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Biomedical subjects

G Michel

Publications and source records attributed to G Michel.

At least 181 records · Page 10Linked to original sources

Risk factors and prevalence of hepatitis E in German immigrants from the former Soviet Union.

Worldwide there is only limited information on the epidemiology of hepatitis E virus (HEV) and its association with other hepatotropic viruses. Endemic regions have been described in some Asian countries, whereas in Europe only sporadic cases have been reported. The prevalence of HEV and a series of other viral hepatitis infections was investigated in a group of 1,025 individuals immigrating into Germany from the former Soviet Union. Serum samples were tested for anti-HEV by a commercial enzyme immunoassay (EIA) based on recombinant proteins, and by peptide EIA and immunoblot. Risk factors and other demographic information were investigated using a questionnaire and a short interview. The overall prevalence of anti-hepatitis E antibodies (anti-HEV) was 2.05%. The following risk factors for HEV infection were identified: age of > 65 years, resident in the south-west part of the former Soviet Union, history of hepatitis B virus (HBV) infection, and employment in health care professions. HEV prevalence is not strikingly different from that observed in Western European countries. However, the different rates found for HEV vs. hepatitis A virus (HAV) are intriguing, since similar routes of transmission (fecal-oral) are well documented for both viruses. Exposure to HBV is surprisingly high, and the number of hepatitis C virus (HCV)-positive individuals was also higher than those reported from Western European areas.

Adolescent↗

Anti-GOR and anti-thyroid autoantibodies in patients with chronic hepatitis C.

Anti-thyroid autoantibodies have been described in anti-hepatitis C virus (HCV)-positive patients. It has been suggested that the anti-GOR response is closely related to HCV infection and may reflect an HCV-associated autoimmune phenomenon. This study was designed to evaluate the humoral anti-GOR response in anti-HCV-positive patients with anti-thyroid autoantibodies (group 1, 22 patients) and to compare it with the response in anti-HCV-positive patients without anti-thyroid autoantibodies (group 2, 44 patients) and in anti-HCV-negative patients with autoimmune thyroiditis (group 3, 28 patients). The prevalences of anti-GOR in groups 1, 2, and 3 were, respectively, 72.7, 61.3, and 3.5%. Anti-GOR levels were higher in group 1 than in group 2 or group 3 (P = 0.0001). Moreover, comparison of the Anti-GOR levels of groups 1 and 2 also revealed a statistically significant difference (P = 0.008). Detection of more elevated anti-GOR levels in group 1 patients suggests that anti-thyroid autoantibodies in anti-HCV-positive patients may be related to HCV.

Aged↗

Cisplatin-based chemotherapy in dysgerminoma of the ovary: thirteen-year experience at the Institut Gustave Roussy.

Twelve patients with dysgerminoma of the ovary were treated with various cisplatin-based chemotherapy regimens. Chemotherapy was delivered as primary postoperative treatment in 6 patients. All of them are free of disease 18 to 180 months after initiation of chemotherapy. Six other patients received chemotherapy as part of the salvage treatment for recurrent disease. Three failures were observed: one toxic death, one primary failure, and one subsequent relapse. Three patients remain free of disease 50 to 95 months after initiation of chemotherapy. The role of chemotherapy in early- and advanced-stage dysgerminoma of the ovary is reviewed.

Adult↗

Heterogeneity of liver-kidney microsomal autoantibodies in chronic hepatitis C and D virus infection.

BACKGROUND/AIMS: Anti-liver-kidney microsomal (LKM) autoantibodies occur in a proportion of patients with chronic hepatitis C and D infections. Because of different immunofluorescence patterns, antibodies in hepatitis C and D were termed LKM-1 and LKM-3, respectively. The aim of the present study was to evaluate the different specificities of LKM-1 and LKM-3 antibodies. METHODS: Forty-nine samples of LKM-1 sera and 16 samples of LKM-3 sera were studied for reactivity against rat and human liver microsomal proteins by immunofluorescence, enzyme-linked immunosorbent assay, and Western blot. RESULTS: Thirty-four percent of the LKM-1 sera reacted with 50-kilodalton cytochrome P4502D6 in Western blot. In addition, a proportion of the sera recognized either a 59- or 70-kilodalton antigen, and 45% of the sera did not react in Western blot. Recently, the major LKM-3 antigen was identified as an autoepitope expressed on uridine diphosphate-glucuronosyltransferases (UGT). Seven LKM-3-positive sera reacted with recombinant rabbit family one UGT. None of the anti-LKM-1-positive hepatitis C sera reacted with UGT. Antibody reactivity against liver microsomal proteins in enzyme-linked immunosorbent assay ended when antigens were pretreated with sodium dodecyl sulfate, confirming that antibodies recognize conformational epitopes. CONCLUSIONS: LKM-1 antibodies in hepatitis C are more heterogeneous and react with different antigens compared with LKM-3 antibodies in hepatitis D.

