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Biochemical and morphological characterization of mycobacteriophage R1.
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Large-scale propagation of mycobacteriophage R1 in broth culture has allowed the isolation of quantities of virus sufficient for characterization of its nucleic acid and lipid components as well as investigation of its ultrastructural attributes. Analysis of R1 DNA indicates that it is double stranded and possesses a molecular weight of 2.5 X 10(7) and a guanine-plus-cytosine content of 65.7 +/- 0.5%. The lipid fraction of R1 accounts for 14% of the total dry weight of the virus, 20% of which was identified as free or esterified sterols. A rapid loss of viral titer occurred after seconds of exposure to organic solvents. This result suggests that the lipid fractions of R1 is essential for its infectivity. Electron microscopic investigation of solvent-extracted R1 showed extensive deterioration of its normal morphology, including nucleocapsid disintegration and base plate separation. Routine phosphotungstate preparations demonstrated a particle with an oval head and a noncontractile tail. Altering the pH of the phosphotungstate negative stain from neutrality damage the viral particles. Uranyl formate-contrasted specimens displayed an elongated hexagonal nucleocapsid with a neck region; the cross-striated tail possessed a starlike base plate.
| 23,439
|
Acetohydroxamic acid: clinical studies of a urease inhibitor in patients with staghorn renal calculi.
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The hydrolysis of urea by the bacterial enzyme urease pathologically increase urinary ammonia, bicarbonate, carconate and alkalinity. These factors contribute to the formation of urinary stones and to the virulence of bacteria. Acetohydroxamic acid, a potent inhibitor of urease, has been administered to 23 patients with staghorn renal calculi and urea-splitting urinary infection. Urinary ammonia and alkalinity has been reduced in every patient. A dose of 1.0 gm. acetohydroxamic acid daily has been well tolerated and effective for 2 to 12 months, even in patients with impaired renal function.
| 23,442
|
A pH-conditional mutant of Escherichia coli.
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Mutants of Escherichia coli have been isolated that are able to grow on lactose at pH 7.0 but not at pH 8.1. One of these mutants was analyzed and shown to map in the Z region of the lactose operon. beta-Galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) activity in toluenized mutant cells at pH 8.0 was one-tenth that at pH 7.0. Enzyme purified to near homogeneity from the pH-conditional mutant similarly exhibited pH-conditional activity under conditions where wild-type enzyme was unaffected over a pH range of 6.0-8.0. The pH-conditional beta-galactosidase was used in vivo as a probe for intracellular pH. We show that an internal pH of approximately 7.8-8.0 is maintained through an external pH range of 5.9-7.8. The phenotype of pH-conditional mutants was defined on medium with lactose as the sole carbon source. Under such conditions the gene product itself, beta-galactosidase, is required to maintain intracellular pH, since such maintenance is clearly energy-dependent. Therefore, we were able to recover a pH-conditional mutant in a cytoplasmic gene product. We predict that with any phenotype independent of energy production, however, pH-sensitive mutants will be recovered only in surface elements.
| 23,535
|
[The prevention of accidents in dental local anesthesia].
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The relatively rare complications developing under local anaesthesia may be due to various causes. The possibilities of the development of accidents under local anaesthesia are outlined; and prophylactic and therapeutic measures are deduced. A schematic premedication cannot prevent the development of complications with a sufficient degree of certainty; for instance, in certain cases the administration of atropine alone will still worsen the course of a complication. On the contrary, an individual premedication should be aimed at, especially in risk patients; the dosage must take into consideration all important factors. Consequently, atropine is of less importance than, for example, psychopharmaca and beta-receptor blockers.
| 23,595
|
[Rat brain and liver glutamine synthetase and gamma-glutamyltransferase activity in alloxan diabetes (IV)].
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Glutamine synthetase and gamma-glutamyltransferase activities of brain and liver homogenates of rats suffering from alloxan diabetes were determined in the soluble fraction (fraction 1) and in that obtained after treatment with 0.2 percent deoxycholate (fraction 2). The results obtained indicate that the activities of these enzymes in homogenates of brain and liver of diabetic animals does not differ from that of normal animals. gamma-Glutamyltransferase activity of brain is significantly reduced (about 5 fold) in the soluble fraction while glutamine synthetase activity is not much changed. The activities of glutamine-synthetase and gamma-glutamyltransferase of the 2-nd fraction obtained from rat brain and liver are very much higher than in the first fraction and are not considerably different from the activities observed in normal animals. In contrast to brain, glutamine synthetase and gamma-glutamyltransferase activities of liver of diabetic animals do not differ from the activities observed in normal animals, both in the homogenates and in the 1-st and 2-nd fractions.
| 23,608
|
[Use of the 25-point ocular grid plate in quantitative-morphological studies of eutopic and dystopic testes of children].
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From plains histologic preparations of children's testicles the volume of seminiferous tubules and extratubular tissue were calculated by use of the points counting method. In ectopic testicles, the extratubular part is significantly larger than in normally descended testes. The range of the values measured by this method diminishes the higher the total count of test points is. The 25-points-test-net of VEB Carl Zeiss Jena in particular met all requirements for quantitative examinations of the morphology of testicles.
| 23,614
|
On the determination of free L-tryptophan.
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The determination of free L-tryptophan depends on several analytical well checked points e.g. absorbing effects, pH of the serum, dependence of the throughput, concentration dependence of retention, volume ultrafiltrated, cut-off, temperature dependence of the binding rate, purification on ion-exchange column, interfering substances of the fluorometric method. Ultrafiltration was compared to an ultracentrifugation technique. In normal human serum the concentration of free L-tryptophan is 3,1 +/- 0,6 microgram/ml and of the bound plus free form 12,2 +/- 1,12 microgram/ml. Both values are dependent on the albumin concentration.
| 23,660
|
Quality assessment of a telephone care system utilizing non-physician personnel.
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An approach to providing medical care by telephone is described and its content and quality assessed by means of an outcome study. Pediatric health assistants have been trained to evaluate, triage and offer home management advice in lieu of an office visit for medical problems presented by parents via telephone. During a four-week study period, data were collected on all calls (N = 2520) using a telephone encounter form. Fifty-nine per cent of all calls involved requests for care of illness, 30 per cent of which were independently handled by the health assistant. Quality of care was evaluated for those cases who received advice in home management by means of a seven day follow-up interview with parents (N = 247). Access, parent satisfaction, residual symptoms, and the need for further care were ascertained. Greater than 90 per cent of parents expressed satisfaction and 92 per cent of problems had resolved. Results indicate that this telephone care system can effectively sort out and advise parents in home management for the many minor problems which occur in a pediatric practice, thereby increasing time for direct contact with patients.
| 23,689
|
Chest pain: coronary or esophageal?
|
Although it is often relatively easy for the clinician to differentiate between the heart and the esophagus as sources of chest pain, there remains a substantial minority of patients in whom this task is difficult. We have attempted to review points of differential significance which can be elicited through assessment of the patient's symptoms. Diagnostic studies for the detection of esophageal disorders have been reviewed, and the relative usefulness of these studies has been emphasized. As the result of advancements in diagnostic techniques as well as better understanding of esophageal pathophysiology, the clinician is now capable of accurately identifying the esophagus as the source of chest pain.
| 23,713
|
Control of the chemotactic behavior of Bacillus subtilis cells.
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The effects of nigericin, valinomycin and some lipophilic cations on the motile behavior of non-starved and methionine-straved Bacillus subtilis cells were studied. For valinomycin and nigericin a quantitative relationship between the flux in the proton-motive force and the duration of the twiddle response was found. Lipophilic cations bind to the ion gate controlling the twiddle frequency and thereby cause the cells to swim smoothly. To explain the transmission of the chemotactic signal a model is given in which receptors, a hyperpolarizing wave, an ion gate and two methylation sites, viz. methyl-accepting chemotaxis proteins and a further methylation site (MT), play a role. For the transmission of the signal caused by an attractant both the hyperpolarizing wave and an interaction between receptor and methylation site (MT) are needed. The methyl-accepting chemotaxis proteins are involved in the adaptation/deadaptation to altered levels of attractant. Artificial changes in the proton-motive force act directly on the ion gate, which finally controlls the twiddle frequency of the cells.
| 23,735
|
The separation and characterization of marmoset kidney beta-D-galactosidase and beta-D-glucosidase.
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beta-D-Galactosidase and beta-D-glucosidase activities were determined in homogenates of marmoset kidney by using the appropriate 4-methylumbelliferyl glycoside, beta-D-Galactosidase activity was separated into two main components by ion-exchange chromatography on DEAE-cellulose, starch-gel electrophoresis, isoelectric focusing and gel filtration on Sephadex G-200. One form designated A had a pI of 5.1, was loosely bound to DEAE-cellulose at pH7.0, remained near the origin on starch-gel electrophoresis at pH 7.0 and had an apparent molecular weight of 160000. The second beta-D-galactosidase component, designated B, was associated with the total beta-D-glucosidase activity, had a pI of 4.3, was firmly bound to DEAE-cellulose, migrated rapidly towards the anode on starch-gel electrophoresis and had an apparent molecular weight of 50000. The optimum pH values of beta-D-galactosidase A and B were 4.5 and 6.0 respectively. beta-D-Galactosidase A was activated by 0.1 M-NaC1 but the activity of the B form was inhibited by 1 M-NaC1 at pH 4.5. beta-D-galactosidase had a bimodal distribution, the A form being recovered in the lysosomal fraction whereas the B form was present in the soluble fraction, as was the major portion of the beta-D-glucosidase activity. The lysosomal and soluble forms were further characterized by DEAE-cellulose chromatography.
| 23,762
|
Effect of halopredone acetate on rat liver tryptophan oxygenase and tyrosine aminotransferase activities.
|
The possible inductive effect of a new local antiinflammatory steroid, 17,21-bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate; Topicon), on the rat liver enzymes tryptophan oxygenase and tyrosine aminotransferase was evaluated. The new steroid, when present in the implanted cotton-pellets or when s.c. injected, unlike the reference compound, fluocinolone acetonide, which induced a large increase in both enzymes, did not modify either tryptophan oxygenase or tyrosine aminotransferase. The results confirm that halopredone acetate elicits potent local antiinflammatory activity in the absence of systemic effects.
| 23,791
|
Intraerythrocyte pH, pCO2 and the hexose monophosphate shunt.
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We have documented a rise in pCO2 when erythrocytes are haemolysed by freeze-thaw using solid CO2 and methanol. This is partially corrected by preventing leakage of CO2 into the system. The remaining increment is partially explained by stimulation of the hexose monophosphate shunt when erythrocytes are haemolysed by this technique.
| 23,823
|
Study on plant RNAases. Isolation and properties of several activities from Vicia faba root cells.
