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Biomedical subjects

G Michel

Publications and source records attributed to G Michel.

At least 19 recordsLinked to original sources
PubMed1995

Treatment of acute graft-versus-host disease with methylprednisolone and cyclosporine with or without an anti-interleukin-2 receptor monoclonal antibody. A multicenter phase III study.

A double-blind, placebo-controlled trial of BT563, including 13 European centers, was initiated in October 1989 to compare the efficacy of the combination of in vivo anti-CD25 mAb (BT 563), cyclosporine, and steroids versus placebo and CSA-steroids in the treatment of grade II and III acute graft-versus-host disease (GVHD). Sixty-nine patients participated in the study, which excluded non-genotypically identical allogeneic bone marrow transplant recipients. No statistically significant differences were observed, clinically or biologically, between the 2 groups before the onset of the treatment. Treatment responses were scored during and after the 3-week treatment period (mAb or placebo). Efficacy was evaluated on days 4, 10, 20, 30, and 60 or on any day the patient's condition was found to be deteriorating. Preceding and systemically untreated GVHD of grade I was observed in 59% of the cases. No statistically clinically significant differences between the 2 groups were observed during or upon completion of treatment in GVHD grade. Nine patients in the placebo group and 6 in the active group were withdrawn of the study. Thirteen of these 15 patients were withdrawn because of failure of GVHD therapy (9 in the placebo group and 4 in the BT563 group). At day 20 after onset of the treatment, the response rate was 63% and 70% for the placebo and BT563 groups, respectively (NS). Probability of survival at 1 year was 59% and 66% (NS) for the placebo and active groups, respectively. In conclusion, despite preliminary promising results in the treatment of steroid-resistant acute GVHD, the role of first-line treatment with an in vivo anti-interleukin-2 receptor mAb remains to be determined.

Acute Disease↗
PubMed1995

[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↗
PubMed1994

Polychlorinated biphenyls modulate protooncogene expression in Chang liver cells.

n Chang liver cells we studied the influence of polychlorinated biphenyls (PCB) on the expression of different protooncogenes. In cells incubated with medium supplemented with PCB we observed an early effect after 3 h on c-erbA and c-erbB RNA level. This reduction of RNA was due to a delayed transcriptional activation of the genes. The PCB congener 3,3',4,4',5-pentachlorobiphenyl (5-CB) in a 1,000-fold lower concentration influenced protooncogene expression in the same manner. In contrast c-raf RNA level increased transiently after 24 h. The fact that persistent chemicals like PCB interfere with protooncogene expression is particularly interesting in view of their tumor promoting activity.

Blotting, Northern↗
PubMed1994

Significance of IgG and IgM HCV antibody secretion in vitro in patients with chronic hepatitis C: correlation with disease activity and response to interferon-alpha.

Hepatitis C virus antibodies are found in the serum of most patients with chronic hepatitis C. However, the significance of the humoral response is still uncertain. In this study, in vitro IgG and IgM anti-hepatitis C virus secretion by peripheral blood mononuclear cells of patients with chronic hepatitis C was analyzed. Peripheral-blood mononuclear cells from 21 of 36 patients (58.3%) secreted IgG anti-hepatitis C virus in vitro, as demonstrated with anti-hepatitis C virus-specific enzyme immunoassays and recombinant immunoblot assays. Ten of the 36 patients (27.8%) showed both IgG and IgM anti-hepatitis C virus core in vitro. In 9 of these 10 patients, IgM anti-hepatitis C virus was also detected in serum. Patients with in vitro IgM or IgG anti-hepatitis C virus secretion had higher ALT levels in serum than did patients without such secretion in vitro (99.5 +/- 22.1 and 85.6 +/- 34.4 vs. 38.1 +/- 37.4 U/L; p < 0.0001, p < 0.001). Furthermore, with a histology activity score it was demonstrated that patients with in vitro IgM or IgG HCV antibodies (or both) had more severe chronic active hepatitis than did patients without in vitro hepatitis C virus antibody secretion (p < 0.01). To analyze the therapy outcome, we included in this study 18 patients who had received interferon-alpha previously. Seven of eight in vitro hepatitis C virus antibody-positive patients were nonresponders, whereas the in vitro hepatitis C virus antibody-negative patients were mostly complete therapy responders (8 of 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1994

A phase II study of high-dose cisplatin, vinblastine, bleomycin, and etoposide (PVeBV regimen) in malignant nondysgerminomatous germ-cell tumors of the ovary.

