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Biomedical subjects

C Marchand

Publications and source records attributed to C Marchand.

At least 55 records · Page 3Linked to original sources

The 2-amino group of guanine is absolutely required for specific binding of the anti-cancer antibiotic echinomycin to DNA.

The 2-amino group of guanine is believed to be a critical determinant of potential DNA binding sites for echinomycin and related quinoxaline antibiotics. In order to probe its importance directly we have studied the interaction between echinomycin and DNA species in which guanine N(2) is deleted by virtue of substitution of inosine for guanosine residues. The polymerase chain reaction was used to prepare inosine-substituted DNA. Binding of echinomycin, assessed by DNAse I footprinting, was practically abolished by incorporation of inosine into one or both strands of DNA. We conclude that both the purines in the preferred CpG binding site need to bear a 2-amino group to interact with echinomycin.

Base Sequence↗

Evidence for diversity of Plasmodium falciparum sporozoite surface antigens derived from analysis of antibodies elicited in humans.

We have compared the reactivities of antibodies developed by individuals frequently exposed to Plasmodium falciparum infections with the epitopes contained within the repeats of the circumsporozoite (CS) protein and their reactivities with the epitopes of a native molecule(s) accessible on the sporozoite surface. Results of direct-binding assays and competition assays between artificial and native molecules or between human antibodies and anti-CS monoclonal antibodies suggest that humans respond preferentially to epitopes not contained within the repeats of the CS protein and probably not contained in the whole CS protein. Human monoclonal antibodies reactive with P. falciparum sporozoite surface antigens were produced by Epstein-Barr virus transformation of human lymphocytes. Their pattern of reactivity with sporozoites from a number of different isolates indicates the existence of several distinct epitopes on the parasite surface. Differences between isolates and between sporozoites within a given sample were observed. No single human monoclonal antibody capable of detecting an epitope expressed in all the parasites studied was found.

Animals↗

How to select Plasmodium falciparum pre-erythrocytic antigens in an expression library without defined probe.

The restricted access to Plasmodium falciparum liver stages has greatly limited the analysis of the antigenic content of that stage. Due to the lack of material to perform immunochemical studies, of access to mRNA, and of monoclonal probes, we decided to screen a genomic library with stage-restricted human antibodies. This strategy led to the identification of a large number of DNA fragments encoding both sporozoite specific as well as liver-stage specific epitopes. Following the initial characterization of one liver-stage antigen, further screening was performed by using additional selective human antibodies. These were defined as having a high degree of reactivity with native antigens on either of the two stages while being negative with the already known molecules of the two stages. From this second screening and the study of cross-reactions, several subsets of DNA clones expressing antigens present on the surface of sporozoites, or in liver stages, or in both, could be identified. In exposed individuals a high prevalence of antibodies to several of these antigens was found.

Animals↗

[Oral hairy leukoplakia in AIDS. Histologic and ultrastructural study of 8 cases].

Oral hairy leukoplakia is a disease of the oral mucosa occurring almost exclusively in HIV-infected (mostly AIDS) patients and due to the opportunistic development of Epstein-Barr virus (EBV) within the oral epithelium. Clinically, it shows as whitish patches with a shaggy surface occurring on the lateral margins of the tongue, less frequently the buccal and labial mucosa or the soft palate. Histologically, it comprises parakeratotic hyperkeratosis, acanthosis and numerous koilocytoid cells within the stratum spinosum, i. e. cells with a pycnotic nucleus surrounded by a clear halo and pale-staining cytoplasm. Electronmicroscopy readily shows abundant Herpes-group viral particles within the upper epithelial layers. By immunohistochemistry, in situ molecular hybridization and Southern-blot EBV antigens and DNA have been demonstrated within the lesions whereas HPV and HIV are generally undetectable. In the present work we studied by light- and electronmicroscopy lesions from 8 HIV-seropositive individuals that fulfilled the clinical and histological criteria of OHL. Ultrastructural examination showed the presence in all cases of Herpes-type virions, which, in two of the cases studied by immunohistochemistry, proved to belong to the EBV. It is concluded that electronmicroscopy is a sufficiently sensitive examination to confirm the diagnosis of OHL suggested in the presence of an appropriate clinico-histological setting.

Acquired Immunodeficiency Syndrome↗

Crossover study of thalidomide vs placebo in severe recurrent aphthous stomatitis.

A multicentric crossover randomized trial of 100 mg of thalidomide vs placebo each for 2 months was conducted in patients with severe aphthous stomatitis of more than 6 months' duration. Seventy-three patients were included. Complete remission was obtained in 32 patients who received thalidomide and in 6 patients who received placebo. The confidence interval of the difference between the two treatments ranged from 25% to 53%. Most of the patients who did not achieve a complete remission had a dramatic improvement with regard to the number of aphthae when they were receiving thalidomide. Thirteen of 17 patients who had a complete remission while they were receiving thalidomide had a recurrence with placebo, 19 +/- 9 (mean +/- SD) days after stopping this drug. Side effects were significantly more frequent with thalidomide, especially drowsiness and constipation. We concluded that thalidomide in a dosage of 100 mg/d is an effective treatment of severe aphthous stomatitis but is not without some risk.

Adult↗

Immunohistochemical study of normal skin of HIV-1-infected patients shows no evidence of infection of epidermal Langerhans cells by HIV.

Langerhans cells (LC) are dendritic epidermal antigen-presenting cells expressing the surface molecule CD4, which renders them theoretical cellular targets for direct infection by the human immunodeficiency virus (HIV). To date, somewhat conflicting results have been reported concerning the in vivo infection of LC by HIV as well as the numerical alteration of these cells in the course of HIV infection. In the present work we studied clinically normal skin of a group of 44 HIV-1-seropositive patients classified according to the Centers for Disease Control (CDC) stages II (n = 14), III (n = 9), and IV (n = 21). Monoclonal antibodies (MAb) to HIV p18, p24, and gp120 and to HLA-DR and CD1a antigens (specific for LC) were applied on frozen skin sections using an amplification biotin-streptavidin-fluorescein technique. The MAb to HIV p18 cross-reacted with a cytoplasmic antigen of epidermal basal keratinocytes also present on HIV-seronegative skin specimens. No other reactivity was observed with any of the three anti-HIV MAb. The quantitative study showed that no significant correlations could be established between the number of LC (evaluated independently by HLA-DR and CD1a antigens) and the number of peripheral blood CD4+ve lymphocytes or the CDC disease stage. These results cast some doubt on the previously reported in vivo infection and numerical decrease in LC in HIV infection. The precise involvement of LC in HIV infection awaits further investigation.

Acquired Immunodeficiency Syndrome↗

Stewart-Treves syndrome: an histogenetic (ultrastructural and immunohistological) study.

One case of the so-called "Stewart-Treves syndrome" (STS), appearing on a lymphoedematous arm complicating radical mastectomy for breast cancer, was characterized electronmicroscopically and immunohistologically, in order to elucidate its disputed (epithelial vs endothelial) histogenesis. Epithelial and endothelial differentiation markers used comprised: antibodies against keratin, vimentin, factor VIII-related antigen (F VIII-RA), HLA-DR antigens and the lectin Ulex europeaus agglutinin I (UEA I). At the ultrastructural level, neoplastic cells were found to contain typical Weibel-Palade bodies, whereas by immunohistological techniques they proved to be keratin-negative/vimentin+, F VIII-RA+, UEAI+, HLA-DR+. These results rule out a possible epithelial differentiation and strongly favour an endothelial one for STS.

Aged↗