Animals↗

Elicitin produced by an isolate of Phytophthora parasitica pathogenic to tobacco.

Elicitin was prepared from a Phytophthora parasitica culture isolated from tobacco in Australia. The protein with elicitor activity was purified and sequenced. This protein, which contains 98 amino acid residues, shows full homology with an elicitin produced by a completely unrelated isolate from carnation, indicating conservation of elicitin sequence within a single species.

Amino Acid Sequence↗

Persistent hepatitis C virus RNA replication in haemophiliacs: role of co-infection with human immunodeficiency virus.

In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs, we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR assay in 57 patients. We found that the vast majority of HCV-infected patients remained viraemic (43/57 = 75%) and higher ALT levels correlated with HCV viraemia. Although indicators of the transfusional viral load (age, severity of haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV seropositivity was strongly associated with persistence of HCV viraemia (23/25 = 92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows more frequent genotype 1 in the HIV-seropositive group (14/23) than in the seronegative group (6/20). Our data emphasize that besides the role of the immunodeficiency status, the genotypes of HCV might be involved in the differences observed in terms of HCV RNA replication between the HIV-seropositive and seronegative haemophiliacs.

AIDS-Related Opportunistic Infections↗

A new neurohypophysial peptide, seritocin ([Ser5,Ile8]-oxytocin), identified in a dryness-resistant African toad, Bufo regularis.

From the pituitary neurointermediate lobe of the African toad Bufo regularis, vasotocin, hydrin 2 (vasotocinyl-Gly) and a mesotocin-like peptide have been isolated by HPLC and characterized by mass spectrometry, amino acid sequence and chromatographic coelution with synthetic peptides. The mesotocin-like peptide has been identified as [Ser5,Ile8]-oxytocin in place of mesotocin ([Ile8]-oxytocin) found in all other amphibians investigated to date. The name seritocin is suggested. The molecule is virtually devoid of oxytocic activity on rat uterus in contrast to mesotocin. On the other hand, the molar ratio of hydrin 2 to vasotocin in the pituitary reaches 2, whereas it is about 1 in toads and frogs from temperate regions. B. regularis is an anuran species able to withstand a hot and dry season by burrowing. The possible relationship between occurrence of seritocin and adaptation to arid environment remains to be demonstrated.

Amino Acid Sequence↗

Novel steroid derivative modulates gene expression of cytokines and growth regulators.

Topical steroid treatment is a common therapy for psoriasis. Steroids are known to bind to specific cytoplasmic receptors and to influence gene expression. We investigated the effects of the novel steroid derivative mometasone furoate on the expression of putative target genes in normal human epidermal cells (KC). Gene expression was measured by semiquantitative mRNA-PCR. In addition, cytokine receptor characteristics were assessed by ligand binding studies. We found a dose-dependent downregulation of proinflammatory mediators (IL-8, TNF alpha). Genes involved in growth regulation (HER-2, p53) were also modulated. IL-8 binding to KC was inhibited. We conclude that modulation of the expression of cytokine, cytokine receptor and growth factor genes may contribute to the antipsoriatic action of steroids.

Administration, Topical↗

Interleukin-8 induces HLA-DR expression on cultured human keratinocytes via specific receptors.

Recent studies suggest that interleukin (IL)-8 exerts a direct influence on several functions such as the chemotaxis or proliferation of human keratinocytes (HK). Since the effects of IL-8 in skin are mediated through specific receptors, we have studied the characteristics of the keratinocyte IL-8 receptor. We could identify specific binding sites for IL-8 in cultured HKs by flow cytometry. Pretreatment of the cells with tumor necrosis factor (TNF)-alpha or IL-1 alpha resulted in a significant increase in IL-8 binding. IL-8 selectively induced expression of HLA-DR antigen, but had no effect on the expression of other cell surface antigens (CD11a, CD18, CD36 and CD54).

Antigens, Surface↗

Myosin light chain-actin interaction regulates cardiac contractility.

