomal space. However, the ATPases are elicited in the guinea pig under the same conditions as in other species. The pH 9.0 enzyme requires Ca++ while the enzyme at pH 7.0 has no ion specificities. Demonstration of these enzymes indicates that mechanisms of acrosome activation, similar to those in other sperm, are relevant to the guinea pig. | Identification of phosphates on the membranes of guinea pig sperm. Guinea pig epididymal sperm, incubated for ATPases at pH 7.0 or pH 9.0, localize reaction product on both the periacrosomal segment of the plasmalemma and the outer acrosome membrane. In other species, e.g., rabbit, Ca++-ATPase is identified with the outer acrosome membrane. It may transport Ca++ into the acrosome for activation of enzymes released during the acrosome reaction. The neutral ATPase is demonstrable on the periacrosomal plasmalemma and possibly modifies Ca++ concentration in the fluid around the acrosome. In guinea pig sperm, Ca++-ATPase is sensitive to centrifugation or washing of sperm which indicates that the ductal fluid has unusual properties for preservation of the acrosome. Inhibition of the enzyme by these treatments suggests that conditions on the plasmalemmal surface affect the acrosome membrane. Inability to separate reaction product on the plasmalemma from that on the acrosome membrane may be due to migration of reaction product across the periacrosomal space. However, the ATPases are elicited in the guinea pig under the same conditions as in other species. The pH 9.0 enzyme requires Ca++ while the enzyme at pH 7.0 has no ion specificities. Demonstration of these enzymes indicates that mechanisms of acrosome activation, similar to those in other sperm, are relevant to the guinea pig. | [
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] |
PMID:25600 | [Mosquito studies on Hiddensee]. | The author reports on the biting activity of mosquitoes during the years 1957-77. His observations were made in the locality called "Duenenheide" on the island of Hiddensee, GDR. This "Duenenheide" is a heath-landscape with downs, situated near the village of Vitte. The daily rhythm of the mosquitoes is analyzed as well as the dependence on wind speed and air temperature near the ground. The results are compared with sporadic data on Stomoxys and on biting midges. The behaviour of chironomids is integrated in this comparison. | [Mosquito studies on Hiddensee]. The author reports on the biting activity of mosquitoes during the years 1957-77. His observations were made in the locality called "Duenenheide" on the island of Hiddensee, GDR. This "Duenenheide" is a heath-landscape with downs, situated near the village of Vitte. The daily rhythm of the mosquitoes is analyzed as well as the dependence on wind speed and air temperature near the ground. The results are compared with sporadic data on Stomoxys and on biting midges. The behaviour of chironomids is integrated in this comparison. | [
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PMID:25601 | Histochemical identification of fiber types in canine skeletal muscle. | Proximal and distal skeletal muscles from pectoral and pelvic limbs were histochemically examined in 18 neuromuscular disease-free dogs. On the basis of the human system of classification and nomenclature and results of standard adenosine triphosphatase (ATPase) and glycine-formaldehyde preincubation procedures, the fiber types identified in immature and mature canine skeletal muscles were I, IIA, and IIC. | Histochemical identification of fiber types in canine skeletal muscle. Proximal and distal skeletal muscles from pectoral and pelvic limbs were histochemically examined in 18 neuromuscular disease-free dogs. On the basis of the human system of classification and nomenclature and results of standard adenosine triphosphatase (ATPase) and glycine-formaldehyde preincubation procedures, the fiber types identified in immature and mature canine skeletal muscles were I, IIA, and IIC. | [
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PMID:25602 | Effect of liver microsome enzyme-inducing drugs on blood serum pentobarbital clearance and sleep time in sheep and rabbits. | Sheep were administered phenobarbital, diphenylhydantoin, chlorcyclizine, or phenylbutazone over 27 days. Rabbits were administered phenobarbital, diphenylhydantoin, or chlorcyclizine for 15 days. After the last treatment, pentobarbital was administered intravenously, and measurements were made of sleep time and blood serum pentobarbital concentrations over a 2-hour period. Treatment of ewes with phenobarbital or phenylbutazone increased the rate of pentobarbital clearance from the circulation and shortened sleep time; treatment with diphenylhydantoin or chlorcyclizine decreased the rates of pentobarbital clearance from blood and increased sleep time. Treatment of rabbits with phenobarbital or diphenylhydantoin accelerated pentobarbital clearance from blood and shortened sleep time; chlorcyclizine had no effect on blood pentobarbital concentrations or sleep time. The results suggest that accelerated or delayed clearance of pentobarbital from the circulation was largely responsible for shortened or prolonged sleep times. Other factors may have been involved to some extent in determining sleep time, because ewes with shortened sleep time tended to awake with lower circulating concentrations of pentobarbital than did control ewes, and those with prolonged sleep time tended to awake with higher pentobarbital values. | Effect of liver microsome enzyme-inducing drugs on blood serum pentobarbital clearance and sleep time in sheep and rabbits. Sheep were administered phenobarbital, diphenylhydantoin, chlorcyclizine, or phenylbutazone over 27 days. Rabbits were administered phenobarbital, diphenylhydantoin, or chlorcyclizine for 15 days. After the last treatment, pentobarbital was administered intravenously, and measurements were made of sleep time and blood serum pentobarbital concentrations over a 2-hour period. Treatment of ewes with phenobarbital or phenylbutazone increased the rate of pentobarbital clearance from the circulation and shortened sleep time; treatment with diphenylhydantoin or chlorcyclizine decreased the rates of pentobarbital clearance from blood and increased sleep time. Treatment of rabbits with phenobarbital or diphenylhydantoin accelerated pentobarbital clearance from blood and shortened sleep time; chlorcyclizine had no effect on blood pentobarbital concentrations or sleep time. The results suggest that accelerated or delayed clearance of pentobarbital from the circulation was largely responsible for shortened or prolonged sleep times. Other factors may have been involved to some extent in determining sleep time, because ewes with shortened sleep time tended to awake with lower circulating concentrations of pentobarbital than did control ewes, and those with prolonged sleep time tended to awake with higher pentobarbital values. | [
