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PMID:16065 | Purification and immunochemical characterization of the outer membrane complex of Bacteroides melaninogenicus subspecies asaccharolyticus. | Morphologic study of Bacteroides melaninogenicus subspecies asaccharolyticus by electron microscopy disclosed the presence of a capsule and a cell wall structure otherwise typical of a gram-negative organism. An outer membrane complex was isolated with use of gentle methods. Relative purity of the preparation was confirmed by electron microscopy and by the formation of a single band in a sucrose density gradient. Gel chromatography was used for separation of the major components of the membrane. Antigenicity of the first component, a protein-polysaccharide complex, which cross-reacted with antiserum to another strain of the same subspecies. This component probably represents the capsular antigen and may prove to be the basis for serogrouping. The second membrane fraction differed chemically from the first fraction and represents the lipopolysaccharide component of the outer membrane. Notably, this component lacks 2-keto-3-deoxyoctonate, one of the backbone sugars of aerobic, gram-negative lipopolysaccharides. | Purification and immunochemical characterization of the outer membrane complex of Bacteroides melaninogenicus subspecies asaccharolyticus. Morphologic study of Bacteroides melaninogenicus subspecies asaccharolyticus by electron microscopy disclosed the presence of a capsule and a cell wall structure otherwise typical of a gram-negative organism. An outer membrane complex was isolated with use of gentle methods. Relative purity of the preparation was confirmed by electron microscopy and by the formation of a single band in a sucrose density gradient. Gel chromatography was used for separation of the major components of the membrane. Antigenicity of the first component, a protein-polysaccharide complex, which cross-reacted with antiserum to another strain of the same subspecies. This component probably represents the capsular antigen and may prove to be the basis for serogrouping. The second membrane fraction differed chemically from the first fraction and represents the lipopolysaccharide component of the outer membrane. Notably, this component lacks 2-keto-3-deoxyoctonate, one of the backbone sugars of aerobic, gram-negative lipopolysaccharides. | [
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|
PMID:16068 | A simple method for the separate measurement of transcobalamins I, II, and III: normal ranges in serum and plasma in men and women. | A simple method for the separate measurement of the unsaturated binding capacity of the three main circulating vitamin B12 binders, transcobalamins (TCs) I, II, and III, is described. The method involves batch separation of TC I and III from TC II by means of Quso G32, followed by batch separation of TC I from TC II with the use of diethylaminoethyl. The present study provides the first complete comparison of unsaturated TC I, II, and III in serum versus fluoridinated plasma of a single group of normal men versus women. There are consistently higher values in serum, largely due to an in vitro increment of TC III, prevented by NaF. The results are compared with values for some of these parameters obtained by others with the use of different methods, providing a standard for evaluating significance of results by various methods. | A simple method for the separate measurement of transcobalamins I, II, and III: normal ranges in serum and plasma in men and women. A simple method for the separate measurement of the unsaturated binding capacity of the three main circulating vitamin B12 binders, transcobalamins (TCs) I, II, and III, is described. The method involves batch separation of TC I and III from TC II by means of Quso G32, followed by batch separation of TC I from TC II with the use of diethylaminoethyl. The present study provides the first complete comparison of unsaturated TC I, II, and III in serum versus fluoridinated plasma of a single group of normal men versus women. There are consistently higher values in serum, largely due to an in vitro increment of TC III, prevented by NaF. The results are compared with values for some of these parameters obtained by others with the use of different methods, providing a standard for evaluating significance of results by various methods. | [
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|
PMID:16069 | Mechanism by which neutral phosphate infusion elevates urine PCO2. | Currently, the ability to elevate the urine PCO2 above that of the arterial blood is employed as an estimate of distal hydrogen ion secretion. Therefore, it is important to establish the mechanisms by which various factors affect the urine CO2 tension. This paper examines the physiologic process by which phosphate elevates the urine PCO2 in the dog. The rise in urine PCO2 due to phosphate could be the result of either (1) a distal mechanism, by affecting the delayed dehydration of carbonic acid, or (2) an increase in the medullary PCO2. The phosphate-induced elevation of urine PCO2 was abolished by carbonic anhydrase infusion. This indicates that a distal mechanism is a major factor in the phosphate effect. Since acid phosphate infusion did not result in an elevated urine PCO2, it is unlikely that changes in the medullary PCO2 occur as a ry an increase in net acid excretion, indicating an increase in hydrogen ion secretion. The increased hydrogen ion secretion and rise in urine PCO2 were reproduced by infusion of the buffer, Tris-(hydroxymethyl)-aminomethane, but not by sodium sulfate administration. These findings suggest that the phosphate-induced rise in urine PCO2 is due to the buffer properties of phosphate rather than to its nonreabsorable anion characteristics. | Mechanism by which neutral phosphate infusion elevates urine PCO2. Currently, the ability to elevate the urine PCO2 above that of the arterial blood is employed as an estimate of distal hydrogen ion secretion. Therefore, it is important to establish the mechanisms by which various factors affect the urine CO2 tension. This paper examines the physiologic process by which phosphate elevates the urine PCO2 in the dog. The rise in urine PCO2 due to phosphate could be the result of either (1) a distal mechanism, by affecting the delayed dehydration of carbonic acid, or (2) an increase in the medullary PCO2. The phosphate-induced elevation of urine PCO2 was abolished by carbonic anhydrase infusion. This indicates that a distal mechanism is a major factor in the phosphate effect. Since acid phosphate infusion did not result in an elevated urine PCO2, it is unlikely that changes in the medullary PCO2 occur as a ry an increase in net acid excretion, indicating an increase in hydrogen ion secretion. The increased hydrogen ion secretion and rise in urine PCO2 were reproduced by infusion of the buffer, Tris-(hydroxymethyl)-aminomethane, but not by sodium sulfate administration. These findings suggest that the phosphate-induced rise in urine PCO2 is due to the buffer properties of phosphate rather than to its nonreabsorable anion characteristics. | [
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PMID:16070 | Kinetics of the cyanate-hemoglobin reaction in whole blood. | The kinetics of the cyanate-hemoglobin reaction in normal whole blood have been investigated. The mechanism was found to be second order, irreversible, bimolecular. The influence of the temperature, pH, Po2, and Pco2 on the reaction rate constant was examined. A temperature change from 37 degrees to 42 degrees C, resulted in a 50 percent increase in the rate constant. The rate constant increased in proportion to the pH decrease, and deoxygenated whole blood was carbamylated approximately twice as fast as oxygenated blood. Carbon dioxide pressures had no influence on rates of carbamylation when a constant pH was maintained. A maximum rate constant of 3.7 M-U min.-u was obtained with conditions which were compatible with the red blood cells. This knowledge of the reaction mechanism and the influence of important system parameters on the reaction rate constant may be applied to the development of an extracorporeal system for the treatment of sickle cell anemia. | Kinetics of the cyanate-hemoglobin reaction in whole blood. The kinetics of the cyanate-hemoglobin reaction in normal whole blood have been investigated. The mechanism was found to be second order, irreversible, bimolecular. The influence of the temperature, pH, Po2, and Pco2 on the reaction rate constant was examined. A temperature change from 37 degrees to 42 degrees C, resulted in a 50 percent increase in the rate constant. The rate constant increased in proportion to the pH decrease, and deoxygenated whole blood was carbamylated approximately twice as fast as oxygenated blood. Carbon dioxide pressures had no influence on rates of carbamylation when a constant pH was maintained. A maximum rate constant of 3.7 M-U min.-u was obtained with conditions which were compatible with the red blood cells. This knowledge of the reaction mechanism and the influence of important system parameters on the reaction rate constant may be applied to the development of an extracorporeal system for the treatment of sickle cell anemia. | [
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PMID:16071 | Use of a competitive protein-binding assay for adenosine 3':5'-phosphate for the study of bovine corpus luteum adenylate cyclase. | The use of a competitive protein-binding assay for cyclic AMP, utilizing the binding protein purified from bovine adrenal cortex, for the study of adenylate cyclase activity of the washed 600 g sediment of bovine corpus luteum is validated. A specific assay for cyclic AMP could only be achieved by removal of the degradation products of ATP on a precipitate of nascent BaSO4. Simple dilution of the sample before assay was not sufficient to eliminate interference from degradation products of ATP. An observed variability in optimal ATP substrate and tissue concentrations is though to reflect variability in the enzymic profile of the cyclic corpus luteum. Optima with respect to F-, Mg2+ and pH are more clearly defined and are similar to those reported for adenylate cyclase systems for other tissues. | Use of a competitive protein-binding assay for adenosine 3':5'-phosphate for the study of bovine corpus luteum adenylate cyclase. The use of a competitive protein-binding assay for cyclic AMP, utilizing the binding protein purified from bovine adrenal cortex, for the study of adenylate cyclase activity of the washed 600 g sediment of bovine corpus luteum is validated. A specific assay for cyclic AMP could only be achieved by removal of the degradation products of ATP on a precipitate of nascent BaSO4. Simple dilution of the sample before assay was not sufficient to eliminate interference from degradation products of ATP. An observed variability in optimal ATP substrate and tissue concentrations is though to reflect variability in the enzymic profile of the cyclic corpus luteum. Optima with respect to F-, Mg2+ and pH are more clearly defined and are similar to those reported for adenylate cyclase systems for other tissues. | [
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|
PMID:16072 | Expression of endogenous murine leukemia viruses during the course of a protracted immunological disorder. | Mice of the low leukemia (BALB/cJ x A/J)F1 hybrid (CAF1) strain express B-and N-tropic infectious murine leukemia virus (MuLV) after the age of 6 mo. Initation of a protracted immunological disorder, the graft-versus-host reaction (GVHR), at 7 wk of age, accelerates the induction of both these mouse-tropic endogenous viruses, and preferentially enhances the replication of B-tropic MuLV. The earlier appearance of B-tropic MuLV in a greater proportion of mice and in higher titer is thought to be casually related to the eventual development of lymphoreticular tumors in the GVHR mice, since previous studies have shown that these same tumors can be reproduced by inoculating syngeneic recipients with serially passaged GVHR extracts containing B-tropic MuLV. | Expression of endogenous murine leukemia viruses during the course of a protracted immunological disorder. Mice of the low leukemia (BALB/cJ x A/J)F1 hybrid (CAF1) strain express B-and N-tropic infectious murine leukemia virus (MuLV) after the age of 6 mo. Initation of a protracted immunological disorder, the graft-versus-host reaction (GVHR), at 7 wk of age, accelerates the induction of both these mouse-tropic endogenous viruses, and preferentially enhances the replication of B-tropic MuLV. The earlier appearance of B-tropic MuLV in a greater proportion of mice and in higher titer is thought to be casually related to the eventual development of lymphoreticular tumors in the GVHR mice, since previous studies have shown that these same tumors can be reproduced by inoculating syngeneic recipients with serially passaged GVHR extracts containing B-tropic MuLV. | [
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|
PMID:16073 | The Ly phenotype of suppressor T cells arising in mice subjected to a graft-versus-host reaction. | T cells with helper and suppressor functions arising during graft-versus-host reaction (B6 vs. BDF1) have been characterized with respect to their Ly surface antigens. Helper cells were found to express the phenotype Ly 1+2- and suppressor cells the phenotype Ly 1+2+. Ly 1-2+ T cells had no suppressive effect in this system. T cells of the host did not contribute to either activity. | The Ly phenotype of suppressor T cells arising in mice subjected to a graft-versus-host reaction. T cells with helper and suppressor functions arising during graft-versus-host reaction (B6 vs. BDF1) have been characterized with respect to their Ly surface antigens. Helper cells were found to express the phenotype Ly 1+2- and suppressor cells the phenotype Ly 1+2+. Ly 1-2+ T cells had no suppressive effect in this system. T cells of the host did not contribute to either activity. | [
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|
PMID:16078 | The pH-dependent rate of action of local anesthetics on the node of Ranvier. | Local anesthetic solutions were applied suddenly to the outside of single myelinated nerve fibers to measure the time course of development of block of sodium channels. Sodium currents were measured under voltage clamp with test pulses applied several times per second during the solution change. The rate of block was studied by using drugs of different lipid solubility and of different charge type, and the external pH was varied from pH 8.3 to pH 6 to change the degree of ionization of the amine compounds. At pH 8.3 the half-time of action of amine anesthetics such as lidocaine, procaine, tetracaine, and others was always less than 2 s and usually less than 1 s. Lowering the pH to 6.0 decreased the apparent potency and slowed the rate of action of these drugs. The rate of action of neutral benzocaine was fast (1 s) and pH independent. The rate of action of cationic quaternary QX-572 was slow (greater than 200 s) and also pH independent. Other quaternary anesthetic derivatives showed no action when applied outside. The result is that neutral drug forms act much more rapidly than charged ones, suggesting that externally applied local anesthetics must cross a hydrophobic barrier to reach their receptor. A model representing diffusion of drug into the nerve fiber gives reasonable time courses of action and reasonable membrane permeability coefficients on the assumption that the hydrophobic barrier is the nodal membrane. Arguments are given that there may be a need for reinterpretation of many published experiments on the location of the anesthetic receptor and on which charge form of the drug is active to take into account the effects of unstirred layers, high membrane permeability, and high lipid solubility. | The pH-dependent rate of action of local anesthetics on the node of Ranvier. Local anesthetic solutions were applied suddenly to the outside of single myelinated nerve fibers to measure the time course of development of block of sodium channels. Sodium currents were measured under voltage clamp with test pulses applied several times per second during the solution change. The rate of block was studied by using drugs of different lipid solubility and of different charge type, and the external pH was varied from pH 8.3 to pH 6 to change the degree of ionization of the amine compounds. At pH 8.3 the half-time of action of amine anesthetics such as lidocaine, procaine, tetracaine, and others was always less than 2 s and usually less than 1 s. Lowering the pH to 6.0 decreased the apparent potency and slowed the rate of action of these drugs. The rate of action of neutral benzocaine was fast (1 s) and pH independent. The rate of action of cationic quaternary QX-572 was slow (greater than 200 s) and also pH independent. Other quaternary anesthetic derivatives showed no action when applied outside. The result is that neutral drug forms act much more rapidly than charged ones, suggesting that externally applied local anesthetics must cross a hydrophobic barrier to reach their receptor. A model representing diffusion of drug into the nerve fiber gives reasonable time courses of action and reasonable membrane permeability coefficients on the assumption that the hydrophobic barrier is the nodal membrane. Arguments are given that there may be a need for reinterpretation of many published experiments on the location of the anesthetic receptor and on which charge form of the drug is active to take into account the effects of unstirred layers, high membrane permeability, and high lipid solubility. | [
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PMID:16079 | Lack of a regulatory function for glutamine synthetase protein in the synthesis of glutamate dehydrogenase and nitrite reductase in Escherichia coli K12. | Synthesis of glutamine synthetase (GS) in anaerobic batch cultures of Escherichia coli was repressed when excess NH4+ was available, but derepressed during growth with a poor nitrogen source. In wild-type bacteria there was only a weak inverse correlation between the activities of GS and glutamate dehydrogenase (GDH) during growth in various media. No positive correlations were found between the activities of GS and nitrite reductase, or between GS and cytochrome c552: both of these proteins were synthesized normally by mutants that contained no active GS. Although activities of GS and GDH were low in two mutants that are unable to synthesize cytochrome c552 or reduce nitrite because of defects in the nirA gene, the nirA defect was separated from the GS and GDH defects by transduction with bacteriophage P1. Attempts to show that catabolite repression of proline oxidase synthesis could be relieved during NH4+ starvation also failed. It is, therefore, unlikely that nitrite reduction or proline oxidation by E. coli are under positive control by GS protein. The regulation of the synthesis of enzymes for the utilization of secondary nitrogen sources in E. coli, therefore, different from that in Klebsiella aerogenes, but is similar to that in Salmonella typhimurium. | Lack of a regulatory function for glutamine synthetase protein in the synthesis of glutamate dehydrogenase and nitrite reductase in Escherichia coli K12. Synthesis of glutamine synthetase (GS) in anaerobic batch cultures of Escherichia coli was repressed when excess NH4+ was available, but derepressed during growth with a poor nitrogen source. In wild-type bacteria there was only a weak inverse correlation between the activities of GS and glutamate dehydrogenase (GDH) during growth in various media. No positive correlations were found between the activities of GS and nitrite reductase, or between GS and cytochrome c552: both of these proteins were synthesized normally by mutants that contained no active GS. Although activities of GS and GDH were low in two mutants that are unable to synthesize cytochrome c552 or reduce nitrite because of defects in the nirA gene, the nirA defect was separated from the GS and GDH defects by transduction with bacteriophage P1. Attempts to show that catabolite repression of proline oxidase synthesis could be relieved during NH4+ starvation also failed. It is, therefore, unlikely that nitrite reduction or proline oxidation by E. coli are under positive control by GS protein. The regulation of the synthesis of enzymes for the utilization of secondary nitrogen sources in E. coli, therefore, different from that in Klebsiella aerogenes, but is similar to that in Salmonella typhimurium. | [
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PMID:16080 | Evaluation of the role of methional, 2-keto-4-methylthiobutyric acid and peroxidase in ethylene formation by Escherichia coli. | During growth of Escherichia coli strain SPA O in the presence of methionine, an intermediate accumulates in the medium. This intermediate reacts with 2,4-dinitrophenylhydrazine, and can be degraded to ethylene either enzymically or photochemically, the latter being stimulated by the addition of a flavin. The pH optimum for the photochemical degradation of this intermediate and 2-keto-4-methylthiobutyric acid (KMBA) is pH 3 whereas the optimum for methional is pH 6. The enzyme which converts the intermediate to ethylene also converts KMBA to ethylene and has many of the properties of a peroxidase including inhibition by catalase, cyanide, azide and anaerobiosis. The enzyme which synthesizes the intermediate is not known but requires oxygen and pyridoxal phosphate. A pathway for ethylene biosynthesis is proposed in which methionine is converted to KMBA which can be degraded either by peroxidase or in a flavin-mediated photochemical reaction. Its relevance to the properties of other ethylene-producing bacteria and to the proposed pathway of ethylene release by higher plants is discussed. | Evaluation of the role of methional, 2-keto-4-methylthiobutyric acid and peroxidase in ethylene formation by Escherichia coli. During growth of Escherichia coli strain SPA O in the presence of methionine, an intermediate accumulates in the medium. This intermediate reacts with 2,4-dinitrophenylhydrazine, and can be degraded to ethylene either enzymically or photochemically, the latter being stimulated by the addition of a flavin. The pH optimum for the photochemical degradation of this intermediate and 2-keto-4-methylthiobutyric acid (KMBA) is pH 3 whereas the optimum for methional is pH 6. The enzyme which converts the intermediate to ethylene also converts KMBA to ethylene and has many of the properties of a peroxidase including inhibition by catalase, cyanide, azide and anaerobiosis. The enzyme which synthesizes the intermediate is not known but requires oxygen and pyridoxal phosphate. A pathway for ethylene biosynthesis is proposed in which methionine is converted to KMBA which can be degraded either by peroxidase or in a flavin-mediated photochemical reaction. Its relevance to the properties of other ethylene-producing bacteria and to the proposed pathway of ethylene release by higher plants is discussed. | [
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PMID:16081 | Effect of chaotropic salts and protein denaturants on the thermal stability of mouse fibroblast interferon. | Altering the aqueous environment, especially with agents that affect hydrogen bonds, markedly affects the stability of mouse L cell interferon. Low pH stabilizes interferon whereas high pH labilizes it; heavy water further enhances interferon thermostability at pH 2 but not at pH 9. Exposure to the protein denaturants, 4 M-guanidine hydrochloride and 6 M-urea, significantly decreases the activity of interferon at pH 2 and pH9; however, the residual interferon activity is relatively thermostable. Certain chaotropic salts protect interferon against thermal destruction, and in terms of effectiveness, their sequence is in the order SCN- greater than 1- larger than or equal to Cl- = CiO4- - Br- greater than NO3-. Interferon becomes more stable to heat as the NaSCN concentration is increased from 0-25 M to 2-0 M. Molecular sieve chromatography of interferon in the presence of 1-5 M-NaSCN at pH 7 shows a shift in its apparent mol. wt. from 25000 to 42000. Unlike most proteins, the unfolded conformation of interferon appears to be more stable to heat than the molecule with a smaller Stokes' radius. | Effect of chaotropic salts and protein denaturants on the thermal stability of mouse fibroblast interferon. Altering the aqueous environment, especially with agents that affect hydrogen bonds, markedly affects the stability of mouse L cell interferon. Low pH stabilizes interferon whereas high pH labilizes it; heavy water further enhances interferon thermostability at pH 2 but not at pH 9. Exposure to the protein denaturants, 4 M-guanidine hydrochloride and 6 M-urea, significantly decreases the activity of interferon at pH 2 and pH9; however, the residual interferon activity is relatively thermostable. Certain chaotropic salts protect interferon against thermal destruction, and in terms of effectiveness, their sequence is in the order SCN- greater than 1- larger than or equal to Cl- = CiO4- - Br- greater than NO3-. Interferon becomes more stable to heat as the NaSCN concentration is increased from 0-25 M to 2-0 M. Molecular sieve chromatography of interferon in the presence of 1-5 M-NaSCN at pH 7 shows a shift in its apparent mol. wt. from 25000 to 42000. Unlike most proteins, the unfolded conformation of interferon appears to be more stable to heat than the molecule with a smaller Stokes' radius. | [
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|
