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Biomedical subjects

J Molnár

Publications and source records attributed to J Molnár.

At least 109 records · Page 6Linked to original sources

Comparative study of antiproliferative effects of chlorpromazine, 7,8-dioxochlorpromazine, amantadine-N-mustard, rutin-N-mustard and alpha, beta and gamma interferon on K-562 cells in vitro.

The effects of rutin-N-mustard, amantadine-N-mustard, chlorpromazine and human interferon types alpha, beta and gamma (IFN-alpha, -beta and -gamma) were studied on the DNA, RNA and protein synthesis of K-562 cells. Monocyte-mediated cytotoxicity and immune spleen cell activity were examined in the presence of the same compounds (except for IFN-beta). The natural killer (NK) cell activity was tested in the presence of the two chlorpromazine compounds and the two N-mustard derivatives. Only 7,8-dioxochlorpromazine exerted an inhibitory effect on DNA synthesis. The protein synthesis of the cells was inhibited in the presence of IFN-alpha, -beta and -gamma. 7,8-Dioxochlorpromazine exerted some inhibition on both NK and immune spleen cell activity, while monocyte-mediated cytolysis was not altered. IFN-alpha, -beta and -gamma activated the cytolytic activity of monocytes and the NK activity in control experiments. Chlorpromazine, rutin-N-mustard and amantadine-N-mustard were ineffective in both tests in vitro. Rutin-N-mustard, 7,8-dioxochlorpromazine and the interferons may be assumed to have quite different antiproliferative mechanisms of actions.

Amantadine↗

Effect of thymectomy in immune diseases other than myasthenia.

In the course of thymectomy of patients with myasthenia gravis, surprising data concerning the recovery or considerable improvement of other immune disorders have been observed. Among these disorders rheumatoid arthritis figured in six instances, immune thrombocytopenia in two cases, polymyositis and psoriasis in one case each. Thymectomy as a powerful immunosuppressive procedure may have a role in the therapeutic management of some immune disorders other than myasthenia gravis.

Adolescent↗

GnRH secreting cultured fetal rat hypothalamic cells do not degrade GnRH.

The possible degradation of GnRH in the hypothalamus was investigated. Rat fetal hypothalamic cells were kept in culture for two weeks and basal and stimulated GnRH release was measured by highly sensitive RIA. These intact hypothalamic cells did not degrade GnRH during 4 hours of incubation, but a 50% degradation occurred after 24 hours incubation followed by HPLC using specifically tritium labeled GnRH or RIA. The rate of degradation or the kinetic of degradation did not change by increasing GnRH concentration in the medium or by mechanical instead of enzymatic dispersion of the cells. For comparison GnRH degradation in homogenized hypothalamic tissue and in synaptosomal preparation was measured and rapid degradation was found. Our results suggest that intact hypothalamic cells under physiological circumstances do not degrade extracellular GnRH.

Animals↗

Inhibition of bacterial plasmid replication by stereoselective binding by tricyclic psychopharmacons.

Several dibenzazepines, thioxanthene, and phenothiazine stereoisomers were studied for their abilities to inhibit plasmid replication, intracellular transfer of R-plasmid, bacterial ATP-ase, and mouse serum cholinesterase isoenzyme. Partially saturated derivative of desipramine inhibited plasmid replication and transfer, but the fully saturated derivative was inactive. The inhibition of plasmid curing and transfer patterns did not correlate with the inhibition of ATP-ase and cholinesterase. Trans-clopenthixol was more effective in plasmid elimination than the cis-isomer. On the other hand, the cis-isomer inhibited ATP-ase and cholinesterase more than the trans-isomer. The levo- and dextro-methoxytrimeprazine also inhibited plasmid replication and enzyme activity. We believe that the tricyclic configuration of the drugs tested for stereospecific binding to bacterial receptors is more important than its side chain orientation. We believe that there is a similarity between bacterial receptor sites and neural receptor sites. Therefore, this model may be useful in the study of neuropharmacological agents as potential antibacterial agents.

Adenosine Triphosphate↗

[Comparison of institutional and ambulatory methods of rehabilitation in myocardial infarct].

