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Biomedical subjects

C Trepo

Publications and source records attributed to C Trepo.

At least 235 records · Page 13Linked to original sources

[Epidemiology of acute hepatitis among outpatients in the urban community of Lyon, 1983].

We conducted in 1983 an hepatitis surveillance programme in collaboration with 93% of the medical analysis laboratories in Lyons' urban area (1,100,000 inhabitants) and diagnosed 1,002 cases of acute hepatitis (incidence : 90.5 cases/10(5) inhabitants; HAV : 50.4 cases/10(5) inhabitants; HBV : 12 cases/10(5) inhabitants; non A non B : 24 cases/10(5) inhabitants; drugs : 4.2 cases/10(5) inhabitants). HBs Ag was undetectable in 12% of acute hepatitis B. Hepatitis A accounted for 91% of children's cases and 48% of cases among adults between 20 and 40 years old. Epidemics were observed among children after summer holidays related to the return of migrants from trips to their native country. For acute hepatitis B and non A non B, classical epidemiological data were observed, but the prevalence of drug addicts and homosexuals was low.

Adult↗

The HBV HBX gene expressed in E. coli is recognised by sera from hepatitis patients.

We have cloned the X gene (HBx) and the HBc antigen (HBc Ag) gene of human hepatitis B virus (HBV) in Escherichia coli as fusion products with beta-galactosidase. Both HBV genes are expressed in E. coli strain CSR 603. Expression is detected by u.v. irradiation of the bacteria, metabolic labelling and electrophoresis of the labelled extracts on SDS-polyacrylamide gels. The HBc Ag protein produced in bacteria can be recognised by anti-HBc sera and peptides derived from the protein are also recognised by anti-HBe sera. The HBx protein is recognised by some, but not all, sera which are anti-HBe positive. HBx Ag is also recognised by a woodchuck antibody similar to anti-HBe (anti-WHe). These results constitute the first proof that the open reading frame X is a true viral gene and is expressed during HBV (and WHV) infection and that an HBx/anti-HBx system, which may have important biological implications, can exist in parallel with the classic HBe/anti-HBe system.

Animals↗

Woodchuck hepatitis virus infection: serologic and histopathologic course and outcome.

Five out of seven American woodchucks inoculated with woodchuck hepatitis virus developed antigenemia after 2 to 13 weeks followed by an antibody response. One animal became a carrier, and another animal exhibited a primary antibody response. Clinical disease was not obvious and aminotransferase elevation could not be demonstrated. Liver biopsy showed mononuclear portal infiltration and little parenchymal cell necrosis.

Animals↗

Comparative study of DHBV DNA levels and endogenous DNA polymerase activity in naturally infected ducklings in France.

Duck hepatitis B virus (DHBV) was found in the serum of 1-6% of Pekin ducklings originated from French commercial flocks. The viremia was followed in the serum of 5 ducklings over a span of 3 mth by monitoring the levels of DHBV DNA and the endogenous DNA polymerase (DNAp) activity. The DHBV DNA levels in serum were quantified either by the DNA dot hybridization technique including counting of retained radioactivity, or by successive dilutions of each serum sample followed by DNA hybridization. The counting of the retained radioactivity was plotted on a curve and its evolution compared with that of viral DNAp activity. DHBV DNA levels in serum, estimated by both methods paralleled those of the DNAp activity, which peaked at the 4th or 5th week posthatch to decrease and fluctuate thereafter. Occasional discordance between DHBV DNA levels and the endogenous DNAp activity was observed, which could be correlated with the degree of repair of the single stranded gap of serum DHBV DNA. Parallel follow up studies comparing quantitative estimations of serum viral DNA and of DNAp activity, as presented here, may provide some clues for the understanding of the mechanisms involved in the establishment of the HEPA DNA virus carrier state. Such comparative studies may also be crucial for optimal monitoring of antiviral drugs in both human clinical trials and animal experimental studies.

Animals↗

[Chronic hepatitis, liver cirrhosis, primary liver cancer and virus HB infection. Epidemiologic study in a sahelian hospital milieu. Apropos of 185 cases].

