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Biomedical subjects

B Kiss

Publications and source records attributed to B Kiss.

At least 19 recordsLinked to original sources

Intravenous "pulse" cyclophosphamide therapy of crescentic glomerulonephritis.

Pulse steroids and monthly intravenous cyclophosphamide with a rapid steroid taper were used to treat seven patients with crescentic glomerulonephritis. Despite major impairment of renal function, all patients had a marked improvement in GFR by six months and improvement in proteinuria occurred in six of the seven patients. Two patients were able to discontinue dialysis. The doses of steroids and cyclophosphamide used were less than in comparable studies and side-effects of therapy were minimal. Repeat renal biopsies at over one year demonstrated marked glomerulosclerosis despite relatively stable renal function. Histologic analysis of total glomerular involvement indices on serial biopsies suggested no recruitment of new glomeruli into the crescenteric process once treatment had been initiated. Thus, intravenous pulse cyclophosphamide with pulse steroid therapy appears to be a safe and effective initial therapy for some patients with RPGN. Significant glomerulosclerosis on repeat biopsies suggests that glomerulosclerosis may be predetermined by the initial degree of irreversible glomerular damage and that the long-term course of the disease remains guarded.

Adult

Vinpocetine preferentially antagonizes quisqualate/AMPA receptor responses: evidence from release and ligand binding studies.

The effect of vinpocetine on excitatory amino acid receptors was examined in the rat brain by two different biochemical approaches. In release experiments with striatal slices, vinpocetine reduced the efflux of dopamine and acetylcholine evoked by glutamate, quisqualate and N-methyl-D-aspartate (NMDA), but not that evoked by kainate. In binding experiments with cortical membranes, vinpocetine reduced the binding of [3H]2-amino-3-3-hydroxy-s-methylisoxasole-4-yl-propionic acid ([3H]AMPA), a quisqualate partial agonist, in an incomplete manner, but failed to influence the binding of [3H]kainate and [3H]3-(2-carboxypyperazine-4-yl)-propyl-1-phosphonic acid ([3H]CPP), an NMDA agonist. These findings suggest that vinpocetine is a quisqualate/AMPA antagonist of some specificity and selectivity.

Acetylcholine

Defective acidification of intracellular organelles in cystic fibrosis.

The phenotype of cystic fibrosis (CF) includes abnormalities in transepithelial transport of Cl- (refs 1-5), decreased sialylation and increased sulphation and fucosylation of glycoproteins, and lung colonization with Pseudomonas. It is not apparent how these abnormalities are interrelated, nor how they result from loss of function of the CF gene-encoded transmembrane regulator (CFTR). We have previously shown that that the pH of a secretory granule is regulated by the vesicular conductance for Cl- (ref. 11). Here we find defective acidification in CF cells of the trans-Golgi/trans-Golgi network, of prelysosomes and of endosomes as a result of diminished Cl- conductance. Sialytation of proteins and lipids is reduced and ligand traffic altered. These abnormalities can result from defective acidification because vacuolar pH regulates glycoprotein processing and ligand transport. The CF phenotype is similar to that of alkalinized cells and acidification-defective mutatants.

Cell Line

Heterogeneity of N-methyl-D-aspartate receptors regulating the release of dopamine and acetylcholine from striatal slices.

In an attempt to examine some functional characteristics of the N-methyl-D-aspartate (NMDA) receptor complex, the NMDA-evoked effluxes of endogenous dopamine (DA) and [3H]acetylcholine ([3H]ACh) were simultaneously examined in a rat striatal slice preparation. NMDA induced release of both DA and ACh in a concentration-dependent, Ca(2+)-, Mg(2+)-, and tetrodotoxin-sensitive manner. These release responses were remarkably reduced by long-term pretreatment with a low concentration of NMDA, an indication of the desensitization of the NMDA receptor. Glycine was potent in reversing the desensitization-related reduction of DA release but failed to reverse the diminution of ACh release in the same slices. Our results indicate that the NMDA receptors regulating the release of DA and ACh are different with respect to their glycine modulatory site. This finding is consistent with a functional heterogeneity of the NMDA receptor complex in the rat striatum.

Acetylcholine

Vinpocetin protects against excitotoxic cell death in primary cultures of rat cerebral cortex.