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Vicia faba root cells contain several nucleolytic activities: phosphomonoesterase and phosphodiesterase (which however were not studied in details), one nuclease and four ribonucleases. These results were obtained by separating the extracted proteins into anionic and cationic species by chromatography on CM-cellulose at pH 5.5 and analysing each kind of proteins. Anionic species were subjected to chromatography on DEAE-cellulose which lead to isolation of one nuclease (A1) and two RNAases (A2, A3), the properties of which were studied. It was shown that the RNAases pH optima are near 6; A2 is more thermolabile than A3; both are endonucleases unable to attack double-stranded structure; studies with homopolymers, i.e. poly(A), poly(I), poly(C), poly(U), showed that their base specificities were analogous to that of already known plant RNAases. The cationic proteins, analysed with CM-cellulose, contain two RNAases (C1, C2). The pH optima were near 6 and 7, respectively; C1 is much more thermolabile than C2; both were endonucleases inactive on double-stranded structures. C1 and C2 hydrolysed poly(C) and poly(U) but not poly(A) and poly(U).
| 23,832
|
Studies of the catalytic properties of an endonuclease isolated from Tetrahymena pyriformis.
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An acid endonuclease hydrolyzing both DNA and RNA was purified from Tetrahymena pyriformis, strain E. The enzyme is distributed in all major subcellular compartments and is excreted into the growth medium towards the middle of the logarithmic phase. It hydrolyzes DNA to penta or hexanucleotides, on the average, bearing the monoesterified phosphate at the 3'-position. Particularly in early phases of the reaction it shows a very pronounced specificity for bases with a keto group at position 4 of the pyrimidine ring, such as guanine and thymine.
| 23,834
|
Indole to phenolate energy transfer, the alkaline quenching mechanism of beta-trypsin fluorescence.
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Evidence that indole to phenolate energy transfer causes the decrease in beta-trypsin fluorescence with increasing alkalinity is obtained indirectly from viscosity, lifetime, wavelength dependence and chemical modification studies which either exclude or minimize the involvement of other possible mechanisms.
| 23,855
|
[Catalytic properties of three isoenzymes possessing pyrophosphatase activity, isolated from baker's yeast].
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A kinetic study of inorganic pyrophosphatase isolated from brewer's yeast was done. It was shown that all three isoenzymes have the same pH-optimum and specificity with respect to substrate and metal activator. Statistical treatment of the kinetic data yielded equilibrium and catalytical constants, describing enzyme interaction with the metal activator and substrate. The catalytic properties of all three isoenzymes are similar to those of the baker's yeast pyrophosphatase. The fluoride inhibition pattern for inorganic pyrophosphatase from brewer's yeast is similar to that for the baker's yeast enzyme.
| 23,871
|
In vivo release of gastrin into human gastric juice.
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The release of antral gastrin has been examined in human subjects by infusing saline and albumin into their stomachs. Immunoreactive gastrin (IRG) was present in fasting serum but not in fasting gastric juice. Intragastric infusions of saline and albumin induced small but significant (P less than 0.05) rises in the serum concentrations of IRG. There was no significant difference between the magnitude of the serum gastrin responses to these two stimuli. The stimuli induced a rise in the luminal concentration of IRG which was sixfold greater than that in the serum concentration of IRG. The response to albumin was significantly greater than the response to saline (P less than 0.05). The IRG in gastric juice was chromatographically similar to heptadecapeptide gastrin. The stimuli also released IRG in patients with duodenal ulcers. The magnitude of the release into serum and gastric juice in these patients was significantly reduced by antrectomy (P less than 0.05).
| 23,884
|
Enteroendocrine cells in the digestive tract of Barbus conchonius (teleostei, cyprinidae).
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Just as in other cyprinids, three zones can be distinguished in the digestive tract of Barbus conchonius. A fat absorptive zone (65--75%), including the intestinal bulb, is followed by a protein absorptive zone (25--35%) and a small ion and water absorptive zone (less than 5%). The main characteristics of these zones are described. Four types of enteroendocrine cells can be distinguished between the intestinal epithelial cells. The number decreases in the caudal direction, and there are very few in the protein absorptive zone. All the enteroendocrine cells are argyrophilic and differ mainly in the size and shape of their secretory granules. Serotonin producing and hence argentaffin cells have not been found. Amine precursor uptake and decarboxylation (APUD) by the enteroendocrine cells of adult fishes has not been observed. The possible functions of the enteroendocrine cells are discussed. (Auto-)phagosomes, common in epithelial cells of the gut of B. conchonius, show similar staining characteristics as the enteroendocrine cells; their function is discussed.
| 23,902
|
Electrostatic interactions at charged lipid membranes. Measurement of surface pH with fluorescent lipoid pH indicators.
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The 5-dimethylaminonapthalene-1-sulfonyl (dansyl) chromophore attached to the polar head groups of lipids has been used as a fluorescent lipoid pH indicator to evaluate the interfacial pH in lipid-water lamellar systems prepared from negatively charged lipids. The pH in the vicinity of the charged lipid bilayers is different from the pH of the bulk aqueous phase and the difference is a function of the electrolyte concentration in the aqueous phase and of the lipid packing in the bilayer. At a fixed electrolyte concentration in the aqueous phase, the observed interfacial pH is 0.6 to 0.7 pH units lower above the thermal phase transition of the lipid than it is below this temperature. A quantitative interpretation of the results is given on the basis of the Gouy-Chapman theory. The results indicate that the dansyl chromophore is located in front of the charged surface and its distance from this surface increases with a decrease in lipid packing.
| 23,947
|
[Effect of the structure of liposomal membrane surface layer on the binding of phenothiazines].
|
By using a fluorescent 3-metoxybenzatrone probe the binding of the phenothiazine series drugs (chlorpromazine, triftazine, aethaperazine) with phospholipid vesicles--liposomes, was investigated. Cholesterol is shown not to affect the binding of these drugs with liposomes. The surface charge of liposomes influences only the combination with the chlorpromazine membranes. With a higher positive charge of the membranes the binding of chlorpromazine diminishes in force.
| 23,960
|
Actions of angiotensin on adrenergic nerve endings.
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In the perfused vascular bed, vasoconstrictor responses to adrenergic nerve stimulation are augmented to a greater degree by angiotensin II than are the responses to injected norepinephrine. Overflow of adrenergic transmitter is also greater during nerve stimulation in the presence of angiotensin than in its absence. The evidence indicates that facilitation of adrenergic transmitter release rather than uptake blockade accounts for these results. In addition, an increased responsiveness of isolated arterial strips to norepinephrine as well as other agonists appears to contribute to the adrenergic potentiating effect of angiotensin II as well as angiotensin III. This action, which appears to be a cell membrane effect, seems to participate in adrenergic potentiation mainly in the arterial segment of the intact vascular bed. Both of these effects of angiotensin, i.e., facilitation of release and increased smooth muscle responsiveness, appear to be mediated by angiotensin receptors.
| 23,967
|
Varicocele: relation between anoxia and hypospermatogenesis.
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Three groups of patients were analysed: varicocele patients with abnormal seminal fluid (17 cases), variococele and normal sperm (seven cases) and normal males (17 cases). Blood gas was secured in the internal spermatic vein, perpheric vein and femural artery, in an attempt to evaluate the possibility of altered gas content as a cause of spermatogenic depression. No statistical differences were found when we compared the three groups. We concluded that anoxia was not the cause of hypospermatogenesis in varicocele patients.
| 24,012
|
The pH of the hamster sperm acrosome.
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The pH of the hamster sperm acrosome was estimated by a method based on the distribution of monoamines between membrane enclosed volumes maintaining pH gradients. A fluorescent amine, 9-aminoacridine, was used to permit both microscopic and fluorometric measurements of amine distribution. Cauda epididymal hamster sperm incubated with 9-aminoacridine accumulated the amine in the acrosomal volume. In the presence of NH4Cl or the ionophore Nigericin (compounds which discharge pH gradients) 9-aminoacridine fluorescence disappeared from the acrosome. Amine distribution between the acrosome and external volume was estimated by fluorometric measurement of sperm filtrates in the presence and absence of NH4Cl and Nigericin. These values, together with an estimated acrosomal volume of 0.4mu3 were used to calculate an acrosomal pH of less than 5. In addition, an acrosomal pH of 5 or less was obtained with 14C-methylamine. We suggest that such an acidic acrosomal pH of 5 or less could serve to inhibit the activation or autoactivation of the acrosomal zymogen proacrosin to acrosin, a trypsin-like enzyme involved in fertilization.
| 24,069
|
Virulence and resistance to superoxide, low pH and hydrogen peroxide among strains of Mycobacterium tuberculosis.
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Six strains of Mycobacterium tuberculosis of different virulence in guinea-pigs were compared with regard to their resistance to low pH, to hydrogen peroxide (H2O2) at different pH values and to superoxide (O2-). Low virulence was associated with susceptibility to H2O2 in native and isoniazid-resistant strains but not in laboratory-attenuated strain H37Ra. H2O2 resistance was only partly related to catalase content. Low virulence was not associated with susceptibility to an acid environment but the tuberculocidal effect of H2O2 was significantly increased at low pH. The strains were uniformly resistant to O2- and contained similar amounts of superoxide dismutase. The implications of these observations are discussed in the context of mechanisms of host defence in tuberculosis.
| 24,084
|
Protein kinase from avian myeloblastosis virus.
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A protein kinase associated with purified virions of avian myeloblastosis BAI strain A was partially purified by ion-exchange chromatography and gel filtration. The transfer of phosphate catalyzed by this enzyme required a divalent metal ion and ATP as phosphate donor. GTP could not be substituted for ATP, and the reaction was unaffected by either cyclic AMP or beef-heart protein-kinase inhibitor. Of the virus and nonvirus proteins tested as phosphate acceptors, only acidic proteins were phosphorylated. In particular, purified preparations of reverse transcriptase from avian myeloblastosis virus did not accept phosphate. The enzyme is a basic protein (pI = 9.3), and, on the basis of molecular sieving through Sephadex G-200 and velocity sedimentation on glycerol gradient, the protein kinase has a molecular weight of 45,000.
| 24,125
|
[Bullet embolism of the median cerebral artery].
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A shot injury to the middle cerebral artery caused occlusion to the vessel by thrombosis and emboly of the missile. The projectil had been removed, but a thrombus formed in the a. cerebri media as a postoperative complication or by progression of a thrombosis in the internal carotid artery and after 19 days the patient died. A focal emollition of the left cerebral hemisphere was found at autopsy.
| 24,153
|
Reactions between peroxidizing lipids and histidyl residue analogues: enhancement of lipid oxidation and browning by 4-methylimidazole.
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As a part of our study on the interactions between peroxidizing lipids and the histidyl imidazole side-chain in simple, low-moisture model systems, 4-methylimidazole (4MI) was reacted with methyl linoleate (ML). This analogue was chosen to avoid interference from other functional groups in histidine (free base) or in proteins. Changes in the concentrations of lipid hydroperoxides, carbonyls, 4MI, and brown pigments were followed over a period of 24 days. The results indicate that 4MI exhibits significant prooxidative activity by reducing the induction period as well as by enhancing the formation of brown pigments. These effects are more pronounced at high 4MI/MI molar ratios and under basic pH's. Upon interactions with peroxidizing ML, as much as 44% of initially present 4MI was destroyed by the sixth day of incubation.
| 24,161
|
Disequilibrium pH and bicarbonate reabsorption: relevance to the pathogenesis of distal renal tubular acidosis.