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PMID:25603 | Cytochemical demonstration of esterases in peripheral blood leukocytes. | Cytochemical methods for alpha naphthyl acetate esterase and chloroacetate esterase have been used to identify human monocytes and granulocytes. In this study, a standard procedure for staining alpha naphthyl acetate and chloroacetate esterase activities was modified by extending the range of pH of the incubation mixture and the duration of staining and was applied to cat, dog, goat, guinea pig, hamster, human, pig, rabbit, rat, and sheep leukocytes. The results for both enzymes showed (1) incubation time and pH had discrete effects on staining and (2) species differences for in vitro conditions to demonstrate esterase activity were pronounced. | Cytochemical demonstration of esterases in peripheral blood leukocytes. Cytochemical methods for alpha naphthyl acetate esterase and chloroacetate esterase have been used to identify human monocytes and granulocytes. In this study, a standard procedure for staining alpha naphthyl acetate and chloroacetate esterase activities was modified by extending the range of pH of the incubation mixture and the duration of staining and was applied to cat, dog, goat, guinea pig, hamster, human, pig, rabbit, rat, and sheep leukocytes. The results for both enzymes showed (1) incubation time and pH had discrete effects on staining and (2) species differences for in vitro conditions to demonstrate esterase activity were pronounced. | [
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PMID:25613 | [Flocculant interaction with native antibiotic solutions. The effect of flocculants on the quality indices of native solutions as dependent on a number of factors]. | Flocculants had a significant effect on the characteristics of the fermentation broth filtrates of some antibiotics. They decreased the filtrate turbidity, concentration of the organic ballast, etc. The size of the floccules depended on a number of factors, including the fluocculant concentration, agitation rate, concentration of the dispersing phase in the initial filtrate. The optimal concentration of the flocculant was defined not only by the type of the antibiotic-producing organism but also by composition of the nutrient medium used for the biosynthesis. Floccculant treatment provided a significant increase in the quality of the fermentation broth filtrates with respect to the main parameters: levels of proteins, pigments, emulgation capacity. | [Flocculant interaction with native antibiotic solutions. The effect of flocculants on the quality indices of native solutions as dependent on a number of factors]. Flocculants had a significant effect on the characteristics of the fermentation broth filtrates of some antibiotics. They decreased the filtrate turbidity, concentration of the organic ballast, etc. The size of the floccules depended on a number of factors, including the fluocculant concentration, agitation rate, concentration of the dispersing phase in the initial filtrate. The optimal concentration of the flocculant was defined not only by the type of the antibiotic-producing organism but also by composition of the nutrient medium used for the biosynthesis. Floccculant treatment provided a significant increase in the quality of the fermentation broth filtrates with respect to the main parameters: levels of proteins, pigments, emulgation capacity. | [
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] |
PMID:25614 | [Rifamycin in B distribution between aqueous and organic phases]. | Dependence of the coefficient of rifamycin B distribution in the system of butyl acetate-buffer solution on pH of the equilibrium acqueous phase, antibiotic concentration in the solution and temperature was studied. It was shown that the coefficient value did not depend on the antibiotic concentration within 1000-2000 gamma/ml and temperature. | [Rifamycin in B distribution between aqueous and organic phases]. Dependence of the coefficient of rifamycin B distribution in the system of butyl acetate-buffer solution on pH of the equilibrium acqueous phase, antibiotic concentration in the solution and temperature was studied. It was shown that the coefficient value did not depend on the antibiotic concentration within 1000-2000 gamma/ml and temperature. | [
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PMID:25615 | Physiological conditions affecting Staphylococcus aureus susceptibility to staphylococcin 1580. | Loss of salt tolerance, irreversible loss of viability, inhibition of l-glutamic acid uptake and effects on the high energy state of the membrane were used as parameters to measure the injury induced by staphylococcin 1580, a bacteriocin of Staphylococcus epidermidis, in susceptible cells of Staphylococcus aureus Oxford 209P. A small part of a growing cell population appeared to be temporarily resistant to the bacteriocin, and the cells were arrested in this stage when suspended in buffer. The proportion of susceptible cells may rapidly shift during exponential growth, apparently concomitantly with a change in cell metabolism. Glucose- and pyruvate-grown cells were equally susceptible to salts after staphylococcin treatment. Only in pyruvate-grown cells was amino acid uptake strongly inhibited, and the membrane potential was abolished after a short lag time. Also, irreversible killing was more distinct in pyruvate-grown cells. The proton gradient across the cell membrane was only slightly disturbed in both types of cells. Specific inhibitors of the energy metabolism revealed that the high energy state of the membrane was largely supported by hydrolysis of adenosine 5'-triphosphate in glucose-grown cells, whereas the oxidative input through electron transport appeared to be relatively more important in pyruvate-grown cells. Staphylococcin 1580 affected primarily the oxidative energy metabolism, although electron transport is not inhibited. Below a distinct incubation temperature cells were completely resistant to the action of the bacteriocin. Varying the growth temperature had only a slight effect on the transition temperature, but growth in the presence of Tween 80, which greatly enhanced the proportion of unsaturated fatty acids, decreased the transition temperature. | Physiological conditions affecting Staphylococcus aureus susceptibility to staphylococcin 1580. Loss of salt tolerance, irreversible loss of viability, inhibition of l-glutamic acid uptake and effects on the high energy state of the membrane were used as parameters to measure the injury induced by staphylococcin 1580, a bacteriocin of Staphylococcus epidermidis, in susceptible cells of Staphylococcus aureus Oxford 209P. A small part of a growing cell population appeared to be temporarily resistant to the bacteriocin, and the cells were arrested in this stage when suspended in buffer. The proportion of susceptible cells may rapidly shift during exponential growth, apparently concomitantly with a change in cell metabolism. Glucose- and pyruvate-grown cells were equally susceptible to salts after staphylococcin treatment. Only in pyruvate-grown cells was amino acid uptake strongly inhibited, and the membrane potential was abolished after a short lag time. Also, irreversible killing was more distinct in pyruvate-grown cells. The proton gradient across the cell membrane was only slightly disturbed in both types of cells. Specific inhibitors of the energy metabolism revealed that the high energy state of the membrane was largely supported by hydrolysis of adenosine 5'-triphosphate in glucose-grown cells, whereas the oxidative input through electron transport appeared to be relatively more important in pyruvate-grown cells. Staphylococcin 1580 affected primarily the oxidative energy metabolism, although electron transport is not inhibited. Below a distinct incubation temperature cells were completely resistant to the action of the bacteriocin. Varying the growth temperature had only a slight effect on the transition temperature, but growth in the presence of Tween 80, which greatly enhanced the proportion of unsaturated fatty acids, decreased the transition temperature. | [
