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M Seman

Publications and source records attributed to M Seman.

79 records · Page 5Linked to original sources

In vitro determination of antiviral activity of MS8209, a new amphotericin B derivative, against primary isolates of HIV1.

MS8209, an amphotericin B derivative, was previously reported to be an inhibitor of HIV1 replication in vitro. In the present study, we determined the 50 and 90% in vitro inhibitory concentrations of MS8209 for 9 HIV1 isolates including both zidovudine-sensitive and zidovudine-resistant isolates and the reference strain Lai, using the peripheral blood mononuclear cell (PBMC) assay. We also evaluated the sensitivity of HIV1 replication to MS8209 during primary isolation from PBMCs. An inhibitory effect of MS8209 in PBMC infection was observed either when the drug was only present during the adsorption step or when the drug was initially absent but maintained throughout the culture period; the combination of these two approaches provided the highest inhibition rate. These results indicate that MS8209 can inhibit the replication of HIV1 isolates in PBMCs and suggest that it mainly acts by blocking the virus entry into cells.

Amphotericin B↗

Differential effects of a new amphotericin B derivative, MS-8209, on mouse BSE and scrapie: implications for the mechanism of action of polyene antibiotics.

Mice were infected intracerebrally with the bovine spongiform encephalopathy (BSE) or the scrapie agent and treated during 8 weeks postinfection to test the protective effect of a new amphotericin B (AmB) derivative, MS-8209, in experimental transmissible spongiform encephalopathies. The results show that (i) the treatment prolonged the incubation period of both BSE-infected and scrapie-infected mice, (ii) MS-8209 and AmB were much more efficient in delaying the onset of scrapie than that of BSE, and (iii) a delay in Prp-res (proteinase K-resistant prion protein) and GFAP (glial fibrillary acidic protein) accumulation was observed in the brains of scrapie-infected mice, but was not significant in BSE-infected mice. The analysis of the molecular and clinical results strongly suggests a common mechanism of action of this category of drugs on the different transmissible spongiform encephalopathy strains. This could be due to an interaction with the PrP transconformation process leading to the formation of PrP-res.

Amphotericin B↗

Control of isotype expression by helper T-cell clones and suppressor cells.

We report here experiments demonstrating the profound influence of T lymphocytes on isotype expression by B lymphocytes. It was shown that in a secondary in vitro response, T helper cells from primed spleen predominantly induced an IgG1 plaque-forming cell (PFC) response, while T helper cells from primed lymph node induced IgG1, IgG2a and IgG2b PFC responses. Under the same experimental conditions, T helper cell clones were able to induce IgG1, IgG2a and IgG2b responses; therefore, T helper cells are not involved in controlling preferential isotype expression. Stimulated spleen cells were shown to contain T suppressor cells which were able to limit the expression of IgG2a and IgG2b responses. Under certain circumstances, IgG1-specific suppressor cells were also demonstrated. A T-cell hybridoma, T2D4, spontaneously produced the IgG-binding factor, thereby suppressing the expression of the three subclasses studied. Exposure of these cells to IgG1 myeloma protein led to selective enhancement for the production of molecules binding to IgG1, and suppression of the IgG1 PFC response. Similar observations were made with IgG2a and IgG2b myeloma proteins, and the specificity of these isotype suppressive factors was demonstrated. The general significance of these observations is discussed.

Animals↗

[What are the prospects for pharmacological treatment of prion disease?].

There is currently no effective therapy available for Creutz-feldt-Jakob disease. However, a limited number of drugs such as polyanions, the amyloid-binding dye Congo red, amphotericin B anthracyclines, dapsone, beta sheet breaker peptides, porphyrines and phtalocyanines have been found to delay the appearance of the clinical signs in experimental prion diseases. Today, the most promising agent would appear to be a less toxic derivative of amphotericin B, MS-8209. Indeed this compound has a wide spectrum of anti-prion activity and is the only molecule capable of prolonging survival time when treatment is performed in the late stages of infection. This result represents an important step forward in therapeutical approaches of prion diseases and justifies the development of new polyene antibiotic derivatives.

Amphotericin B↗

Helper cells from lymph node or spleen induce different 7S antibody responses.

The helper activity of GAT (L-glutamic acid 60-L-alanine 30-L-tyrosine 10)-specific T cells from BALB/c mice has been characterized. The isotypic pattern of the PFC response (plaque-forming cell) obtained in vitro is different depending on the origin of the T helper cells. T helper cells from primed spleen induce a very predominant IgG1 PFC response while T helper cells from primed lymph node induce IgG1-IgG2a- and IgG2b-PFC responses. When primed spleen cells are added to primed lymph node cells in vitro, the IgG2a- and IgG2b-PFC responses are abolished. This results suggests the presence of isotype-specific suppressor cells in the spleen of immunized mice.

Animals↗

[Evaluation of intestinal pathogenicity of Yersinia spp. strains isolated from human feces].

BACKGROUND: Yersinia enterocolitica is a human pathogen which an acts on the intestine by basically enteroinvasive mechanism. Its virulence has been related with the presence of a plasmid of 40-50 MD which codes a series of properties. There are strains of Y. enterocolitica and of other species assimilated to the Y. enterocolitica group which lack the virulence plasmid. In these cases there is a problem in evaluating the pathogenic ability on the intestine of these bacterias when isolated in faeces. METHODS: A study of 30 Yersinia spp. strains including growth in a magnesium oxalate medium, Reg-Congo and agar (CR-MOX), sculine hydrolisis (Sc), pyrazinamidase activity (Pyz) and salicine fermentation (Sal) was performed. In addition, the presence of virulence plasmid (VP) was determined. RESULTS: Twenty-two strains identified as Y. enterocolitica presented the virulence pattern (CR-MOX+, Pyz-, Sal/Sc-) and 21 were VP+. Seven strains isolated were CR-MOX-, Pyz+, Sal/Sc+ and VP- being typed as Y. fredericksenii (6) and Y. kristensenii (1). The remaining strain was CR-MOX- and VP- but Pyz, Sal/Sc were also negative, being identified as Y. enterocolitica. CONCLUSIONS: By the tests referred the authors were able to identify and evaluate the pathogenicity of Yersinia spp. isolated in faeces. These techniques may be used in the microbiology laboratory as a method which aids to evaluate the diagnosis of intestinal infections caused by Yersinia spp.

Bacterial Typing Techniques↗