PMID:16082 | Changes in primary process expression in hospitalized schizophrenics treated with phenothiazines: two projective tasks compared. | It was hypothesized that primary process expression on Gottschalk's Five Minute Verbalization Task (FMV) would be more representative of clinical status in schizophrenia than primary process expression on the Rorschach. Ss were 21 males and 15 females, ages 19-41 years, newly admitted to the hospital and treated with phenothiazines. The FMV was administered at predrug, five weeks, and 13 weeks, and the Rorschach at predrug and five weeks. Primary process scoring was according to the Holt system. Clinical improvement was measured by the Lorr IMPS and the Burdock Ward Behavior Scale. Over time, Ss produced less primary process on the FMV (p less than .001), while on the Rorschach scores did not change significantly. The scores on the FMV but not on the Rorschach paralleled some measures of clinical improvement (p less than .05). In a factor analysis, scores on the FMV and Rorschach were related to specific but different symptoms. It was concluded that the FMV was more effective in determining clinical improvement, while the Rorschach was perhaps more valuable in assessing the nature of the primary process thinking. | Changes in primary process expression in hospitalized schizophrenics treated with phenothiazines: two projective tasks compared. It was hypothesized that primary process expression on Gottschalk's Five Minute Verbalization Task (FMV) would be more representative of clinical status in schizophrenia than primary process expression on the Rorschach. Ss were 21 males and 15 females, ages 19-41 years, newly admitted to the hospital and treated with phenothiazines. The FMV was administered at predrug, five weeks, and 13 weeks, and the Rorschach at predrug and five weeks. Primary process scoring was according to the Holt system. Clinical improvement was measured by the Lorr IMPS and the Burdock Ward Behavior Scale. Over time, Ss produced less primary process on the FMV (p less than .001), while on the Rorschach scores did not change significantly. The scores on the FMV but not on the Rorschach paralleled some measures of clinical improvement (p less than .05). In a factor analysis, scores on the FMV and Rorschach were related to specific but different symptoms. It was concluded that the FMV was more effective in determining clinical improvement, while the Rorschach was perhaps more valuable in assessing the nature of the primary process thinking. | [
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|
PMID:16083 | Effect of curare on responses to different putative neurotransmitters in Aplysia neurons. | We have studied the effects of curare on responses resulting from iontophoretic application of several putative neurotransmitters onto Aplysia neurons. These neurons have specific receptors for acetylcholine (ACh), dopamine, octopamine, phenylethanolamine, histamine, gamma-aminobutyric acid (GABA), aspartic acid, and glutamic acid. Each of these substances may on different specific neurons elicit at least three types of response, caused by a fast depolarizing Na+, a fast hyperpolarizing Cl-, or a slow hyperpolarizing K+ conductance increase. All responses resulting from either Na+ or Cl- conductance increases, irrespective of which putative transmitter activated the response, were sensitive to curare. Most were totally blocked by less than or equal to 10-4 M curare. GABA responses were less sensitive and were often only depressed by 10-3 M curare. K+ conductance responses, irrespective of the transmitter, were not curare sensitive. These results are consistent with a model of receptor organization in which one neurotransmitter receptor may be associated with any of at least three ionophores, mediating conductance increase responses to Na+, Cl-, and K+, respectively. In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na+ and Cl- responses. | Effect of curare on responses to different putative neurotransmitters in Aplysia neurons. We have studied the effects of curare on responses resulting from iontophoretic application of several putative neurotransmitters onto Aplysia neurons. These neurons have specific receptors for acetylcholine (ACh), dopamine, octopamine, phenylethanolamine, histamine, gamma-aminobutyric acid (GABA), aspartic acid, and glutamic acid. Each of these substances may on different specific neurons elicit at least three types of response, caused by a fast depolarizing Na+, a fast hyperpolarizing Cl-, or a slow hyperpolarizing K+ conductance increase. All responses resulting from either Na+ or Cl- conductance increases, irrespective of which putative transmitter activated the response, were sensitive to curare. Most were totally blocked by less than or equal to 10-4 M curare. GABA responses were less sensitive and were often only depressed by 10-3 M curare. K+ conductance responses, irrespective of the transmitter, were not curare sensitive. These results are consistent with a model of receptor organization in which one neurotransmitter receptor may be associated with any of at least three ionophores, mediating conductance increase responses to Na+, Cl-, and K+, respectively. In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na+ and Cl- responses. | [
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|
PMID:16091 | Role of the posterior hypothalamus in the development of acute brain swelling. | Destructive stereotaxic lesions were made in the posterior hypothalamus, unilaterally or bilaterally, in 26 dogs. In 21 dogs the intracranial pressure (ICP) was maintained in normal range, and in five dogs the ICP was artificially elevated to 300 to 400 mm h2o, preceding the procedures to the hypothlamus. Arterial oxygen and carbon dioxide pressure ((PaO2 and PaCO2) were maintained in the normal range. Before and after each procedure, systemic arterial pressure (SAP) was elevated by intravenous injection of norepinephrine (5 X 10(-3) mg/kg) to determined whether the ICP increases coincidentally with elevation of the systemic arterial pressure. The intracranial pressure/mean arterial pressure ratio of elevation by injection of norepinephrine was not significant regardless of the level of the ICP, or of uni-or bilateral lesions of the hypothalamus. The authors conclude that dysfunction of posterior hypothalamus does not play a specific role in the development of vasomotor paralysis leading to acute brain swelling, under conditons of normal or moderately raised ICP with normal PaCO2 and Pato2 levels. | Role of the posterior hypothalamus in the development of acute brain swelling. Destructive stereotaxic lesions were made in the posterior hypothalamus, unilaterally or bilaterally, in 26 dogs. In 21 dogs the intracranial pressure (ICP) was maintained in normal range, and in five dogs the ICP was artificially elevated to 300 to 400 mm h2o, preceding the procedures to the hypothlamus. Arterial oxygen and carbon dioxide pressure ((PaO2 and PaCO2) were maintained in the normal range. Before and after each procedure, systemic arterial pressure (SAP) was elevated by intravenous injection of norepinephrine (5 X 10(-3) mg/kg) to determined whether the ICP increases coincidentally with elevation of the systemic arterial pressure. The intracranial pressure/mean arterial pressure ratio of elevation by injection of norepinephrine was not significant regardless of the level of the ICP, or of uni-or bilateral lesions of the hypothalamus. The authors conclude that dysfunction of posterior hypothalamus does not play a specific role in the development of vasomotor paralysis leading to acute brain swelling, under conditons of normal or moderately raised ICP with normal PaCO2 and Pato2 levels. | [
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|
PMID:16092 | Studies on the labeling of streptokinase with 99mTc for use as a radiopharmaceutical in the detection of deep-vein thrombosis: concise communication. | Streptokinase was labeled with 99mTc using both stannous chloride and stannous pyrophosphate as reducing agents. Sixty to seventy-five percent of the 99m Tc was incorporated into streptokinase using stannous chloride as a reducing agent at pH 1-2, wheras 50-60% was incorporated using stannous pyrophosphate at neutral pH. Increasing the pH from 2 to 7 in the presence of stannous chloride caused the release of 15-20% of the protein-bound 99mTc. Incorporation of 99mTc into protein was relatively slow: labeling required 2-3 hr at room temperature. The concentration of stannous pyrophosphate required for optimum labeling varied between 10(-5) and 10(-2) M. Polyacrylamide-gel electrophoresis showed that the filler substance in commercial streptokinase was also labeled with 99mTc. However pure streptokinase gave a homogenous protein band after polyacrylamide-gel electrophoresis. This protein band coincided with the peak of streptokinase-bound 99mTc. The results obtained may partially explain why 99mTc-labeled streptokinase lacks the necessary specificity for the satisfactory location of blood clots in vivo. | Studies on the labeling of streptokinase with 99mTc for use as a radiopharmaceutical in the detection of deep-vein thrombosis: concise communication. Streptokinase was labeled with 99mTc using both stannous chloride and stannous pyrophosphate as reducing agents. Sixty to seventy-five percent of the 99m Tc was incorporated into streptokinase using stannous chloride as a reducing agent at pH 1-2, wheras 50-60% was incorporated using stannous pyrophosphate at neutral pH. Increasing the pH from 2 to 7 in the presence of stannous chloride caused the release of 15-20% of the protein-bound 99mTc. Incorporation of 99mTc into protein was relatively slow: labeling required 2-3 hr at room temperature. The concentration of stannous pyrophosphate required for optimum labeling varied between 10(-5) and 10(-2) M. Polyacrylamide-gel electrophoresis showed that the filler substance in commercial streptokinase was also labeled with 99mTc. However pure streptokinase gave a homogenous protein band after polyacrylamide-gel electrophoresis. This protein band coincided with the peak of streptokinase-bound 99mTc. The results obtained may partially explain why 99mTc-labeled streptokinase lacks the necessary specificity for the satisfactory location of blood clots in vivo. | [
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PMID:16099 | Integration of clinical and academic nursing at the hospital clinical unit level. | In a successful attempt to solve problems in Pediatric Nursing at the Medical University of South Carolina, a Department Chairman was named Director-Chairman of Pediatric Nursing and given operational authority over both clinical and academic nursing in Pediatrics. The results were more efficient administration, a higher quality of patient care and an enriched environment for student learning. | Integration of clinical and academic nursing at the hospital clinical unit level. In a successful attempt to solve problems in Pediatric Nursing at the Medical University of South Carolina, a Department Chairman was named Director-Chairman of Pediatric Nursing and given operational authority over both clinical and academic nursing in Pediatrics. The results were more efficient administration, a higher quality of patient care and an enriched environment for student learning. | [
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PMID:16100 | Effect of dietary DL-ethionine and/or DL-methionine on egg laying and activities of some cytoplasmic NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica. | The effect of dietary DL-ethionine and/or DL-methionine on egg laying, and activities of some NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica was investigated. A 0.30% DL-ethionine plus 0.30% DL-methionine supplemented diet reversed partially the egg laying inhibited by the diet with 0.30% DL-ethionine alone. No inhibitory effect on egg laying was observed for the diet supplemented with 0.30% DL-methionine alone. In marked contrast to the decreased activity of L-glycerol 3-phosphate dehydrogenase and malate dehydrogenase, significantly increased activity of lactate dehydrogenase was obtained for quail fed the DL-ethionine, and the DL-ethionine plus the DL-methionine supplemented diet, respectively. No marked changes in activities of these three dehydrogenases were obtained for quail fed the diet supplemented with DL-methionine alone. Although decreased activity was observed for all of the four NADPH-producing enzymes in quail fed the diet supplemented with DL-ethionine alone, the DL-ethionine plus DL-methionine, the smallest decrease was obtained for NADP-isocitrate dehydrogenase. The diet supplemented with DL-methionine alone induced markedly the respective activity of malic enzyme and glucose 6-phosphate dehydrogenase. These results indicate a relatively important function of NADP-isocitrate dehydrogenase for NADPH-production even under DL-ethionine toxicity and suggest complicated relationships between egg production and activities of enzymes associated with carbohydrate and lipid metabolism in quail liver. | Effect of dietary DL-ethionine and/or DL-methionine on egg laying and activities of some cytoplasmic NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica. The effect of dietary DL-ethionine and/or DL-methionine on egg laying, and activities of some NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica was investigated. A 0.30% DL-ethionine plus 0.30% DL-methionine supplemented diet reversed partially the egg laying inhibited by the diet with 0.30% DL-ethionine alone. No inhibitory effect on egg laying was observed for the diet supplemented with 0.30% DL-methionine alone. In marked contrast to the decreased activity of L-glycerol 3-phosphate dehydrogenase and malate dehydrogenase, significantly increased activity of lactate dehydrogenase was obtained for quail fed the DL-ethionine, and the DL-ethionine plus the DL-methionine supplemented diet, respectively. No marked changes in activities of these three dehydrogenases were obtained for quail fed the diet supplemented with DL-methionine alone. Although decreased activity was observed for all of the four NADPH-producing enzymes in quail fed the diet supplemented with DL-ethionine alone, the DL-ethionine plus DL-methionine, the smallest decrease was obtained for NADP-isocitrate dehydrogenase. The diet supplemented with DL-methionine alone induced markedly the respective activity of malic enzyme and glucose 6-phosphate dehydrogenase. These results indicate a relatively important function of NADP-isocitrate dehydrogenase for NADPH-production even under DL-ethionine toxicity and suggest complicated relationships between egg production and activities of enzymes associated with carbohydrate and lipid metabolism in quail liver. | [
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|
PMID:16101 | Stimulation of neutral amino acid transport by fructose in epithelial cells isolated from rat intestine. | Interest in the nutritional and physiological implications of the high dietary intakes of fructose from sucrose and isomerized corn sweeteners has directed attention to the specific metabolic properties of this monosaccharide. Epithelial cells isolated from the small intestine of Wistar rats fed a stock diet showed 24% to 57% higher transport of 1 mM leucine, isoleucine, valine, alanine, phenylalanine tryptophan and histidine in the presence of 10 mM fructose than in its absence. In contrast, 10mM glucose generally inhibited the transport of these amino acids and 10mM sorbose had no effect on leucine transport. Fructose failed to consistently stimulate the transport of basic amino acids and generally inhibited the transport of glucose and galactose, indicating that the stimulation was relatively specific for neutral amino acids. Cells preloaded with fructose optimally stimulated leucine transport in the absence of extracellular fructose. Ouabain and dinitrophenol inhibited the stimulation of leucine transport by intracellular fructose after 2 minutes. A stimulation mediated by an exchange transport mechanism was rejected on the basis of the failure of 1 mM neutral amino acids either to inhibit the transport of 10 mM fructose or to accelerate the movement of fructose out of fructose-loaded cells. Although the mechanism remains unknown, these results demonstrate a specific effect of fructose at the intestinal level that produces a stimulation of neutral amino acid transport. | Stimulation of neutral amino acid transport by fructose in epithelial cells isolated from rat intestine. Interest in the nutritional and physiological implications of the high dietary intakes of fructose from sucrose and isomerized corn sweeteners has directed attention to the specific metabolic properties of this monosaccharide. Epithelial cells isolated from the small intestine of Wistar rats fed a stock diet showed 24% to 57% higher transport of 1 mM leucine, isoleucine, valine, alanine, phenylalanine tryptophan and histidine in the presence of 10 mM fructose than in its absence. In contrast, 10mM glucose generally inhibited the transport of these amino acids and 10mM sorbose had no effect on leucine transport. Fructose failed to consistently stimulate the transport of basic amino acids and generally inhibited the transport of glucose and galactose, indicating that the stimulation was relatively specific for neutral amino acids. Cells preloaded with fructose optimally stimulated leucine transport in the absence of extracellular fructose. Ouabain and dinitrophenol inhibited the stimulation of leucine transport by intracellular fructose after 2 minutes. A stimulation mediated by an exchange transport mechanism was rejected on the basis of the failure of 1 mM neutral amino acids either to inhibit the transport of 10 mM fructose or to accelerate the movement of fructose out of fructose-loaded cells. Although the mechanism remains unknown, these results demonstrate a specific effect of fructose at the intestinal level that produces a stimulation of neutral amino acid transport. | [
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|
PMID:16102 | Influence of dietary lipid on lipogenic enzyme activities in coho salmon, Oncorhynchus kisutch (Walbaum). | Coho salmon (Oncorhynchus kisutch), 8 to 18 months of age, were maintained in culture tanks and were fed three semipurified diets. The diets contained 40% of energy from protein and 11.5%, 23%, or 46% of energy from lipid. The body weight gain and food conversion factors were similar among groups of fish fed the diets in each of the three experiments. Wet weight of mesenteric adipose tissue increased with increased amount of lipid in the diet; however, epaxial muscle lipid content was not influenced by the lipid content of the diet. Several hepatic and adipose tissue lipogenic enzymes (fatty acid synthetase, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-isocitrate dehydrogenase) were assayed. These lipogenic enzymes exhibited high activities in liver and relatively low concentration in adipose tissue of the fish. The activities of all the hepatic lipogenic enzymes assayed, except for NADP-isocitrate dehydrogenase, were depressed as the level of lipid in the diet was increased; however, the activities of these enzymes in mesenteric adipose tissue were not influenced by the diets fed. The results of this study indicate that dietary lipid depresses hepatic lipogenic enzyme activities and that the liver may be a more important site for fatty acid synthesis than is adipose tissue in coho salmon. | Influence of dietary lipid on lipogenic enzyme activities in coho salmon, Oncorhynchus kisutch (Walbaum). Coho salmon (Oncorhynchus kisutch), 8 to 18 months of age, were maintained in culture tanks and were fed three semipurified diets. The diets contained 40% of energy from protein and 11.5%, 23%, or 46% of energy from lipid. The body weight gain and food conversion factors were similar among groups of fish fed the diets in each of the three experiments. Wet weight of mesenteric adipose tissue increased with increased amount of lipid in the diet; however, epaxial muscle lipid content was not influenced by the lipid content of the diet. Several hepatic and adipose tissue lipogenic enzymes (fatty acid synthetase, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-isocitrate dehydrogenase) were assayed. These lipogenic enzymes exhibited high activities in liver and relatively low concentration in adipose tissue of the fish. The activities of all the hepatic lipogenic enzymes assayed, except for NADP-isocitrate dehydrogenase, were depressed as the level of lipid in the diet was increased; however, the activities of these enzymes in mesenteric adipose tissue were not influenced by the diets fed. The results of this study indicate that dietary lipid depresses hepatic lipogenic enzyme activities and that the liver may be a more important site for fatty acid synthesis than is adipose tissue in coho salmon. | [
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|
PMID:16103 | The immediate nucleotide precursor, guanosine triphosphate, in the riboflavin biosynthetic pathway. | In the present paper, the nucleotide precursor of riboflavin was investigated by experiments with labeled purines using non-growing cells of Eremothecium ashybii. The added purines, at 10(-4) M, were effectively incorporated into riboflavin at an early stage of riboflavin biosynthesis under the experimental conditions. In particular, both labeled xanthine and labeled guanine were specifically transported to guanosine nucleotides, GMP, GDP, GDP-Mannose and GTP, in the course of the riboflavin biosynthesis. A comparison of specific activities of labeled guanosine nucleotides and labeled riboflavin indicated that the nucleotide precursor of riboflavin is guanosine triphosphate. From the results obtained, a biosynthetic pathway of riboflavin is proposed under "DISCUSSION." | The immediate nucleotide precursor, guanosine triphosphate, in the riboflavin biosynthetic pathway. In the present paper, the nucleotide precursor of riboflavin was investigated by experiments with labeled purines using non-growing cells of Eremothecium ashybii. The added purines, at 10(-4) M, were effectively incorporated into riboflavin at an early stage of riboflavin biosynthesis under the experimental conditions. In particular, both labeled xanthine and labeled guanine were specifically transported to guanosine nucleotides, GMP, GDP, GDP-Mannose and GTP, in the course of the riboflavin biosynthesis. A comparison of specific activities of labeled guanosine nucleotides and labeled riboflavin indicated that the nucleotide precursor of riboflavin is guanosine triphosphate. From the results obtained, a biosynthetic pathway of riboflavin is proposed under "DISCUSSION." | [
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|
PMID:16104 | Reconstitution of T-cell function in severe combined immunodeficiency disease following transplantation of early embryonic liver cells. | In a 51/2-month-old male infant with adenosine deaminase-positive severe combined immunodeficiency disease, who had no suitable bone marrow donor, immunologic reconstitution was attempted with lymphoid cells obtained from the liver of a 4- to 5-week-old-male human embryo. A mild graft-versus-host reaction began three weeks later. T-cells, which were absent prior to infusion of hepatic lymphoid cells, rose to a maximum of 554/mm3 at 16 weeks post transplantation. A normal lymphocyte response to pokeweek mitogen was not present until 25 to 30 weeks and to allogeneic cells until 39 weeks. Postive in vitro lymphocyte responses to Candida albicans were found repeatedly after 52 weeks. Twenty months following transplantation the patient is free of clinical infection, although he requires regular injections of gamma globulin. | Reconstitution of T-cell function in severe combined immunodeficiency disease following transplantation of early embryonic liver cells. In a 51/2-month-old male infant with adenosine deaminase-positive severe combined immunodeficiency disease, who had no suitable bone marrow donor, immunologic reconstitution was attempted with lymphoid cells obtained from the liver of a 4- to 5-week-old-male human embryo. A mild graft-versus-host reaction began three weeks later. T-cells, which were absent prior to infusion of hepatic lymphoid cells, rose to a maximum of 554/mm3 at 16 weeks post transplantation. A normal lymphocyte response to pokeweek mitogen was not present until 25 to 30 weeks and to allogeneic cells until 39 weeks. Postive in vitro lymphocyte responses to Candida albicans were found repeatedly after 52 weeks. Twenty months following transplantation the patient is free of clinical infection, although he requires regular injections of gamma globulin. | [
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|
PMID:16105 | Peritoneal dialysis for severe methyprylon intoxication. | The appropriate therapy for methyprylon (Noludar) poisoning has remained controversial, owing to a lack of reliable pharmacologic data concerning the most effective way to remove the drug after a large ingestion. We recently employed peritoneal dialysis to treat a 16-year-old girl, who had ingested 6.3 gm of methypyrlon, and were able to recover more than 80% of the unmetabolized drug in the dialysate. Clinical recovery was complete within eight hours. This appears to be a safe and effective method to remove the drug in the child or adult with a serious intoxication. | Peritoneal dialysis for severe methyprylon intoxication. The appropriate therapy for methyprylon (Noludar) poisoning has remained controversial, owing to a lack of reliable pharmacologic data concerning the most effective way to remove the drug after a large ingestion. We recently employed peritoneal dialysis to treat a 16-year-old girl, who had ingested 6.3 gm of methypyrlon, and were able to recover more than 80% of the unmetabolized drug in the dialysate. Clinical recovery was complete within eight hours. This appears to be a safe and effective method to remove the drug in the child or adult with a serious intoxication. | [
