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Biomedical subjects

J Molnár

Publications and source records attributed to J Molnár.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cytotoxicities and anti-herpes simplex virus activities of diterpenes isolated from Euphorbia species.

The cytotoxicities of nine diterpene polyesters obtained from Euphorbia species were assayed by measuring their effects on the growth of Vero cells. Their antiviral effects on the multiplication of Herpes simplex virus type 2 (HSV-2) were studied by using the virus yield reduction method in cell cultures. With the exception of the strongly cytotoxic 2alpha,5alpha,14beta-triacetoxy-3beta-benzoyloxy-8alpha,15beta-dihydroxy-7beta-isobutanoyloxy-9alpha-nicotinoyloxyjatropha-6(17),11E-diene (CC(50) 3.5 microg/ml), all the tested diterpenes exhibited a pronounced or moderate anti-herpes virus effect (IC(50) values between 2.5 and 8.3 microg/ml). The observed HSV-2 inhibitory activities were not associated with virucidal effects.

Animals↗
PubMed2001

Double-stranded rna elements and virus-like particles in Aspergilli.

Mycoviruses with double-stranded RNA (dsRNA) genomes are frequently encountered in Aspergillus isolates. A detailed study of such dsRNA elements in black Aspergillus isolates collected worldwide was carried out, and the data were analysed. The results indicate that about 10% of black Aspergilli are infected. However, the geographic distribution of infected isolates exhibits large variations; 3-13% of the isolates collected from different continents were found to carry dsRNA elements. Hybridization experiments indicated that electrophoretic banding patterns are not reliable tools for estimating the diversity of these mycovirus genomes. Among strains representing other Aspergillus sections, dsRNA segments indicative of mycovirus infection were observed for the first time in 4 species (A. leporis, A. petrakii, A. fumigatus and A. primulinus). The latter species is able to reproduce sexually. This is the second report on the detection of naturally-occurring dsRNAs in sexually reproducing Aspergillus species. The presence of virus-like particles in these and other Aspergilli was also examined by electron microscopy. Most infected Aspergillus isolates examined were found to carry virus-like particles in the size range 36-40 nm.

Aspergillus↗
PubMed2000

Conformational consequences of coupling bullous pemphigoid antigenic peptides to glutathione-S-transferase and their diagnostic significance.

Recombinant epitopic peptides BP1 and BP2 representing the Bullous pemphigoid autoantigens of BP230 and BP180 bound to the fusion partner glutathione-S-transferase (pGEX-4T-2, Pharmacia) have been previously shown to increase the efficacy of diagnosis of the disease. Using glutathione-S-transferase-bound monomer peptides, the sensitivity of the immunological reaction exceeded that of the free synthetic epitopes and was further increased with the number of epitopic blocks in the multimer fusion products. This has been explained by the avidity effect of the fusion partner dimer formation and the high ligand affinity due to the tandem repetitions of epitopic sequences. However, a beneficial conformation of the bound epitopic peptides might also contribute to the above phenomenon. Circular dichroism (CD) and Fourier transform infrared (FTIR) absorption spectroscopic studies revealed the importance of glutathione-S-transferase to induce and stabilize ordered secondary structures of the epitopic peptides. The free monomer and multimer peptides in aqueous buffer were present as a mixture of unordered and beta-sheet conformation, while binding them to the fusion partner the proportion of ordered secondary structures increased in parallel with the number of antigenic epitopes. The most prominent changes in the conformational state of the monomers in the fusion form were the increase of alpha-helical and beta-sheet and the decrease of unordered conformation, while in the case of oligomeric peptides the adoption of a helical conformation was accompanied by the decrease of beta-sheet structure. An outstanding alpha-helix content (46%) was detected in the case of the trimeric BP1 in its recombinant fusion form.

Autoantigens↗
PubMed2000

Development of a system for detection of circulating antibodies against hemidesmosomal proteins in patients with bullous pemphigoid.

