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Stimulation by cyclic GMP of sodium efflux in barnacle muscle fibres.
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1. The ouabain-insensitive Na efflux in barnacle muscle fibres is promptly stimulated by injection of cyclic GMP. The minimal effective injected concentration is found to be about 10(-7) M. This effect of cyclic GMP could not be mimicked by injecting 5'-GMP. 2. External application of ouabain (10(-4) M) to fibres not pretreated with ouabain during the stimulatory response to cyclic GMP causes some inhibition of the Na efflux indicating that cyclic GMP does not cause appreciable inhibition of the Na:K pump. 3. The magnitude of the stimulatory response to injected cyclic GMP depends on the external Ca2+ concentration, as well as pHe but not on the Na+, K+ or Mg2+ concentration. It also depends on pHi, since acidification of HCO3-containing ASW leads to a greater enhancement of the response to cyclic GMP than is observed with acidified HERPES-ASW. 4. Stabilization of myoplasmic pCa by injecting 100 mM-EGTA before or after cyclic GMP fails to alter the magnitude of the response to the nucleotide. Enrichment of the fibre with Mg2+ at the time of injection of cyclic GMP leads to a reduced response. No change in response, however, is seen when the internal free Mg concentration is suddenly reduced by injecting 0.05 M-pyrophosphate with cyclic GMP. 5. Injection of cyclic GMP-dependent protein kinase stimulatory modulator before cyclic GMP fails to enhance the response to the nucleotide. The same is true of the phosphodiesterase inhibitor protein. However pre-injection of 10(-2) M-papaverine enhances the response to a subsequent injection of 10(-3) M-cyclic GMP. 6. Injection of pure protein kinase inhibitor (1.6 x 10(-4) M) before 10(-3) M-cyclic GMP reduces the response to the nucleotide. 7. The argument is put forward that injected cyclic GMP stimulates the ouabain-insensitive Na efflux mainly by activating cyclic AMP-protein kinase rather than cyclic GMP-proton kinase.
| 41,090
|
The nature of the negative endocochlear potentials produced by anoxia and ethacrynic acid in the rat and guinea-pig.
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1. The alterations in the Na+ and K+ concentrations of the cochlear endolymph and in the endocochlear potential were followed simultaneously by means of ion-sensitive and conventional micro-electrodes during simple anoxia, during anoxia after i.v. ethacrynic acid and after i.v. ethacrynic acid alone. The endolymphatic pH changes were measured separately and the effect of perilymphatic ethacrynic acid upon the endocochlear potential was investigated. 2. The over-all Na+:K+ permeability ratio for the endolymph system was determined in individual animals for the first time using an indirect method. The normal mean values of 0.27 (rat) and 0.38 (guinea-pig) were increased after ethacrynic acid. Permeability changes occurred during anoxia but were delayed in onset. 3. The negative endocochlear potentials in each situation behaved quantitatively like modified K+ diffusion potentials largely dependent upon the K+ and Na+ gradients between endolymph and perilymph.
| 41,092
|
Circumventing the Henderson-Hasselbalch equation.
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Prompt blood-gas analysis consisting of pH, PCO2, and PO2 is now almost universally accessible. PCO2 directly conveys the role of the respiratory mechanism in any acid-base disturbance. The metabolic condition, however, is hidden in a relationship between pH and PCO2 that is most faithfully expressed by the cumbersome Henderson-Hasselbalch equation (HHE). Two methods of quickly determining metabolic status from pH and PCO2, without resorting to the HHE, are discussed. The first method is well known and adjusts pH to represent only metabolic state by quantitatively cancelling the influence of hyper- or hypoventilation. The second method, not previously reported, uses measured pH to estimate the ratio [HCO3-]/PCO2, which, when multiplied by PCO2, equals bicarbonate ion concentration.
| 41,124
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[Characteristics of the changes in the intra- and extracellular K+ and Na+ concentrations and the intra- and extracellular pH in the area of cardiac ishemia in experimental myocardial infarct complicated by ventricular fibrillation].
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Localized ischemia of the heart complicated by ventricular fibrillation is characterized by a tendency to a higher rate of decrease in intra- and extracellular K+ gradient and intracellular pH in the myocardium as compared to cases without fibrillation. The higher rate of K+ escape from the ischemic cells may be linked with a sharper intracellular oxidation, evidence of which is the correlative dependence between the severity of disorders of K+ balance and decrease in intracellular pH in the myocardium in ischemia.
| 41,134
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Quinacrine-binding nerves: presence in the mouse ano-coccygeus muscle, disappearance after muscle transsection.
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The anococcygeus muscle exhibits non-cholinergic, non-adrenergic, inhibitory neurotransmission. In the present paper we describe the presence of quinacrine-binding beaded nerve fibres in the mouse anococcygeus muscle. A large number of fibres were running parallel to the smooth muscle bundles. A second distribution of fibres formed an irregular plexus. No quinacrine-binding nerve cell bodies were found within the muscle. When the anococcygeus muscle was cut close to its insertion in the rectum, the proximal part lost most of its quinacrine-binding nerves 2-7 days after transsection. The results demonstrate a correlation between presumed non-cholinergic non-adrenergic neurotransmission and quinacrine-binding nervous elements.
| 41,143
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Interferon and cytotoxic factor (cytotoxin) released in the blood of mice infected with Mycobacterium bovis BCG. I. Enhanced production of interferon and appearance of cytotoxin stimulated by capsular polysaccharide of Klebsiella pneumoniae or bacterial lipopolysaccharide.
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Interferon production stimulated by the active substance (neutral fraction) of the capsular polysaccharide of Klebsiella pneumoniae (neutral CPS-K) in BCG-infected mice was compared with that by bacterial lipopolysaccharide (LPS). Prior infection with BCG increased the responsiveness of mice to the lethal effect of neutral CPS-K as well as to that of LPS. Associated with this, BCG-infected mice showed a markedly enhanced ability to produce interferon after stimulation not only by LPS but also by neutral CPS-K. In addition, a cytotoxic factor (cytotoxin) was found to be released in the serum of BCG-infected mice after injection of these inducers. The kinetics of production of interferon and cytotoxin stimulated by neutral CPS-K were very similar to those stimulated by LPS. The time pattern of cytotoxin production was not in parallel with that of interferon production. Interferon reached a peak 2 hr and cytotoxin 3 hr after injection with these inducers. Interferon and cytotoxin produced by neutral CPS-K showed essentially the same stabilities to heating at 56 C and to treatment at pH 2 respectively as those produced by LPS. Interferon was inactivated by heating at 56 C more rapidly than cytotoxin. Cytotoxin was inactivated by treatment at pH 2 for 24 hr, whereas interferon activity was well preserved after this treatment. These results suggest that both activities are the result of different substances.
| 41,163
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[Proteolytic enzymes produced by Aspergillus ochraceus in relation to their plasma coagulating and fibrinolytic activities].
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The paper describes some properties of coagulases and fibrinolytic enzymes isolated from a proteolytic complex produced by Aspergillus ochraceus HP-19 during submerged cultivation on a synthetic medium. Proteolytic enzymes with the plasmocoagulating activity hydrolyzed casein at the maximum rate at 45 degrees C and pH 8.0--10.0. The coagulases were stable at pH 5.0--7.0 and were rather resistant to low pH values. The enzymes were entirely inactivated at 55 degrees C within 20--30 min. The activity of the coagulases was inhibited with the ions of Cu, Co, Ag, Pb, Mn, Zn and Hg (1.10(-3) M) by 100, 91, 85, 50, 50, 38 and 25%, respectively. The coagulases were entirely inhibited with EDTA whereas PCMB and PMSF inhibited their activity only to a small extent. The mechanism for blood clotting with the coagulases of Aspergillus ochraceus HP-19 is presumed to consist in the activation of protrombin via its limited specific proteolysis. The fibrinolytic enzymes of Aspergillus ochraceus HP-19 had the optimal pH 8.5 for casein, were stable at pH 6.0, and entirely inactivated at 55 degrees C within 5 min. In contrast to coagulases, they were resistant to the action of heavy metal ions. The enzymes were stabilized by the ions of Ca. The activity of the fibrinolytic enzymes of Aspergillus ochraceus HP-19 was completely inhibited with PMSF. Therefore, they belong to the class of serine proteases.
| 41,165
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Antidepressant and antipsychotic agents.
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Numerous studies have been reviewed concerning the relationship of the catecholamines and indoleamines to depression and its treatment with antidepressant drugs. The profusion of data on the subject suggests the amines may be implicated in the disease, however no convincing hypothesis is available which unites the two. A similar situation seems to exist concerning the antipsychotic agents, dopamine and schizophrenia. The evidence appears to be overwhelming relating dopamine in the action of these agents and yet serious inconsistencies have been reported suggesting the need for a revision of the hypothesis regarding the mode of action of antipsychotic agents.
| 41,188
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Alpha adrenoceptors in rat brain: direct identification with prazosin.
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Tritiated prazosin was used to characterize high affinity binding sites with characteristics similar to alpha 1 adrenoceptors in rat brain membranes. These sites were compared with alpha 2 adrenoceptors labeled with tritiated clonidine. The prazosin sites had an association constant of 2 nM-1 and bound to ligand optimal around pH 7.0. The density of the sites was 300 fmoles per mg of protein; the half time of dissociation of prazosin was 7 min at 30 degrees C. The order or potencies of agonists, determined from binding-inhibition experiments with labeled prazosin, was: naphazoline greater than clonidine greater than adrenaline greater than noradrenaline greater than phenylephrine greater than alpha-methylnoradrenaline greater than dopamine. The order of potencies of antagonists was: prazosin greater than phenoxybenzamine greater than phentolamine greater than clozapine greater than yohimbine. Sodium ions and divalent cations as well as guanyl nucleotides have little or no effect on the binding of the labeled antagonist. This is in contrast to the binding of the labeled agonist clonidine (Glossmann and Presek, 1979a, 1979b). Labeled prazosin may be a useful tool to characterize alpha 1 adrenoceptors.
| 41,192
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Dopaminergic antagonism of L-5-hydroxytryptophan-induced myoclonic jumping behavior.
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We studied the effect of dopamine agonists (levodopa, apomorphine, lergotrile, and M-7 [2(dimethylamino)5,6-dihydroxytetralin] on myoclonic jumping behavior in young male guniea pigs. All these agents had a significant antagonistic effect on the frequency of this serotonin-mediated behavior. The duration of the antagonism corresponded in all cases to the duration of stereotyped chewing behavior induced by these agents alone. The dopamine antagonist haloperidol potentiated jumping behavior. Therefore myoclonic jumping behavior is influenced by dopaminergic mechanisms, and this behavior may be the result of interaction between dopaminergic and serotonergic activity. The role of dopaminergic mechanisms in human myoclonic disorders needs further clarification.
| 41,197
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Controlled intravenous bicarbonate and fetal-maternal acid-base balance. I. The primipara.
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The effects of a controlled sodium bicarbonate (SB) infusion on the acid-base balance of the primiparous mother and fetus at labor and delivery were evaluated. Two identical groups of primiparas with normal labor and delivery were studied. According to acid-base parameters observed in the mothers and fetuses of a control group, the pharmacologic dynamics, and the space of distribution of SB, 2 mEq/1 kg of total body weight were administered to the mothers of the study group, beginning at a cervical dilation of 6 cm until full dilation occurred. Highly significant changes in pH, base excess (BE), and plasma bicarbonate were observed in both the mothers and fetuses. In the latter, the significant changes appeared after a time lag of about 2 hours. No adverse effects in the mothers and fetuses were observed. The significant reduction of the relative fetal acidosis by the controlled SB infusion justifies further studies on the therapy potentials of this method in high-risk deliveries and during intrapartum fetal distress.
| 41,200
|
Effect of chronic reserpine administration on K+ and amylase release from the rat parotid gland.
