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Biomedical subjects

M Seman

Publications and source records attributed to M Seman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Innate resistance to infection by intracellular bacterial pathogens differs in mice selected for maximal or minimal acute inflammatory response.

The intensity of nonspecific immune reaction and the host resistance to facultative intracellular pathogens are found to be associated in lines of mice selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory reactivity. AIRmax are more resistant than AIRmin mice to Salmonella typhimurium and Listeria monocytogenes infection, the differences between lines in LD50 being > 1000 and 100 times, respectively. This difference was shown to be related to the initial bacterial containment at the infectious focus, and to the control of bacterial multiplication in the spleen during the 1st week after s. c. inoculation of the bacteria. Specific immune responses were not deeply affected by the selective process: antibody production and delayed-type hypersensitivity were both of similar intensity in AIRmax and AIRmin mice. The differential susceptibility to infection seems independent of the Nramp-1 locus polymorphism; therefore, these two lines represent a powerful model for investigating the role of other genetic loci regulating the nonspecific immunity effectors in the course of infectious diseases.

Acute-Phase Reaction↗
PubMed1997

Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry.

The human cytomegalovirus encodes a beta-chemokine receptor (US28) that is distantly related to the human chemokine receptors CCR5 and CXCR4, which also serve as cofactors for the entry into cells of human immunodeficiency virus-type 1 (HIV-1). Like CCR5, US28 allowed infection of CD4-positive human cell lines by primary isolates of HIV-1 and HIV-2, as well as fusion of these cell lines with cells expressing the viral envelope proteins. In addition, US28 mediated infection by cell line-adapted HIV-1 for which CXCR4 was an entry cofactor.

AIDS-Related Opportunistic Infections↗
PubMed1997

Biological activity of new aza analogues of quinolones.

A series of novel derivatives of 4H-pyrido[1,2-]pyrimidine, 1,4-dihydro-4-oxo-1,5-naphthyridine and 1,4-dihydro-4-oxo-1,6-naphthyridine were prepared and their biological activity was compared with that of nalidixic acid. The in vitro antibacterial activity of the tested compounds was lower than that of nalidixic acid except for two agents, 1b and 2c, with a higher activity against Enterococcus faecalis. The compounds were tested for their ability to cure four plasmids from two species of Enterobacteriaceae. The derivatives eliminated three plasmids (pKM101, pBR322, F'lac) at one-half or one-quarter of the minimal inhibitory concentration. Plasmid RP4 was unaffected by the treatment. None of these compounds showed better antichloroplast activity than nalidixic acid.

Animals↗
PubMed1997

NMDA receptor complex blockade by oral administration of magnesium: comparison with MK-801.

The ion channel of the N-methyl-D-aspartate (NMDA) receptor complex is subject to a voltage-dependent regulation by Mg2+ cations. Under physiological conditions, this channel is supposed to be blocked by a high concentration of magnesium in extracellular fluids. A single dose of magnesium organic salts (i.e., aspartate, pyroglutamate, and lactate) given orally to normal mice rapidly increases the plasma Mg2+ level and reveals a significant dose-dependent antagonist effect of magnesium on the latency of NMDA-induced convulsions; this effect is similar to that seen after administration of the dizocilpine (MK-801) channel blocker. An anticonvulsant effect of Mg2+ treatment is also observed with strychnine-induced convulsions but not with bicuculline-, picrotoxin-, or pentylenetetrazol-induced convulsions. In the forced swimming test, Mg2+ salts reduce the immobility time in a way similar to imipramine and thus resemble the antidepressant-like activity of MK-801. This activity is masked at high doses of magnesium by a myorelaxant effect that is comparable to MK-801-induced ataxia. Potentiation of yohimbine fatal toxicity is another test commonly used to evaluate putative antidepressant drugs. Administration of Mg2+ salts, like administration of imipramine strongly potentiates yohimbine lethality in contrast to MK-801, which is only poorly active in this test. Neither Mg2+ nor MK-801 treatment can prevent reserpine-induced hypothermia. These data demonstrate that oral administration of magnesium to normal animals can antagonize NMDA-mediated responses and lead to antidepressant-like effects that are comparable to those of MK-801. This important regulatory role of Mg2+ in the central nervous system needs further investigation to evaluate the potential therapeutic advantages of magnesium supplementation in psychiatric disorders.

