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[NADPH-dependent oxidation in endoplasmic reticulum of rat liver after valexon administration].
|
Changes of different type are detected in components of NADPH-dependent oxidation. The changes begin in different periods (1, 5, 15 days) after administration of valexon to the animals. In the first day the hydroxylase activity is inhibited against a background of the uridine diphosphate glucuronyl transferase activity increase and intensification of ascorbic acid excretion with urine. Five days after the uridine diphosphate glucuronyl transferase activity becomes normal, the ascorbic acid excretion remains intensified and the demethylase and hydroxylase activities increase. Fifteen days later the hydroxylase activity becomes normal, but the demthylase activity and intensity of ascorbic acid excretion are still increased.
| 34,910
|
Chronic graft versus host disease: a syndrome of disordered immunity.
|
A chronic, debilitating syndrome related to graft-versus-host disease (GVHD) has been recognized in long-term survivors following allogeneic bone marrow transplantation. In six of 20 marrow graft recipients who survived for more than one year after receiving a transplant, this complication developed; they were studied to better define the syndrome. There was no association between the sex of either donor or recipient, HLA type, blood group, conditioning regimen or marrow cell dose and subsequent development of chronic GVHD. All six patients had mild to moderate manifestations of acute GVHD following prompt engraftment. Chronic GVHD was characterized in each patient by progression to scleroderma-like skin involvement with hyperkeratosis, reticular hyperpigmentation, atrophy with ulceration and fibrosis with limitation of joint movement. A sicca syndrome was prominent in five patients. Four patients had idiopathic interstitial pneumonitis. Infectious complications were frequent, and DNA viral infections were prominent. Autoimmune hemolytic anemia was present in three patients, and one patient had antinuclear antibody (ANA). A spectrum of immune abnormalities was observed including hypergammaglobulinemia, immunoglobulin M (IgM) paraprotein, elevated circulating immune complexes, plasma cell hyperplasia, lymphocytotoxic antibodies and autoantibodies to autologous or donor lymphocytes. Despite clinical similarity to collagen vascular diseases, none of these patients had anti-DNA antibodies or antibodies to smooth muscle, thyroid or extractable nuclear antigens. In one patient, a skin graft from the marrow donor remained healthy despite progressive involvement in recipient skin, whereas unrelated skin grafts were rejected. Immunosuppressive therapy and plasmapheresis have not been effective. Four patients have died (median survival 458 days from transplantation). Chronic GVHD appears to be a syndrome of disordered immune regulation features of immunodeficiency and autoimmunity.
| 35,001
|
Acid-base equilibrium during acute long-lasting experiments in artificially ventilated cats.
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Experiments were carried out to study blood acid-base equilibrium in the cat during experiments with artificial ventilation. Blood acid-base equilibrium was examined in the arterial and venous blood by analyzing pH, carbon dioxide and oxygen partial pressure, and plasma bicarbonates. Artificial ventilation was regulated on the basis of this analysis; CO2 concentration in expired air was monitored throughout the experiment. An attempt was made to verify if artificial ventilation could be regulated indirectly only on the basis of CO2 concentration in expired air. The most appropriate acid-base equilibrium was maintained when CO2 concentration in expired air was kept within the range of 3.9-4.1%.
| 35,011
|
Comparison of the effects of nine beta-adrenergic blocking agents on intraocular pressure in rabbits.
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The intraocular pressure lowering effects of nine beta-adrenergic receptor blocking agents were compared using two different models of experimental ocular hypertension in rabbits. All the nine drugs possess, to different extents, a clear pressure-lowering action after topical administration into the conjunctival sac. For potency and duration of action, the best results were obtained with timolol and sotalol. Pindolol, oxprenolol, practolol, and propranolol are also fairly potent while less impressive effects were produced by atenolol, butidrine, and metoprolol. With the exception of propranolol, all the drugs were well tolerated by the ocular tissues.
| 35,031
|
Effects of volatile anesthetics on directly and indirectly stimulated skeletal muscle.
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Isolated guinea pig nerve-lumbrical muscle preparations were exposed to halothane, methoxyflurane, isoflurane, enflurane, fluroxene, and diethyl ether. The temporal courses of the effects on indirectly and directly elicited twitch responses were determined over a range of concentrations for each agent. When the anesthetics were compared at concentrations equivalent in terms of minimum alveolar concentration (MAC), a spectrum was observed in which halothane, methoxyflurane and isoflurane depressed the indirect twitch response at 3.5--5 MAC and the direct twitch response at 8--10 MAC. Diethyl ether and fluroxene depressed the indirect twitch response at 2--3.5 MAC and the direct twitch response at 3--6 MAC. Enflurane depressed the indirect response at 1.5--2.5 MAC and the direct response at 6--8 MAC. When the anesthetics were compared at concentrations equivalent in terms of their abilities to depress end-plate depolarization, however, all anesthetics were equipotent. Depression of the indirect twitch response occurred only when anesthetic concentrations were great enough to depress depolarization by 50 per cent.
| 35,042
|
[Metabolic effects of barbiturates on the anoxic brain:free radical trapping].
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Different mechanisms have been proposed to explain the protector effect of barbiturates in cerebral ischemia. Among these is the particularly attractive hypothesis that the protection is obtained by an inhibition of the oxydo-reduction process in the respiratory chain in the mitochondria upstream of the Q coenzyme. Keeping this enzyme in the quinone state prevents the formation of the three radical at the level of lipoid complexes of the cellular and sub-cellular membranes, thus assuring the upkeep of the integrity of these structures. The absence of the free radicals equally protects the morphology of the endothelium, in limiting the aggregation of platelets in the arterial vessel lumens. The existence of the three radicals in the organism and their noxious effects are well established, however, that the protection brought about by the barbiturates be the results of free radical trapping remains still an hypothesis.
| 35,052
|
[Comparative study of the effects of dobutamine and dopamine in septic shock].
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This work aims at the evaluation of the effects of dobutamine in the effects of dobutamine in the treatment of septic shock and to compare them to the effects of dopamine used in the same conditions. Eleven patients presenting with both a state of septic shock and confirmed cardiac insufficiency were submitted to the protocol. The dosage was determined by the clinical results : 6.22 microgram/kg/min for dopamine and 4.2 to 25 microgram/kg/min for dobutamine. The results show that although the effect on cardiac output is comparable with the two drugs, some differences in their effects delineates their respective distinct indications. Indeed, although dobutamine seems less arythmic, lovers more the ventricular filling pressure and increases less the intra-pulmonary shunt, dopamine causes less reduction in the systemic resistance which in the case of septic shock seems more logical. Nevertheless dobutamine is perhaps easier to handle.
| 35,059
|
[The effects of dobutamine in postoperative disorders of left ventricular function in coronary patients undergoing abdominal surgery. Apropos of 18 cases].
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Increasing doses of dobutamine were administered to the first group of 10 coronarians having undergone and abdominal surgical procedure, and presenting, one hour after awakening from the anesthesia, hemodynamic modifications with a diminution of cardiac index (CI), systolic index (SI), systolic work index of the left ventricle (SWILV) increase in the pulmonary capillary pressure (PCP), and in the total peripheral resistance (TPR), as well as an acceleration of the cardiac rate (CR). Doses of dobutamine of 5 or 7.5 microgram.kg-1.min-1 corrected the IC, PCP and TPR. Dobutamine ameliorated the SI and SWILV in an increasing fashion up to a dose of 10 microgram.kg-1.min-1 only and without restoring them to the control values of the pre-operative period. CR progressively increased with the increasing of the doses reaching 126 +/- 21.5 beats min-1 for 15 microgram.kg-1.min-1. Extrasystoles appeared at dose levels of 12.5 and 15 microgram.kg-1.min-1 in two patients. Tests of vascular filling (pre-charge tests) carried out in the second group of patients under 10 microgram,kg-1.min-1 of dobutamine and in a third group under 15 microgram.kg-1.min-1 showed a good cardiac adaptation to filling, equal or superior to that of the pre-operative period. It also appeared that the amelioration of CF obtained with a moderate vascular filling (300 ml of low molecular weight dextran) under 10 microgram.kg-1.min-1 of dobutamine is greatly superior to the amelioration obtained by 10 to 15 microgram.kg-1.min-1 of dobutamine.
| 35,061
|
[Hemodynamic effects of dopamine, dobutamine and isoproterenol in chronic respiratory insufficiency].
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A study of the effects of dopamine, dobutamine and of isoprenaline was carried out in 20 patients with chronic respiratory insufficiency, 16 of whom had pulmonary arterial hypertension (PAP: 22 mmHg). The following findings emerged: --absence of any significant effect of dobutamine on heart rate,--increase in systolic and mean PAP, after infusion of dobutamine,--increase in systolic and mean PAP, after infusion of dopamine,--decrease in BP after administration of infusion of dobutamine,--decrease in pulmonary arterial resistances under the influence of isoprenaline,--decrease in total systemic resistances after the administration of dobutamine,--increase in ventricular, systolic work after the infusion of dopamine.
| 35,062
|
[Value of and indications for noxythiolin in generalized peritonitis].
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The favourable experience of M. BROWN with noxythiolin in fecal peritonitis has prompted us, over the last seven years, to use this product in all forms of generalized peritonitis. This study involved 187 cases of generalized peritonitis : 102 males and 85 females, whose mean age was 53 years. Noxythiolin was reserved for severe cases (after having deliberately decided not to perform a comparative control series), the severity being related to the advanced age of the patients, the delay in intervention, and preexisting disorders. It was used in the form of a peroperative lavage of the peritoneal cavity and a postoperative instillation. The overall survival (71 p. 100) and that observed in particular in peritonitis of colonic origin (58 p. 100), seem to be arguments in favour of the beneficial effect of the product. Noxythiolin contributes to the sterilization of the peritoneal cavity. By virtue of its efficacy, the simplicity of its use, and its innocuousness, it merits a place in the therapeutic arsenal for treatment of generalized peritonitis, in combination with systemic treatments.
| 35,068
|
[Acute renal insufficiency caused by phenyl-indane-dione. Apropos of 1 case].
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One case of Phenindione (PID) adverse reaction is reported. The patient showed a typical picture of immunological reaction to the drug. In spite of severe bacteremia, she recovered. Only 33 cases of PID intolerance are reported in the literature. In all these patients, renal failure occurred. Superinfection is the most frequent cause of death. PID adverse reaction should be evoqued in the presence of signs such a fever, asthenia, anorexia and cutaneous reaction. The PID should be stopped immediatly but renal failure yet develops. During a PID treatment, frequent evaluation of blood azotemia, creatinine and proteinuria should be performed.
| 35,076
|
Formation of N-nitrosamines from seconday animes and nitrite by resting cells of Escherichia coli B.
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In the presence of resting cells of Escherichia coli B, the formation of N-nitrosamines from nitrite and secondary amines, such as dimethylamine and piperidine, was proportional to the incubation time and to the cell concentration. Optimum pH was 8.0. Boiled cells were incapable of nitrosating secondary amines. Although these experiments were carried out by using intact cells of E. coli B, the reaction followed Michaelis-Menten kinetics, and the apparent Km values calculated from Lineweaver-Burk plots were 0.12 +/- 0.03 M for dimethylamine and 0.07 +/- 0.02 M for nitrite. The apparent Km for piperidine was 0.15 +/- 0.05 M. The nitrosation was inhibited by high substrate concentrations. These results suggested that the formation of n-nitrosamines by resting cells of E. coli B apparently depends on their enzyme activities.
| 35,098
|
Subendocardial protection during cardiopulmonary bypass. Its use with methylprednisolone and glucose-insulin-potassium.
|
Fifteen adult dogs were equally divided into three groups: group 1 (control) received no medication before or after cardiopulmonary bypass (CPB), group 2 was administered glucose-insulin-potassium (GIK) according to Maroko's protocol before, during, and after CPB, whereas group 3 was treated with methylprednisolone (30 mg/kg) 30 minutes prior to and near the end of CPB. Moderately severe subendocardial hemorrhage was present in 80% of group 1, 50% of group 2, and only 20% of group 3 ventricles. Endocardial viability ratios after CPB were greater than 0.75 in 20% of group 1, 80% of group 2, and 100% of group 3 animals. Both GIK and steroids improved subendocardial perfusion after anoxic arrest and CPB compared with controls. However, steroid-treated dogs exhibited less endocardial hemorrhage, improved contractility, and more rapid return to baseline conditions than either GIK or control animals. These data suggests that steroids could be considered whenever normothermic anoxic cardiac arrest is used for cardiac operations.
| 35,133
|
Zinc(II) binding to apo-(bovine erythrocyte superoxide dismutase).