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After chronic administration of reserpine, slices of the rat parotid gland incubated in vitro were found to release significantly more K+ and significantly less amylase than similar slices from untreated control animals. The extent of K+ release in the gland slices of the drug-treated animals shows no dependency on external Na+ or Ca++ and is probably enhanced because of a decreased activation of K+ uptake by the Na+-K+ pump. This effect may also involve a defective generation of cyclic GMP, which was found to enhance K+ uptake and, thus, to inhibit K+ release in control slices. The inhibition of amylase release observed after treatment with reserpine most likely results from a deficient level or utilization of the energy or nucleotide sources required for enzyme secretion, because a similar inhibition was observed in control slices after incubation in the absence of the purines inosine and adenine. These results indicate that chronic reserpine administration impairs the stimulus-secretion coupling mechanism in the rat parotid gland and results in abnormal responses from both alpha and beta adrenergic receptors.
| 41,213
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Stability of the unique anticodon loop conformation of E.coli tRNAfMet.
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Initiator tRNAs have an anticodon loop conformation distinct from that of elongation tRNAs as detected by susceptibility to S1 nuclease. We now find the anticodon loop conformation of E. coli tRNAfMet to be stable under different salt conditions as detected by using S1 nuclease as a structural probe. In contrast, a conformational change is observed in the T- and D- loop of this tRNA in the absence of added Mg2+. This change can be suppressed by spermine. Even under those conditions effecting a change in T- and D- loop conformation, the anticodon loop does not change. This suggests that the conformational shift is controlled by Mg2+ and restricted to the D- and T- loop region only without affecting the anticodon domain. The use of S1 nuclease as a conformational probe requires the use of kinetic studies to determine the initial cleavage sites. Thus, the use of a strong inhibitor which immediately stops the action of this nuclease is necessary. ATP is shown to be such an inhibitor.
| 41,223
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Nitrogen control in Salmonella: regulation by the glnR and glnF gene products.
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The product of the glnR gene is required for nitrogen regulation of the synthesis of glutamine synthesis (Gln synthetase) [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] and two periplasmic transport proteins that are subject to nitrogen control in Salmonella. Strains with mutations to loss of function of the glnR product [e.g., a strain with a Tn10 insertion or one with an ICR-induced (frameshift) mutation in glnR] have about 3% as much Gln synthetase as a fully derepressed wild-type strain and are unable to increase synthesis of this enzyme or periplasmic transport proteins in response to nitrogen limitation. The structural gene for Gln synthetase, glnA, and those for the periplasmic transport proteins are unlinked on the chromosome; thus, glnR appears to encode a diffusible positive regulatory element. Consistent with this, the mutant glnR allele is recessive to the wild-type allele with regard to expression of glnA (synthesis of Gln synthetase). Although glnR is closely linked to glnA, strains with mutations to complete loss of function of the glnR product can be distinguished from glnA strains by their ability to produce detectable Gln synthetase and to grow in the absence of glutamine. To demonstrate unequivocally that glnR is distinct from glnA, we have purified and characterized Gln synthetase from a strain with a Tn10 insertion in glnR. Because the properties of Gln synthetase from the insertion mutant, most importantly the carboxyl-terminal sequence of amino acids, are the same as those of synthetase from wild type, the Tn10 insertion cannot be in glnA (if it were, the carboxyl terminus of Gln synthetase would have to be altered); therefore we conclude that the Tn10 insertion is in a regulatory gene, glnR, which is distinct from glnA. A model for the function of the glnR product together with the previously defined glnF product in mediating nitrogen control is discussed.
| 41,244
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Partial anxiolytic action of morphine sulphate following microinjection into the central nucleus of the amygdala in rats.
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In the social interaction test of anxiety, bilateral microinjections of morphine sulphate (10 microgram) into the central nucleus of the amygdala counteracted the reduction in social interaction normally seen when the test arena is unfamiliar to rats. However, these injections did not counteract the decrease in social interaction that is observed as illuminance of the arena is increased. Morphine injections into the medial site depressed social interaction below the levels shown by control animals. In the open field test, morphine produced a facilitation of peripheral activity when injected into the central nucleus whilst a decrease in rearing was observed following similar injections into the medial nucleus. Overall, these data indicate a partial anxiolytic action of morphine in the central amygdaloid nucleus. Results are discussed in relation to possible differences in opioid peptide innervation of these two amygdaloid nuclei.
| 41,266
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Intraventricular self-administration of acetaldehyde, but not ethanol, in naive laboratory rats.
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For 11 consecutive days, naive rats were maintained in operant chambers where they were given the opportunity to self-administer acetaldehyde (1,2, or 5% v/v), ethanol (2 or 10% v/v), or pH control solutions directly into the cerebral ventricles. Only the animals that had access to the 2 and 5% acetaldehyde solutions showed rates of lever pressing significantly higher than controls. It is suggested that acetaldehyde rather than ethanol itself may mediate the positive reinforcing effects of ethanol in the brain.
| 41,277
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The isoelectric point of thrombin and its behaviour compared to prothrombin at some solid surfaces.
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We have shown that the isoelectric point of thrombin is high and that thrombin is a cation at the pH of blood. On the other hand, prothrombin has a low isoelectric point, being more anionic at the pH of blood. It was also found that thrombin adsorbs readily to surfaces, especially negatively charged surfaces, like behenic acid surfaces at pH 8.2. Furthermore, thrombin adsorbed onto behenic acid was active in the sense that it coagulated fibrinogen. The significance of the electric charge of the thrombin molecule in the mechanism of atherosclerosis is discussed.
| 41,337
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Effect of substance P on CCK- or VIP-induced choleresis in anesthetized dogs.
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10 anesthetized dogs were provided with acute common bile duct fistulas and the gallbladder was excluded. Hepatic bile output and biliary content of sodium, potassium and amylase were studied. 6 caval infusions were administered of CCK, 0.3 Ivy U.kg-1.min-1, with a superimposed infusion of SP, 20 ng.kg-1.min-1. 7 caval infusions were given of VIP, 50 ng.kg-1.min-1, with a superimposed infusion of SP, 20 ng. kg-1.min-1. CCK increased bile output and biliary content of sodium, potassium and amylase by 78-110%. The corresponding increase induced by VIP was 55-85%. Biliary pH was not influenced. SP abolished the effects of both CCK and VIP. It is suggested that all peptides studied influenced canalicular bile secretion by changing the electrolyte excretion.
| 41,410
|
Latent herpesvirus hominis 1 in the central nervous system of psychotic patients.
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Cerebrospinal fluids (CSF) from 35 patients with senile or presenile dementia and from 13 patients with schizophrenia and related syndromes were examined in cell cultures with the aim to isolate Herpesvirus hominis 1 (HVH 1) or other viruses. Serum and CSF antibodies to HVH 1 and/or interferon in the patients indicated a recent HVH 1 antigenic or viral activity. In the CSF of two senile demented patients and of one patient with schizoaffective psychosis, agents of low virulence, causing a cytopathic effect in 3 or 4, but not more, subsequent passages were detected and identified as HVH 1 by immunofluorescence. A focus of cells containing HVH 1 antigen at the cell membrane and in cytoplasm was visualized by immunofluorescence in an explant from nucleus amygdalae from 1 of 6 patients with schizophrenia and related syndromes examined. In the original biopsy materials, various virus-like structures were found in nuclei and cytoplasm of astrocytes and neurocytes and in axons in the neuropil.
| 41,436
|
Pharmacokinetics and metabolism of various benzodiazepines used as hypnotics.
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1 In the management of insomnia with drugs, any action should be restricted to the duration of the night and residual effects should be absent during the day-time. The intermittent type of drug action desired is fundamentally different from drug treatment where a constant effect is sought. 2 Duration of drug action is dependent on the kinetics of distribution and elimination of the parent drug and its effective metabolites. In addition biopharmaceutical factors, such as those which promote a rapid rate of absorption, are important. 3 These considerations serve as a guide for a review of the kinetics and metabolism of various benzodiazepines.
| 41,545
|
Influence of biogenic amines on the growth of xenografted human colorectal carcinomas.
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The influence of some biogenic amines and amine-receptor-blocking drugs in the growth rate of human colorectal carcinomas propagated as s.c. xenografts in immune-deprived mice was studied. In mice treated with adrenaline, a beta-adrenergic agonist, the growth of xenografts was suppressed for 2 days, after which growth was resumed at a rate similar to that in control animals. Treatment with the phosphodiesterase inhibitor theophylline prolonged the adrenaline-induced inhibition of growth. Treatment with the beta-adrenergic antagonist sotalol or practolol increased the rate of tumour growth. Treatment with either serotonin or the histamine H2-receptor agonist Dimiprit had no effect on tumour growth rate. However, the antiserotoninergic drug BW 501C and the histamine H2-receptor antagonist cimetidine each caused short-term suppression of tumour growth.
| 41,563
|
[Mitochondrial transhydrogenase: general principles of functioning].
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A new mechanism for the functioning of mitochondrial transhydrogenase has been proposed. This mechanism makes it possible, without additional postulates, to explain the generation of delta muH+ of different signs in the forward and reverse transhydrogenase reactions and why this generation is not accompanied by the membrane uncoupling. It is suggested that the reduced nicotinamide rings of NADH and NADPH participate in a relay transfer of H+ ions across the membrane, while the oxidized nicotinamide rings of NAD+ and NADP+ block the H+-transporting paths in the transhydrogenase.
| 41,597
|
Induction of foci of altered hepatocytes by a single injection of azaserine to rats.
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The induction of foci of altered, gamma-glutamyltranspeptidase (GGT)-positive hepatocytes by azaserine was investigated. After injection of a single dose of azaserine, many foci developed in male Wistar rats fed a choline-devoid (CD) diet containing acetylaminofluorene (AAF), but only a few in rats fed a choline-supplemented (CS) diet containing AAF. Similar results were obtained in rats fed a plain CD diet or a plain CS diet and injected with a single dose of azaserine after a partial hepatectomy. These findings indicate that azaserine is an effective initiator of liver carcinogenesis in rats, and that a CD diet acts as a strong promoter of the evolution initiated liver cells to foci of altered, GGT-positive hepatocytes.
| 41,634
|
New experiments of biotin enzymes.
