[G. Orth, D. Dompmartin, P. Agache, M. Faure, O. Croissant: "The plurality of human papillomaviruses". 1978].
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Biomedical subjects
Publications and source records attributed to M Faure.
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T cell tolerance is established and maintained through various mechanisms, the critical component being the persistence of the specific Ag. However, at the molecular level, the nature of the recovering TCR repertoire following breakdown of tolerance is unknown. We address this important question by following kappa light chain constant region (C kappa)-specific CD4+ T cells of kappa light chain knock-out (kappa-/-) mice born to kappa+/- mothers. These cells, which were in contact with maternal kappa+ Igs from early ontogeny until weaning, were strongly tolerized. Tolerance was reversible and waned with the disappearance of peptide C kappa 134-148 presentation in lymphoid organs, including the thymus. Whereas three specific V beta-J beta rearrangements emerged in the peptide C kappa 134-148-specific CD4+ T cell response of all regular kappa-/- mice, soon after breakdown of tolerance only one of these rearrangements was detected. The two others displayed a significant delay in reappearance and were still rare at 26 wk of age, while the control proliferative response had already recovered 3 mo earlier. At 52 wk of age, a complete recovery of the three canonical V beta-J beta rearrangements was observed. Thus, although profoundly perturbed for several months, the T cell repertoire returns to equilibrium, highlighting the resilient nature of this system.
Langerhans cell histiocytosis (LCH) is related to the proliferation of cells, which are similar to Langerhans cells (LC) but possess many abnormal characteristics. Lesions are widespread and this fact suggests that LCH cells or their precursors are present in the blood of patients. In five adult patients, we have isolated and cultured CD34+ blood progenitors of dendritic cells. We studied their phenotype by flow cytometry and their functional properties in mixed culture with heterologous lymphocytes and with autologous lymphocytes in the presence of tri-nitro-phenyl antigen (TNP). The amount of CD34+ precursors was dramatically higher than controls but a high mortality occurred during the in vitro differentiation. The phenotype of surviving cells was similar to LC phenotype (CD1a+, CD83+, Lag+) but some of them expressed CD2. These cells were able to induce T cell proliferation in mixed culture. They could not initiate primary response to TNP, except in a patient treated with thalidomide. In our hands, these CD34+ cells may be precursors of LCH cells.
This paper presents the first purification of the mitochondrial branched-chain amino acid aminotransferase (BCATm) from sheep placenta. It is a homodimer with an apparent subunit molecular mass of 41 kDa. The enzyme differs from those of the rat and human as it appears to form at least one intermolecular disulfide bond. The sheep BCATm cDNA (1.4 kb) encodes a mature polypeptide of 366 amino acids with a calculated molecular mass of 41 329 Da and a partial mitochondrial targeting sequence of seven amino acids. The sheep BCATm sequence shares higher identity with other mammalian BCATm isoenzymes (82-85%) than with the cytosolic isoenzymes (60%). By Northern blot analysis, a message of 1.7 kb was detected in sheep placenta and skeletal muscle. Measurements of BCAT activity, mRNA and BCATm protein in sheep placenta and skeletal muscle revealed that BCATm is the sole BCAT isoenzyme expressed in placenta, whereas it contributes 57 and 71% of the BCAT activity in tensor fascia latae and masseter muscles from weaned lambs respectively. Skeletal muscle, the main site of branched-chain amino acid transamination, exhibits significantly lower BCAT activity in sheep than in rat. Our results suggest that the low BCATm mRNA level probably accounts for the low BCAT activity in sheep skeletal muscle, and that the metabolic scheme for branched-chain amino acid catabolism is specific to each species.
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BACKGROUND: Preliminary studies have suggested that paroxetine may be effective in social phobia/social anxiety disorder. AIMS: To assess the efficacy and tolerability of paroxetine in the acute (12-week) treatment of social phobia. METHOD: Two-hundred and ninety patients with social phobia were assigned randomly to paroxetine (20-50 mg/day flexible dose) or placebo for 12 weeks of double-blind treatment. Primary efficacy outcomes were the Liebowitz Social Anxiety Scale (LSAS) total score (patient-rated) and the Clinical Global Impression (CGI) scale global improvement item. The secondary efficacy variables included CGI scale severity of illness score and the patient-rated Social Avoidance and Distress Scale. RESULTS: Paroxetine produced a significantly greater reduction in LSAS total score (mean change from baseline: -29.4 v. -15.6; P < or = 0.001) and a greater proportion of responders (score < or = 2 on CGI global improvement) (65.7% v. 32.4%; P < 0.001) compared with placebo at the end of the 12-week study period. Both primary efficacy variables were statistically significant compared with placebo from week 4 onwards. Paroxetine was generally well tolerated. CONCLUSIONS: Paroxetine is an effective, well-tolerated treatment for patients with social phobia.