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The binding of zinc(II) ions to apo-(bovine erythrocytes superoxide dismutase) was studied by 1H n.m.r. spectroscopy. Two zinc(II) ions bind to each subunit of the apoenzyme, and the first has a binding constant at least an order of magnitude larger than the second. The nature of the spectral changes that occur on binding the first zinc(II) ion are interpreted in terms of a change in the structure of the protein around the active site to one very similar to that of the holoenzyme, thus pre-forming the second zinc(II) binding site. The binding of the second zinc(II) ion effects changes in the environment of only those residues involved in its co-ordination.
| 35,154
|
Artificially induced active transport of amino acid driven by the efflux of a sugar via a heterologous transport system in de-energized Escherichia coli.
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Consistent with the model of an H+ cotransport, amino acid uptake can be driven by a proton gradient generated by an efflux of sugar when the normal energy sources are suppressed. Heterologous countertransport is completely inhibited by uncouplers unlike homologous countertransport. Positive coupling was obtained with methyl thiogalactoside/proline, methyl thiogalactoside/phenylalanine, gluconate/proline; however, the poor coupling efficiency suggests a more complex sequence of reactions.
| 35,159
|
[The influence of 2-ethyl-3-(4-hydroxy-benzoyl)- benzofuran on the contraction of pial arterial muscles (author's transl)].
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By means of perivascular perfusion of thin sections of pial arteries with differently composed cerebrospinal fluid (CSF) the vessel diameters can be influenced. In cats, anesthetized with pentobarbital, addition of serotonin, norepinephrine or calcium to an artificial CSF which was infused through micropipettes into the perivascular space of the pial arteries, caused constrictions of the arteries contacting the modified CSF. Hyperventilation or perivascular perfusion of alkaline CSF also caused reduction of the pial arterial diameters. 2-Ethyl-3-(-hydroxy-benzoyl)-benzofuran (benzarone) inhibited or abolished the constrictions elicited by the above mentioned stimuli. The effect was dose-dependent. High doses of benzarone caused pial arterial dilations: The inhibition of the calcium induced constriction especially, seems worth mentioning since this ion plays a central role in the contraction mechanisms of the vascular smooth muscle cells.
| 35,167
|
Kinetics of degradation of cefazolin and cephalexin in aqueous solution.
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The kinetics of degradation of cefazolin and cephalexin in aqueous solution were investigated at 60 degrees C and constant ionic strength over the entire pH range. The observed degradation rates were obtained by measuring the residual cephalosporin and were shown to follow pseudo-first-order-kinetics. They were influenced significantly by solvolytic and hydroxide ion catalysis. No primary salt effect was observed in the acid or basic pH region. Of the buffer systems employed in the kinetics studies only the phosphate buffer system showed a catalytic effect. The pH-rate profile for cefazolin showed a degradation minimum between pH 5.5 and 6.5. Cephalexin did not show a pH minimum in that region. The apparent energies of activation were determined for cefazolin and cephalexin at pH 5.5 and were calculated to be 24.3 Kcal/mole and 26.2 Kcal/mole, respectively. The agreement between the calculated theoretical pH-rate profiles and the experimental points for both compounds support the hypothesis presented concerning the reactions involved in their respective degradation pathways.
| 35,181
|
Single daily dose treatment of anxiety with clobazam or dipotassium clorazepate.
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1 Forty-four clinically anxious patients entered a comparative double-blind trial of clobazam 20 mg, clobazam 30 mg and dipotassium clorazepate 15 mg, all drugs given as a single dose at night. 2 Assessment by the Hamilton Anxiety Scale, Morbid Anxiety Inventory (Salkind) and a Visual Analogue Scale showed a statistically significant improvement for all treatment groups after 2 weeks, with continued improvement after a further 2 weeks. 3 Daytime drowsiness was the commonest side-effect in all treatment groups but there was a tendency for a lower incidence in patients on clobazam. There was no evidence of a dose-related incidence of drowsiness in the clobazam 20 mg and 30 mg groups. Other side-effects were few and nonspecific. 4 Clobazam is a 1,5-benzodiazepine with an elimination half-life of 18 hours. When given in single doses of 20-30 mg at night it has an equivalent effect to dipotassium clorazepate 15 mg.
| 35,192
|
Pharmacokinetics of single and multiple doses of clobazam in humans.
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1. The pharmacokinetics of clobazam and its biotransformation product N-desmethylclobazam were investigated after single and multiple doses in normal subjects. 2. The relevant physicochemical properties of clobazam were measured and are presented. Different assay methods (radiochemical, fluorimetric and gas chromatographic) were applied and the results correlated. 3. After single doses the pharmacokinetic profile of clobazam includes time to peak levels 1--4 h after dosing, peak levels increasing linearly with the logarithm of dose, and terminal half-lives of about 18 hours. At least 87% of an oral dose is absorbed, as indicated by urinary recovery of labelled material. 4. In multiple-dose studies unchanged clobazam levelled off at minimum steady-state concentrations within one week of dosing. During 28 d of medication N-desmethylclobazam accumulated to near steady-state levels about eight times higher than those of the unchanged compound. 5. No pharmacokinetic interactions were discovered between clobazam and the antidepressant nomifensine.
| 35,205
|
Pharmacology of anti-anxiety drugs with special reference to clobazam.
|
1 In several studies clobazam exhibited a potency which ranges between that of chlordiazepoxide and diazepam. Its anxiolytic and anti-aggression effects are produced by doses usually ranging below those that cause disorders in motor activity. 2 This separation was demonstrable to an even greater degree with the desmethyl metabolite. The activity of the metabolite, however, was weaker than that of the original substance. 3 The advantage of clobazam compared with the 1.4 benzodiazepines lies mainly in the fact that motor activity is influenced only after very high doses, these doses being markedly above those required to induce tranquillizing and anti-agression activities. 4 Clobazam has no marked effect on the cardiovascular system, respiration of excretion.
| 35,209
|
Studies of clobazam and car-driving.
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1 The methodology used in studies to assess the effects of drugs on car-driving performance is reviewed. 2 Clobazam 20 mg, diazepam 10 mg or placebo were administered daily for 3 d to 24-male students with a high neuroticism score (on the Cattell Personality Factors Questionnaire). 3 Car driving performance was assessed on the second day in real traffic conditions; tests of attention and concentration and subjective assessments were made on the third day. 4 Diazepam 10 mg significantly impaired braking reaction time in comparison with clobazam 20 mg and placebo (P less than 0.01). Subjects also reported feeling more 'depressed' and lethargic after diazepam.
| 35,213
|
Conformational transitions and vibronic couplings in acid ferricytochrome c: a resonance Raman study.
|
Resonance Raman spectral changes in ferricytochrome c as a function of pH between 6.7 and 1.0 are reported and the structural implication is discussed in terms of the "core-expansion" model advanced by L. D. Spaulding et al. [(1975) J. Am. Chem. Soc. 97, 2517]. The data are interpreted as indicating the iron in high-spin ferricytochrome c (at pH 2.0) with two water molecules as axial ligands lies in the plane of the porphyrin ring. At pH 1.0 there is a different high-spin form of cytochrome c which has an estimated iron out-of-plane distance of approximately 0.46 A. The effect of a monovalent anion at pH 2.0 is to produce a thermal spin mixture with predominant low-spin species. Excitation at approximately 620 nm in acid cytochrome c (pH 2.0) enhances only three depolarized ring vibrations at 1623, 1555, and 764 cm-1. Marked enhancement of depolarized modes relative to polarized and anomalously polarized modes is attributed to the vibronic coupling between porphyrin pi leads to pi and porphyrin pi leads to iron (dpi) charge-transfer states.
| 35,223
|
The enzymatic preparation of [alpha-(32)P]nucleoside triphosphates, cyclic [32P] AMP, and cyclic [32P] GMP.
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A method has been developed for the enzymatic preparation of alpha-(32)P-labeled ribo- and deoxyribonucleoside triphosphates, cyclic [(32)P]AMP, and cyclic [(32)P]GMP of high specific radioactivity and in high yield from (32)Pi. The method also enables the preparation of [gamma-(32)P]ATP, [gamma-(32)P]GTP, [gamma-(32)P]ITP, and [gamma-(32)P]-dATP of very high specific activity and in high yield. The preparation of the various [alpha-(32)P]nucleoside triphosphates relies on the phosphorylation of the respective 3'-nucleoside monophosphates with [gamma-(32)P]ATP by polynucleotide kinase and a subsequent nuclease reaction to form [5'-(32)P]nucleoside monophosphates. The [5'-(32)P]nucleoside monophosphates are then converted enzymatically to the respective triphosphates. All of the reactions leading to the formation of [alpha-(32)P]nucleoside triphosphates are carried out in the same reaction vessel, without intermediate purification steps, by the use of sequential reactions with the respective enzymes. Cyclic [(32)P]AMP and cyclic [(32)P]GMP are also prepared enzymatically from [alpha-(32)P]ATP or [alpha-(32)P]GTP by partially purified preparations of adenylate or guanylate cyclases. With the exception of the cyclases, all enzymes used are commerically available. The specific activity of (32)P-labeled ATP made by this method ranged from 200 to 1000 Ci/mmol for [alpha-(32)P]ATP and from 5800 to 6500 Ci/mmol for [gamma-(32)P]ATP. Minor modifications of the method should permit higher specific activities, especially for the [alpha-(32)P]nucleoside triphosphates. Methods for the use of the [alpha-(32)P]nucleoside phosphates are described for the study of adenylate and guanylate cyclases, cyclic AMP- and cyclic GMP phosphodiesterase, cyclic nucleotide binding proteins, and as precursors for the synthesis of other (32)P-labeled compounds of biological interest. Moreover, the [alpha-(32)P]nucleoside triphosphates prepared by this method should be very useful in studies on nucleic acid structure and metabolism and the [gamma-(32)P]nucleoside triphosphates should be useful in the study of phosphate transfer systems.
| 35,231
|
Inactive 3-hydroxy-3-methylglutaryl-coenzyme A reductase in broken cell preparations of various mammalian tissues and cell cultures.
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Preincubation of broken cell preparations from a variety of tissues and cell cultures resulted in an apparent increase in the level of 3-hydroxy-3-methylglutaryl-CoA reductase activity. However, apparent activation of the reductase in mouse liver, hepatomas and primary liver cell cultures was attributed largely to the loss, during the preincubation period, of an interfering enzyme, 3-hydroxy-3-methylglutaryl-CoA lyase. Among non hepatic cells and tissues (which did not contain appreciable lyase activity) the proportion of latent reductase was high in sonicates of fetal brain and in L cells and was independent of the level of total enzyme activity present. Activation of the reductase was blocked by hydroxymethylglutaryl-CoA and NADPH as well as by KF so that activation did not occur under the conditions of the enzyme assay. The enzyme was activated slowly at 4 degrees C, so that partial activation of the latent form occurred during isolation of the microsomal fraction by differential centrifugation. The reductase present in sonicates of cells with either a high or low proportion of the latent enzyme was inactivated by incubation with ATP and Mg2+. Suppression of reductase activity in L cell cultures by treatment with 25-hydroxycholesterol and an age-related decline in brain enzyme activity did not involve reversible conversion of the reductase to an inactive form.
| 35,236
|
The interference of plasmic degradation products of human crosslinked fibrin with clot formation.