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The objects of structural studies on biotin-enzymes were acetyl CoA-carboxylase and pyruvate carboxylase of Saccharomyces cerevisiae and beta-methylcrotonyl CoA-carboxylase and acetyl CoA-carboxylase of Achromobacter IV S. It was found that these enzymes can be arranged in three groups. In the first group, as represented by acetyl CoA-carboxylase of Achromobacter, the active enzyme could be resolved in three types of functional components: (1) the biotin-carboxyl carrier protein, (2) the biotin carboxylase, and (3) the carboxyl transferase. In the second group, as represented by beta-methylcrotonyl CoA-carboxylase from Achromobacter only two types of polypeptides are present. The one carries the biotin carboxylase activity together with the biotin-carboxyl-carrier protein, the other one carries the carboxyl transferase activity. In this third group, as represented by the two enzymes of yeast, all three catalytic functions are incorporated in one multifunctional polypeptide chain. The evolution of the different enzymes is discussed. The animal tissues acetyl CoA-carboxylase is under metabolic control, as known from previous studies. It thus has to be expected that the levels of malonyl CoA in livers of rats in all states of depressed fatty acid synthesis are much lower than under normal conditions because the carboxylation of acetyl CoA is strongly reduced and cannot keep pace with the consumption of malonyl CoA by fatty acid synthetase. A new highly sensitive assay method for malonyl CoA was developed which uses tritiated NADPH and measures the incorporation of radioactivity into the fatty acids formed from malonyl CoA in the presence of purified fatty acid synthetase. The application of this method to liver extracts showed that the level of malonyl CoA which amounts to about 7 nmoles per gram of wet liver drops to less than 10% within a starvation period of 24 hr and even further if the starvation period is extended to 48 hr. A low malonyl CoA concentration is also found in the alloxan diabetic animals and in animals being fed a fatty diet after starvation. On the other hand, feeding a carbohydrate rich diet leads to malonyl CoA levels surpassing the levels found after feeding a balanced diet. These observations reconfirm the concept that fatty acid synthesis is principally regulated by the carboxylation of acetyl CoA.
| 41,682
|
The significance of 2,3-DPG in red blood cell transfusions.
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This review will begin by giving the highlights of the history and explain development of the basic science knowledge of hemoglobin chemistry, function, and physiology. The necessary involvement of red cell metabolism, as it pertains to the maintenance of 2,3-diphosphoglycerate (2,3-DPG) levels, both normally and under the perturbed and experimental conditions of blood storage, will be given as part of the basic science data. The clinical science and transfusion data will comprise the main critical aspects of the paper. Analysis and comment of over 20 studies will be given on the effects of animal and human transfusions with altered 2,3-DPG levels. Decreased survival and organ function have been demonstrated with transfusion of low 2,3-DPG red cells, with or without anemia, in the conditions of exercise, shock, hypotension, ischemia, cardiac surgery, hypoxia, sepsis, and acidosis. By critical analysis of these studies, recommendations on general and specific patient needs for red cell transfusions with normal or high 2,3-DPG levels are given.
| 41,684
|
[Gastroesophageal reflux: a factor eliciting esophageal variceal hemorrhage?].
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Following a hemorrhage, ten patients with esophageal varices were examined by means of gastroscopy and functional analysis of the esophagus with special regard to gastroesophageal reflux. A pathological gastroesophageal reflux was not confirmed. These results plus previously published findings lead to the assumption that reflux is of not importance in the initiation of esophageal variceal bleeding.
| 41,687
|
Screening in diabetes mellitus: report of the Atlanta workshop.
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A Diabetes Screening Workshop was held in Atlanta, Georgia, May 15--17, 1978, which was sponsored by the Center for Disease Control, the American Diabetes Association, and the National Institute of Arthritis, Metabolism, and Digestive Diseases. The workshop formulated the following recommendations for the use of screening procedures in diabetes mellitus from a community control viewpoint: (1) screening for asymptomatic glucose intolerance should be done among pregnant women as part of a well-coordinated program to decrease perinatal morbidity and mortality; (2) screening programs to detect asymptomatic glucose intolerance per se are not recommended as health services in nonpregnant populations; (3) screening for diabetes or its complications for research purposes should be done only as part of well-designed studies focusing on identification of predictive factors, implementation and effectiveness of preventive and therapeutic measures, descriptive epidemiology in selected populations, dynamic and economic factors of the medical care system related to case detection and management, and the nature and effects of screening processes; (4) information and education programs for health care providers, parents, and the general public should be implemented to bring about increased awareness of the clinical signs and symptoms of diabetes; and (5) all persons known to have diabetes should be evaluated regularly for the detection and management of the common chronic complications of the disease.
| 41,691
|
Procollagen processing. Limited proteolysis of COOH-terminal extension peptides by a cathepsin-like protease secreted by tendon fibroblasts.
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An enzymatic activity, capable of removing the COOH-terminal extensions of type I chick procollagen, has been demonstrated in embryonic chick tendons and in cultured tendon fibroblasts utilizing two new methods of analysis. The protease was purified by a combination of ultrafiltration concanavalin A affinity chromatography and gel filtration. The isolated protein has an apparent Mr of 43,000 by gel filtration and sodium dodecyl sulfate gel electrophoresis. The enzyme shows a major pH optimum at 4.2 and is susceptible to inhibitors such as pepstatin and leupeptin; it therefore seems related to the cathepsins. The possibility that this enzyme plays a role in the limited proteolytic processing of procollagen is discussed.
| 41,715
|
The renal effects of clonidine in unanesthetized rats.
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Clonidine s.c. (0.01-0.3 mg/kg), in unanesthetized rats, caused an initial rise (+20 mm Hg), followed by a continuous fall of BP and a dose-dependent natriuresis and diuresis for up to 2 h. Glomerular filtration rate (GFR) (CIn) increased during the first 20 min, while effective renal plasma flow (ERPF) (CPAH) remained normal. Subsequently, between 20 and 60 min after injection, ERPF (CPAH) decreased considerably while GFR had reverted to its normal value. In saline-infused rats clonidine diuresis was accompanied by an "inappropriate" positive free water clearance. Pentobarbital anesthesia suppressed the initial BP peak and the diuresis. Phenoxybenzamine (1 mg/kg i.v.) was antinatriuretic in saline diuresis; the effect of phenoxybenzamine + clonidine on diuresis and salt excretion represented the sum of the effects of both drugs, but phenoxybenzamine enhanced the clonidine-induced increase of GFR. Neither haloperidol (1 mg/kg i.v.) nor bulbocapnine (3 mg/kg i.v.) interfered with the renal effects of clonidine. Clonidine s.c. caused hyperglycemia and glucosuria which did not account for the natriuresis. Clonidine thus appears to increase the GFR and "filtration fraction" (FF) by a phenoxybenzamine-insensitive rise of glomerular ultrafiltration, to depress ERPF by alpha-adrenergic afferent vasoconstriction, to induce natriuresis by a tubular action not blocked by phenoxybenzamine and to exert an antivasopressin effect, either by depressing pituitary vasopressin secretion or the renal response to vasopressin.
| 41,724
|
Tricyclic antidepressants: potent blockade of histamine H1 receptors of guinea pig ileum.
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Six tricyclic antidepressants were tested for their ability to antagonize histamine actions at histamine H1 receptors in a bioassay for these receptors (histamine-induced contractions of guinea pig ileum). All compounds were competitive antagonists with equilibrium dissociation constants in the range of 5.6 x 10(-11) M to 1.5 x 10(-7) M. Doxepin hydrochloride and amitriptyline hydrochloride were the most potent compounds of the series and may be the most potent antihistamines known. Antagonism at histamine H1 receptors by these compounds may explain their sedative effects.
| 41,726
|
Dopamine agonist-induced hyperglycemia in rats: effects of lergotrile mesylate.
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Lergotrile and apomorphine, two direct-acting dopamine agonists, caused marked hyperglycemia in fasted rats, while compounds which release endogenous dopamine (amphetamine, methylphenidate) or inhibit dopamine reuptake (LR5182), failed to elevate blood glucose. The effect of lergotrile was dose dependent, causing blood glucose to rise 3-fold above resting levels at 5 mg/kg (i.p.). Blood glucose increased prior to the onset of the behavioral signs of dopamine stimulation. The effect of lergotrile was attenuated by phentolamine, propranolol or butaclamol. Adrenalectomy also prevented lergotrile-induced hyperglycemia. These data indicate that hyperglycemia is not a property of all compounds that cause dopaminergic effects. The action of lergotrile might be indirect, perhaps mediated through release of catecholamines from the adrenal glands.
| 41,730
|
Amphotericin B induced structural changes of the erythrocyte membrane.
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Incubation of human erythrocytes in isotonic NaCl-sucrose medium with a relative high concentration of amphotericin B results in the occurrence of distinct structures on the membrane faces as visible by freeze-fracturing. Such kind of structures is known to be formed by phase separation of the lipid components (domain formation). The induction of phase separation is considered to be an additional effect of amphotericin B.
| 41,735
|
Direct measurement of the pH in the stomach of the conscious rat, using a special electrode.
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The construction and use of a specially designed electrode to measure gastric pH in the conscious rat is described. Measurement of gastric hydrogen ion activity with this device is rapid and reproducible in starved rats. A dose-related increase of gastric pH was obtained after s.c. injection of the anticholinergic isopropamide.
| 41,736
|
Maternal mortality in an Israeli hospital: a review of 23 years.
|
In spite of great strides in obstetrics, maternal mortality has been completely eliminated. Possible changes in the causes of mortality are examined for three periods of time (1954-1961, 1962-1971 and 1972-1976). The overall incidence was 3.6/10 000, changing through the three periods from 4.9 to 4.3 and finally to 3.0/10 000. Vascular accidents were the cause of death in almost one third of the cases, emerging as the most important etiologic factor. Older age and higher parity did not seem to influence the incidence of obstetric deaths. Cesarean section was involved in ten of 23 cases in which the death was directly related to the pregnancy and delivery. In six patients there was a rupture of the uterus. The number of preventable deaths has decreased steady, but research into the problem of vascular accidents and dampening of the enthusiasm for cesarean sections may further improve the situation.
| 41,762
|
Birth weight, gestational age and other indices of fetal maturity.
|
A number of indices for evaluating the maturity of the newborn were studied. Indices of anthropometric, anatomic, reflex and physiologic development were examined to evaluate their association with birth weight and gestational age; the validity of these diagnostic indices is discussed. Studies are recommended to establish a maturity score to identify high-risk infants at birth.
| 41,766
|
Occurrence of old yellow enzyme in Gluconobacter suboxydans, and the cyclic regeneration of NADP.
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Old yellow enzyme system has been found in the cytosol fraction of Gluconobacter suboxydans. This is the first time that the enzyme has been found in organisms other than yeast cells. Old yellow enzyme [EC 1.6.99.1], D-glucose-6-phosphate dehydrogenase [EC 1.1.1.49], and catalase were isolated and crystallized separately from the organism. The old yellow enzyme from G. suboxydans showed catalytic and physicochemical properties almost identical with those of the enzyme from yeast cells. NADPH was specifically oxidized by the old yellow enzyme and the reduced enzyme was spontaneously reoxidized by atmospheric oxygen. The old yellow enzyme from G. suboxydans also contained FMN as a prosthetic group, and two mol of FMN were found per mol of enzyme (molecular weight, 88,000 as determined by gel filtration). In the oxidation of D-glucose-6-phosphate to 6-phospho-D-gluconate, cyclic regeneration of NADP occurred smoothly in the presence of D-glucose-6-phosphate dehydrogenase and catalase, even when a limited amount of NADP or NADPH was present in the reaction mixture.
| 41,838
|
Transmitter mediated arginine vasopressin release from superfused hypothalamus and pituitary gland.
