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Biomedical subjects

A Dufour

Publications and source records attributed to A Dufour.

At least 37 records · Page 2Linked to original sources
PubMed1999

Immunological effects of in vivo interferon-beta1b treatment in ten patients with multiple sclerosis: a 1-year follow-up.

Ten patients with multiple sclerosis and treated with interferon-beta1b (IFN-beta1b) were followed-up for 1 year with quantitation of serum VCAM-1 and ICAM-1 levels, mean fluorescence intensity of HLA-DR, VLA-4, CD11a, and CD18 on peripheral blood monocytes and lymphocytes, and adhesion of peripheral blood monocytes and CD45+ cells on endothelial cell monolayers. Adhesion molecule expression and adhesion of peripheral blood monocytes to endothelium were also monitored in healthy controls. No differences in adhesion were detected between MS patients before treatment and healthy controls, while after 1 year a marked decrease in the number of monocytes and mononuclear cells adhering to human umbilical vein endothelial cell monolayers was observed in patients treated with IFN-beta1b. After 1 year of treatment a significant increase in HLA-DR on peripheral blood monocytes was also detected. Our findings regarding lowered adhesion add information to available evidence of the mechanisms of action of IFN-beta1b in MS.

Adjuvants, Immunologic↗
PubMed1999

The extrinsic/intrinsic classification of two-dimensional motion signals with barber-pole stimuli.

The perceived direction of different barber-pole stimuli was assessed by adjusting an arrow on the screen. The terminator ratio (TR: number of terminators moving along the long side divided by the number of terminators moving along the small side) was either one or three. In this latter case, the aperture orientation was either vertical or horizontal. The grating was either in the same plane as the aperture (intrinsic condition) or behind the aperture--the frame containing the aperture had a crossed disparity relative to the grating--(extrinsic condition). A nested design with 120 observers was used for the whole study. Five grating orientations were intermingled within any session. With a terminator ratio of three, the results depend strongly on the aperture's orientation. When the rectangular aperture is horizontal, the perceived direction of an intrinsic grating is horizontal (the typical barber-pole illusion), whereas it is only slightly biased towards orthogonal one-dimensional (1D) motion signals (Vp) in the extrinsic condition. When the aperture is vertical, the perceived direction in the intrinsic condition is largely biased toward Vp, and on average it is close to Vp in the extrinsic condition. In this latter case, however, analysing the distributions of responses shows that many responses do not lie around Vp but are clustered near vertical or horizontal. This motion capture depends on the grating's orientation. With a terminator ratio of one, motion capture is present in both the extrinsic and intrinsic conditions. Moreover, a global bias toward horizontal is observed: this horizontal bias is much larger in the extrinsic condition. Altogether, these results suggest that binocular disparity alone is a weak determinant of the extrinsic/intrinsic classification of two-dimensional (2D) motion signals compared to the occlusion cues provided by unpaired regions in binocular images. Second, truly extrinsic 2D motion signals are not suppressed but rather actively compete against each other to capture the 1D motion signals. This results in a perceptual multistability which is much stronger with extrinsic signals. Finally, given the inherent multistability of barber-pole stimuli, high-level factors can alter the strength of this competition and prime any of the 2D motion signals.

Discrimination, Psychological↗
PubMed1999

Factors associated with hepatitis B vaccination among men having sexual relations with men in Montreal, Quebec, Canada. Omega Study Group.

OBJECTIVE: To determine factors associated with hepatitis B virus (HBV) vaccination status among HIV-uninfected men who have affective and sexual relations with men (MASM) in Montreal, Quebec, Canada. METHODS: The Omega Cohort is a study of the incidence and psychosocial determinants of HIV infection among MASM in Montreal. Participants complete a questionnaire and are HIV-tested every 6 months. At baseline, we also performed testing for HBV markers and collected data on HBV vaccination history. RESULTS: Forty-six percent of 653 participants had received at least one dose of HBV vaccination, whereas 28% were completely vaccinated. Lack of vaccination was associated with injection drug use, having > or =20 regular lifetime partners, living outside Montreal, not having sex in bathhouses, and not having consulted a physician aware of the participant's sexual orientation. Among vaccinated MASM, incomplete vaccination was associated with having <20 lifetime casual partners, trading sex for drugs, having given goods for sex, having had unprotected anal sex with regular partners, and having no history of a previous sexually transmitted disease. CONCLUSION: A significant proportion of Montreal's MASM, some of whom are at risk of contracting HBV through sexual and parenteral transmission, have not been vaccinated for HBV. Men who have affective and sexual relations with men should be educated about the risk of HBV transmission and the seriousness of the disease.