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The role of plasmic degradation products of human crosslinked fibrin on polymerization of fibrin monomer and clot formation was studied. Both reactions were inhibited by Fragment DD, which formed a complex with fibrin monomer in a molar ratio 1 : 1. The rate of polymerization was slightly increased by Fragment E but it was not affected by (DD)E complex and Fragment A. Approximately the same amount of fibrin was formed in the presence and absence of Fragments A, E and the complex. It was concluded that of the degradation products of crosslinked fibrin, only Fragment DD is a potent anticoagulant at physiologic pH. The (DD)E complex is inert and Fragments A and E have only marginal effects.
| 35,237
|
[Role of proton motive force in the infection of E. coli K-12 cells by bacteriophage T4].
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It was shown that infection of E. coli cells by phage T4 is suppressed, when the cells are treated by oxidative phosphorylation uncouplers. The inhibiting effects of the uncouplers manifest themselves at the stage of phage DNA entry into the cells. Study of the E. coli cells devoid of their H+-ATPase activity due to mutation showed that the infection is suppressed by a switch-off of the respiratory chain, the only generator of the proton motive force (PMF) in mutated cells. Infection of the E. coli cells containing intact H+-ATPase occured even in the case when the respiratory chain activity was inhibited. The kinetic studies showed that generation of PMF is necessary during phage DNA transport into the cells and is indispensable for phage DNA entry into bacterial cells.
| 35,241
|
[Isolation and properties of N-acetyl-beta-D-hexosaminidase from the fungus Hohenbuechelia serotina].
|
N-Acetyl-beta-D-hexosaminidase (EC 3.2.1.52) isolated from the fruit bodies of Hohenbuechelia serotina (Fr.) splits N-acyl-p-nitrophenyl-beta-D-glucosaminides acylated at the amino group of the aminosugar by fatty acids, substituted benzoic acids and some amino acids and peptides. The enzyme was purified about 210-fold by chromatography on CM-Sephadex C-50 and DEAE--Sephadex A-50 and by gel filtration of Sephadex G-200 with a yield of 4%. The enzyme had pI 6,6. Some properties of the enzyme, pH-optimum, thermal stability and substrate specificity were studied. The Michaelis constants for some p-nitrophenyl-beta-D-glucosaminides were were calculated. p-Nitrophenyl N-acetyl-beta-D-glucosaminides were calculated. p-Nitrophenyl N-acetyl-beta-D-glucosaminide and D-galactosaminide at concentrations more than 0,3 mM inhibited the enzyme.
| 35,252
|
[Changes in postsynaptic excitation processes in the presence of phenazepam].
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The new psychotropic drug phenazepam inhibits the impulse activity of the neurons which compose visceral ganglia of the garden snail (Helix aspersa) and suppresses stimulating postsynaptic potentials arising in application of acetylcholine to the membrane of isolated neurons. The electrostimulating membrane parameters are not generally changed. Postsynaptic depression of the stimulation of the cholinoreceptive membrane is suggested to be one of the possible mechanisms of the pharmacological action of the drug.
| 35,258
|
Characterization of an enzyme from Rhizoctonia praticola which polymerizes phenolic compounds.
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An extracellular phenol oxidase from the fungus Rhizoctonia praticola which polymerizes various xenobiotic phenols was isolated and characterized. The enzyme was purified by DEAE-cellulose and Sephadex G-200 chromatography followed by preparative polyacrylamide gel electrophoresis. Atomic absorption and EPR spectroscopy indicated the presence of copper, and SDS gel electrophoresis revealed a molecular weight of 78,000. With 2,6-dimethoxyphenol as substrate, the enzyme showed a pH optimum of 6.7--6.9, and a temperature optimum of 40 degrees C. According to these and additional characteristics it appears that the enzyme belongs to the class of laccases.
| 35,275
|
Agenesis or atrophy of the testis and vas deferens.
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In this study the author examines the relationship between agenesis or atrophy of the testis and of the vas deferens. From a prospective study of 237 cases of unilateral and bilateral undescended testis, 12 cases of agenesis of a testis were seen; 9 of the 12 cases were associated with agenesis of the vas deferens and in 3 of these unilateral renal agenesis was also present, not necessarily ipsilaterally. Three other cases of testicular agenesis and four cases of extreme testicular atrophy were seen. In all seven, the vas deferens was present in part or in its entirety and roentgenography disclosed a normal upper urinary tract. Agenesis of the vas deferens was seen only in patients with monorchism. No patient was anorchid. It is concluded that an important link exists between agenesis of the vas deferens and agenesis of the testis.
| 35,276
|
Evaluation of the cytotoxicity of dihydroxytryptamines and 5-hydroxytryptamine antagonists as cytotoxic agents in dimethylhydrazine-induced adenocarcinomata.
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The cytotoxicity of 5,6-dihydroxytryptamine (5,6-DHT), 5,7-dihydroxytryptamine (5,7-DHT), bromolysergic acid diethylamide (BOL), methysergide, and cyproheptadine, and also of 5,6-DHT together with either BOL, methysergide, or cyproheptadine in dimethylhydrazine-induced (DMH) carcinomata of rat colon was evaluated by estimating the percentage of necrotic cells in histological sections of tissues taken 15 h after injection of each of the drugs. In addition, the influence of methysergide and cyproheptadine on the tumour cell mitotic rate was estimated by means of a stathmokinetic technique. Both 5,6-DHT and 5,7-DHT were cytotoxic at each dose tested and for each of these agents the percentage of necrotic cells was directly correlated with the dose of drug used. BOL was not found to be cytotoxic to the colonic carcinomata, whereas both methysergide and cyproheptadine did cause detectable tumour cell necrosis. Methysergide was also found to accelerate tumour cell proliferation, whereas cyproheptadine did not. BOL competitively inhibited the cytotoxicity of 5,6-DHT and neither methysergide nor cyproheptadine potentiated the effect of 5,6 DHT.
| 35,286
|
N-Acetyl-beta-D-glucosaminidase activity in normal and chronic lymphocytic leukaemic lymphocytes.
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N-Acetyl-beta-D-glucosaminidase (EC 3.2.1.30) activity was measured fluorimetrically in: (a) lymphocytes from 20 normal donors, (b) enriched B and T lymphocyte populations prepared by E rosette sedimentation from 8 normal subjects, (c) lymphocytes from 15 untreated B cell chronic lymphocytic leukaemic patients. The pH profiles and optima (4.7) were similar in all preparations. Normal B lymphocytes had higher activity than normal T lymphocytes and both these preparations and normal unfractionated lymphocytes had significantly higher activity than chronic lymphocytic leukaemic lymphocytes. The apparent Michaelis constants were similar in normal unfractionated, B enriched and T enriched lymphocytes, whereas a reduced affinity for the enzyme was observed in the leukaemic lymphocytes. The difference in enzyme content between normal and chronic lymphocytic leukaemic lymphocytes cannot therefore be explained on the basis of a high B cell percentage in patients with chronic lymphocytic leukaemia.
| 35,292
|
Isolation of kidney brush border gamma-glutamyl transpeptidase from urine by specific antibody gel chromatography.
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The IgG fraction of antiserum directed against gamma-glutamyl transpeptidase (gammaGTP, EC 2.3.2.2) isolated from human kidney brush border membranes after limited proteolysis, was covalently bound to cyanogen bromide-activated Sepharose. With this antibody-gel, gammaGTP present in the urine of patients as a result of tubular damage was immunospecifically prepared by affinity chromatography. The enzyme isolated from the urine samples gave a complete cross-reaction wiht gammaGTP artificially cleaved off from brush border fragments. Since labelled anti-gammaGTP sera gave a specific immunofluorescence only of the luminal portion of cortical tubule, the use of immunosorption chromatography appears to be an important approach for the isolation of urinary kidney tissue antigens of a defined origin.
| 35,293
|
Evaluation of a community-based poison education program.
|
This study suggests that: (1) a program directed at a specific town and coordinated by a local community group is more effective in transmitting poison control knowledge than is a statewide poison prevention week effort; (2) that transmission of educational material is optimized through programs directed at a specific age group (in this study ages 6 through 14); and, (3) that information about where to get the poison center number and actual acquisition of Ipecac syrup in homes was well transmitted.
| 35,303
|
The metabolic disposition of norgestrel in female rhesus monkeys.
|
Following single intragastric doses of d- and dl-[24C]norgestrel (Ng), rhesus monkeys excreted 29.5 +/- 2.0 (SE) and 52.6 +/- 5.4% of the administered radioactivity in urine. Fecal excretion accounted for 57.1 +/- 4.0 and 37.2 +/- 4.4%, respectively. Urinary radioactivity was separated into neutral, acidic, and conjugated fractions. The neutral and conjugated fractions contained Ng; 2 alpha, 16 alpha- and 16 beta-hydroxy-Ng; 3 alpha,5 beta-tetrahydro-Ng and 16 beta-hydroxy-3 alpha,5 beta-tetrahydro-Ng and their glucuronides. However, the bulk of the radioactivity in these fractions was associated with more polar metabolites. The acidic fraction contained unstable metabolies which lose 14CO2 at pH values below 5. The most abundant of these metabolites was isolated as its stable methyl ester. The structure of a 13-ethyl-D-homogon-4-ene-3,17 alpha-dione-17 carboxylic acid is proposed for the metabolite which decomposes to 13-ethyl-D-homogon-4-ene-3,17 alpha-dione [D-homo-G]. The probable mechanism of the metabolite's formation is postulated. Quantitative differences in urinary metabolite patterns were observed following the administration of d- and dl-Ng. Ng is the major identified drug-related entity in plasma. The d-Ng concentrations in plasma measured by radioimmunoassay were in good agreement with those determined by fractionation and radiometry. The latter method indicated the presence of D-homo-G and a glucuronide of 3 alpha,5 beta-tetrahydro-Ng following the administration of d- and dl-Ng.
| 35,318
|
Neuropsychological correlates of anticonvulsants and epileptiform discharges in adult epileptics.
|
Neuropsychological correlates of anticonvulsants and of EEG epileptiform discharges were examined through the administration of neuropsychological measures to groups of adult epileptics. Among the anticonvulsants, performances with high and low serum phenytoin levels were compared and performances with sulthiame vs. phenytoin and carbamazepine vs. phenytoin were evaluated. Various drug effects from these studies were noted and there was some suggestion that the neuropsychological impacts of specific anticonvulsants may be selective rather than general. The neuropsychological correlates of the topographic distribution and average rate of occurrence of discharges were considered. Striking neuropsychological correlates were found with the poorest performances in connection with discharges which were generalized and those which were at a rate greater than 1/min. The importance of using a broad range of neuropsychological measures was stressed.
| 35,335
|
[Effect of tranquilizers on impulse conduction in the afferent pathways of visceral nerves].
|
Experiments on pyrolaxon-immobilized cats evidence that diazepam produces depression of evoked potentials in the specific, nonspecific and associative brain structures upon an electric stimulation of the visceral and somatic nerves, and also with accoustic and photostimulation; Meprotan (meprobamate) in doses of 40-100 mg/kg neither changes nor increases, and in doses of 100-150 mg/kg, reduces the amplitude of evoked potentials and at the sme time forces down the arterial pressure. Amizyl (benactyzine) inhibits the potentials evoked by stimulation of the vagus. The amplitude of responses arising on stimulation of the inferior cardiac, celiac and sciatic nerves, and also with acoustic and photostimulation neither changes nor increases.