INTRODUCTION: The high mortality at 1 year of patients with bullous pemphigoid is considered to be due mainly to systemic corticosteroids. We report 20 cases of bullous pemphigoid treated solely with class I topical corticosteroid. PATIENTS AND METHODS: Twenty patients with bullous pemphigoid grade 1 and grade 2 were treated with clobetasol propionate 0.05 p. 100 cream at the initial dose of 12 mg/m2/day, progressively tapered over months. Severe forms of bullous pemphigoid covering more than 60 p. 100 of total body area were excluded. RESULTS: 35 p. 100 of the patients obtained a remission and 35 p. 100 healed (62.5 p. 100 of the mild forms, 16.7 p. 100 of the moderate forms). The average follow up was 11 months after the end of treatment. Side-effects were mild (cutaneous infections, dermal atrophy). Transitory biological anomalies were observed, mainly related to systemic absorption of clobetasol propionate. Some systemic adverse reactions were noted not necessarily attributed to treatment. DISCUSSION: Topical steroid treatment was efficient in patients with mild bullous pemphigoid. Our results were comparable to those reported in the literature except for some cutaneous side effects.
INTRODUCTION: Organ-graft recipients are at increased risk for developing cutaneous tumors, mostly carcinomas; however, melanocytic nevi (MN) also develop in excess numbers in these patients. The aim of this study was to assess whether MN developing in pediatric organ graft recipients (OGR-MN) have a higher proliferative profile than similar lesions developing in non-immunosuppressed subjects (C-MN), a fact that could confer to them potential for malignant transformation into melanoma. MATERIAL AND METHODS: The immunohistochemical expression of two proliferation-associated markers (MIB1/Ki67 and PCNA) and of p53 oncoprotein was comparatively studied in a group of 10 and OGR-MN and 12 C-MN. RESULTS: MIB1/Ki67 and p53 were very weakly, if at all, expressed in all tumors, whereas PCNA was expressed in the majority of tumor cells in both groups of lesions. Overall, no significant differences were found between the two groups studied. DISCUSSION: Melanocytic nevi developing in organ transplant children do not have a higher proliferative potential, and therefore do not seem to be intrinsically more prone to malignant transformation than similar lesions appearing in non-immunosuppressed children; however the possibility exists that the decreased immune defense mechanisms indirectly favors the growth of these lesions.
Although the influence of maternal Ig on the B cell repertoire and subsequent Ab response has been extensively studied, much less attention has been devoted to their effects on T cell responses of the offspring. To address this question, we have studied the influence of maternal kappa-positive Ig (Ig kappa) on the C kappa-specific CD8+ T cell response of kappa knock-out (kappa-/-) pups resulting from various crosses and foster nursings. These systems allowed control of physiologic transmission of Ig kappa at defined periods of ontogeny. Our data show that conventional transfer of maternal Ig via the placenta plus colostrum/milk or adoptive transfer via only the colostrum/milk were the most efficient at tolerizing C kappa-specific CD8+ responses. Surprisingly, tolerance was not detected in kappa-/- pups born to kappa+/- females obtained by cesarean delivery and suckled by kappa-/- mothers (transplacental supply only). Tolerance, which was strong until 5 wk of age, was reversible and waned with the decrease of Ig kappa serum concentration. Depletion of CD4+ T cells at the time of C kappa peptide immunization abolished the tolerance of C kappa-specific CD8+ T cells. These data suggest that an oral supply of Ig is very efficient at inducing and maintaining tolerance of C kappa-specific CD8+ T cells, at least for several weeks after birth, and that suppression rather than deletion is responsible for this tolerance. In addition, they strengthen the view that tolerance of CD8+ T cells to a soluble Ag is never permanently acquired even if it is present in large quantities during ontogeny.