The amino-terminal domain of the essential myosin light chain (MLC-1) binds to the carboxy terminus of the actin molecule. We studied the functional role of this interaction by two approaches: first, incubation of intact and chemically skinned human heart fibers with synthetic peptide corresponding to the sequences 5 through 14 (P5-14), 5 through 8 (P5-8), and 5 through 10 (P5-10) of the human ventricular MLC-1 (VLC-1) to saturate actin-binding sites, and second, incubation of skinned human heart fibers with a monoclonal antibody (MabVLC-1) raised against the actin-interacting N-terminal domain of human VLC-1 using P5-14 as antigen to deteriorate VLC-1 binding to actin. P5-14 increased isometric tension generation of skinned human heart fibers at both submaximal and maximal Ca2+ activation, the maximal effective peptide dosage being in the nanomolar range. A scrambled peptide of P5-14 with random sequence had no effects up to 10(-8) mol/L, ie, where P5-14 was maximally effective. P5-8 and P5-10 increased isometric force to the same extent as P5-14, but micromolar concentrations were required. Amplitude of isometric twitch contraction, rate of tension development, rate of relaxation, and shortening velocity at near-zero load of electrically driven intact human atrial fibers increased significantly on incubation with P5-14. These alterations were not associated with modulation of intracellular Ca2+ transients as monitored by fura 2 fluorescence measurements. Incubation of skinned human heart fibers with MabVLC-1 increased isometric tension at both submaximal and maximal Ca2+ activation levels, having a maximal effective concentration in the femtomolar range.

Actins↗

Alpha-melanocyte stimulating hormone induces collagenase/matrix metalloproteinase-1 in human dermal fibroblasts.

Recent reports have suggested that alpha-melanocyte stimulating hormone (alpha-MSH) plays an important role in untraviolet (UV) irradiation mediated skin changes including pigmentation, inflammation and connective tissue damage. alpha-MSH synthesis has been found to be induced in human keratinocytes following UV irradiation. In order to test the hypothesis whether UV induced alpha-MSH - via a paracrine loop - regulates the synthesis and the activity of collagenase/MMP-1, we studied the effects of alpha-MSH on the expression of MMP-1 and its tissue inhibitor of matrix metalloproteinases (TIMP-1). Confluent human dermal fibroblast cultures from foreskin biopsies of healthy human donors were treated with 10(-5)M, 10(-8)M and 10(-11)M alpha-MSH for 30 min. As determined by Northern blot analysis 10(-5)M and 10(-8)M alpha-MSH dose- and time-dependently induced steady state levels of MMP-1 mRNA up to 9-fold compared to untreated controls. TIMP-1 mRNA steady state levels were also slightly induced, however, the increased MMP-1/TIMP-1 ratio when normalized to beta-actin reflected an unbalanced synthesis. MMP-1 protein expression was studied with an immunofluorescence technique using a monoclonal antibody against MMP-1. After alpha-MSH treatment an increased number of fibroblasts revealed an intense perinuclear staining pattern compared to the less intense staining of control fibroblasts. The overall collagenolytic activity of supernatants from alpha-MSH treated fibroblasts was increased by 35%. Our data support the view that UV induced alpha-MSH - by the stimulation of collagenase/MMP-1 - may contribute to the loss of interstitial collagen related to cutaneous photoaging.

Cell Extracts↗

[Desmoplastic small round cell tumors in adults: a new entity].

Desmoplastic small round cell tumor is a recently recognized clinicopathologic entity with distinctive morphologic and immunohistochemical features. Moreover, specific cytogenetic and molecular characteristics have been described. We report here five new adult cases. The median age was 22 years. The clinical presentation was intra-abdominal in four patients and para-testicular in one patient. In patients with intra-abdominal disease, the initial surgery consisted of suboptimal debulking in three patients and only biopsies in the fourth. The patient with para-testicular tumor underwent an orchiectomy. Chemotherapy including cisplatin, etoposide, cyclophosphamide and doxorubicin or epirubicin (PAVEP/PEVEP regimen) was delivered after initial surgery in patients with intra-abdominal presentation or at relapse in the patient with para-testicular tumor. Only one persistent complete response was obtained and no salvage treatment was active in the other patients who died of progressive disease. A review of the literature concerning the clinicopathologic, cytogenetic and molecular features of this new entity is exposed.

Abdominal Neoplasms↗

[Value of inhibin as a tumor marker in granulosa cell tumors. Apropos of 6 new cases treated at the Gustave-Roussy Institute].