Specific antibodies directed against special hemidesmosomal proteins are involved in the pathogenesis of bullous pemphigoid (BP), and detection of these antibodies is crucial for a correct diagnosis. As the BP autoantigen primary structures are known, the question was addressed as to whether it is possible to demonstrate circulating antibodies against BP autoantigens (BPAG1 and BPAG2) by means of an ELISA system, using antigenic epitopes. With the help of the programs Peptidestructure and Plotstructure, antigenic epitopes of BP antigens were predicted, chemically synthesized and screened using serum from 43 proven BP patients. The coding sequences of the best antigenic epitopes were then chemically synthesized and inserted as monomer and homo- or hetero-oligomer forms into fusion-expression plasmids (PGEX-4T, Pharmacia) in-frame to the C-terminus of glutathione-S-transferase. Fusion products were expressed and purified from Escherichia coli cells by affinity chromatography. The recombinant proteins were used for the detection of antibodies in the serum of 43 BP patients and of 60 controls (including 30 healthy persons, 22 patients with pemphigus vulgaris and 8 patients with other bullous dermatoses). Use of the homo- and hetero-oligomers of the recombinant fusion peptides increased the sensitivity of the disease-specific antibody detection. When a mixture of the best recombinant fusion proteins was used, the sensitivity of the ELISA assays in the case of the BP patients' serum was 0.90. This system could form the basis of a rapid and simple system for the diagnosis of BP.

Aged↗
PubMed2000

PACAP38 and PACAP27 administered intracerebroventricularly have an opposite effect on LH secretion.

The effect of PACAP38 on the LH surge and ovulation was compared with that of PACAP27 and VIP in the same model. The peptides were administered intracerebroventricularly before the critical period of the proestrous stage. PACAP38 was able to inhibit ovulation and to prevent the preovulatory LH surge; however, PACAP27 did not inhibit the ovulation and VIP inhibited the ovulation in 2/11 animals. In those animals of the last two groups in which ovulation occurred, the preovulatory LH surge was higher than in control rats. It is speculated that the opposite effect of PACAP38 and PACAP27 on the preovulatory LH surge and ovulation is possibly mediated through different receptors.

Animals↗
PubMed2000

Immunomodulating effect of 2,3,4,5-tetrahydro-1H-3-benzazepines (a new class of non-nucleoside inhibitors of reverse transcriptase).

The effects of newly synthesized, reverse transcriptase inhibitors, 3-benzazepines, for their effects on natural killer (NK) cell and blast transformation in human peripheral blood mononuclear cells were investigated. The most effective reverse transcriptase inhibitors were KF1, KF2 and KF3, which primarily suppressed immunological functions. Besides the inhibition of T cell proliferation, the benzazepines also show inhibitory effect on NK cell functions, in particularly, against large granular lymphocytes and monocytes. The B lymphocytes and Fc mediated killer functions were less inhibited.

Adjuvants, Immunologic↗
PubMed2000

Guanine-cytosine rich regions of plasmid DNA can be the target in anti-plasmid effect of phenothiazines.

The antiplasmid effects of promethazine on E. coli is the consequence of special complex formed with a covalently closed circular (ccc) form of plasmid DNA. The exact target in this macromolecule, however, was not clarified until recently. Caffeine and the chemically similar guanosine-5'- monophosphate (GMP) could compete with the antiplasmid effect of promethazine, showing that promethazine or other phenothiazines preferentially bind to xanthine type molecules. Among the xanthines, GMP was more effective at complex-forming than adenosine-5'-monophosphate (AMP). In addition, the Z-DNA was more susceptible than B-DNA. Therefore, one could suppose that guanine-cytosine (G-C) rich regions have higher affinity than adenine-thymine (A-T) rich region on phenothiazines. Because the G-C rich regions have a special role in the DNA stability via three hydrogen bonds, we suppose that these regions could have a key role in some biological effects such as antiplasmid and anticancer activity.

Binding Sites↗
PubMed2000

Interaction between antibiotics and non-conventional antibiotics on bacteria.

