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S Belaich

Publications and source records attributed to S Belaich.

At least 19 recordsLinked to original sources
PubMed2006

1,25-Dihydroxyvitamin D3 protects human pancreatic islets against cytokine-induced apoptosis via down-regulation of the Fas receptor.

Beta cell loss occurs at the onset of type 1 diabetes and after islet graft. It results from the dysfunction and destruction of beta cells mainly achieved by apoptosis. One of the mediators believed to be involved in beta cell apoptosis is Fas, a transmembrane cell surface receptor transducing an apoptotic death signal and contributing to the pathogenesis of several autoimmune diseases. Fas expression is particularly induced in beta cells by inflammatory cytokines secreted by islet-infiltrating mononuclear cells and makes cells susceptible to apoptosis by interaction with Fas-ligand expressing cells. We have previously demonstrated that 1,25(OH)2D3, the active metabolite of vitamin D, known to exhibit immunomodulatory properties and prevent the development of type 1 diabetes in NOD mice, is efficient against apoptosis induced by cytokines in human pancreatic islets in vitro. The effects were mainly mediated by the inactivation of NF-kappa-B. In this study we demonstrated that 1,25(OH)2D3 was also able to counteract cytokine-induced Fas expression in human islets both at the mRNA and protein levels. These results were reinforced by our microarray analysis highlighting the beneficial effects of 1,25(OH)2D3 on death signals induced by Fas activation. Our results provides additional evidence that 1,25(OH)2D3 may be an interesting tool to help prevent the onset of type 1 diabetes and improve islet graft survival.

Adult↗
PubMed2004

[Vinblastine treatment for extensive non-X histiocytosis (xanthoma disseminatum)].

INTRODUCTION: Xanthoma disseminatum is a non-Langerhans histiocyte proliferation, described by Montgomery in 1938. This rare entity is characterized by skin and mucous membrane xanthomatosis, associated with diabetes insipidus and normal lipid metabolism. In this case report, vinblastine produced the regression of the lesions. OBSERVATION: A 51 year-old man presented in 1999 with a four-year history of progressive xanthomatous papulonodular lesions of his trunk, axillary and inguinal folds, neck and face (leonin facies). Treatment with thalidomide for 6 months was ineffective. A rapid extension of the lesions to the pharynx, larynx and trachea with dyspnea occurred and required a tracheotomy. Histopathological study showed a dense histiocytic infiltrate within the upper and mid dermis with Touton giant cells and inflammatory cells. The histiocyte cells were positive for CD68. Neither lungs nor hypophysis were involved. A treatment with 6 cures of cyclophosphamide was insufficient. Vinblastine therapy (32 cycles: 0.1 mg/kg/cycle) produced a spectacular regression of the mucous-cutaneous papulonodular lesions leaving cheloid scars. The patient required a transitory tracheotomy and a bilateral commissuroplasty. DISCUSSION: Prognosis of xanthoma disseminatum is in related to the mucous membrane manifestations (50 p. 100 of cases) and involvement of the upper respiratory tract. The response to any form of therapy in xanthoma disseminatum is unsatisfactory. Surgical excision or laser therapy can improve physical and functional aspects but the evolution is characterized by very frequent relapses. Treatment with antimitotic drugs seems to be ineffective in many cases. In our patient, vinblastine induced a spectacular regression of mucocutaneous lesions without neurologic toxicity. To our knowledge, this is the first report of vinblastine efficacy in this rare and severe disorder.

Antineoplastic Agents, Phytogenic↗
PubMed2002

[Retroperitoneal fibrosis secondary to metastatic neoplasm revealed by a leg lymphedema].

INTRODUCTION: Diagnosis of retroperitoneal fibrosis is generally delayed and revealed by various non-specific signs. We report the case of an isolated lymphedema of the lower limb revealing retroperitoneal fibrosis complicating a metastatic squamous cell carcinoma. CASE REPORT: In an 83-year-old women, a lymphedema appeared that remained isolated for several months before being associated with alteration in general health. Morphological examinations showed bilateral compression of the urinary excretory tracts and led to the diagnosis of retroperitoneal fibrosis. Histological examination of a sub-clavicular adenopathy that had evolved over 9 months, confirmed the diagnosis of a metastatic squamous cell carcinoma of pulmonary cancer. DISCUSSION: Retroperitoneal fibrosis is an exceptional etiology that must be recognized in isolated lymphadomas of the lower limbs. In view of the possible tumoral origin of retroperitoneal fibrosis, any evocative sign accompanying the lymphedema must be searched for.

Aged↗
PubMed2001

Identification and purification of functional human beta-cells by a new specific zinc-fluorescent probe.

