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Biomedical subjects

O Picard

Publications and source records attributed to O Picard.

At least 55 records · Page 3Linked to original sources

A 2-year follow-up of an anti-HIV immune reaction in HIV-1 gp160-immunized healthy seronegative humans: evidence for persistent cell-mediated immunity.

The first trial of an anti-HIV immunization, using a recombinant vaccinia virus expressing gp160 (rV) for priming and paraformaldehyde-fixed rV-infected PBLs and soluble gp 160 for boosting, clearly showed an in vitro HIV-protective immune reaction. This result led us to carry out an additional 2 year Phase I clinical trial in 25 HIV-seronegative volunteers, using HIV gp 160 antigens for immunization in four different protocols. The 2 year trial showed (a) the safety of the preparations, (b) a transient humoral immunity following each boost, and (c) a long-lasting memory T-cell response. Memory cytotoxic T-lymphocytes (CTLs) induced by gp 160 antigen with or without vaccinia vector lysed HLA class I restricted target cells expressing HIV-1 env antigens. These results are consistent with CTLs being an effective component of an AIDS vaccine to control cell-to-cell viral replication, dissemination in the organism, and subsequent evolution toward AIDS.

AIDS Vaccines↗

HGP-30, a synthetic analogue of human immunodeficiency virus (HIV) p17, is a target for cytotoxic lymphocytes in HIV-infected individuals.

Evaluation of the immune response of individuals exposed to human immunodeficiency virus (HIV) is an important component of any plan designed to lead toward the development of an AIDS vaccine. Since the levels of antibodies to HIV p17 and the synthetic p17 peptide HGP-30 correlate with stages of progression to AIDS, studies were initiated to determine whether cytotoxic lymphocytes directed toward target cells pulsed with HGP-30 and radioactive chromium were present in seropositive individuals. The significance of such cells in controlling HIV viral infection has recently been enhanced by reports that HIV p17 is on the surface of infected cells and that an inactivated virus vaccine depleted of viral envelope appears to be effective in controlling expression. The selection of HGP-30 as the p17 peptide to be evaluated in early studies is based on the presence of both T-cell and B-cell epitopes as predicted by computer modeling and mouse studies and the demonstration of in vitro neutralization activity by antibodies to the epitope. By using B-lymphoblastoid cells pulsed with HGP-30 and radioactive chromium as autologous targets and mixed leukocyte culture-expanded peripheral blood lymphocytes as effectors, CD8+ cytotoxic T lymphocytes against HGP-30-coated targets were identified in seropositive individuals. In this report we demonstrate that a synthetic p17 epitope can be a target for major histocompatibility complex-restricted cytotoxic T lymphocytes in HIV-infected individuals.

Cells, Cultured↗

Discriminating between protective and enhancing HIV antibodies.

Most attempts to produce a vaccine against HIV-1 infection are utilizing envelope protein components. Hypothetically such vaccine candidates could stimulate production of antibodies that enhance HIV-1 infection via the macrophage route of entry and, consequently, cannot be detected in the conventional neutralization assay. To study this hypothesis we report an assay designed to evaluate the protective/enhancing activity of serum from seropositive immunized or infected individuals. Highly purified activated FcR-bearing monocytes-macrophages were infected with HIV-1 in the presence of the sera, then washed and cocultured with activated peripheral blood mononuclear cells (PBMC) from a normal donor. Productive viral infection, as evaluated by p24 antigen semiquantitative assay in the culture supernatants, allow evaluation of protective/enhancing activity of the sera. The data clearly show that protective rather than enhancing activity is present in the serum of env protein-immunized individuals.

Acquired Immunodeficiency Syndrome↗

[Recurrence of atypical pulmonary pneumocystosis treated with pentamidine aerosol].

Two cases are reported of atypical relapses of pneumocystosis in AIDS patients treated with aerosol pentamidine for 14 and 22 months. These pneumopathies are unusual because of their pitted aspect and recurrent spontaneous pneumothoraxes in spite of repeated drainage. They are difficult to diagnose because bronchoalveolar lavage fluid is negative for Pneumocystis carinii, despite their presence in lung biopsies. Histological lesions vary, being granulomatous, necrotizing and invasive, with involvement of the pleura and lymph nodes. Although a highly effective therapy against P. carinii pneumonia, aerosol pentamidine may play a role in these atypical episodes: either by causing bronchial obstructions beyond which the pneumocytotic lesions cannot be reached by lavage and become necrotic, or by favoring the extrapulmonary spread of P. carinii.

Acquired Immunodeficiency Syndrome↗

[The surgeon and AIDS].

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Acquired Immunodeficiency Syndrome↗

Fibroblast-dependent tumorigenicity of cells in nude mice: implication for implantation of metastases.