The individual activity of antibiotics such as ampicillin, tetracycline, erythromycin and gentamicin in combination with compounds known to modify bacterial resistance to given antibiotics was studied using the checkerboard method. The combination of promethazine with either ampicillin, tetracycline or erythromycin or the combination of methylene blue and erythromycin produced significant synergistic activity against Escherichia coli. Verapamil, however, in combination with ampicillin reduced the activity of ampicillin against E. coli. Combinations of clomipramine with either tetracycline or erythromycin, promethazine and erythromycin or verapamil and ampicillin were synergistic against Staphylococcus epidermidis that was resistant to these antibiotics. The only synergy against Pseudomonas aeruginosa was shown by the combination of methylene blue and gentamicin.

Ampicillin↗
PubMed2000

Synthesis and biological activity of N-acylphenothiazines.

Previous studies have demonstrated the relationship between radical intensity and cytotoxic activity in water-soluble compounds. This relationship was investigated in lipophilic compounds. Several N-acylphenothiazines showed higher cytotoxic activity against human leukemic and squamous carcinoma cell lines than phenothiazine, the parent compound. Electron spin resonance (ESR) spectroscopy showed that these active compounds produced much lower amounts of radicals than phenothiazine. Several compounds failed to inhibit the cytopathic effects of human immunodeficiency virus (HIV) infection in MT-4 cells. It suggested that the radical-mediated-mechanisms has not involved in the induction of cytotoxic activity by lipophilic compounds, such as N-acylphenothiazines.

Anti-HIV Agents↗
PubMed2000

Primary mono-layer cell cultures as model system for studying of environmental toxic agents: organochlorine compounds.

Organic pollution of water and soil has various harmful effects on biological systems (1). Chlorine substituted benzol compounds are one these xenobiotic substances, which are toxic to the environment (2). They can also accumulate in plant and animal tissues (3), which provides ample reason to study the effects of sublethal doses of chloro-benzols on various cell cultures. In this study the toxic effects of chloro-benzols were investigated on avian fibroblast and mammalian hepatocyte cultures. The fibroblast cultures were prepared from eggs preadapted to chloro-benzol during a fourteen-day-long incubation period. The Wistar rat hepatocyte monolayer cultures were exposed to a direct treatment of 1,2,4-tri-chloro-benzol (0.01 microgram/ml-1 microgram/ml) for 3 hours. Following the treatment with chloro-benzol, the viability of the cells was measured, together with lactic dehydrogenase activity, in both kinds of cultures. The effect of tri-chloro-benzol treatment on chicken eggs was not significant. The cells of chicken embryos were not damaged after the 1,2,4-tri-chloro-benzol treatment. The hepatocyte cultures showed the toxic effects of 1,2,4-tri-chloro-benzol after the direct and acute treatment. The cell viability decreased and the LDH activity increased significantly. These results show that the primary cell cultures are suitable for studying the effects of organochlorine compounds.

Animals↗
PubMed2000

Functional membrane changes due to tumor induction in rat pituitary cell cultures.

Membrane functions in tumorous cells are different from those in healthy cells. The aim of the present study was to investigate the changes in pituitary cell membrane functions and hormone secretion after tumor induction in vivo and in vitro. Prolactinomas were induced in vivo in female Wistar rats with estrone acetate. Normal anterior pituitaries and prolactinomas of female Wistar rats were dissociated enzymatically and mechanically, then cultured on collagen-treated plastic dishes. Some normal anterior pituitary cultures were treated with benz(c)acridines as tumorigenic agents in vitro. Intracellular 3',5'-cyclic-adenosine monophosphate (cAMP) levels were determined by a competitive binding technique, membrane fluidity was assayed by fluorescence anisotropy, and ATP-ase activities were estimated via ATP loss. The results indicated decreased membrane fluidity in tumorous cell cultures. However, in vitro benz(c)acridine treatment exerted more pronounced effects than those observed after in vivo estrone treatment. The ATP-ase activities were highly increased in benz(c)acridine-treated cells and in estrogen-induced prolactinoma cells, more strongly so in the former ones. The intracellular cAMP levels were higher than normal in both of them. The results concerning the ACTH, alpha-MSH, PRL and GH levels of normal and tumorous cell cultures were published in our previous study. Our findings show that the tumorous transformation of pituitary cells can cause significant changes in functional membrane parameters and hormone secretion. Decreased membrane fluidity was accompanied by an increased exocytosis (hormone release) and adenylate cyclase activity in tumorous cells.