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PMID:25616 | Partial characterization of a beta-lactamase from Vibrio parahaemolyticus by a new automated microiodometric technique. | A number of characteristics were determined with a new automated method for a partially purified beta-lactamase from Vibrio parahaemolyticus. The enzyme had a molecular weight of 28,000 by gel filtration, a pH optimum between 6.5 and 7.0, and a temperature optimum at 36 degrees C. With penicillin G as the substrate, the K(m) value for the beta-lactamase was 54.4 muM. The beta-lactamase was inhibited by cloxacillin but not by p-chloromercuribenzoate. The enzyme was similar but not identical to beta-lactamases from gram-negative, "nonhalophilic" organisms described by other workers. The microiodometric assay to measure beta-lactamase activity was automated with the use of a centrifugal analyzer that permitted 14 simultaneous determinations. Within-run precision was tested by putting the same reaction mixture in each well, and the coefficient of variation was only about 3%. Four extracts from different strains of halophilic vibrios were used to demonstrate that reaction rates were linear with enzyme concentration. The correlation coefficient of activity by the automated method with activity by the spectrophotometric method was 0.9721, demonstrating that the methods compared favorably with each other. The automated method greatly facilitated the characterization of the beta-lactamase. | Partial characterization of a beta-lactamase from Vibrio parahaemolyticus by a new automated microiodometric technique. A number of characteristics were determined with a new automated method for a partially purified beta-lactamase from Vibrio parahaemolyticus. The enzyme had a molecular weight of 28,000 by gel filtration, a pH optimum between 6.5 and 7.0, and a temperature optimum at 36 degrees C. With penicillin G as the substrate, the K(m) value for the beta-lactamase was 54.4 muM. The beta-lactamase was inhibited by cloxacillin but not by p-chloromercuribenzoate. The enzyme was similar but not identical to beta-lactamases from gram-negative, "nonhalophilic" organisms described by other workers. The microiodometric assay to measure beta-lactamase activity was automated with the use of a centrifugal analyzer that permitted 14 simultaneous determinations. Within-run precision was tested by putting the same reaction mixture in each well, and the coefficient of variation was only about 3%. Four extracts from different strains of halophilic vibrios were used to demonstrate that reaction rates were linear with enzyme concentration. The correlation coefficient of activity by the automated method with activity by the spectrophotometric method was 0.9721, demonstrating that the methods compared favorably with each other. The automated method greatly facilitated the characterization of the beta-lactamase. | [
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PMID:25617 | Secretion of cell wall polymers into the growth medium of lysis-defective pneumococci during treatment with penicillin and other inhibitors of cell wall synthesis. | Autolysin-defective pneumococci secrete into the growth medium choline-containing macromolecules during treatment with any one of a large number of inhibitors of cell wall biosynthesis, including beta-lactams, beta-halogeno-d-alanines, cephalosporins, and d-cycloserine. Secretion is closely related to the dose response of the bacteria to the various drugs: (i) secretion can already be detected at the minimum inhibitory concentration; (ii) the rate and extent of secretion is dependent upon the drug concentration; and (iii) secretion commences within minutes after the addition of the antibiotics to the cultures. Reversal of the growth-inhibitory effect of benzylpenicillin (by penicillinase addition) is accompanied by a halt in secretion just at the time when the bacteria resume normal growth. Secretion of the choline-containing macromolecules seems to be a specific consequence of the inhibition of peptidoglycan biosynthesis, since inhibition of growth by drugs affecting protein, ribonucleic acid, or deoxyribonucleic acid synthesis does not cause secretion. The choline-containing macromolecules include both the pneumococcal lipid-containing teichoic acid (Forssman antigen) and wall teichoic acids made after the addition of antibiotics. The appearance of these macromolecules in the growth medium is not due to the hydrolytic activity of an autolysin, since penicillin-induced secretion could be demonstrated in autolysin-defective mutants, in pneumococci grown on ethanolamine-containing medium (such cells are known to have defective autolytic systems), and in wildtype pneumococci grown under conditions nonpermissive for lysis. | Secretion of cell wall polymers into the growth medium of lysis-defective pneumococci during treatment with penicillin and other inhibitors of cell wall synthesis. Autolysin-defective pneumococci secrete into the growth medium choline-containing macromolecules during treatment with any one of a large number of inhibitors of cell wall biosynthesis, including beta-lactams, beta-halogeno-d-alanines, cephalosporins, and d-cycloserine. Secretion is closely related to the dose response of the bacteria to the various drugs: (i) secretion can already be detected at the minimum inhibitory concentration; (ii) the rate and extent of secretion is dependent upon the drug concentration; and (iii) secretion commences within minutes after the addition of the antibiotics to the cultures. Reversal of the growth-inhibitory effect of benzylpenicillin (by penicillinase addition) is accompanied by a halt in secretion just at the time when the bacteria resume normal growth. Secretion of the choline-containing macromolecules seems to be a specific consequence of the inhibition of peptidoglycan biosynthesis, since inhibition of growth by drugs affecting protein, ribonucleic acid, or deoxyribonucleic acid synthesis does not cause secretion. The choline-containing macromolecules include both the pneumococcal lipid-containing teichoic acid (Forssman antigen) and wall teichoic acids made after the addition of antibiotics. The appearance of these macromolecules in the growth medium is not due to the hydrolytic activity of an autolysin, since penicillin-induced secretion could be demonstrated in autolysin-defective mutants, in pneumococci grown on ethanolamine-containing medium (such cells are known to have defective autolytic systems), and in wildtype pneumococci grown under conditions nonpermissive for lysis. | [