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An augmented renal capacity to reabsorb bicarbonate (RHCO3) has been noted in patients with distal renal tubular acidosis (dRTA), and construed as evidence that the basic defect in dRTA is abnormal distal tubular permeability. According to this interpretation, the absence of a disequilibrium pH due to a back-leak of H2C03 permits increased distal H+ secretion and results in an increased RHCO3. To test this assumption, we have evaluated the effect of acute elimination of the disequilibrium pH by carbonic anhydrase infusion. The results establish that this maneuver doses not cause a rise in RHCO3. Thus, the elevated value of RHC3 described in dRTA cannot be the consequence of increased back-diffusion of H2CO3 and is more likely due to coexisting extracellular volume depletion and/or postassium deficiency.
| 24,188
|
[Development of hematopietic and lymphoid tissues in conjoint bone marrow and thymus transplants].
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The model of heterotopic transplantation of the mixture of bone marrow and thymus fragments was used to study the interaction of hemopoietic and lymphoid tissues under their direct contact. The bone marrow and thymus fragments of adult mice F1 (CBAXXC57BL) were transplanted separately or in the mixture under the kidney capsule of mice of the same strain. During the whole period of observation (from 10 days up to 14 months), the development of bone marrow and thymus fragments in the joint transplants proceeded independently, no "mixed" stroma appeared, and the stroma of each organ ensured the differentiation characteristic of its organ. The development of joint transplants somewhat differs from that of isolated transplants: on the 10th day a greater amount of hemopoietic tissues was noted in the former; the bone marrow component increases continuously up to 6 months (vs. 1--2 months in the isolated transplants); the bone and hemopoietic tissues predominate in the joint transplants by 14 months, the amount of thymic tissue markedly decreases but it does not disappear completely.
| 24,196
|
Granulomatous ileocolitis (Crohn's disease).
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In a clinical survey, the symptoms, associated diseases, and local and metabolic complications of Crohn's disease are discussed. Medical treatment (with SASP, corticosteroids, and immunosuppressives), as well as treatment for malnutrition, is of special importance.
| 24,234
|
The effect of agitation of stored human blood on microaggregate formation.
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Microaggregates (MA) composed of platelets and white blood cells form during the storage of human blood. These particles are believed to be a cause of pulmonary insufficiency in patients receiving massive blood transfusions. The present controlled study determined the effect of constant gentle agitation of CPD-anticoagulated blood, during storage at 4 C, on the formation of MA. Using a Model T Coulter Counter, it was found that agitated blood contained significantly lower volumes of MA at 7 and 14 days than did nonagitated controls. However, significant elevations, above control levels, of plasma free hemoglobin, lactic dehydrogenase, and potassium indicated significant injury to cellular components of agitated blood. This study raises serious doubts concerning the potential clinical usefulness of blood agitation during storage to prevent MA formation.
| 24,292
|
[Some properties of Mg 2+, Ca 2+-AtPase of brain microsomal fractions and synaptic plasma membranes in the solubilized state].
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Digitonin-solubilized Mg2+, Ca2+-ATPases of the brain microsomal fraction and synaptic plasma membranes are activated against a background of 6.0 mM Mg2+ by 0.001 and 0.03 mM of the added Ca2+ and manifest maximum activity at temperatures or 40-45 and 35-42 degrees C, respectively. The enzymes of the initial membrane preparations are activated by the same concentrations of the added Ca2+ and are characterized by the same temperature dependence. The values of pH-optima of the enzyme activity of both solubilized preparations are 7.0-7.3 and in comparison with pH-dependence of the initial membrane preparations are shifted towards acid side.
| 24,293
|
The disposition of phentermine and its N-oxidized metabolic products in the rabbit.
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1. When phentermine was injected intraperitoneally to rabbits, 77% of the dose was excreted in the urine within 2 days; N-oxidized metabolic products accounted for 62% dose. Major excretion products were N-hydroxyphentermine (28% dose), conjugated N-hydroxyphentermine (32% dose) and unchanged phentermine (16% dose). 2. Similarly injected N-hydroxyphentermine was excreted (62% dose) in the urine in 2 days; only 4% dose was recovered unchanged. Major routes of metabolism of N-hydroxyphentermine was conjugation (36% dose) and reduction to the parent amine (15% dose). Conditions for hydrolysis of urine to liberate N-hydroxyphentermine from its conjugates were studied; N-hydroxyphentermide decomposes in strong acid. 3. Only 10% of injected alpha, alpha-dimethyl-alpha-nitroso-beta-phenylethane was excreted in the urine in 2 days. 4. N-Oxidations is the major pathway of metabolism of phentermine in rabbits; the present results suggest that some biological activity may be mediated by the pharmacologically active N-hydroxyphentermine.
| 24,306
|
[Dialysis technic for regulation of the internal milieu in acute poisoning].
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In 72 patients with acute poisoning (15 patients without unconsciousness with 80% of acute renal and hepatic failure, and 57 patients with unconciousness with 10.5% of acute renal and hepatic failure) the significance of the continuous prolonged haemodialysis lasting on an average 12 hours, respectively 18 hours, with the maximum of 33 and 82 hour, respectively. The duration of the haemodialysis was in close correlation with the pH-value of the blood and the duration of the unconciousness. One half of the unconscious patients suffered from dehydration (of them up to 40.3%), which was valuated by the height of the central venous blood pressure. It was also referred to the necessity of the correction of the potassiaemia and glycaemia.
| 24,313
|
"False positive" acidified serum test in a preleukemic dyserythropoiesis.
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In a case of preleukemic dyserythropoiesis, in vitro red cell lysis tests showed a positive acidified serum test whose characteristics are described. The positive acidified serum test occurred in 10 normal sera, in 1 serum with complete deficiency of the fourth component of complement and in 1 serum with complete deficiency of the second component of complement. The test was found negative with 2 hyperlipemic sera. The other in vitro red-cell lysis tests were negative. The results of the in vitro lysis tests were different from the results obtained in paroxysmal nocturnal hemoglobinuria and congenital dyserythropoietic anemias.
| 24,320
|
Norepinephrine: hormone and neurotransmitter in man.
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To determine whether norepinephrine could subserve a hormonal as well as a neurotransmitter function, norepinephrine was infused for 60 min into each of five normal young men in doses of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min. After infusion, the plasma norepinephrine concentration fell with a mean (+/-SD) half-time of 2.4 +/- 0.7 min. The mean (+/-SD) norepinephrine metabolic clearance rate was 3,070 +/- 200 ml/min. The calculated basal plasma norepinephrine production rate was 0.7 microgram/min. The blood pressure and circulating glycerol, acetoacetate, beta-hydroxybutyrate, and glucose (increased) and the heart rate and circulating insulin, lactate, pyruvate, and alanine (decreased) exhibited highly significant parabolic relationships with the steady-state plasma norepinephrine concentrations. However, norepinephrine levels in excess of 1,800 pg/ml were required to produce hemodynamic and/or metabolic effects. Thus, under usual conditions, the biologic actions of norepinephrine can be attributed only to its sympathetic neurotransmitter function. Plasma norepinephrine concentrations do at times exceed 1,800 pg/ml during exercise and during major acute illness. Thus, under conditions of stress, norepinephrine may subserve a hormonal, as well as a neurotransmitter, function.
| 24,347
|
Acetazolamide and renal ammoniagenesis.
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The effect of acetazolamide on ammonia-producing enzyme systems was determined in vitro at concentrations comparable to those which have been shown to abolish ammonium excretion in vivo. No change in the activity of glutaminase or gamma-glutamyl transpeptidase could be observed at concentrations up to 0.2 mM acetazolamide, and concentrations up to 1 mM were without effect on D-glutamyltransferase activity. Therefore, the effect of acetazolamide to abolish ammonium excretion cannot be explained by an action of the drug to inhibit ammoniagenesis.
| 24,348
|
[Metabolic disorders in experimental hepatic insufficiency and parenteral feeding].
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Anhepatia is a complete experimental model for the study of metabolic disturbances associated with hepatic insufficiency. The authors report their experience based upon 16 cases of total hepatectomy in the dog. The animals received different types of hepatic assistance : group 1 (2 dogs), carbohydrate assistance (glucose 7 g/kg/24 h) ; group II (2 dogs), carbohydrate and haemostatic assistance : homologous plasma 50 ml/kg body weight per 24 hours previously stored at - 80 degrees C ; group III (2 dogs) same nutrition as in group II, combined with amino acids : leucine 53, 3 mg, isoleucine 46, 6 mg ; valine 53,3 mg alpha-ketonic acid (lg/kg/24 h) ; group IV (10 dogs, same nutrition as in group III, combined with supplements in neuro transmitter precursors : 6 dopa 1,66 mg, 5 hydroxy-tryptophane 2 mg and choline 16, 66 mg/kg/24h. Metabolic disturbances and their course were analysed in detail. Results : (mean survival) - group I : 24 +/- 4 hours; group II : 36 +/- 9 hours; group III : 42 +/- 4 hours; group IV : 90 +/- 9 hours. The average survival differed significantly for groups III and IV (p less than 0,01) in comparison with control groups I and II. The replacement of essential hepatic functions such as blood glucose regulation, coagulation, detoxication and the provision of neurotransmitter precursors made possible 4 days survival after total hepatectomy.
| 24,386
|
[Hydrogen ion metabolism and parenteral alimentation].
|
The necessity of using solutions and emulsions in parenteral nutrition of solutions directly utilisable by the cell has led to the manufactur of substances with a composition and physico-chemical nature which greatly alters H+ ions balance. Theoretical calculation and various experimental protocois have shown that the production of H+ ions may be multiplied by 3 or 4. This explains the complications of metabolic acidosis seen in association with prolonged parenteral nutrition. There are two main sources : lipid emulsions and amino-acid solutions. One litre of lipid emulsion may provide 37 to 60 mEq of H+ ions. According to their formula, amino acid solutions may consume, or more often provide, large amounts of H+ ions (up to 20 mEq/gram of nitrogen). These physiopathological concepts should be taken into consideration in defining the compositions of fluids for parenteral nutrition, in particular when renal function is impaired.
| 24,390
|
[Metabolic problems associated with ethanol administration].
|
After reviewing the effects of ethanol on different metabolic processes, the author defines the doses of this alcohol which may be used in parenteral alimentation, its advantages and disadvantages. The latter in general outweigh the advantages and limit its use in parenteral nutrition.
| 24,391
|
Stability and blood level determinations of cefaclor, a new oral cephalosporin antibiotic.