Adolescent↗
PubMed1998

Modulation of ICAM-1, VCAM-1 and HLA-DR by cytokines and steroids on HUVECs and human brain endothelial cells.

The in vitro effects of dexamethasone (Dx) and low and high-dose 6-methylprednisolone (MP) on the expression of adhesion molecules ICAM-1,VCAM-1 and class II antigen HLA-DR on human brain endothelial cells (HBECs) was studied. HBECs were obtained from the surgical specimen of a multiple sclerosis patient undergoing brain surgery for vascular aneurysm. HBECs obtained from apparently normal brain capillaries of surgical specimens of two patients undergoing brain surgery for a meningioma and a low-grade glioma, respectively, were used as controls. The effect of steroids was studied both in the basal condition and after stimulation with proinflammatory cytokines (gamma-IFN and TNF-alpha). In order to detect possible endothelium local tissue specific differences, the experiment was repeated using human umbilical vein endothelial cells (HUVECs). Only high-dose MP was able to down-regulate TNF-alpha-induced VCAM-1 expression on endothelial cells.

Adult↗
PubMed1998

Immunocompetence of human microvascular brain endothelial cells: cytokine regulation of IL-1beta, MCP-1, IL-10, sICAM-1 and sVCAM-1.

Endothelia from the brains of four patients undergoing neurosurgery, including one multiple sclerosis (MS) patient, were studied in vitro to determine cytokine and chemokine production; the release of soluble adhesion molecules was also investigated. The same procedure was repeated on human umbilical vein endothelial cells (HUVECs) in order to detect possible district-specific differences. After isolation, the endothelium was cultured and stimulated with gamma-interferon (IFN), tumour necrosis factor alpha (TNF-alpha) and LPS. The results showed that brain endothelium, in our experimental conditions, does not produce interleukin (IL)-10 and produces lower amounts of IL-1beta and soluble intercellular adhesion molecule-(sICAM-1) than HUVECs do; no differences were detected in soluble vascular cell adhesion molecule-(sVCAM-1) production. MCP-1 mRNA was detected both without and after stimulation with TNF-alpha and gamma-IFN in HUVECs and MS human brain endothelial cells (HBECs), while in non-MS-HBECs it was found only after gamma-IFN stimulation.

Adult↗
PubMed1998

Novel genes that upregulate the Proteus mirabilis flhDC master operon controlling flagellar biogenesis and swarming.

By screening for restoration of multicellular migration in a non-swarming but motile Proteus mirabilis mutant lacking the FIgN facilitator of flagella assembly, we identified four distinct genes that, in trans and multicopy, increased flagella production and cell length. Each of the genes upregulated expression of the flhDC master operon that controls flagellar biogenesis, cell division and swarming, not only in the mutant but also in the wild type. The genes were named umoA, umoB, umoC and umoD. Disruption of each of the wild-type chromosomal umo genes caused corresponding reductions in swarming and cell elongation, which correlated with decreased expression of the flhDC operon. The umoA, umoB, umoC and umoD genes are not closely linked, and only umoB is part of an operon. The sequences of the calculated gene products, UmoA (20.6 kDa), UmoB (78.0 kDa), UmoC (15.2 kDa) and UmoD (19.2 kDa), contain putative N-terminal secretion signals and predict a location in the cell membranes or periplasm. UmoB and UmoD have sequence similarity to the Escherichia coli uncharacterized open reading frames YrfF and YcfJ respectively; UmoA and UmoC have no known homologues. The umoB and umoC gene transcripts were present at very low levels, but umoA and umoD expression was similar to that of flhDC and increased in parallel with flhDC expression during differentiation into elongated hyperflagellated swarm cells. Like flhDC, umoA and umoD expression was subject to negative feedback in aflagellar assembly mutant lacking the FlhA inner membrane component of the export machinery. Assays of umo gene expression and cross-complementation indicated that the umo genes do not act in sequence within a pathway to upregulate flhDC, but revealed that umoA and umoD are reciprocally upregulated by FlhDC. Our findings strengthen the picture of the flhDC master operon as a major assimilatory checkpoint in Proteus mirabilis and other Gram-negative bacteria and expand the view of a complex regulatory network coupled to flagellar biogenesis.