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PMID:25618 | Characterization of cell wall polymers secreted into the growth medium of lysis-defective pneumococci during treatment with penicillin and other inhibitors of cell wall synthesis. | Autolysin-defective pneumococci secrete large quantities of choline-containing cell wall polymers into the growth medium during treatment with inhibitors of peptidoglycan synthesis. The secreted polymers were separated into three fractions by a combination of gel filtration on agarose and sodium dodecyl sulfate-gel electrophoresis. Fraction I had a high apparent molecular size and contained the Forssman antigen in complex with material exhibiting properties of cell wall teichoic acid. Choline-containing polymers of as yet uncharacterized structure were present in both fractions IIA and IIB, and fraction IIA also contained peptidoglycan components. | Characterization of cell wall polymers secreted into the growth medium of lysis-defective pneumococci during treatment with penicillin and other inhibitors of cell wall synthesis. Autolysin-defective pneumococci secrete large quantities of choline-containing cell wall polymers into the growth medium during treatment with inhibitors of peptidoglycan synthesis. The secreted polymers were separated into three fractions by a combination of gel filtration on agarose and sodium dodecyl sulfate-gel electrophoresis. Fraction I had a high apparent molecular size and contained the Forssman antigen in complex with material exhibiting properties of cell wall teichoic acid. Choline-containing polymers of as yet uncharacterized structure were present in both fractions IIA and IIB, and fraction IIA also contained peptidoglycan components. | [
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PMID:25620 | Production of trypsin inhibitor by a Cephalosporium sp. | Conditions for the production of the trypsin inhibitor from Cephalosporium sp. KM 388 were investigated. Polypeptone-meat extract-glucose medium supported excellent production of the trypsin inhibitor. In this medium, polypeptone and meat extract were utilized both as carbon and nitrogen sources and as limiting substrates for the cell growth. Glucose was consumed during the stationary growth phase and prevented the disappearance of inhibitor activity. Cephalosporium sp. KM 388 grew at a rate of a first-order reaction for the cell concentrations. Trypsin inhibitor production paralleled cell growth. At 27 degrees C the maximum specific rates of growth and inhibitor production were 0.14 h-1 and 2.1 U of inhibitor/h per mg of cell, respectively. The production rate and the maximum yield of the inhibitor were increased 1.5- and 1.2-fold, respectively, when the initial pH 6.3 was maintained throughout the fermentation. | Production of trypsin inhibitor by a Cephalosporium sp. Conditions for the production of the trypsin inhibitor from Cephalosporium sp. KM 388 were investigated. Polypeptone-meat extract-glucose medium supported excellent production of the trypsin inhibitor. In this medium, polypeptone and meat extract were utilized both as carbon and nitrogen sources and as limiting substrates for the cell growth. Glucose was consumed during the stationary growth phase and prevented the disappearance of inhibitor activity. Cephalosporium sp. KM 388 grew at a rate of a first-order reaction for the cell concentrations. Trypsin inhibitor production paralleled cell growth. At 27 degrees C the maximum specific rates of growth and inhibitor production were 0.14 h-1 and 2.1 U of inhibitor/h per mg of cell, respectively. The production rate and the maximum yield of the inhibitor were increased 1.5- and 1.2-fold, respectively, when the initial pH 6.3 was maintained throughout the fermentation. | [
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PMID:25621 | Role of lime treatment in the removal of bacteria, enteric viruses, and coliphages in a wastewater reclamation plant. | Lime flocculation/sedimentation in the first process unit of a 4,500-m3/day wastewater reclamation plant reduced numbers of microorganisms extensively when operated at pH 11.2. The efficiency was much less at lower pH values, and some bacteria even multiplied at pH 9.6. Data on reduction in the number of microorganisms in the lime treatment and subsequent units indicate that inactivation by hydroxide alkalinity plays an important role in the efficiency of lime treatment. Reductions in the numbers of enteric viruses were higher than those of coliphages, enterococci, and total plate and coliform bacteria, which indicate that lime treatment can be monitored by means of coliphage and conventional bacteriological tests. This paper illustrates the valuable role of high-pH lime treatment in reducing the load of pathogenic microorganisms on subsequent units, including ultimate disinfection processes, which is important in the multiple safety barrier concept of wastewater reclamation processes. | Role of lime treatment in the removal of bacteria, enteric viruses, and coliphages in a wastewater reclamation plant. Lime flocculation/sedimentation in the first process unit of a 4,500-m3/day wastewater reclamation plant reduced numbers of microorganisms extensively when operated at pH 11.2. The efficiency was much less at lower pH values, and some bacteria even multiplied at pH 9.6. Data on reduction in the number of microorganisms in the lime treatment and subsequent units indicate that inactivation by hydroxide alkalinity plays an important role in the efficiency of lime treatment. Reductions in the numbers of enteric viruses were higher than those of coliphages, enterococci, and total plate and coliform bacteria, which indicate that lime treatment can be monitored by means of coliphage and conventional bacteriological tests. This paper illustrates the valuable role of high-pH lime treatment in reducing the load of pathogenic microorganisms on subsequent units, including ultimate disinfection processes, which is important in the multiple safety barrier concept of wastewater reclamation processes. | [
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PMID:25622 | Hydrogen production by Anabaena cylindrica: effects of varying ammonium and ferric ions, pH, and light. | Anabaena cylindrica sparged with argon gas produced H2 continuously for 30 days under limited light conditions (6.0 W/m2) and for 18 days under elevated light conditions (32 W/m2) in the absence of exogenous nitrogen. The efficiency of converting visible light energy (32 W/m2) into chemical energy that is trapped as H2 ranged between 0.35 and 0.85% (approximately 13 microliter of H2 per mg [drywt] per h). Ammonium additions (0.2 mM NH4+) at various times destabilized the system and eventually suppressed H2 production completely, as compared with the control. Cultures grown with 5.0 mg of Fe3+ per liter produced H2 at a rate about twice that of cultures with 0.5 mg of Fe3+ per liter. Cultures grown at pH 7.4 produced H2 at the same initial rates as cultures that were grown at pH 9.4; however, the latter cultures continued to produce H2 after CO2 deprivation. | Hydrogen production by Anabaena cylindrica: effects of varying ammonium and ferric ions, pH, and light. Anabaena cylindrica sparged with argon gas produced H2 continuously for 30 days under limited light conditions (6.0 W/m2) and for 18 days under elevated light conditions (32 W/m2) in the absence of exogenous nitrogen. The efficiency of converting visible light energy (32 W/m2) into chemical energy that is trapped as H2 ranged between 0.35 and 0.85% (approximately 13 microliter of H2 per mg [drywt] per h). Ammonium additions (0.2 mM NH4+) at various times destabilized the system and eventually suppressed H2 production completely, as compared with the control. Cultures grown with 5.0 mg of Fe3+ per liter produced H2 at a rate about twice that of cultures with 0.5 mg of Fe3+ per liter. Cultures grown at pH 7.4 produced H2 at the same initial rates as cultures that were grown at pH 9.4; however, the latter cultures continued to produce H2 after CO2 deprivation. | [