The protective effect of vinpocetin, a drug clinically useful in brain hypoxia/ischemia, was examined in vitro on cerebrocortical cultures treated with glutamate and related excitotoxins. The extent of cell death was quantified by measuring lactic dehydrogenase activity released from damaged cells into the culture medium. Vinpocetin partially protected the cortical cells against cell death induced by N-methyl-D-aspartate, quisqualate and kainate, indicating that the drug exerts a direct protective action on cerebrocortical cells bearing excitatory amino acid receptors.

Amino Acids

Inhibitory effect of hypoxic condition on acetylcholine release is partly due to the effect of adenosine released from the tissue.

Isolated longitudinal muscle strip with Auerbach's plexus attached was used to study the stimulation-evoked release of 3H-acetylcholine (3H-ACh) under normoxic and hypoxic conditions. Hypoxia reduced the release of ACh. Theophylline, a purinoceptor P1 antagonist and vinpocetine, an antiischemic compound partly reversed the effect of hypoxia. Unlike theophylline, the effect of vinpocetine was not mediated via adenosine action, since it failed to affect the presynaptic action of adenosine, and the effect of theophylline and vinpocetine was additive. When they were added together the effect of hypoxia was almost completely antagonized. Dipyridamole, an adenosine uptake inhibitor, potentiated the effect of hypoxia and the presynaptic inhibitory action of adenosine on ACh release. Evidence was obtained that the effect of hypoxia is at least partly due to adenosine formed from purine nucleotides.

Acetylcholine

Synthesis of N-(phosphonoacetyl)-dipeptide derivatives and evaluation of their antihypertensive activity.

A series of N-(phosphonoacetyl)-dipeptide derivatives was synthesized for pharmacological testing as antihypertensive compounds. Several of these compounds demonstrated a moderate antihypertensive effect in Wistar spontaneous hypertensive rats (SHR) with p.o. dosing. ACE inhibition by the compounds was studied using ACE from rat plasma and lung. Inhibitors containing esterified C-termini are pro-drugs and showed activity only for plasma ACE.

Angiotensin-Converting Enzyme Inhibitors

[Prognosis of stomach cancer patients in the age of complex diagnostic methods].

A retrospective study was done in 1986-87 on the survival of patients with stomach cancer. Their disease was established with complete diagnostic methods between 1975-87. In 244 patients diagnosis had been set up more than five years before. The survival of these patients was 19.4%, i.e. 47 of them were alive five years after the diagnosis. Both operability and resectability improved when compared to the earlier results (between 1965-74.). The most favourable 5-year survival and resectability were found in patients with intestinal type cancer. Early cancer was 8.3% of total, however, when only those patients were taken into consideration who had been treated either surgically or underwent surgical or endoscopic polypectomy, the percentage markedly increased 22.7%. The survival of patients with early stomach cancer was excellent: 34/37 (91.9%). A significant decrease of the incidence of stomach cancer in the region so far could not be observed.

Gastrectomy

Age-related changes of noradrenergic innervation of rat splanchnic blood vessels: a histofluorescence and neurochemical study.

The influence of ageing on the noradrenergic innervation of superior mesenteric artery and vein, renal artery and vein, and portal vein was studied in male Wistar rats by means of catecholamine histofluorescence, image analysis techniques and high pressure chromatography with electrochemical detection. Old age was accompanied by a marked increase in the density of noradrenergic innervation and an increase of noradrenaline levels in superior mesenteric artery, renal artery, and portal vein. In contrast, no significant age-related changes were observed in the density of noradrenergic innervation or in noradrenaline levels in superior mesenteric and renal vein. The present data indicate that, at least in superior mesenteric and renal artery and portal vein, senescence is not accompanied by loss or by lack of change in the noradrenergic innervation as commonly believed to be the case in many vascular trees. On the basis of our findings it cannot be excluded that increased plasma catecholamine levels observed in senescence derive, in part, from perivascular sympathetic endings.

Adrenergic Fibers

[Effects of electron radiation on lung tissue in the postoperative irradiation of breast carcinoma].

The changes in lung tissue density arrived during the postoperative irradiation of 21 patients between February, 1984 and March, 1985 were investigated by means of a computer tomograph type Medicor-Pfizer 0100. It was shown that the influence of ionizing radiation produced an increased density of the pulmonary tissue even in case of the most precise radiophysical plan and the optimum energy. In all cases the density measured by CT after the irradiation was higher than before radiotherapy. This might be a very early sign of radiogenic late effects. An adequate modification of the irradiation plan has therefore to be carried out in the manner of a feedback.