The authors compared the results of their own methods of rehabilitation after myocardial infarction, applied in two groups: 92 patients who were trained in the institute, and in other 92 patients who performed their rehabilitation training for some weeks at home. In all patients the working capacity (bicycle ergometry), psychosocial state and rate of return into professional activity over one year after infarction were examined. No statistically significant differences in the results obtained in both groups were found except for the working capacity, the improvement of which was significantly more pronounced in patients who performed their rehabilitation training in the institute.

Adaptation, Psychological↗

Structural characterization of nuclear poly(A)-protein particles in rat liver.

Poly(A)-protein particles were prepared from rat liver nuclear extract after digestion with pancreatic ribonuclease and ribonuclease T1 by sucrose gradient centrifugation. The particles were sedimented in a range of 9-23S with a peak at 16S. The particles isolated in this manner were 99-100% resistant to further pancreatic ribonuclease treatment and contained more than 90% adenylic acid. In CsCl density gradient the nuclear poly(A)-protein particles banded in a narrow density range of 1.28-1.32 g/cm3 with a peak at 1.30 g/cm3, which corresponds to about 90% of protein in the particles. The average length of the poly(A) molecules prepared from the 16-S particles was about 140 nucleotides. Urea/sodium dodecyl sulphate/polyacrylamide gel electrophoresis demonstrated two major polypeptide components with Mr of 63 000 and 90 000 and at least ten minor polypeptides in the 45 000-130 000-Mr range. In sodium dodecyl sulphate/polyacrylamide gels the 63 000-Mr polypeptide was the only one major component. Amino acid analysis of the polypeptides bound to nuclear poly(A) revealed that the polypeptides contained a relatively large amount of aspartic acid + asparagine and glutamic acid + glutamine (24%). Treatment of glutaraldehyde-fixed particles with micrococcal nuclease showed that more than 90% of the poly(A) was accessible to the enzyme, thus almost the entire poly(A) should be located on the surface of the particles. On the basis of the results a model for the 'average' 16-S particle was constructed.

Animals↗

Andrologic aspects of varicocele.

The changes in the spermatogram subsequent to surgery for varicocele because of infertility were examined, consideration being given to the various sperm parameters. Improvement of one parameter or more was demonstrable in 30 out of 40 surgical cases. The parameters indicative of motility showed the most marked improvement. The andrologic significance of early diagnosis is emphasized.

Adult↗

Desensitization of luteinizing hormone release in cultured pituitary cells by gonadotropin-releasing hormone.

Preincubation of cultured pituitary cells with GnRH caused a marked decrease in subsequent LH release. The rate of desensitization increased when the preincubating concentration of GnRH and the preincubation time were increased. Pituitary cells obtained from male rats were not as sensitive to GnRH as cells obtained from female rats and the extent of desensitization was also smaller in cells from male rats. Densensitization was found to be a long-lasting effects, without any change in the viability of the cells. A superactive analogue of GnRH (D-Phe6-GnRH) caused almost complete desensitization of LH secretion, while a competitive inhibitory analogue of GnRH caused a much smaller decrease in LH response which could be overcome by increasing the concentration of GnRH used for reincubation. These data suggest that the desensitization is closely related to the biological activity of GnRH and does not correlate with receptor binding. High concentrations of potassium also induced desensitization, although to a lower extent than GnRH. Since K+ induces LH release by a different mechanism than GnRH, our data suggest that the desensitization phenomenon cannot be explained only at the receptor level. The time curve of desensitization supports the idea that GnRH action has two-phases: an acute effect which cannot be desensitized, and a secondary phase which can be densensitized.

Animals↗

Quantitative thin-layer chromatography of cobalamin complexes.

Quantitative thin-layer chromatography was used to study the hydroxo-, cyano- and dicyanocobalamin transformation equilibria. A new stereoisomer of cyanocobalamin was shown to be formed from dicyanocobalamin on the chromatographic plate. The formation, stability and UV spectrum of this compound (isocyanocobalamin) was studied.

Journal Article↗

Inhibition of the adhesion of E. coli on cultured human epithelial cells in the presence of promethazine or imipramine.