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PMID:25623 | Regiospecific synthesis of isoapocodeine from 10,11-dimethoxyaporphine by using Cunninghamella elegans. | A preparative-scale regiospecific conversion of 10,11-dimethoxyaporphine to isoapocodeine was conducted with Cunninghamella elegans ATCC 9245. This biotransformation proceeded quantitatively in suspensions and was pH dependent. The influence of antioxidants on the conversion was studied. Attempts to preserve the activity of isolated C. elegans cells by a number of methods were unsuccessful. | Regiospecific synthesis of isoapocodeine from 10,11-dimethoxyaporphine by using Cunninghamella elegans. A preparative-scale regiospecific conversion of 10,11-dimethoxyaporphine to isoapocodeine was conducted with Cunninghamella elegans ATCC 9245. This biotransformation proceeded quantitatively in suspensions and was pH dependent. The influence of antioxidants on the conversion was studied. Attempts to preserve the activity of isolated C. elegans cells by a number of methods were unsuccessful. | [
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PMID:25624 | Immobilization of Aspergillus beta-glucosidase on chitosan. | beta-Glucosidase of Aspergillus phoenicis QM 329 was immobilized on chitosan, using the bifunctional agent glutaraldehyde. The most active preparation based on the amount of support contained a 1:2.5 enzyme-to-chitosan ratio (wt/wt). However, the specific activity of the bound enzyme decreased from 10 to 1% with increasing enzyme-to-chitosan ratio. Compared with free beta-glucosidase, the immobilized enzyme exhibited: (i) a similar pH optimum but more activity at lower pH values; (ii) improved thermal stability; (iii) a similar response to inhibition by glucose; and (iv) mass transfer limitations as reflected by higher apparent Km and lower energy of activation. | Immobilization of Aspergillus beta-glucosidase on chitosan. beta-Glucosidase of Aspergillus phoenicis QM 329 was immobilized on chitosan, using the bifunctional agent glutaraldehyde. The most active preparation based on the amount of support contained a 1:2.5 enzyme-to-chitosan ratio (wt/wt). However, the specific activity of the bound enzyme decreased from 10 to 1% with increasing enzyme-to-chitosan ratio. Compared with free beta-glucosidase, the immobilized enzyme exhibited: (i) a similar pH optimum but more activity at lower pH values; (ii) improved thermal stability; (iii) a similar response to inhibition by glucose; and (iv) mass transfer limitations as reflected by higher apparent Km and lower energy of activation. | [
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PMID:25625 | Physiology of L-asparaginase synthesis in recombinants of Escherichia coli A-1. | A mating between Escherichia coli 4318 (thi leu Las- Hfr) and E. coli A-1 (Met- Las+ F-) resulted in the formation of prototrophic recombinants having L-asparaginase activities at three distinct levels. The physiology of L-asparaginase synthesis in these recombinants is decribed. One class of recombinants produced significantly more L-asparaginase than E. coli A-1. L-Asparaginase synthesis in the recombinants was inhibited by the presence of dissolved oxygen in the medium and was transiently repressed by the presence of glucose in the same manner as that observed in the parental strains. L-Asparaginase activity was increased by the addition of oxalacetate as well as other members of the tricarboxylic acid cycle. | Physiology of L-asparaginase synthesis in recombinants of Escherichia coli A-1. A mating between Escherichia coli 4318 (thi leu Las- Hfr) and E. coli A-1 (Met- Las+ F-) resulted in the formation of prototrophic recombinants having L-asparaginase activities at three distinct levels. The physiology of L-asparaginase synthesis in these recombinants is decribed. One class of recombinants produced significantly more L-asparaginase than E. coli A-1. L-Asparaginase synthesis in the recombinants was inhibited by the presence of dissolved oxygen in the medium and was transiently repressed by the presence of glucose in the same manner as that observed in the parental strains. L-Asparaginase activity was increased by the addition of oxalacetate as well as other members of the tricarboxylic acid cycle. | [
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PMID:25626 | PR toxin production in different Penicillium roqueforti strains. | Different Penicillium roqueforti strains from the American Type Culture Collection were tested for the production of PR toxin. All four strains were able to produce the toxin on semisynthetic medium at 24 degrees C after certain periods of incubation. The yields were correlated with the pH of the medium. Timing of the harvest influenced both the yield and purification of the toxin. | PR toxin production in different Penicillium roqueforti strains. Different Penicillium roqueforti strains from the American Type Culture Collection were tested for the production of PR toxin. All four strains were able to produce the toxin on semisynthetic medium at 24 degrees C after certain periods of incubation. The yields were correlated with the pH of the medium. Timing of the harvest influenced both the yield and purification of the toxin. | [
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PMID:25628 | Endocrine studies in Fanconi's anaemia. Report of 4 cases. | Four boys with Fanconi's anaemia and growth hormone (GH) deficiency are reported. Case 1 had isolated GH deficiency and responded to HGH and to oxandrolone treatment. Case 2, his brother, had milder haematological and dysmorphic manifestations and maintained a low-normal growth rate without treatment in spite of laboratory evidence of GH deficiency. Case 3 had multiple hypothalamopituitary defects, including deficiencies of GH, ACTH, and gonadotrophins. Case 4 had isolated GH deficiency and responded moderately well to HGH treatment. 3 of the 4 patients had bilateral cryptorchidism, 2 with increased plasma gonadotrophins, indicating primary testicular failure. We conclude that GH deficiency, isolated or combined with other hypothalamopituitary defects, and primary testicular failure with cryptorchidism are frequent but not constant features of Fanconi's anaemia. | Endocrine studies in Fanconi's anaemia. Report of 4 cases. Four boys with Fanconi's anaemia and growth hormone (GH) deficiency are reported. Case 1 had isolated GH deficiency and responded to HGH and to oxandrolone treatment. Case 2, his brother, had milder haematological and dysmorphic manifestations and maintained a low-normal growth rate without treatment in spite of laboratory evidence of GH deficiency. Case 3 had multiple hypothalamopituitary defects, including deficiencies of GH, ACTH, and gonadotrophins. Case 4 had isolated GH deficiency and responded moderately well to HGH treatment. 3 of the 4 patients had bilateral cryptorchidism, 2 with increased plasma gonadotrophins, indicating primary testicular failure. We conclude that GH deficiency, isolated or combined with other hypothalamopituitary defects, and primary testicular failure with cryptorchidism are frequent but not constant features of Fanconi's anaemia. | [