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The Thomsen-Friedenreich (T) antigen is the core disaccharide of cancer-associated carbohydrates, whose expression allegedly correlates with the prognosis of some carcinomas. We studied the expression of the T antigen and its precursor (Tn) with monoclonal antibodies in formalin-fixed specimens of normal skin and various benign cutaneous tumours and inflammatory lesions (n: 105). In normal skin, both antigens were consistently expressed within the cytoplasm of mature sebocytes and rarely over the luminal surface of secretory sweat gland cells. All (21/21) sebaceous tumours showed strong T/Tn positivity; several (9/16) sweat-gland tumours were also immunoreactive, although more weakly. Pilar (n = 11), non-adnexal tumours (n = 45) and inflammatory lesions (n = 12) were as a rule unreactive. These results suggest that the T antigen is a sensitive marker of sebaceous differentiation that can be used for the study of adnexal skin tumours in routinely processed tissue specimens.
AIM: To study the immunohistochemical expression of the Thomsen-Friedenreich antigen (T) and its precursor, Tn, in the skin in various cancers. METHODS: T and Tn antigens were studied with monoclonal antibodies in 91 primary premalignant and malignant lesions, 13 cases of Paget's disease, and 26 carcinomas metastatic to the skin. The material had been collected over a 10 year period, formalin fixed, and paraffin embedded. Diagnoses had been made after examination of standard histological sections, supplemented when needed by appropriate immunohistochemical staining. RESULTS: 21% and 29% of the primary cutaneous premalignant and malignant epithelial tumours expressed the Tn and T antigens, respectively. By contrast, 81% of metastatic carcinomas to the skin were Tn positive, while only 23% of them expressed the T antigen. All cases of Paget's disease were Tn positive but only 15% of them expressed the T antigen. The 21 nonepithelial tumours (including melanomas) were as a rule unreactive. CONCLUSIONS: The accumulation of the precursor (Tn) antigen in tumours metastasising to the skin highlights the incomplete glycosylation of carbohydrate antigens occurring in these tumours. The predominant Tn versus T antigen expression appears to be a useful immunohistochemical feature which may aid in the differentiation of primary cutaneous carcinomas from metastatic tumours.
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BACKGROUND: Merkel cells are neuro-endocrine cells present in the basal layer of the human epidermis and the outer root sheath of hair follicles. OBJECTIVE AND METHOD: In order to gain further insight into the as yet ill-defined involvement of Merkel cells in skin diseases, we studied the distribution of these cells in formalin-fixed, paraffin-embedded sections of 165 inflammatory, hyperplastic or tumoral skin lesions of various anatomic locations, with a monoclonal antibody to keratin 20. RESULTS: Lesions with frequently increased Merkel Cell numbers included actinic keratosis, fibrous papules of the face and some conditions with (immature) hair follicle differentiation. CONCLUSION: These results suggest that Merkel cell hyperplasia is unrelated to epidermal proliferation but that it is rather specific to a limited number of skin diseases.
The ability of blood coagulation factor XIII (FXIII) to affect collagen synthesis and degradation led to its use in the treatment of scleroderma. Encouraging initial results were achieved principally in terms of skin sclerosis, musculoskeletal involvement and weakness. Further assessment of this treatment in scleroderma was abandoned when, following the HIV epidemic, FXIII use became strictly regulated. Safer concentrates are now available which may allow us to reconsider this therapy. This paper, which briefly reviews available data related to FXIII use in scleroderma and which proposes general rules for prescribing, is aimed at generating an open debate as to the need to widen the regulated use of FXIII to scleroderma.
INTRODUCTION: Epidermolysis bullosa acquisita is a bullous dermatosis. Its etiology remains unknown and the efficacy of its treatment is low. OBSERVATION: We report the first association between epidermolysis bullosa acquisita, chronic hepatitis C and cryoglobulinemia, healing with interferon alpha and ribavirine. DISCUSSION: We suggest a role for hepatitis C virus in the pathogenesis of epidermolysis bullosa acquisita. We suppose a synthesis of autoimmune antibodies in a dysimmune environment. Interferon alpha and ribavirine might be a new therapeutic avenue but further studies are necessary to confirm it.
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