| 35,365
|
Assessment of uteroplacental hemodynamics in complicated pregnancy.
|
Examination of the uteroplacental hemodynamics was performed on 109 occasions in women admitted to the hospital in the third trimester because of various complications of pregnancy. The radioactive tracer 113m In was injected intravenously and the build-up and equilibrium times were measured over the placenta, myometrium and heart. The placental build-up times were most informative, with prolonged values being recorded in about one quarter of these cases. When those extending beyond three minutes were further studied, they were usually found to be associated with severe complications of pregnancy. This did not obtain in cases with shorter placental build-up times.
| 35,387
|
An antacid comparison trial.
|
A trial is described in which patients going into labour were randomly allocated to treatment with either Andursil or Magnesium Trisilicate Co. Following delivery of the baby the stomach is emptied and the volume and pH are measured. Table 5 summarizes the results of 1106 patients. Andursil was found to be more palatable by patients than was Magnesium Trisilicate Co, but the incidence of nausea and vomiting was similar in the two groups.
| 35,428
|
Some observations on human semen analysis.
|
Semen analysis of 66 unmarried medical students in the age group of 17-21 years was carried out. A higher liquefaction time pH, motility, lower sperm count and abnormal forms were observed compared to reported values. Liquefaction time, pH and sperm count was found significantly different in non-vegetarians and vegetarians, perhaps due to difference in their dietary proteins.
| 35,465
|
Mammalian and microbial cell-free conversion of anthracycline antibiotics and analogs.
|
Cell-free preparations of Streptomyces nogalater and rat liver catalyze reduced pyridine nucleotide dependent conversion of nogalamycin to 7-deoxynogalarol and nogalose (Scheme 1). The mammalian process requires TPNH and has a specific activity of 85 nmoles of 7-deoxynogalarol formed per hour per mg of protein while the bacterial process prefers DPNH and has a specific activity of 5. The oxygen-sensitive conversions have pH optima of 7.5 (rat) and 9 (S. nogalater). Other anthracycline substrates converted to their 7-deoxyaglycones by both systems include nogamycin, 7(R)-O-methylnogarol, 7(R)-O-methylnogalarol, doxorubicin (Adriamycin), steffimycin, and steffimycin B.
| 35,508
|
Identification and partial purification of an ATP-stimulated alkaline protease in rat liver.
|
Extracts from rat liver contain a sulfhydryl-dependent endoprotease which degrades [methyl-14C]globin or 125I-hemoglobin to acid-soluble peptides. This enzyme was isolated from the 100,000 x g supernatant of the homogenate. It showed a pH optimum between 7.5 and 9.5 and very little activity below pH 7.0. The enzyme has an apparent molecular weight of 550,000 as determined on Sepharose 6B column chromatography and sucrose density gradient centrifugation. ATP, at physiological concentrations, as well as pyrophosphate, stimulated the protease activity in these partially purified preparations up to 3-fold. Nonionic detergents such as Triton X-100 increased proteolytic activity and the stimulation by ATP. Other nucleotide triphosphates and ADP also increased proteolysis but less effectively than ATP. Sodium phosphate, creatine phosphate, and EDTA had no stimulatory effect.
| 35,530
|
Rapid diagnosis of meningitis with use of selected clinical data and gas-liquid chromatographic determination of lactate concentration in cerebrospinal fluid.
|
The usefulness of determination of lactate concentration in cerebrospinal fluid (CSF) for differentiation between various types of meningitis was evaluated. Lactate concentration in the CSF was assayed by gas-liquid chromatography for 115 patients, 17 of whom had serous meningitis and 38 had bacterial meningitis. The mean lactate concentration in the CSF of patients with bacterial meningitis was significantly higher than in the CSF of patients with serous meningitis and in a control group. The mean concentration in patients with serous meningitis was significantly higher than in controls. The highest lactate level in serous meningitis overlapped with the lowest level in bacterial meningitis. Elevated lactate concentrations in CSF were found also in patients with noninfectious disorders of the central nervous system. Misleading results may therefore be obtained if the lactate concentration in CSF alone is used to distinguish between serous and bacterial meningitis. The study suggests, however, that measurements of lactate levels in CSF, when combined with clinical and conventional laboratory observations, can increase the reliability of rapid diagnosis of bacterial meningitis.
| 35,573
|
Interaction of amiloride and lithium on distal urinary acidification.
|
The interaction of amiloride and LiCl administration on renal HCO3 handling was studied in hydropenic rats. Amiloride administration resulted in a significant increase in Na, Cl, and HCO3 excretion, whereas K excretion decreased significantly. LiCl administration resulted in a significant increase in Na, Cl, K, and HCO3 excretion. LiCl administration to animals receiving amiloride led to a significant increase in HCO3 excretion but failed to cause an increase in Na or K excretion. Addition of amiloride to animals receiving LiCl resulted in a significant increase in Na and HCO3 excretion. The net increase in fractional HCO3 excretion seen in this group was greater than that seen in all other groups. The finding that the net increase in FEHCO3 was greater in animals receiving amiloride after administration of LiCl than in animals receiving LiCl after amiloride administration indicates that amiloride blunted the effect of LiCl on HCO3 excretion. Administration of amiloride to both normal rats and to rats infused with Li during HCO3 administration resulted in a significant decrease in U-B Pco2 which could not be explained by the decrease in urine HCO3 concentration. These data demonstrate that amiloride inhibits distal acidification in vivo. LiCl administration also resulted in a decrease in U-B Pco2 which could be explained by the decrease in urine HCO3 concentration. LiCl administration also resulted in a decrease in TcH2O which could be prevented by prior administration of amiloride. These data indicate that amiloride blunts the effect of LiCl on urinary acidification, an effect similar to that observed on urinary concentration. These data suggest that the effect of Li on urinary acidification is in part dependent on Li entry into the cell.
| 35,580
|
GLC analysis of theophylline, hydroxyethyltheophylline, and diphenylpyraline hydrochloride syrup.
|
A GLC method for determining theophylline, hydroxyethyltheophylline, and diphenylpyraline hydrochloride is presented. The method permits the separation and quantitative determination of the therapeutically active ingredients with a single injection in an overall time of approximately 2.5 hr.
| 35,600
|
Renal handling of zomepirac sodium (McN-2783-21-98) in the rat.
|
The plasma and renal clearance of zomepirac, a weak organic acid, was investigated in anesthetized CR Wistar rats after administration of single bolus i.v. injections or continuous i.v. infusions of the 14C-labeled compound. Adjustment of urine pH to the alkaline range caused more than an 8-fold lowering of the plasma elimination half-life (from 7.0 to 0.8 hr) and enhanced renal clearance by a factor of 53 compared to control. Acidification of the urine or probenecid administration increased the elimination half-life (to 10.9 and 17.5 hr, respectively), and decreased renal and plasma clearance of zomepirac. Since zomepirac is highly bound to plasma proteins (approximately 98%), only a small fraction of the drug is available for filtration at the glomerulus. Therefore, the renal elimination of zomepirac is accomplished mainly by active tubular secretion. Passive nonionic reabsorption is a major factor in determining the net clearance of the drug.
| 35,605
|
Pathophysiologic effects distal to a tourniquet in the dog.
|
Intramuscular tissue pO2, pCO2, and pH were monitored distal to a pneumatic tourniquet in a dog hindleg preparation. A severe state of tissue hypoxia, hypercarbia, and acidosis was quantitated. The recovery time for tissue gases following release increased with increasing tourniquet time. Elevated c.p.k. and lactic acid values were noted at 2 hours of ischemia, reflecting the muscle changes at that time. Histologic sections revealed early signs of degeneration by 1 hour which progressively increased with increased tourniquet ischemia. On the basis of this study, we conclude that ischemia should not exceed 1 to 1 1/2 hours if significant pathophysiologic tissue changes are to be avoided. If longer time is required, intermittent release of the tourniquet for 10 minutes at the end of each hour of inflation will avoid complications.
| 35,619
|
[Surgical and radiological anatomy of the mandibula (author's transl)].
|
One of the risks in dysgnathia-operations performed on the mandibula is the injury to the anatomic formations inside the mandibular channel. The paper deal with anatomic sites recommended in the literature for measurements. The occurrence of a sulcus colli mandibulae and the depth of the bone groove is investigated, and their part as an operative risk factor is presented. Attention is drawn consequently to individual variations and a careful surgical technique is recommended.
| 35,699
|
[Ganglion in the ulnar nerve groove (author's transl)].
|
Two cases of a rare localisation of ganglion is reported in this paper. A ganglion in the ulnar nerve presented by complete loss in ulnar nerve function. Attention is drawn to the importance of early diagnosis, and to the fact, that in cases of ulnar nerve lesions of unknown origin tumors in the ulnar groove must be considered.
| 35,700
|
Myosin polymorphism in human skeletal muscles.
|
Myosins isolated from individual human muscles (primarily normal muscles) were investigated with respect to their structural and catalytic properties. The results indicate unexpected elements of uniformity shared by the several myosins, such as a three-banded, electrophoretic pattern of light chains in sodium dodecylsulfate (SDS) gels and a low degree of alkaline lability. The pH activity profile and the effect of KCl on myosin ATPase activities were also found to be the same for the myosins from predominantly fast (e.g., vastus lateralis and rectus abdominis) and slow (e.g,, soleus and pectoralis minor) muscles. Coelectrophoretic experiments lend further credence to the interrelationship between human myosin light chains and the light chains of rabbit fast-muscle myosin. However, several kinds of circumstantial evidence, such as that derived from the study of myosin in nemaline myopathy, suggest that one shoould exercise caution in interpreting these results. On the other hand, human muscle myosins, like those of other mammalian species, can be divided into two main categories according to the peptide composition of tryptic heavy meromyosin (HMM) and the banding pattern of light meromyosin (LMM) paracrystals. These results, which are indicative of differences in the primary structure of the heavy chains, allow us to identify these heavy chains as the main site of heterogeneity among myosins in human mucles.
| 35,746
|
Studies on the PR toxin of Penicillium roqueforti.
|
A mycotoxin, confirmed by chemical, physical and spectroscopic data as the PR toxin described by Ru-Dong Wei and coll. (15) has been isolated from culture filtrates of Penicillium roqueforti Thom. Factors affecting the toxin and mycelium production, acute and chronic toxicity in experimental animals and the frequency of toxinogenesis of 21 isolates of P. roqueforti (including a brown mutant) isolated from different materials, foods especially, were also studied. An hypothesis on the absence of PR toxin in cheeses fermented with P. roqueforti is also advanced.
| 35,751
|
[The prehypophyseal-gonadal system in the normal male and in some forms of testicular dyscrinism. Evaluation studies in basic conditions and after stimulation].
|
The secretion values of the two seric gonadotropins and of plasmatic testosterone have been estimated in a casuistry of normal males subdivided in groups of 8 to 95 years of age, and of primitive and secondary testicular dyschrinia. In one part of this casuistry, normal and primitive hypogonadics, we have estimated the response to the intravenous administration of Gn-RH. Among the results which have been obtained, it appears that physiologic hypogonadism of the elderly is a primary phenomenum, not hypophyso-dependent. In the hypophysiary stimulus test, the response of gonadotropins in those old men moves away from the response of hypogonadics considered, by a behaviour much more similar to that of normal adults, even if delayed and prolonged. In all the cases, normal and pathologic, the response of testosterone is variable, perhaps owing to the relation with the various factor which have been noted.
| 35,768
|
Tsetse movement in wind fields: possible epidemiological and entomological implications for trypanosomiasis and its control.