The adhesion and multiplication of E. coli strain K12 with a derepressed synthesis of sex pili and of a nephropathogenic E. coli strain isolated from the urine of a patient with pyelonephritis, were demonstrated on the surface of cultured HEp-2 cells. The adhesion of the two E. coli strans was inhibited in the presence of 0.5-5.0 micrograms/ml promethazine or imipramine, but the multiplication of the bacteria on the monolayers was not decreased significantly in the presence of the two drugs. A scanning electronmicroscopic technique was developed to study bacterial adhesion and colony formation on epithelial cells.

Adhesiveness↗

(3H)-imipramine binding and plasmid replication sites in Escherichia coli.

Binding of (3H)-imipramine to F'lac plasmid-carrying E.coli was studied. The binding was saturated at 500 mM imipramine in the case of F'lac cells, and the imipramine binding of plasmid-carrying bacteria was inhibited by several tricyclic compounds, such as acridine orange, desimpramine and promethazine. Methylene blue enhanced the (3H)-imipramine binding of bacteria. Binding of radioactively labelled pBR322 plasmid DNA to the internal membrane was more efficient in the presence of plasmid-eliminating drugs than in that of their ineffective derivatives. It is concluded that a structural association exists between imipramine binding and plasmid replication sites in bacteria. The plasmid DNA is assumed to bind irreversibly to its replication site in the presence of the drug and this process can lead to plasmid elimination.

Antidepressive Agents, Tricyclic↗

Isolation and characterization of nuclear hnRNP complexes from Drosophila melanogaster tissue culture cells.

Fractionation on sucrose gradients of nuclear described extracts prepared from cultured Drosophila melanogaster cells by sonication of the nuclei in the presence of rat liver cytosol RNAase inhibitor revealed a complex polysome-like pattern of nuclear ribonucleoprotein complexes. The bulk of these heterogeneous ribonucleoprotein (hnRNP) complexes sedimented in the 30S to 80S zone of the sucrose gradient. According to biochemical and morphological data, the monomer particle proved to be the 45S hnRNP and its average diameter was found by electron microscopy to be 24-26 nm. The buoyant density of both the mono and polyparticles was about 1.4 g/cm3, with a slight degree of heterogeneity. The proteins from different zones of the sucrose gradient were composed primarily of similar polypeptides of 47 000, 56 000, 64 000, 96 000 and 130 000 daltons. Complete dissociation of nuclear hnRNP complexes was observed by resedimentation of the particles in the presence of 0.7 M NaCl or 4 M urea. RNAase A digestion (0.1 microgram/ml at 0 degree C for 10 min) resulted in the solubilization of part of the hnRNP and aggregation of some particles. The bulk of the RNA isolated from the different sized hnRNP complexes sedimented in the 7 to 11S region in the sucrose gradient. The large hnRNP complexes contained hnRNA strands larger than 15S, up to 28S. The base composition of the RNA from the 45S monoparticles proved to be AU type: A + U/G + C = 1.7. The RNAs from the 60-75S and 90- 100S polyparticles were also AU type, with an A + U/G + C ratio of 1.46 and 1.21, respectively. The hnRNP complexes exhibited marked heterogeneity in the electron microscope. Our biochemical and morphological observation point to a nonrandom organization of hnRNP particles in Drosophila melanogaster nuclei.

Animals↗

The effect of rutin-N-mustard on the survival of NK/Ly ascites tumour-bearing mice.

A newly synthetized rutin derivative, rutin-N-mustard, showed a marked antiproliferative effect on NK/Ly ascites tumour cells in vivo. When administered i.p. or i.v., this compound increased the survival time of the animals, but oral administration had no such effect. The drug was not able to kill the tumour cells, since the chromium release from the rutin-N-mustard-treated tumour cells was the same as in the case of the controls. Tumour growth was completely inhibited in the animals when the cells were pretreated with 100 mg/kg rutin-N-mustard before transplantation. The results also showed that rutin-N-mustard has little effect on the xenogenization of NK/Ly tumour cells. We presume that the antiproliferative action of rutin-N-mustard is due to its alkylating activity.

Administration, Oral↗