[Acne, hyperandrogenism and resistance to oral isotretinoin: 23 cases].
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Biomedical subjects
Publications and source records attributed to M Faure.
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BACKGROUND: Papuloerythroderma of Ofuji is an uncommon condition characterized by diffuse pruriginous eruptions of infiltrating papulae. The large folds are not involved. The eruptions are associated with lymphopenia and eosinophilia. Very few cases have been reported in the literature and because of their heterogeneous nature, there is some debate as to whether this is a single clinical entity or a particular presentation of erythrodermia; Immunomodulation is recommended. CASE REPORT: A 73 year-old man of asian origin living in France presented chronic pruriginous erythrodermia with flat purplish-brown confluent papulae which did not involve the large folds. Eosophilia and lymphopenia were present. The biopsy specimen evidenced dermal infiltration with CD4+CD45+RO+ T cells, eosinophils and DC1a+ dendritic cells. Further explorations did not reveal any sign favoring lymphoma, carcinoma or underlying infection. Dermocorticoids, PUVA-therapy and interferon-alpha were ineffective. Considerable clinical improvement was obtained with cyclosporine A. DISCUSSION: We used ciclosporine A in our patient after repeated failure of other therapies reported to be effective in this dermatosis. Despite the favorable outcome, this therapeutic approach should be used with prudence.
Candidiasis, infection due to Trichomonas vaginalis and bacterial vaginosis (Gardnerella vaginalis and/or other species) represent the major three causes of vulvo-vaginitis. Other are rare bacterial infections and non infectious vaginitis such as allergic and post-menopausal vaginitis with epithelial atrophy. Clues for the diagnosis include the clinical features of vaginal discharge, cytological examinations, bacterial and fungal cultures. Only T. vaginalis seems to be responsible of sexually transmitted disease. All appropriate antibacterial or anticandidosic treatment are immediately effective, but the mechanisms of recurrent candidiasis and vaginosis are still unclear.
In contrast to H-2d kappa light chain-deficient mice (kappa-/-), BALB/c (kappa+/+) mice fail to respond to kappa light chains (L kappa). This suggests that C kappa-specific T cells are tolerant to this self-antigen in kappa+/+ mice. To get insights into the cellular and molecular basis of this tolerance, we first characterized the presented L kappa-derived C kappa-peptidic region(s). Among a library of overlapping peptides spanning the whole C kappa sequence, only three consecutive peptides are recognized by CD4+ T cell hybridomas obtained in L kappa-immunized kappa-/- mice. This C kappa-peptidic region, which is also the only one containing the I-Ed-binding consensus motif, is immunogenic since it is able to prime lymph node cells of kappa-/- mice to subsequent in vitro proliferative response to either L kappa or kappa+/+ APC. Conversely, no kappa+/+ T cell proliferation is observed under the same conditions. Activation of our hybridomas by cells from central and peripheral lymphoid tissues reveals that this C kappa region is naturally expressed on BALB/c kappa+/+ APC. In addition to B cells, macrophages and dendritic cells are able to present this region. Taken together our data suggest that the described self-C kappa region is implicated in the C kappa-specific CD4+ T cell tolerization in BALB/c mice.
Mouse SC1 fibroblasts can support reovirus multiplication although they exhibit a partial resistance to viral-induced cytopathology; a significant percentage of infected SC1 cells can remain viable while becoming persistently infected by the virus. In the present study, the possible role of interferon on the fate of reovirus-infected cells was investigated. Treatment of mouse L fibroblasts with beta-interferon resulted in a reduced viral efficiency of plating while essentially no effect was observed on SC1 cells; the results were similar with the unrelated encephalomyocarditis virus. This suggests that the interferon-regulated pathways are somehow deficient in SC1 cells even though these cells do respond to interferon treatment, as evidenced by an increase in the level of active interferon-inducible protein kinase double-stranded RNA-dependent (PKR) enzyme. Persistently infected SC1 cells constitutively release interferon even though treatment with anti-interferon antiserum suggests that interferon presence is unrelated to maintenance of the persistent state. The possible significance of the correlation between the lack of interferon-induced antiviral effect and relative resistance of SC1 cells to viral-induced cytopathology is briefly discussed.