|
This paper presents evidence that tsetse flies (Glossina) can be dispersed by wind. This dispersal in West Africa is suggested to be along a south-west north-east axis. The implications of wind dispersal of Glossina for chemical and genetic control operations is discussed. Field experiments necessary to test this hypothesis are recommended. A study of human trypanosomiasis foci in West Africa has revealed that foci are orientated in roughly parallel lines in a south-west north-east direction. This directionally was significant when compared with 7 other compass points. It is proposed that foci could be populated by infected flies dispersed from the south west, where denser populations exist, on the prevailing winds in the late dry/early rainy season. The significance of these ideas in relation to the epidemiology of Trypanosoma brucei rhodesiense in Ethiopia and T. evansi are discussed.
| 35,935
|
Influence of the isolation procedure on the structure, neuraminidase and heamagglutinating activities of Sendai virus envelope glycoproteins.
|
The influence of the isolation procedure of Sendai virus glycoproteins from the virus surface on their neuraminidase and haemagglutinating activities, as well as on some structural properties was studied. These glycoproteins exhibited lower specific neuraminidase and haemagglutinating activities than those of intact virus. Neuraminidase activity was expressed when the glycoproteins were constituted in forms with molecular weights of about 70,000 (monomer), 160,000 (dimer), 300,000 (tetramer) or 600,000 (octamer), whereas haemagglutinating activity was only found for the glycoproteins aggregated in a high mol. wt. (approximately 10(6) daltons) form. The isolated glycoproteins contained two subunits revealed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and three distinct antigenic components revealed by rocket immunoelectrophoresis. Different treatments of the glycoproteins after their isolation altered their structure. Consequently either neuraminidase and haemagglutinating activities were signicantly reduced, or one of these activities was not expressed.
| 35,940
|
The influence of temperature and pH on the growth of Rickettsia conorii in irradiated mammalian cells.
|
The temperature range for optimum growth of Rickettsia conorii in suspension culture of gamma-irradiated L cells was 32-38 degrees C, resulting in rickettsial doubling times between 4.1 and 6.0 hr. An asynchronous release of R. conorii from host cells was suggested by the constant increase in percent cells infected over a 36 hr period. Rickettsial growth was optimal at neutral to slightly alkaline extracellular pH levels. A moderately acidic pH, however, resulted in an increase in doubling time from 4.1 to 7.8 hr.
| 35,961
|
Isolation of Tettnang virus from ticks, mosquitoes and small rodents.
|
Seven strains of Tettnang virus were isolated in Czechoslovakia: 3 from Ixodes ricinus tick nymphs, males and females, one from Dermacentor reticulatus tick females, one from Aedes cantans mosquitoes and two strains from the brains of Clethrionomys glareolus and Apodemus flavicollis small rodents.
| 35,963
|
Radiographic manifestations of bone marrow transplantation in children.
|
Radiographically detectable complications in 35 children after bone marrow transplant are reviewed. These complications are most frequently due to infection, chemoradiotherapeutic toxicity, and graft versus host disease (a transplant rejection phenomenon peculiar to bone marrow transplant patients). The pulmonary complications within the first 2 months are secondary to a form of interstitial lung disease. Interstitial lung disease has a strong correlation with graft versus host disease. Extrapulmonary visceral complications include hepatosplenomegaly, nephromegaly, and hemorrhagic cystitis. These are due to graft versus host disease, radiation, and chemotherapeutic toxicities, respectively. Sinusitis, cerebral atrophy, and intracerebral hematomas are less frequent complications. Osteoporosis due to steroids is the single most important osseous complication.
| 35,966
|
Fiber of the maize tortilla.
|
Fiber concentrations were measured in maize tortillas and in masa, the lime-treated dough from which they are made, with the aid of Van Soest's methods. Neutral detergent fiber of tortillas was 6.60 +/- 0.98% (mean and SD) and acid detergent fiber 3.75 +/- 0.83% of the dry weight corrected for ash. The hemicellulose fraction was 2.89 +/- 0.94%. Both neutral and acid detergent fiber were significantly higher in tortilla than in masa. The gain in fiber by tortillas during baking is attributed to the formation of browning reaction (Maillard) products resistant to the detergent-containing fiber reagents.
| 35,971
|
Effect of gastrin I and gastrin II on canine bile flow.
|
The role of gastrin in the hormonal control of canine hepatic bile flow was evaluated. Because of the importance of the presence of sulfation of the carboxyl terminal peptide in the function of other cholecystokinetic hormones and peptides in the biliary tract, the choleretic properties of sulfated gastrin II were compared to the choleretic properties of nonsulfated gastrin I. Exogenous administration of gastrin I and II to dogs with chronic bile fistulas demonstrated that gastrin II, but not I, significantly increased hepatic bile flow. Chemical stimulation of the release of endogenous gastrin in dogs with denervated antral pouches did not increase hepatic bile flow, whereas a choleresis resulted when the innervated antrum was stimulated. Serum gastrin values obtained during the infusion of gastrin II at doses that produced a choleresis resulted in serum gastrin values that were greater than those produced by a more physiological stimulus, such as chemical antral stimulation. The results of this study suggest that only the sulfated gastrin II, not gastrin I, is a choleretic agent in dogs and only at pharmacological, not physiological doses.
| 35,983
|
No barbiturate protection in a dog model of complete cerebral ischemia.
|
Complete global ischemia was produced in 39 dogs by temporary ligation of the aorta. Prior to the ischemic episode, pentobarbital (30 to 45 mg per kilogram of body weight) was administered to 19 of these dogs. The neurological effects of cerebral ischemia episodes lasting 8, 9, or 10 minutes were compared in dogs treated with pentobarbital and those not treated. At 48 hours following the ischemic episode most of the dogs made ischemic for 8 minutes were normal, whereas most animals made ischemic for 10 minutes were dead or comatose. The 9-minute ischemic period resulted in a relatively even distribution of normal and damaged dogs. There were no differences between treated and untreated dogs. Cerebral blood flow, cerebral metabolic rate for oxygen, and various cerebral metabolites were measured in dogs surviving 48 hours. Again, there were no differences between treated and undertreated dogs. We conclude that barbiturates provide no protection in this model of complete global ischemia. This conclusion supports the hypothesis that the likely mechanism of barbiturate protection in models of incomplete ischemia or hypoxia is based on cerebral metabolic depression; such a mechanism would not be expected to be effective in complete global ischemia.
| 36,025
|
Human tear buffering capacity.
|
With the use of a closed chamber microelectrode system, we measured the relative buffering capacities of 490 human tear samples from young healthy adults. The buffering capacities of the 457 waking-hour samples did show small but regular oscillations that were similar to those previously reported for blood and tear pH, but only rarely did the buffering capacity of one sample approach double that of another. The buffering capacities of 33 tear samples, associated with periods of prolonged eye closure (sleep), were not significantly different (P less than 0.5) from those of the open eye.
| 36,059
|
The binding of rat liver cell multiplication-stimulating activity (MSA) to human placenta and serum proteins.
|
Multiplication-stimulation activity (MSA) from the medium of BRL-3A rat liver cells in culture binds to cell membrane and cytosol receptors from human placenta and to serum proteins. The binding of MSA to placental cell membranes is dependent on time, temperature, pH and divalent ion concentration. MSA bound to placental cytosol receptor and serum is not displaced by insulin, whereas that bound to placental cell membranes is displaced by insulin and insulin-like peptides. The affinity of the three receptors for MSA is similar [approximately 10(8) M(-1)]. An assay using 125I-MSA and placental membrane receptor detects somatomedin-like receoptor activity (SmLRA) in unextracted sera from man and animals. A binding protein in serum that competes for 125I-MSA with receptor could not be completely separated from SmLRA by heating, acidification, charcoal treatment and gel chromatography of the serum. The relative activities of SmLRA and serum binding protein remained constant in three disorders of human growth (acromegaly, growth hormone deficiency and Laron's dwarfism) in which values of SmLRA varied widely. However, the binding protein is only partly responsible for the apparent SmLRA of unextracted serum. It is concluded that MSA is a suitable radioligand for the investigation of somatomedin disorders in man either by receptor assays or by studies of tissue receptors.
| 36,062
|
Electron-transport pathway of the NADH-dependent haem oxygenase system of rat liver microsomal fraction induced by cobalt chloride.
|
The hepatic microsomal haem oxygenase activity of rats treated with CoCl2 was studied kinetically by measuring biliverdin, the immediate product of the reaction. Biliverdin was extracted with diethyl ether/ethanol mixture, and was determined by the difference between A690 and A800. The apparent Km value for NADPH (at 50 microM-haematin) was about 0.2 microM when an NADPH-generating system was used, whereas that for NADH was about 630 microM. Essentially the same Vmax. values were obtained for both the NADH- and NADPH-dependent haem oxygenase reactions. No synergism was observed with NADH and NADPH. The NADH-dependent reaction was competitively inhibited by NADP+, with a Ki of about 10 microM. The inhibitoin of the NADH-dependent reaction by the antibody against rat liver microsomal NADPH-cytochrome c reductase was essentially complete, with a pattern similar to that of the NADPH-dependent reaction. The immunochemical experiment and the comparison of the kinetic values with the reported data on isolated NADH-cytochrome b5 reductase and NADPH--cytochrome c reductase indicated the involvement of the latter enzyme in NADH-dependent haem oxygenation by microsomal fraction in situ.
| 36,076
|
Maprotiline in adult depressed patients. A study of the relation between clinical efficacy and serum concentrations after repeated intravenous and peroral administration.
|
Maprotiline was administered initially i.v. and then p.o. to 15 adult depressive in-patients daily for three weeks in various dosages. Serum concentrations were monitored in an attempt to find a correlation to clinical response. The steady-state serum concentration attained is independent of the dosage administered. The results suggest that patients who maintain a high serum concentration will show a better therapeutic response to the drug. In 11 out of 14 patients evaluated after three weeks of daily maprotiline therapy the clinical response could be described as excellent or very good. The drug was well tolerated when given by either route.
| 36,112
|
Comparison of the actions of diazepam and lorazepam.
|
Diazepam and lorazepam differ in potency and in the time-course of their action. As a sedative, diazepam 10 mg is equivalent to lorazepam 2-2.5 mg. Diazepam is better absorbed after oral than after i.m. administrations but this does not apply to lorazepam. The clinical effect and amnesia begin more rapidly with diazepam, but last longer following lorazepam. Lorazepam is more effective than diazepam in blocking the emergence sequelae from ketamine. Lorazepam i.v. is followed by a lesser frequency of venous thrombosis.
| 36,117
|
Kinetics of Mg2+ flux into rat liver mitochondria.
|
Unidirectional fluxes of Mg2+ across the limiting membranes of rat liver mitochondria have been measured in the presence of the respiratory substrate succinate by means of the radioisotope 28Mg. Rates of both influx and efflux of Mg2+ are decreased when respiration is inhibited. A linear dependence of the reciprocal of the Mg2+ influx rate on the reciprocal of the Mg2+ concentration is observed. The apparent Km for Mg2+ averages about 0.7 mM. N-Ethyl-maleimide, an inhibitor of transmembrane phosphate-hydroxyl exchanges, enhances the observed pH dependence of Mg2+, influx. In the presence of MalNEt, the apparent Vmax of Mg2+ influx is greater at pH 8 than at pH 7, and there is a linear dependence of the Mg2+ influx rate on the external OH- concentration. The K+ analogue Tl+ inhibits Mg2+ influx, while La3+, an inhibitor of mitochondrial Ca2+ transport, has no effect on Mg2+ influx. Mg2+ competitively inhibits the flux of K+ into rat liver mitochondria. The mechanism(s) mediating mitochondrial Mg2+ and K+ fluxes appear to be similar in their energy dependence, pH dependence, sensitivity to Tl+, and insensitivity to La3+.
| 36,136
|
Urate transport in human red blood cells. Activation by ATP.