Adrenergic alpha-Agonists↗
PubMed1997

Late treatment with polyene antibiotics can prolong the survival time of scrapie-infected animals.

Amphotericin B (AmB) is one of the few drugs able to prolong survival times in experimental scrapie and delays the accumulation of PrPres, a specific marker of this disease in the brain in vivo. Previous reports showed that the AmB effect is observed only if the drug is administered around the time of infection. In the present study, intracerebrally infected mice were treated with AmB or one of its derivatives, MS-8209, between 80 and 140 days postinoculation. We observed an increased incubation time and a delay in PrPres accumulation and glial fibrillary acidic protein gene expression. Treatment starting at 80 days postinoculation was as efficient as long-term treatment starting the day of inoculation. Our results indicate that polyene antibiotics may interfere, throughout the course of the experimental disease, with the propagation of the scrapie agent.

Amino Acid Sequence↗
PubMed1997

[Subspecific classification of 11 clinical strains of Klebsiella pneumoniae based on their biochemical, antibiotic and plasmid profiles].

The paper summarizes at a subspecific level 11 clinical strains of K. pneumoniae. The objective of the work was to determine in a simple and effective way differences between different strains of the mentioned taxon. Biochemical characteristics, antibiogram and part of the plasmid spectrum were used for assessment of inter-species differences between different strains and at the same time their use as simple markers of epidemiological analyses is presented.

Bacterial Typing Techniques↗
PubMed1996

Possible role of the V3 domain of gp120 in resistance to an amphotericin B derivative (MS8209) blocking human immunodeficiency virus entry.

MS8209, an amphotericin B derivative blocking human immunodeficiency virus type 1 (HIV-1) entry after CD4 binding, neutralized the HIV-2 strains EHO and ROD10 but not ROD(CEM). In the V3 domain of gp120, ROD(CEM) differed from ROD10 at two positions (a threonine instead of an isoleucine at position 312 and an arginine instead of a glutamine at position 329), and drug resistance was conferred to HIV-1 by substitution of the ROD(CEM) V3 but not the ROD10 V3. V3 mutations may prevent the interaction of gp120 with MS8209 or modify the mechanism of virus entry, rendering it less accessible to neutralization.

Amino Acid Sequence↗
PubMed1995

Critical role of endogenous Mtv in acute lethal graft-versus-host disease.

Little is known about the etiology of the graft-versus-host disease (GVHD) occuring after transplantation of lymphoid cells incompatible for minor histocompatibility antigens (mHAg). Here, the potential role of host endogenous mouse mammary tumor virus (Mtv)-encoded superantigens (SAg) in the development of lethal GVHD was investigated. In a combination of H-2d compatible mice, the presence of Mtv-7 and, to a lesser extent, of Mtv-1, -6, -13 in the host genome, highly increases the rate and severity of GVHD. Kinetic analyses of TCR V beta gene expression in recipient mice consistently indicate a dramatic but transient infiltration of GVHD target organs by Mtv-SAg-specific T cells. This suggests that SAg encoded by endogenous Mtv, by activating large T cell subpopulations, would help the response to mHAg and thus play a critical role in the initiation or aggravation of GVHD.

Acute Disease↗
PubMed1995

MS-8209, a new amphotericin B derivative, provides enhanced efficacy in delaying hamster scrapie.

To test the efficacy of a new amphotericin B derivative, MS-8209, in delaying scrapie, hamsters were infected intracerebrally with the 263K scrapie agent and treated with MS-8209 either early in the course of the disease or continuously. The results show that (i) all treatments lengthened the incubation period of hamster scrapie, (ii) continuous treatment with MS-8209 doubled the length of the incubation period compared with that observed in infected, untreated animals, and (iii) all treatments delayed the accumulation of a proteinase-resistant prion protein and glial fibrillary acidic protein in the brain. These findings suggest that MS-8209 is a powerful tool for investigating the pathogenesis of transmissible subacute spongiform encephalopathies.