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PMID:25629 | Luteinising hormone-releasing hormone nasal spray as therapy for undescended testicle. | Twenty-two prepubertal children with unilateral cryptorchidism were treated. None had undergone previous medical or surgical to modify the abnormal position of the testes, all of which were located inthe inguinal canal. Treatment was with luteinising hormone-releasing hormone (LH-RH) nasal spray given for 7 days. 9 boys insufflated 100 microgram LH-RH in each nostril 6 times per 24 hours (1200 microgram/24 h); the remaining 13 boys insufflated 500 microgram 12-hourly (1000 microgram/24 h). An LH-RH test (500 microgram IV) was carried out before and after therapy. Full descent of the testis into the scrotum was obtained in 7 out of the 22 cases; in a further 6 cases the testis moved down the inguinal canal. Basal values of luteinising hormone and follicle-stimulating hormone and those for pituitary reserve remained unchanged before and after therapy, and were similar to the values of a control group. No correlation was found between response to therapy and bone age, testosterone level in serum, basal values or pituitary reserve of luteinising hormone or follicle-stimulating hormone. | Luteinising hormone-releasing hormone nasal spray as therapy for undescended testicle. Twenty-two prepubertal children with unilateral cryptorchidism were treated. None had undergone previous medical or surgical to modify the abnormal position of the testes, all of which were located inthe inguinal canal. Treatment was with luteinising hormone-releasing hormone (LH-RH) nasal spray given for 7 days. 9 boys insufflated 100 microgram LH-RH in each nostril 6 times per 24 hours (1200 microgram/24 h); the remaining 13 boys insufflated 500 microgram 12-hourly (1000 microgram/24 h). An LH-RH test (500 microgram IV) was carried out before and after therapy. Full descent of the testis into the scrotum was obtained in 7 out of the 22 cases; in a further 6 cases the testis moved down the inguinal canal. Basal values of luteinising hormone and follicle-stimulating hormone and those for pituitary reserve remained unchanged before and after therapy, and were similar to the values of a control group. No correlation was found between response to therapy and bone age, testosterone level in serum, basal values or pituitary reserve of luteinising hormone or follicle-stimulating hormone. | [
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PMID:25631 | Acute response to acid-base stress. | A method previously established in the experimental animal for predicting the acute response to either metabolic stress (bicarbonate administration) or respiratory stress(manipulation of oxygenator gas during cardiopulmonary bypass) has been extended to man. The method is based on a single nomogram. The accuracy of the nomogram is demonstrated using data from 13 patients on cardiopulmonary bypass. Similar agreement obtains between the nomogram and data reported by others. The nomogram can be used to estimate the therapeutically required dose of bicarbonate. | Acute response to acid-base stress. A method previously established in the experimental animal for predicting the acute response to either metabolic stress (bicarbonate administration) or respiratory stress(manipulation of oxygenator gas during cardiopulmonary bypass) has been extended to man. The method is based on a single nomogram. The accuracy of the nomogram is demonstrated using data from 13 patients on cardiopulmonary bypass. Similar agreement obtains between the nomogram and data reported by others. The nomogram can be used to estimate the therapeutically required dose of bicarbonate. | [
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PMID:25632 | Renal concentration gradients of salicylic acid and its metabolic congeners in the dog. | Salicylic acid and its principal metabolic product, salicyluric acid, are ultrafiltered at the glomeruli, secreted by the proximal segment and undergo back diffusion; the net effect being an accumulation of salicylates in the cortex. The back diffusion of salicylate is pH-sensitive (salicylurate is not) and its secretion is less sensitive than that of salicylurate to depression by probenecid. There was an increasing concentration gradient of these salicylates from outer cortex to innermost medulla. The clearance of salicyluric acid exceeded glomerular filtration rate even at very low urine flow and was not pH-dependent, so that total salicylate accumulation in the medulla was less affected by adjustment of urinary pH. Increasing perfusion of the nephron markedly reduced the inner medulla/cortical concentration ratios and segmental concentrations of salt and urea and reduced the cortical concentrations of salicylates. Diuresis may decrease the medullary concentration of salicylates, depending on the rate and duration of increased urine flow. | Renal concentration gradients of salicylic acid and its metabolic congeners in the dog. Salicylic acid and its principal metabolic product, salicyluric acid, are ultrafiltered at the glomeruli, secreted by the proximal segment and undergo back diffusion; the net effect being an accumulation of salicylates in the cortex. The back diffusion of salicylate is pH-sensitive (salicylurate is not) and its secretion is less sensitive than that of salicylurate to depression by probenecid. There was an increasing concentration gradient of these salicylates from outer cortex to innermost medulla. The clearance of salicyluric acid exceeded glomerular filtration rate even at very low urine flow and was not pH-dependent, so that total salicylate accumulation in the medulla was less affected by adjustment of urinary pH. Increasing perfusion of the nephron markedly reduced the inner medulla/cortical concentration ratios and segmental concentrations of salt and urea and reduced the cortical concentrations of salicylates. Diuresis may decrease the medullary concentration of salicylates, depending on the rate and duration of increased urine flow. | [