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory dermatosis that probably involves a dysregulated activation of helper T cells, type 2 (Th2 cells). Severe refractory AD can be controlled by cyclosporine treatment. OBJECTIVE: We attempted to determine whether short-term CD4 monoclonal antibody (mAb) therapy could improve severe AD in adults. METHODS: The CD4 mAb, B-F5, was infused over 2 days in three patients with severe refractory AD and, for control purposes, in two patients with severe psoriasis. RESULTS: Administration of B-F5 was well tolerated, despite moderate first dose side effects. Clinical improvement was observed in two patients. In the third patient, a dramatic worsening occurred between 8 and 30 days after treatment, associated with an increased percentage of activated CD4+, CD25+, HLA-DR+, and CD45RO+ cells and peripheral blood eosinophilia. The same CD4 mAb administered to two patients with severe psoriasis induced marked clinical improvement of the lesions. CONCLUSION: Although CD4 mAb infusion may be potentially useful in the treatment of AD, the risk of aggravating the Th1/Th2 imbalance in AD should be considered in the design of future protocols.
The glycine decarboxylase complex consists of four different component enzymes (P-, H-, T- and L-proteins). The 14-kDa lipoamide-containing H-protein plays a pivotal role in the complete sequence of reactions since its prosthetic group (lipoic acid) interacts successively with the three other components of the complex and undergoes a cycle of reductive methylamination, methylamine transfer and electron transfer. The X-ray crystal structure of different forms of the H-protein has shown a unique conformation of the protein. This leads to the hypothesis of a three-dimensional recognition of the H-protein by the other components of the system and also by the ligase which lipoylates the H-protein. Striking structural similarities are observed between the H-protein and other lipoate domains of 2-oxo acid dehydrogenases and with the biotin carrier protein of acetyl-CoA carboxylase. In the H-protein, the lipoamide arm is free to move in the solvent when oxidized but is pivoted and tightly bound into a cleft at the protein surface when methylamine-loaded. This implies that the H-protein and the T-component form a stable complex during the catalytic transfer of the methylene unit to the tetrahydrofolate cofactor of the T-protein. This complex has been detected by small angle scattering experiments. In conclusion, in the glycine decarboxylase system, the lipoamide arm does not swing freely from one catalytic site to another as was proposed in other systems.
The effect of a high dose of 3-hydroxy-3-methylbutyrate (HMB, a leucine catabolite) on protein metabolism was investigated in growing male lambs fed on hay and concentrate. Concentrate was supplemented with either Ca(HMB)2 (4 g/kg) or Ca(CO3)2 in experimental (HMB) and control groups respectively. Both groups consisted of six 2-month old lambs. Three complementary methods to study protein metabolism were carried out consecutively 2.5 months after beginning the dietary treatment: whole body phenylalanine fluxes, postprandial plasma free amino acid time course and fractional rates of protein synthesis in skeletal muscles. Feeding a high dose of HMB led to a significant increase in some plasma free amino acids compared with controls. Total, oxidative and non-oxidative phenylalanine fluxes were not modified by dietary HMB supplementation. Similarly, an acute infusion of HMB, in the control group, did not change these fluxes. In skeletal muscles, fractional rates of protein synthesis were not affected by long-term dietary supplementation with HMB. Taken together our results showed that administration of a high dose of HMB to lambs was able to modify plasma free amino acid pattern without any effect on whole-body protein turnover and skeletal muscle protein synthesis.
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In 1994, a study of nickel release and allergic contact dermatitis from nickel-plated metals and stainless steels was published in this journal. It was shown that low-sulfur stainless steel grades like AISI 304, 316L or 430 (S < or = 0.007%) release less than 0.03 microgram/cm2/week of nickel in acid artificial sweat and elicit no reactions in patients already sensitized to nickel. In contrast, nickel-plated samples release around 100 micrograms/cm2/week of Ni and high-sulfur stainless steel (AISI 303-S approximately 0.3%) releases about 1.5 micrograms/cm2/week in this acid artificial sweat. Applied on patients sensitized to nickel, these metals elicit positive reactions in 96% and 14%, respectively, of the patients. The main conclusion was that low-sulfur stainless steels like AISI 304, 316L or 430, even when containing Ni, should not elicit nickel contact dermatitis, while metals having a mean corrosion resistance like a high-sulfur stainless steel (AISI 303) or nickel-plated steel should be avoided. The determining characteristic was in fact the corrosion resistance in chloride media, which, for stainless steels, is connected, among other factors, to the sulfur content. Thus, a question remained concerning the grades with an intermediate sulfur content, around 0.03%, which were not studied. They are the object of the study presented in this paper. 3 tests were performed: leaching experiments, dimethylglyoxime and HNO3 spot tests, and clinical patch tests; however, only stainless steels were tested: a low-sulfur AISI 304 and AISI 303 as references and 3 grades with a sulfur content around 0.03%: AISI 304L, AISI 304L added with Ca, AISI 304L+Cu. Leaching experiments showed that the 4 non-resulfurised grades released less than 0.5 microgram/cm2/week in acid sweat while the reulfurized AISI 303 released around or more than 0.5 microgram/cm2/week. This is explained by the poorer corrosion resistance of the resulfurized grade. Yet all these grades had the same reaction to the DMG test (negative result), which shows again its lack of sensitivity. In contrast, the HNO3 spot test distinguished AISI 303 from the non-resulfurized grades. Clinical patch tests again showed that some patients (4%) were intolerant to AISI 303, while none were intolerant to the other grades. Thus, this study confirms that non-resulfurized stainless steels (S < or = 0.03%) like Ni-containing 304 and 304L should not elicit Ni contact dermatitis, while the resulfurized grades (S > 0.1%) should be avoided.