|
Urate transport in human erythrocytes were measured and compared to previous observations by other authors regarding inorganic anions, especially chloride. Conclusions wwere as follows: 1. Urate influx as a function of increasing concentrations showed saturation kinetics. 2. The effects of pH and of several passive anion transport inhibitors such as dinitrofluorobenzene, sodium salicylate, sodium benzoate and phenylbutazone suggest that urate and chloride are transported by different mechanisms. 3. Urate influx seems to depend on intracellular glycolysis. The results obtained on red blood cells after glycolysis inhibition agree with those obtained on ghosts where metabolism does not take place. 4. The large drop in urate influxes into erythrocytes in the presence of a glycolysis inhibitor and of a passive ion transport inhibitor seems to argue in favour of a dual urate transport mechanism, one for passive diffusion and the other connected with glycolysis. 5. The drop in the urate influx into ghosts in the absence of ATP suggests that the latter might intervene in urate transport by human red cell membranes.
| 36,146
|
Clustering of fatty acids in phospholipid bilayers.
|
From electrophoresis experiments it is concluded that acidic phospholipids incorporated in liquid crystalline phosphatidylcholine bilayers at neutral pH are randomly distributed. The same is true for spin-labelled fatty acids. In contrast, long chain fatty acids are not fully ionized at neutral pH and appear to be clustered, i.e. they segregate out into patches. Only at pH greater than 11 is the fatty acid-COOH group fully ionized and charge repulsion leads to a random distribution of the fatty acid within the plane of the bilayer.
| 36,148
|
Hydrogen cyanide and cyanogen chloride formation by the myeloperoxidase-H2O2-Cl- system.
|
The chlorination of glycine by the myeloperoxidase-H2O2-Cl- system at acidic pH values yielded N-monochloroglycine and a mixture of HCN and ClCN. HCN was formed as a product of N-dichloroglycine decomposition and cyanogen chloride formation resulted from simultaneous chlorination of HCN by N-chloroglycine or directly by the myeloperoxidase-H2O2-Cl- system. HCN was readily chlorinated by the myeloperoxidase-H2O2Cl- system yielding cyanogen chloride. This dissociation constants of the myeloperoxidase-CN- complex were estimated as 2.5.10(-6)--1.15.10(-5) M within the pH range of 6.2 to 3.4, respectively. Chloride competed with cyanide for binding at the active site of myeloperoxidase. The lower the pH the more pronounced was the competitive effect of chloride. This accounted for chlorination by myeloperoxidase in the presence of CN-.
| 36,154
|
Some properties of starch phosphorylase from cotyledons of germinating seeds of Voandzeia subterranea.
|
Two isoenzymes (Forms I and II) of starch phosphorylase (1,4-alpha-D-glucan: orthophosphate alpha-glucosyltransferase, EC 2.4.1.1) were found in cotyledons of germinating seeds of Voandzeia subterranea L. Thouars. Phosphorylase I, which was the major component, had a pH optimum of 5.5--5.6, whereas phosphorylase II had a pH optimum of 6.1--6.3. Phosphorylase I had a molecular weight of 204 000 +/- 4000 and a subunit molecular weight of about 95 000. Phosphorylase I was stimulated by Mg2+, Mn2+, AMP, cyclic AMP, pyruvate and EDTA, but inhibited by Fe2+, Cu2+, Zn2+ and ATP. Stimulation of phosphorulase I by AMP was accompanied by changes in the affinity of the enzyme for glucose-1-phosphate in the presence of increasing AMP concentrations, and of AMP in the presence of increasing glucose-1-phosphate concentrations. Double-reciprocal plots of initial velocity data were non-linear (convex up) at low glucose-1-phosphate concentrations but became linear in the presence of AMP or ATP. Double-reciprocal plots were linear at high glucose-1-phosphate concentrations in the absence or presence of modifiers.
| 36,156
|
The sulphatase of ox liver. XXII. Further observations on the cerebroside sulphatase activity of sulphatase A.
|
Further studies have been made of the cerebroside sulphatase activity of the sulphatase A (aryl-sulphate sulphohydrolase, EC 3.1.6.1) of ox liver. It is concluded that a cerebroside sulphate-modified form of the enzyme is not produced and that the kinetics of the reaction can be explained by the utilisation of the substrate and accumulation of (SO4)2-. The hypothesis is advanced that this difference between the cerebroside sulphatase and arylsulphatase activities arises from non-polar binding of the cerebroside to the enzyme. Possible reasons for the differences between these results and those of other (Stinshoff, K. and Jatzkewitz, H. (1975) Biochim. Biophys. Acta 377, 126-138) are considered.
| 36,164
|
Characterization of specific differences in protein phosphorylation of the plasma membrane and the endoplasmic reticulum of mouse fibroblasts.
|
Endogenous phosphorylation was studied with highly purified fractions of the plasma membrane and the endoplasmic reticulum of SV40-transformed mouse fibroblasts using [gamma-32P]ATP and [gamma-32P]GTP as precursors. With ATP maximum overall incorporation of 32P into both membrane fractions occurred at pH 7.8 in the presence of 10 mM MgCl2 after incubation for 1 min. GTP could be utilized only by the plasma membrane fraction showing maximum incorporation of 32P at pH 7.8 and 10 mM MgCl2 after incubation for 3 min. The pattern of phosphoproteins of the plasma membrane is represented by more than 15 proteins whereas the endoplasmic reticulum essentially contained only one phosphorylated component of 35 000 molecular weight. The comparison of ATP- and GTP-specific phosphorylation of the plasma membrane revealed GTP to be a less efficient precursor yielding a similar phosphoprotein pattern with one significant difference: the GTP-specific main component exhibited a molecular weight of about 100 000 and the ATP-specific main component a molecular weight of 110 000. The relative distribution of individual phosphoproteins in the pattern of the plasma membrane was dependent on pH but not on MgCl2 concentration or time of incubation. Increasing concentrations of plasma membrane protein altered the patterns of phosphoproteins dramatically: At high protein concentrations the ATP-specific main component (Mr = 110 000) was no more phosphorylated whereas with GTP the main component Mr = 100 000 was essentially the sole phosphorylated protein.
| 36,172
|
Effects of cholesterol, hydroxycholesterols and calcium on pregnenolone production rates in mitochondrial fractions from rat testes.
|
The in vitro regulation of the mitochondrial conversion of cholesterol to pregnenolone in rat testis tissue has been further investigated. Pregnenolone production rates by isolated mitochondrial fractions could be stimulated by the addition of cholesterol. The stimulation was always highest in mitochondria isolated from lutropin-treated testes relative to control and cycloheximide treated testes. Addition 20- or 25-hydroxycholesterol resulted in a greater stimulation of pregnenolone production rates and these rates were unaffected by prior treatment with cycloheximide. When both cholesterol and 20- or 25-hydroxycholesterol were present in the incubation medium, pregnenolone production rates were mainly influenced by the hydroxycholesterol, even in the presence of a ten-fold excess of cholesterol. Ca2+ in vitro stimulated pregnenolone production rates from endogenous cholesterol as well as from added cholesterol. However, pregnenolone production rates in the presence of hydroxycholesterol were not influence by the addition of Ca2+ in vitro.
| 36,174
|
Nonfatal graft-versus-host disease occurring after transfusion with leukocytes and platelets obtained from normal donors.
|
There have been two previous reports of fatal graft-versus-host (GVH) disease following transfusion of leukocytes from normal donors for the supportive care of leukemic patients. We have reported a nonfatal case of GVH disease in a child with acute monoblastic leukemia who received leukocyte and platelet transfusions from normal donors. The dose of lymphocytes contained in both leukocyte and platelet concentrates obtained with a semicontinuous-flow cell separator is sufficient to cause GVH disease. Irradiation of all blood products administered to severely immunocompromised and myelosuppressed patients should be considered.
| 36,181
|
The effect of temperature and wavelength on the measurement of creatinine with the Jaffe procedure.
|
Studies were conducted to determine the effect of temperature and wavelength on the absorbance of alkaline solutions of picric acid in the presence and absence of creatinine. Absorbance values of an alkaline solution of picric acid were found to be influenced by temperature. At wavelength settings between 475 and 520 nm, absorbance values increased as the temperature increased. The magnitude of the thermochromic response (temperature-induced increase in absorbance) was found to be a function of wavelength: At 490 nm, the response was about three times greater than it was at 500 nm and about fifteen times greater than it was at 520 nm. Other experiments demonstrated that the response was: quantitatively related to picric acid concentration, reversible, rapid, and independent of creatinine concentration.
| 36,238
|
Tyrosine hydroxylase and the conversion of L-thyroxine into 3',3,5-triiodo-L-thyronone in the rat.
|
We have studied the effects of alpha-methyl-p-tyrosine (alpha-MPT), an inhibitor of tyrosine hydroxylase, on the in vivo conversion of L-T4 (T4) to 3',3,5-triiodo-L-thyronine (T3), and on the biological effectiveness of T4. Thyroidectomized rats were used and were injected daily with T4 maintenance doses. Three different types of experiments were carred out. The first involved isotopic equilibration with 125I-labeled T4 and measurement of urinary 125I excretion. The second series involved the injection of a single dose of [125I]T4, with the amounts of [125I]T3 in different tissues being studied 7 or 20 h later. The third series involved daily treatment for 13 days with T4 and alpha-MPT, at the end of ehich the liver alpha-glycerophosphate dehydrogenase activity was measured as a parameter of the biological effects of the hormone. Though the experimental approaches used clearly disclosed the well known effects of 6-propyl-2-thiouracil, no clear-cut effects of alpha-MPT were observed. It is concluded that alpha-MPT neither inhibits the conversion of T4 to T3 in vivo in rats nor affects the biological potency of a given dose of T4, at least to an extent compararble to that observed when 6-propyl-2-thiouracil is used. Thus, present results do not support the hypothesis that tyrosine hydroxylase is involved in the extrathyroidal deiodination of T4 to T3.
| 36,273
|
Beta-adrenoceptor blocking drugs, heart rate and genetic hypertension development in rats.
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In spontaneously hypertensive rats (SHRs) chronically treated during their growth with beta-adrenoceptor blocking drugs, no correlation was found between the reduction in heart rate and the prevention of genetic hypertension development.
| 36,293
|
Effects of drugs on brain neurotransmitter and pituitary-testicular function in male rats.