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|
PMID:16106 | Development of Haemonchus contortus in vitro and the stimulus from the host. | Infective larvae of Haemonchus contortus which have been exposed for about 9 hr to relatively high partial pressures of carbon dioxide at near-neutral pH, as they might be in the rumen, develop slowly to the fourth stage or not at all. But following this treatment, exposure to lower partial pressures of carbon dioxide and higher concentrations of hydrogen ions, such as might be encountered in the abomasal mucosa, brings about development at a rate comparable with that in the sheep. | Development of Haemonchus contortus in vitro and the stimulus from the host. Infective larvae of Haemonchus contortus which have been exposed for about 9 hr to relatively high partial pressures of carbon dioxide at near-neutral pH, as they might be in the rumen, develop slowly to the fourth stage or not at all. But following this treatment, exposure to lower partial pressures of carbon dioxide and higher concentrations of hydrogen ions, such as might be encountered in the abomasal mucosa, brings about development at a rate comparable with that in the sheep. | [
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|
PMID:16111 | In vitro adsortpion of acetaminophen onto activated charcoal. | In vitro experiments supported in vivo evidence that activated charcoal is effective in adsorbing acetaminophen. In the physiologic pH range, adsorption was rapid and pH independent. Adsorption, however, was dependent upon the quantity of activated charcoal employed, becoming more complete as the quantity of activated charcoal was increased. | In vitro adsortpion of acetaminophen onto activated charcoal. In vitro experiments supported in vivo evidence that activated charcoal is effective in adsorbing acetaminophen. In the physiologic pH range, adsorption was rapid and pH independent. Adsorption, however, was dependent upon the quantity of activated charcoal employed, becoming more complete as the quantity of activated charcoal was increased. | [
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|
PMID:16112 | Conformational studies of antiradiation agents by NMR: cysteamine and its derivatives. | The conformations of cysteamine, thiazolidine, and thiazolidine-4-carboxylic acid were determined in aqueous solutions using NMR spectroscopy. At physiological pH, the population ratio of gauche- and trans-conformers was 3:1. The gauche-rotamer is probably responsible for the antiradiation activity and acts through metal chelation involving sulfur and nitrogen atoms. The puckering of the thiazolidine ring was calculated using NMR coupling constants. The observed results were compared with those obtained in the solid state using X-ray diffraction. | Conformational studies of antiradiation agents by NMR: cysteamine and its derivatives. The conformations of cysteamine, thiazolidine, and thiazolidine-4-carboxylic acid were determined in aqueous solutions using NMR spectroscopy. At physiological pH, the population ratio of gauche- and trans-conformers was 3:1. The gauche-rotamer is probably responsible for the antiradiation activity and acts through metal chelation involving sulfur and nitrogen atoms. The puckering of the thiazolidine ring was calculated using NMR coupling constants. The observed results were compared with those obtained in the solid state using X-ray diffraction. | [
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|
PMID:16113 | Solubility studies of silver sulfadiazine. | The solubility of silver sulfadiazine as a function of pH was determined in nitric acid-potassium nitrate buffer for pH 2-3 and in 2-(N-morpholino)ethanesulfonic acid buffer for pH 6-7. As the salt of a weak organic acid, silver sulfadiazine exhibits the anticipated increase in solubility with an increasing hydrogen-ion concentration. Measurement of the silver-ion concentration was carried out using a silver-ion selective electrode. The methods of known subtraction and known addition were utilized to measure the total concentration of the silver ion in solution. Evidence was obtained to indicate that the salt is completely ionized in aqueous solution. | Solubility studies of silver sulfadiazine. The solubility of silver sulfadiazine as a function of pH was determined in nitric acid-potassium nitrate buffer for pH 2-3 and in 2-(N-morpholino)ethanesulfonic acid buffer for pH 6-7. As the salt of a weak organic acid, silver sulfadiazine exhibits the anticipated increase in solubility with an increasing hydrogen-ion concentration. Measurement of the silver-ion concentration was carried out using a silver-ion selective electrode. The methods of known subtraction and known addition were utilized to measure the total concentration of the silver ion in solution. Evidence was obtained to indicate that the salt is completely ionized in aqueous solution. | [
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|
PMID:16114 | Metal-ion interaction with penicillins: kinetics of complexation of nickel(II). | The kinetics of complexation of nickel(II) with some penicillins and related compounds show that the zwitterionic form of the ligand has very low reactivity compared to the anionic form. The resolved rate constants are interpreted in terms of binding to the ring nitrogen and carboxyl group and not to the side chain. | Metal-ion interaction with penicillins: kinetics of complexation of nickel(II). The kinetics of complexation of nickel(II) with some penicillins and related compounds show that the zwitterionic form of the ligand has very low reactivity compared to the anionic form. The resolved rate constants are interpreted in terms of binding to the ring nitrogen and carboxyl group and not to the side chain. | [
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|
PMID:16116 | Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines II: oxazepam and diazepam. | The hydrolysis kinetics of oxazepam and diazepam leading to a benzophenone product and a glycine derivative were quantified from pH 1 to 11. For oxazepam, two intermediates were isolated and identified, indicating a parallel consecutive reaction mechanism. The hydrolysis occurred uncatalyzed and demonstrated acid-base catalysis for both reaction steps. One intermediate was observed by TLC for diazepam hydrolysis. This intermediate, resulting from breakage of the azomethine linkage, was different than the major intermediate isolated for oxazepam hydrolytic degradation (amide hydrolysis preferred). Stability parameters involving rate constant-temperature dependence are reported. | Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines II: oxazepam and diazepam. The hydrolysis kinetics of oxazepam and diazepam leading to a benzophenone product and a glycine derivative were quantified from pH 1 to 11. For oxazepam, two intermediates were isolated and identified, indicating a parallel consecutive reaction mechanism. The hydrolysis occurred uncatalyzed and demonstrated acid-base catalysis for both reaction steps. One intermediate was observed by TLC for diazepam hydrolysis. This intermediate, resulting from breakage of the azomethine linkage, was different than the major intermediate isolated for oxazepam hydrolytic degradation (amide hydrolysis preferred). Stability parameters involving rate constant-temperature dependence are reported. | [
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|
PMID:16115 | Mechanism of histamine binding II: effect of alkali metal and alkaline earth cations on histamine binding to peptide H. | The association constants of histamine with Mg2+, Ca2+, Sr2+, and Ba2+ were determined in buffer solutions at constant pH using an ion selective electrode. These cations enabled histamine to bind to peptide H. A minimum cation binding concentration was required for histamine binding. A linear relationship existed between the minimum cation binding concentration and the log of the equilibrium constant for the histamine-cation complexes, indicating that the specificity of the alkaline earth cations in promoting histamine binding was due to the difference in their ability to complex with histamine. The monovalent cations, Nat, Kt, and Cst inhibited histamine binding to peptide H, with the extent of inhibition dependent on cation concentration. An ion-exchange mechanism or a conformation change in the peptide may account for the inhibition. | Mechanism of histamine binding II: effect of alkali metal and alkaline earth cations on histamine binding to peptide H. The association constants of histamine with Mg2+, Ca2+, Sr2+, and Ba2+ were determined in buffer solutions at constant pH using an ion selective electrode. These cations enabled histamine to bind to peptide H. A minimum cation binding concentration was required for histamine binding. A linear relationship existed between the minimum cation binding concentration and the log of the equilibrium constant for the histamine-cation complexes, indicating that the specificity of the alkaline earth cations in promoting histamine binding was due to the difference in their ability to complex with histamine. The monovalent cations, Nat, Kt, and Cst inhibited histamine binding to peptide H, with the extent of inhibition dependent on cation concentration. An ion-exchange mechanism or a conformation change in the peptide may account for the inhibition. | [
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|
PMID:16117 | Motor innervation of the smooth muscle of the rat seminal vesicle. | Frequency-related isovolumetric contractions of the rat seminal vesicle elicited with transmural electrical stimulation were blocked by tetrodotoxin but unaffected by hexamethonium. The postganglionic motor innervation of the rat seminal vesicle is purely excitatory and contains both an adrenergic and a cholinergic component which are excited simultaneously during transmural stimulation. Contractions elicited by adrenergic nerve stimulation were mediated by norepinephrine acting via alpha adrenoceptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous norepinephrine were antagonized by phentolamine and potentiated by cocaine, 2) pretreatment of animals with reserpine or 6-hydroxydopamine produced a marked depletion of tissue norepinephrine concentration and reduced the responses to transmural stimulation to a level which resembled that of untreated organs in the presence of phentolamine, 3) the residual responses of vesicles from pretreated rats were not modified by phentolamine or cocaine, and 4) responses to tyramine in untreated organs were antagonized by phentolamine but not by cocaine and were observed in organs from reserpine-pretreated rats only after repletion with exogenous norepinephrine. Responses elicited by cholinergic nerve stimulation were mediated by acetylcholine through muscarinic receptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous acetylcholine were antagonized by atropine, 2) the residual responses to transmural stimulation of vesicles from animals pretreated with reserpine of 6-hydroxydopamine were nearly abolished by atropine and 3) physostigmine potentiated and prolonged the responses of organs from untreated and reserpine-pretreatd animals to transmural stimulation; these effects of physostigmine were abolished by atropine. | Motor innervation of the smooth muscle of the rat seminal vesicle. Frequency-related isovolumetric contractions of the rat seminal vesicle elicited with transmural electrical stimulation were blocked by tetrodotoxin but unaffected by hexamethonium. The postganglionic motor innervation of the rat seminal vesicle is purely excitatory and contains both an adrenergic and a cholinergic component which are excited simultaneously during transmural stimulation. Contractions elicited by adrenergic nerve stimulation were mediated by norepinephrine acting via alpha adrenoceptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous norepinephrine were antagonized by phentolamine and potentiated by cocaine, 2) pretreatment of animals with reserpine or 6-hydroxydopamine produced a marked depletion of tissue norepinephrine concentration and reduced the responses to transmural stimulation to a level which resembled that of untreated organs in the presence of phentolamine, 3) the residual responses of vesicles from pretreated rats were not modified by phentolamine or cocaine, and 4) responses to tyramine in untreated organs were antagonized by phentolamine but not by cocaine and were observed in organs from reserpine-pretreated rats only after repletion with exogenous norepinephrine. Responses elicited by cholinergic nerve stimulation were mediated by acetylcholine through muscarinic receptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous acetylcholine were antagonized by atropine, 2) the residual responses to transmural stimulation of vesicles from animals pretreated with reserpine of 6-hydroxydopamine were nearly abolished by atropine and 3) physostigmine potentiated and prolonged the responses of organs from untreated and reserpine-pretreatd animals to transmural stimulation; these effects of physostigmine were abolished by atropine. | [
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|
PMID:16118 | Organ culture of rat superior cervical ganglia. | The maintenance of adrenergic function has been investigated in organ cultures of adult rat superior cervical ganglia. Tyrosine hydroxylase and monoamine oxidase activities decreased gradually through 72 hours of culture. Dopamine beta-hydroxylase activity gradually increased in the cultured ganglia to 150% of that seen in fresh ganglia after 14 hours in culture. The level of norepinephrine increased in the cultured ganglia to a maximum of 225% of that seen in control ganglia. The increases in both dopamine beta-hydroxylase activity and in norepinephrine levels required protein synthesis but they were not dependent on the presence of nerve growth factor. The accumulation of norepinephrine in the cultured ganglia could not be explained by an increased rate of amine synthesis. Turnover measurements suggest that the accumulation can be explained by a decreased rate of amine metabolism in the cultured ganglia. A comparison of the distribution of amine storage vesicles showed that the number of heavy vesicles was greater in cultured than in fresh ganglia. The results suggest that sympathetic ganglia develop an increased capacity for amine storage in culture and that this leads to an increase in intracellular levels of norepinephrine. | Organ culture of rat superior cervical ganglia. The maintenance of adrenergic function has been investigated in organ cultures of adult rat superior cervical ganglia. Tyrosine hydroxylase and monoamine oxidase activities decreased gradually through 72 hours of culture. Dopamine beta-hydroxylase activity gradually increased in the cultured ganglia to 150% of that seen in fresh ganglia after 14 hours in culture. The level of norepinephrine increased in the cultured ganglia to a maximum of 225% of that seen in control ganglia. The increases in both dopamine beta-hydroxylase activity and in norepinephrine levels required protein synthesis but they were not dependent on the presence of nerve growth factor. The accumulation of norepinephrine in the cultured ganglia could not be explained by an increased rate of amine synthesis. Turnover measurements suggest that the accumulation can be explained by a decreased rate of amine metabolism in the cultured ganglia. A comparison of the distribution of amine storage vesicles showed that the number of heavy vesicles was greater in cultured than in fresh ganglia. The results suggest that sympathetic ganglia develop an increased capacity for amine storage in culture and that this leads to an increase in intracellular levels of norepinephrine. | [
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|
PMID:16119 | Effects of ethosuximide on transmission of repetitive impulses and apparent rates of transmitter turnover in the spinal monosynaptic pathway. | The effects of ethosuximide on spinal monosynaptic transmission were studied in cats. The drug in doses of 200 or 400 mg/kg deepened the decline of monosynaptic response amplitude evoked by trains of 10 stimuli to a motor nerve at 2, 5 or 10 Hz, without affecting the transmission of single isolated impulses. The patterns of decline were analyzed under the assumption that they reflect a partial depletion of the apparent transmitter stores in the presynaptic terminals, each incoming volley releasing a constant fraction of the store while a constant fraction of the instant size of the depleted part is being replenished per second. Ethosuximide increased the fractional release without a consistent effect on the fractional rate of replenishment. It is suggested that the resulting more rapid and more profound depletion of the apparent transmitter store could account for the observed preferential depression of repetitive transmission in the spinal monosynaptic pathway by this drug. | Effects of ethosuximide on transmission of repetitive impulses and apparent rates of transmitter turnover in the spinal monosynaptic pathway. The effects of ethosuximide on spinal monosynaptic transmission were studied in cats. The drug in doses of 200 or 400 mg/kg deepened the decline of monosynaptic response amplitude evoked by trains of 10 stimuli to a motor nerve at 2, 5 or 10 Hz, without affecting the transmission of single isolated impulses. The patterns of decline were analyzed under the assumption that they reflect a partial depletion of the apparent transmitter stores in the presynaptic terminals, each incoming volley releasing a constant fraction of the store while a constant fraction of the instant size of the depleted part is being replenished per second. Ethosuximide increased the fractional release without a consistent effect on the fractional rate of replenishment. It is suggested that the resulting more rapid and more profound depletion of the apparent transmitter store could account for the observed preferential depression of repetitive transmission in the spinal monosynaptic pathway by this drug. | [
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|
PMID:16120 | The binding of strychnine and strychnine analogs to synaptic membranes of rat brainstem and spinal cord. | Crude synaptic membranes were isolated from rat pons, medulla and spinal cord by differential centrifugation. The specific binding of [3H]strychnine, obtained by subtracting from the bound radioactivity the amount not displaced by 50 micronm unlabeled strychnine, was saturable with a KD value of 12 nM. The dissociation constants (KD values) for the binding of several strychnine analogs to the strychnine site in vitro were determined and found to be highly correlated with the convulsant and lethal effects in the mouse. However, neither the biological activities in the mouse nor the binding activity in vitro correlated with the n-octanol-water distribution coefficients. The results are in accord with the concept that the [3H]strychnine binding site detected in vitro is the site of pharmacological activity in vivo. | The binding of strychnine and strychnine analogs to synaptic membranes of rat brainstem and spinal cord. Crude synaptic membranes were isolated from rat pons, medulla and spinal cord by differential centrifugation. The specific binding of [3H]strychnine, obtained by subtracting from the bound radioactivity the amount not displaced by 50 micronm unlabeled strychnine, was saturable with a KD value of 12 nM. The dissociation constants (KD values) for the binding of several strychnine analogs to the strychnine site in vitro were determined and found to be highly correlated with the convulsant and lethal effects in the mouse. However, neither the biological activities in the mouse nor the binding activity in vitro correlated with the n-octanol-water distribution coefficients. The results are in accord with the concept that the [3H]strychnine binding site detected in vitro is the site of pharmacological activity in vivo. | [
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|
PMID:16121 | Serotonin and dopamine as neurotransmitters in mytilus: block of serotonin receptors by an organic mercurial. | The effects of mersalyl, bromo-LSD (BOL) and methysergide (UML) on the relaxation of catch by certain indole and catechol derivatives were studied in the anterior byssus retractor muscle of Mytilus. Mersalyl antagonized relaxation in response to serotonin whereas BOL and UML were less effective. Two other indole derivatives, ergotamine and gramine, were also blocked by mersalyl; BOL and UML antagonized relaxation in response to dopamine more effectively than did mersalyl. Two other catechols, epinephrine and norepinephrine, were also blocked more effectively by BOL and UML than by mersaly. Relaxation in response to neural stimulation was blocked more effectively by mersalyl than by BOL. The blocking action of mersalyl on neural relaxation reversed very poorly after washing the drug, but complete reversal was induced by brief exposure to dithiothreitol. It is concluded that the evidence supports an hypothesis that the transmitter released by relaxing nerves is serotonin. It is suggested that mersalyl blocks serotonin by combining with a sulfhydryl group at or near the site on the receptor to which the indole nitrogen attaches. | Serotonin and dopamine as neurotransmitters in mytilus: block of serotonin receptors by an organic mercurial. The effects of mersalyl, bromo-LSD (BOL) and methysergide (UML) on the relaxation of catch by certain indole and catechol derivatives were studied in the anterior byssus retractor muscle of Mytilus. Mersalyl antagonized relaxation in response to serotonin whereas BOL and UML were less effective. Two other indole derivatives, ergotamine and gramine, were also blocked by mersalyl; BOL and UML antagonized relaxation in response to dopamine more effectively than did mersalyl. Two other catechols, epinephrine and norepinephrine, were also blocked more effectively by BOL and UML than by mersaly. Relaxation in response to neural stimulation was blocked more effectively by mersalyl than by BOL. The blocking action of mersalyl on neural relaxation reversed very poorly after washing the drug, but complete reversal was induced by brief exposure to dithiothreitol. It is concluded that the evidence supports an hypothesis that the transmitter released by relaxing nerves is serotonin. It is suggested that mersalyl blocks serotonin by combining with a sulfhydryl group at or near the site on the receptor to which the indole nitrogen attaches. | [
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|
PMID:16122 | Specific enhancement of norepinephrine-induced contraction in rat veins after beta adrenergic antagonists. | Propranolol markedly increased the norepinephrine-induced maximal force in circular smooth muscle of the rat portal, mesenteric, renal and, to a lesser extent, femoral veins without affecting aortic or mesenteric artery responses to norepinephrine. Furthermore, two other beta receptor antagonists, practolol and N-isopropylmethoxamine, specifically enhanced maximal venous responses to norepinephrine. Contractions to norepinephrine, but not to serotonin, were increased by propranolol only in veins, even after the vasodilator, papaverine. The ability of propranolol to enhance norepinephrine-induced contraction in these rat veins paralleled the effectiveness of isoproterenol to relax such tissues. In addition, beta receptor antagonists enhanced the response of veins to the field stimulated release of norepinephrine from sympathetic nerves. These data support the conclusion that beta adrenergic stimulation modulates norepinephrine-induced constriction in certain rat veins but not in the aorta or mesenteric artery. | Specific enhancement of norepinephrine-induced contraction in rat veins after beta adrenergic antagonists. Propranolol markedly increased the norepinephrine-induced maximal force in circular smooth muscle of the rat portal, mesenteric, renal and, to a lesser extent, femoral veins without affecting aortic or mesenteric artery responses to norepinephrine. Furthermore, two other beta receptor antagonists, practolol and N-isopropylmethoxamine, specifically enhanced maximal venous responses to norepinephrine. Contractions to norepinephrine, but not to serotonin, were increased by propranolol only in veins, even after the vasodilator, papaverine. The ability of propranolol to enhance norepinephrine-induced contraction in these rat veins paralleled the effectiveness of isoproterenol to relax such tissues. In addition, beta receptor antagonists enhanced the response of veins to the field stimulated release of norepinephrine from sympathetic nerves. These data support the conclusion that beta adrenergic stimulation modulates norepinephrine-induced constriction in certain rat veins but not in the aorta or mesenteric artery. | [
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|