|
Cefaclor solutions in pH 2.5 and 4.5 buffers contained at least 90% of their initial activity after 72 h at 4 degrees C. Samples in pH 6.0, 7.0, and 8.0 buffers contained 70, 46, and 34%, respectively, of their initial activity after 72 h at 4 degrees C. After 72 h at 25 degrees C, samples prepared with pH 2.5, 4.5, 6.0, 7.0, and 8.0 buffers contained 95, 69, 16, 5, and 3%, respectively, of their initial activity. After 72 h at 37 degrees C, cefaclor solutions in pH 2.5 buffer contained 80% of the initial activity, whereas samples prepared in pH 4.5, 6.0, 7.0, and 8.0 buffers contained less than 20%. Laboratory-prepared plasma and serum samples showed an 8% loss in activity when incubated for 6 h at 4 degrees C, a 51% loss when incubated for 6 h at 25 degrees C, and a 48% loss when incubated for 2 h at 37 degrees C. Clinical samples demonstrated a similar stability pattern. Degradation rates for cefaclor in commercially prepared serum increased from 4- to 10-fold in comparison to rates obtained when samples were made in human serum freshly prepared in our laboratory. Consequently, serum standards should be made in freshly prepared human serum.
| 24,410
|
Allergic angiitis and granulomatosis. Prolonged remission induced by combined prednisone--azathioprine therapy.
|
Two patients with acute, rapidly progressive generalized vasculitis initially had symptoms of asthma. Progressive increase in severity of asthma was followed by systemic disease, including pulmonary infiltrative disease, mononeuritis multiplex, and abdominal pain. Examination of the tissues demonstrated vasculitis with eosinophilia, and clinically both cases appeared in a near terminal state. High-dose prednisone did not induce a remission. In particular, the lesions of mononeuritis multiplex progressed after initiation of high-dose prednisone. The addition of azathioprine to the regimen was followed by a gradual and then complete remission of clinical and laboratory abnormalities, except for some residual nerve damage and asthma of varying severity in the two patients. These two patients, whose cases are classified as the allergic granulomatosis variant of polyarteritis nodosa, have had a remission of seven and almost two years, respectively, after combined prednisone-azathioprine therapy.
| 24,429
|
Partial purification and characterization of a pyruvate dehydrogenase-complex-inactivating enzyme from rat liver.
|
An enzyme inactivating the pyruvate dehydrogenase complex (inactivase) was purified about 8000-fold from rat liver by differential centrifugation, acid extraction of a lysosomerich 25000 g pellet, acetone fractionation, and adsorption on calcium phosphate gel. By exclusion chromatography on Sephadex G-100 a molecular weight of 21 000 was estimated. The purified enzyme was most stable at pH 5.8 in potassium phosphate buffer, and at pH 4.5 in McIlvaine buffer. At high dilutions the enzyme was very labile and was remarkably stabilized by high salt concentrations. Enzyme activity is inhibited by native rat blood serum, iodoacetamide and leupeptin, but not by phenylmethanesulphonyl fluoride, suggesting that it belongs to the class of thiol proteinases. Among various enzymes tested, only 2-oxoglutarate dehydrogenase was attacked by the inactivase to a similar extent to the pyruvate dehydrogenase complex. Studies on the inactivation mechanism indicate that although the overall reaction is completely lost after treatment with inactivase, each individual step of the multienzyme complex retains full catalytic activity. As judged from sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the transacetylase subunit appears to be degraded into several smaller fractions.
| 24,442
|
Renal tubular function in normal pregnancy.
|
Maternal plasma and urine concentrations of beta2- microglobulin and gamma-glutamyl transpeptidase (EC:2.3.2.2) were measured serially in normal pregnancy. These parameters remained constant throughout and can therefore be used to evaluate tubular function in pregnancies complicated by renal disorders.
| 24,460
|
Spin-trapping of the trichloromethyl radical produced during enzymic NADPH oxidation in the presence of carbon tetrachloride or bromotrichloromethane.
|
Utilizing the spin-trapping agent phenyl-t-butyl nitrone, a free radical has been detected which is produced from carbon tetrachloride or bromotrichloromethane during the enzymic oxidation of NADPH by rat liver microsomes. The presence of NADPH is obligatory for generation of the radical. The formation of the trichloromethyl radical-phenyl-t-butyl nitrone adduct is an enzymic process, as evidenced by the inhibition of its formation in systems containing heated microsomes and in systems containing p-hydroxymercuribenzoate. A computer-simulated ESR spectrum for the trichloromethyl adduct of phenyl-t-butyl nitrone can reproduce the essential features of the spectrum of the spin-trapped radical produced enzymically from CCl4. A mechanism is proposed for the formation of the trichloromethyl radical from CCl4 or BrCCl3.
| 24,480
|
[Cardiomyopathies].
|
A) Definition and classification. Cardiomyopathy is defined as a dysfunction of cardiac muscle of unknown origin and classified according to genetic, morphological and functional criteria as follows: 1. cardiomyopathy of autosomal dominant inheritance with asymmetric septal hypertrophy (ASH) a) obstructive b) non obstructive 2. cardiomyopathy of autosomal dominant inheritance without ASH 3. cardiomyopathy of autosomal recessive inheritance 4. sporadic cardiomyopathy. It is assumed that at least the cardiomyopathies listed here are heterogeneous groups that have to be subdivided as soon as further discriminating findings--structural or enzymatic--are available. B) Diagnosis, prognosis, treatment. The diagnostic methods are evaluated, the prognosis and the treatment of the cardiomyopathies are reviewed.
| 24,578
|
Endocoagulation: a new and completely safe medical current for sterilization.
|
Tubal sterilization via pelviscopy with low current represents a unique method: the risk of high-frequency is thereby eliminated, and the application of the Crocodile-Forceps is relatively simple. The mouth of the Crocodile-Forceps grasps the tube under pelviscopic control. Tubal coagulation succeeds under electronic control at 100 degrees C and the area of coagulation measures 6-8 mm in length. In case additional separation of the tube is desired it may be performed bloodlessly with a scissor-like movement. The Crocodile-Clamp is electronically monitored by the "Tube-Coagulator" or the universal endoscopic "Endo-Coagulator." Since 1973 964 tubal coagulations by means of cutting have been performed without postoperative hemorrhage or other complications (pregnancy rate 0).
| 24,602
|
Metropolitan jail psychiatric clinic: a year's experience.
|
The behavioral, demographic and psychiatric characteristics of 524 inmates examined over a one year period in a metropolitan jail psychiatric treatment clinic are described. The psychiatric problems were sufficiently acute that over one-third of all patients were examined and treated within 24 hours of booking. Two psychiatric syndrome and intervention profiles emerged. The most commonly seen were misdemeanants, with psychotic illnesses who required long term antipsychotic medications and close contact with community treatment resources. Situational reactions with suicidal ideation in patients with character disorder diagnoses were seen less frequently. They were treated with short term anti-anxiety medications and environmental manipulation.
| 24,617
|
Purification and properties of mosquito DNA polymerase.
|
For the first time, DNA polymerase in a postembryonic insect has been purified and characterized. This enzyme from mosquito larvae was purified 1700-fold and was free of deoxyribonuclease and protease activities, which hindered previous investigations of insect polymerases. The enzyme had a molecular weight of 132,000 by gen filtration and aggregated to higher molecular weights when concentrated. With an activated DNA template, the pH optimum was 7.2 in phosphate buffer, and the Mg2+ concentration optimum was 5 to 10 mM. Polymerase activity was inhibited by the antisulfhydryl reagents, N-ethylmaleimide and p-mercuribenzoate, and by KCl. These properties indicate that the mosquito enzyme resembles mammalian alpha-polymerase but differs in its lack of inhibition to low ethanol concentrations. There was no evidence of a beta-polymerase form in the mosquito.
| 24,632
|
Purification and properties of an NADPH-dependent 21-oxo-20-hydroxysteroid reductase (17beta-aldol reductase) from sheep liver. Isolation of the 20beta-glycol product.
|
This investigation was undertaken to test the hypothesis that steroidal 20-hydroxy-21-aldehydes are intermediates in an alternative pathway of corticosteroid metabolism leading to steroidal 20,21-diols. A NADPH-dependent 21-oxo-20-hydroxysteroid reductase which catalyzed the reduction of 11beta,17,20beta-trihydroxy-3-keto-4-pregnen-21-al (isocortisol) to 11beta,17,20beta,21-tetrahydroxy-4-pregnen-3-one (Reichstein's compound E) was prepared from sheep liver. Other steroidal 17-aldols were also good substrates. Some steroidal 17-oxoaldehydes, D-, and L-glyceraldehyde were reduced, but less effectively than the steroidal aldols. Steroidal ketols and 21-oic acids were not substrates. The enzyme contains--SH groups, has a pH optimum of 6.9 to 7.5 and a molecular weight of about 28,000. Reversibility of the enzymic reaction could not be demonstrated. The reduction product obtained from isocortisol was isolated and characterized. Other 17-glycols were derived from their respective steroid aldols. Reductase activity was also present in hamster and rat liver. From a comparison of 21-oxo-20-hydroxysteroid reductase and 21-hydroxysteroid dehydrogenase with respect to pH optima, substrate specificity, stability to heat, and kinetic constants, we conclude that the two enzymes are distinct.
| 24,635
|
Differential inhibition of glutamine and gamma-glutamylcysteine synthetases by alpha-alkyl analogs of methionine sulfoximine that induce convulsions.
|
The alpha-methyl and alpha-ethyl analogs of methionine sulfoximine, like methionine sulfoximine, induce convulsions in mice and inhibit glutamine synthetase irreversibly; alpha-ethylmethionine sulfoximine is approximately 50% as inhibitory as methionine sulfoximine and alpha-methylmethionine sulfoximine. However, whereas alpha-methylmethionine sulfoximine and methionine sulfoximine inhibit gamma-glutamylcysteine synthetase markedly, alpha-ethylmethionine sulfoximine does not, nor does administration of the alpha-ethyl analog produce the decrease in tissue glutathione levels found after giving methionine sulfoximine or its alpha-methyl analog. The findings strongly indicate that methionine sulfoximine-induced convulsions are closely associated with inhibition of glutamine synthetase rather than with inhibition of gamma-glutamylcysteine synthetase. The alpha-alkyl methionine sulfoximine analogs cannot be catabolized via the corresponding alpha-keto or alpha-imino acids, and, like other alpha-substituted amino acids, are probably not metabolized to a significant extent in vivo; this suggests that the amino acid sulfoximine molecules themselves, rather than their metabolites, are directly involved in the induction of convulsions. Possible explanations for the reported lack of correlation between the occurrence of convulsions and the levels of glutamine synthetase activity (and its substrates and product) are considered. The findings suggest that studies on the mechanism of induction of convulsions may be extended significantly and refined in biochemical terms by the use of other structurally modified convulsant molecules.
| 24,637
|
Circling behaviour in the rat following unilateral injections of p-chlorophenylalanine and ethanolamine-O-sulphate into the substantia nigra.
|
Circling behaviour following the unilateral intranigral injection of the gamma-aminobutyric acid (GABA) transaminase inhibitor ethanolamine-O-sulphate, (EOS), or the tryptophan hydroxylase inhibitor p-chlorophenylalanine (pCPA) was compared, both for spontaneous circling and for circling induced by apomorphine administration. EOS-injected rats exhibited spontaneous contralateral rotation for up to 3 h after such injections. pCPA-injected rats showed only a slight ipsilateral postural asymmetry, both groups of rats elicited ipsilateral rotation upon apomorphine challenge. Increased ipsilateral dopamine release within the corpus striatrum accompanied this response. It is proposed that GABA and 5-HT may be closely related in modifying the nigrostriatal impulse flow.