The inadequate nature of the microenvironment is one of several factors considered in the failure of tumor engraftment in athymic mice; in the present work, we have tried to more adequately reconstitute it by injecting tumor cells together with fibroblasts. We have demonstrated that the s.c. co-inoculation of fibroblasts with different kinds of tumor cells of animal origin [rat rhabdomyosarcoma (RMS) 9-4/0, rat hepato-carcinoma FAO] or human origin (colonic adenocarcinoma HT29, Ewing's sarcoma pleural metastasis EW-S1) is necessary for tumor take and growth when the number of tumor cells alone is below the tumorigenic dose. We have shown that the s.c. coinoculation of 10(6) fibroblasts and 10(2) RMS 9-4/0 tumor cells induced a tumor take in all the recipient mice, while 10(2) tumor cells alone never gave any tumor. With a tumorigenic number of RMS 9-4/0 tumor cells (10(4), addition of 10(6) fibroblasts decreased the delay between cell injection and tumor appearance, thereby increasing tumor take and growth rate. These results were observed not only in nude animals (mice and rats) used as recipient animals but also in normal WAG rats receiving the syngeneic RMS 9-4/0 tumor cells, and they were independent of the nature or origin of the different fibroblasts cells. This helper effect has also been observed in the normal WAG rats. I.v. injection of tumor cells from a poorly metastatic 9-4/8 subline, derived from the RMS 9-4/0 line and mixed with 10(6) fibroblasts, gave a high number of lung colonies. Addition of 10(6) irradiated 9-4/8 tumor cells instead of fibroblasts did not increase the lung colonizing potential. Fibroblast-conditioned medium mixed with tumor cells instead of fibroblasts also enhanced tumor take and size but to a lesser extent than did the fibroblasts themselves. Only endothelial cells cultured from porcine aorta had a similar helper effect among the cells tested. It is argued in the discussion that the proliferating state of cultivated fibroblasts is a determinant factor conferring upon them the ability to promote tumor cell growth, while fibroblasts very numerous at the implantation site but quiescent might not be efficient in cooperation. Changes in fibroblast morphology and physiology may be necessary in order for tumor cells to express their tumorigenicity.

Animals↗

[Principal muco-cutaneous aspects encountered in AIDS].

Due to the high frequency and variety of the mucous cutaneous signs, the dermatologists are facing many cases of AIDS. These signs are no specific but only the consequence of a cellular immunodeficiency; they can be encountered in other situations, more specifically after an immunosuppressive treatment. Therefore, the diagnosis can be evocated only from AIDS association of the mucous cutaneous manifestations with other clinical, epidemiological and biological signs. The Kaposi's sarcoma which is present in 35 of the observed AIDS is in fact the cutaneous aspect of a cellular immunodeficiency. In one hand, the clinical lesions have a quiet involvement without any associated disorder. At the opposite, cutaneous lesions have a fulminant dissemination associated to lymph nodes and/or visceral involvement and opportunistic infections: these cases have a very severe prognosis. Kaposi's sarcoma is not observed in the cases of post-transfusional AIDS. Chronical herpes occurs frequently during this syndrome, the lesions lasting above six weeks associated to anal or genital localizations. Chronical candidosis, clinically associated, has a mucous cutaneous localization with involvement of the oral cavity, progressively extending digestive system and respiratory tracts.

Acquired Immunodeficiency Syndrome↗

[Fibroblast cooperation in the graft of tumor cells in nude mice].

The occurrence and growth of xenogenic tumors in athymic Mice depend on å number of factors: the level of the immune response, the number of the injected tumor cells and the microenvironment of the tumor cells. We have demonstrated that the addition of cultivated fibroblasts to murine sarcoma cells was necessary for tumors to take. The addition of irradiated fibroblasts or of a medium conditioned by fibroblasts had the same effect. We therefore hypothesize an interaction between the fibroblasts which produce factors necessary for tumor cells and murine sarcoma cells which then initiate a tumor in the host. In vivo, tumor cells could induce host fibroblasts to produce growth factor(s) which in turn would help to initiate and maintain tumor growth.

Animals↗

[Kaposi's disease. 2 recent cases].

Known since 1872, the multifocal angiosarcoma called Kaposi's sarcoma takes different forms in different communities. It develops slowly among the mediterranean populations and Jewish Central Europe and most rapidly among Bantus, in Africa, and white homosexuals. Another aspect of the disease has been described in patients with transplanted kidney, where it seems to be associated with immunosuppressive treatments. The recent outbreak of Kaposi's sarcoma among homosexuals in New York and San Francisco raises new and difficult problems concerning its aetiology, as the outbreak cannot be entirely explained by pressure from sexually transmissible diseases. Having observed two new cases in France, the authors have attempted to re-evaluate the pathophysiological factors of the disease, the most constant of which seems to be a considerable degree of immunodepression, perhaps partly due to chronic infection.

Adult↗