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Nm23 is a gene with a putative metastasis-suppressor function, whose expression is inversely correlated with the metastatic potential of some solid malignancies. Because very few data exist concerning the role of nm23 in skin tumors, we studied the immunohistochemical expression of nm23 gene product in frozen sections of normal skin and of 104 cutaneous benign or malignant, epithelial and mesenchymal tumors. Nm23 was found expressed within basal cells of the epidermis and its appendages. All basal cell carcinomas showed diffuse immunoreactivity predominating within cells located at the periphery of tumor masses; in contrast, most squamous cell carcinomas, premalignant lesions and the benign epithelial lesions studied showed very weak, if any, immunoreactivity. Benign nevi and most malignant melanomas expressed nm23 immunoreactivity and the pattern observed was similar between primary and metastatic lesions. These results show that nm23 is differentially expressed in cutaneous tumors. It seems likely that the strong immunoreactivity of basal cell carcinomas, contrasting with the almost non-expression in squamous cell carcinomas, reflects the different metastatic potential of these two types of tumors. In melanomas, no direct correlation between the metastatic phenotype and nm23 expression could be detected. Our results suggest that the nm23 gene is involved in cutaneous carcinogenesis; its precise role deserves further study.
Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1+ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a+ cells and a moderate increase of HLA-DR+ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1+ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.
Squamous cell carcinomas (SCC) are the most frequent tumours complicating organ transplantation. Whereas most SCC can be successfully treated with conventional surgery, other lesions show an aggressive course with recurrence and metastases. We assessed the value of nuclear morphometry in detecting tumours with an ab initio potential for aggressive course. Nuclear perimeter, area, feret X and feret Y were calculated semi-automatically on an image analyzer on histological sections of 15 non-aggressive, 15 aggressive and 6 recurrent SCC developed in seven organ graft recipients. We found statistically significant differences for all the parameters studied between recurrent and initially aggressive SCC, and, to a lesser extent, between non-aggressive and aggressive SCC. These results suggest that some SCC have ab initio a potential for more aggressive evolution; morphometry can be a useful adjunct in order to better study these lesions.
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BACKGROUND AND DESIGN: In a series of patients treated at a university department of dermatology, we assessed the clinicopathologic features of external anogenital lesions in organ transplant recipients. For 6 years, 1002 recipients with various dermatologic problems underwent assessment for the presence of proliferative external anogenital lesions; these lesions were examined histologically and virologically for the presence of human papillomaviruses (HPV). RESULTS: Twenty-three patients (2.3%) presented with anogenital lesions, women being more often involved. Clinicopathologic examination revealed 18 anogenital warts, 3 cases of bowenoid papulosis, 1 giant condyloma, and 1 in situ carcinoma. Other viral coinfections were frequent. The lesions were extensive and refractory to treatment in 13 patients, but lesions in 7 were cured alter the immunosuppressive treatment was tapered of discontinued. Dysplastic changes were frequent on histologic examination. Twenty-one lesions contained HPV; 6 of 13 patients with HPV DNA in their lesions harbored oncogenic types that predominated in dysplastic lesions. In some patients, the same HPV types were detected within cutaneous and anogenital lesions, suggesting self-contamination. CONCLUSIONS: External anogenital lesions are more rare than cutaneous lesions in organ transplant recipients. These lesions may represent a marker of immunosuppression, especially when they are extensive. Their clinical aspect is often misleading; furthermore, because of the presence of dysplastic histologic aspects and oncogenic HPV types, they could be susceptible to malignant transformation, necessitating regular surveillance.