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The study was designed to investigate the effect of various neurotransmitters on the hypothalamus and pituitary gland to determine the sites of their action. Superfused isolated rat hypothalami and pituitary glands demonstrated basal secretion of arginine vasopressin (AVP) and repeated response to stimulation thus showing the viability of the preparation. Acetylcholine and histamine stimulated the release of AVP at the hypothalamic and pituitary levels; dopamine and norepinephrine released AVP in a dose related manner only from the hypothalamus; angiotensin II released AVP in the same fashion only from the pituitary gland. AVP secretion stimulated by dopamine and norepinephrine may represent synaptic inputs which are localized at the hypothalamus and must be distinguished from the site of action at the pituitary gland of angiotensin II.
| 41,869
|
The longevity and hatchability of Philophthalmus megalurus and P. gralli miracidia in different environmental conditions.
|
The effects of salinity, pH, and temperature on the longevity and hatchability of miracidia of Philophthalmus megalurus and P. gralli were determined. Miracidia of both species are able to hatch and survive at saline concentrations much above physiological levels, although these processes are reduced in 2.0--2.4% saline and completely inhibited at 2.6%. The greatest hatching rates for both species were found near neutrality (pH 6--8) but some miracidia hatched at the extreme pH levels of 3 and 12. Philophthalmus megalurus miracidia exhibited longer half-lives under acid conditions (pH 2--6) than P. gralli miracidia; conversely, P. gralli miracidia showed longer half-lives in alkaline conditions (pH 8--11). Hatching and longevity were much greater below room temperature (5--20 C) than above (30--50 C) for miracidia of both species. Temperatures above 50 C proved lethal for eyefluke eggs. Except in acid pH, P. gralli miracidia showed longer half-lives than miracidia of P. megalurus. Comparison to studies on schistosomes revealed that the inhibitory effects of physiological saline and host body temperature on the hatching process of schistosome eggs does not occur in these 2 species of eyeflukes.
| 41,894
|
Prostaglandin E-2-9-ketoreductase in ovarian tissues.
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The existence of the enzyme prostaglandin E-2-9-ketoreductase which can convert prostaglandin E-2 to prostaglandin F-2 alpha was indicated in experiments with pig and human ovarian tissues in vitro, using radioimmunoassay methods and a superfusion technique. Further studies involving radiotracer techniques demonstrated that the enzyme was localized in the high-speed (105 000 g) supernatant fraction of human, pig and rat luteal tissue and human stromal tissue. The enzyme was shown to be NADPH-dependent and its activity in luteal tissue increased in the order : pig less than human less than rat.
| 41,947
|
"Fingerprinting" beta-haemolytic streptococci by their production of and sensitivity to bacteriocine-like inhibitors.
|
A scheme for the "fingerprinting" of streptococci according to their production of (P typing) and sensitivity to (S typing) bacteriocine-like inhibitory substances has been developed. P typing of 450 beta-haemolytic streptococci by their action on a set of nine standard indicator strains revealed that 80% of strains produced one or more detectable inhibitors, and that 17 different P types could be recognised. Production of some inhibitors seemed to be a property of strains of a particular serological group or type. Bacteriocine-like substances were produced by streptococci of serological groups, A, B, C, D, E, F and G. Nine strains were selected as standard producers for S typing. These strains differed in their spectra of inhibition, but all seemed to be active only against gram-positive bacteria. One producer, a group-F streptococcus, specifically inhibited group-A streptococci. The conditions of incubation were critical for demonstration of inhibitor production. A requirement for blood and for incubation at 32 degrees C were important factors. None of the inhibitors was induced by ultraviolet irradiation. The observed inhibitory effects were not attributable to either hydrogen peroxide or low pH, but to the production of a variety of substances having diverse physicochemical properties and production requirements. Most of the inhibitors do not seem to be produced in liquid media. The "fingerprinting" procedure is simple and inexpensive, and provides a reliable means of subdividing streptococcal strains that may find application as a supplement to the existing serological typing schemes.
| 41,951
|
Fatty metaplasia in a postpubertal undescended testis: a case report.
|
The first case of intratesticular fatty metaplasia in a postpubertal undescended testis is presented. Its differential diagnosis and etiology are discussed briefly.
| 41,954
|
alpha-Glucosidase in Pompe's disease.
|
Isoelectric precipitation at pH 5.0 and the use of the inhibitors, turanose, maltose and citrate, enabled the diagnosis of Pompe's disease to be made in dextran-isolated leucocytes using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate. These techniques were unnecessary with lymphocytes as the deficiency of acid alpha-glucosidase could be shown directly.
| 41,974
|
Diagnosis and management of fetal distress.
|
Both biophysical and biochemical techniques may be used to diagnose fetal distress. Fetal heart rate monitoring should be thought of as a screening technique to define a population at significant risk for fetal acidosis. The addition of fetal scalp blood sampling improves the clinician's diagnostic accuracy. The hallmark of treatment is to alleviate the stress on the fetus, to restore intervillous and cord blood flow, and, hence, to improve fetal oxygenation. This improvement may be accomplished by (1) discontinuing oxytocin, (2) correcting maternal hypotension, (3) administering oxygen to the mother, and (4) attempting to alleviate cord compression by changing the relationship of the fetal presenting part to the umbilical cord and pelvis.
| 41,983
|
Evolution of enzyme structure.
|
Three-dimensional structures of enzymes offer evidence about their evolution. There are clear examples of divergent families (e.g. mammalian serine proteases) and convergence (e.g. chymotrypsin and subtilisin). Topological similarities in dehydrogenases may reflect an ancient divergence or merely chemical constraints on protein architectures. Further experimental evidence is desirable to back up arguments based on molecular morphology. By growing microorganisms on novel foodstuffs in a chemostat, one can focus selective pressure on a specific enzyme activity. Experiments will be described in which such pressure is focused on pentitol metabolism. Examination of the fine structure of the genes responsible for this pentitol metabolism has given clues about the volution of metabolic pathways.
| 42,054
|
The evolution of genetic diversity.
|
The existence within natural populations of large amounts of genetic variation in molecules and morphology presents an evolutionary problem. The 'neutralist' solution to this problem, that the variation is usually unimportant to the organism displaying it, has now lost much of its strength. Interpretations that assume widespread heterozygous advantage also face serious difficulties. A resolution is possible in terms of frequency-dependent selection by predators, parasites and competitors. The evidence for pervasive frequency-dependent selection is now very strong. It appears to follow naturally from the behaviour of predators, from the evolutionary lability of parasites, from the ecology of competition and, at the molecular level, from the phenomena of enzyme kinetics. Such selection can explain the maintenance not only of conventional polymorphism but also of continuous variation in both molecular and morphological characters. It can account for the occurrence of diversity within groups of haploid and self-fertilizing organisms, and for the evolution of differences between individuals in their systems of genetic control.
| 42,055
|
[Organoleptic and biochemical changes in beef during refrigeration and storage].
|
Studies were carried out on the changes taking place in the organoleptic properties and the pH values of m. longissimus dorsi of carcass quarters of cattle, subjected to various ways of chilling and storage. It was found that in quickly chilled beef (immediately following slaughter) the processes of ripening were very slow, and the organoleptic indices were lower as against meat that was slowly cooled. The pH values of quickly chilled beef dropped at a very slow rate, and it was not until the ninth day that they reached the range below 6.0. The organoleptic properties of quickly chilled beef, including a preliminary phase (6 hours at 18-20 degrees C) were formed rapidly, and on the 7th-11th day the subjective evaluations became the same as those of slowly cooled beef.
| 42,194
|
The effect of retinol (vitamin A) on human lymphocytes stimulated by phytohaemagglutinin. An ultrastructural study.
|
Retinol (Vitamin A) has been found to inhibit the stimulation of lymphocytes by certain mitogens. The ultrastructural morphology of phytohaemagglutinin-stimulated lymphocytes exposed to retinol 10 microgram/ml and 20 microgram/ml show that disaggregation of polyribosomes and formation of autophagic vacuoles ensue in the majority of the cells. Some of the lymphocyte clumps are unaffected and continue to show normal mitosis. The changes in the affected cell are similar to those seen in a cell undergoing hormonal involution and it is postulated that the effects of the retinol may be mediated by a retinol binding protein in the susceptible cells.
| 42,208
|
[Effect of neurotoxins on mediator release from the motor nerve endings of the Drosophila melanogaster larva].
|
Spontaneous miniature junctional potentials and induced by motor nerve stimulation junctional potentials were recorded in muscle fibres of the third instar Drosophila larvae. Presynaptically active neurotoxins isolated from the snake venoms (beta-bungarotoxin 4.5 x 10(-7) M, notexin and notechis-II-51 X 10(-7) M, Crotoxin 9 x 10(-8) M, phospholipase from the venom of cobra 4 x 10(-6) M did not induce any changes in transmitter release during 60--120 min of contact with Drosophila preparation, although these concentrations exceed those used in frog or mice preparations. On the contrary, bee venom phospholipase (1.25 x 10(-7) M) turned out to be even more active than in frog or mice junctions. A similar sequence of three phases of the presynaptic blocking effect was found: initial decrease followed by a period of increase and finally -- depression of both spontaneous and evoked release. Bee venom phospholipase was ineffective in Ca2+-free solution but its irreversible binding to nerve endings took place evidently in spite of Ca lack.
| 42,240
|
NADPH-dependent electron transport chain in microsomes and lipid peroxidation catalyzed by metal ions.
|
Like iron ions copper ions are also able to stimulate the NADPH-dependent lipid peroxidation in rat liver microsomes. This effect is strongly dependent on the concentration of Cu2+ added. Initial concentrations of Cu2+ above 50 microM completely inhibit the formation of malonaldehyde. The activator and inhibitor functions may be interpreted by a simultaneous participation of Cu+ ions formed in the chain branching and termination reaction of the free radical lipid peroxidation process. Inhibition studies with pCMB and the His-reagent diethyl pyrocarbonate indicate an essential role of cysteine and histidine residues in the Cu+-NADPH-dependent lipid peroxidation process.
| 42,249
|
Properties of influenzavirus nucleocapsids in nonpermissive cells.
|
The properties of fowl plague virus (Influenzavirus A) nucleocapsids isolated from the cytoplasm of infected Ehrlich ascites carcinoma cells and chick embryo cells were compared. Nucleocapsids isolated from both systems possessed similar polypeptides (P and NP) but differed in their biophysical characteristics. Nucleocapsids from ascites cells sedimented in velocity sucrose gradients slower (from 25 to 50 S) and the majority of them banded at higher density in CsCl gradients (rho 1.38 as compared to 1.34 g/ml) than nucleocapsids from chick embryo cells. In the electron microscope they appeared as thin threads 3--4 nm in diameter.
| 42,293
|
Isolation and characterization of influenza A viruses from wild ducks in northern Japan: appearance of HSW1 antigens in the Japanese duck population.
|
Twenty-six influenza A viruses were isolated from cloacal and tracheal samples of 235 resident and 396 migratory ducks in Miyagi prefecture, Japan, in 1977--78. Of these, twelve were antigenically related to the avian-origin HSW1 virus, A/duck/Alberta/35/76 (HSW1N1), but their neuraminidase antigens were characterized as Nav2-3, Nav4 or N2. These antigenic configuration have not previously been reported. In addition, one strain in which the neuraminidase antigen was identified as Nav4, was demonstrated to be a mixture of two haemagglutinins, HSW1 and Hav7. Two distinct strains were separated from the mixture and characterized as HSW1Nav4 and Hav7Nav4. The antigenic identification of an additional 13 influenza A viruses revealed the presence of six haemagglutinin subtypes (Hav1, Hav3, Hav4, Hav6, Hav7, and Hav8) and five neuaraminidase subtypes (Nav1, Nav2-3, Nav4, Neq2, and N2) in various combinations. The results suggest that the avian influenza A viruses among feral ducks may be isolated in various combinations of haemagglutinins and neuraminidase subtypes in Japan, and that feral ducks may be the site of genetic recombination occurring as a result of dual infection with different subtypes of influenza A virus.
| 42,296
|
Effect of incubation temperature on infectivity titration of mouse brain-passaged avian infectious bronchitis virus in laboratory host systems.