Bacterial Proteins↗
PubMed1997

IL-10 production in multiple sclerosis patients, SLE patients and healthy controls: preliminary findings.

IL-10 is a cytokine with suppressive effects on (auto) antigen presentation and T-cell-mediated immune reactions, but is also capable of stimulating polyclonal IgG synthesis. Recent evidence suggests its involvement in multiple sclerosis (MS) and systemic lupus erythematosus (SLE). We assessed PBMNC IL-10 release in MS and SLE patients before and after in vivo prednisone or methylprednisolone treatment. The SLE patients showed a high level of IL-10 release by unstimulated PBMNCs, whereas the PHA-stimulated PBMNCs from MS patients produced large amounts of the cytokine.

Adult↗
PubMed1997

Immunological monitoring of azathioprine treatment in multiple sclerosis patients.

Despite the longstanding clinical use of azathioprine as an immunosuppressive agent in multiple sclerosis, little is known about the action of this drug on a number of parameters of putative pathogenic relevance in the disease. Eleven patients with multiple sclerosis, treated with azathioprine 2.5-3 mg/kg per day, and six untreated patients were studied with serial blood sampling for 1 year. The following immunological parameters were investigated: peripheral blood lymphocyte subsets, natural killer activity, serum IgG, IgM, ICAM-1 and tumour necrosis factor alpha (TNF-alpha). The most relevant changes included a decrease in CD3- CD56+ cells, an increase in CD4+ CD45RA+ cells and a decrease in TNF-alpha levels only in treated patients, while no changes occurred in untreated patients over a 1-year period. The decrease in TNF-alpha levels and the increase in "suppressor-inducer" lymphocytes could reduce chronic inflammation in multiple sclerosis, and paralleled an overall favourable clinical response to azathioprine treatment in our patients.

Azathioprine↗
PubMed1997

Effects of beta-IFN-1b treatment in MS patients on adhesion between PBMNCs, HUVECs and MS-HBECs: an in vivo and in vitro study.

The in vivo effects on the expression of adhesion molecules and on the adhesion between mononuclear cells and multiple sclerosis human brain endothelial cells (MS-HBECs) were investigated at the beginning of beta-IFN-1b treatment of MS patients. MS-HBECs were isolated from a surgical specimen obtained from an MS patient undergoing brain surgery for vascular aneurysm. 48 h after the first single administration of beta-IFN-1b, PBMNCs of 10 MS patients were analyzed for HLA-DR, CD11a, CD18 and VLA-4 expression and the adhesion between PBMNCs and both stimulated and unstimulated MS-HBECs evaluated. sICAM-1 and sVCAM-1 dosage in the serum of the patients was checked as well. The experiments were repeated using HUVECs in order to detect possible endothelial organ-specific differences. The experiments were also performed after six months of beta-INF-1b treatment on HUVECs. No significant effects on mononuclear cells/endothelium adhesion were detected at 48 h, but adhesion of PBMNCs to HUVECs decreased at six months. An increase in HLA-DR and VLA-4 and a decrease of CD18 was detected in monocytes. The serum level of sVCAM-1 increased at T2 and was still higher than at T0 at six months. The effect of the beta-IFN-1b treatment on both MS-HBECs and HUVECs, was selectively studied in vitro by testing the expression of cytokine-induced adhesion molecules HLA-DR, ICAM-1 and VCAM-1. The in vitro experiments confirmed that beta-IFN-1b is able to antagonize gamma-IFN-induced HLA-DR expression on MS human brain endothelial cells without relevant effects on VCAM-1 and ICAM-1.

Adult↗
PubMed1997

A motile but non-swarming mutant of Proteus mirabilis lacks FlgN, a facilitator of flagella filament assembly.

