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Biomedical subjects

I Lengyel

Publications and source records attributed to I Lengyel.

32 records · Page 2Linked to original sources

Pathological phosphorylation causes neuronal death: effect of okadaic acid in primary culture of cerebellar granule cells.

We have investigated the role of protracted phosphatase inhibition and the consecutive protracted protein phosphorylation on neuronal viability. We found that in primary cultures of cerebellar granule neurons, the protracted (24-h) inhibition of the serine/threonine protein phosphatases 1 and 2A (EC 3.1.3.16) by treatment of the cultures with okadaic acid (OKA; 5-20 nM) caused neurotoxicity that could be inhibited by the protein kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) or by the previous down-regulation of the neuronal protein kinase C (PKC; ATP:protein phosphotransferase; EC 2.7.1.37). PKC was down-regulated by exposure of the cultures for 24 h to 100 nM phorbol 12-myristate 13-acetate (TPA). The effect of the drugs used in the viability studies on the pattern of protein phosphorylation was measured by quantitative autoradiography. In particular, the 50- and 80-kDa protein bands showed dramatic changes in the degree of phosphorylation: increase by OKA and brief TPA treatment; decrease by H7 or 24 h of TPA treatment; and inhibition of the OKA-induced increase by H7 or 24 h of TPA treatment. The results suggest that the protracted phosphorylation, in particular that mediated by PKC, may lead to neuronal death and are in line with our previous suggestion that prolonged PKC translocation is operative in glutamate neurotoxicity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Hyperuricacidemic nephrogenic diabetes insipidus].

Five weeks following the removal of the urate calculus the 58-year-old patient suffered from anadipsia and drank 6-8 litre of water daily. Uric acid level was high in the serum and the carbamide-N and creatinine showed also increased values. Upon the administration of adiuretin the polyuria and polydipsia ceased, yet the specific weight of the urine stayed under 1010.

Diabetes Insipidus↗

Calcium dobesilate (CLS 2210) protects the myocardium in early acute myocardial infarction: a preliminary randomized, double-blind, placebo-controlled study of its effects on biochemical markers.

To determine the effect of calcium dobesilate (CLS 2210) on biochemical markers of acute myocardial infarction, and thereby assess its action in limiting myocardial necrosis, this compound was administered intravenously by a randomized, double-blind technique to 23 of 41 patients suffering their first infarction. The remaining 18 patients received a placebo. Administration was begun within 3 h of onset of symptoms and continued for 72 h. Before and during treatment, blood samples were taken for measurement of the serum activity of creatine kinase and its isoenzyme MB, and the serum and urinary concentrations of myoglobin and glycosaminoglycans. Serum creatine kinase and serum and urinary myoglobin were significantly lower in the CLS 2210-treated patients than in the placebo patients throughout the 72 h (p = 0.01, 0.005, and 0.004, respectively). Serum creatine kinase MB and serum glycosaminoglycan in the CLS 2210 patients were initially higher than in the controls, but fell below the control levels between the 40th and 55th hours (p = 0.89 and 0.02, respectively). The glycosaminoglycan urinary concentrations alone were higher in the CLS 2210 group than in the placebo group throughout (p = 0.0005). These findings suggest that CLS 2210 reduces myocardial infarct size in human subjects, as it is already known to do in animals.

Acute Disease↗

Histomorphological and pathobiochemical changes of varicose veins. A possible explanation of the development of varicosis.

The authors should like to contribute to the unsettled problem of the development of varicose venous disease with their own experience. They evaluate parallel the histomorphological observations and certain pathobiochemical changes which can be recognized in exstirpated varicose veins. Fourty five stripped saphenas have been studied. They were divided into two groups: a macroscopically normal and a varicose one. The varicose patients were divided again into two subsamples according to the occurrence or lack of thrombophlebitis in their medical case history. The authors were looking for the appropriate pathobiochemical changes of the vessel walls running parallel to the usual histopathological changes. It seems quite possible that the effect which triggers the development of the disease could be anything which causes hypoxia, alters the energy metabolism of the otherwise bradytrophic vascular tissues. Accumulation of proteoglycans, as well as collagen and elastic fibers in place of the smooth muscle cells may cause a decrease in the elasticity of the veins and may produce favourable conditions to thrombus formation and local inflammation.

Carbon Dioxide↗

[Biochemical serum parameter changes during and after autologous small intestine transplantation in animal experiments. I. Intra- and immediate postoperative period].

Biochemical parameters sodium, potassium, lactate, alkaline phosphatase, ASAT, and ALAT were examined at the beginning of the operation, before, and 0, 2, 4, 6 hours after implantation of a small bowel autograft in an autologous model of intestinal transplantation in dogs. By the way of these early biochemical studies we have got information about metabolic situation during organ transplantation, efficiency of preservation and vitality of the graft. Using the given method safe preservation of small bowel can be guaranteed. Postoperatively only little changes of laboratory parameters occur.