PMID:16123 | Urinary carbon dioxide tension in lithium carbonate-treated patients. | Renal acidification was studied in 12 lithium carbonate-treated psychiatric patients. The urinary Pco2 response to oral sodium bicarbonate loading, a qualitative index of distal hydrogen ion secretion, was evaluated in all patients and the results were compared with those obtained in 10 control subjects. The average maximal urine to arterial blood Pco2 difference (U-A Pco2) in the psychiatric patients [26 +/- 3 (S.E.) mm Hg] was significantly lower (P less than .001) than that of control subjects (51 +/- 3 mm Hg) and only three patients had values greater than 31 mm Hg (2 S.D. below the mean control value). Eight of these patients were also evaluated with NH4CL acid loading. Seven of eight patients had a minimal urine pH less than 5.30 after NH4CL administration; only one of the seven had a normal U-APco2 after bicarbonate loading. Three patients were evaluated prior to treatment and after 2 weeks of lithium administration. Pretreatment U-APco2 values were normal. After therapy the values were lower in all three patients becoming definitely abnormal in two. The present investigation, in concert with previous animal studies, demonstrates that chronic lithium carbonate therapy in man may result in decreased U-A Pco2. | Urinary carbon dioxide tension in lithium carbonate-treated patients. Renal acidification was studied in 12 lithium carbonate-treated psychiatric patients. The urinary Pco2 response to oral sodium bicarbonate loading, a qualitative index of distal hydrogen ion secretion, was evaluated in all patients and the results were compared with those obtained in 10 control subjects. The average maximal urine to arterial blood Pco2 difference (U-A Pco2) in the psychiatric patients [26 +/- 3 (S.E.) mm Hg] was significantly lower (P less than .001) than that of control subjects (51 +/- 3 mm Hg) and only three patients had values greater than 31 mm Hg (2 S.D. below the mean control value). Eight of these patients were also evaluated with NH4CL acid loading. Seven of eight patients had a minimal urine pH less than 5.30 after NH4CL administration; only one of the seven had a normal U-APco2 after bicarbonate loading. Three patients were evaluated prior to treatment and after 2 weeks of lithium administration. Pretreatment U-APco2 values were normal. After therapy the values were lower in all three patients becoming definitely abnormal in two. The present investigation, in concert with previous animal studies, demonstrates that chronic lithium carbonate therapy in man may result in decreased U-A Pco2. | [
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|
PMID:16124 | The development of some metabolic responses to hypoxia in the foetal sheep. | 1. Foetal and maternal plasma metabolite and catecholamine concentrations have been measured in chronically catheterized sheep, 95-145 days pregnant. 2. With increasing gestational age there was rise in foetal plasma lactate, free fatty acid and ketone body concentration and in maternal plasma in free fatty acid and ketone body concentration. With the exception of alpha-amino nitrogen none of the plasma metabolites showed any correlation with foetal blood gas or pH values; alpha-amino N was inversely related to foetal blood pH. 3. Hypoxia in the foetuses was induced by causing the ewe to breathe 9% O2 with 3% CO2 in N2. This had a small effect on plasma metabolites in the ewe, mainly producing an increase in free fatty acid and ketone body concentration. 4. In the foetus hypoxia was associated with a large rise in plasma lactate and a small rise in alpha-amino N, the magnitudes of which did not change over the gestational range studied. Consistent and large increases in foetal plasma glucose, free fatty acid and ketone body concentration in response to hypoxia were seen only between 130 and 145 days. 5. In foetuses of 130-145 days the magnitude of the hypoxia-induced rise in plasma glucose and free fatty acid concentration was proportional to the plasma catecholamine concentration. 6. The concentration of acetate in foetal plasma was lower than and proportional to that in the maternal plasma. Neither concentration changed significantly during hypoxia. 7. The results are discussed in relation to the ability of the foetal sheep independently to control the concentration of its plasma metabolites and to mobilize its carbon stores at times of need. They indicate that in the sheep plasma catecholamines are important regulators of plasma glucose and free fatty acid concentrations late in foetal life. | The development of some metabolic responses to hypoxia in the foetal sheep. 1. Foetal and maternal plasma metabolite and catecholamine concentrations have been measured in chronically catheterized sheep, 95-145 days pregnant. 2. With increasing gestational age there was rise in foetal plasma lactate, free fatty acid and ketone body concentration and in maternal plasma in free fatty acid and ketone body concentration. With the exception of alpha-amino nitrogen none of the plasma metabolites showed any correlation with foetal blood gas or pH values; alpha-amino N was inversely related to foetal blood pH. 3. Hypoxia in the foetuses was induced by causing the ewe to breathe 9% O2 with 3% CO2 in N2. This had a small effect on plasma metabolites in the ewe, mainly producing an increase in free fatty acid and ketone body concentration. 4. In the foetus hypoxia was associated with a large rise in plasma lactate and a small rise in alpha-amino N, the magnitudes of which did not change over the gestational range studied. Consistent and large increases in foetal plasma glucose, free fatty acid and ketone body concentration in response to hypoxia were seen only between 130 and 145 days. 5. In foetuses of 130-145 days the magnitude of the hypoxia-induced rise in plasma glucose and free fatty acid concentration was proportional to the plasma catecholamine concentration. 6. The concentration of acetate in foetal plasma was lower than and proportional to that in the maternal plasma. Neither concentration changed significantly during hypoxia. 7. The results are discussed in relation to the ability of the foetal sheep independently to control the concentration of its plasma metabolites and to mobilize its carbon stores at times of need. They indicate that in the sheep plasma catecholamines are important regulators of plasma glucose and free fatty acid concentrations late in foetal life. | [
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|
PMID:16125 | Possible explanations for the differences in secretory characteristics between conjugated and free bile acids. | 1. The hepatic extraction fraction and maximum excretory rate of conjugated cholate are greater than those of free cholate (studied after acute taurine depletion); the possibility that this difference might be due to greater bile-to-blood back-diffusion of un-ionized cholic acid (pKa 5-5) compared to that of taurocholic acid (pKa 2) has been investigated by varying the pH of bile by secretin or acetazolamide administration in the anaesthetized dog. 2. The mean biliary pH during free cholate excretion in the control state in twenty-three experiments was 7-5 (at which approximately 1% of cholate is un-ionized). Three to fourfold changes in the hydrogen ion activity of bile (which resulted in changes of the same magnitude in the percentage of un-ionized cholic acid) had no significant effect on the total (mainly free) cholate maximum excretory rate. It is concluded that back-diffusion of un-ionized cholic acid in the bile ducts is not an important determinant of the secretory performance of free cholate. 3. The bile flow rate associated with mainly free cholate excretion is much higher than that associated with taurocholate excretion at the same rate; the extra bile flow appears to arise largely by means that are independent of the osmotic effect of cholate excretion, as the osmotic coefficient (osmolality/total solute concentration) of bile containing mainly free free cholate (calculated directly) was only slightly greater than that of bile containing mainly taurocholate (obtained by extrapolation) at the same total cholate concentration. 4. The peak hepatic excretory rate of taurocholate following the instillation of the entire contents of the gall-bladder of a fasted dog into the distal ileum was only about one fifth of the maximum rate attainable; at the peak rate taurocholate is almost completely removed in the first passage of blood through the liver. | Possible explanations for the differences in secretory characteristics between conjugated and free bile acids. 1. The hepatic extraction fraction and maximum excretory rate of conjugated cholate are greater than those of free cholate (studied after acute taurine depletion); the possibility that this difference might be due to greater bile-to-blood back-diffusion of un-ionized cholic acid (pKa 5-5) compared to that of taurocholic acid (pKa 2) has been investigated by varying the pH of bile by secretin or acetazolamide administration in the anaesthetized dog. 2. The mean biliary pH during free cholate excretion in the control state in twenty-three experiments was 7-5 (at which approximately 1% of cholate is un-ionized). Three to fourfold changes in the hydrogen ion activity of bile (which resulted in changes of the same magnitude in the percentage of un-ionized cholic acid) had no significant effect on the total (mainly free) cholate maximum excretory rate. It is concluded that back-diffusion of un-ionized cholic acid in the bile ducts is not an important determinant of the secretory performance of free cholate. 3. The bile flow rate associated with mainly free cholate excretion is much higher than that associated with taurocholate excretion at the same rate; the extra bile flow appears to arise largely by means that are independent of the osmotic effect of cholate excretion, as the osmotic coefficient (osmolality/total solute concentration) of bile containing mainly free free cholate (calculated directly) was only slightly greater than that of bile containing mainly taurocholate (obtained by extrapolation) at the same total cholate concentration. 4. The peak hepatic excretory rate of taurocholate following the instillation of the entire contents of the gall-bladder of a fasted dog into the distal ileum was only about one fifth of the maximum rate attainable; at the peak rate taurocholate is almost completely removed in the first passage of blood through the liver. | [
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PMID:16126 | The effect of calcium injection on the intracellular sodium and pH of snail neurones. | 1. Ion-sensitive glass micro-electrodes were used to measure the intracellular pH (pHi) and the intracellular sodium ion concentration, [Na+]i, in identified Helix aspersa neurones. 2. The injection of small volumes of 0-1 McaCl2, which increased the membrane potential by 10-15 mV for 1-2 min, had little or no effect on [Na+]i. Increases of up to 1 mM in [Na+]i could be reversibly induced by larger injections. 3. Calcium injection caused an immediate decrease in pHi, which appeared to be directly proportional to the amount of calcium injected. Injections causing hyperpolarizations of 10-20 mV which recovered in 2-5 min caused pHi decreases of 0-04-0-15 units. After each of these injections both pHi and the membrane potential recovered exponentially but with different time constants. 4. The injection of calcium at a low rate could decrease pHi without affecting the membrane potential. 5. Neither membrane potential nor pHi were affected by the injection of small volumes of 0-1 M-MgCl2, Injection of CoCl2 produced a large transient decrease in pHi but no significant change in membrane potential. 6. Exposure of the cell to saline equilibrated with 2-5% CO2 greatly reduced the pHi decrease caused by calcium injection but had only small effects on the membrane potential response. 7. It is concluded that most of the injected calcium is exchanged for protons inside the cell. | The effect of calcium injection on the intracellular sodium and pH of snail neurones. 1. Ion-sensitive glass micro-electrodes were used to measure the intracellular pH (pHi) and the intracellular sodium ion concentration, [Na+]i, in identified Helix aspersa neurones. 2. The injection of small volumes of 0-1 McaCl2, which increased the membrane potential by 10-15 mV for 1-2 min, had little or no effect on [Na+]i. Increases of up to 1 mM in [Na+]i could be reversibly induced by larger injections. 3. Calcium injection caused an immediate decrease in pHi, which appeared to be directly proportional to the amount of calcium injected. Injections causing hyperpolarizations of 10-20 mV which recovered in 2-5 min caused pHi decreases of 0-04-0-15 units. After each of these injections both pHi and the membrane potential recovered exponentially but with different time constants. 4. The injection of calcium at a low rate could decrease pHi without affecting the membrane potential. 5. Neither membrane potential nor pHi were affected by the injection of small volumes of 0-1 M-MgCl2, Injection of CoCl2 produced a large transient decrease in pHi but no significant change in membrane potential. 6. Exposure of the cell to saline equilibrated with 2-5% CO2 greatly reduced the pHi decrease caused by calcium injection but had only small effects on the membrane potential response. 7. It is concluded that most of the injected calcium is exchanged for protons inside the cell. | [
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|
PMID:16129 | Facilitation of transmitter secretion from toad motor nerve terminals during brief trains of action potentials. | 1. End-plate potentials produced by brief trains of action potentials (5-7 at 50-100 Hz) were recorded at toad sciatic-sartorius neuromuscular junctions. When transmitter secretion was depressed in solutions containing magnesium, the increase in amplitude (growth pattern) of successive end-plate-potentials was greater than could be accounted for by arithmetic summation of facilitation (arithmetic model) as proposed by Mallart & Martin (1967). 3. With e.p.p.s of normal quantral content or in solutions in which the calcium concentration was lowered, growth patterns were occasionally reasonably close to those predicted by the arithmetic model but there was always some degree of disparity. 4. A simple, two-step, kinetic model is described which is more consistent with the varied growth patterns of end-plate potentials that have been recorded. The model can predict growth patterns of e.p.p.s with high or low quantal content. | Facilitation of transmitter secretion from toad motor nerve terminals during brief trains of action potentials. 1. End-plate potentials produced by brief trains of action potentials (5-7 at 50-100 Hz) were recorded at toad sciatic-sartorius neuromuscular junctions. When transmitter secretion was depressed in solutions containing magnesium, the increase in amplitude (growth pattern) of successive end-plate-potentials was greater than could be accounted for by arithmetic summation of facilitation (arithmetic model) as proposed by Mallart & Martin (1967). 3. With e.p.p.s of normal quantral content or in solutions in which the calcium concentration was lowered, growth patterns were occasionally reasonably close to those predicted by the arithmetic model but there was always some degree of disparity. 4. A simple, two-step, kinetic model is described which is more consistent with the varied growth patterns of end-plate potentials that have been recorded. The model can predict growth patterns of e.p.p.s with high or low quantal content. | [
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PMID:16128 | Extracellular potassium and trasmitter release at the giant synapse of squid. | 1. The effects of changes in extracellular K concentration, [K]0, on synaptic transmission were studied at the squid giant synapse with intracellular recording from the presynaptic terminal and post-synaptic axon. 2. The amplitudes of both the presynaptic spike and the e.p.s.p. varied inversely with [K]0. On the average, a 10 mV change in spike height was accompanied by a 3-1 mV change in e.p.s.p. amplitude. 3. The amplitude of the presynaptic spike after-hyperpolarization (AH) varied inversely with [K]0. On the average, increasing [K]0 resulted in a 20% change in e.p.s.p. amplitude per mV change in presynaptic spike AH. 4. Repetitive antidromic stimulation of the post-synaptic giant axon resulted in an exponential decline in the post-synaptic spike AH, a depolarization of the presynaptic membrane potential and a reduction in the AHs of presynaptic spikes. This suggests that the K which accumulates in the extracellular spaces around the post-synaptic axon also affects the presynaptic terminal. 5. Repetitive antidromic stimulation of the post-synaptic axon resulted in a reduction in the amplitude of e.p.s.p.s. elicted by stimulation of the presynaptic axon. The reduction in e.p.s.p. amplitude relative to the change in presynaptic spike AH was quantitatively close to the change produced by increasing [K]0, suggesting that the reduction in e.p.s.p. amplitude is due to the accumulation of extracellular K at the presynaptic terminal. 6. Repetitive stimulation of the presynaptic axon reduced the amplitudes of the e.p.s.p. and the presynaptic spike AH. On the average, a 1 mV change in presynaptic spike AH was accompanied by a 204% change in e.p.s.p. amplitude, suggesting that K accumulation may only contribute to a small extent, under these conditions, to the depression of transmitter release. | Extracellular potassium and trasmitter release at the giant synapse of squid. 1. The effects of changes in extracellular K concentration, [K]0, on synaptic transmission were studied at the squid giant synapse with intracellular recording from the presynaptic terminal and post-synaptic axon. 2. The amplitudes of both the presynaptic spike and the e.p.s.p. varied inversely with [K]0. On the average, a 10 mV change in spike height was accompanied by a 3-1 mV change in e.p.s.p. amplitude. 3. The amplitude of the presynaptic spike after-hyperpolarization (AH) varied inversely with [K]0. On the average, increasing [K]0 resulted in a 20% change in e.p.s.p. amplitude per mV change in presynaptic spike AH. 4. Repetitive antidromic stimulation of the post-synaptic giant axon resulted in an exponential decline in the post-synaptic spike AH, a depolarization of the presynaptic membrane potential and a reduction in the AHs of presynaptic spikes. This suggests that the K which accumulates in the extracellular spaces around the post-synaptic axon also affects the presynaptic terminal. 5. Repetitive antidromic stimulation of the post-synaptic axon resulted in a reduction in the amplitude of e.p.s.p.s. elicted by stimulation of the presynaptic axon. The reduction in e.p.s.p. amplitude relative to the change in presynaptic spike AH was quantitatively close to the change produced by increasing [K]0, suggesting that the reduction in e.p.s.p. amplitude is due to the accumulation of extracellular K at the presynaptic terminal. 6. Repetitive stimulation of the presynaptic axon reduced the amplitudes of the e.p.s.p. and the presynaptic spike AH. On the average, a 1 mV change in presynaptic spike AH was accompanied by a 204% change in e.p.s.p. amplitude, suggesting that K accumulation may only contribute to a small extent, under these conditions, to the depression of transmitter release. | [
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|
PMID:16130 | [Arteriographic appearances seen in the course of development of the lesions of polyarteritis nodosa (author's transl)]. | Three cases of polyarteritis nodosa (P.A.N.) studied by abdominal arteriography with a follow-up examination between the 6th and 9th month are reported. In the first case, the initial arteriogram showed only the appearances of endarteritis. The second arteriogram, 9 months later, following a worsening of general condition, revealed diffuse aneurysms in the abdomen. In the second patient, who had multiple aneurysms at the time of the initial examination, arteriography agter 6 months following a new episode of the disease with an acute abdominal syndrome and collapse revealed, alongside the multiplication of the aneurysms with rupture of one of them, the disappearance of some ectasias with the obliteration of certain arteries. In the third patient, the follow-up arteriogram after treatment showed disappearance of the renal arteriograms which the first study had revealed 7 months before. These three cases give an idea of the different radiological appearances of P.A.N. The appearance of endarteritis with no specific characteristics indicates and inflammatory localisation of the disease. This is an initial stage leading to ectasia. Aneurysms may progress to rupture or may multiply. Endarteritis and ectasia may also progress towards scarring and disappear. A method of early diagnosis, arteriography makes it possible to institute treatment before the lesions reach a stage at which they must inevitably develop either into aneurysms or lead to obstruction with distal ischaemia. | [Arteriographic appearances seen in the course of development of the lesions of polyarteritis nodosa (author's transl)]. Three cases of polyarteritis nodosa (P.A.N.) studied by abdominal arteriography with a follow-up examination between the 6th and 9th month are reported. In the first case, the initial arteriogram showed only the appearances of endarteritis. The second arteriogram, 9 months later, following a worsening of general condition, revealed diffuse aneurysms in the abdomen. In the second patient, who had multiple aneurysms at the time of the initial examination, arteriography agter 6 months following a new episode of the disease with an acute abdominal syndrome and collapse revealed, alongside the multiplication of the aneurysms with rupture of one of them, the disappearance of some ectasias with the obliteration of certain arteries. In the third patient, the follow-up arteriogram after treatment showed disappearance of the renal arteriograms which the first study had revealed 7 months before. These three cases give an idea of the different radiological appearances of P.A.N. The appearance of endarteritis with no specific characteristics indicates and inflammatory localisation of the disease. This is an initial stage leading to ectasia. Aneurysms may progress to rupture or may multiply. Endarteritis and ectasia may also progress towards scarring and disappear. A method of early diagnosis, arteriography makes it possible to institute treatment before the lesions reach a stage at which they must inevitably develop either into aneurysms or lead to obstruction with distal ischaemia. | [
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|
PMID:16131 | The role of the urologist in barren marriages. | This paper is addressed to the gynecologist, who is generally the first to be consulted by the patient because of her failure to conceive. Early in the study there arises the problem of assigning individual factors. Is the patient involved solely, or is there also a male factor? Excluding the female's role to bear and nurture the fertilized cell until maturity, the frequency of subfertility in the male is just as great as it is in the female. Evaluation of the male should be done early in the study of the childless couple because it is less complex and less time consuming. Assignment of the relative fertility of husband and wife depends on the correlation of the findings in each. For that reason, also, treatment of the subfertile husband should not be undertaken until it is definitely determined that his wife is either reproductively normal or has remediable abnormalities. On the other hand, improvement of the fertility of one partner may be sufficient to induce pregnancy. Frequent communication between gynecologist and urologist is of utmost importance. An attempt is made to clarify for the gynecologist the abnormalities that may be encountered, the treatment to be employed and the prognosis. The mere fact that hormone administration is generally not effective in the male should not lead to the conclusion that treatment of the male is useless and that nothing can be done to improve his semen quality. | The role of the urologist in barren marriages. This paper is addressed to the gynecologist, who is generally the first to be consulted by the patient because of her failure to conceive. Early in the study there arises the problem of assigning individual factors. Is the patient involved solely, or is there also a male factor? Excluding the female's role to bear and nurture the fertilized cell until maturity, the frequency of subfertility in the male is just as great as it is in the female. Evaluation of the male should be done early in the study of the childless couple because it is less complex and less time consuming. Assignment of the relative fertility of husband and wife depends on the correlation of the findings in each. For that reason, also, treatment of the subfertile husband should not be undertaken until it is definitely determined that his wife is either reproductively normal or has remediable abnormalities. On the other hand, improvement of the fertility of one partner may be sufficient to induce pregnancy. Frequent communication between gynecologist and urologist is of utmost importance. An attempt is made to clarify for the gynecologist the abnormalities that may be encountered, the treatment to be employed and the prognosis. The mere fact that hormone administration is generally not effective in the male should not lead to the conclusion that treatment of the male is useless and that nothing can be done to improve his semen quality. | [
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|