Adult

Stimulus-evoked efflux of GABA from preloaded slices of the rabbit oviduct.

The effect of electrical and chemical stimulation on the efflux of [3H]gamma-aminobutyric acid (GABA) from preloaded slices of the rabbit oviduct was examined. Electrical field stimulation significantly increased the outflow of [3H]GABA. This effect could not be prevented by tetrodotoxin or by the removal of Ca2+ from the medium. High K+ concentrations, veratrine and ethylenediamine also evoked a remarkable elevation in the efflux. The release induced by veratrine was completely abolished in a Ca2+-free medium or in the presence of tetrodotoxin, while the release evoked by high K+ or ethylenediamine was resistant to both conditions. These findings indicate that GABA can be released from the oviduct under the effect of depolarizing stimuli, raising the possibility of a physiological interaction between oviductual GABA and its receptors. The characteristics of oviductal GABA efflux differ from those of neuronal and glial GABA release.

Animals

Presence of gamma-aminobutyric acid and its specific receptor binding sites in the human term placenta.

The concentration of gamma-aminobutyric acid (GABA), the activity of glutamate decarboxylase (GAD), and the presence of specific GABA receptor binding sites have been examined in human term placentas. The estimated values of GABA concentration and GAD activity in the placenta were about 50 nmol/g tissue and 1.1 nmol/mg protein/h, respectively. A remarkable density of high-affinity and specific GABA binding sites has also been demonstrated in membranes of the human term placenta. These binding sites showed the properties of a GABAA receptor. The present findings suggest a possible role of GABA in the function of human placenta.

Female

An integrated scheme for the simultaneous determination of biogenic amines, precursor amino acids, and related metabolites by liquid chromatography with electrochemical detection.

A new method using high-performance liquid chromatography with electrochemical detection (HPLC-ED) for the simultaneous determination of monoamines, their precursor amino acids, and related major metabolites in small samples of brain tissue weighing from 0.5 to 50 mg is described. The method is based on the preliminary isolation of monoamines (dopamine, norepinephrine, epinephrine, and serotonin), their precursor amino acids (tyrosine, 3,4-dihydroxyphenylalanine, tryptophan and 5-hydroxytryptophan), and their major metabolites (3-methoxytyramine, normetanephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, vanillylmandelic acid, 3-methoxy-4-hydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid) by chromatography on small columns of Amberlite CG-50 and Dowex 50W, and by ethyl acetate extraction. All the compounds in the four isolated fractions were measured by HPLC-ED on a reversed-phase column under four different conditions. The sensitivity was from 0.1 to 40 pmol, depending on the substances analysed. This newly established method was applied to the study of the effects of an aromatic L-amino acid decarboxylase inhibitor (NSD-1015) and a monoamine oxidase inhibitor (pargyline) on the levels of monoamines, their precursor amino acids and their major metabolites in brain regions of mice.

Amino Acids

Comparative characterization of glutamate decarboxylase in crude homogenates of oviduct, ovary, and hypothalamus.

Some biochemical characteristics of L-glutamate decarboxylase (GAD) were compared using crude homogenates of the rat oviduct, ovary, and hypothalamus. As estimated by the measurement of CO2 production, the specific activities of oviductal and ovarian GAD were about 10 and 3% of the hypothalamic value, respectively. Stoichiometric formation of gamma-aminobutyric acid (GABA) and CO2 from L-glutamate could be observed in oviduct and hypothalamus, while in ovarian homogenates the production of CO2 was more than nine times that of GABA. Hypothalamic and tubal GAD showed similar time course, temperature dependence, and pH dependence. The dependence on protein concentration and on exogenous cofactor supply was also similar in these two tissues. The kinetic constant for L-glutamate as a substrate was nearly the same in oviduct (1.30 mM) and hypothalamus (1.64 mM). The responsiveness of tubal and hypothalamic GAD to various inhibitors was also similar. The present findings indicate that the oviductal and the hypothalamic GAD may be identical, and they suggest a possible GABAergic innervation of the Fallopian tube.

Animals