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Biomedical subjects

R el Habib

Publications and source records attributed to R el Habib.

8 recordsLinked to original sources
PubMed1993

Immunological parameters during treatment with ditiocarb (Imuthiol).

OBJECTIVES: To examine the effect of ditiocarb (DTC) treatment on immunological parameters of HIV infection. Immunophenotyping included CD4+ T-cell counting and the analysis of activation markers on CD8+ T cells. Anti-CD3-induced proliferation and anti-CD3-mediated cytotoxicity were monitored as indexes of T-cell function. In addition to the clinical evolution, HIV antigen and anti-p24 levels were monitored during treatment. DESIGN: In this double-blind, placebo-controlled study, 50 HIV-seropositive patients belonging to all clinical disease stages were randomized to treatment with DTC or placebo and followed for 4 months. METHODS: Immunophenotyping on whole blood was performed by flow cytometry, using combinations of anti-CD8 with anti-CD4, anti-HLA-DR, anti-CD38, anti-CD45RO and anti-CD57. Patient lymphocytes were freshly assayed for cytolytic capacity against OKT3-coated targets. T-cell proliferation was measured after 3 days of OKT3-stimulation. RESULTS: No effect was observed on CD4 and CD8+ T-cell counts or on CD8+ T-cell activation markers, except for a selective increase in HLA-DR expressing CD8 cells in the DTC-treated group. Decline in anti-CD3-induced T-cell proliferation and rise in anti-CD3-mediated T-cell cytotoxicity were observed in the DTC and placebo groups. No effect on HIV antigen and anti-p24 antibody titres was observed. The incidence of clinical complications was similar in each group. CONCLUSION: No beneficial immunomodulatory effect of DTC was demonstrated.

Adult↗
PubMed1992

Diethyldithiocarbamate (ditiocarb sodium) effect on arachidonic acid metabolism in human mononuclear cells. Glutathione peroxidase-like activity.

Diethyldithiocarbamate (DTC), a thiol delivery agent, has been shown to significantly reduce the frequency of primary opportunistic infections in HIV-infected patients. This therapeutic effect has been related to the capacity of DTC to reverse the deleterious effects of the oxidative stress occurring in HIV infection. The influence of DTC on the oxygenated metabolism of arachidonic acid (AA) was investigated in mitogen-stimulated human peripheral blood mononuclear cells (PBMC). Upon incubation with PBMC previously labelled with [3H]AA, Concanavalin A (Con A) markedly increased cyclooxygenase and lipoxygenase activities, within 30 min, as judged by thromboxane B2 (TxB2) and hydroxyeicosatetraenoic acid (HETE) production. Con A activation of [3H]AA platelets also increased 12-HETE production but did not induce any TxB2 synthesis. Micromolar concentrations of DTC, added simultaneously with the mitogen, significantly enhanced the synthesis of HETEs above the Con A-induced level while TxB2-induced synthesis was inhibited but only at DTC concentrations higher than 50 microM. In the presence of nordihydroguaiaretic acid, a lipoxygenase inhibitor, which inhibited the Con A-induced synthesis of HETEs by 78%, DTC no longer stimulated HETE production above the Con A-induced level. Reverse phase HPLC analysis showed that Con A increased the PBMC production of 5-, 12- and 15-HETEs. In the presence of 5 microM DTC, 5-HETE production was entirely suppressed whereas the 15-HETE level was markedly enhanced, 12-HETE production by the contaminating platelets remained unchanged. In vitro experiments indicated that DTC alone did not significantly influence 15-hydroperoxyeicosatetraenoic (15-HPETE) production by the soybean 15-lipoxygenase but, in the presence of added reduced glutathione, DTC markedly reduced 15-HPETE into 15-HETE. In addition, DTC was able to substitute for cellular extract in the glutathione peroxidase (GPx) assay system. Taken together, these results indicate that DTC, through its "GPx-like" activity is able to modify the lipoxygenase cascade. Its ability to selectively reduce 15-HPETE known to stimulate immunosuppressive T-cells might help to explain its positive regulatory effect upon the immune system.

Arachidonic Acid↗
PubMed1991

Intravenous gamma-globulin in myasthenia gravis: interaction with anti-acetylcholine receptor autoantibodies.

Clinical improvement has been observed in myasthenia gravis patients treated by intravenous immunoglobulin (IVIg). In order to investigate the mechanism of action of these IVIg, we looked for an in vitro interaction between IVIg and the anti-acetylcholine receptor autoantibodies. Significant inhibition by IVIg of anti-acetylcholine receptor autoantibody activity from 30 MG sera was observed and binding of anti-acetylcholine receptor autoantibodies on IVIg was found for four of five myasthenia gravis sera. These observations suggest that IVIg contains Ig directly binding to and inhibiting pathogenic autoantibodies.

Adolescent↗
PubMed1989

[Lysosomal enzyme deficiency: in vitro correlation of deficient cells using a conditioned medium or by co-culturing with non-deficient cells].

We demonstrate that lysosomal enzyme (alpha-L-fucosidase) can enrich deficient fibroblasts, with purified enzyme brought by the medium, or with an enzyme supply by various cell sources. The co-culture systems lead to a deficient cell correction, whatever donor cells are lymphocytes or lymphoblastoid cells. This correction arise only with alive cells, and is strongly inhibited by mannose-6-phosphate. Our results do not support the hypothesis that cell to cell contact independently of mannose-6-phosphate binding site is necessary for transfer of lysosomal enzyme from lymphocytes to fibroblasts. We suggest that the neighbourhood of cells leads to a phosphorylated precursor increase in the pericellular area, which creates an enzyme stabilizing effect favourable at its incorporation.

Cell Communication↗
PubMed1987

Prevalence of CMV ELISA antibody: titer and neutralizing activity in intramuscular immune globulin of placental origin.

The treatment of human CMV infection in transplant recipients by intravenous or intramuscular administration with high doses of hyperimmune or normal Ig showed inconsistent results. In fact, all hyperimmune Ig preparations were produced from high anti-CMV Ab titer plasma selected either by ELISA, complement fixation, or indirect hemagglutination test. These tests may not investigate the neutralizing activity of antibodies (Ab). We, therefore compared the ELISA titers with the neutralizing Ab titers in various normal Ig preparations from plasma or placenta and for intramuscular or intravenous use. Hyperimmune plasmatic Igs were also included. All the preparations were tested at a 5% dilution. We report the following data: (1) There is a poor correlation between ELISA and neutralization test. (2) The Igs of placental origin have significantly higher ELISA anti-CMV Ab titers than plasmatic normal Igs. They show the same neutralizing activity. (3) When compared with the normal intravenous Ig, normal intramuscular Igs show significantly higher titers with both techniques (P less than .0001). (4) Normal intramuscular Igs from placenta offer similar ELISA Ab titers and similar or higher neutralizing activity than hyperimmune Igs purified from plasma. It would be worth using Igs with high neutralizing activity in CMV prophylaxis in order to correlate in vitro tests and in vivo protection. In this respect, normal intramuscular Igs from placenta might be challenged in a clinical trial.

Antibodies, Viral↗