Amphotericin B↗
PubMed1995

Amphotericin B derivative blocks human immunodeficiency virus type 1 entry after CD4 binding: effect on virus-cell fusion but not on cell-cell fusion.

The antiviral effect of MS8209, an amphotericin B derivative, was studied in CD4+ cells transfected with a lacZ gene inducible upon human immunodeficiency virus type 1 (HIV-1) infection. MS8209 was shown to block virus entry after receptor binding and probably before virus-cell membrane fusion, but it had no effect on syncytium formation, although both processes are mediated by HIV-1 envelope proteins and CD4.

Amphotericin B↗
PubMed1994

[Immune tolerance].

Immune tolerance reflects the absence of immune reactions to self-antigens (natural tolerance) or exogenous antigens, at least in experimental models (acquired tolerance). It results in part from central mechanisms leading to the elimination or deletion of auto-reactive B or T cell clones by apoptosis in primary lymphoid organs. In the periphery, this is reflected by more-or-less reversible states of anergy, which arise from a time or spatial discordance between the different signals required for lymphocyte activation, or from a network of interactions between lymphocytes leading to the production of antagonistic signals. The reversibility of anergy-inducing mechanisms, a deregulation of the production of certain cytokines, or incomplete clonal deletion mechanisms could explain the emergence of autoimmune diseases by a rupture of self-tolerance. As these mechanisms are not fully understood, clinical induction of tolerance by the use of nonspecific immunodepressive agents is not yet possible.

Animals↗
PubMed1994

Negative segregation of Mtv loci in H-2E+ mice selected for high antibody response.

Endogenous mouse mammary tumor proviruses (Mtvs) encode superantigens (Sags), which can delete T lymphocytes expressing particular Tcrb-V genes when associated with the H-2E molecule. In the present work, distribution of Mtvs was investigated in six independent pairs of mouse lines genetically selected for high (H) or low (L) Ab production to specific T-cell-dependent Ags. These experiments were performed to evaluate the role of Mtv-encoded Sags in the determination of H and L phenotypes. No systematic difference is observed in Mtv segregation between H-2E- H and L mouse lines. However, a clear differential segregation of Mtv loci is observed between H-2E+ H and L mice from three independent selections. The number of endogenous Mtvs in L lines is close to that found in laboratory mice. In contrast, Mtv loci-encoding Sags are almost absent in H animals. Although Sags profoundly affect the available Tcrb-V repertoire in H-2E+ L mice, it seems unlikely that Mtvs account for the L phenotype which can be achieved independently of Mtv segregation in H-2E- lines. More importantly, the results suggest that negative segregation of Mtv-encoding Sags contribute to determine the super-responder phenotype of H lines.

Animals↗
PubMed1994

Pharmacological studies of a new derivative of amphotericin B, MS-8209, in mouse and hamster scrapie.

Transmissible subacute spongiform encephalopathies (TSSE) are neurodegenerative diseases characterized by the presence of a modified, partially proteinase-resistant host protein, PrPSc, which accumulates in the brains of infected individuals. Recently it has been reported that amphotericin B (AmB) treatment of hamsters infected with scrapie strain 263K prolongs the incubation period of the disease, and dissociates in vivo replication of the scrapie agent from PrPSc accumulation. We report here on data obtained after treatment with AmB and one of its derivatives, MS-8209, in experimental scrapie of mouse and hamster. Treatment was carried out by the intraperitoneal route 6 days per week, at three different dosages initiated at the time of infection. Two regimens were used: during the early time of infection or throughout the experimental infection. Results indicate that MS-8209 was as efficient as AmB in prolonging the incubation time and decreasing PrPSc accumulation in the hamster scrapie model. A dose-dependent response was observed in mice treated early after experimental infection. At a dose of 2.5 mg/kg, MS-8209 significantly prolonged the incubation period (by 11.9%). In long-term treatment of mice, MS-8209 and AmB markedly reduced PrPSc levels in the preclinical stage of the disease. These data demonstrate that the effect of AmB is not restricted to one model (hamster-263K). This regimen leads to an inversion of the PrPSc to proteinase-sensitive protein (PrPSens) ratio, suggesting PrPSens (presumably cellular PrPC) accumulation occurs before its conversion into PrPSc. As it has been shown that AmB does not modify the infectivity titre, we conclude that the drugs could act by inhibiting either the interaction of the scrapie agent with PrPSens during the early times of infection or the conversion of PrPSens into PrPSc.