PMID:16132 | Synthesis and biological activity of some vinyl-substituted 2-nitroimidazoles. | In previous studies 1-methyl-2-nitro-1H-imidazole-5-carboxaldehyde and 1-methyl-2-nitro-5-vinyl-1H-imidazole were found to posses interesting antimicrobial activities. We have now prepared some 2-nitro-1H-imidazoles in which the 5-vinyl chain bears selected functional groups (CHO, COCH3, NO2) as well as nitrogen-condensation derivatives of the carbonyl functions. Furthermore, 5-methyl-2-nitro-1-vinyl-1H-imidazole has been synthesized. All the compounds, and some intermediates, have been assayed for antimicrobial activity. Several of them exhibited significant antibacterial and antitrichomonal activity in mice. | Synthesis and biological activity of some vinyl-substituted 2-nitroimidazoles. In previous studies 1-methyl-2-nitro-1H-imidazole-5-carboxaldehyde and 1-methyl-2-nitro-5-vinyl-1H-imidazole were found to posses interesting antimicrobial activities. We have now prepared some 2-nitro-1H-imidazoles in which the 5-vinyl chain bears selected functional groups (CHO, COCH3, NO2) as well as nitrogen-condensation derivatives of the carbonyl functions. Furthermore, 5-methyl-2-nitro-1-vinyl-1H-imidazole has been synthesized. All the compounds, and some intermediates, have been assayed for antimicrobial activity. Several of them exhibited significant antibacterial and antitrichomonal activity in mice. | [
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|
PMID:16133 | N-(2,4,5-Trihydroxyphenehtyl)normetazocine, a potential irreversible inhibitor of the narcotic receptor. | The reaction of N-2,4,5-tribenzyloxyphenyl)ethyl methanesulfonate, prepared in a seven-step sequence, with normetazocine followed by hydrogenolysis of the benzyloxy-protecting groups, gave N-(2,4,5-trihydroxyphenethyl)normetazocine. This compound was prepared to study the effect of a narcotic analgesic containing a functional group which could be activated in situ to a moiety potentially capable of reacting irreversibly with the narcotic receptor. This 6-hydroxydopamin derivative of normetazocine did not prove to be a useful affinity label. Its low toxicity could indicate the necessity for the formation of an aminochrome system for the expression of toxicity by 6-hydroxydopamine. | N-(2,4,5-Trihydroxyphenehtyl)normetazocine, a potential irreversible inhibitor of the narcotic receptor. The reaction of N-2,4,5-tribenzyloxyphenyl)ethyl methanesulfonate, prepared in a seven-step sequence, with normetazocine followed by hydrogenolysis of the benzyloxy-protecting groups, gave N-(2,4,5-trihydroxyphenethyl)normetazocine. This compound was prepared to study the effect of a narcotic analgesic containing a functional group which could be activated in situ to a moiety potentially capable of reacting irreversibly with the narcotic receptor. This 6-hydroxydopamin derivative of normetazocine did not prove to be a useful affinity label. Its low toxicity could indicate the necessity for the formation of an aminochrome system for the expression of toxicity by 6-hydroxydopamine. | [
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|
PMID:16134 | 5-allyl-9-oxobenzomorphans. 3. Potent narcotic antagonists and analgesics-antagonists in the series of substituted 2',9beta-dihydroxy-6,7-benzomorphans. | 5-Allyl-2'-methoxy-2-methyl-9-oxo-6,7-benzomorphan methiodide (1) has been converted in a selective two-step process to the corresponding 9beta-hydroxy intermediates 4 and 6, which in turn were transformed via modified von Braun demethylation-acylation to the amides 11 and 21, respectively. These were reduced and demethylated to give a series of 5-allyl-2',9beta-dihydroxy-2-substituted 6,7-benzomorphans 13 and 23, some of which have been found to be highly potent narcotic antagonists and/or analgesics. The resolution of the most interesting compounds (23a and 23b) and pharmacological properties of the optical isomers are also described. Reduction of the double bond in 13 and 23 to give 14 and 24, with one exception, did not appreciably alter pharmacological profiles, while cyclization to the tetrahydrofuranobenzomorphans 25 substantially reduced the level of activities. | 5-allyl-9-oxobenzomorphans. 3. Potent narcotic antagonists and analgesics-antagonists in the series of substituted 2',9beta-dihydroxy-6,7-benzomorphans. 5-Allyl-2'-methoxy-2-methyl-9-oxo-6,7-benzomorphan methiodide (1) has been converted in a selective two-step process to the corresponding 9beta-hydroxy intermediates 4 and 6, which in turn were transformed via modified von Braun demethylation-acylation to the amides 11 and 21, respectively. These were reduced and demethylated to give a series of 5-allyl-2',9beta-dihydroxy-2-substituted 6,7-benzomorphans 13 and 23, some of which have been found to be highly potent narcotic antagonists and/or analgesics. The resolution of the most interesting compounds (23a and 23b) and pharmacological properties of the optical isomers are also described. Reduction of the double bond in 13 and 23 to give 14 and 24, with one exception, did not appreciably alter pharmacological profiles, while cyclization to the tetrahydrofuranobenzomorphans 25 substantially reduced the level of activities. | [
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|
PMID:16135 | Synthesis and narcotic agonist-antagonist evaluation of some 2,6-methano-3-benzazocine-11 propanols. Analogues of the ring C bridged oripavine-7-mehtanols. | A general synthesis of variously substituted 2,6-methano-3-benzazocine-11-propanols is described. Nine N-CH3 derivatives and their corresponding N-cyclopropylmethyl counterparts were prepared and studied in the mouse acetylcholine induced writhing and rat phenazocine antagonism tests. The results are compared with literature information on the bridged oripavine methanols. It is concluded that the synthetic analogues have a different structure-activity profile, in general being weak agonists but potent antagonists. | Synthesis and narcotic agonist-antagonist evaluation of some 2,6-methano-3-benzazocine-11 propanols. Analogues of the ring C bridged oripavine-7-mehtanols. A general synthesis of variously substituted 2,6-methano-3-benzazocine-11-propanols is described. Nine N-CH3 derivatives and their corresponding N-cyclopropylmethyl counterparts were prepared and studied in the mouse acetylcholine induced writhing and rat phenazocine antagonism tests. The results are compared with literature information on the bridged oripavine methanols. It is concluded that the synthetic analogues have a different structure-activity profile, in general being weak agonists but potent antagonists. | [
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|
PMID:16136 | Adrenergic agents. 4. Substituted phenoxypropanolamine derivatives as potential beta-adrenergic agonists. | A series of 1-(substituted phenoxy)-3-(tert-butylamino)-2-propanols in which the ring substituents were 3,4-dihydroxy (6f), 3- and 4-hydroxy (6g and 6h, respectively), 3-hydroxy-4-methylsulfonamido (6i), its 3,4-transposed isomer (6j), and 4-methylsulfonylmethyl (6k) was prepared and examined for beta-adrenergic agonist and/or antagonist properties. Two of these compounds, 6f and 6j, were potent beta-adrenoreceptor agonists in in vitro tests that measure a compound's ability to relax guinea pig tracheal smooth muscle and to increase the rate of contraction of guinea pig right atria. Several compounds had a dose-dependent effect. Although they produced potent beta-adrenergic agonist activity at low concentrations, 6g, 6h, and 6j antagonized the effects of a standard beta-adrenoreceptor agonist at higher concentrations. The methylsulfonylmethyl derivative 6k produced beta-adrenergic blocking effects as demonstrated by attenuation of isoproterenol-induced increases in the rate of contraction of an isolated rabbit heart preparation. On the basis of these pharmacological results, coupled with NMR spectral data, it appears that the previous suggestion that aryloxypropanolamines interact with beta-adrenocreceptors as a consequence of their ability to assume an orientation in which the benzene ring the ethanolamine moieties can be superimposed on those of corresponding adrenergic phenylethanolamines is invalid. An alternative "bicyclic" rigid conformation involving two intramolecular hydrogen bonds in the protonated form of the aryloxypropanolamines is suggested to account for the similar beta-adrenoreceptor activity of these compounds and related phenylethanolamines. | Adrenergic agents. 4. Substituted phenoxypropanolamine derivatives as potential beta-adrenergic agonists. A series of 1-(substituted phenoxy)-3-(tert-butylamino)-2-propanols in which the ring substituents were 3,4-dihydroxy (6f), 3- and 4-hydroxy (6g and 6h, respectively), 3-hydroxy-4-methylsulfonamido (6i), its 3,4-transposed isomer (6j), and 4-methylsulfonylmethyl (6k) was prepared and examined for beta-adrenergic agonist and/or antagonist properties. Two of these compounds, 6f and 6j, were potent beta-adrenoreceptor agonists in in vitro tests that measure a compound's ability to relax guinea pig tracheal smooth muscle and to increase the rate of contraction of guinea pig right atria. Several compounds had a dose-dependent effect. Although they produced potent beta-adrenergic agonist activity at low concentrations, 6g, 6h, and 6j antagonized the effects of a standard beta-adrenoreceptor agonist at higher concentrations. The methylsulfonylmethyl derivative 6k produced beta-adrenergic blocking effects as demonstrated by attenuation of isoproterenol-induced increases in the rate of contraction of an isolated rabbit heart preparation. On the basis of these pharmacological results, coupled with NMR spectral data, it appears that the previous suggestion that aryloxypropanolamines interact with beta-adrenocreceptors as a consequence of their ability to assume an orientation in which the benzene ring the ethanolamine moieties can be superimposed on those of corresponding adrenergic phenylethanolamines is invalid. An alternative "bicyclic" rigid conformation involving two intramolecular hydrogen bonds in the protonated form of the aryloxypropanolamines is suggested to account for the similar beta-adrenoreceptor activity of these compounds and related phenylethanolamines. | [
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|
PMID:16138 | Plasmalemma transport of OH- in Chara corallina: dynamics of activation and deactivation. | The light-mediated, time-dependent rise in the pH value at the center of an alkaline band was analyzed using the methods of numerical analysis. From this analysis an expression of the time-dependent build-up of OH- efflux was obtained for these bands. This information can now be employed to determine whether the light-activated transport of OH- and HCO3- influences the electrical properties of the plasmalemma. The dark-induced deactivation of OH- transport was also characterized, revealing a transition from efflux to a transient influx phase during deactivation. Numerical analysis of the steady-state OH- diffusion pattern, established along the surface of an alkaline band, revealed that the OH- efflux width was wider than previously envisaged. It was also found the OH- sink regions exist on either side of the efflux zone. These, and other characteristics revealed by the numerical analysis, enabled us to extend the OH- transport model proposed by Lucas (J. Exp. Bot. 1975, 26:347). | Plasmalemma transport of OH- in Chara corallina: dynamics of activation and deactivation. The light-mediated, time-dependent rise in the pH value at the center of an alkaline band was analyzed using the methods of numerical analysis. From this analysis an expression of the time-dependent build-up of OH- efflux was obtained for these bands. This information can now be employed to determine whether the light-activated transport of OH- and HCO3- influences the electrical properties of the plasmalemma. The dark-induced deactivation of OH- transport was also characterized, revealing a transition from efflux to a transient influx phase during deactivation. Numerical analysis of the steady-state OH- diffusion pattern, established along the surface of an alkaline band, revealed that the OH- efflux width was wider than previously envisaged. It was also found the OH- sink regions exist on either side of the efflux zone. These, and other characteristics revealed by the numerical analysis, enabled us to extend the OH- transport model proposed by Lucas (J. Exp. Bot. 1975, 26:347). | [
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PMID:16141 | Growth of a heterologous tumor cell line in neonatal rats with graft-versus-host disease. | The ability of a hamster tumor cell line (T20) to grow and exhibit type H virus particles was significantly enhanced in neonatal DA rats with graft-versus-host disease (GVHD). Tumor growth peaked on days 4 and 7 in control littermates receiving adult syngeneic cells or no cells at birth, respectively, and then subsequently disappeared. However, tumor nodules in animals with GVHD became significantly larger than those in controls by day 7 and continued to grow until death. In addition, a marked plasma cell infiltration was noticed in such rapidly growing tumors from animals with GVHD only. In the light of previous studies, evidence is discussed for an environment within animals with GVHD conducive for tumor cell growth because of a depletion of T-cell areas within their tissues. | Growth of a heterologous tumor cell line in neonatal rats with graft-versus-host disease. The ability of a hamster tumor cell line (T20) to grow and exhibit type H virus particles was significantly enhanced in neonatal DA rats with graft-versus-host disease (GVHD). Tumor growth peaked on days 4 and 7 in control littermates receiving adult syngeneic cells or no cells at birth, respectively, and then subsequently disappeared. However, tumor nodules in animals with GVHD became significantly larger than those in controls by day 7 and continued to grow until death. In addition, a marked plasma cell infiltration was noticed in such rapidly growing tumors from animals with GVHD only. In the light of previous studies, evidence is discussed for an environment within animals with GVHD conducive for tumor cell growth because of a depletion of T-cell areas within their tissues. | [
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|
PMID:16142 | Carcinoma in situ of the ectopic testis. | A young man with a palpable ectopic testis underwent right testis biopsy and orchiopexy. Since histological findings of the biopsy specimen revealed an unsuspected intratubular carcinoma in situ and evidence of diminished spermatogenic potential, an inguinal orchiectomy was done. This appears to be the first reported case of a tumor of this type developing in an undescended testis. | Carcinoma in situ of the ectopic testis. A young man with a palpable ectopic testis underwent right testis biopsy and orchiopexy. Since histological findings of the biopsy specimen revealed an unsuspected intratubular carcinoma in situ and evidence of diminished spermatogenic potential, an inguinal orchiectomy was done. This appears to be the first reported case of a tumor of this type developing in an undescended testis. | [
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|
PMID:16143 | Childhood gonadoblastoma and seminoma in a dysgenetic cryptorchid gonad. | A case of gonadoblastoma and seminoma occurring in a genotypic male child with ambiguous genitalia is presented. A review of the literature establishes that children with intersex disorders who possess a Y chromosome and undescended gonads stand a particularly high risk of having this type of gonadal neoplasm and should be explored. | Childhood gonadoblastoma and seminoma in a dysgenetic cryptorchid gonad. A case of gonadoblastoma and seminoma occurring in a genotypic male child with ambiguous genitalia is presented. A review of the literature establishes that children with intersex disorders who possess a Y chromosome and undescended gonads stand a particularly high risk of having this type of gonadal neoplasm and should be explored. | [
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|
PMID:16144 | Acute bacteremia in asplenic renal transplant patients. | Four cases of overwhelming bacteremia were observed in asplenic renal transplant patients 12 to 20 months after transplantation. The bacteriologic findings and presentation of these infections are characteristic of post-splenectomy sepsis reported in nontransplant patients. It is suggested that the absence of the spleen, more than immunosuppression with azathioprine and prednisone, predisposes to these late, uncommon infections after transplantation. | Acute bacteremia in asplenic renal transplant patients. Four cases of overwhelming bacteremia were observed in asplenic renal transplant patients 12 to 20 months after transplantation. The bacteriologic findings and presentation of these infections are characteristic of post-splenectomy sepsis reported in nontransplant patients. It is suggested that the absence of the spleen, more than immunosuppression with azathioprine and prednisone, predisposes to these late, uncommon infections after transplantation. | [
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|
PMID:16145 | Prune-belly syndrome in a 54-year-old man. | A 54-year-old man was diagnosed as having prune-belly syndrome, a deficiency of abdominal musculature, cryptorchidism, abnormalities of the urinary tract, and chronic renal failure. The patient was asymptomatic until the diagnosis was made at the age of 54 years; he is one of the oldest living patients to be reported in detail. Recognition of the syndrome in adults with chronic renal failure is important. | Prune-belly syndrome in a 54-year-old man. A 54-year-old man was diagnosed as having prune-belly syndrome, a deficiency of abdominal musculature, cryptorchidism, abnormalities of the urinary tract, and chronic renal failure. The patient was asymptomatic until the diagnosis was made at the age of 54 years; he is one of the oldest living patients to be reported in detail. Recognition of the syndrome in adults with chronic renal failure is important. | [
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|
PMID:16149 | Antibiotic susceptibility of Streptococcus pneumoniae isolated from clinical materials (author's transl). | We tested the drug-susceptibility of 112 strains of Streptococcus pneumoniae isolated from various clinical materials since January 1975 to May 1976, and observed the changes of susceptibility of this pathogen. All strains tested remained very sensitive to benzylpenicillin and cephaloridine, but 59.8% of strains were resistant to tetracycline and 44.7% to chloramphenicol, and about 90% of chloramphenicol-resistant strains were also resistant to tetracycline. The percentage of resistant strains to tetracycline or chloramphenicol is increasing. Cross-resistance between tetracycline and doxycycline or chloramphenicol and thiamphenicol was observed. On this time we found three strains resistant to macrolides. Two of these strains were resistant to erythromycin, josamycin, oleandomycin, spiarmycin, mydecamycin, lincomycin, clindamycin and tetracycline, but one was resistant to josamycin, spiramycin, mydecamycin and chloramphenicol. | Antibiotic susceptibility of Streptococcus pneumoniae isolated from clinical materials (author's transl). We tested the drug-susceptibility of 112 strains of Streptococcus pneumoniae isolated from various clinical materials since January 1975 to May 1976, and observed the changes of susceptibility of this pathogen. All strains tested remained very sensitive to benzylpenicillin and cephaloridine, but 59.8% of strains were resistant to tetracycline and 44.7% to chloramphenicol, and about 90% of chloramphenicol-resistant strains were also resistant to tetracycline. The percentage of resistant strains to tetracycline or chloramphenicol is increasing. Cross-resistance between tetracycline and doxycycline or chloramphenicol and thiamphenicol was observed. On this time we found three strains resistant to macrolides. Two of these strains were resistant to erythromycin, josamycin, oleandomycin, spiarmycin, mydecamycin, lincomycin, clindamycin and tetracycline, but one was resistant to josamycin, spiramycin, mydecamycin and chloramphenicol. | [
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|
PMID:16151 | T cell function detected in murine bone marrow cells. | Mouse bone marrow cells were fractionated by BSA discontinuous density gradient centrifugation, and a small lymphocyte rich fraction was obtained at the high density. Cells of this fraction were shown to respond in vitro to T cell mitogens and alloantigens. Furthermore, they were able to mount a graft-versus-host reaction when assessed by spleen weight assay and by the method of inhibiting erythroid cell growth by allogeneic lymphoid cells. The results indicate that these lymphocytes possess T cell functions. On the other hand they were found to carry only little theta antigen assessed by the cytotoxic test and by the absorption test. It is presumed, therefore, that the amount of theta antigen on a cell might not correlate with T cell functions, and these lymphocytes might be mature ones in the course of postthymic maturation. Hemopoietic stem cells were determined by spleen colony formation and the peak of colony-forming efficiency was seen at the low density. These observations imply that immunocompetent cells causing GVHR can be separated from hemopoietic stem cells. This procedure may be applied for prevention and reduction of GVHR in allogeneic bone marrow transplantation in human. | T cell function detected in murine bone marrow cells. Mouse bone marrow cells were fractionated by BSA discontinuous density gradient centrifugation, and a small lymphocyte rich fraction was obtained at the high density. Cells of this fraction were shown to respond in vitro to T cell mitogens and alloantigens. Furthermore, they were able to mount a graft-versus-host reaction when assessed by spleen weight assay and by the method of inhibiting erythroid cell growth by allogeneic lymphoid cells. The results indicate that these lymphocytes possess T cell functions. On the other hand they were found to carry only little theta antigen assessed by the cytotoxic test and by the absorption test. It is presumed, therefore, that the amount of theta antigen on a cell might not correlate with T cell functions, and these lymphocytes might be mature ones in the course of postthymic maturation. Hemopoietic stem cells were determined by spleen colony formation and the peak of colony-forming efficiency was seen at the low density. These observations imply that immunocompetent cells causing GVHR can be separated from hemopoietic stem cells. This procedure may be applied for prevention and reduction of GVHR in allogeneic bone marrow transplantation in human. | [
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|
PMID:16152 | Physicochemical properties of a liquid ion exchanger microelectrode and its application to biological fluids. | Double-barreled potassium or chloride ion-selective microelectrodes were constructed using a liquid ion exchanger. Technical details of the fabrication of double-barreled microelectrodes, having a PD sensor as one barrel and an ionic sensor as the other, are described. The sensitivity of K+ or CI- ion-selective microelectrodes exhibited an approximately Nernstian response over a temperature range of 7 degrees-37 degrees C, and the electromotive force (EMF) was stable within +/- mV for a few hours. The rise time was less than 1 sec. The effect of pH on the electrode response was negligible over a physiological range of pH 5.6 to 7.8. The selectivity constants of the K+ microelectrode to other cations were 0.011 for Na+, 0.200 for NH+4, and less than 0.002 and 0.001 for Ca++ and Mg++, respectively, while that of the CI- microelectrode was 0.067 for HCO-3. Glucose or urea has no effect on the EMF. Protein has a significant effect on ion exchanger membrane only when the concentration of the tested ion is low and protein is high. On the basis of this background the determination of K+ and CI- activity was carried out both in vivo and in vitro on several biological samples, such as serum, tissue and cellular fluids, and other protein-containing fluids. The values obtained with the microelectrode were consistent with those obtained with the other conventional methods or with the current theory on electrolyte solutions. These results were taken to assure the practical application of these electrodes to biological studies in many fields. | Physicochemical properties of a liquid ion exchanger microelectrode and its application to biological fluids. Double-barreled potassium or chloride ion-selective microelectrodes were constructed using a liquid ion exchanger. Technical details of the fabrication of double-barreled microelectrodes, having a PD sensor as one barrel and an ionic sensor as the other, are described. The sensitivity of K+ or CI- ion-selective microelectrodes exhibited an approximately Nernstian response over a temperature range of 7 degrees-37 degrees C, and the electromotive force (EMF) was stable within +/- mV for a few hours. The rise time was less than 1 sec. The effect of pH on the electrode response was negligible over a physiological range of pH 5.6 to 7.8. The selectivity constants of the K+ microelectrode to other cations were 0.011 for Na+, 0.200 for NH+4, and less than 0.002 and 0.001 for Ca++ and Mg++, respectively, while that of the CI- microelectrode was 0.067 for HCO-3. Glucose or urea has no effect on the EMF. Protein has a significant effect on ion exchanger membrane only when the concentration of the tested ion is low and protein is high. On the basis of this background the determination of K+ and CI- activity was carried out both in vivo and in vitro on several biological samples, such as serum, tissue and cellular fluids, and other protein-containing fluids. The values obtained with the microelectrode were consistent with those obtained with the other conventional methods or with the current theory on electrolyte solutions. These results were taken to assure the practical application of these electrodes to biological studies in many fields. | [