Pancreatic beta-cells contain large amounts of zinc. We took advantage of this to try to localize, quantify, and isolate insulin-producing cells from islet preparations. Our study was designed to identify a non-toxic zinc-sensitive fluorescent probe able to selectively label labile zinc in viable beta-cells and to exhibit excitation and emission wavelengths in the visible spectrum, making this technique exploitable by most instruments. We tested Newport Green, a probe excitable at 485 nm with a dissociation constant in the micromolar range corresponding to a low affinity for zinc. The loading of the lipophilic esterified form of Newport Green was easy, rapid, specific, and non-toxic to cells. Confocal microscopy highlighted an intense fluorescence associated with secretory granules. Regression analyses showed a good relationship between zinc fluorescence and islet number (r = 0.98) and between zinc fluorescence and insulin content (r = 0.81). The determination of Zn fluorescence per DNA enabled us to assess the quality of the different islet preparations intended for islet allografting in terms of both purity and viability. Cell sorting of dissociated Newport Green-labeled cells resulted in a clear separation of beta-cells, as judged by insulin content per DNA and immunocytochemical analysis. This zinc probe, the first able to specifically label living cells in the visible spectrum, appears very promising for beta-cell experimentation, both clinically and for basic research.

Adult↗
PubMed2001

Beneficial effect of 1,25 dihydroxyvitamin D3 on cytokine-treated human pancreatic islets.

We examined whether 1,25 dihydroxyvitamin D(3) (1,25 D(3)), the active form of vitamin D involved in the regulation of the immune system, may also protect human pancreatic islet cells from destruction induced by cytokines. In this study, we specifically investigated the effect of 1,25 D(3) on oxidative stress and major histocompatibility complex (MHC) induction, both implicated in cytokine-induced islet cell dysfunction and destruction. We also investigated the effects of 1,25 D(3) on interleukin (IL)-6, a pleiotropic cytokine implicated in the pathogenesis of immunoinflammatory disorders. Human pancreatic islets, isolated from heart-beating donors, were treated with a combination of three cytokines, IL-1beta+tumor necrosis factor alpha+interferon gamma, in the presence or absence of vitamin D, and compared with with untreated control cells. Metabolic activity was assessed by cell viability and insulin content. Oxidative stress was estimated by heat shock protein 70 (hsp70) expression, cell manganese superoxide dismutase (MnSOD) activity and nitrite release, a reflexion of nitric oxide (NO) synthesis. Variation of immunogenicity of islet preparations was determined by analysis of the MHC class I and class II transcripts. Inflammatory status was evaluated by IL-6 production. After 48 h of contact with cytokines, insulin content was significantly decreased by 40% but cell viability was not altered. MHC expression significantly increased six- to sevenfold as well as NO and IL-6 release (two- to threefold enhancement). MnSOD activity was not significantly induced and hsp70 expression was not affected by the combination of cytokines. The addition of 1,25 D(3) significantly reduced nitrite release, IL-6 production and MHC class I expression which then became not significantly different from controls. These results suggest that the effect of 1,25 D(3) in human pancreatic islets cells may be a reduction of the vulnerability of cells to cytotoxic T lymphocytes and a reduction of cytotoxic challenge. Hence, 1,25 D(3) might play a role in the prevention of type 1 diabetes and islet allograft rejection.

Calcitriol↗
PubMed2001

Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms.

BACKGROUND: There is a current debate regarding the association of human herpesvirus 6 (HHV-6) infection and drug reaction with eosinophilia and systemic symptoms (DRESS). METHODS: Seven consecutive patients hospitalized with DRESS were enrolled in a prospective study to evaluate evidence of active HHV-6 infection. OBSERVATIONS: The imputable drugs were carbamazepine (5 patients), ibuprofen (1 patient), and sulfasalazine (1 patient). All patients were seropositive for anti-HHV-6 IgG antibodies. Anti-HHV-6 IgM antibodies were detected in 4 of the 7 patients with a seroconversion in 2 patients. Neither anti-cytomegalovirus nor anti-Epstein-Barr virus early antigen IgM antibody was detected. Human herpesvirus 6 genome was not detected by polymerase chain reaction in the first serum sample of all patients. It was weakly detected in skin lesions in the last patient tested by polymerase chain reaction but was not found in uninvolved skin. CONCLUSIONS: The results suggest an association between HHV-6 active infection (primo-infection or reactivation) and severe DRESS. Absence of anti-cytomegalovirus or anti-Epstein-Barr virus early antigen IgM antibodies argues against a nonspecific viral reactivation. Human herpesvirus 6 infection may play a role in the development of DRESS in susceptible patients. Some drugs with reactive metabolites could favor reactivation and propagation of HHV-6.

Adult↗
PubMed2001

[Mycobacterium kansasii skin infection at insulin injection sites].