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The effects of different drugs influencing brain neurotransmitter contents have been tested on the pituitary-testicular function in male rats. L-dopa (200 mg/kg body weight, i.p.) increased the dopamine and noradrenaline contents of the hypothalamus, amygdala, striatum and mesencephalon, but it was ineffective as regards the 5-hydroxytryptamine contents of the same brain areas, and increased the plasma testosterone level. alpha-Methyl-p-tyrosine (250 mg/kg b.w., i.p.) decreased the dopamine and noradrenaline contents of these brain areas, but it was ineffective to 5-hydroxytryptamine, and decreased the plasma testosterone level. Diethyldithiocarbamate (400 mg/kg b.w., i.p. twice a day) increased the dopamine levels in the hypothalamus, amygdala, striatum and mesencephalon, decreased the noradrenaline contents in the same brain regions but had no effect on the 5-hydroxytryptamine contents of these brain areas or on the testosterone level in the peripheral blood. p-Chlorophenylalanine (300 mg/kg b.w., i.p.) decreased the 5-hydroxytryptamine contents of the different brain areas, while it had no effect on the dopamine and noradrenaline levels or on the plasma testosterone level. 5-Hydroxytryptophan (200 mg/kg b.w., i.p.) increased the 5-hydroxytryptamine contents of all brain areas studied, but was without effect on the dopamine and noradrenaline contents or the plasma testosterone level. The data suggest that both dopamine and noradrenaline may be involved in the regulation of the pituitary-testicular function, and the ratio of the two transmitters might be more important that their actual levels in definite brain areas.
| 36,334
|
Innovators gather at conference.
|
The AHA's Center for Health Promotion invited innovators in the field of community health education programming to exchange ideas and learn from expert consultants.
| 36,341
|
Clinical studies of thyrotropin-releasing hormone tartrate (TRH-T) as a direct stimulant to the central nervous system.
|
Thyrotropin-releasing hormone tartrate (TRH-T) was administered in 17 cases of organic brain lesions and 2 cases of disturbed mental activity (psychical depression), and its effect, mainly on the level of consciousness and electroencephalogram, was examined. Ten consecutive administrations of 0.5--1.0 mg/day TRH-T, as TRH, resulted in improvement of disturbance of consciousness in 8 of 16 cases. This effect was not necessarily correlated with the degree of disturbance or the site of the lesion. Improvement was seen even in those cases where disturbance of consciousness had been fixed over a long period. The effect on the electroencephalogram was small and did not parallel the degree of improvement of the level of consciousness. Abnormal TSH and thyroid hormone values were not seen despite the continued administration of TRH-T. These results would appear to indicate that the continuous administration of TRH-T has a mild activating effect directly on the central nervous system, and not through the endocrine mechanism, and exerts no damage on the internal environment in vivo.
| 36,357
|
Dibenzepin as an antifibrillatory agent for spontaneously terminating electrically induced ventricular fibrillation.
|
The effect of dibenzepin, a tricyclic antidepressant drug, on electrically induced ventricular fibrillation was studied in 20 cats and nine dogs. The ventricular fibrillation threshold and the ability of the ventricle to defibrillate spontaneously were determined before and after the administration of dibenzepin, with each animal serving as its own control. The drug raised the ventricular fibrillation threshold in all the animals tested. Before treatment, spontaneous ventricular defibrillation occurred in only 8 of the 20 cats and in none of the dogs. After treatment, all of the cats and eight of the dogs exhibited spontaneous ventricular defibrillation. The study of drugs that have a self-defibrillatory effect may serve to further understanding of the mechanism of ventricular fibrillation and its spontaneous termination.
| 36,362
|
Influence of hydrogen and chloride ions on the interaction between sulfaethidole and bovine serum albumin studied by microcalorimetric and acid-base titrimetric methods.
|
From earlier studies it is known that bovine serum albumin has one high affinity binding site and several lower affinity sites for the sulfa drug N1-(5-ethyl-1,3,4-thiadiazol-2-yl)sulfanilamide (sulfaethidole) (Kostenbauder, H.B., Jawad, M.J., Perrin, J.H., and Averhart, V. (1971) J. Pharm. Sci. 60, 1658-1660). This binding has been further studied using equilibrium dialysis, microcalorimetry, and pH titration technique. Results of these studies show that the binding of sulfaethidole to the first (high affinity) site may be accompanied by an uptake of protons. Proton uptake is found to be zero at pH 7.4 and approximately 0.6 at pH 8.5 for each sulfaethidole molecule bound. The other binding sites for sulfaethidole are not proton linked. The first, and probably the other binding sites, are also Cl- ion linked; for example, the binding of sulfaethidole to the first binding site is accompanied by the displacement of (on average) one Cl- ion at pH 7.4 in 0.1 M NaCl. This explains the observation that the heat of binding of sulfaethidole to the high affinity site is -33.0 kJ.mol-1 in the absence of chloride ions, but only -22.8 kJ.mol-1 in the presence of 0.1 M Cl- (at pH 7.4).
| 36,383
|
Acid ribonuclease from HeLa cell lysosomes.
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An acid ribonuclease has been purified from HeLa cell lysosomes. The specific activity of the RNase in lysosomes is 8-fold higher than that in nuclei and 15-fold higher than that in the postlysosomal fraction. The purified enzyme showed no detectable DNase, phosphodiesterase, phosphatase, or alkaline RNase activity. The acid RNase binds to Con A-agarose and is inferred to be a glycoprotein. It has a low isoelectric point at pH 3.0 to 3.5, and the optimal pH for activity is between 5.0 and 5.5. The enzyme requires no divalent cation for optimal activity and is totally inhibited by 1 mM Cu2+ or Hg2+. Monovalent cations including Na+, K+, and NH4+ stimulate the activity in low ionic strength buffer. The enzyme degrades rRNA faster than tRNA, and tRNA faster than poly(U); poly(A) and poly(C) are highly resistant. The products from rRNA are mostly oligonucleotides with 3'-phosphate ends. An acid RNase is also present in the lysosomes of L-cells grown in a medium free of serum; it is probably identical to the one described here.
| 36,388
|
Regulation of the interaction of purified human erythrocyte AMP deaminase and the human erythrocyte membrane.
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The binding of purified human erythrocyte AMP deaminase to human erythrocyte membranes and the effect of binding on enzyme catalytic activity was investigated. AMP deaminase binds preferentially and specifically to the cytoplasmic surface of the erythrocyte membrane. The binding is saturable, reversible, and responsive to alterations of pH, of ionic strength, and of ATP and AMP concentrations. A limited number (approximately equal to 2.2 X 10(4) per erythrocyte) of apparently homogeneous high affinity (Ka approximately equal to 2.6 X 10(7) M-1) binding sites is present. The stability of purified and endogenously bound AMP deaminase is markedly improved by the interaction with the membrane, whereas the catalytic activity of AMP deaminase is sharply reduced. AMP deaminase displaces membrane bound glyceraldehyde 3-phosphate dehydrogenase in roughly a dose-response manner. No evidence for binding of AMP deaminase to spectrin or band 3 (the G3PD binding protein) was found in sucrose gradients, however. The interaction of AMP deaminase with the erythrocyte membrane may play an important role in the regulation of cellular adenine nucleotide metabolism.
| 36,405
|
Synthesis of hemoglobin Aic and related minor hemoglobin by erythrocytes. In vitro study of regulation.
|
Factors that influence hemoglobin (Hb)A(Ic) synthesis by intact erythrocytes were studied in vitro. After incubation cells were lysed, and hemoglobins were separated by isoelectric focusing on polyacrylamide slab gels and quantitated by microdensitometry. HbA(Ic) increased with time, glucose concentrations (5-500 mM), and incubation temperature (4 degrees -37 degrees C). Low temperatures allowed prolonged incubations with minimal hemolysis. At 4 degrees C HbA(Ic) increased linearly with time for 6 wk; after incubation at the highest glucose concentration, HbA(Ic) comprised 50% of total hemoglobin. Insulin (1 and 0.1 mU/ml) did not affect HbA(Ic) synthesis in vitro. In addition to glucose, galactose and mannose, but not fructose, served as precursors to HbA(Ic). A good substrate for hexokinase (2-deoxyglucose) and a poor hexokinase substrate (3-O-methylglucose), were better precursors for HbA(Ic) synthesis than glucose, suggesting that enzymatic phosphorylation of glucose is not required for HbA(Ic) synthesis. Autoradiography after erythrocyte incubation with (32)P-phosphate showed incorporation of radioactivity into HbA(Ia1) and A(Ia2), but not HbA(Ib), A(Ic), or A. Acetylated HbA, generated during incubation with acetylsalicylate, migrated anodal to HbA(Ic) and clearly separated from it. Erythrocytes from patients with insulinopenic diabetes mellitus synthesized HbA(Ic) at the same rate as controls when incubated with identical glucose concentrations. Likewise, the rate of HbA(Ic) synthesis by erythrocytes from patients with cystic fibrosis and congenital spherocytosis paralleled controls. When erythrocytes from cord blood and from HbC and sickle cell anemia patients were incubated with elevated concentrations of glucose, fetal Hb, HbC, and sickle Hb decreased, whereas hemoglobins focusing at isoelectric points near those expected for the corresponding glycosylated derivatives appeared in proportionately increased amounts.
| 36,412
|
Role of glucagon, catecholamines, and growth hormone in human glucose counterregulation. Effects of somatostatin and combined alpha- and beta-adrenergic blockade on plasma glucose recovery and glucose flux rates after insulin-induced hypoglycemia.
|
To further characterize mechanisms of glucose counterregulation in man, the effects of pharmacologically inducd deficiencies of glucagon, growth hormone, and catecholamines (alone and in combination) on recovery of plasma glucose from insulin-induced hypoglycemia and attendant changes in isotopically ([3-(3)H]glucose) determined glucose fluxes were studied in 13 normal subjects. In control studies, recovery of plasma glucose from hypoglycemia was primarily due to a compensatory increase in glucose production; the temporal relationship of glucagon, epinephrine, cortisol, and growth hormone responses with the compensatory increase in glucose appearance was compatible with potential participation of all these hormones in acute glucose counterregulation. Infusion of somatostatin (combined deficiency of glucagon and growth hormone) accentuated insulin-induced hypoglycemia (plasma glucose nadir: 36+/-2 ng/dl during infusion of somatostatin vs. 47+/-2 mg/dl in control studies, P < 0.01) and impaired restoration of normoglycemia (plasma glucose at min 90: 73+/-3 mg/dl at end of somatostatin infusion vs. 92+/-3 mg/dl in control studies, P<0.01). This impaired recovery of plasma glucose was due to blunting of the compensatory increase in glucose appearance since glucose disappearance was not augmented, and was attributable to suppression of glucagon secretion rather than growth hormone secretion since these effects of somatostatin were not observed during simultaneous infusion of somatostatin and glucagon whereas infusion of growth hormone along with somatostatin did not prevent the effect of somatostatin. The attenuated recovery of plasma glucose from hypoglycemia observed during somatostatin-induced glucagon deficiency was associated with plasma epinephrine levels twice those observed in control studies. Infusion of phentolamine plus propranolol (combined alpha-and beta-adrenergic blockade) had no effect on plasma glucose or glucose fluxes after insulin administration. However, infusion of somatostatin along with both phentolamine and propranolol further impaired recovery of plasma glucose from hypoglycemia compared to that observed with somatostatin alone (plasma glucose at end of infusions: 52+/-6 mg/dl for somatostatin-phentolamine-propranolol vs. 72+/-5 mg/dl for somatostatin alone, P < 0.01); this was due to further suppression of the compensatory increase in glucose appearance (maximal values: 1.93+/-0.41 mg/kg per min for somatostatin-phentolamine-propranolol vs. 2.86+/-0.32 mg/kg per min for somatostatin alone, P < 0.05). These results indicate that in man (a) restoration of normoglycemia after insulin-induced hypoglycemia is primarily due to a compensatory increase in glucose production; (b) intact glucagon secretion, but not growth hormone secretion, is necessary for normal glucose counterregulation, and (c) adrenergic mechanisms do not normally play an essential role in this process but become critical to recovery from hypoglycemia when glucagon secretion is impaired.
| 36,413
|
Effect of naloxone on the sensitivity of the vas deferens to various agonists.