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|
PMID:16153 | Effects of intracellular pH on plateau formation following the action potential of squid giant axons. | When squid giant axons were intracellularly perfused for about 10 min with 100 mM K+ solutions containing Pronase or Protease Type VII at a concentration of 0.1-0.5 mg/ml, the action potential developed a long-lasting plateau. The plateau persisted after switching to an enzyme-free solution at standard pH (7.3 +/- 0.1) as the intracellular perfusate. The plateau was promptly and completely suppressed when the intracellular pH was lowered below 6.5. Upon increase of pH again to the standard level, the plateau promptly reappeared. With alkaline intracellular pH plateau formation was enhanced. Lowering the pH of the extracellular medium to 5 did not influence the plateau. The duration of the action potential under bi-ionic conditions (inside Cs+, outside Ca++) decreased with low intracellular pH and increased with high intracellular pH. The plateau duration of the action potential from axons intracellularly perfused with solutions containing 10 mM tetraethylammonium also decreased with low intracellular pH and increased with high intracellular pH. The underlying mechanisms for the pH effects remain to be explored. | Effects of intracellular pH on plateau formation following the action potential of squid giant axons. When squid giant axons were intracellularly perfused for about 10 min with 100 mM K+ solutions containing Pronase or Protease Type VII at a concentration of 0.1-0.5 mg/ml, the action potential developed a long-lasting plateau. The plateau persisted after switching to an enzyme-free solution at standard pH (7.3 +/- 0.1) as the intracellular perfusate. The plateau was promptly and completely suppressed when the intracellular pH was lowered below 6.5. Upon increase of pH again to the standard level, the plateau promptly reappeared. With alkaline intracellular pH plateau formation was enhanced. Lowering the pH of the extracellular medium to 5 did not influence the plateau. The duration of the action potential under bi-ionic conditions (inside Cs+, outside Ca++) decreased with low intracellular pH and increased with high intracellular pH. The plateau duration of the action potential from axons intracellularly perfused with solutions containing 10 mM tetraethylammonium also decreased with low intracellular pH and increased with high intracellular pH. The underlying mechanisms for the pH effects remain to be explored. | [
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|
PMID:16154 | Effects of sodium bicarbonate administration during cardiopulmonary resuscitation. | To study whether sodium bicarbonate given in cardiopulmonary resuscitation may produce life-threatening hyperosmolality or hypernatremia, arterial blood was analysed for blood gas, alcohol, blood urea nitrogen, electrolyte and osmolality. The blood was drawn after resuscitation in successful cases, and while effective massage and ventilation were being applied in unsuccessful resuscitations. Seven of the 17 resuscitations were successful. Serum sodium concentrations ranged from 135 to 154 with one exception and did not correlate with the amount of sodium bicarbonate administered. Arterial pH ranged from 6.38 to 7.71; only one patient had metabolic alkalosis. Serum osmolality ranged from 301 to 407. The data suggests a net increase in osmolality of 6 mOsm/50 mEq of sodium bicarbonate. | Effects of sodium bicarbonate administration during cardiopulmonary resuscitation. To study whether sodium bicarbonate given in cardiopulmonary resuscitation may produce life-threatening hyperosmolality or hypernatremia, arterial blood was analysed for blood gas, alcohol, blood urea nitrogen, electrolyte and osmolality. The blood was drawn after resuscitation in successful cases, and while effective massage and ventilation were being applied in unsuccessful resuscitations. Seven of the 17 resuscitations were successful. Serum sodium concentrations ranged from 135 to 154 with one exception and did not correlate with the amount of sodium bicarbonate administered. Arterial pH ranged from 6.38 to 7.71; only one patient had metabolic alkalosis. Serum osmolality ranged from 301 to 407. The data suggests a net increase in osmolality of 6 mOsm/50 mEq of sodium bicarbonate. | [
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|
PMID:16155 | Cryptorchidism and abdominal pain. | In this case report, abdominal symptoms simulating acute appendicitis were due to recurrent torsion of an intra-abdominal testicle. Cryptorchidism frequently goes unnoted. Most undescended testicles are in the groin and easily palpable. If not, they can be absent, retroperitoneal or intra-abdominal. An intra-abdominal testicle is more likely to occur on the right than the left. | Cryptorchidism and abdominal pain. In this case report, abdominal symptoms simulating acute appendicitis were due to recurrent torsion of an intra-abdominal testicle. Cryptorchidism frequently goes unnoted. Most undescended testicles are in the groin and easily palpable. If not, they can be absent, retroperitoneal or intra-abdominal. An intra-abdominal testicle is more likely to occur on the right than the left. | [
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|
PMID:16156 | Acid-base relationships in the different body compartments: the basis for a simplified diagnostic approach. | Special characteristics of cellular buffering must be taken into account in order to describe accurately acid-base relationships in the whole body. In particular, tissues other than blood are able to neutralize mineral acid independent of changes in Pco(2) and hence independent of large changes in extra- and intracellular pH. Although mechanistic details remain to be clarified, relationships that describe this tissue buffering in quantitative terms are well established. In this report, emphasis is placed on quantitative relationships that stress the need for diagnostic interpretation derived from acid-base changes within the whole body rather than simply within the blood compartment. Theoreticalproblems with respect ot buffering mechanisms in various body compartments are reviewed and analyzed. | Acid-base relationships in the different body compartments: the basis for a simplified diagnostic approach. Special characteristics of cellular buffering must be taken into account in order to describe accurately acid-base relationships in the whole body. In particular, tissues other than blood are able to neutralize mineral acid independent of changes in Pco(2) and hence independent of large changes in extra- and intracellular pH. Although mechanistic details remain to be clarified, relationships that describe this tissue buffering in quantitative terms are well established. In this report, emphasis is placed on quantitative relationships that stress the need for diagnostic interpretation derived from acid-base changes within the whole body rather than simply within the blood compartment. Theoreticalproblems with respect ot buffering mechanisms in various body compartments are reviewed and analyzed. | [
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|
PMID:16157 | [Use of coronaroactive agents with beta-stimulating effect in ischemic heart disease]. | In feline experiments and 65 clinical cases of ischaemic heart disease the efficacy of a new beta-stimulating agetn -- Ildamen -- was studied, the obtained effect was compared to that of Euphillin. Ildamen was found to be highly effective in patients with a moderately decreased coronary reserve and without atherosclerotic lesions in the coronary vessels. | [Use of coronaroactive agents with beta-stimulating effect in ischemic heart disease]. In feline experiments and 65 clinical cases of ischaemic heart disease the efficacy of a new beta-stimulating agetn -- Ildamen -- was studied, the obtained effect was compared to that of Euphillin. Ildamen was found to be highly effective in patients with a moderately decreased coronary reserve and without atherosclerotic lesions in the coronary vessels. | [
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|
PMID:16160 | Acidifying defect induced by amphotericin B: comparison of bicarbonate and hydrogen ion permeabilities. | The defect in urinary acidification induced by amphotericin B (AMB) was further characterized in turtle bladder. Since AMB has been shown to increase the hydrogen ion (H+) permeability of this epithelium in the absence of exogenous bicarbonate ions (HCO3-), we explored the permeability characteristics in the presence of imposed bicarbonate ion gradients, comparable to those occurring in vivo. With mucosal (M) pH lowered to the point of zero net hydrogen ion secretion, the transepithelial flow of bicarbonate ions (JHCO3) from serosa (S) to M was 0.91 +/- .06 y mole/hr in response to a 20 mM HCO3- gradient. After AMB addition to M, back diffusion of hydrogen ions from M to S (-JH) increased from zero to 0.36+/-0.05 micronmole/hr, whereas bicarbonate ion transport from S to M (JHCO3) failed to increase (0.91+/-0.06 before and 0.82+/-0.09 micronmole/hr after AMB). In contrast to M addition, S addition of AMB had no effect on either -JH or JHCO3. The defect in urinary acidification induced by AMB is characterized by a large increase in the permeability for hydrogen ions rather than that for bicarbonate ions and depends on direct exposure of the luminal cell membrane to AMB. The permeability increase is cation selective, not only for hydrogen ions but also, as shown previously, for potassium ions, and to a lesser extent, for sodium ions. The results are consistent with the formation by AMB of aqueous half pores in the luminal membrane. Although the passive permeabilities for bicarbonate and chloride ions are not affected primarily, they may increase after prolonged exposure, probably as a results of paracellular leaks that are not specific for AMB. | Acidifying defect induced by amphotericin B: comparison of bicarbonate and hydrogen ion permeabilities. The defect in urinary acidification induced by amphotericin B (AMB) was further characterized in turtle bladder. Since AMB has been shown to increase the hydrogen ion (H+) permeability of this epithelium in the absence of exogenous bicarbonate ions (HCO3-), we explored the permeability characteristics in the presence of imposed bicarbonate ion gradients, comparable to those occurring in vivo. With mucosal (M) pH lowered to the point of zero net hydrogen ion secretion, the transepithelial flow of bicarbonate ions (JHCO3) from serosa (S) to M was 0.91 +/- .06 y mole/hr in response to a 20 mM HCO3- gradient. After AMB addition to M, back diffusion of hydrogen ions from M to S (-JH) increased from zero to 0.36+/-0.05 micronmole/hr, whereas bicarbonate ion transport from S to M (JHCO3) failed to increase (0.91+/-0.06 before and 0.82+/-0.09 micronmole/hr after AMB). In contrast to M addition, S addition of AMB had no effect on either -JH or JHCO3. The defect in urinary acidification induced by AMB is characterized by a large increase in the permeability for hydrogen ions rather than that for bicarbonate ions and depends on direct exposure of the luminal cell membrane to AMB. The permeability increase is cation selective, not only for hydrogen ions but also, as shown previously, for potassium ions, and to a lesser extent, for sodium ions. The results are consistent with the formation by AMB of aqueous half pores in the luminal membrane. Although the passive permeabilities for bicarbonate and chloride ions are not affected primarily, they may increase after prolonged exposure, probably as a results of paracellular leaks that are not specific for AMB. | [
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|
PMID:16171 | [The role of proximal osteomy of the tibia in the treatment of arthrosis of the knee joint]. | The results of heigh tibia osteotomy performed between 1970 and 1975 in 20 cases in the material of the Orthopaedic Department of the "Semmelweis" University Medical School, Budapest, are reported. In 13 cases good--in 6 cases satisfactory results have been obtained. In 1 case the surgical intervention was of no effect. With regard to the explicit pain-relieving effect the operation is recommended by the authors in the treatment of knee arthrosis. | [The role of proximal osteomy of the tibia in the treatment of arthrosis of the knee joint]. The results of heigh tibia osteotomy performed between 1970 and 1975 in 20 cases in the material of the Orthopaedic Department of the "Semmelweis" University Medical School, Budapest, are reported. In 13 cases good--in 6 cases satisfactory results have been obtained. In 1 case the surgical intervention was of no effect. With regard to the explicit pain-relieving effect the operation is recommended by the authors in the treatment of knee arthrosis. | [
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|
PMID:16172 | [Restoration problems in frontoglabellar skull defects]. | Replacement problems of frontoglabellar skull defects and their recent operative methods come under review. A new method for the prevention of infection of paranasal sinus origin is reported in the article. Possibilities for producing good contour frontal area prothesis are considered here. The new method developed by the authors for orbital roof replacement is justified not only by cosmetics but physiology as well. | [Restoration problems in frontoglabellar skull defects]. Replacement problems of frontoglabellar skull defects and their recent operative methods come under review. A new method for the prevention of infection of paranasal sinus origin is reported in the article. Possibilities for producing good contour frontal area prothesis are considered here. The new method developed by the authors for orbital roof replacement is justified not only by cosmetics but physiology as well. | [
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|
PMID:16173 | [Post-traumatic protrusion of the hip joint]. | 23 patients with post-traumatic protrusion of the hip joint--due to fracture of the base of the acetabulum--have been re-examined by the authors. On the basis of the radiomorphological alterations developed in consequence of the fracture and according to the severity of the articular deformation the cases have been classified into four categories. The relationship between the morphological alteration, the functional ability of the joint and the subsequent arthrosis--as well as the problems of the social rehabilitation are discussed. | [Post-traumatic protrusion of the hip joint]. 23 patients with post-traumatic protrusion of the hip joint--due to fracture of the base of the acetabulum--have been re-examined by the authors. On the basis of the radiomorphological alterations developed in consequence of the fracture and according to the severity of the articular deformation the cases have been classified into four categories. The relationship between the morphological alteration, the functional ability of the joint and the subsequent arthrosis--as well as the problems of the social rehabilitation are discussed. | [
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|
PMID:16174 | [Malignant degeneration of chronic suppurative bone diseases]. | Out of 1189 patients with osteomyelitis of the Hungarian Institute of Medical Rehabilitation malignant degeneration in the region of purulent bone process has been observed in 6 cases by the authors. Out of them 5 cases were carcinoma planocellulare and 1 case was sarcoma gigantocellulare. During the detailed analyses of the cases it is pointed out by the authors that on the basis of the standpoint established regarding the rehabilitation in locomotor diseases the indication of the amputation in patients with osteomyelitis is not absolutely limited to the cases undoubtedly malignized. Rehabilitation and resocialization of the patients is better promoted with the performed amputation and the up-to-date manufactured prosthesis than by a series of unsuccessful and hazardous therapeutical experiments. | [Malignant degeneration of chronic suppurative bone diseases]. Out of 1189 patients with osteomyelitis of the Hungarian Institute of Medical Rehabilitation malignant degeneration in the region of purulent bone process has been observed in 6 cases by the authors. Out of them 5 cases were carcinoma planocellulare and 1 case was sarcoma gigantocellulare. During the detailed analyses of the cases it is pointed out by the authors that on the basis of the standpoint established regarding the rehabilitation in locomotor diseases the indication of the amputation in patients with osteomyelitis is not absolutely limited to the cases undoubtedly malignized. Rehabilitation and resocialization of the patients is better promoted with the performed amputation and the up-to-date manufactured prosthesis than by a series of unsuccessful and hazardous therapeutical experiments. | [
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|
PMID:16175 | [Ultrastructural changes in the skeletal muscles following nerve and tendon injuries in man. II. Nerve injuries]. | The alterations occuring in the fine structure of the man's hand muscles after traumatic nerve injuries have been examined by the authors. In the muscle portions taken in the 6th--16th weeks after the injury considerable atrophy of the contractile components, the desorganisation of the myofilaments, and the atropy of the mitochondrium and the sarcoplasmatic reticulum have been observed. The motor end-organs are athropic or their place is indicated but by a single great vacuolum. In the motor nerve fibres the typical picture of Waller's degeneration was seen. | [Ultrastructural changes in the skeletal muscles following nerve and tendon injuries in man. II. Nerve injuries]. The alterations occuring in the fine structure of the man's hand muscles after traumatic nerve injuries have been examined by the authors. In the muscle portions taken in the 6th--16th weeks after the injury considerable atrophy of the contractile components, the desorganisation of the myofilaments, and the atropy of the mitochondrium and the sarcoplasmatic reticulum have been observed. The motor end-organs are athropic or their place is indicated but by a single great vacuolum. In the motor nerve fibres the typical picture of Waller's degeneration was seen. | [
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|
PMID:16176 | [Structure and configuration of human tendons. II. Development of tendon structure during ontogenesis]. | In infants born in the 24th--30th weeks of the gravidity the praenatal development and the process of the organization of the tendinous structure have been examined by the authors. By means of photo- and polarization microscopic examinations it was found that the tendon of the flexor hand muscles (M. flexor carpi radialis, M. flexor digitorum comm.) shows mature tendinous structure earlier, than the tendons of the flexor muscles of the lower extremity (M. semitendinosus femoris, M. triceps surae). The tendons of the extensor muscles of the lower extremity (M. quadriceps femoris, M. tibialis ant.) are underdeveloped and inordinate in the foetal life--their structure develops only during the postnatal life. | [Structure and configuration of human tendons. II. Development of tendon structure during ontogenesis]. In infants born in the 24th--30th weeks of the gravidity the praenatal development and the process of the organization of the tendinous structure have been examined by the authors. By means of photo- and polarization microscopic examinations it was found that the tendon of the flexor hand muscles (M. flexor carpi radialis, M. flexor digitorum comm.) shows mature tendinous structure earlier, than the tendons of the flexor muscles of the lower extremity (M. semitendinosus femoris, M. triceps surae). The tendons of the extensor muscles of the lower extremity (M. quadriceps femoris, M. tibialis ant.) are underdeveloped and inordinate in the foetal life--their structure develops only during the postnatal life. | [
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|
PMID:16177 | [Synovial chondrochromatosis of the metacarpophalangeal joint]. | A rare case of synovial chondromatosis sited on the IVth metacarpophalangeal articulation of the left hand of a women is reported. The pathogenesis, the histology and the method of treatment are discussed. 2 years after the operation the patient is symptom-free and without complaints. | [Synovial chondrochromatosis of the metacarpophalangeal joint]. A rare case of synovial chondromatosis sited on the IVth metacarpophalangeal articulation of the left hand of a women is reported. The pathogenesis, the histology and the method of treatment are discussed. 2 years after the operation the patient is symptom-free and without complaints. | [
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|
PMID:16178 | [Oto-palato-digital (Taybi) syndrome]. | A case of dysmorphogenetic syndrome, described by Taybi, is reported. The syndrome is characterized by hardness of hearing of conduction type, submucous cleft palate and anomalies involving the bony frame, especially the digits. | [Oto-palato-digital (Taybi) syndrome]. A case of dysmorphogenetic syndrome, described by Taybi, is reported. The syndrome is characterized by hardness of hearing of conduction type, submucous cleft palate and anomalies involving the bony frame, especially the digits. | [
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|
PMID:16179 | [Luxation fracture of the hip joint. I. Posterior fractures with dislocation]. | 41 cases of posterior sprain fracture are analysed by the authors. 4--10 years after the injury 31 patients appeared at the check-inspection. On the basis of the late results it is stated by the authors that the immediate diagnosis and the reposition of the luxation are of the greatest importance. Conservative treatment yields generally satisfactory results. In the authors' opinion, osteosynthesis is indicated but in fractures concomitant with the fracture and dislocation of great piece of the acetabulum and in juvenile patients. | [Luxation fracture of the hip joint. I. Posterior fractures with dislocation]. 41 cases of posterior sprain fracture are analysed by the authors. 4--10 years after the injury 31 patients appeared at the check-inspection. On the basis of the late results it is stated by the authors that the immediate diagnosis and the reposition of the luxation are of the greatest importance. Conservative treatment yields generally satisfactory results. In the authors' opinion, osteosynthesis is indicated but in fractures concomitant with the fracture and dislocation of great piece of the acetabulum and in juvenile patients. | [
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|
PMID:16180 | [Local soft tissue ossification of traumatic origin]. | Under the effect of trauma, in 4 patients the development of metaplastic bone-tissue in the soft-parts of mesenchymal origin has been observed by the author. In 3 patients the development of supernumerary articulations proved the appearance of cartilaginous tissue; in consequence, the presence of cartilaginous tissue may play an important role in the metaplastic soft-parts ossification. | [Local soft tissue ossification of traumatic origin]. Under the effect of trauma, in 4 patients the development of metaplastic bone-tissue in the soft-parts of mesenchymal origin has been observed by the author. In 3 patients the development of supernumerary articulations proved the appearance of cartilaginous tissue; in consequence, the presence of cartilaginous tissue may play an important role in the metaplastic soft-parts ossification. | [
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|
PMID:16184 | A systems analysis of the impact of physician extenders on medical cost and manpower requirements. | This paper presents a descriptive narrative of a mathematical manpower model and the results of an analysis of the effect physician extenders have on medical costs and manpower requirements. The model is extensively developed, through the use of a new medical classification system in the area of delegation of specific task areas and patient visits to physician extenders. Additionally the models incorporate a complete cost structure for a group practice. Field trials in seven HMOs indicate that the models accurately represent the actual system and can be used effectively as planning aids. Results are presented that analyze the use of physician extenders from the following viewpoints: minimum cost solution for adult medicine, pediatrics and obstetrics/gynecology (OB/GYN); maximum physician extender use; effect of physician extender salary on minimum cost utilization; level of independence exercised; size of clinic and regional manpower planning; and a case study of HMO planning. The type of results presented include cost analysis, manpower analysis, and the types of patient visits best delegated to physician extenders (PE). | A systems analysis of the impact of physician extenders on medical cost and manpower requirements. This paper presents a descriptive narrative of a mathematical manpower model and the results of an analysis of the effect physician extenders have on medical costs and manpower requirements. The model is extensively developed, through the use of a new medical classification system in the area of delegation of specific task areas and patient visits to physician extenders. Additionally the models incorporate a complete cost structure for a group practice. Field trials in seven HMOs indicate that the models accurately represent the actual system and can be used effectively as planning aids. Results are presented that analyze the use of physician extenders from the following viewpoints: minimum cost solution for adult medicine, pediatrics and obstetrics/gynecology (OB/GYN); maximum physician extender use; effect of physician extender salary on minimum cost utilization; level of independence exercised; size of clinic and regional manpower planning; and a case study of HMO planning. The type of results presented include cost analysis, manpower analysis, and the types of patient visits best delegated to physician extenders (PE). | [