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Mouse brain-passaged infectious bronchitis virus (IBV) could not be assayed for its infectivity at 39.5 degrees C, but could be so at 37 degrees C and 39.5 degrees C. Antigen accumulation was not detected by immunofluorescence in CEK cells infected with mouse brain-passaged IBV at 39.5 degrees C, perhaps due to the difference in the cellular environments.
| 42,299
|
Hemoglobin Cowtown (beta 146 HC3 His-Leu): a mutant with high oxygen affinity and erythrocytosis.
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A new mutant, hemoglobin Cowtown, has been found in a white man and his father, both of whom have erythrocytosis. The father had previously been treated with 32P for polycythemia vera. The abnormal hemoglobin is not detectable on electrophoresis in alkaline buffers, but it resolves distinctively on electrophoresis in citrate agar, pH 6.0; similarly, the abnormal beta-globin chain does not separate from beta-A in urea 2-mercaptoethanol buffers of pH 8.9, but it moves anodically to beta-A at pH 6.0. Peptide chromatography and amino acid analysis of the beta chain reveal that the C-terminal histidine residue (beta 146) has been replaced by leucine. Like several other hemoglobins substituted at this residue, Hb Cowtown has a high oxygen affinity and a diminished Bohr effect.
| 42,311
|
pH modification of the effects of detergents on the stability of enteric viruses.
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The effect of detergents on the stability of enteric viruses was found to be highly dependent on pH. This was demonstrated primarily with two ionic detergents, sodium dodecyl sulfate (an anionic detergent) and dodecyltrimethylammonium chloride (a cationic detergent). Both detergents were shown to be potent virucidal agents for reovirus, but the effects of sodium dodecyl sulfate were minimal near neutrality and much more pronounced at low than at high pH values. Dodecyltrimethylammonium chloride was extremely virucidal at high pH's but had little observable effect on reovirus stability at low pH values. In contrast, both detergents protected enteroviruses against heat at neutral and alkaline pH's. However, as was found with reovirus, sodium dodecyl sulfate was extremely virucidal at pH values below 5, even when the virus samples were incubated in ice. At different pH's the effects of detergents on the stabilities of coliphages T4, f1, and Q beta were qualitatively similar to those found with reovirus. Differences in viral stability in these experiments appeared to be due to the effects of pH on the ionic states of the viral capsid proteins.
| 42,351
|
[Epidemiology of measles (author's transl)].
|
A detailed analysis of epidemiology of measles in pre-vaccinal era is reported for both isolated, underdeveloped and developed populations, together with the most recent knowledge on epidemiological changes tooking place in those countries which introduced large-scale vaccination with live, further attenuated measles vaccines: reduction of morbidity mortality and complication rates, morbidity age shift, etc. Results obtained in U.S.A., where vaccination was introduced in 1963, are analyzed also considering that it never spanned above 66% of children 1-4 year. Suggestions derive after the american experience for a correct strategy of the incoming vaccination in this Country.
| 42,364
|
Stimulation of phosphatidylinositol turnover in various tissues by cholinergic and adrenergic agonists, by histamine and by caerulein.
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Studies are reported of the biochemical and pharmacological characteristics of the stimulation of phosphatidylinositol metabolism that is produced in appropriate target tissues by stimulation of various receptors that use Ca(2+) as their second messenger. (1) Muscarinic cholinergic and alpha-adrenergic phosphatidylinositol responses were observed in rat lacrimal gland, and a response to caerulein was detected in the longitudinal smooth muscle of guinea-pig ileum. (2) The muscarinic cholinergic phosphatidylinositol response of rat lacrimal gland, like that of several other tissues, is not dependent on the availability of extracellular Ca(2+). (3) Three phosphatidylinositol responses, namely to histamine in guinea-pig ileum smooth muscle, to alpha-adrenergic stimulation in rat vas deferens and to muscarinic cholinergic stimulation in rat lacrimal gland, were all found to involve phosphatidylinositol breakdown. (4) The stereospecificity of the muscarinic receptor responsible for the phosphatidylinositol response of guinea-pig pancreas was tested by using the two stereoisomeric forms of acetyl-beta-methylcholine; the S-isomer was very much more active than the R-isomer in provoking both phosphatidylinositol breakdown and its labelling with (32)P, as it is in provoking other physiological responses such as contractility or secretion. (5) Pilocarpine, a muscarinic partial agonist, provoked a significantly smaller phosphatidylinositol breakdown in rat parotid fragments than did carbamoylcholine, a potent muscarinic agonist. (6) All of these results are consistent with, but do not prove, a previously offered hypothesis that suggests that phosphatidylinositol breakdown is a reaction essential to stimulus-response coupling at a variety of cell-surface receptors that mobilize Ca(2+) from and through the plasma membranes of target tissues.
| 42,389
|
A study of the plasma concentrations of lorazepam in mother and neonate.
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A standard dose of lorazepam 2.5 mg was given i.v. to two groups of mothers: (a) before surgical induction of labour and (b) at the beginning of the second stage of labour. A group of non-pregnant women was studied as control. Plasma concentrations of lorazepam were measured by gas-liquid chromatography, in the mothers before delivery, and in the mother and neonate at delivery and 24 and 48 h thereafter. Concentrations at delivery in the neonates were similar to those in the mothers in group (a), but significantly less in group (b). Fetal concentration rarely exceeded that in the mother. Measurements after delivery indicated that the neonates were able to metabolize lorazepam at the same rate as the mothers. Of the 22 neonates studied only one had an Apgar score of less than 8 at 5 min and this score was 10 at 10 min.
| 42,422
|
Stability of phage T4 lysozymes. II. Unfolding with guanidinium chloride.
|
The denaturation by guanidinium chloride of three phage lysozymes (wild type and two mutants) was investigated. The study of solvent denaturation permitted the investigation of the relative stabilities of the proteins at neutral pH, in contrast to thermal denaturation studies reported earlier which could only be performed in acid pH. The results were interpreted assuming that the free energy of solution of proteins is a linear function of denaturant concentration. Using standard thermodynamic formulas this permits the calculation of the stabilities of the three proteins in the absence of guanidinium chloride. The single point mutation Trp 138 leads to Tyr leads to relatively large changes in stability and the interaction of the protein with guanidinium chloride. The changes associated with the subsequent double mutation, Trp 126 leads to Tyr, Trp 158 leads to Tyr, are much smaller indicating a relatively smooth adjustment of the protein structure to the changed side chains. Models of the structural effects of point mutations are discussed. It is found that the mutation at position 138 does not fit a model in which the effect of a substitution is to introduce an energetic strain in the structure. It does fit a model in which there is a partial unravelling of the structure as a result of the mutation. However, there are no changes in the backbone circular dichroism spectra associated with the mutation. The two observations are not necessarily in conflict. Further physical studies are required for the resolution of the problem.
| 42,444
|
Effects of microiontophoretically applied flurazepam on responses of cerebral cortical neurones to putative neurotransmitters.
|
Utilizing standard microiontophoretic techniques and recording extracellularly in cats, we studied the effects of flurazepam, a water-soluble benzodiazepine, on the spike activity of single cerebral neurones and its interactions with several excitatory and inhibitory putative neurotransmitters. Large iontophoretic doses (5--30 nA, 0.1 M solution) of flurazepam induced a depression of spike amplitude. Smaller doses (less than 5 nA, 0.1 M solution or 20--50 nA, 20 mM in 0.16 M NaCl) reduced the excitation produced by glutamate, aspartate, and homocysteate, but antagonism of acetylcholine-evoked excitations required large flurazepam doses (up to 30 nA, 0.1 M solution). Even lower doses of flurazepam (less than 10 nA, 20 mM in 0.16 M NaCl) enhanced the inhibitory effect of gamma-aminobutyric acid (GABA) but antagonized that of 5-hydroxytryptamine, and had no effect on dopamine-induced inhibition of firing. Hence, only GABA-evoked inhibitions were significantly potentiated by flurazepam. These results demonstrate the multiple possible interactions between a benzodiazepine and different putative neurotransmitters in the mammalian cerebral cortex.
| 42,477
|
Capillary filtration coefficient: the technique and its application to the small intestine.
|
In this review, we discuss the physiological basis of the capillary filtration coefficient (Kf,c), and its measurement in the small intestine. First the various techniques by which Kf,c can be measured are discussed and assessed; the second part of the review considers the volumetric method of determining Kf,c in more detail, in an attempt to identify the causes of variability in published values for intestinal Kf,c. Finally, we discuss changes in intestinal Kf,c due to sympathetic nerve stimulation and the administration of drugs and hormones. The majority of estimates of intestinal Kf,c are about 0.38 to 0.60 (innervated) to 0.60 to 0.75 (denervated) cm3 . min-1 . kPa-1 . 100g-1. These values are increased by most vasodilator drugs and hormones, and decreased by sympathetic nerve stimulation and by vasoconstrictor drugs.
| 42,491
|
[Comparison of glutamate dehydrogenase and glutamine synthetase activities in the roots and aerial organs of an obligate halophyte: Suaeda maritima var. macrocarpa and a glycophyte: Phaseolus vulgaris, grown in presence of different concentration of NaCl].
|
The glutamate dehydrogenase and glutamine synthetase activities of an obligate halophyte, Suaeda maritima var. macrocarpa and a glycophyte. Phaseolus vulgaris are compared in function of salinity (increasing concentrations of NaCl) of the culturing solution. In culture, addition of NaCl stimulates glutamine synthetase activity and lowers glutamine dehydrogenase activity in the aerial organs and in the roots of Suaeda as opposed to what is observed in the glycophyte. Hence the obligatory halophily of Suaeda is related to an increase of the glutamine synthetase activity in a sal-trich medium corresponding to the stimulation of nitrate reductase and proteogenesis.
| 42,495
|
The effect of pentobarbitone on plasma and intracellular sodium, potassium and pH in rabbit cardiac and skeletal muscle.
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1. Pentobarbitone anaesthesia, in rabbits, produces (i) hypokalaemia, (ii) increased intracellular potassium and reduced intracellular sodium in cardiac and skeletal muscle. 2. These changes suggest that the hypokalaemia which accompanies anaesthesia results from movement of potassium between the extracellular and intracellular compartments.
| 42,507
|
Crystallization and properties of cathepsin B from rat liver.
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Cathepsin B from rat liver was purified to apparent homogeneity by cell-fractionation, freezing and thawing, acetone treatment, gel filtration, DEAE-Sephadex and CM-Sephadex column chromatography, and was crystallized. The purified enzyme formed spindle-shaped crystals and its homogeneity was proved by disc gel electrophoresis in the presence of sodium dodecyl sulfate and by ultracentrifugal analysis. Its s20,w value was 2.8 S and its relative molecular mass was calculated to be 22,500 (+/- 900) by sedimentation equilibrium analysis. Crystalline cathepsin B was shown to consist of four isozymes with isoelectric points between pH 4.9 and 5.3, the main isozyme having an isoelectric point of pH 5.0. The enzyme was irreversibly inactivated by exposure to weak alkali. The pH optimum was 6.0 with alpha-N-benzoyl-DL-arginine-4-nitroanilide as substrate. Amino acid analysis showed that the enzyme contained hexosamine, glucosamine and galactosamine. Cathepsin B inactivated aldolase, glucokinase, apo-ornithine aminotransferase, and apo-cystathionase, but the rates of inactivation of glucokinase, apo-ornithine aminotransferase, and apocystathionase were lower than that of aldolase. Studies by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate showed that cathepsin B degraded apo-ornithine aminotransferase to two polypeptide chains differing in relative molecular mass and electrophoretic mobility.
| 42,540
|
Presynaptic noradrenergic alpha-receptors and modulation of 3H-noradrenaline release from rat brain synaptosomes.
