Intracellular expression of type VII collagen in squamous cell carcinoma complicating dystrophic epidermolysis bullosa.
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Biomedical subjects
Publications and source records attributed to H Barthélémy.
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In rodent thymus, associations between dendritic cells (DC) and thymocytes have been suggested to be implicated in differentiation and/or maturation processes. In this study, we report intimate associations formed between human thymic DC and thymocytes in culture and we analyze their ultrastructural cell phenotype. Observations by phase contrast microscopy showed that DC present long and thin dendrites and bind many thymocytes. Transmission (TEM) and scanning electron microscopy (SEM) revealed that both cellular populations were in close connection and tight membrane contact could be observed. The phenotype of DC and attached thymocytes was characterized with a series of monoclonal antibodies by protein A-gold TEM and SEM immunolabelings. Quantitative evaluation of immunolabeling (number of gold granules/microns of cellular membrane) suggests the presence of two subpopulations of CD1+ thymic DC (strong and weak), whereas this discrepancy is not observed in DR+ and CD4+ DC populations. On the other hand, the majority of thymocytes bound to DC strongly express the CD1, CD4, CD8 and CD2 antigens and weakly the CD3 antigen, indicating that they represent double-positive immature thymocytes. Uniform distribution of DC and thymocytes membrane antigens was confirmed with a backscattered SEM study. This morphological and immunolabeling TEM and SEM analysis demonstrates that human thymic DC may form associations with CD4+CD8+CD3weak thymocytes and raises questions about their physiological relationship.
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The phenotypic analysis of human thymic dentritic cells (DC) in culture and in purified suspensions has been studied with light and electron microscopic (EM) immunolabelling techniques. Using a series of monoclonal antibodies (mAb) and a protein A-gold technique, we demonstrated that DR- and T6-positive cultured DC strongly bind the 9.3F10 mAb, an anti-DR-related antibody produced against human blood DC, and weakly express the T4 antigen, a membrane marker shared by Langerhan's cells (LC). On the other hand, thymic-cultured DC are negative for the other T-cell and monocyte-macrophage antigens. These results support the hypothesis that human thymic DC may be related to blood DC and epidermal LC. Moreover DC, unlike thymic macrophages, do not phagocytose latex particles, opsonized sheep red blood cells (SRBC) or Candida albicans. An efficient two-step technique of isolation, using a Percoll density gradient followed by an indirect panning technique, yields a purified (70-80%) thymic DC population, OKIa1-, 9.3F10- and OKT6-positive and esterase-negative. Immunolabelling and electron microscopy confirm that these isolated DC present similar phenotypic and ultrastructural features to human thymic DC in situ and in culture. Purified DC, used as stimulator cells in mixed leucocyte reaction (MLR), induce stronger proliferative responses than peripheral blood monocytes used as a control; blocking assays with OKIa1 mAb plus complement greatly reduced this stimulatory potency. These functional assays demonstrate that we obtained a purified typical DC population that can be used in immunological functional studies to elucidate the specific role of DC in human thymus.
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Cyclosporin A (CyA) is a fungal peptide used as immunosuppressor in human organ transplantation. Increased hair growth appears to be a common side-effect of treatment, occurring in almost all patients treated with oral CyA. The development of hypertrichosis during CyA administration is not hormone-dependent; it may be mediated by a direct effect of the drug on the hair growth process. We used CyA topically (5 p. 100 oily solution) in 14 patients with severe alopecia areata (totalis 5, ophiasis 3, bald plaques 6). The drug was applied on the alopecia twice a day for 5 +/- 1.5 months. Patients were examined monthly. No clinical adverse effect was observed. Routine blood examination did not show any change, except for a transient increase of hepatic enzymes in one patient. CyA determinations were performed monthly by radioimmunoassay. No CyA was detected in the patients' serum. Treatment resulted in no regrowth in 8 patients, development of vellus hair in 3 patients (alopecia areata totalis 2, ophiasis 1) at the end of therapy, and normal hair growth in 3 patients with bald plaques. We may conclude that CyA is capable of inducing regrowth of hair when applied topically. However, the drug does not seem to be useful for the treatment of alopecia areata.
Bullous pemphigoid is a typical autoimmune disease. It is classically treated with systemic corticosteroids alone or combined with immunosuppressants. Cyclosporine A (CyA), a new immunosuppressive agent with high activity in organs and bone marrow transplantation, could be expected to prove effective in this disease owing to its action on lymphocytes. Seven patients with bullous pemphigoid were treated with CyA in daily doses of 6 to 8 mg/kg bodyweight. Treatment was monitored by measurements of serum CyA, creatinine and liver enzyme levels. The effectiveness of treatment was assessed on clinical changes. The seven cases are dealt with individually, with a brief case-report for each of them. The only side-effects observed were reversible rises in serum creatinine levels and hypertrichosis in two cases; these are usual reactions to the drug. Hormonal assays were normal in two female patients. Concerning results, our patients fell into two groups. Among those treated with CyA alone there were two failures and two sustained satisfactory results. Treatment was successful in all patients treated with CyA during relapses under corticosteroid therapy, but two patients relapsed after CyA was discontinued. It is concluded that CyA is of no interest in the acute phase of bullous pemphigoid, that the long-term stability of the results obtained is doubtful and that this potentially nephrotoxic drug should be avoided or administered with extreme caution in elderly people, since their renal function may be at the limit of normality.
In situ, two types of dendritic cells (DCs) have been characterized in more detail: the interdigitating DCs of peripheral lymphoid tissues and the epidermal Langerhans cells. In order to characterize human thymic DCs, normal human thymus specimens were obtained from children undergoing cardiovascular surgery. In culture, DCs could be easily differentiated from macrophages and epithelial cells by their long fine processes, irregular nucleus, and dark, membrane-bound granules. By immunoelectron microscopy, using the protein A-gold and the avidin-biotinperoxidase complex techniques, cultured DCs were strongly labeled with anti-Ia and anti-OKT6 monoclonal antibodies. These results demonstrate that the phenotype of thymic DCs is similar to that of epidermal Langerhans cells and suggest that they may belong to the same cellular lineage.
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The entity of the Dühring-Brocq's disease (11, 12, 20) has be cut off by the immunofluorescence (7, 39, 40). We have studied three of the diseases which originally were included in this description: bullous pemphigoid (BP), cicacial pemphigoid (CP) and herpes gestationis (HG). This work is at the same time prospective and retrospective. The linear IgA dermatosis are excluded (17).
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