Lappöhn et al showed that inhibin can be used as a marker of granulosa cell tumors (GCT). Inhibin ia s glycoprotein specifically produced by ovarian granulosa cells. This peptide has been given in six women of 45 patients with a GCT who were referred for treatment or judgment in the Institut Gustave Roussy of Villejuif. Inhibin remained undetectable in four patients without evidence of disease. In one of them, inhibin level decreased progressively after surgical resection (for 10 months). Inhibin was also given in two patients with recurrence: in one case inhibin level was very high, and in one case it was barely detectable. In finding with other publications, inhibin can be used as a maker for reccurent disease, when patients are menopaused even when tumor does not produce steroids.

Adult↗

Long-term side-effects in children receiving allogeneic bone marrow transplantation in first complete remission of acute leukaemia.

We evaluated the long-term side-effects of allogeneic BMT performed early in the course of childhood acute leukaemia (first complete remission and interval between diagnosis and BMT not exceeding 6 months). Thirteen patients fulfilled these criteria. Conditioning regimens included TBI in eight cases. Evaluation of growth and pubertal development, ophthalmological examination, assessment of thyroid, cardiac and pulmonary functions were performed. Neuropsychological evaluation included IQ score, memory tests and cranial MRI. Median follow-up after BMT was 5 years (range 2-10 years). Growth was normal in seven patients. Six patients experienced a decrease in SD score for height (range -0.1 to -1.9). Four children were evaluable for puberty: pubertal development was normal in three children and delayed in one case. Thyroid and left ventricular function were normal in all cases. Three patients had mild abnormalities of pulmonary function. In two patients cataracts were noted 7 and 10 years after fTBI. Mean full-scale IQ score was 102. Memory tests, performed in 12 cases, were in the normal range for 11 patients. In our study, frequency and severity of long-term side-effects following BMT for leukemia appeared lower than usually reported. A possible explanation is that children were transplanted very early in the course of their disease with neither cranial irradiation nor long exposure to chemotherapy prior to transplant.

Acute Disease↗

Allogeneic bone marrow transplantation following a busulfan-based conditioning regimen in young children with acute lymphoblastic leukemia: a Cooperative Study of the Société Française de Greffe de Moelle.

A subgroup of children with ALL remains at high risk of relapse despite the administration of intensive chemotherapeutic protocols and may benefit from allogeneic BMT. The cytoreductive regimen used most often combines TBI with cyclophosphamide. Nevertheless, miscellaneous long-term sequelae have been consequent upon radiotherapy, especially in young children. This retrospective multicentric study analyzes the outcome of children with ALL under 4 years of age receiving an HLA-genoidentical BMT following a radiation-free preparative regimen. A busulfan-based regimen with cyclophosphamide or melphalan +/- etoposide +/- cytarabine was given to 21 children (median age: 28 months, range 6-48). Sixteen patients with initial poor prognostic factors were transplanted in first complete response (CR) and five patients in relapse or second CR. With a median follow-up of 47 months, the results show an overall 4-year DFS of 61.1%. Leukemic recurrence was observed in eight patients. The preparative regimen was well-tolerated and there were no transplant-related deaths. A busulfan-based BMT preparative regimen may be a therapeutic alternative to TBI-containing regimens in young children. Efforts are currently aimed at reducing the relapse rate in these children by optimizing the tumoricidal potential of chemotherapy and the graft-versus-leukemia effect of allogeneic BMT.

Antineoplastic Combined Chemotherapy Protocols↗

Possibilities of scar treatment after thoracic surgery.

During a ten year observation period it was found that scar formation after thoracic surgery is influenced by various factors: metabolism, operative technique and factors of a general nature. On the basis of these findings, a study was carried out to investigate the effect of the scar-specific Contractubex gel (Merz+Co., D-Frankfurt/Main), containing 10% onion extract, 50 U sodium heparin per g of gel and 1% allantoin, in the treatment of children who underwent thoracic surgery and to evaluate its effect on scar development. Before and during the six-month treatment period, both macromorphology and scar colour were assessed; furthermore, a global evaluation of the therapeutic result was made. Additionally, the scars were characterized after a six-month treatment-free follow-up period. The results of 38 Contractubex-treated and 27 untreated patients were compared. In the treated scars, the global evaluation of the therapeutic result was better than in the untreated scars. In the Contractubex group, the rating was "good" and "very good" in 84% of cases, as compared to 59% of the untreated cases. In the treated group, the increase in scar size was markedly lower than in the untreated patients. The treated scars showed a tendency towards quicker paling than the untreated scars. In the treated group, the conversion of primary physiological scars to unphysiological scars (hypertrophic or keloidal scars) was less frequent than in the untreated group. The tolerability of the product was very good in 37 of the 38 treated patients, and good in one patient. All scar-specific effects of Contractubex continued to persist after the end of treatment.

Administration, Topical↗