A TnphoA mutant of Proteus mirabilis was isolated, which had lost the ability to swarm, yet was still motile. The transposon had inserted into flgN, a flagella gene encoding a 147-amino-acid protein of undefined function. Proteus flgN is arranged in an operon with the class III anti-sigma28 gene, flgM, flanked by the class II genes, flgA, flgBCD and flhBA, and a novel putative virulence-related gene. The flgN mutation caused a substantial reduction in cell surface-associated flagellin, particularly during differentiation to the normally hyperflagellated swarm cell. This was not due to an effect on flagella gene expression or a typical defect in the flagella export apparatus as there was no class III gene downregulation by FlgM feedback, or intracellular flagellin accumulation. Loss of FlgN nevertheless caused a severe reduction in the incorporation of pulse-labelled flagellin into the membrane/flagellum fraction of differentiating cells. Substantial amounts of both non-oligomeric flagellin and flagellin degradation products appeared in the extracellular medium, although the few mature filaments made by the mutant were no more sensitive to proteolysis than those of the wild type. FlgN appeared soluble and active in the cytosol. The data suggest that the function of FlgN is to facilitate the initiation of flagella filament assembly, a role that may be especially critical in attaining the much higher concentration of surface flagellin required for swarming. Proteus FlgN has leucine zipper-like motifs arranged on potential amphipathic helices, a feature conserved in cytosolic chaperones for the exported substrates of flagella-related type III virulence systems. While gel filtration of FlgN from the soluble cell fraction did not establish an interaction with flagellin, it indicated that FlgN may associate with an unknown component and/or form an oligomer.

Amino Acid Sequence↗
PubMed1997

Reduced adhesion of PBMNCs to endothelium in methylprednisolone-treated MS patients: preliminary results.

Methylprednisolone (MP) is a synthetic steroid commonly used in the treatment of multiple sclerosis (MS) relapses. It has a wide spectrum of activities on immune cells: it might also act by preventing mononuclear cell/endothelium adhesion. We studied adhesion phenomena between cultured human umbilical vein endothelial cells (HUVECs) and PBMNCs (CD45+, CD14+) from 6 MS patients treated in vivo with MP. We also studied fluctuations in CD11a and CD18 levels on lymphocytes and monocytes, as well as changes in serum sICAM-1 and sVCAM-1 concentrations. After MP treatment, PBMNCs adhesion to endothelium decreased at 3 h, while it went back to baseline levels at 24 h. A tendency to increase in both CD11a and CD18 on the surface of lymphocytes was detected, while an increase in serum sVCAM-1 was seen at 3 h.

Adult↗
PubMed1997

Characterization of the lacticin 481 operon: the Lactococcus lactis genes lctF, lctE, and lctG encode a putative ABC transporter involved in bacteriocin immunity.

The lantibiotic lacticin 481 is a bacteriocin produced by Lactococcus lactis strains. The genetic determinants of lacticin 481 production are organized as an operon encoded by a 70-kb plasmid. We previously reported the first three genes of this operon, lctA, lctM, and lctT, which are involved in the bacteriocin biosynthesis and export (A. Rincé, A. Dufour, S. Le Pogam, D. Thuault, C. M. Bourgeois, and J.-P. Le Pennec, Appl. Environ. Microbiol. 60:1652-1657, 1994). The operon contains three additional open reading frames: lctF, lctE, and lctG. The hydrophobicity profiles and sequence similarities strongly suggest that the three gene products associate to form an ABC transporter. When the three genes were coexpressed into a lacticin 481-sensitive L. lactis strain, the strain became resistant to the bacteriocin. This protection could not be obtained when any of the three genes was deleted, confirming that lctF, lctE, and lctG are all necessary to provide immunity to lacticin 481. The quantification of the levels of immunity showed that lctF, lctE, and lctG could account for at least 6% and up to 100% of the immunity of the wild-type lacticin 481 producer strain, depending on the gene expression regulation. The lacticin 481 biosynthesis and immunity systems are discussed and compared to other lantibiotic systems.

ATP-Binding Cassette Transporters↗
PubMed1996

Role of adenosine nucleotides in the regulation of a stress-response transcription factor in Bacillus subtilis.