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|
PMID:16185 | Physician receptivity to nurse practitioners: a study of the correlates of the delegation of clinical responsibility. | A survey to measure physician receptivity to nurse practitioners was conducted in North Carolina in 1973. All North Carolina physicians were asked to rate a list of 35 clinical tasks of varying levels of difficulty and responsibility according to their willingness to delegate these tasks to nurse practitioners. Using eight items from this list that were good discriminants of physician attitudes towards delegating responsibility, task delegation scores were correlated with physician characteristics and their responses to questions about recruitment, training, reimbursement, and willingness to hire nurse practitioners. Thirty-four per cent of the respondents would hire a nurse practitioner, whereas 52% approved of the concept but would not hire one. Physicians who had previously worked with a nurse practitioner were more willing to hire one and had a higher task delegation score. Sixty-eight per cent of respondents would share their load with nurse practitioners in their offices, while 6% would have them work in satellite clinics away from the physicians' offices. Most physicians wanted their own nurse trained as a nurse practitioner in a program that combined a didactic course at a medical center with on-the-job training. The authors conclude that there is a potential demand for nurse practitioners in North Carolina and that the training program must prepare the nurse practitioners for the tasks physicians are willing to delegate to them. | Physician receptivity to nurse practitioners: a study of the correlates of the delegation of clinical responsibility. A survey to measure physician receptivity to nurse practitioners was conducted in North Carolina in 1973. All North Carolina physicians were asked to rate a list of 35 clinical tasks of varying levels of difficulty and responsibility according to their willingness to delegate these tasks to nurse practitioners. Using eight items from this list that were good discriminants of physician attitudes towards delegating responsibility, task delegation scores were correlated with physician characteristics and their responses to questions about recruitment, training, reimbursement, and willingness to hire nurse practitioners. Thirty-four per cent of the respondents would hire a nurse practitioner, whereas 52% approved of the concept but would not hire one. Physicians who had previously worked with a nurse practitioner were more willing to hire one and had a higher task delegation score. Sixty-eight per cent of respondents would share their load with nurse practitioners in their offices, while 6% would have them work in satellite clinics away from the physicians' offices. Most physicians wanted their own nurse trained as a nurse practitioner in a program that combined a didactic course at a medical center with on-the-job training. The authors conclude that there is a potential demand for nurse practitioners in North Carolina and that the training program must prepare the nurse practitioners for the tasks physicians are willing to delegate to them. | [
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|
PMID:16191 | Comparative effects of (--)-hydroxycitrate and (+)-allo-hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo. | (--)-Hydroxycitrate and (+)-allo-hydroxycitrate were investigated for their effects on lipid synthesis in vivo under conditions of either high carbohydrate feeding or 24 hr fasting. Changes in rates of lipid synthesis resulting from the oral administration of these compounds were monitored with the use of radiolabeled H2O, alanine, and acetate. In the fed rat, (--)-hydroxycitrate significantly reduced the incorporation of H2O and alanine into fatty acids and cholesterol. An increased incorporation of labeled H2O into fatty acids but no change in cholesterol synthesis in the fasted rat suggested that (--)-hydroxycitrate may be an activator of acetyl CoA carboxylase. With (--)-hydroxycitrate administration, acetate incorporation into fatty acids and cholesterol was subject to pool dilution effects under fed or fasted states. (+)-allo-Hydroxycitrate was ineffective in modulating the rates of fatty acid synthesis under either nutritional condition. Both (--)-hydroxycitrate and (+)-allo-hydroxycitrate were shown to be in vitro activators of acetyl CoA carboxylase, the former being a much stronger activator than the latter. Thus, stereospecificity of the hydroxycitrate isomers was demonstrated in both the inhibition of lipid synthesis (previously shown to occur at adenosine triphosphate citrate lyase) and the stimulation of fatty acid synthesis (possibly occurring at acetyl CoA carboxylase). | Comparative effects of (--)-hydroxycitrate and (+)-allo-hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo. (--)-Hydroxycitrate and (+)-allo-hydroxycitrate were investigated for their effects on lipid synthesis in vivo under conditions of either high carbohydrate feeding or 24 hr fasting. Changes in rates of lipid synthesis resulting from the oral administration of these compounds were monitored with the use of radiolabeled H2O, alanine, and acetate. In the fed rat, (--)-hydroxycitrate significantly reduced the incorporation of H2O and alanine into fatty acids and cholesterol. An increased incorporation of labeled H2O into fatty acids but no change in cholesterol synthesis in the fasted rat suggested that (--)-hydroxycitrate may be an activator of acetyl CoA carboxylase. With (--)-hydroxycitrate administration, acetate incorporation into fatty acids and cholesterol was subject to pool dilution effects under fed or fasted states. (+)-allo-Hydroxycitrate was ineffective in modulating the rates of fatty acid synthesis under either nutritional condition. Both (--)-hydroxycitrate and (+)-allo-hydroxycitrate were shown to be in vitro activators of acetyl CoA carboxylase, the former being a much stronger activator than the latter. Thus, stereospecificity of the hydroxycitrate isomers was demonstrated in both the inhibition of lipid synthesis (previously shown to occur at adenosine triphosphate citrate lyase) and the stimulation of fatty acid synthesis (possibly occurring at acetyl CoA carboxylase). | [
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PMID:16194 | Fetal fuels. I. Utilization of ketones by isolated tissues at various stages of maturation and maternal nutrition during late gestation. | The availability and utilization of B-hydroxybutyrate as an alternate oxidative fuel during fasting hypoglycemia has been examined in the rat conceptus at 18 and 20 days gestation. A 48-hr maternal fast between days 16 and 18 or 18 and 20 resulted in a 50% fall in fetal glucose levels and a marked rise in B-hydroxybutyrate, i.e., 30-fold at 18 and 60-fold at 20 days. Tissue concentrations of B-hydroxybutyrate or acetoacetate did not exceed extracellular levels. Placenta, fetal brain, carcass, and liver all oxidized 14C-labeled B-hydroxybutyrate to 14CO2 when incubated in vitro in the presence of B-hydroxybutyrate. Highest rates of oxidation were apparent in the placenta, followed by brain, liver, and carcass. The D isomer of B-hydroxybutyrate appeared to be oxidized preferentially by all tissues studied. Despite levels of 3-ketoacid CoA transferase and acetoacetyl CoA thiolase lower at 18 than at 20 days, rates of oxidation in individual tissues incubated under identical concentrations of substrate were similar at both times. In liver and brain, increasing rates of 14CO2 generation proportionate to graded concentrations of B-hydroxybutyrate in vitro indicated that such rates were probably determined by substrate availability. B-hydroxybutyrate oxidation in extrahepatic fetal tissues was unaffected by maternal fasting. By contrast, fetal liver derived from fasted mothers generated significantly less 14CO2 from B-hydroxybutyrate than livers from fed mothers. It has been suggested that capabilities for ketone utilization are widespread in tissues of the conceptus, and that such utilization may fulfill in part the oxidative demands for continued anabolic growth during fasting hypoglycemia in the mother. | Fetal fuels. I. Utilization of ketones by isolated tissues at various stages of maturation and maternal nutrition during late gestation. The availability and utilization of B-hydroxybutyrate as an alternate oxidative fuel during fasting hypoglycemia has been examined in the rat conceptus at 18 and 20 days gestation. A 48-hr maternal fast between days 16 and 18 or 18 and 20 resulted in a 50% fall in fetal glucose levels and a marked rise in B-hydroxybutyrate, i.e., 30-fold at 18 and 60-fold at 20 days. Tissue concentrations of B-hydroxybutyrate or acetoacetate did not exceed extracellular levels. Placenta, fetal brain, carcass, and liver all oxidized 14C-labeled B-hydroxybutyrate to 14CO2 when incubated in vitro in the presence of B-hydroxybutyrate. Highest rates of oxidation were apparent in the placenta, followed by brain, liver, and carcass. The D isomer of B-hydroxybutyrate appeared to be oxidized preferentially by all tissues studied. Despite levels of 3-ketoacid CoA transferase and acetoacetyl CoA thiolase lower at 18 than at 20 days, rates of oxidation in individual tissues incubated under identical concentrations of substrate were similar at both times. In liver and brain, increasing rates of 14CO2 generation proportionate to graded concentrations of B-hydroxybutyrate in vitro indicated that such rates were probably determined by substrate availability. B-hydroxybutyrate oxidation in extrahepatic fetal tissues was unaffected by maternal fasting. By contrast, fetal liver derived from fasted mothers generated significantly less 14CO2 from B-hydroxybutyrate than livers from fed mothers. It has been suggested that capabilities for ketone utilization are widespread in tissues of the conceptus, and that such utilization may fulfill in part the oxidative demands for continued anabolic growth during fasting hypoglycemia in the mother. | [
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|
PMID:16196 | Studies on the toxin of Aspergillus fumigatus. VII. Purification and some properities of hemolytic toxin (asp-hemolysin) from culture filtrates and mycelia. | A hemolytic toxin has been obtained from mycelia and culture filtrates of Aspergillus fumigatus by the procedures that included precipitation with ammonium sulfate, chromatography of DEAE-Sephadex, affinity chromatography on Concanavalin A-Sepharose and gell filtration on Sephadex G-50, G-100 AND G-150. The purified homolytic toxin was homogeneous on immunological and disk electrophoretic analysis, and the toxin from culture filtrates was identical with that from mycelia by the immunodiffusion technique. The hemolytic toxin was obtained for the first time from fungi and designated as Asp-hemolysin. The molecular weight of Asp-hemolysin was estimated to be appoximately 30,000 by the gel-filtration technique and its isoelectric point was found to be around pH 4.0. This Asp-hemolysin contained large amounts of protein and very small amounts of carbohydrate. The UV absorption spectrum of Asp-hemolysin showed a maximum absorption at 280 nm and minimum absorption at 251 nm. The extinction coefficient at 280 nm and minimum absorption at 251 nm. The extinction coefficient at 280 nm, E 1% 1CM, was 12.4 and the ratio of absorbance at 280 nm to that at 260 nm was 2.3. The optimum pH for the hemolytic activity of the toxin toward chicken erythrocytes was 5.0 at room temperature and it was active in the pH range of 3.5 to 10.5. The optimum temperature was 21 C and about 50% of the activity was lost by incubation at 50 C for 5 min or 45 C for 23 min. The hemolytic activity was remarkably inhibited by Hg2+, Cu2+, Fe2+, Ag1+, iodine and p-CMB, but enhanced slightly by Zn2+ and Co2+. | Studies on the toxin of Aspergillus fumigatus. VII. Purification and some properities of hemolytic toxin (asp-hemolysin) from culture filtrates and mycelia. A hemolytic toxin has been obtained from mycelia and culture filtrates of Aspergillus fumigatus by the procedures that included precipitation with ammonium sulfate, chromatography of DEAE-Sephadex, affinity chromatography on Concanavalin A-Sepharose and gell filtration on Sephadex G-50, G-100 AND G-150. The purified homolytic toxin was homogeneous on immunological and disk electrophoretic analysis, and the toxin from culture filtrates was identical with that from mycelia by the immunodiffusion technique. The hemolytic toxin was obtained for the first time from fungi and designated as Asp-hemolysin. The molecular weight of Asp-hemolysin was estimated to be appoximately 30,000 by the gel-filtration technique and its isoelectric point was found to be around pH 4.0. This Asp-hemolysin contained large amounts of protein and very small amounts of carbohydrate. The UV absorption spectrum of Asp-hemolysin showed a maximum absorption at 280 nm and minimum absorption at 251 nm. The extinction coefficient at 280 nm and minimum absorption at 251 nm. The extinction coefficient at 280 nm, E 1% 1CM, was 12.4 and the ratio of absorbance at 280 nm to that at 260 nm was 2.3. The optimum pH for the hemolytic activity of the toxin toward chicken erythrocytes was 5.0 at room temperature and it was active in the pH range of 3.5 to 10.5. The optimum temperature was 21 C and about 50% of the activity was lost by incubation at 50 C for 5 min or 45 C for 23 min. The hemolytic activity was remarkably inhibited by Hg2+, Cu2+, Fe2+, Ag1+, iodine and p-CMB, but enhanced slightly by Zn2+ and Co2+. | [
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PMID:16197 | Resistance mechanism of chloramphenicol in Streptococcus haemolyticus, Streptococcus pneumoniae and Streptococcus faecalis. | The chloramphenicol resistance of Streptococcus haemolyticus, Streptococcus pneumoniae and Streptococcus faecalis isolated from clinical materials was proved to be due to an inactivating enzyme produced by these bacteria. The inactivated products of chloramphenicol were identified as 1-acetoxy, 3-acetoxy and 1,3-diacetoxy derivatives by thin-layer chromatography and infrared spectroscopy. The responsible enzyme was thus confirmed to be chloramphenicol acetyltransferase. The enzyme was inducible. It was partially purified by ammonium sulfate precipitation, DEAE-cellulose chromatography and gel filtration on Sephadex G-150. The enzymes obtained from S. haemolyticus, S. pneumoniae and S. faecalis have been compared with the conclusion that they are identical with respect to molecular weight (approximately 75,000-80,000), optimum pH and heat stability. | Resistance mechanism of chloramphenicol in Streptococcus haemolyticus, Streptococcus pneumoniae and Streptococcus faecalis. The chloramphenicol resistance of Streptococcus haemolyticus, Streptococcus pneumoniae and Streptococcus faecalis isolated from clinical materials was proved to be due to an inactivating enzyme produced by these bacteria. The inactivated products of chloramphenicol were identified as 1-acetoxy, 3-acetoxy and 1,3-diacetoxy derivatives by thin-layer chromatography and infrared spectroscopy. The responsible enzyme was thus confirmed to be chloramphenicol acetyltransferase. The enzyme was inducible. It was partially purified by ammonium sulfate precipitation, DEAE-cellulose chromatography and gel filtration on Sephadex G-150. The enzymes obtained from S. haemolyticus, S. pneumoniae and S. faecalis have been compared with the conclusion that they are identical with respect to molecular weight (approximately 75,000-80,000), optimum pH and heat stability. | [
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|
PMID:16198 | [Physiologo-biochemical properties of a chemostatic culture of Bacillus megaterium at different pH values]. | Properties of the chemostat culture of Bacillus megaterium were studied during its growth in the state of stress caused by unfavourable acid and alkaline values of pH. The effect of pH is not specific since changes occur in both energy exchange and constructive metabolism. The common action of hydrogen and hydroxyl ions is a decrease in the economic coefficient as greater amounts of the energy substrate are being used, the repression of oxidative enzymes, a decrease in the pool of ATP, and an increase in the respiration quotient. Protein synthesis is inhibited and synthesis of nitrogenless reserve substances is stimulated. Acid and alkaline conditions have also a specific action in the cells of Bac. megaterium. In the alkaline medium, metabolites are liberated into the medium, the cells are enriched with carbohydrates, and acetate is accumulated in the medium. In the acid medium, the cells are enriched with acid insoluble polyphosphates. Idle consumption of the energy substrate takes place. | [Physiologo-biochemical properties of a chemostatic culture of Bacillus megaterium at different pH values]. Properties of the chemostat culture of Bacillus megaterium were studied during its growth in the state of stress caused by unfavourable acid and alkaline values of pH. The effect of pH is not specific since changes occur in both energy exchange and constructive metabolism. The common action of hydrogen and hydroxyl ions is a decrease in the economic coefficient as greater amounts of the energy substrate are being used, the repression of oxidative enzymes, a decrease in the pool of ATP, and an increase in the respiration quotient. Protein synthesis is inhibited and synthesis of nitrogenless reserve substances is stimulated. Acid and alkaline conditions have also a specific action in the cells of Bac. megaterium. In the alkaline medium, metabolites are liberated into the medium, the cells are enriched with carbohydrates, and acetate is accumulated in the medium. In the acid medium, the cells are enriched with acid insoluble polyphosphates. Idle consumption of the energy substrate takes place. | [
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|
PMID:16203 | Cimetidine in the treatment of duodenal ulcer. | In a double-blind trial performed in two centres, 67 outpatients with endoscopically confirmed duodenal (55) or pyloric canal (12) ulcers received cimetidine (34 patients) or placebo (33 patients) for six weeks. At 6 weeks complete healing of ulcers was significantly increased in patients receiving cimetidine (82%) compared with those receiving placebo (39%) (chi2=11-27; P less than 0-0008). Patients receiving cimetidine had significantly less daytime pain and required less antacid than those receiving placebo. Gastric acid secretion measured one week after cessation of treatment demonstrated that there was no rebound hypersecretion of acid in patients who had received cimetidine. The pretrial basal acid output of those patients whose ulcers failed to heal during cimetidine therapy was significantly greater than that of those whose ulcers healed during treatment with the drug (P less than 0-001). No side effects were encountered. | Cimetidine in the treatment of duodenal ulcer. In a double-blind trial performed in two centres, 67 outpatients with endoscopically confirmed duodenal (55) or pyloric canal (12) ulcers received cimetidine (34 patients) or placebo (33 patients) for six weeks. At 6 weeks complete healing of ulcers was significantly increased in patients receiving cimetidine (82%) compared with those receiving placebo (39%) (chi2=11-27; P less than 0-0008). Patients receiving cimetidine had significantly less daytime pain and required less antacid than those receiving placebo. Gastric acid secretion measured one week after cessation of treatment demonstrated that there was no rebound hypersecretion of acid in patients who had received cimetidine. The pretrial basal acid output of those patients whose ulcers failed to heal during cimetidine therapy was significantly greater than that of those whose ulcers healed during treatment with the drug (P less than 0-001). No side effects were encountered. | [
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|
PMID:16199 | [Methanol oxidation by the NAD-specific dehydrogenase of methane-assimilating yeasts]. | The activity of NAD-specific dehydrogenase (NAD-DH) capable of methanol oxidation was found in cell-free extracts of methanol assimilating yeast cultures Pichia pinus and Candida boidinii. The optimum pH of the incubation mixture for the enzyme is 7.8--7.9; the value of Km of the enzyme for methanol is 1.4-10(-4) M in P. pinus and 1.04-10(-3) M in C. boidinii. NAD-DH is absent from the cells cultivated on glucose, and is induced with growth on a medium containing methanol. | [Methanol oxidation by the NAD-specific dehydrogenase of methane-assimilating yeasts]. The activity of NAD-specific dehydrogenase (NAD-DH) capable of methanol oxidation was found in cell-free extracts of methanol assimilating yeast cultures Pichia pinus and Candida boidinii. The optimum pH of the incubation mixture for the enzyme is 7.8--7.9; the value of Km of the enzyme for methanol is 1.4-10(-4) M in P. pinus and 1.04-10(-3) M in C. boidinii. NAD-DH is absent from the cells cultivated on glucose, and is induced with growth on a medium containing methanol. | [
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PMID:16201 | [Properties of the hexulose phosphate synthase of methylotrophic yeasts and bacteria]. | Properties of hexulose phosphate synthase (HPS) were studied in extracts of the methanol assimilating yeast Candida methylica and the bacterium Arthrobacter globiformis B-175 assimilating methylated amines. HPS is an inducible enzyme which is localized in the soluble fraction of the cells. The effect of the pH of the reaction mixture, temperature, metal ions, and the concentration of substrates on the activity of HPS was studied. Properties of the enzyme were different in the yeast and the bacterium. The activity of HPS was strongly stimulated by ATP in C. methylica and was not affected in A. globiformis. | [Properties of the hexulose phosphate synthase of methylotrophic yeasts and bacteria]. Properties of hexulose phosphate synthase (HPS) were studied in extracts of the methanol assimilating yeast Candida methylica and the bacterium Arthrobacter globiformis B-175 assimilating methylated amines. HPS is an inducible enzyme which is localized in the soluble fraction of the cells. The effect of the pH of the reaction mixture, temperature, metal ions, and the concentration of substrates on the activity of HPS was studied. Properties of the enzyme were different in the yeast and the bacterium. The activity of HPS was strongly stimulated by ATP in C. methylica and was not affected in A. globiformis. | [
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|
PMID:16202 | A study of cancer of the breast with special reference to its causation and prevention. | Breast feeding, lactational histories, parity, age at marriage, and socio-economic status were compared in 24 patients with carcinoma of breast, 24 healthy controls, and 48 patients suffering from other diseases. They were matched for age, social class and work or trade of the husbands. Breast cancer patients married later, had shorter lactational histories and had fewer children as compared with controls. Studies in six healthy mothers showed that milk became more alkaline on stasis in the breast. This study confirms the view that breast feeding protects against breast cancer. It suggests that one carcinogenic factor may be an alkaline milieu produced by the statis of milk in the breasts. An alkaline milieu surrounding epithelial surfaces produces cell proliferation and a marked increase in mitotic activity which may eventually lead to metaplasia and neoplasia. | A study of cancer of the breast with special reference to its causation and prevention. Breast feeding, lactational histories, parity, age at marriage, and socio-economic status were compared in 24 patients with carcinoma of breast, 24 healthy controls, and 48 patients suffering from other diseases. They were matched for age, social class and work or trade of the husbands. Breast cancer patients married later, had shorter lactational histories and had fewer children as compared with controls. Studies in six healthy mothers showed that milk became more alkaline on stasis in the breast. This study confirms the view that breast feeding protects against breast cancer. It suggests that one carcinogenic factor may be an alkaline milieu produced by the statis of milk in the breasts. An alkaline milieu surrounding epithelial surfaces produces cell proliferation and a marked increase in mitotic activity which may eventually lead to metaplasia and neoplasia. | [