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The depolarization (15 mM K+)-induced release of 3H-NA from superfused rat brain synaptosomes and the effects of alpha-noradrenergic drugs thereon were studied. Noradrenaline (NA; in the presence of the uptake inhibitor desipramine) reduced synaptosomal 3H-NA release. Reduction of the concentration of calcium ions in the medium during K+ stimulation greatly enhanced the sensitivity of 3H-NA release to alpha-receptor-mediated inhibition. Under these conditions NA dose-dependently inhibited 3H-NA release from synaptosomes obtained from cortex or hypothalamus, but did not affect 3H-NA release from striatal (i.e dopaminergic) synaptosomes. Adrenaline, clonidine and oxymetazoline potently inhibited 3H-NA release from cortex synaptosomes at concentrations in the nanomolar range. Phentolamine by itself did not affect synaptosomal 3H-NA release, but antagonized the inhibitory effects of both noradrenaline and adrenaline. The data obtained further substantiate the hypothesis that the alpha-receptors mediating a local negative feedback control of NA release are localized on the varicosities of central noradrenergic neurons, Furthermore, noradrenergic nerve terminals in the hypothalamus appear to be less senstive to alpha-receptor-mediated presynaptic inhibition than those in the cortex.
| 42,548
|
Antihypertensive and cardiac effects of two novel beta-adrenoceptor blocking drugs.
|
Two new beta-adrenoceptor blocking drugs with acute antihypertensive and positive inotropic effects are described: Compound A (2-[4-(3-tert.butylamino-2-hydroxypropoxy)phenyl]-4-trifluoromethylimidazole) and MK-761 (2-(3-tert.butylamine-2-hydroxypropoxy)-3-cyanopyridine hydrochloride). In SH rats both compounds, given orally, lowered arterial pressure and were more potent than hydralazine. The antihypertensive effect of compound A but not of MK-761 was antagonized by timolol. Both compounds had positive inotropic activity on cat heart papillary muscles; these effects were antagonized by timolol. The pretreatment of animals with reserpine greatly reduced the positive inotropic effect of MK-761 but not of compound A. The acute antihypertensive and positive inotropic effects of compound A are like to be at least partially due to stimulation of beta-adrenoceptors, e.g. intrinsic sympathomimetic activity. The effects of MK-761 on the same parameters appear to be mediated by different mechanisms.
| 42,553
|
Increased release of tumour cells by collagenase at acid pH: a possible mechanism for metastasis.
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The ability of collagenase to disaggregate a solid metastasizing lymphosarcoma has been shown to considerably increase with reducing environmental pH. It is suggested that this effect may be operating in vivo to release cells from a primary tumour.
| 42,555
|
[Effect of vasocative substances on resistance and capacitance vessels under high altitude conditions].
|
In cats, i.a. administration of adrenaline (10 microgram), serotonin (30 microgram), and acetylcholine (10 microgram) on the 3rd, 15th, and 30th days of animals stay at 3200 m altitude induced different vasomotor responses in precapillary and postcapillary portions of intestine vascular net during different periods of high altitude adaptation. Changes of reactivity in different receptor structures of smooth muscles, the initial tonus of the small intestine resistance vessels associated with the whole adaptive rearrangement of the organism functional state in the high altitude extreme conditions, are the possible mechanisms of detected changes.
| 42,566
|
Modification of response of mouse neuroblastoma cells in culture by serum type.
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The effect of various types of serum on morphological and biochemical changes in mouse neuroblastoma cells (clone NBP2) in culture was studied. The extent of spontaneous morphological differentiation varied markedly depending upon the type of serum and was maximal in agammaglobulin calf serum (CS). The extent of morphological differentiation after treatment of cells with cyclic AMP-stimulating agents was also dependent upon serum type and was least pronounced in fetal calf serum. The doubling time and extent of clumping varied with the type of serum. The activity of tyrosine hydroxylase (TH) in NB cells was dependent upon serum type and it was highest in newborn CS and agammaglobulin CS. Although elevation of intracellular levels of cyclic AMP in NBP2 clone invariably stimulates neurite formation and TH activity, these functions were increased in certain sera without a significant increase in the cellular cyclic AMP levels. The present study shows that neurite formation, growth rate and TH activity are regulated by more than one mode, one of which is mediated by cyclic AMP. The above changes are independently regulated in the sense that the expression of one can be increased in the absence of others.
| 42,611
|
Solid phase synthesis of the protected 27--42 hexadecapeptide of the heavy chain from myeloma immunoglobulin M603. Elimination of side reactions associated with glycyl-2-oxypropionyl-resin.
|
A fully protected 27--42 hexadecapeptide of the variable region of myeloma immunoglobulin M603 was synthesized on a 2-bromopropionyl-resin by the solid phase method. Side reactions due to cyclization of glycyl-2-oxypropionyl-resin were studied under different reaction conditions. The loss of peptide chains at the dipeptide and tripeptide stages due to diketopeperazine formation was also examined. These side reactions were circumvented by using a combination of fragment and stepwise coupling methods. The synthesized protected peptide was removed from the resin in 85% yield by photolysis, and purified by crystallization and by chromatography on a Sephadex LH-60 column.
| 42,624
|
Effects on learning and memory of 2-week treatments with chlordiazepoxide lactam, N-desmethyldiazepam, oxazepam and methyloxazepam, alone or in combination with alcohol.
|
A double-blind study with 40 healthy students was done in order to measure the effects of a 2-week treatment with chloridiazepoxide lactam (5 mg), nordiazepam (10 mg), oxazepam (15 mg) and methyloxazepam (20 mg) on immediate memory and associative learning. The drugs were administered t.i.d. and the tests were done after the very last capsule was given. It was ingested with a placebo drink and 0.5 g alcohol/kg body weight. Oxazepam and methyloxazepam alone behaved similar to the placebo. Immediate memory was significantly impaired following the treatment with nordiazepam, chlordiazepoxide lactam, alcohol, and after the simultaneous administration of nordiazepam and chlordiazepoxide lactam with alcohol. Chlordiazepoxide lactam was the only drug which alone impaired associative learning. Also alcohol alone, and all the drugs in combination with alcohol retarded learning acquisition.
| 42,628
|
Isolation and properties of the protease from the wild-type and mutant strains of Pseudomonas fragi.
|
A simplified procedure for the purification of the extracellular protease of Pseudomonas fragi was developed. The enzyme was isolated from a derepressed mutant producing 40 times the enzyme level of the parental organism. It was collected from culture filtrates by ammonium sulfate precipitation, and it was obtained in pure form by single chromatography on a column of diethylaminoethyl cellulose. The protease had a molecular weight of 52,000 as estimated by sodium dodecyl sulfate-gel electrophoresis and had properties of a classical neutral endopeptidase with the exception of its substrate specificity. Mutants of P. fragi producing proteases of altered substrate specificities were isolated from plates containing elastin as the sole carbon source. The SP-Sephadex elution patterns of enzymes extracted from each mutant examined were complex, suggesting that either the enzyme was autodigested or several active forms could be generated from a common precursor. The substrate specificities of the mutant enzymes were different from that produced by the parental strain.
| 42,639
|
Preparation and characterization of an active lysozyme derivative: Kyn 62-lysozyme.
|
A novel method for the preparation of Kyn 62-lysozyme, in which tryptophan 62 is replaced by kynurenine, is reported. Hen egg-white lysozyme was ozonized in aqueous solution to yield one N'-formylkynurenine residue and deformylated with hydrochloric acid in frozen solution at -10 degrees C. Crude Kyn 62-lysozyme was purified by affinity and Bio Rex 70 chromatography successively. Kyn 62-lysozyme retains affinity for chitin and is essentially an active enzyme with a slightly weakened but distinct catalytic activity. After this modification, the enzyme activity was changed differently depending on the kind of substrate. At the individual optimum pH's, lytic activity was largely retained (80% active), but the catalytic efficiency for hydrolyzing glycol chitin was relatively low (30% active). Lysis of M. lysodeikticus cell suspensions was optimally catalyzed by Kyn 62-lysozyme at pH 6.2 and at 0.088 ionic strength. These values are lower by 1.3 pH unit and 0.04 ionic strength, respectively, than those of intact lysozyme. The optimum pH and ionic strength for the hydrolysis of neutral substrates were scarcely affected. These results suggest the significance of electrostatic interaction in the lysis of lysozyme. Relatively limited loss of activity induced by modification of the 62nd residue, which is thought to participate directly in the binding of the substrate at subsite C, is discussed on the basis of the similarity of side chain structure in tryptophan and kynurenine.
| 42,644
|
Anatomy and ultrastructure of the axons and terminals of neurons R3-R14 in Aplysia.
|
Using light and electron microscopy and autoradiography, we have traced the axons of neurons R3-R14 in the parietovisceral ganglion (PVG) of Aplysia to terminal fields associated with vascular tissue. The axons are identified by their large size (15-30 micrometer diameter), extensive glial infolding, characteristic dense core vesicles (DCV; approximately 180 nm diameter), and specific, rapid uptake of 3H-glycine. Each neuron in this homogeneous group sends an axon via the branchial nerve to the pericardial region surrounding the junction of the efferent gill vein and the heart. R14 also sends axons to major arteries near the PVG. The R3-R14 axons branch extensively; we estimate that there are at least several hundred per cell. Branches along axons in the branchial nerve exit the nerve, subdivide, and end blindly in the sheath which is bathed by hemolymph. Similar blind endings from R3R14 occur in the sheath of the PVG (Coggeshall, '67). Axonal branches in the pericardial region and the special R14 axons in the arterial walls form both varicose endings near and terminals in contact with vasvular smooth muscle. All R3-R14 endings are free of glia, packed with DCV, show occasional omega-shaped profiles and rapidly take up 3H-glycine. R3-R14 manufacture specific low molecular weight peptides (Gainer and Wollberg, '74), and both the cell bodies (Iliffe et al., '77) and the germinals contain unusually high concentrations of glycine. The presence of peptides as putative neurohormones and sheath endings (neurohormonal release areas) are consistent with R3-R14 being neurosecretory (Coggeshall et al., '66). While glycine could not be a circulating hormone due to its high circulating levels (Iliffe et al., '77), glycine could act as a local chemical messenger between R3-R14 and smooth muscle. The terminal morphology of R3-R14 is consistent with these neurons having both synaptic-type and neurosecretory-type functions.
| 42,652
|
Cleavage of thiamine by chlorine in tap water.
|
We have clarified that thiamine is cleaved by residual chlorine in proportion to the rise in temperature, pH and concentration of residual chlorine. When rice was boiled in an electric rice cooker, the thiamine in the rice was cleaved by residual chlorine. It is assumed that thiamine is cleaved into hydroxymethylpyrimidine and the thiazole moiety.
| 42,668
|
Effects of handling stress on plasma enzymes in harp seals, Phoca groenlandica.
|
Three harp seal pups, Phoca groenlandica, were captured on the ice of the Gulf of St. Lawrence, and subjected to 3 h of transportation and handling stress. The activities of creatine kinase (CK), aspartate aminotransferase (AspAT), aldolase, alanine aminotransferase, gamma glutamyl transpeptidase, and leucine aminopeptidase were determined in serial blood samples collected for 4 d following the stress episode. Marked elevation of plasma CK activity was observed 3 h after capture. Values returned to normal in 12 h in two seals, and by 24 h in the third. Slight elevations in AspAT were also noted; the remaining enzymes were unaffected. Plasma CK is recommended as a sensitive indicator of handling stress in seals.