Fourteen patients with malignant nondysgerminomatous germ-cell tumors of the ovary were treated with a combination of high-dose cisplatin, vinblastine, bleomycin, and etoposide (PVeBV regimen). Nine patients received PVeBV as primary postoperative therapy, of whom four had no residual disease. Four patients received PVeBV for recurrent disease. One patient underwent PVeBV therapy as second-line treatment. Three patients with initial poor prognostic features were treated with early high-dose chemotherapy with autologous bone marrow rescue as consolidation therapy after two cycles of PVeBV. Ten of 14 patients (71%) are progression-free with a median follow-up of 6 year. Equal efficacy and less toxicity favor the combination of bleomycin, etoposide, and cisplatin (BEP) as standard treatment of ovarian germ-cell tumors in the 1990s.

Adolescent↗
PubMed1994

In vitro secretion of anti-GOR protein and anti-hepatitis C virus antibodies in patients with chronic hepatitis C.

BACKGROUND/AIMS: Anti-GOR antibodies may reflect hepatitis C virus (HCV)--related autoimmunity or cross-reactivity with HCV core antigen. This study aimed to evaluate the clinical significance of anti-GOR antibodies. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with HCV and 48 controls and cultured for 8 days. The in vitro antibody secretion by PBMC was determined using specific enzyme-linked immunosorbent assays and recombinant immunoblot assay. RESULTS: In 22 of 35 patients with HCV (62.9%), PBMCs secreted anti-c22-3 or anti-c33c antibodies. However, in 3 of 48 controls (6.2%), PBMCs secreted anti-c33c antibodies alone. A significant in vitro anti-GOR response was found in 13 of 35 patients (37.1%) with HCV in relation to 4 of 48 controls (8.3%). In 12 of these patients (92.3%), anti-GOR were found in vitro and in serum. Two patients with HCV produced in vitro anti-GOR but not anti-c22-3 antibodies. Regarding disease activity, in vitro anti-GOR-positive patients with HCV had significantly higher alanine aminotransferase levels (108.8 +/- 17.8 U/L vs. 64.5 +/- 7.6 U/L; P < 0.01) and more frequent signs of chronic active hepatitis (10 of 13 [76.9%] vs. 10 of 22 [45.5%]) than patients with HCV without in vitro anti-GOR response. CONCLUSIONS: The humoral anti-GOR response in vitro is closely related to HCV infection and disease activity. Anti-GOR and anti-HCV core antibodies are regulated independently. It is likely that anti-GOR may reflect an HCV-associated autoimmune phenomenon.

Adult↗
PubMed1994

Long-term results of two VAB-like regimens (vinblastine + actinomycin-D + bleomycin + cyclophosphamide + cisplatin) in malignant germ cell tumours of the ovary.

21 patients with malignant germ cell tumours of the ovary were treated with two chemotherapy regimens including vinblastine, actinomycin-D, bleomycin, cyclophosphamide and cisplatin. Chemotherapy was delivered as primary postoperative therapy in 15 patients and for recurrent disease in 6 patients. 3 of 4 patients with pure dysgerminomas and 10 of 17 patients with non-dysgerminomatous tumours are alive without evidence of disease. The overall progression-free survival is 62% (95% confidence interval 45-77) with a median follow-up of 7 years. Two toxic deaths were observed. Less toxicity and better efficacy favour etoposide- and cisplatin-based regimens as standard chemotherapy for germ cell tumours of the ovary.