BACKGROUND: Insulin injection sites rarely become infected. We report a case of Mycobacterium kansasii infection at the sites of insulin injection. CASE REPORT: An 84-year-old woman with insulin-dependent diabetes consulted for lesions on the anterior aspect of the thighs. She had papulonodules at the sites of insulin injection. These lesions progressed to hard fibrinonecrotic ulcerations with a raised erythematous border. There were no enlarged nodes locally. Laboratory tests were normal. Bacteriological samples were negative at direct examination. Histology was not specific. The biopsy cultures finally found an atypical mycobacteria, Mycobacterium kansasii. The clinical course was favorable with clarithromycin alone. DISCUSSION: Only 35 cases of Mycobacterium kansasii skin infections have been reported in the literature. This is the first case observed in a diabetic subject and the first treated with clarithromycin alone. This case illustrates the potential, though exceptional, risk of insulin bottle contamination by an environmental germ.

Aged↗
PubMed2000

A paraneoplastic mixed bullous skin disease: breakdown in tolerance to multiple epidermal antigens.

We report a new type of paraneoplastic mixed bullous skin disease in a patient with a B-cell lymphoma associated with monoclonal IgM kappa paraproteinaemia. The patient's clinical and histological features were reminiscent of bullous pemphigoid. Characterization of antiepidermal antibodies by immunoblotting and indirect immunoelectron microscopy demonstrated a novel pattern of reactivity: IgG antibodies were directed against desmoplakins I-II and BPAG2, and were associated with antidesmoglein 3 polyclonal IgM antibodies. Such an autoreactive pattern involving antidesmoplakins, anti-BPAG2 and antidesmoglein 3 antibodies has not been previously reported. It reflects the breakdown of tolerance to multiple epidermal antigens observed in some patients with malignancy.

Autoantibodies↗
PubMed2000

Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in humans.

Human pancreatic cells with a typical ductal phenotype and potential to proliferate can be obtained in vitro, but the differentiation capacity of these putative human pancreatic stem cells remains to be documented. We investigated the protein and mRNA expression of insulin promoter factor 1 (IPF-1) (or pancreas/duodenal homeobox 1), a transcription factor critical for pancreatic development and endocrine cell neogenesis, in human pancreatic ductal cells derived from cultured exocrine tissue. In vitro, exocrine cells rapidly adhered (within 12 h) and were de-/transdifferentiated to ductal cells after 3 days with a dramatic loss of amylase protein (n = 4, 92 +/- 3.3%, P < 0.05 vs. day 1) and a simultaneous increase of ductal cytokeratin 19 protein (n = 4, 3.4-fold on day 3 and 7-fold on day 9, P < 0.05 vs. day 1). IPF-1 protein and mRNA levels were low to undetectable in exocrine preparations before culture. After 2 days of culture, a 3.2-fold increase in IPF-1 protein was observed, corresponding to the characteristic 46-kDa protein in Western blots. Reverse transcriptase-polymerase chain reaction confirmed a 10.5-fold increase in IPF-1 mRNA levels after 3 days of culture (n = 5, P < 0.001 vs. day 1). Double immunocytochemistry showed direct evidence that IPF-1 appeared during culture in these exocrine-derived ductal cells (cytokeratin 7-positive) and was not merely in contaminating endocrine cells (chromogranin A-positive). In conclusion, we describe herein the first converging evidence on both the molecular and protein level that human cells with a typical ductal phenotype derived ex vivo from pancreatic exocrine tissue (obtained from healthy donors) can reexpress IPF-1 in culture, suggesting their pancreatic precursor/stem cell potential.

Adult↗
PubMed2000

[Alpha interferon-induced eczema in atopic patients infected by hepatitis C virus: 4 case reports].

OBJECTIVES: We report four cases of eczema induced by alpha interferon in atopic patients treated for chronic hepatitis C. CASE REPORTS: Eczema developed in 4 patients with certain (3 cases) or possible (1 case) atopy treated by subcutaneous injections of alpha interferon for hepatitis C virus infections. Delay to onset was 3 weeks to 6 months. Interferon was highly likely the causal agent: lesions started at site of interferon injection, followed the rhythm of interferon injections (three cases), disappeared at interferon withdrawal. In two patients, the lesions diffused to other sites. Both Introna and Roféron were used. Three patients also took ribavirine. The possible role of a contact factor (antiseptic.) was ruled out. Skin tests (patch tests, prick tests, intradermal reactions) were negative for interferon alpha and for a standard battery. DISCUSSION: The role of interferon in the induction of skin diseases or its influence on the course of certain dermatoses is well known. In atopic patients, interferon might induce eczema via an immunomodulator rather than an allergic mechanism since skin tests (performed in one patient) were negative. This observation is similar to that in psoriasis induced by interferon in predisposed subjects who develop skin lesions at injection sites which sometimes diffuse to distant localizations. The role of other factors (hepatitis C virus infection, ribavirine) remains unknown; they might participate in this mechanism by aggravating skin dryness.