| 24,688
|
Possible differences in alpha-adrenoceptors in rabbit ileum and spleen.
|
In isolated tissues from reserpinized rabbits (5 mg kg-1, i.m. 20 h before experiment) and in the presence of cocaine (3 x 10(-5) M), corticosterone (2.8 x 10(-5)M), tropolone (3 x 10(-5) M), propranolol (4 x 10(-5)M) and disodium EDTA (3 X 10(-5)M), the potency ratios (relative to (-)-noradrenaline) of (-)adrenaline, (-)-phenylephrine and (+/-)-methoxamine were (m+/-s.e.) 2.03 +/- 0.13, 0.045 +/- 0.003 and 0.0062 +/- 0.0018 respectively in splenic strips and 1.77 +/- 0.41, 0.093 +/- 0.018 and 0.029 +/- 0.004 respectively in isolated ileum. Although the pA2 values for phentolamine and thymoxamine against (-)-noradrenaline in the two tissues were very similar there was a statistically significant difference when using yohimbine as the alpha-adrenoceptor blocking agent (pA2 = 6.80 +/- 0.30 in spleen; 5.60 +/- 0.12 in ileum). These differences suggest that the alpha-adrenoceptor in the two tissues is not identical. The pA2 value of phentolamine in rabbits ileum was not significantly different whether (-)noradrenaline or (+/-) methoxamine was used as agonist (7.91 +/- 0.07 and 7.97 +/- 0.06 respectively) while that of yohimbine was 5.56 +/- 0.10 using (-)noradrenaline and 6.19 +/- 0.12 using (+/-)methoxamine. In the light of this latter result and, considering the scatter of the experimentally determined values, there may be two alpha-adrenoceptors in rabbit ileum and either or both may not be identical in all respects to the alpha-adrenoceptor found in rabbit spleen.
| 24,690
|
Aggregation of antidepressant drugs in aqueous solution.
|
Light scattering, conductivity and pH methods have been used to examine the aggregation in aqueous solution of a series of antidepressant drugs. The drugs investigated included the hydrochlorides of amitriptyline, butriptyline, protriptyline, nortriptyline, imipramine, desipramine, clomipramine, dothiepin, dibenzepin, opipramol, iprindole, doxepin, mianserin and maprotiline. No significant association of dibenzepin, mianserin or maprotiline hydrochlorides could be detected up to their respective solubility limits. A micellar pattern of association was established for all other compounds. Critical micelle concentrations and micellar properties are reported.
| 24,692
|
The effect of various topical antibiotic and antibacterial agents on the middle and inner ear of the guinea-pig.
|
The topical application of antibiotics and anti-inflammatory agents is used to reduce inflammation of the middle ear mucosa and irradicate infection. Many of the antibiotic and anti-inflammatory preparations so used contain compounds known to be or are potentially ototoxic. Eighteen antibiotic, antibacterial, antifungal and anti-inflammatory compounds and four commonly used solvents were screened for the absence of ototoxicity and inflammation to the middle ear mucosa. All compounds were injected intra-tympanically and sensory hair cells loss recorded graphically. Inflammation of the middle ear mucosa was assessed macroscopically. Of the 18 compounds only three, penicillin, carbenicillin and nystatin were free of hair cell toxicity and inflammatory effects on the middle ear mucosa. Only one of the commonly used solvents was free of side effects.
| 24,712
|
Chloride conductance of the amphiuma red cell membrane.
|
Like most other red cells, the giant erythrocytes of Amphiuma means possess a system for rapid exchange of chloride across the membrane. Also, there are indications that the net transport of chloride in these cells is slow. The size of Amphiuma erythrocytes allows direct measurements of membrane potential with microelectrodes. The present work exploits the possibility that such measurements can be used to give a quantitative estimate of the chloride conductance (GCl) of the Amphiuma red cell membrane. The membrane potential was measured as a function of extracellular chloride concentration (5-120mM), using an impermeant anion (Para-amino-hippurate) as a substitute. Furthermore, the effect of different pH values (6.0-7.2) was studied. For each extracellular chloride concentration the membrane potential was determined at a pH at which hydroxyl, hydrogen, and bicarbonate ions were in electrochemical equilibrium. From these membrane potentials and the corresponding chloride concentrations in the medium (at constant intracellular ion concentrations), the GCl of the membrane was calculated to be 3.9 x 10-7 omega-1 cm-2. This value is some six orders of magnitude smaller than that calculated from the rate of tracer exchange under equilibrium conditions. The experimental strategy used gives the values for a "partial transference number" which takes into account only ions which are not in electrochemical equilibrium. Whereas this approach gives a value for GCl, it does not permit calculation of the overall membrane conductance. From the calculated value of GCl it is possible to estimate that the maximal value of the combined conductances of hydroxyl (or proton) and bicarbonate ions is 0.6 x 10-7 omega-1 cm-2. The large discrepancy between the rate of exchange of chloride and its conductance is in agreement with measurements on human and sheep red cells employing the ionophore valinomycin to increase the potassium conductance of the membrane. The results in the present study were, however, obtained without valinomycin and an accompaning assumption of a constant field in the membrane. Therefore, the present measurements give independent support to the above mentioned conclusions.
| 24,748
|
Resistance to Marek's disease. Effect of Corynebacterium parvum and Marek's tumor cell vaccines on tumorigenesis in chickens.
|
A study of nonspecific stimulation of the avian immune system with Corynebacterium parvum and specific stimulation with Marek's tumor cell vaccines revealed that nonspecifically stimulated outbred White Leghorn-type cockerels had higher incidences of tumors than did controls. A study of tumor cell cytotoxicity of sera from Marek's disease virus exposed birds indicated that humoral factors may play some role in tumor resistance.
| 24,754
|
The inhibitory effect of papaverine on respiration-dependent contracture of guinea pig taenia coli in high-K medium. I. The relationship between contracture and respiration.
|
Papaverine (Pap) inhibited a tonic tension development in guinea pig taenia coli induced by an elevation of the potassium concentration of the medium to 40 mM (40-K). The ID50 of Pap was 4.5 x 10(-6) M. Inhibition of the 40-K induced tonic tension by Pap was dependent on the calculated concentration of non-ionized form, but not the ionized form. Inhibition of the tonic tension by Pap and various metabolic inhibitors was not antagonized by raising the Ca++ concentration in the medium. Results obtained from simultaneous measurement of the 40-K induced O2 consumption and tension illustrated that the inhibition of O2 consumption rapidly induced the inhibition of the tension. Furthermore, glucose removal, amytal or Pap resulted in a progressive relationship between the inhibition of O2 consumption and the inhibition of tension. The inhibition of Pap as determined by O2 consumption was not reversed by application of 10(-4) M 2,4-dinitrophenol (DNP). These results plus graphical analysis of the mechanical response suggest that Pap may penetrate the cell membrane and inhibit mitochondrial respiration, thereby inhibiting this very respiration-dependent contracture.
| 24,778
|
[Stationary kinetics of catalysis by the hydrogenase of Thiocapsa roseopersicina].
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Forward and reverse reactions of catalysis by a hydrogenase from T. roseopersicina in steady state have been investigated. The dependance of reaction rate on the concentration of substrates and of hydrogen ions has been studied. Detailed formal-kinetic analysis of possible mechanisms of enzyme action has been carried out and the classification of mechanisms of the reaction has been given. Comparison of experimental data with the equations obtained from formal-kinetic analysis has been undertaken and mechanisms compatible with experimental data were sorted out. Kinetic and molecular mechanism of the catalytic activity of hydrogenase has been proposed and elementary rate constants for the activation of molecular hydrogen have been calculated.
| 24,804
|
[Treatment of acute asthma. Comparison of the effectiveness of corticosteroids and of a combination of corticosteroids and an adrenergic beta-stimulant (author's transl)].
|
Two comparable groups of patients hospitalised for acute asthma received an intravenous infusion for two hours, containing corticosteroids in the first group and corticosteroids combined with an adrenergic beta-stimulant in the second. Course was assessed by the hourly measurement of forced expiratory volumen in one second (FEV1), heart rate and blood pressure. It was found that corticosteroids alone had a modest action (5,1% improvement in FEV1). By contrast, the combination of corticosteroids with an adrenergic beta-stimulant resulted in a rapid and pronounced improvement in FEV1 (19,9%), without producing any undisrable side-effects. No changes in arterial blood gases were noted under the influence of treatment. Injectable adrenergic beta-stimulants are therefore worthy of use in the treatment of an asthma attack, in the absencd of any contraindication.
| 24,829
|
Choosing a drug regimen for obstructive pulmonary disease. 1. Agents to achieve bronchodilatation.
|
Many patients with pulmonary disease may have significant airflow obstruction. Bronchodilatation is an important aspect of treatment and can be achieved with beta-adrenergic agonists, methylxanthine derivatives, and anticholinergic agents. These can be used singly or in combination, depending on the severity of obstruction.
| 24,835
|
Interaction of human chorionic gonadotropin with membrane components of rat testes.
|
Previous studies demonstrating that gangliosides interacted with thyrotropin and human chorionic gonadotropin (hCG) suggested that gangliosides participate in the transduction of the hormonal message across the target cell membrane. As a continuation of these investigations, we examined the effects of down-regulation of hCG receptors on the interaction of hCG with rat testis membrane components. Rat testes contained a complex ganglioside pattern that did not appear to change qualitatively or quantitatively after the injection of hCG into the animals, although testis membranes from hCG-treated rats lost their capacity to bind (125)I-labeled hCG ((125)I-hCG). Gangliosides extracted from the testes of control and treated animals were equally effective inhibitors of (125)I-hCG binding to testis membranes. However, inhibition of binding was observed only under conditions (pH 6.0, low ionic strength) such that unlabeled hCG (>2500-fold excess) did not block (125)I-hCG binding, and (125)I-hCG bound similarly to testis membranes from control and treated rats. Under conditions such that hCG binding was specific (blocked by 250-fold excess of unlabeled hCG), testis gangliosides were noninhibitory. Liposomes containing gangliosides from the testes of control or hCG-treated rats bound similar small amounts of (125)I-hCG. These same liposomes bound 50 and 1000 times more thyrotropin and cholera toxin, respectively, than hCG. Oligosaccharides derived from gangliosides did not inhibit (125)I-hCG binding to testis membranes nor did they alter the fluorescence of hCG conjugated with fluorescent probes, whereas the gangliosides themselves were inhibitory and enhanced the fluorescence intensity of the hCG derivatives. Exposure of testis membranes from hCG-treated rats to 4 M MgCl(2), which displaces bound hCG [Chen, Y.-D. I. & Payne, A. H. (1977) Biochem. Biophys. Res. Commun. 74, 1589-1596], did not restore their ability to bind (125)I-hCG. When membranes were solubilized with Triton X-100, a solubilized receptor was detected from testis membranes of control but not hCG-treated rats. These findings and the absence of demonstrable changes in the composition or quantity of rat testis gangliosides when hCG receptors are down-regulated suggest that gangliosides do not represent the primary binding determinants of hCG receptors.
| 24,844
|
[Purification and properties of the NADP-specific glutamate dehydrogenase of Candida tropicalis feed yeasts].