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|
PMID:16209 | [Cogans's syndrome in childhood (author's transl)]. | A case--report is given of a patient with Cogan's syndrome in childhood. This syndrome consists of non-syphilitic interstitial keratitis and vestibuloauditory symptoms. Visual loss is rare but hearing loss is rapidly progressive. A relation to autoimmune diseases especially to panarteriitis nodosa has been suggested by a number of authors. | [Cogans's syndrome in childhood (author's transl)]. A case--report is given of a patient with Cogan's syndrome in childhood. This syndrome consists of non-syphilitic interstitial keratitis and vestibuloauditory symptoms. Visual loss is rare but hearing loss is rapidly progressive. A relation to autoimmune diseases especially to panarteriitis nodosa has been suggested by a number of authors. | [
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|
PMID:16212 | Enzyme replacement therapy of exocrine pancreatic insufficiency in man. Relations between in vitro enzyme activities and in vivo potency in commercial pancreatic extracts. | I assayed 16 commercially available pancreatic extracts (representing capsules, tablets and enteric-coated tablets) for enzyme activities and the relation between the in vitro activities and in vivo potency evaluated in man. Lipase activity ranged from 10 to 3600 units per unit, with 11 preparations containing less than 600 units per unit. The preparations with the highest lipase activities were llozyme, 3600, Kuzyme HP, 2330, Festal, 2073, Cotazym, 2014, and Viokase, 1636 units. Lipase activity in vitro correlated with potency in vivo for tablets and capsules, with tablets and capsules being effective in reducing steatorrhea by 56.1 +/- 9 per cent and 48.6 +/- 10 per cent (mean +/- S.E.M.) respectively, P less than 0.001. Enteric-coated tablets were less effective (20 +/- 13 per cent reduction, P greater than 0.02). The longer the gastric pH remained greater than or equal to 4 (r = 0.915, P less than 0.01) and the higher the average duodenal pH (r = 0.966, P less than 0.01), the more marked the reduction in steatorrhea. | Enzyme replacement therapy of exocrine pancreatic insufficiency in man. Relations between in vitro enzyme activities and in vivo potency in commercial pancreatic extracts. I assayed 16 commercially available pancreatic extracts (representing capsules, tablets and enteric-coated tablets) for enzyme activities and the relation between the in vitro activities and in vivo potency evaluated in man. Lipase activity ranged from 10 to 3600 units per unit, with 11 preparations containing less than 600 units per unit. The preparations with the highest lipase activities were llozyme, 3600, Kuzyme HP, 2330, Festal, 2073, Cotazym, 2014, and Viokase, 1636 units. Lipase activity in vitro correlated with potency in vivo for tablets and capsules, with tablets and capsules being effective in reducing steatorrhea by 56.1 +/- 9 per cent and 48.6 +/- 10 per cent (mean +/- S.E.M.) respectively, P less than 0.001. Enteric-coated tablets were less effective (20 +/- 13 per cent reduction, P greater than 0.02). The longer the gastric pH remained greater than or equal to 4 (r = 0.915, P less than 0.01) and the higher the average duodenal pH (r = 0.966, P less than 0.01), the more marked the reduction in steatorrhea. | [
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|
PMID:16210 | A possible histochemical mechanism of dihydrofolate reductase reaction. | The authors propose a hypothesis concerning the mechanism of dihydrofolate reductase reaction, suggesting a combined action of transhydrogenases and diaphorase particularly for this enzyme activity, and generally for the reductases. | A possible histochemical mechanism of dihydrofolate reductase reaction. The authors propose a hypothesis concerning the mechanism of dihydrofolate reductase reaction, suggesting a combined action of transhydrogenases and diaphorase particularly for this enzyme activity, and generally for the reductases. | [
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|
PMID:16213 | Fate of orally ingested enzymes in pancreatic insufficiency. Comparison of two dosage schedules. | To assess the fate and efficacy of orally ingested enzymes in pancreatic insufficiency, we administered pancreatin to six patients by two schedules--eight tablets with a standard meal or two tablets hourly--and in six normal controls, quantified duodenal enzyme activity and related inactiviation of ingested enzymes to gastric and duodenal pH; in the six patients we measured malabsorption by fecal balance studies. Postprandially, gastric pH was similar in health and pancreatic insufficiency, and below 4 after 40 minutes. Duodenal pH in pancreatic insufficiency declined to approximately 4 beyond 100 minutes--lower than in health (P less than 0.05). Approximately 22 per cent and 8 per cent of trypsin and lipase activity ingested with either schedule was delivered to the ligament of Treitz. Prandial was as effective as hourly administration in decreasing steatorrhea and perhaps more effective in abolishing azotorrhea, and since it is also more convenient, we recommend it. | Fate of orally ingested enzymes in pancreatic insufficiency. Comparison of two dosage schedules. To assess the fate and efficacy of orally ingested enzymes in pancreatic insufficiency, we administered pancreatin to six patients by two schedules--eight tablets with a standard meal or two tablets hourly--and in six normal controls, quantified duodenal enzyme activity and related inactiviation of ingested enzymes to gastric and duodenal pH; in the six patients we measured malabsorption by fecal balance studies. Postprandially, gastric pH was similar in health and pancreatic insufficiency, and below 4 after 40 minutes. Duodenal pH in pancreatic insufficiency declined to approximately 4 beyond 100 minutes--lower than in health (P less than 0.05). Approximately 22 per cent and 8 per cent of trypsin and lipase activity ingested with either schedule was delivered to the ligament of Treitz. Prandial was as effective as hourly administration in decreasing steatorrhea and perhaps more effective in abolishing azotorrhea, and since it is also more convenient, we recommend it. | [
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|
PMID:16215 | [Determination of riboflavin in foods]. | The author examined the conditions under which the lumiflavin method may be used for the determination of riboflavin. Neither the presence of various cations and anions, nor the presence of cellulose, starch and protein exerted any effect on the oxidation with potassium permanganate. The riboflavin losses increased when potassium permanganate was used at a concentration of more than 2%. The losses were considerably lower it the purification of the extracts by means of potassium permanganate was performed after photolysis. The most favourable results were obtained when the extracts were shaken with chloroform prior to photolysis to eliminate interfering substances. These findings were corroborated by comparative analyses on 3 standard samples. | [Determination of riboflavin in foods]. The author examined the conditions under which the lumiflavin method may be used for the determination of riboflavin. Neither the presence of various cations and anions, nor the presence of cellulose, starch and protein exerted any effect on the oxidation with potassium permanganate. The riboflavin losses increased when potassium permanganate was used at a concentration of more than 2%. The losses were considerably lower it the purification of the extracts by means of potassium permanganate was performed after photolysis. The most favourable results were obtained when the extracts were shaken with chloroform prior to photolysis to eliminate interfering substances. These findings were corroborated by comparative analyses on 3 standard samples. | [
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|
PMID:16219 | Comparative neutron small-angle scattering study of small spherical RNA viruses. | Small-angle neutron scattering from solutions of small RNA viruses has been used to study protein-nucleic acid organisation. In the five viruses investigated the RNA is confined to a sphere of about 100 A radius, with a central hole (with one possible exception). The interpenetration of RNA and protein varies with viruses and seems to be related to the natrue of the forces stabilising the virus. | Comparative neutron small-angle scattering study of small spherical RNA viruses. Small-angle neutron scattering from solutions of small RNA viruses has been used to study protein-nucleic acid organisation. In the five viruses investigated the RNA is confined to a sphere of about 100 A radius, with a central hole (with one possible exception). The interpenetration of RNA and protein varies with viruses and seems to be related to the natrue of the forces stabilising the virus. | [
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|
PMID:16224 | Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum. | The characteristics of 3H-DA release from striatal slices by electrical stimulation were analyzed and the effects of a number of neuroleptics thereon were examined under different experimental conditions. The butyrophenones, haloperidol and spiroperidol, already at low concentrations (0.1 - 1 micronM) increased basal tritium efflux in a dose-dependent manner. The phenothiazines, chlorpromazine and fluphenazine, were much less effective in this respect. The butyrophenones strongly inhibited the electrically stimulated overflow of both 3H-DA and 14C-GABA, while the phenothiazines again had little effect. The action of 1 micronM haloperidol on 3H-DA release could be blocked by 10 micronM cocaine, but not with 1 micronM apomorphine. Apomorphine itself had no significant effect on 3H-DA release. Our data do not support the suggestion that presynaptic DA receptors on dopaminergic nerve terminals may modulate the release of newly taken-up 3H-DA. Some neuroleptics, particularly the butyrophenones may have presynaptic effects not related to interaction with DA receptors. It is suggested that different mechanisms may be involved in the local presynaptic receptor-mediated feedback regulation of transmitter release in noradrenergic and dopaminergic systems in the CNS. | Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum. The characteristics of 3H-DA release from striatal slices by electrical stimulation were analyzed and the effects of a number of neuroleptics thereon were examined under different experimental conditions. The butyrophenones, haloperidol and spiroperidol, already at low concentrations (0.1 - 1 micronM) increased basal tritium efflux in a dose-dependent manner. The phenothiazines, chlorpromazine and fluphenazine, were much less effective in this respect. The butyrophenones strongly inhibited the electrically stimulated overflow of both 3H-DA and 14C-GABA, while the phenothiazines again had little effect. The action of 1 micronM haloperidol on 3H-DA release could be blocked by 10 micronM cocaine, but not with 1 micronM apomorphine. Apomorphine itself had no significant effect on 3H-DA release. Our data do not support the suggestion that presynaptic DA receptors on dopaminergic nerve terminals may modulate the release of newly taken-up 3H-DA. Some neuroleptics, particularly the butyrophenones may have presynaptic effects not related to interaction with DA receptors. It is suggested that different mechanisms may be involved in the local presynaptic receptor-mediated feedback regulation of transmitter release in noradrenergic and dopaminergic systems in the CNS. | [
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|
PMID:16229 | [Quantitative relationship between neurons of a different mediator nature in the motor nuclei of the cat spinal cord cervical thickening]. | A histochemical analysis of the neuronal composition of the motor nuclei was performed on the cat cervical spinal cord. Motoneurons were distinguished by the location of AChE in the perinuclear space, on the membranes of the granular reticulum, on the axolemma, neurofilaments and neurotubuli, in the synaptosomes and the synaptic cleft; this evidences for the perinuclear synthesis of this enzyme and its transport within the axoplasm. Their amount reached 40-65% of the whole neuronal population. AChE identification together with autoradiographic tracing of glycine showed that large cholinergic motoneurons are accompanied by small glycine-accumulating neurons with short processes which form axo-somatic and axo-dendritic contacts with large neurons. The cholinergic motoneurons have polyreceptive properties, as can be concluded from the presence of AChE and glycine-containing terminals on their soma and processes, as well as some noradrenergic and serotoninergic and many unidentified terminals. | [Quantitative relationship between neurons of a different mediator nature in the motor nuclei of the cat spinal cord cervical thickening]. A histochemical analysis of the neuronal composition of the motor nuclei was performed on the cat cervical spinal cord. Motoneurons were distinguished by the location of AChE in the perinuclear space, on the membranes of the granular reticulum, on the axolemma, neurofilaments and neurotubuli, in the synaptosomes and the synaptic cleft; this evidences for the perinuclear synthesis of this enzyme and its transport within the axoplasm. Their amount reached 40-65% of the whole neuronal population. AChE identification together with autoradiographic tracing of glycine showed that large cholinergic motoneurons are accompanied by small glycine-accumulating neurons with short processes which form axo-somatic and axo-dendritic contacts with large neurons. The cholinergic motoneurons have polyreceptive properties, as can be concluded from the presence of AChE and glycine-containing terminals on their soma and processes, as well as some noradrenergic and serotoninergic and many unidentified terminals. | [
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|
PMID:16232 | Salivary levels of anticonvulsants: a practical approach to drug monitoring. | Phenobarbital, phenytoin, carbamazepine, primidone, and ethosuximide were measured in saliva and plasma obtained simultaneoulsy from 115 patients. A method to correct for the effect of salivary pH on phenobarbital concentration of saliva was developed. Salivary concentrations of these drugs were found to be equivalent to the plasma free drug and to correlate closely with the total plasma levels. Expressed as percent of total plasma drug, the salivary (S) and plasma free (P) concentrations were: phenytoin, S 11.1 +/- 2.0 percent (mean +/- SD), P 10.1 +/- 2.4 percent (r = 0.97); carbamazepine, S 26.0 +/- 2.4 percent, P 25.9 +/- 3.4 percent (r = 0.97); phenobarbital, S 43.1 +/- 5.2 percent, P 40.8 +/- 7.9 percent (r = 0.91); primidone, S 75.4 +/- 24.9 percent, P 66.4 +/- 8.8 percent (r = 0.76). Ethosuximide was not bound by plasma proteins, and its plasma and salivary levels were equal. | Salivary levels of anticonvulsants: a practical approach to drug monitoring. Phenobarbital, phenytoin, carbamazepine, primidone, and ethosuximide were measured in saliva and plasma obtained simultaneoulsy from 115 patients. A method to correct for the effect of salivary pH on phenobarbital concentration of saliva was developed. Salivary concentrations of these drugs were found to be equivalent to the plasma free drug and to correlate closely with the total plasma levels. Expressed as percent of total plasma drug, the salivary (S) and plasma free (P) concentrations were: phenytoin, S 11.1 +/- 2.0 percent (mean +/- SD), P 10.1 +/- 2.4 percent (r = 0.97); carbamazepine, S 26.0 +/- 2.4 percent, P 25.9 +/- 3.4 percent (r = 0.97); phenobarbital, S 43.1 +/- 5.2 percent, P 40.8 +/- 7.9 percent (r = 0.91); primidone, S 75.4 +/- 24.9 percent, P 66.4 +/- 8.8 percent (r = 0.76). Ethosuximide was not bound by plasma proteins, and its plasma and salivary levels were equal. | [
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|
PMID:16235 | [Guide to the automated calculation of acid-base equilibrium]. | The sequence of calculations that can be entered in the memory of a desk computer for the automatic calculation of acid base balance parameters using data obtained with Astrup's tonometric method is described. A statistical comparison is also made between manually obtained results and those obtained with computer assistance. For clinical purposes the comparison is satisfactory. | [Guide to the automated calculation of acid-base equilibrium]. The sequence of calculations that can be entered in the memory of a desk computer for the automatic calculation of acid base balance parameters using data obtained with Astrup's tonometric method is described. A statistical comparison is also made between manually obtained results and those obtained with computer assistance. For clinical purposes the comparison is satisfactory. | [
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|
PMID:16240 | Cataract and gamma-glutamyl cycle in myotonic dystrophy. | Gamma-Glutamyl transpeptidase (gamma-GT) may be responsible for the rapid catabolism and low levels of lenticular glutathione often associated with cataract formation. Elevated levels of serum gamma-GT in patients with myotonic dystrophy suggest that since the defect could be present in all tissues it might be responsible for the cataracts frequently observed in this genetic disease. | Cataract and gamma-glutamyl cycle in myotonic dystrophy. Gamma-Glutamyl transpeptidase (gamma-GT) may be responsible for the rapid catabolism and low levels of lenticular glutathione often associated with cataract formation. Elevated levels of serum gamma-GT in patients with myotonic dystrophy suggest that since the defect could be present in all tissues it might be responsible for the cataracts frequently observed in this genetic disease. | [
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|
PMID:16242 | Are infantile periarteritis nodosa with coronary artery involvement and fatal mucocutaneous lymph node syndrome the same? Comparison of 20 patients from North America with patients from Hawaii and Japan. | We reviewed available clinical and pathologic autopsy material from 20 patients with infantile periarteritis nodosa with coronary artery involvement (IPN) from the continental United States, two Hawaiian patients with fatal mucocutaneous lymph node syndrome (MCLS; Kawasaki disease), and three patients with classical periarteritis nodosa (CPN). Comparison of the findings in patients with IPN and in patients with MCLS from Hawaii to material from patients with fatal MCLS from Japan showed no definite clinical reason to distinguish IPN from MCLS; neither gross nor microscopic features of the vascular lesions nor their pattern of distribution appears to warrant separation of IPN from fatal MCLS. CPN differs, both clinically and pathologically, from IPN/MCLS, and may well have a different etiology. | Are infantile periarteritis nodosa with coronary artery involvement and fatal mucocutaneous lymph node syndrome the same? Comparison of 20 patients from North America with patients from Hawaii and Japan. We reviewed available clinical and pathologic autopsy material from 20 patients with infantile periarteritis nodosa with coronary artery involvement (IPN) from the continental United States, two Hawaiian patients with fatal mucocutaneous lymph node syndrome (MCLS; Kawasaki disease), and three patients with classical periarteritis nodosa (CPN). Comparison of the findings in patients with IPN and in patients with MCLS from Hawaii to material from patients with fatal MCLS from Japan showed no definite clinical reason to distinguish IPN from MCLS; neither gross nor microscopic features of the vascular lesions nor their pattern of distribution appears to warrant separation of IPN from fatal MCLS. CPN differs, both clinically and pathologically, from IPN/MCLS, and may well have a different etiology. | [
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|
PMID:16244 | [Variation of plasma amino acids in severe hepatitis with encephalopathy 10 cases]. | Plasma levels of different amino acids were observed in 10 patients with severe hepatitis, 9 viral in origin and 1 toxic, over the course of the disease. There would appear to be a close relationship between the onset of encephalopathy and the appearance of a particular pattern in plasma amino acid equilibrium, characterised by a significant fall in the molar ratio existing between ramified amino acids (valine, leucine, isoleucine) and aromatic amino acids (phenylalanine and tyrosine). The role of these disturbances in the physiopathology of the encephalopathy and their effects on the synthesis of normal neurotransmitters and the intracerebral accumulation of false neurotransmitters is discussed. | [Variation of plasma amino acids in severe hepatitis with encephalopathy 10 cases]. Plasma levels of different amino acids were observed in 10 patients with severe hepatitis, 9 viral in origin and 1 toxic, over the course of the disease. There would appear to be a close relationship between the onset of encephalopathy and the appearance of a particular pattern in plasma amino acid equilibrium, characterised by a significant fall in the molar ratio existing between ramified amino acids (valine, leucine, isoleucine) and aromatic amino acids (phenylalanine and tyrosine). The role of these disturbances in the physiopathology of the encephalopathy and their effects on the synthesis of normal neurotransmitters and the intracerebral accumulation of false neurotransmitters is discussed. | [
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|
PMID:16252 | Analgesic action of alpha-adrenolytics in albino mice. | The effect of alpha-adrenolytics: phenoxybenzamine, phentolamine, aceperone, dihydroegotamine, and yohimbine, was tested on reactivity to pain, and on the analgesic action of morphine and pethidine in albino mice. The compounds exert an analgesic effect by themselves, and potentiate the analgesic action of threshold doses of morphine and pethidine. The results seem to provide another proof that the cerbral noradrenaline neurons participate in central mechanisms of pain perception. | Analgesic action of alpha-adrenolytics in albino mice. The effect of alpha-adrenolytics: phenoxybenzamine, phentolamine, aceperone, dihydroegotamine, and yohimbine, was tested on reactivity to pain, and on the analgesic action of morphine and pethidine in albino mice. The compounds exert an analgesic effect by themselves, and potentiate the analgesic action of threshold doses of morphine and pethidine. The results seem to provide another proof that the cerbral noradrenaline neurons participate in central mechanisms of pain perception. | [
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|
PMID:16256 | The different effects of sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin in man. | The influence of oral sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin has been studied in normal volunteers. While sodium bicarbonate appeared to increase indomethacin absorption, aluminium hydroxide markedly reduced both the rate and extent of absorption. The buccal absorption of indomethacin over the pH range 5-9 was also studied in normal volunteers, and showed that the percentage absorption increased markedly as the pH was reduced. The clinical importance both of pH-partition and of adsorption are discussed in the context of antacid interactions. It is concluded that caution must be exercised when prescribing an antacid with other orally-administered drugs. | The different effects of sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin in man. The influence of oral sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin has been studied in normal volunteers. While sodium bicarbonate appeared to increase indomethacin absorption, aluminium hydroxide markedly reduced both the rate and extent of absorption. The buccal absorption of indomethacin over the pH range 5-9 was also studied in normal volunteers, and showed that the percentage absorption increased markedly as the pH was reduced. The clinical importance both of pH-partition and of adsorption are discussed in the context of antacid interactions. It is concluded that caution must be exercised when prescribing an antacid with other orally-administered drugs. | [
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|
PMID:16253 | Factors which might modify analgesic effect of morphine in differentially housed rats. | The analgesic effect of morphine was studied by tail compression method in grouped and chronically isolated Wistar male rats developing muricide behavior showed increased pain threshold whilst indifferent (non-killer) showed reduced responses to the analgesic action of morphine. "Natural" killer (housed in groups) showed, on the other hand, increased sensitivity to morphine. The role of factors such as isolation period, behavioral pattern and contact with the victim was discussed. | Factors which might modify analgesic effect of morphine in differentially housed rats. The analgesic effect of morphine was studied by tail compression method in grouped and chronically isolated Wistar male rats developing muricide behavior showed increased pain threshold whilst indifferent (non-killer) showed reduced responses to the analgesic action of morphine. "Natural" killer (housed in groups) showed, on the other hand, increased sensitivity to morphine. The role of factors such as isolation period, behavioral pattern and contact with the victim was discussed. | [
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|
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