| 42,815
|
[Bone marrow transplantation in severe aplastic anemia and acute leukemia].
|
Much progress has been made in allogeneic bone marrow transplantation for severe aplastic anemia (SAA) and acute leukemia (AL). In SAA it was shown that hemopoietic chimerism and apparently permanent cures can be achieved in the majority of patients by conditioning with cyclophosphamide followed by bone marrow transplantation (BMT) from an HLA-identical sibling. The previous transfusion history is crucial for failure or success: untransfused patients do very well while graft rejection is an enormous problem in most polytransfused ones. We have shown that most patients without HLA-identical sibling donors can be adequately helped as well. After conditioning with ALG followed by transfusion of haploidentical marrow and low dose androgens there is partial to complete autologous hemopoietic reconstitution in virtually all patients. This points to the fact that most of these patients have pluripotent hemopoietic stem cells that are intact, but apparently unable to differentiate to mature cells, because they are inhibited by autoimmune mechanisms. The results of BMT in patients with endstage leukemia are modest. New pilotstudies with early marrow grafts, i.e. for ANLL in first remission and for ALL in second remission indicate that with this type of approach potentially over 50% of all patients with HLA-identical siblings can be cured. We recommend that HLA-typing should be performed early in families with SAA and AL and that the possibility of a marrow graft should be seriously considered before the patients have endstage disease. Marrow grafts are technically simple but they may pose enormous problems such as graft versus host reaction (GvH), interstitial pneumonia, graft rejection and leukemic recurrence. Therefore, the procedure should only be performed in highly specialized centers with much knowledge and experience in the immunobiology of bone marrow transplantation.
| 42,865
|
[Influences of different anaesthetic techniques on serum levels of hepatic enzymes and of bilirubin (author's transl)].
|
The influence of four different types of anaesthesia -- halothane and enflurane inhalation anaestheis, neurolept analgesia and epidural analgesia with single shot technique -- on the serum levels of GOT, GPT, GLDH, LDH, AP, LAP, gamma-GT, total protein and bilirubin was examined in 104 comparable cases undergoing gynaecological surgery. A significant increase in GOT, GPT, GLDH, AP, and gamma-GT levels was observed between the 6th and 9th postoperative day with all types of anaesthesia. The serum levels remained elevated until the 15th postoperative day. There was no significant difference between the four types of anaesthesia as regarded their effects on the serum constituents investigated. The same applied to the serum CHE activity which reached a minimum on the 3rd postoperative day followed by a steady rise. The results indicate that the postoperative changes of the liver enzyme pattern are not related to the type of anaesthesia used. Bilirubin was elevated on the first postoperative day, then dropped rapidly and stayed below the pre-operative values until the 12th postoperative day. There was no difference between the four types of anaesthesia. Glucuronisation of bilirubin may be inhibited initially by the anaesthetic agents. The subsequent rapid fall of the bilirubin levels may be the result of enzyme induction.
| 42,895
|
Structural order of lipids and proteins in membranes: evaluation of fluorescence anisotropy data.
|
The limiting long-time value of fluorescence anisotropy in membranes is correlated with the orientational order parameter, which characterizes the structural anisotropy of membranes. Existing experimental results for diphenylhexatriene in lipid bilayers are evaluated for the order parameter of lipid order. Steady-state measurements of fluorescence anisotropy can provide the order parameter in good approximation. Proteins in a fluid lipid phase increase the lipid order parameter so determined. Upon comparison with the order parameter from deuterium magnetic resonance, it is concluded that proteins increase the order of the surrounding lipids in off-normal directions. Order parameters of protein order obtained from the limiting value of protein fluorescence anisotropy are discussed with respect to the influence of lipid order on protein order.
| 42,914
|
Effects of D- and L- enantiomers of adenosine, AMP and ADP and their 2-chloro- and 2-azido- analogues on human platelets.
|
Aggregation of human platelets by ADP and the inhibition of this effect by adenosine are apparently mediated by different receptors. One of the criteria for receptors is that they show stereospecificity for their ligands. We have synthesized L-enantiomers of D-adenosine, AMP and ADP, together with their corresponding photolysable 2-azido analogues so that platelet receptors could be tested for stereospecificity. All of the L-enantiomers were completely inactive as aggregators or inhibitors of platelet function. None of the L-enantiomers changed levels of platelet cAMP. 2-Azido-L-adenosine, AMP and ADP are proposed as useful controls in photoaffinity experiments for non-specific labelling.
| 42,919
|
Membrane potential and ion concentration stability conditions for a cell with a restricted extracellular space.
|
For an isolated membrane, the resting (zero current) potential is stable is the slope conductance is positive, and is unstable if the slope conductance is negative. Recent work suggests that the properties of many preparations are influenced by the presence of an extracellular space that is not in good diffusive contact with the bulk extracellular fluid. Ionic current flow across the membrane changes the ion concentrations in this space. These concentration changes affect the stability of the membrane potential. Even if the slope conductance is negative, the presence of the extracellular space can confer stability on the resting potential. Conversely, even if the slope conductance is positive, the extracellular space can produce instability of the resting potential. Evaluation of the relevant parameters for cardiac Purkinje fibres, from published experimental data, suggests that concentration changes in the extracellular space may play a significant role in determining when an action potential is initiated.
| 42,920
|
Effect of beta-adrenergic drugs on plasma glucose and glucagon in Japanese quail: a preliminary report.
|
The present study was conducted to determine the effects of beta-adrenergic stimulation on plasma glucose and glucagon (IRG) levels in Japanese quail. Isoproterenol, epinephrine and three relatively selective beta-adrenoceptor agonists (terbutaline, salbutamol and reproterol) produced dose-related hyperglycemia and hypoglucagonemia. This study demonstrates that beta-adrenoceptor agonists produce hyperglycemia in birds as they do in mammals, but that the rise in plasma glucose in birds, unlike mammals, is accompanied by a profound fall in plasma IRG levels.
| 42,957
|
[Chronic lymphocytic leukaemia with cutaneous lesions and deafness following periarteritis nodosa (author's transl)].
|
A case is reported of a 49 years-old man who presented with cutaneous and muscular manifestations revealing periarteritis nodosa. Two years after detection of this disease occured a preleukemic condition and four years later a chronic lymphocytic leukaemia is discovered. In clinical course appeared a tuberous infiltration of the face and a sudden bilateral deafness. Regression of these two abnormalities is obtained after administration of prednisolone. The patient died of generalized infectious process postoperatively. From these clinical and pathological findings relations between periarteritis and CLL, occurence of deafness and cutaneous lesions are discussed. The relationship between the development of CLL and the immunosuppressive treatment is considered.
| 42,979
|
Diffuse glomerulosclerosis--a dysfunction of the mesangium? A morphometric study of the rat's kidney.
|
The phagocytic capacity of the glomerular mesangial cells in 42 rats was inhibited by the prolonged injection of PVA. Morphometric evaluation of electron microscopic sections showed that this treatment leads to an accelerated thickening of the lamina densa of the glomerular basement membrane and of the mesangial matrix (early glomerulosclerosis). This suggests that a disturbance of lysosomal degradation can lead to glomerulosclerosis, and that the possibility of mesangial dysfunction should always be considered as a possible factor in the pathogenesis of all types of diffuse glomerulosclerosis.
| 43,014
|
Stereological study of endoplasmic reticulum, Golgi complex and secretory granules in the B-cells of normal and alloxan-treated mice.
|
Different B-cell organelles (lamellar and vesicular endoplasmic reticulum, Golgi complex, whole secretory granules and secretory granule cores) were studied stereologically in pancreatic islets from control mice and mice killed 10 or 60 min following alloxan injection. Ten min following alloxan a significant decrease was observed in the volume, surface and numerical densities of whole secretory granules and their cores, and a significant increase was found in the volume and surface densities of vesicular endoplasmic reticulum. At the 60 min observation time, a significant decrease was seen in the volume density of lamellar endoplasmic reticulum and Golgi complex, and in the volume, surface and numerical densities of whole secretory granules and their cores, and a significant increase was observed in the volume and surface densities of vesicular endoplasmic reticulum, and in the mean values for volume and surface of whole secretory granules and their cores. The stereological data indicate swelling of endoplasmic reticulum, decreased Golgi area, and decreased number and total volume and surface of secretory granules during the first hour after alloxan administration to mice. The observations may be consistent with inhibited insulin synthesis.
| 43,017
|
The calcium selective electrode--a possible tool in dental research.
|
Ion selective potentiometry is widely used for analytical purposes in biologic research. The Ca selective electrode offers an inexpensive and easily handled means for studying ionized calcium. It does not affect the process studied, and may, for example, combined with an automatic recorder, give running information on dynamic systems. The calcium electrode responds in accordance with the Nernst equation and has a theoretical range of 1--10(-6) M Ca2+. The electrode is influenced by changes in temperature, in pH and also in concentration of buffer solution. The Ca sensitive membrane is adversely affected by acetic acid but tolerates lactate/lactic acid buffers. Best linearity in calibration curves for Ca2+ in lactate buffers is found in concentrations from 10(-4) M to 10(-2) M Ca. In a 5% Na lactate/lactic acid buffer, pH 5, with 0.5 M KNO3 as an ionic strength adjuster, a straight calibration curve, Nernstian slope factor 27 mV/decade, is found from 10(-4) to 1 M Ca.
| 43,066
|
Effects on fetal breathing movements of maternal challenges. Cross-over study on dynamic work, static work, passive movements, hyperventilation and hyperoxygenation.
|
Ten women in the last trimester of a normal pregnancy were subjected to five different loads in a cross-over study. Fetal breathing movements (FBM), fetal heart rate (FHR), maternal heart rate (MHR), and mean arterial pressure (MAP), maternal transcutaneously measured pO2 (Tc-pO2), and the energy supply to the Tc-pO2 electrode were recorded continuously before, during, and after the load. Maternal capillary pH and pCO2 were measured at three representative time points. The immediate responses of the incidence of FBM to the different challenges were: increase after dynamic work (bicycle test); no change after static work (isometric muscle contraction) and passive movements; decrease after hyperventilation and hyperoxygenation. FHR was unaffected by all challenges. The FBM incidence varied in parallel with pCO2 after dynamic work and hyperventilation and inversely with the Tc-pO2 rise caused by hyperoxygenation. Maternal pH was increased after passive movements (no change in FBM) and after hyperventilation (decreased incidence of FBM), FBM seem to be more sensitive to environmental changes than is the FHR. Mechanical stimuli to the uterus were not responsible for the augmentation of FMB seen after the bicycle test. The present observations reveal the multifactorial nature of the regulation of FBM, and support the role of CO2 as a major stimulator of breathing movements also in prenatal life.
| 43,068
|
In vivo negative staining of the midgut continuous junction in the mosquito, Culex tarsalis (Diptera: Culicidae).
|
The midguts of female mosquitoes, Culex tarsalis, were examined electron microscopically during the digestion of a meal from either artificial sources (i.e., 100% serum or defibrinated rabbit blood) or vertebrate hosts. Intense intercellular staining was apparent when the meal was derived from the vertebrate host or defibrinated rabbit blood; less intense staining with 100% serum. The staining was attributed to the "leakage" of a component of whole blood, presumably hemoglobin, into the intercellular junctional spaces. The staining component demonstrated an affinity for the outer membrane leaflet of the plasma membrane. This study provides evidence in support of "leaky guts" as a means of infecting an arthropod host without a midgut amplification cycle. The ramifications of this concept are pointed out with reference to vector competence and midgut barriers to infection by arboviruses.