Adolescent↗
PubMed1992

Fosfomycin enhances the expression of penicillin-binding protein 2 in methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains.

The effects of fosfomycin on penicillin-binding proteins (PBPs) were studied on the methicillin-resistant Staphylococcus aureus strain CIP (Collection de l'Institut Pasteur, Paris, France) 65-25 and on a methicillin-susceptible S. aureus strain CIP 65-6. The combinations of fosfomycin and oxacillin were synergistic, additive or antagonistic, depending on antibiotic concentrations. Fosfomycin induced modifications of the PBP profile of the two strains studied. In particular, it increased the expression of PBP2. This suggested that this protein is inducible; the only PBP not affected by fosfomycin was PBP3.

Bacterial Proteins↗
PubMed1992

Biosynthesis of bacillomycin D by Bacillus subtilis. Evidence for amino acid-activating enzymes by the use of affinity chromatography.

Bacillomycin D is an antifungal lipopeptide produced by B. subtilis. The formation of the peptidyl bonds of bacillomycin D occurs non-ribosomally, as demonstrated by the use of chloramphenicol, an inhibitor of protein biosynthesis. Amino acid-activating enzymes were found in B. subtilis cell lysates purified by affinity chromatography on a gel containing L-Pro, an amino acid of bacillomycin D. Presence of ATP during this purification increases the binding of enzymatic proteins and their activity. An enzyme, with an apparent molecular weight of 230 kDa, catalyzed ATP-PPi exchange reactions, which were mediated by specific amino acids, corresponding to a partial sequence of bacillomycin D.

Adenosine Triphosphate↗
PubMed1992

Interleukin-8 receptor-mediated chemotaxis of normal human epidermal cells.

Normal human keratinocytes show chemotactic behavior towards interleukin-8 (IL-8). Under physiological conditions this cytokine seems to be present in an equilibrium between monomeric and dimeric forms, as indicated by Western blotting data. Radioligand binding studies suggest that keratinocyte chemotaxis is mediated by receptors specific for IL-8 dimers. IL-8 receptor-specific mRNA can be detected in a keratinocyte cell line by polymerase chain reaction.

3T3 Cells↗
PubMed1992

Cloning and nucleotide sequence of the gene encoding the gamma-D-glutamyl-L-diamino acid endopeptidase II of Bacillus sphaericus.

The gene encoding the Bacillus sphaericus gamma-D-glutamyl-L-diamino acid endopeptidase II, a cytoplasmic enzyme involved in cell sporulation [1], contains the information for a 271-amino acid protein devoid of a signal peptide. The endopeptidase lacks sequence relatedness with other proteins of known primary structure except that its C-terminal region has significant similarity with the C-terminal region of the 54-kDa P54 protein of Enterococcus faecium, of unknown function [2].

Amino Acid Sequence↗
PubMed1992

Anti-GOR and hepatitis C virus in autoimmune liver diseases.

Anti-GOR is an autoantibody found in hepatitis C virus (HCV) infection. We have studied the specificity of this antibody for HCV infection in various groups of autoimmune liver diseases. Anti-HCV was detected by a second generation HCV enzyme-linked immunosorbent assay in 14 of 29 patients with liver-kidney-microsomal (LKM-1) -antibody-positive autoimmune hepatitis type 2 and in all 6 control patients with HCV-RNA-positive chronic hepatitis C. Anti-HCV was not found in those with antinuclear-antibody-positive autoimmune hepatitis type 1 (10 patients), with soluble-liver-protein-antibody-positive autoimmune hepatitis type 3 (8), with primary biliary cirrhosis (9), with systemic lupus erythematosus (SLE) (10), or in healthy controls (13). Anti-GOR was detected in 11 of 14 patients with autoimmune hepatitis type 2 who were all positive for anti-HCV but only in 1 of 15 LKM-1 patients who were negative for anti-HCV. We did not find anti-GOR in any other group of autoimmune liver disease, SLE, or control sera, but this antibody was detected in 3 of 6 patients with chronic hepatitis C. Autoimmune hepatitis type 2 patients who were anti-GOR positive and anti-HCV positive were less likely to be female, were older (p less than 0.001), and had lower LKM-1 antibody titres (p less than 0.001), lower disease activity, and responded less effectively to immuno- suppression than did those who were anti-HCV negative/anti-GOR negative. The findings show that anti-GOR reflects HCV-specific autoimmunity. HCV seems to induce autoimmunity to both GOR (an HCV-specific autoepitope) and LKM-1 (an epitope that is also recognised by autoimmune hepatitis sera of a different cause). Anti-GOR and LKM-1 antibodies contribute to a better differentiation of chronic hepatitis, a finding that has therapeutic implications.