Adrenal Cortex Hormones↗
PubMed1999

[Paraneoplastic pemphigus].

A RARE DISEASE: Paraneoplastic pemphigus is an rare autoimmune bullous skin disease recently recognized. About 50 cases have been reported since its first description in 1990. CLINICAL MANIFESTATIONS: Clinical signs are polymorphous resembling the cutaneomucosal manifestations of pemphigus vulgar (skin and mucosa erosions, fragile interdermal bullae), pemphigoid (urticaria, distended subepidermal bullae), and polymorphous erythema (plaque lesions). Mucosal erosions predominate however. ASSOCIATED CANCERS: Most cancers associated with paraneoplastic pemphigus are hematologic diseases (non-Hodgkin's lymphomas, chronic lymphoid leukemia). SEVERE PROGNOSIS: No standard treatment has been defined. General corticosteroids and treatment of the causal disease are indicated. The clinical course of paraneoplastic pemphigus does not always follow the course of the associated neoplasm. POSITIVE DIAGNOSIS: Pathology criteria (keratinocyte necrosis, suprabasal keratinocyte vacuolization, intraepidermal acantholysis) and immunohistological findings (antibody and complement deposits at the dermo-epidermal junction and within the keratinocytes on different epithelial substrates) are insufficient for positive diagnosis. Autoantibodies must be identified by immunoprecipitation or immunoblotting to identify the target antigen complex plakin components (desmoplakin I and II, periplakin, envoplakin), the major pemphigoid antigen, desmoglein 3, and certain yet unidentified antigens with a molecular weight of 170 kD. PATHOGENESIS: Paraneoplastic pemphigus appears as a model autoimmune paraneoplastic disease. Its origin remains elusive. It has been hypothesized that tumor-induced inhibition of tolerance to certain antigens implicated in the keratinocyte junctional systems could be involved.

Autoantigens↗
PubMed1999

Longitudinal melanonychia in children: a clinical and histopathologic study of 40 cases.

OBJECTIVE: Very little has been published on longitudinal melanonychia in children. Our objective was to determine the nature of melanocytic lesions in pediatric patients with longitudinal or total melanonychia and to look for correlations between clinical and histologic features. METHODS: All patients younger than 16 years of age with longitudinal or total melanonychia who were evaluated at our nail disorder outpatient clinic between September 1993 and September 1996 were included. The clinical and histologic features of the nail condition were determined in each case. RESULTS: Forty patients were included. The final diagnosis was nevus in 19 cases (junctional in 17 cases and compound in 2), lentigo in 12 cases, and functional longitudinal melanonychia in 9. The latter corresponded to a hyperpigmentation caused by melanocytic activation with no increase in the number of melanocytes. None of the patients had melanoma. Appearance within the first year of life, periungual pigmentation, and total melanonychia were consistent features in patients with melanocytic hyperplasia (lentigo or nevus). Early onset of a dark broad lesion in a white patient was typical of melanocytic hyperplasia, although none of these features were pathognomonic. CONCLUSION: Benign melanocytic hyperplasia (lentigo or nevus) was the cause of 77.5% of cases of longitudinal melanonychia in our overall pediatric population and of 85% of cases in the subset of white patients. All the remaining cases of longitudinal melanonychia were the result of melanocytic activation.

Adolescent↗
PubMed1999

Skin pigmentary anomalies and mosaicism for an acentric marker chromosome originating from 3q.

We report on a 22 year old man with hyperpigmentation distributed along the lines of Blaschko in whom cytogenetic analysis showed mosaicism for an unusual supernumerary marker chromosome. The patient was of normal intelligence and was not dysmorphic. The marker was present in 30% of his lymphocytes and in 6% of his skin fibroblasts from a dark area, while fibroblasts from a light area showed a normal karyotype, 46,XY. We have identified the origin of the marker using fluorescence in situ hybridisation (FISH) with whole chromosome painting probes and YAC specific clones. The marker was found to consist of duplicated chromosome material from the distal part of chromosome 3q and was interpreted as inv dup(3)(qter-->q27.1::q27.1-->qter). Hence, this marker did not include any known centromeric region and no alpha satellite DNA could be detected at the site of the primary constriction. The patient was therefore tetrasomic for 3q27-q29 in the cells containing the marker chromosome. We postulate that, in our case, pigmentary anomalies may result directly from the gain of specific pigmentation genes localised on chromosome 3q.

Adult↗