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The effect of naloxone in vitro, on noradrenaline (NA)-induced responses in guinea-pig isolated vas deferens was studied. The responses of NA were potentiated by naloxone (3 microM). It potentiated the responses to methoxamine which has least affinity for uptake sites. Responses induced by acetylcholine and potassium chloride were also potentiated by naloxone. Low calcium (0.8 mM) in the medium antagonized the potentiating action of naloxone. It is suggested that naloxone produces non-specific potentiation, by promoting calcium influx at the post-synaptic site.
| 36,460
|
More acidic metabolites of delta1-tetrahydrocannabinol isolated from rabbit urine.
|
The in vivo metabolism of delta1-tetrahydrocannabinol (delta1-THC) was further investigated in the rabbit after i.v. administration. Nine acidic metabolites were isolated from a previously not investigated fraction of the urine and identified by gas chromatography-mass spectrometry and by proton magnetic resonance spectroscopy. The major metabolites were side-chain hydroxylated monocarboxylic acids. Three side-chains monocarboxylic acids hydroxylated in allylic positions in the isoprene moiety were also characterized. The metabolites 4''-hydroxy-delta1-THC-7-oic acid and 7-hydroxy-4'',5''-bisnor-delta1-THC-3''-oic acid were hitherto not identified. An earlier described dicarboxylic metabolite was present in high concentration. Further, the identity of an O-glucuronide as an in vivo urinary metabolite of delta1-THC was here for the first time unambiguously established by m.s. and p.m.r.
| 36,463
|
Effects of procaine on the ventricular muscle of bullfrog.
|
The effects of procaine on the contractility of the bullfrog's ventricular muscle were investigated. The addition of 10(-5) g/ml of procaine potentiated the twitch tension which was accompanied by an elevation as well as a prolongation of the action potential plateau. This positive inotropism of procaine was not induced by endogenous catecholamine because a beta-blocking agent did not influence this twitch potentiation. The twitch potentiation was increased in proportion to the external Ca concentration, suggesting the possibility of augmentation of Ca influx during the action potential. In normal Ringer solution, procaine suppressed potassium contracture which was composed of two components: an initial phasic component and a late tonic one. Potassium contracture after perfusion with Ca-free solution was also suppressed by procaine. However, potassium contracture which had been treated previously with La was composed of only a tonic component and was potentiated by procaine in spite of perfusion with Ca-free solution. The tonic component of potassium contracture may be considered to occur with intracellular Ca. Procaine may increase the Ca inward current, acting on the intracellular Ca storage site and consequently accelerate the excitation-contraction coupling in frog ventricular muscle.
| 36,489
|
[Dislocations of the talus (author's transl)].
|
Authors analysing 31 case histories of talus fractures and following the results in 22 cases over a period of 3--12 years support the general view, that the healing of such injuries is satisfactory but partial or even total necrosis may occur. They emphasize the importance of X-ray investigation and occasional phlebography in order to clear up the state of circulation in the bone. Weight bearing should be decided in accordance with these examinations.
| 36,506
|
[The part taken by X-ray investigation for closed soft tissue injuries on the extremities (author's transl)].
|
Special X-ray pictures taken of soft tissues for the treatment of closed soft tissue injuries on the extremities, give valuable diagnostic advises. Rupture on the surface of muscles, the lesion to the tendon Achilles and the lig. patellae proprium, tumours, muscle waisting following plexus or periferial nerve lesions etc. by X-ray investigation can be exactly delineated and the site, extension and type of damage defined.
| 36,513
|
Juvenile-onset metachromatic leukodystrophy: biochemical and electrophysiologic studies.
|
A 15-year-old girl with juvenile-onset metachromatic leukodystrophy (MLD) had markedly decreased leukocyte arylsulfatase A activity and low levels of leukocyte beta galactosidase and serum acid phosphatase. There was marked slowing of nerve condition velocity, and metachromasia was seen in biopsied sural nerve. Leukocyte arylsulfatase A activity was decreased in all members of the girl's family, and sural nerve action potentials were abnormal in two asymptomatic siblings. Electrophysiologic studies combined with biochemical studies may aid in the identification of presymptomatic metachromatic leukodystrophy homozygotes or asymptomatic heterozygotes.
| 36,575
|
From extracellular to intracellular: the establishment of mitochondria and chloroplasts.
|
Paracoccus and Rhodopseudomonas are unusual among bacteria in having a majority of the biochemical features of mitochondria; blue-green algae have many of the features of chloroplasts. The theory of serial endosymbiosis proposes that a primitive eukaryote successively took up bacteria and blue-green algae to yield mitochondria and chloroplasts respectively. Possible characteristics of transitional forms are indicated both by the primitive amoeba, Pelomyxa, which lacks mitochondria but contains a permanent population of endosymbiotic bacteria, and by several anomalous eukaryotic algae, e.g. Cyanophora, which contain cyanelles instead of chloroplasts. Blue-green algae appear to be obvious precursors of red algal chloroplasts but the ancestry of other chloroplasts is less certain, though the epizoic symbiont, Prochloron, may resemble the ancestral green algal chloroplast. We speculate that the chloroplasts of the remaining algae may have been a eukaryotic origin. The evolution or organelles from endosymbiotic precursors would involve their integration with the host cell biochemically, structurally and numerically.
| 36,620
|
The Rhizobium--legume symbiosis.
|
The rhizobia are soil microorganisms that can interact with leguminous plants to form root nodules within which conditions are favourable for bacterial nitrogen fixation. Legumes allow the development of very large rhizobial populations in the vicinity of their roots. Infections and nodule formation require the specific recognition of host and Rhizobium, probably mediated by plant lectins. Penetration of the host by a compatible Rhizobium species usually provokes host root cell division to form the nodule, and a process of differentiation by both partners then ensues. In most cases the rhizobia alter morphologically to form bacteroids, which are usually larger than the free-living bacteria and have altered cell walls. At all stages during infection, the bacteria are bounded by host cell plasmalemma. The enzyme nitrogenase is synthesized by the bacteria and, if leghaemoglobin is present, nitrogen fixation will occur. Leghaemoglobin is a product of the symbiotic interaction, since the globin is produced by the plant while the haem is synthesized by the bacteria. In the intracellular habitat the bacteria are dependent upon the plant for supplies of energy and the bacteroids, in particular, appear to differentiate so that they are no longer able to utilize the nitrogen that they fix. Regulation of the supply of carbohydrate and the use of the fixed nitrogen thus appear to be largely governed by the host.
| 36,624
|
Effect of desglycinamide(9)-lysine(8)-vasopressin and prolyl-leucyl-glycinamide on oral ethanol intake in the rat.
|
Rats given ethanol in their drinking water at a concentration that permitted adequate fluid intake gradually accepted higher concentrations and consumed larger amounts of ethanol. These increases were augmented when daily subcutaneous injections of 1 microgram of desglycinamide9-lysine8-vasopressin (DGLVP) or 10 microgram of prolyl-leucyl-glycinamide (PLG) were given concomitantly. Nonsignificant changes in ethanol consumption were seen with injections of 1 microgram PLG, or 0.42 or 42 microgram of lysine8-vasopressin (LVP). In a second experiment 4 microgram DGLVP given every second day as a long-acting zinc phosphate complex, commencing after the increases in ethanol intake had taken place, failed to produce any change in ethanol consumption subsequently. In both Experiments 1 and 2, the rats were switched from forced ethanol intake to a choice between ethanol and tap water. On these tests there was only marginal evidence of peptide-produced changes in ethanol intake.
| 36,634
|
[Endoscopic diagnosis and therapy of colorectal tumours (author's transl)].
|
1. If endoscopy leads to the suspicion of an exulcerated and/or polypous carcinoma of the colon, surgical intervention is the primary therapy. Histological classification of the tumour should be effected by means of endoscopic biopsy. 2. (Familial) adenomatosis of the colon requires colectomy. 3. Broad-based polypi resembling a lawn where a large wound area must be expected by electrocoagulation (risk of perforation), and pediculate polypi of the (rare) size of 3 cm and more (risk of haemorrhage) should not be resected via endoscopy but by surgery. 4. Solitary or multiple polypi of the colon not covered by points 1 to 3 above, are primarily for reasons of diagnosis an indication for endoscopic polypectomy. Biospy in the case of adenomas to clarify the histological structure and to obtain qualitative and quantitative information regarding malignant degeration, must be discouraged (""partial diagnosis''.) 5. Basing on the current state of knowledge it is assumed that effective prohylaxis of cancer is achieved by the endoscopic removal of benign adenomas of the colon. 6. It is also assumed that effective cancer therapy can be realised by the endoscopic removal of adenomas which have already undergone malignant degeration (adenoma with severe cellular atypia, invasive differntiated adenocarcinoma in the head of the adenoma.)
| 36,656
|
Embryonic development of identified neurons: temporal pattern of morphological and biochemical differentiation.
|
Individually identified neurons can be recognized in grasshopper embryos, and are accessible to examination by morphological, physiological, and biochemical techniques from their birth to their maturation. Only after the axon of an identified neuron reaches its postsynaptic target does the neurotransmitter accumulate, the soma rapidly enlarge, and the central arborizations greatly expand.
| 36,661
|
Food deprivation increases oral and intravenous drug intake in rats.
|
Rats given continuous access to etonitazene hydrochloride in their drinking water (5 micrograms per milliliter) more than doubled their drug intake while deprived of food. Another group of rats with implanted jugular catheters self-administered etonitazene (10 micrograms per kilogram) intravenously on a continuous reinforcement schedule, and the number of infusions increased significantly on days when they were deprived of food. These results suggest that feeding condition may be a powerful determinant of drug-reinforced behavior.
| 36,665
|
Orchidopexy in cryptorchidism assessed by clinical, histologic and sperm examinations.
|
A study was undertaken of 187 patients with unilateral and 41 patients with bilateral cryptorchidism before and after orchidopexy. The mean tubular diameter and the mean tubular fertility index were used as quantitative criteria for assessment of the development of the testes. Before orchidopexy, no significant differences were found between scrotal and cryptorchid testes in patients up to six years of age. Thereafter, the scrotal testis showed marked development in distinction to the cryptorchid testis. After orchidopexy, follow-up examinations were carried out when the patients had reached the age, at least, 18 years. Based on the results of the mean tubular diameter and the mean tubular fertility index, a reasonable degree of fertility would be expected in both the unilateral and the bilateral cryptorchid testes. However, histologic assessment of spermatogenesis in the unilateral cryptorchid testes after orchidopexy showed spermatogenic arrest in 81 per cent and in all patients with bilateral cryptorchid testes after orchidopexy. In the unilateral orchidopexy patients, in distinction to the histologic assesment of spermatogenesis, sperm counts gave good results in 80 per cent; evidently, in these patients, the source of the spermatozoa was the contralateral scrotal testis. That spermatogenesis was defective in 20 per cent of the patients after unilateral orchidopexy suggests and underlying systemic factor affecting both testes.
| 36,676
|
Gastroesophageal reflux and pulmonary aspiration: incidence, functional abnormality, and results of surgical therapy.
|
The incidence of aspiration, the causative esophageal pathophysiology, and the results of surgical therapy were evaluated in 100 patients with abnormal gastroesophageal reflux documented by 24-hour esophageal pH monitoring. Based on historical evidence, 48 patients were suspected to be aspirators. Eight patients had documented episodes of aspiration (drop on esophagela pH, followed by acid taste in mouth and onset of cough or wheezing spell) during the monitoring period. Nine patients were considered to be potential aspirators because they presented oral acid regurgitation without development of pulmonary symptoms. In five patients a primary respiratory disorder (PRD) induced gastroesophageal reflux. The remaining 78 patients had abnormal reflux without aspiartion or regurgitation. Aspirators had a 75% incidence of esophageal motor abnormality on manometry, and the clearance of refluxed acid was significantly delayed in the supine position. A history of heartburn and endoscopic evidence of esophagitis were present in only half of the patients who were documented aspirators. Potential aspirators were spared from aspiration by rapid esophageal clearance of refluxed acid unaffected by changes in body position. Patients with a PRD had higher distal esophageal segment (DES) pressure and normal esophageal motility with minimal esophagitis. Nonaspirators significantly improved their clearance while in the supine position, emphasizing the protective effect of esophageal peristalsis against aspiration. An antireflux procedure in five aspirators raised the DES pressure significantly and returned the reflux status to normal by 24-hour pH-monitoring standards. The incidence of aspiration appears to be less than that suspected by history and is due to a motor disorder that interferes with the ability of the esophagus to clear reflex acid. Abnormal pulmonary symptoms can induce or result from gastroesophageal reflux and, when the latter occurs, an antireflex procedure stops both reflux and aspiration.
| 36,677
|
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