| 43,090
|
Methanol precipitation of transmissible gastroenteritis virus.
|
Methanol precipitation of transmissible gastroenteritis virus was tested at Ph 4.0, 5.0, 6.0, and 7.0 and at methanol concentrations of 15%, 25%, and 30%. Supernatant and precipitate fractions were tested for complement-fixing and agar-diffusion soluble antigens and plaque-forming units, and were examined by electron microscopy. Virus could be obtained free of detectable agar-diffusion antigens and most of the complement-fixing antigens. Most of the virions were without peplomers after methanol treatment but they retained infectivity.
| 43,107
|
Partial trisomy 22q with elevated arylsulfatase-A activity.
|
A two years-old, severely mentally retarded male is reported with 22q trisomy. After the recent confirmation of the localisation of arylsulfatase-A (ARSA) on chromosome 22, the elevated activity of this enzyme (about 1,5 times the normal values) in the present patient may be another example of a gene dosage effect in autosomal imbalance.
| 43,111
|
Haemoglobin from the tadpole shrimp, Lepidurus apus lubbocki Characterization of the molecule and determination of the number of polypeptide chains.
|
Haemoglobin from the tadpole shrimp, Lepidurus apus lubbocki, was found to have a sedimentation coefficient (s020,w) of 19.3 +/- 0.2 S and a molecular weight, as determined by sedimentation equilibrium, of 798000 +/- 20000. The amino acid composition showed the lack of cysteine and cystine residues. A haem content of 3.55 +/- 0.03% was determined, corresponding to a minimal mol.wt. of 17400 +/- 200. The pH-independence in the range pH 5-11 of the sedimentation coefficient indicates a relatively high stability of the native molecule. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis gave one band with mobility corresponding to a mol.wt. of 34000 +/- 1500. The molecular weight of the polypeptide chain was determined to be 32800 +/- 800 by sedimentation equilibrium in 6 M-guanidinium chloride and 0.1 M-2-mercaptoethanol. The findings indicate that Lepidurus haemoglobin is composed of 24 identical polypeptide chains, carrying two haem groups each.
| 43,134
|
Linked transport of phosphate, potassium ions and protons in Escherichia coli.
|
Pi entry into Escherichia coli cells through either of the two Pi-transport systems (Pit or Pst) prompts the influx of K+ and H+ in a ratio that depends on the external pH. The entry of Pi is absolutely dependent on the presence of K+, and the entry of K+ is equally dependent on the presence of Pi. Experiments with a number of mutants carrying any one functional Pi-transport system and one or more of the individual K+-transport systems indicate a permissive type of linkage of the two transports, in that there is no obvious preference by any of the Pi-transport systems for a particular K+-transport system for the concomitant entry of the two ions.
| 43,137
|
The stimulus--secretion coupling 4-methyl-2-oxopentanoate-induced insulin release.
|
1. Pancreatic islet insulin secretion and 45Ca uptake showed similar responses to variation in the extracellular concentration of 4-methyl-2-oxopentanoate with a threshold at 4 mM and a maximal response at a 25 mM concentration. 2. Islet respiration, acetoacetate production and rates of substrate utilization, oxidation and amination all changed as a simple hyperbolic function of 4-methyl-2-oxopentanoate concentration and exhibited a maximal response at 25 mM. 3. The responses of ATP content, [ATP]/[ADP] ratio, adenylate energy charge and [NADH]/[NAD+] ratio were also hyperbolic in nature but were maximally elevated at lower concentrations of the secretagogue. The islet [NADPH]/[NADP+] ratio, however, was tightly correlated with parameters of metabolic flux, 45Ca uptake and insulin release. 4. NH4+ and menadione, agents that promote a more oxidized state in islet NADP, did not affect islet ATP content or the rates of [U-14C]4-methyl-2-oxopentanoate oxidation or amination, but markedly inhibited islet 45Ca uptake and insulin release. 5. It is proposed that changes in the redox state of NADP and Ca transport may serve as mediators in the stimulus-secretion coupling mechanism of insulin release induced by 4-methyl-2-oxopentanoate.
| 43,144
|
Cardiovascular dynamics after acute and long-term alpha- and beta-adrenoceptor blockade at rest, supine and standing, and during exercise.
|
1 After acute intravenous administration labetalol reduced mean values for BP, total peripheral resistance, heart rate and cardiac output. All changes were more pronounced during bicycle exercise. 2 After a mean duration of 20 months' treatment with oral labetalol the haemodynamic findings were broadly similar except for a more marked reduction in the total peripheral resistance and cardiac output had returned to pretreatment level due to an increased stroke volume which had counter balanced the reduction in heart rate. These changes occurred at rest, in the erect position and during exercise but the reductions in BP and peripheral resistance were most marked during exercise. 3 Left ventricular filling pressures and stroke volume/filling pressure ratios were not significantly altered after intravenous labetalol compared with pretreatment values. 4 Systolic BP x heart rate product was lowered particularly during exercise after both intravenous and oral labetalol. 5 After long-term oral labetalol, the most striking haemodynamic change was in the elevated resting stroke volume supine and standing.
| 43,162
|
[Porta-biliary area modifications during the graft-versus-host reaction in chick embryo and rat fetus].
|
Our results (light and electron microscopic study) show that both in chick embryos engrafted with fowl homologous spleen cells and in rat fetuses receiving blood cells from their own mother (homologous system) histologic changes occur in porta-biliary areas consisting in paravascular infiltrates (P.V.I.), bile ducts disorganization and periportal hepatocyte alterations. These modifications are closely similar to those described in other post-natal Graft Versus Host Reaction models. Yet, in both cases, the cells of the P.V.I. are chiefly of the granulocytic serie instead of the classical lymphoïd P.V.I.
| 43,189
|
Biotransformation of furosemide in patients with acute pulmonary edema.
|
Furosemide (20-80 mg) was administered iv over 5 min to 16 patients with the diagnosis of acute pulmonary edema due to left heart failure. Serum and urine samples collected during the 24 hr after administration were assayed for furosemide and its biotransformation products by gas-liquid chromatography. A biexponential decay of serum furosemide concentrations vs. time was observed. Recovery of furosemide and its metabolites from urine in 24 hr varied between 30 and 98% of the administered dose. The excretion of unchanged drug accounted for 22.6-73.4% of the dose. The excretion of the glucuronide metabolite and 2-amino-4-chloro-5-sulfamoylanthranilic acid accounted for 3.3-40.4% and from 0.13-3.92% of the dose, respectively. Urinary excretion of furosemide was less in patients with, than in those without, myocardial infarction. Urinary excretion of the oxidative acidic metabolite was increased in patients with reduced creatinine clearance. The glucuronide metabolite of furosemide was the major biotransformation product in these patients with acute pulmonary edema.
| 43,224
|
Adaptive changes in the responsiveness of adenylate cyclase to catecholamines.
|
Exposure of the intact astrocytoma cell to isoproterenol not only causes the activation of adenylate cyclase and the accumulation of cyclic AMP but sets in motion a complicated series of events designed to down-regulate the system if exposure to the agonist is extended in time. We have identified at least three of these processes: (1) a rapid uncoupling of the beta-receptor--adenylate cyclase system with subsequent loss of beta-receptors; (2) a slower, nonspecific desensitization of adenylate cyclase to the effects of all classes of receptor agonists by a process that may be mediated by cyclic AMP; and (3) a slow induction of phosphodiesterase activity that is probably mediated by cyclic AMP.
| 43,242
|
Therapy of cluster headache with histamine H1 and H2 receptor antagonists.
|
Treatment with the histamine H2 receptor antagonist, cimetidine, alone and/or in combination with the histamine H1 receptor antagonist, chlorpyramine, in 13 patients showed that cimetidine alone was ineffective. 7 of 9 patients taking the combination of H1 and H2 receptor antagonists responded well to the treatment; in 1 patient, medication was ineffective and in 1 patient, success was doubtful. In 3 patients with chronic cluster headache, the effect faded after 4 weeks. The results are discussed.
| 43,254
|
Correlation of cholesterol and bilirubin solubilization in bile salt solution.
|
Not only cholesterol but also bilirubin were considered to be solubilized by bile salt micelles. The correlation of cholesterol and bilirubin solubilization in aqueous conjugated and unconjugated bile salts solution and the effect of calcium on their solubilization were studied in this report. Cholesterol solubilization was usually reduced to some extent with increasing amount of added bilirubin. Bilirubin solubilization was always reduced by the co-existence of solubilized cholesterol. It was found that the addition of calcium increased cholesterol solubilization in conjugated bile salts system. On the other hand, calcium reduced bilirubin solubilization due to the formation of insoluble calcium bilirubinate especially in a high pH range of unconjugated bile salts system. Cholesterol solubilization in conjugated bile salts system was relatively lower than unconjugated bile salts system with or without added calcium, however co-existing bilirubin minimized these differences. The pH-dependency of cholesterol and bilirubin solubilization was small in conjugated bile salts system. On the contrary, it was remarkably bigger in unconjugated bile salts-calcium system.
| 43,271
|
Immunocytochemical localization of tyrosine hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase in the adrenal glands of the frog and rat by a peroxidase-antiperoxidase method.
|
The subcellular localizations of tryrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) in the adrenal glands of the frog and rat have been examined by a peroxidase-antiperoxidase (PAP) method. TH was localized in the ground substance of the adrenaline-containing cells and noradrenaline-containing cells, but not in the nucleus or in the mitochondria. TH was also located on the outside of the membrane of the chromaffin granules. DBH was observed only inside the granules. PNMT was found not only in the ground substance but also on the membrane of some adrenaline-containing granules. Cortical lipid cells of the frog adrenals did not show TH-, DBH-, and PNMT-reactions. The negative reactions to TH-, DBH-, and PNMT-antiserum exhibited by the summer cells of the frog adrenals prove that they belong to the cortical cells.
| 43,302
|
Experimental otitis media in chinchillas following nasal colonization with type 7F Streptococcus pneumoniae: prevention after vaccination with pneumococcal capsular polysaccharide.
|
Chinchillas were colonized intranasally with type 7F Streptococcus pneumoniae, and pneumococcal otitis media developed in greater than 50% of the animals during the first week after negative middle ear pressure (-25 mm Hg) was briefly applied. Twenty-three chinchillas were vaccinated subcutaneously with the capsular polysaccharde of type 7F S. pneumoniae to determine whether vaccination could prevent the development of experimental otitis media. Following vaccination, 14 animals seroconverted with at least a twofold rise in serum antibody concentration; nine animals that were vaccinated did not seroconvert. All of 23 vaccinated animals and 42 of 42 unvaccinated control animals became colonized after intranasal inoculation with pneumococci. Only one (7%) of the vaccinated seroconverting animals developed pneumococcal otitis media, whereas 26 (62%) of the control animals developed middle ear infection with type 7F pneumococci. Four (44%) of nine vaccinated nonseroconverting animals developed pneumococcal otitis media. Protection was associated with high levels of serum antibody prior to intranasal inoculation. Higher antibody levels were found in sterile middle ear effusions than in S. pneumoniae-infected effusions. Vaccination with type 7F pneumococcal capsular polysaccharide significantly reduced the incidence of pneumococcal otitis media following intranasal inoculation of type 7F S. pneumoniae in chinchillas.
| 43,345
|
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