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From the cell-free extract of fodder yeast Candida tropicalis NADP-specific glutamate dehydrogenase was isolated and partially purified (75-fold) by means of fractional precipitation by ammonium sulphate and ion-exchange chromatography on DEAE-cellulose. The preparation was investigated with the aid of polyacrylamide gel electrophoresis. Kinetic characteristics of the enzyme in the cell-free extract and partially purified preparation were derived.
| 24,841
|
[Hypoglycemic effect of nicotinamide in rats with alloxan diabetes].
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Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide.
| 24,843
|
The role of fibrin formation in the pathogenesis of bacteremic shock in the primate.
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In this study, an attempt was made to elucidate further the role of intravascular fibrin formation in the pathogenesis of sepsis in the primate. It was found that injected live Escherichia coli caused death in primates within four to 11 hours as a result of microcirculatory failure and acidosis. Pretreatment with Arvin did not prolong the survival rate, probably because of an overloading of the reticuloendothelial system with fibrin degradation products. This study does not support an obligatory role for intravascular coagulation or fibrin formation in primate sepsis and coincides with an earlier report (6) from this laboratory on cats. Vascular damage and malfunction, secondary to mediators released by platelets, leukocytes, red cells or Hageman factor, are not ruled out.
| 24,899
|
Pathology of germ cell tumors of the testis.
|
Testicular germ cell tumors form a complex group of interrelated entities. Problems of nomenclature remain, but there does appear to be a close agreement between the major classifications in use. The identification of clinically useful markers for certain germ cell testicular tumors has provided a major impetus in this field. Information gained from the study of these markers has promoted an understanding of the histogenesis of germ cell tumors, has improved standard nomenclature, and has stimulated progress in patient care. Radioimmunoassay techniques are now frequently used to measure beta-human chorionic gonadotrophin and alpha-fetoprotein levels in evaluating the clinical course of patients with nonseminomatous germ cell tumors of the testis. It is hoped that the use of these markers will permit earlier detection of tumor recurrence, prompt treatment, and an improved survival rate. The knowledge of the production of alpha-fetoprotein by the human yolk sac has further refined tumor classification. It is against this general background that we have outlined the standard pathology of germ cell tumors of the testis.
| 24,912
|
Dehydrogenation of indanol by rabbit liver 3-hydroxyhexobarbital dehydrogenase.
|
1. Among the several enzyme activities in rabbit liver cytosol able to dehydrogenate 1-indanol, only the main activity was not separable from 3-hydroxyhexobarbital dehydrogenase during purification including polyacrylamide gel disc electrophoresis. 2. Results of mixed substrate method indicated that the same enzyme catalyses the dehydrogenation of 1-indanol and 3-hydroxyhexobarbital. The ratio between the two dehydrogenation activities was almost constant as the enzyme underwent thermal inactivation. The Ki values of p-chloromercuribenzoate, the Km values for NAD+, and the Km values for NADP+ were very similar for the two dehydrogenations. These results lead to the conclusion that the same enzyme catalyses the dehydrogenation of 3-hydroxyhexobarbital and 1-indanol. 3. 1-Tetralol, 1-acenaphthenol, 9-fluorenol, thiochroman-4-ol and 4-chromanol also served as substrate of the enzyme, but 2-indanol, 2-tetralol, and trans- and cis-indan-1,2-diol were not oxidized. 4. Reversibility of the reaction was also confirmed using 1-indanone as substrate.
| 24,923
|
Three years' maintenance neuroleptic treatment in schizophrenia--before and beyond.
|
A group of patients with schizophrenia, initially 67 patients, was studied over a period of 3 years. After three years 36 out of 67 patients were still on the same depot neuroleptic. The main aim was to describe and compare maintenance neuroleptic therapy using two depot neuroleptics, fluphenazine decanoate and pipotiazine palmitate, given monthly. Before the outpatient care the patients had participated in the department's comprehensive hospital treatment including depot neuroleptic medication. After a 1-year clinical trial with frequent assessments of the patients, significant symptom reductions were found on all rating scales. During the last 2 years of the study only drug therapy was given. Improvement concerning social function in the community and work level as well as the low-rated psychopathology noted at the start of study also persisted at the 3-year follow-up. The side effects were low in frequency and quality. These results show the clinical value of long-term maintenance treatment with depot neuroleptics. The results also confirm that the favourable effects of the hospital treatment demonstrated before the start of the clinical trial could be maintained. The possibilities of further improving aftercare and outpatient treatment beyond medication alone are discussed.
| 24,981
|
The nature of the renal response to chronic disorders of acid-base equilibrium.
|
The rate of acid excretion by the kidney appears to be determined by factors regulating the site and the rate of sodium reabsorption, rather than by a homeostatic mechanism that responds to systemic pH. This hypothesis, although unconventional, is supported by much experimental evidence, and it accounts for a wide variety of clinical and physiologic findings that heretofore have been difficult or impossible to explain.
| 25,016
|
Biochemical tests for the detection of alcoholism: comparison of plasma alpha-amino-n-butyric acid with other available tests.
|
The measurement of AANB relative to leucine was found to be a useful biochemical test for the detection of chronic alcohol consumption. This test, in combination with GGTP determinations, provided a sensitive means of detection (81% positive) for chronic alcohol consumption with a minimum of false positive determinations (2%).
| 25,029
|
Arterialized capillary blood used to determine the acid-base and blood gas status of dogs.
|
Blood samples were collected by microhematocrit tube from posterior medial margin of the shaved, but otherwise untreated, canine ear. Acid-base and blood gas values of these samples were compared with the values of samples obtained simultaneously from the carotid artery. The arterialized nature of capillary blood from the canine ear was demonstrated under various degrees of chemical restraint and during conditions of extreme hypoxic acidosis to hyperventilatory alkalosis. Once a week determinations of acid-base and blood gas status with such arterialized capillary blood from a group of awake dogs showed within-subject variance to be significantly less (P less than 0.05) than between-subject variance; thus, uniqueness of individual dogs was reliably revealed. This technique also was used to demonstrated breed differences for acid-base and blood gas characteristics.
| 25,031
|
Clear, defined medium for the sporulation of Clostridium perfringens.
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A new, defined medium for the sporulation of Clostridium perfringens is presented. Sporulation levels exceeding 10(6) to 10(7) heat-resistant spores per ml were obtained for seven strains: PS49, PS52, FD-1, T-65, NCTC strains 8798, 8238, and 10240. In the presence of theophylline, a methylxanthine, higher levels of heat-resistant spores were attained for strains PS49, PS52, FD-1, ant T-65; photomicrographs demonstrated a higher fraction of sporulating cells when these strains were grown in the presence of methylxanthines. Use of washed, highly diluted (less than 100 cells) inocula resulted in no reduction in spore yield. Strain KA3 grew well but sporulated poorly on this medium. The medium was clear and free of precipitate when small amounts (100 microgram/ml) of methylxanthine were incorporated.
| 25,045
|
Poly(adenosine dephosphate ribose) metabolism and regulation of myocardial cell growth by oxygen.
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Control of the rate of cardiac cell division by oxygen occurs most probably by altering the redox state of a control substance, e.g. NAD(+)right harpoon over left harpoonNADH. NAD(+) (and not NADH) forms poly(ADP-ribose), an inhibitor of DNA synthesis, in a reaction catalysed by poly(ADP-ribose) polymerase. Lower partial pressure of oxygen, which increases the rate of division, would shift NAD(+)-->NADH, decrease poly(ADP-ribose) synthesis, and increase DNA synthesis. Chick-embryo heart cells grown in culture in 20% O(2) (in which they divide more slowly than in 5% O(2)) did exhibit greater poly(ADP-ribose) polymerase activity (+83%, P<0.001) than when grown in 5% O(2). Reaction product was identified as poly(ADP-ribose) by its insensitivity to deoxyribonuclease, ribonuclease, NAD glycohydrolase, Pronase, trypsin and micrococcal nuclease, and by its complete digestion with snake-venom phosphodiesterase to phosphoribosyl-AMP and AMP. Isolation of these digestion products by Dowex 1 (formate form) column chromatography and paper chromatography allowed calculation of average poly(ADP-ribose) chain length, which was 15-26% greater in 20% than in 5% O(2). Thus in 20% O(2) the increase in poly(ADP-ribose) formation results from chain elongation. Formation of new chains also occurs, probably to an even greater degree than chain elongation. Additionally, poly(ADP-ribose) polymerase has very different K(m) and V(max.) values and pH optima in 20% and 5% O(2). These data suggest that poly(ADP-ribose) metabolism participates in the regulation of heart-cell division by O(2), probably by several different mechanisms.
| 25,065
|
Fazadinium in anaesthesia.
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The clinical use of the neuromuscular blocking agent fazadinium was investigated in a survey of 500 patients. Rapid conditions for tracheal intubation followed by excellent relaxation and easy antagonism were obtained. It is suggested that these findings commend it as an alternative to suxamethonium. Tachycardia appeared to be the only disadvantage associated with its use.
| 25,077
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The kinetics and equilibria of squirrel-fish hemoglobin. A Root effect hemoglobin complicated by large subunit heterogeneity.
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The functional properties of squirrel-fish hemoglobin have been measured by studying ligand binding equilibria and kinetics. The results show that squirrel-fish hemoglobin has a Root effect with a corresponding stabilization of the low affinity state. The properties of this state are pH dependent even in the absence of cooperativity. The effect of ATP shifts the overall ligant affinity towards the low affinity state and is characteristic of the allosteric effect caused by organic phosphates. Under pH and ATP conditions favoring the low affinity conformational state, a 10-fold difference in the binding kinetics of carbon monoxide to the alpha and beta subunits is observed.
| 25,086
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A protease-like permeability factor in the guinea pig skin. 1. Partial purification and characterization.
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A permeability factor was extracted in a latent form from guinea pig skin and separated by ammonium sulfate fractionation into the pseudoglobulin fraction (30--50% saturation). The activation of the latent form of the permeability factor seemed to be caused in the desalting step by gel filtration with Sephadex G-50. The factor was partially purified by streptomycin treatment and column chromatography using hydroxyapatite, diethylaminoethyl cellulose and Sephadex G-75, in this order. Gel filtration showed that its molecular weight was approx. 35000. Its permeability activity was heat stable at 61 degrees C for 60 min at neutral pH, resistant at pH 5--10 and at ionic strengths from deionized water to 1 M NaCl at 4 degrees C. Its activity was transient and suppressed by guinea pig serum, but insensitive to an anti-histamic agent (triprolidine). Furthermore, its permeability activity was inhibited by diisopropylfluorophosphate, soybean trypsin inhibitor and leupeptin, and completely adsorbed by soybean trypsin inhibitor affinity column. These findings suggested that the permeability factor was a serine-type protease.
| 25,092
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Effects of a new selective beta1-adrenoceptor agonist on amylase secretion from the rat parotid gland.