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PMID:25633 | Effects of l-penbutolol (Hoe 893d) on the transmembrane potentials of canine purkinje fibers and ventricular muscle fibers. | Intrinsic membrane effects (non-specific effects) and beta-adrenergic blocking action (specific effects) of l-penbutolol were studied using intracellular microelectrode techniques. l-Penbutolol in concentrations above 0.1 mg/L reduced the maximum rate of depolarization at phase O of both Purkinje fibers and ventricular muscle fibers without affecting their maximum diastolic potential. The action potential duration of Purkinje fibers were also shortened. The shortening of action potential duration and enhancement of automaticity in Purkinje fibers, normally induced by isoproterenol (0.2 mg/L), were antagonized by l-penbutolol in much lower concentraions (0.1--1.0 microgram/L) than those at which nonspecific effects are observed. The difference between these two concentration ranges is sufficient to suggest that l-penbutolol might be a highly specific beta-adrenergic blocking agent. | Effects of l-penbutolol (Hoe 893d) on the transmembrane potentials of canine purkinje fibers and ventricular muscle fibers. Intrinsic membrane effects (non-specific effects) and beta-adrenergic blocking action (specific effects) of l-penbutolol were studied using intracellular microelectrode techniques. l-Penbutolol in concentrations above 0.1 mg/L reduced the maximum rate of depolarization at phase O of both Purkinje fibers and ventricular muscle fibers without affecting their maximum diastolic potential. The action potential duration of Purkinje fibers were also shortened. The shortening of action potential duration and enhancement of automaticity in Purkinje fibers, normally induced by isoproterenol (0.2 mg/L), were antagonized by l-penbutolol in much lower concentraions (0.1--1.0 microgram/L) than those at which nonspecific effects are observed. The difference between these two concentration ranges is sufficient to suggest that l-penbutolol might be a highly specific beta-adrenergic blocking agent. | [
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PMID:25634 | Inhibition of experimental immediate hypersensitivity reactions by a novel xanthone, RU 31156. | RU 31156, the tris-(hydroxymethyl)-aminomethane salt of 7-(S-methylsulphonimidoyl)-5-(n-hexyl)-xanthen-9-one-2-carboxylic acid has been found to be a potent inhibitor of experimental immediate hypersensitivity reactions in vivo. In the IgE-mediated rat PCA test, RU 31156 had an ED50 of 0.0046 (00037--0.0057) mg/kg which compared to a figure of 1.21 (1.04--1.42) mg/kg for disocium cromoglycate (DSCG), both compounds being administered intravenously. RU 31156 was also active when administered orally, having an ED50 of 0.19 (0.07--0.30) mg/kg when given 10 min before antigen. RU 31156 partially inhibited an IgG-mediated PCA reaction in the rat. Both RU 31156 and DSCG inhibited anaphylactic bronchoconstriction in the rat, giving bell-shaped dose-response curves. From the upward part of the curves, approximate ED30 values of 0.02 and 2.0 mg/kg were obtained for RU 31156 AND DSCG respectively. Anaphylactic bronchoconstriction in the guinea-pig was not affected by RU 31156 and pinnal anaphylaxis was inhibited at only relatively high doses of 1--10 mg/kg i.v. The effects of both histamine and 5-hydroxytryptamine in the mouse pinna were not affected by RU 31156. In PCA experiments, RU 31156 showed self-tachyphylaxis following both intravenous and oral administration. It also showed cross-tachyphylaxis with DSCG, indicating that these compounds are likely to share a similar mode of action. | Inhibition of experimental immediate hypersensitivity reactions by a novel xanthone, RU 31156. RU 31156, the tris-(hydroxymethyl)-aminomethane salt of 7-(S-methylsulphonimidoyl)-5-(n-hexyl)-xanthen-9-one-2-carboxylic acid has been found to be a potent inhibitor of experimental immediate hypersensitivity reactions in vivo. In the IgE-mediated rat PCA test, RU 31156 had an ED50 of 0.0046 (00037--0.0057) mg/kg which compared to a figure of 1.21 (1.04--1.42) mg/kg for disocium cromoglycate (DSCG), both compounds being administered intravenously. RU 31156 was also active when administered orally, having an ED50 of 0.19 (0.07--0.30) mg/kg when given 10 min before antigen. RU 31156 partially inhibited an IgG-mediated PCA reaction in the rat. Both RU 31156 and DSCG inhibited anaphylactic bronchoconstriction in the rat, giving bell-shaped dose-response curves. From the upward part of the curves, approximate ED30 values of 0.02 and 2.0 mg/kg were obtained for RU 31156 AND DSCG respectively. Anaphylactic bronchoconstriction in the guinea-pig was not affected by RU 31156 and pinnal anaphylaxis was inhibited at only relatively high doses of 1--10 mg/kg i.v. The effects of both histamine and 5-hydroxytryptamine in the mouse pinna were not affected by RU 31156. In PCA experiments, RU 31156 showed self-tachyphylaxis following both intravenous and oral administration. It also showed cross-tachyphylaxis with DSCG, indicating that these compounds are likely to share a similar mode of action. | [
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PMID:25635 | Acute nephritis and pulmonary alveolitis following pneumococcal pneumonia. | Acute glomerulonephritis developed in a man with pneumococcal pneumonia. Serum complement studies revealed decreased levels of C4, properdin, and C3. Renal immunofluorescence studies demonstrated pneumococcal antigen, C1q, C4, C3 proactivator, properdin, C3, IgG, and IgM. Circulating cryoglobulin contained pneumococcal antigen and antibody, C3, and immunoglobulins. Serial pneumococcal antigen and antibody levels did not display patterns that were characteristic of classical immune elimination, but the patterns may have been influenced by the reentry of antigen. A diffuse, pulmonary alveolitis also developed in the patient. Lung immunofluorescence studies revealed pneumococcal antigen, IgG, and C3 in alveolar walls and capillary basement membranes. The glomerulonephritis and alveolitis resolved after a prolonged course. These findings provide presumptive evidence for pneumococcal, immune complex glomerulonephritis with complement activation via both classical and alternative pathways and suggest an immunologic pathogenesis for the pulmonary alveolitis. | Acute nephritis and pulmonary alveolitis following pneumococcal pneumonia. Acute glomerulonephritis developed in a man with pneumococcal pneumonia. Serum complement studies revealed decreased levels of C4, properdin, and C3. Renal immunofluorescence studies demonstrated pneumococcal antigen, C1q, C4, C3 proactivator, properdin, C3, IgG, and IgM. Circulating cryoglobulin contained pneumococcal antigen and antibody, C3, and immunoglobulins. Serial pneumococcal antigen and antibody levels did not display patterns that were characteristic of classical immune elimination, but the patterns may have been influenced by the reentry of antigen. A diffuse, pulmonary alveolitis also developed in the patient. Lung immunofluorescence studies revealed pneumococcal antigen, IgG, and C3 in alveolar walls and capillary basement membranes. The glomerulonephritis and alveolitis resolved after a prolonged course. These findings provide presumptive evidence for pneumococcal, immune complex glomerulonephritis with complement activation via both classical and alternative pathways and suggest an immunologic pathogenesis for the pulmonary alveolitis. | [