The RNA polymerase sigma factor sigma B is a stress-response regulatory protein in Bacillus subtilis. The activity of sigma B is controlled in part by RsbW, a protein that inhibits sigma B, and RsbV, a protein that counteracts this inhibition. We now demonstrate that purified RsbW is capable of forming alternative complexes with either sigma B or RsbV. Sigma B in the RsbW. sigma B complex was transcriptionally inactive. RsbV reversed this inhibition by sequestering RsbW in a RsbW-RsbV complex, thereby allowing sigma B to remain free and active. In contrast to interactions among the components of the homologous regulatory system for the sporulation transcription factor sigma F, the binding of RsbW to RsbV and sigma B did not require adenosine nucleotides. Experiments involving the exchange of proteins between the two regulatory systems demonstrated that RsbW and its homolog in the sigma F system, SpoIIAB, exhibit strong preference in binding to RsbV and sigma B, and SpoIIAA and sigma F, respectively, and that the difference in nucleotide-dependence of binding between these two systems is attributable to a difference between RsbW and SpoIIAB. In confirmation and extension of previous results, we show that RsbW is also a protein kinase that uses ATP to phosphorylate RsbV, thereby blocking the capacity of RsbV to bind to RsbW and activate transcription. A close correlation was observed between the concentration of ATP required for efficient RsbW-mediated phosphorylation of RsbV, inhibition of RsbW.RsbV comlex formation, and inhibition of sigma B-directed transcription. These results are consistent with the hypothesis that activation of sigma B under certain stress condition is due to a decrease in cellular ATP levels.

Adenosine Diphosphate↗
PubMed1996

Low serum interleukin-10 levels in multiple sclerosis: further evidence for decreased systemic immunosuppression?

Serum interleukin 10 (IL10) levels were assessed in patients with multiple sclerosis who were either in a stable or active clinical condition. The levels were compared with values in healthy controls. Lower IL10 levels than in controls were seen in multiple sclerosis patients, regardless of clinical disease activity. Low IL10 levels were also seen in patients with systemic lupus erythematosus. No clear-cut relationships emerged between IL10 levels and those of tumour necrosis factor alpha and transforming growth factor beta, or between IL10 and lymphocyte subsets in peripheral blood.

Adult↗
PubMed1996

Intrathecal immunotherapy in CNS tumors disseminating via CSF: preliminary evaluation using different treatment schedules.

Eight patients affected by central nervous system tumours disseminating via cerebrospinal fluid received rIL-2 immunotherapy according to three different protocols involving intrathecal administration followed or not by systemic infusion. Immunological monitoring included serial evaluation of CSF leukocytes, CSF and peripheral blood CD3-CD56+ cells, and NK activity. The most marked rise in CSF leukocyte levels was induced by daily intrathecal rIL2 administration, which also induced increased PB NK activity. Systemic rIL2 infusion following intrathecal treatment maintained a high percentage of CSF CD3-CD56+ cells, but not CSF leukocytes at high levels. Clinical conditions improved after treatment in two patients, worsened in one and remained substantially unchanged in the remaining five. The side effects of intrathecal rIL2 treatment included fever, confusion, and seizures, and there were marked interindividual variations in the immunological response.

Adolescent↗
PubMed1996

Human brain endothelial cells and astrocytes produce IL-1 beta but not IL-10.

The ability of human brain endothelial cells to produce mRNA for interleukin-10, and release IL-10 in culture supernatants after in vitro stimulation with LPS, TNF-alpha and gamma-IFN was assessed and compared to that of astrocytes, peripheral blood mononuclear cells and human umbilical vein endothelial cells. IL-1 beta and beta 2-microglobulin release were also analysed. IL-10 and TNF-alpha mRNA presence was investigated in normal brain as well as in three plaques from two multiple sclerosis patients. While increased IL-1 beta and beta 2-microglobulin release in the supernatants of stimulated cells could be detected in all the studied cell lineages, IL-10 mRNA and protein release was only seen in LPS-stimulated PBMNCs. Similarly, mRNA for IL-10 was not detected in CNS tissues, while TNF-alpha was present in all plaques. The lack of production of significant amounts of IL-10 by astrocytes and human brain endothelial cells suggests that these cells may not be the primary source of in vivo IL-10-mediated down-regulation of immune reactions within the central nervous system.

Adult↗