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The effects of a new selective beta1-adrenoceptor agonist, (--)-1-(4-hydroxyphenoxy)-3-isopropyl-amino-propanol-2-hydrochloride (H 133/22), on amylase secretion from the rat parotid gland were investigated in an in vitro system. The results were compared to the secretory responses obtained with noradrenaline, adrenaline, methoxyamine and terbutaline. H 133/22 was found to be a potent enzyme secretagogue and appeared even more effective than noradrenaline and adrenaline, particularly at low concentrations. The beta1-adrenoceptor agonist, terbutaline, also stimulated amylase discharge from the parotid gland but was much less potent than H 133/22. Methoxyamine had no effect on enzyme secretion. We suggest that the adrenergic stimulation of amylase secretion from the rat parotid gland is mainly mediated by beta1-receptors.
| 25,100
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Enzymatic determination of blood ethanol, with amperometric measurement of rate of oxygen depletion.
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A rapid electrochemical measurement of blood ethanol is proposed. Alcohol is oxidized by NAD+ in the presence of alcohol dehydrogenase; and the NADH produced is aerobically oxidized by horseradish peroxidase. The rate of depletion of buffer-carried oxygen, which is directly proportional to the alcohol concentration in the sample, is amperometrically monitored with a membrane oxygen-sensing electrode. Only a 5-microliter sample of whole blood is required, with no deproteinization, incubation, extraction, or dilution. Results, obtained in less than 1 min, correlate well with those obtained by gas-chromatographic and spectrophotometric methods.
| 25,144
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Kinetics, salivary excretion of amphetamine isomers, and effect of urinary pH.
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Amphetamine was administered to healthy subjects as the racemic mixture and as (+)- and (-)-isomers under conditions of urine acidification and alkalinization. Plasma and saliva concentration of each isomer was measured and the kinetics of the individual isomers were determined. (+)-amphetamine was eliminated more rapidly than the (-)-isomer. The difference in half-life between isomers was maximal under basic urinary pH conditions. Saliva amphetamine levels were higher than plasma levels and in the postabsorptive phase were predictably proportional to plasma drug levels.
| 25,157
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Loxapine: a review of its pharmacological properties and therapeutic efficacy as an antipsychotic agent.
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Loxapine is a dibenzoxazepine, tricyclic compound recommended for the treatment of acute and chronic schizophrenia. In its therapeutic effectiveness and profile and incidence of side-effects, loxapine closely resembles the traditional antipsychotic agents. Although loxapine has tended to be less effective than some standard antipsychotic drugs in a few short-term (3 to 4 weeks) studies, it has been superior to a placebo and about as effective as chlorpromazine, haloperidol, trifluoperazine or thiothixene when evaluated after 4 to 12 weeks. Like the phenothiazine (e.g. chlorpromazine) and butyrophenone (e.g. haloperidol) antipsychotic agents, loxapine causes a high incidence of extrapyramidal reactions. Sedation occurs frequently, especially during early stages of treatment. Other, less common side-effects such as anticholinergic effects (dry mouth, blurred vision, etc.), hypotension, tachycardia and precipitation of epileptic seizures, which occur with the older antipsychotic drugs, have also been reported with loxapine.
| 25,167
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Synthesis and biological activity of ovine beta-lipotropin-(41--91)-henkaipentekontapeptide.
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The 51-residue peptide ovine beta-lipotropin-(41--91) has been synthesized by the solid-phase method in about 5% overall yield. The synthetic product was characterized by partition chromatography on agarose gel, thin-layer chromatography in two solvent systems, paper electrophoresis at two pH values, polyacrylamide gel electrophoresis, amino acid analyses of acid and enzymic hydrolysates, and bioassay for lipolytic and melanotropic activities. The synthetic peptide is about 5.4 times as active on a weight basis as ovine beta-lipotropin in the lipolytic assay. In the melanotropic assay, it was about 2.4 times more active than the beta-lipotropin but only 5% as active as bovine beta-melanotropin. It had negligible opiate activity in the guinea pig ileum assay.
| 25,245
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Characterization of impurities in sulfasalazine.
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The chemical structures of four impurities isolated from sulfasalazine were determined. Three impurities are the by-products of the reaction process in drug synthesis, i.e., during diazotization of sulfapyridine and during coupling with salicylic acid. Only one contaminant was identified as a starting material, sulfapyridine, in the drug synthesis. The four impurities were characterized as 2-[[p-(2-pyridylsulfamoyl)-phenyl]azo]hydroxybenzene (I), 3-[[P-(2-pyridylsulfamoyl) phenyl]-azo]salicylic acid (II), 5-[[p-[4-(2-pyridylanilino)]-N-phenyl]azo]salicylic acid (III), and sulfapyridine (IV). Compounds I-III are novel molecules, and IV is the precursor of sulfasalazine. The isolation of the impurities was accomplished by TLC and liquid extraction procedures. The methods used to characterize the impurities were a combination of IR, UV, and NMR spectroscopy, mass spectrometry, and TLC. For I and III, comparisons also were made with the synthesized materials to supplement the evaluation.
| 25,326
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In vitro evaluation of three commercial sustained-release papaverine hydrochloride products.
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Three commercial sustained-release papaverine hydrochloride products in the form of microencapsulated pellets were evaluated. Three different dissolution apparatuses were used: a continuous flow apparatus, the USP rotating basket apparatus, and a modified reciprocating basket apparatus. The frequency rate of the reciprocating basket apparatus could be varied from 0 to 31 strokes/min. Salicylic acid compacts were used as a standard to characterize each apparatus. A linear log--log correlation between dissolution rate and apparatus speed or flow rate was obtained. Release of papaverine hydrochloride from the commercial preparations was affected significantly by the pH of the dissolution media but not by the agitation intensity.
| 25,329
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Prodrug approaches to enhancement of physicochemical properties of drugs IX: acetaminophen prodrug.
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The synthesis, hydrolysis rate, and bioavailability of 1-(p-acetaminophenoxy)-1-ethoxyethane, an acetaminophen prodrug, are described. The prodrug is less soluble than acetaminophen and stable at neutral pH. However, in an acidic environment, the compound cleaves rapidly, generating acetaminophen. When both the prodrug and acetaminophen were administered to dogs in equivalent amounts, the blood acetaminophen levels were comparable.
| 25,330
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Nucleoside transport in mammalian cell membranes. IV. Organomercurials and organomercurial-mercaptonucleoside complexes as probes for nucleoside transport systems in hamster cells.
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Organomercurials form stable stoichiometric complexes with thiolated nucleosides. The complexes inhibited uptake of ribonucleosides and cytosine arabinoside (CAR) in various types of normal and transformed cells. The inhibition was competitive and reversible (Ki = 3--6 micrometer). The interaction between complexes and transport system displayed a 1:1 stoichiometry. Chemical factors which contributed to the inhibitory power were evaluated with a series of S-alkylated derivatives and S--Hg--R complexes of mercaptonucleosides. The inhibitory potency was not determined exclusively by the hydrophobic nature of either the S-alkylated or the S--Hg--R moieties. Chemical modification of cells with penetrating and nonpenetrating organomercurials lead to stimulation of nucleoside uptake and to an increase in its susceptibility to inhibition by S--Hg--R complexes or S-aklylated derivatives of mercaptopurine ribosides. The kinetic and chemical data obtained with nucleoside analogs and with chemical modifiers suggested complex features of nucleoside transport systems. Four distinct classes of sites were implied: (i) a substrate binding site susceptible directly to competitive inhibition by organomercurial-mercaptonucleoside complexes, (ii) an additional site susceptible either to S-arylalkylated or S-mercuriated derivatives of 6-mercaptopurine ribosides, (iii) SH-containing modifier sites which stimulate uridine uptake upon binding of organomercurials, and (iv) SH-containing modifier sites which inhibit the function upon binding of organomercurials. From the observation that only SH sites related to stimulation were susceptible to modification by macromolecular-SH modifier probes, some conclusions can be drawn regarding the disposition of the various sites in the cell membrane in general and among membrane components in particular.
| 25,341
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Current-voltage relationships for the plasma membrane and its principal electrogenic pump in Neurospora crassa: I. Steady-state conditions.
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The nonlinear membrane current-voltage relationship (I-V curve) for intact hyphae of Neurospora crassa has been determined by means of a 3-electrode voltage-clamp technique, plus "quasi-linear" cable theory. Under normal conditions of growth and respiration, the membrane I-V curve is best described as a parabolic segment convex in the direction of depolarizing current. At the average resting potential of - 174 mV, the membrane conductance is approximately 190 micronhos/cm2; conductance increase to approximately 240 micronhos/cm2 at -300 mV, and decreases to approximately 130 micronhos/cm2 at 0 mV. Irreversible membrane breakdown occurs at potentials beyond this range. Inhibition of the primary electrogenic pump in Neurospora by ATP withdrawal (with 1 mM KCN) depolarizes the membrane to the range of -40 to -70 mV and reduces the slope of the I-V curve by a fixed scaling factor of approximately 0.8. For wild-type Neurospora, compared under control conditions and during steady-state inhibition by cyanide, the I-V difference curve--presumed to define the current-voltage curve for the electrogenic pump--is a saturation function with maximal current of approximately 20 muA/cm2, a half saturation potential near -300 mV, and a projected reversal potential of ca. -400 mV. This value is close to the maximal free energy available to the pump from ATP hydrolysis, so that pump stoichiometry must be close to 1 H+ extruded:1 ATP split. The time-courses of change in membrane potential and resistance with cyanide are compatible with the steady-state I-V curves, under the assumption the cyanide has no major effects other than ATP withdrawal. Other inhibitors, uncouplers, and lowered temperature all have more complicated effects. The detailed temporal analysis of voltage-clamp data showed three time-constants in the clamping currents: one of 10 msec, for charging the membrane capacitance (0.9 muF/cm/2); a second of 50-75 msec; and a third of 20-30 sec, perhaps representing changes of intracellular composition.
| 25,343
|
[Use of beta-adrenergic blockaders in the treatment of arterial hypertension].
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The results of treatment of over 300 patients suffering from hypertensive disease with beta-blocking agents Obsidan and Visken are analysed and the place of these agents among other hypotensive drugs is discussed. The therapeutic effect was most evident in patients with the early stages of the disease and hyperkinetic type of circulation. The daily doses were from 60 to 240 mg. The hemodynamic shifts were displayed by a decrease in the cardiac output and rate of cardiac contractions and reflex, ususlly moderate, increase in general peripheral resistance, as a result the arterial pressure decreased gradually. In 1 to 6 months general peripheral resistance diminished in half of the patients, evidently due to the gradual adaptation of the vascular tone to the chronic reduction of the cardiac output. Treatment with beta-blocking agents led to non-uniform changes in regional hemodynamics: the tone of the cerebral arteries significantly reduced, the tone of the arteries of the lower extremities had a tendency to increase. This gives rise to the conclusion that alpha-adrenergic receptors predominate in the vessels of the lower extremities. In the treatment of patients with high and stable hypertension, it is advisable to combine beta-blocking agents with saluretics, vasodilators, hemiton, and other hypotensive drugs.
| 25,351
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Submandibular salivary pH as a diagnostic aid for prognosis of facial palsy.