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PMID:25636 | Effects of host aging, ions, and pH on the adsorption of the cyanovirus N-1 to Nostoc muscorum. | The adsorption rate of the cyanovirus N-1 infecting the nitrogen-fixing blue-green alga Nostocmuscorum decreased with aging of algal cultures and the virus failed to adsorb to the dead host cells. The adsorption rate declined in saline magnesium chloride solution compared to that in algal growth medium. The addition of amino acids like L-tryptophan and L-phenylalanine failed to enhance the adsorption rate of the virus. Optimal pH of adsorption was 7.6 to 8;1. | Effects of host aging, ions, and pH on the adsorption of the cyanovirus N-1 to Nostoc muscorum. The adsorption rate of the cyanovirus N-1 infecting the nitrogen-fixing blue-green alga Nostocmuscorum decreased with aging of algal cultures and the virus failed to adsorb to the dead host cells. The adsorption rate declined in saline magnesium chloride solution compared to that in algal growth medium. The addition of amino acids like L-tryptophan and L-phenylalanine failed to enhance the adsorption rate of the virus. Optimal pH of adsorption was 7.6 to 8;1. | [
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PMID:25639 | A comparative study of five commercial reagents for the Coulter Model S: a proposed method for reagent evaluation. | A comparative study of five competitive commercial reagents for the Coulter Model S was performed jointly by two large, busy hospital laboratories with active quality control programs. Both laboratories, independently using the same reagent systems, studied 20 consecutive blood samples from patients from their own respective hospital for 20 days. Data from both laboratories were analyzed by standard and nonstandard statistical methods, and the results from both laboratories were compared. Although all reagent systems performed reasonably well in a clinical setting, highly significant statistical differences in their precisions were demonstrated by using univariate and multivariate techniques. The statistical method developed in this study can be applied to other systematic investigations that compare reagent systems. | A comparative study of five commercial reagents for the Coulter Model S: a proposed method for reagent evaluation. A comparative study of five competitive commercial reagents for the Coulter Model S was performed jointly by two large, busy hospital laboratories with active quality control programs. Both laboratories, independently using the same reagent systems, studied 20 consecutive blood samples from patients from their own respective hospital for 20 days. Data from both laboratories were analyzed by standard and nonstandard statistical methods, and the results from both laboratories were compared. Although all reagent systems performed reasonably well in a clinical setting, highly significant statistical differences in their precisions were demonstrated by using univariate and multivariate techniques. The statistical method developed in this study can be applied to other systematic investigations that compare reagent systems. | [
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PMID:25642 | Acidification of rat colon with lactulose. Its effects on the healing of colonic anastomoses. | Preoperative preparation of rats with lactulose, 2.5 ml/kg of a 52.5% w/w solution, for two days resulted in increased bursting pressure and bursting wall tension of low colonic anastomoses three days postoperatively when compared with unprepared controls (85.8, viz, 36.1 mm Hg and 0.55, viz, 0.19 dynes/cm X 10(-5). After seven days, there was no appreciable difference in the rats with colonic acidification and in the controls. | Acidification of rat colon with lactulose. Its effects on the healing of colonic anastomoses. Preoperative preparation of rats with lactulose, 2.5 ml/kg of a 52.5% w/w solution, for two days resulted in increased bursting pressure and bursting wall tension of low colonic anastomoses three days postoperatively when compared with unprepared controls (85.8, viz, 36.1 mm Hg and 0.55, viz, 0.19 dynes/cm X 10(-5). After seven days, there was no appreciable difference in the rats with colonic acidification and in the controls. | [
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PMID:25644 | Instability of the bovine MOR-2AB (mitochondrial malate: NAD oxidoreductase) heterodimeric molecule of heterozygous subjects after isoelectric focusing. | The heterodimeric molecule which is characteristic of animals heterozygous for the MOR-2 polymorphism and which is readily seen on enzymograms after electrophoresis is reported to be absent from zymograms performed after isoelectric focusing. A possible explanation is presented based on monomer--dimer equilibrium at pH 8.0--8.5. | Instability of the bovine MOR-2AB (mitochondrial malate: NAD oxidoreductase) heterodimeric molecule of heterozygous subjects after isoelectric focusing. The heterodimeric molecule which is characteristic of animals heterozygous for the MOR-2 polymorphism and which is readily seen on enzymograms after electrophoresis is reported to be absent from zymograms performed after isoelectric focusing. A possible explanation is presented based on monomer--dimer equilibrium at pH 8.0--8.5. | [
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PMID:25645 | Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1c) from wild mice. | We have found a new allele at the structural locus for glucosephosphate isomerase (called Gpi-1c) in a population of wild mice. The Gpi-1c allele codes for an enzyme of greater cathodal electrophoretic mobility than either the Gpi-1a or Gpi-1b alleles found in the wild and in the SM/J and C57BL/6J inbred strains. Mice homozygous for Gpi-1c have erythrocyte enzyme activity reduced to 33% of normal levels, altered pH profile, lowered heat stability, and normal Km's when compared with SM/J and C57BL/6J mice. The activity of the enzyme in brain, liver, and kidney is not so markedly lowered, although the electrophoretic mobility, pH profile, and heat stability are altered in these tissues. Deficiencies of erythrocyte glucosephosphate isomerase in man, to this level, can cause severe hemolytic anemia. Homozygotes for Gpi-1c show only mild hematological symptoms. The frequency of Gpi-1c in wild populations of mice is discussed and the occurrence of a further rare allele Gpi-1d is reported. | Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1c) from wild mice. We have found a new allele at the structural locus for glucosephosphate isomerase (called Gpi-1c) in a population of wild mice. The Gpi-1c allele codes for an enzyme of greater cathodal electrophoretic mobility than either the Gpi-1a or Gpi-1b alleles found in the wild and in the SM/J and C57BL/6J inbred strains. Mice homozygous for Gpi-1c have erythrocyte enzyme activity reduced to 33% of normal levels, altered pH profile, lowered heat stability, and normal Km's when compared with SM/J and C57BL/6J mice. The activity of the enzyme in brain, liver, and kidney is not so markedly lowered, although the electrophoretic mobility, pH profile, and heat stability are altered in these tissues. Deficiencies of erythrocyte glucosephosphate isomerase in man, to this level, can cause severe hemolytic anemia. Homozygotes for Gpi-1c show only mild hematological symptoms. The frequency of Gpi-1c in wild populations of mice is discussed and the occurrence of a further rare allele Gpi-1d is reported. | [
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