Acridines↗
PubMed1999

Trinucleotide repeat polymorphism at five disease loci in mixed Hungarian population.

In apparently healthy, unrelated Hungarians we examined triplet repeat length polymorphism at Huntington disease (HD), spinal and bulbar muscular atrophy (SBMA), spinocerebellar ataxia type 1 (SCA-1), dentatorubral-pallidoluysian atrophy (DRPLA), and myotonic dystrophy (MD) loci. The distribution of alleles of the SCA-1 locus was markedly different compared with Asians and Caucasian samples examined by Watkins WS, Bamshad M, and Jorde LB [1995: Hum Mol Genet 4:1485-1491]. The unimodal distribution of peaks was shifted towards the shorter repeats on the average with 4-5 repeats. Alleles under 21 repeats at the SBMA locus were significantly less frequent in Hungarians than in Asians and Caucasians. We also found significant difference in the distribution of DRPLA allele size at repeat length over 15 repeats; these alleles were less frequent in Hungarians compared with Asians and Caucasians. No significant differences were found in alleles at the MD and also at the HD loci compared with the other groups. These findings suggest that these trinucleotide sites in combination with other markers are particularly useful for determination of the genetic origin of a population, if they can be compared with similar subset of data of other populations. The present results could not confirm the large genetic distance between Hungarian and Oriental races and the relatively short distance between Hungarian and other European populations suggested in earlier reports [Czeizel A, Benkmann H-G, Goedde HW, editors. 1991: Genetics of the Hungarian population. Budapest: Akadémiai Kiadó. p 82-334].

Alleles↗
PubMed1999

[Reversal of drug resistance in bacteria and tumor cells. (Drug research based on computer-predicted activity)].

This paper present a short overview on the new perspectives in drug-design against drug resistance phenomena focusing on the infectious antibiotic resistance of bacteria. The role of plasmids in resistance of bacteria, the mode of transmissions were analyzed in details. The elimination of plasmids--the genetic basis of bacterial resistance located extrachromosomally--was studied systematically with several heterocyclic compounds. Correlations were analyzed between the anti-plasmids++ effects and chemical structure of tricyclic compounds in quantitative structure activity relationship (QSAR) studies. A hypothesis was presented to exploit the analogous mechanisms of multidrug resistance in bacterial and cancer cells by inhibiting the action of drug exporter proteins in the presence of compounds synthetized on the basis of computer aided drug design.

Antineoplastic Agents↗
PubMed1999

Anti-psychotic drugs reverse multidrug resistance of tumor cell lines and human AML cells ex-vivo.

Anti-psychotic drugs are used in cancer patients undergoing chemotherapy frequently and the concomitantly used drugs may alter the pharmacokinetics of each other. One reason for the alteration of pharmacokinetics may be the modulation of the function of P-glycoprotein, whose efflux pump occurs in resistant cancer cells, in human intestine and in the blood-brain barrier. For this reason we tested the effect of several anti-psychotic drugs on the multidrug-resistant pump, P-glycoprotein. We found that in the MDR gene transfected L121C MDR, L5178 MDR and in the KB-V-1 cells selected for resistance some antipsychotic drugs block the function of P-glycoprotein. Blood cells of two treatment-resistant leukemic patients also showed increased uptake of daunorubicin if treated ex vivo with the anti-psychotic drugs. Our results suggest that pharmacokinetic studies should be performed prior to concomitant clinical use of such drugs which block P-glycoprotein function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