Adolescent↗
PubMed1992

Synthesis of beta-hydroxy fatty acids and beta-amino fatty acids by the strains of Bacillus subtilis producing iturinic antibiotics.

The iturinic antibiotics, which contain long chain beta-amino acids, are produced by Bacillus subtilis. Screening these strains for the presence of a possible precursor of the iturinic antibiotics, we isolated a lipopeptide containing beta-hydroxy fatty acids. The structure of this compound was studied and it appears to be identical or structurally very similar to surfactin. The carbon chain of its beta-hydroxy fatty acids was n C16, iso C16, iso C15 or anteiso C15. The percentages of each beta-hydroxy fatty acids varied according to the strain producing iturinic antibiotics and were influenced by addition of branched-chain alpha-amino acids to the culture medium. These results demonstrate for the first time that iso C14 beta-hydroxy fatty acid is a constituent present in such a surfactin like lipopeptide. Besides, the presence of radioactive beta-hydroxy fatty acids in the phospholipids when the strains were grown in the presence of sodium [14C]acetate seems also characterize the different strains producing iturinic antibiotics.

Amino Acid Sequence↗
PubMed1992

Composition and immunogenicity of the polysaccharide components of the thermostable macromolecular antigen group of mycobacterial antigens.

The thermostable macromolecular antigen (TMA) group includes major components of the mycobacterial cell envelope and cytoplasm, which elicit humoral and cellular immune reactions, and seems to play important roles in infectious diseases. The best known member of this group, antigen A60 of Mycobacterium bovis BCG, was previously shown to contain three moieties of polysaccharides, free lipids, and polypeptides. In this work, the TMA polysaccharides of three pathogenic mycobacteria (M. avium, M. bovis and M. paratuberculosis) have been analyzed by coupled gas chromatography-mass spectrometry. In all cases the cores of the TMA complexes were represented by branched glucans of high molecular mass (about 10(6) daltons), for which structural models have been proposed. The immunogenicity of the polysaccharide components from the three TMA was verified with several immunological procedures (immunodiffusion and immunoelectrophoresis of the antigen, and immunoblotting of the corresponding electrofocused immunoglobulins). All tests tallied in showing a negligible immunogenicity of the glucans examined (inability to produce, upon injection, the synthesis of specific immunoglobulins), thus pointing to the protein moiety of TMA as the one responsible for the high immunoreactivity of the complexes.

Animals↗
PubMed1992

Arterioureteral fistula after extended resection of pelvic tumors: report of three cases and review of the literature.

Arterioureteral fistulas are rare. Three patients with arterioureteral fistulas complicating extended resection of pelvic tumors associated with bilateral cutaneous ureterostomy in the right lower quadrant are reported. In one case, the fistula involved the left ureter, the right common iliac artery, and the inferior mesenteric artery. Pathological iliac artery, pelvic cancer, or operated ureteral stones are often incriminated in the genesis of ureteroarterial fistulas. Insertion of a ureteral catheter has been found to be the main promoting factor. The common iliac artery is involved frequently. Clinical presentation is often limited to gross hematuria, whereas complementary investigations have not proved to be sensitive. Surgical treatment is often complex, but must be undertaken early, even in the absence of absolute proof of diagnosis, in order to preclude uncontrollable massive hemorrhage.

Female↗