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Biomedical subjects

M Faure

Publications and source records attributed to M Faure.

At least 19 recordsLinked to original sources

Purification and cloning of the mitochondrial branched-chain amino acid aminotransferase from sheep placenta.

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.

Amino Acid Sequence

[Prospective study of treatment of bullous pemphigoid by a class I topical corticosteroid].

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.

Administration, Topical

Role of maternal Ig in the induction of C kappa-specific CD8+ T cell tolerance.

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.

Administration, Oral

Thomsen-Friedenreich and its precursor (Tn) antigen expression in normal skin and in benign cutaneous tumours: a marker for sebaceous differentiation.

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.

Antigens, Neoplasm

Differential expression of the cancer associated antigens T (Thomsen-Friedenreich) and Tn to the skin in primary and metastatic carcinomas.

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.

Antigens, Neoplasm

Merkel cells in hyperplastic and neoplastic lesions of the skin. An immunohistochemical study using an antibody to keratin 20.

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.

Antigen-Antibody Reactions

Coagulation factor XIII in scleroderma.

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.

Adult

[Epidermolysis bullosa acquisita and hepatitis C].

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.

Adult

[Ofuji's papulo-erythroderma: treatment with cyclosporin A].

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.

Aged

[Vulvovaginitis].

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.

Candidiasis, Vulvovaginal

T cell tolerance to kappa light chain (L kappa): identification of a naturally processed self-C kappa-peptidic region by specific CD4+ T cell hybridomas obtained in L kappa-deficient mice.

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.

Amino Acid Sequence

Interferon has no protective effect during acute or persistent reovirus infection of mouse SC1 fibroblasts.

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.

Acute Disease

CD4 monoclonal antibody administration in atopic dermatitis.

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.

Adult

Structural studies of the glycine decarboxylase complex from pea leaf mitochondria.

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.

Amino Acid Oxidoreductases