Amphotericin B↗
PubMed1993

Co-selection of the rare T cell receptor-gamma B haplotype in mouse lines selected for low responsiveness to red blood cell antigens.

T cell receptor (TcR)-gamma haplotype was investigated in seven pairs of murine Biozzi lines selected for low and high antibody (Ab) response to different antigens (Ag). High-responder lines (H) express gamma A or gamma C haplotypes irrespective of the selecting Ag. In contrast, the gamma B haplotype, which is rare in laboratory mouse strains, is found in all low-responder lines (L) to sheep erythrocyte Ag (SE). However, the TcR-gamma B locus might only have a low penetrance in the control of the SE response. Moreover, investigations using LIVA mice, which were selected for low SE response from homozygous gamma A founder parents, indicate that the gamma B haplotype is neither necessary nor sufficient to achieve a low-responder phenotype. The gamma B haplotype might, thus, be co-selected to confer to L mice an improved resistance to bacterial infections mediated by gamma delta T cells compensating the profound and nonspecific immune perturbation associated with the low Ab response.

Animals↗
PubMed1993

New T-cell receptor gamma haplotypes in wild mice and evidence for limited Tcrg-V gene polymorphism.

Tcrg gene polymorphism was investigated by Southern blot analysis on a panel of laboratory and wild mouse strains using a set of probes which identify all known Tcrg-V and -C genes. Only three haplotypes are found in laboratory mice: gA, gB, and gC which are represented by BALB/c, AKR, and DBA/2 prototypes respectively. gA and gC haplotypes are the most frequent among laboratory mice whereas gB is poorly represented. Seven new haplotypes are described among 23 wild mice corresponding to four Mus musculus subspecies (Mus mus domesticus, castaneus, musculus, and molossinus). However, only a few new alleles of individual genes are observed. Tcrg-V genes located at the 5' end of the Tcrg locus (V7 and V4) appear to be nonpolymorphic whereas two Tcrg-V3, -V5, -V6, -C4 and three Tcrg-V1, -V2, -C1, -C2, and -C3 specific restriction fragment length polymorphisms are detected. These results indicate a relatively high degree of conservation of Tcrg genes as compared to other members of the immunoglogulin (Ig) gene family and might be related to the specifity and function of gamma delta T cells. Several of the new haplotypes described here result from point mutations in noncoding Tcrg-V or -C gene-flanking regions. Recombinations may have also participated in the evolution of the Tcrg locus. Finally, these new Tcrg haplotypes are unequally distributed among the four M. m. subspecies and support the idea that the gA and gC haplotypes found in laboratory mice are inherited from M. m. domesticus whereas gB might originate from asian subspecies (castaneus, musculus or molossinus).

Animals↗
PubMed1993

Rearrangement by chromosomal inversion in the T cell receptor gamma locus in a murine alpha beta T cell clone.

Analyzing the T-cell receptor (TCR) repertoire of T lymphocytes specific for minor histocompatibility antigens, we isolated a TCR-alpha beta bearing T cell clone, TGVH9, which also expresses three different TCR-gamma mRNA. The sequences of these messengers indicate that one of them results from the rearrangement of V gamma 1 and J gamma 2 genes. Since these two segments are in inverted genomic transcriptional orientation, the joining of V gamma 1 to J gamma 2 occurred by chromosomal inversion. This mechanism, which was previously reported in TCR-beta and TCR-delta loci, can thus also occur to enlarge the diversity of the TCR-gamma repertoire.

Amino Acid Sequence↗