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The present paper aims at introducing a new method of testing the function of the chorda tympani with the aid of submandibular salivary pH. This method has several advantages: (1.) it enables the measurement of the function of only the paralyzed side; (2.) it accurately predicts the outcome of facial palsy at an early stage; and (3.) the method is simple and inexpensive.
| 25,361
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Substrate binding to solubilized cytochrome P-450 from rabbits at different temperatures.
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The binding affinities of selected type I- and type II-substrates to partially purified cytochrome p-450 from rabbit liver microsomes were studied and found to differ from those of rats. The temperature dependence of the apparent binding constants qualitatively exhibited the same characteristics compared with that of rats. For type I-substrates endothermic and for type II-substrates exothermic reaction characteristics were observed. Taking into account the partition coefficients of the substrates so far investigated it is obvious that type I substrates with increasing hydrophobicity are bound more strongly while type II-substrates show a more complicated behvaiour. This may due to the fact that other types of binding are included besides the hydrophobic interactions.
| 25,548
|
Acid-base status during reconstructive surgery of the abdominal aorta.
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Abolition of a temporary occlusion of the circulation in the legs during surgical reconstruction of the abdominal aorta generally exerts but little influence on the patient's acid-base status. The changes in acid-base status can be corrected by the patient himself. Routine administration of sodium bicarbonate or Tham is unnecessary. However, respiration, circulation and electrolyte balance should be carefully monitored to ensure that any disturbances in this respect can immediately be given adequate treatment. Determination of the acid-base status during the operation is a valuable aid in evaluation of the patient's condition and can be used as a guideline in therapy.
| 25,556
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Relationship between adrenergic blocking and antihypertensive effects of beta receptor antagonists.
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In hypertensive patients, whose blood pressure was decreased by racemic propranololthe dextrorotatory isomer had no antihypertensive effect. The differences in antihypertensive activity of racemic and dextrorotatory propranolol cannot be explained by different plasma levels; the data indicate that the hypotensive effect of propranolol is due to beta receptor blockade.
| 25,567
|
Cardiac pacemakers in absence of the SA node: responses to exercise and autonomic blockade.
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Surgical excision of the sinoatrial node, verified histologically, is followed by a supraventricular (atrial) rhythm in both resting and exercising dog whether anesthetized or conscious. The ECG is characterized by a definitive P wave and associated atrial electrograms. Waxing and waning in heart rate, generally referred to as sinus arrhythmia continues in the awake animal after complete excision of the SA node. This arrhythmia is responsive to both adrenergic and cholinergic interventions, thus indicating the presence of both sympathetic and parasympathetic regulation of subsidiary atrial pacemaking tissues.
| 25,585
|
Characterization of cell wall polymers secreted into the growth medium of lysis-defective pneumococci during treatment with penicillin and other inhibitors of cell wall synthesis.
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Autolysin-defective pneumococci secrete large quantities of choline-containing cell wall polymers into the growth medium during treatment with inhibitors of peptidoglycan synthesis. The secreted polymers were separated into three fractions by a combination of gel filtration on agarose and sodium dodecyl sulfate-gel electrophoresis. Fraction I had a high apparent molecular size and contained the Forssman antigen in complex with material exhibiting properties of cell wall teichoic acid. Choline-containing polymers of as yet uncharacterized structure were present in both fractions IIA and IIB, and fraction IIA also contained peptidoglycan components.
| 25,618
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Physiology of L-asparaginase synthesis in recombinants of Escherichia coli A-1.
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A mating between Escherichia coli 4318 (thi leu Las- Hfr) and E. coli A-1 (Met- Las+ F-) resulted in the formation of prototrophic recombinants having L-asparaginase activities at three distinct levels. The physiology of L-asparaginase synthesis in these recombinants is decribed. One class of recombinants produced significantly more L-asparaginase than E. coli A-1. L-Asparaginase synthesis in the recombinants was inhibited by the presence of dissolved oxygen in the medium and was transiently repressed by the presence of glucose in the same manner as that observed in the parental strains. L-Asparaginase activity was increased by the addition of oxalacetate as well as other members of the tricarboxylic acid cycle.
| 25,625
|
Inhibition of experimental immediate hypersensitivity reactions by a novel xanthone, RU 31156.
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RU 31156, the tris-(hydroxymethyl)-aminomethane salt of 7-(S-methylsulphonimidoyl)-5-(n-hexyl)-xanthen-9-one-2-carboxylic acid has been found to be a potent inhibitor of experimental immediate hypersensitivity reactions in vivo. In the IgE-mediated rat PCA test, RU 31156 had an ED50 of 0.0046 (00037--0.0057) mg/kg which compared to a figure of 1.21 (1.04--1.42) mg/kg for disocium cromoglycate (DSCG), both compounds being administered intravenously. RU 31156 was also active when administered orally, having an ED50 of 0.19 (0.07--0.30) mg/kg when given 10 min before antigen. RU 31156 partially inhibited an IgG-mediated PCA reaction in the rat. Both RU 31156 and DSCG inhibited anaphylactic bronchoconstriction in the rat, giving bell-shaped dose-response curves. From the upward part of the curves, approximate ED30 values of 0.02 and 2.0 mg/kg were obtained for RU 31156 AND DSCG respectively. Anaphylactic bronchoconstriction in the guinea-pig was not affected by RU 31156 and pinnal anaphylaxis was inhibited at only relatively high doses of 1--10 mg/kg i.v. The effects of both histamine and 5-hydroxytryptamine in the mouse pinna were not affected by RU 31156. In PCA experiments, RU 31156 showed self-tachyphylaxis following both intravenous and oral administration. It also showed cross-tachyphylaxis with DSCG, indicating that these compounds are likely to share a similar mode of action.
| 25,634
|
Chemical and enzymic studies on the characterization of intermediates during the removal of the 14alpha-methyl group in cholesterol biosynthesis. The use of 32-functionalized lanostane derivatives.
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By using cell-free preparations of rat liver it was shown that the removal of the 14alpha-methyl group (C-32) of steroids containing either a delta7(8) or a delta8(9) double bond is attended exclusively by the formation of the corresponding 7,14- and 8,14-dienes respectively (structures of types III and VIII). Cumulative evidence from a variety of experimental approaches had led to the deduction that delta8(14)-steroids are not involved as intermediates on the major pathway of cholesterol biosynthesis. The metabolism of [32-3H]lanost-7-ene-3beta,32-diol (structure of type I) results in the formation of radioactive formic acid, no labelled formaldehyde being formed. By using appropriately labelled species of the compound (I) it was found that the release of formic acid and the formation of 4,4-dimethylcholesta-7,14-dien-3beta-ol (strurcture of type III) were closely linked processes, and that in the conversion of compound (I) into compound (III), 3-beta-hydroxylanost-7-en-32-al (II) is an obligatory intermediate. Both the conversion of lanost-7-ene-3beta,32-diol (I) into 3beta-hydroxylanost-7-en-32-al (II) and the further metabolism of the latter (II) to 4,4-dimethylcholesta-7,14-dien-3beta-ol (III) exhibited a requirement for NADPH and O2. This suggests that the oxidation of the 32-hydroxy group of compound (I) to the aldehyde group of compound (II) does not occur by the conventional alcohol dehydrogenase type of reaction, but may proceed by a novel mechanism involving the intermediacy of a gem-diol. A detailed overall pathway for the 14alpha-demethylation in cholesterol biosynthesis is considered, and proposals about the mechanism of individual steps in the pathway are made.
| 25,646
|
The biochemical pathway for the breakdown of N4-ethyl-L-asparagine in the bacterium Pseudomonas stutzeri.
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N4-Ethyl-L-[u-14C]asparagine and L-[U-14C]aspartate give identical metabolites, mainly intermediates of the tricarboxylic acid cycle and related amino acids, in whole cells of Pseudomonas stutzeri. The labelled asparagine derivative is converted into [14C]-aspartate by cell-free extracts, and this reaction, which has an optimum pH of 8.8 +/- 0.2, is neither inhibited by unlabelled asparagine nor enhanced by unlabelled 2-oxoglutarate. No labelled keto acid corresponding to N4-ethylasparagine was detected in either whole cells or cell-free extracts. Thus N4-ethyl-L-asparagine, like asparagine, must be broken down by hydrolysis, at least in this bacterium.
| 25,650
|
Characterization of marrow granulocyte development: enzyme-specific activity profiles in response to inflammatory reactions.
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Isopycnic sedimentation has been used to separate granulocytes of varying stages of maturity from the bone marrows of normal rabbits and rabbits stimulated to undergo an intense inflammatory response. The separated cell populations were in turn utilized to study the specific activities of six intracellular enzymes. The study revealed an increase with cell maturation in the specific activities of myeloperoxidase, NADPH oxidase, alkaline phosphatase and acid phosphatase in normal animals; in stimulated animals only myeloperoxidase and NADPH oxidase increased significantly with cell maturation. Glucose-6-phosphate dehydrogenase showed no change in specific activity in all animals studied. Malate dehydrogenase tended to show a specific activity decrease in the maturing cells of normal but not in those of stimulated animals.
| 25,666
|
Nonenzymatic hydrolysis reactions of adenosine 5'-triphosphate and its related compounds. III: Catalytic aspects of some cobalt(III) complexes in ATP-hydrolysis.
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Trichlorodiethylenetriaminecobalt (III), [CoCl3dien], which is provided with three good leaving ligands and, hence, capable of binding ATP in a characteristic mode, accelerated effectively and specifically hydrolysis of ATP to ADP and Pi. A kinetic study of the reaction indicated that the rate of hydrolysis was first order with respect to the concentration of ATP in the presence of an excess of [CoCl3dien]. The rate constant was calculated to be 1.05 X 10(-2) min-1 at pH 4.0 (50 degrees C), corresponding to a catalysis of the hydrolysis of ATP by a factor of 150. The complex possessing one good leaving ligand, chlorotetraethylenepentaminecobalt(III), and that having two of them in trans-position, dichlorobis(dimethylglyoximato)cobalt(III) only slightly enhanced the hydrolysis of ATP. Dichloro-cis-alpha- and dichloro-cis-beta-triethylenetetraminecobalt(III) complexes, which have two good leaving ligands and allow chelation of ATP in their coordination sphere, exhibited fairly good activities, although the hydrolysis reactions of ATP occurred in two modes as ATP leads to ADP + Pi and ATP leads to AMP + PPi. The mechanism of ATP-hydrolysis reaction with [CoCl3dien] was also discussed on the basis of the kinetic data.
| 25,675
|
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