Alanine Transaminase↗

Kinetics of protein phosphorylation in microvessels isolated from rat brain: modulation by second messengers.

The role of second messengers in the regulation of protein phosphorylation was studied in microvessels isolated from rat cerebral cortex. The phosphoproteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the kinetics of 32P incorporation into specific protein substrates were evaluated by computer-aided x-ray film densitometry. With the use of this method, Ca2+-calmodulin (CAM)-, Ca2+/phospholipid (PK C)-, cyclic GMP (cGMP)-, and cyclic AMP (cAMP)-dependent protein kinases were detected. CAM-dependent protein kinase proved to be the major phosphorylating enzyme in the microvascular fraction of the rat cerebral cortex; the activity of cGMP-dependent protein kinase was much higher than that of the cAMP-dependent one. Autophosphorylation of both the alpha- and beta-subunits of CAM-dependent protein kinase and the proteolytic fragment of the PK C enzyme was also detected. The kinetics of phosphorylation of the individual polypeptides indicate the presence in the cerebral endothelium of phosphoprotein phosphatases. The phosphorylation of proteins in the cerebral capillaries was more or less reversible; the addition of second messengers initiated a very rapid increase in 32P incorporation, followed by a slow decrease. Because the intracellular signal transducers like Ca2+ and cyclic nucleotides are frequently regulated by different vasoactive substances in the endothelial cells, the modified phosphorylation evoked by these second messengers may be related in vivo to certain changes in the transport processes of the blood-brain barrier.

Animals↗

Inosine increases anoxic tolerance and postischaemic restitution of the heart: experimental studies on possible mechanism(s) of action.

Various experimental models were utilized to determine the in vivo cardiac actions underlying the presumptive therapeutic benefit of the naturally occurring adenine nucleoside, inosine. 1. In pentobarbital-anaesthetized dogs coronary vasodilator responses to arterial hypoxia were augmented and postanoxic depression of cardiac contractile force was prevented by i.v. infusion of inosine (5 mg X kg-1 X min-1). 2. Thermographic observations demonstrated in the in situ dog heart a significant inosine-induced epicardial warming (coronary flow increase) which was resistant to P1-purinergic blockade (aminophylline). 3. Following total cardiopulmonary bypass and cardioplegic cardiac arrest of 90 min duration in the dog, inosine administration (5 mg X kg-1 X min-1) evoked a lasting increase in myocardial contractile force and cardiac output. 4. In Langendorff perfused guinea pig hearts subjected to normothermic ischaemia of 1 hour duration and treated with inosine (0.05 mg X min-1), the release of cytoplasmatic enzymes (CK-MB, alpha-HBDH) and myoglobin was significantly less than in untreated ischaemic controls. In the two latter series of experiments (3 and 4) the inosine action was contrasted by the deleterious effect of catecholamines (noradrenaline and isoproterenol) administered in moderate or small doses, respectively. It was concluded that inosine has cardioprotective actions partly related to and partly independent of its influence on coronary blood supply, suggesting that administration of the nucleoside may be useful in various surgical attempts directed to myocardial salvage.

Animals↗

ABO blood typing of human skeletal remains in Hungary.

The author reports about the theoretical effects of his paleoserologic investigations on some historical population genetics problems. First he refers to the essence of the two modifications by the help of which the fluorescent antibody method can be made suitable for blood typing or archeological skeletal remains and determines his working units (sample, series, "population") used in the paleoserologic researches. The benefits of the projection of the ABO blood typing results on the map of the cemetaries are demonstrated. The distribution of the several phenotypes are collated to the character or richness of the grave goods and to the taxonomic features of the late individuals. The thorough examination of the serogenetic distances among the several samples of a given historical period may cast more light on the ethnic interrelations of the earlier populations living in the same geographic area. Following up the serogenetic changes of a population during subsequent historical periods, new ideas can be gained about the importance of the environmental, economic, and demographic factors shaping the serogenetic profile of the population.

ABO Blood-Group System↗

Clinical and experimental study of cold cardioplegic myocardial protection.

The authors used a multi-dimensional approach to the study of the effects of intra-operative myocardial protection; the results of three series of investigations are reported. First, conditions underlying the effectiveness of the authors' modified cardioplegic solution were studied by laboratory and histological methods in ex vivo guinea pig hearts. Evidence is presented for the detrimental effects of catecholamines and the beneficial action of inosine. The second part of the report deals with problems of effective myocardial cooling in partially ischaemic canine hearts, investigated by infrared thermographic examinations of temporal and spatial thermal distribution over the entire visible cardiac surface. At last the authors present the result of their complex intra- and postoperative enzyme analysis combined with mathematical evaluation (cluster analysis in a group of patients suffering from ischaemic heart disease).

Animals↗