From December 1982 to June 1985, 185 patients with signs of chronic liver disease are investigated in National Hospital (Niamey, Republic of Niger). A first group ("Hepatopathy") of 131 patients (75 males, 56 females) is made of 3 chronic liver diseases: 35 chronic hepatitis (CH), 58 hepatic cirrhosis (HC), 38 hepatocellular carcinoma (HCC). A second group ("Controls") of 54 patients (29 males, 25 females) is made of miscellaneous diseases other than CH, HC, HCC. In the first group ("Hepatopathy") serum hepatitis B virus (HBV) surface antigen (HBsAg-radioimmunoassay) is present in 64.9% (85/131). In the second group ("Controls") serum HBsAg is present in 3.7% (2/54) (Chi-2 test P less than 10(-9)). Serum HBsAg prevalence is more than 50% in each group of CH, HC and HCC. A maximum value is observed in males with HCC (75.7%). These results demonstrate the importance of evolutive HBV infection in the course of CH, HC and HCC in the sahelian region.

Adult↗

[Prevalence of markers of viral hepatitis B in northern Cameroon].

The authors report the results of a sample survey made in January 1985 in a Northern Cameroon Division following the observation of a very high mortality rate by serious jaundice in 1983 and 1984. Within a representative population sample of 395 persons of more than 4 years old, they observed that: 100 were HBs antigen carriers (detected by ELISA), 25.3% +/- 5.5%, 19 were HBe antigen carriers (RIA), 4.8% +/- 2.4%, and 202 were HBs antigen or HBs antibody carriers: 51.1% +/- 6.5%, There was only one carrier of delta antigen. There is no difference in HBs antigen bearing according to sex or age, but HBe antigen appears to be more frequent among young people.

Adolescent↗

[Spontaneous and experimental infection of alpine marmots (Marmota marmota) by the North American woodchuck hepatitis virus (Marmota monax). Initial results].

Summer's discovery in 1978 of a DNA virus, very close to human Hepatitis B virus in a woodchuck population in the U.S.A. (Pennsylvania) was a confirmation of the first description made by Snyder at Penrose Research Laboratory (Philadelphia). It was the first animal model of human B hepatitis infection. The comparative study of morphological, ecological and ethological characteristics of the marmot (Marmota marmota) and the woodchuck (Marmota monax) enables an easy distinction between these two species. The natural infection of M. monax by the WHV shows that the woodchuck is a good model for human B hepatitis and should be extended to M. marmota. A sample of 24 marmots caught in the Alpes of Haute-Provence has not revealed any spontaneous infection in these animals by the woodchuck virus. The failure of experimental inoculation of the marmot (24 animals) with the WHV confirms the refractory status of this species (no viremia and very low and short serological response with or without an immunosuppressive treatment). These preliminary results require a confirmation in other animals of different age and geographical region and also by using more specific tests such as molecular hybridization, research on DNA polymerase and direct transfection trials.

Age Factors↗

Inhibition of human and woodchuck hepatitis virus DNA polymerase by the triphosphates of acyclovir, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine and E-5-(2-bromovinyl)-2'-deoxyuridine.

The triphosphates of acyclovir (ACV), 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) and E-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) have been examined for their inhibitory effects on the endogenous DNA polymerase reactions of human hepatitis B virus (HBV) and woodchuck hepatitis virus (WHV). All three triphosphates (ACVTP, FIACTP and BVdUTP) inhibited the HBV and WHV DNA polymerases by competing with the corresponding natural substrates. FIACTP was the most potent inhibitor of HBV and WHV DNA polymerase while ACVTP was the least effective inhibitor. The inhibitory properties of these compounds were compared with those of the 5'-triphosphates of 1-beta-arabinofuranosyl-cytosine (ara-CTP) and 1-beta-arabinofuranosylthymine (ara-TTP). The 50% inhibitory doses for HBV and WHV DNA polymerases were in the following order: FIACTP less than BVdUTP less than ara-TTP less than ACVTP less than ara-CTP. BVdUTP appeared to be an efficient alternate substrate to dTTP for HBV DNA polymerase while FIACTP was much less efficient when substituted for dCTP. ACVTP did not act as an alternate substrate to dGTP and appeared to prevent DNA chain elongation.

Acyclovir↗

Comparison of properties of woodchuck hepatitis virus and human hepatitis B virus endogenous DNA polymerases.

The principal properties of the DNA polymerases of woodchuck hepatitis virus and human hepatitis B virus were compared. The enzymes of both viruses exhibited optimal activities in the same range of pH, ionic strength, and MgCl2 concentration. Like human hepatitis B virus DNA polymerase, the woodchuck hepatitis virus DNA polymerase was strongly inhibited by phosphonoformic acid but not by phosphonoacetic acid and aphidicolin. Similar inhibition patterns for both enzymes were observed with arabinofuranosyl nucleotides (9-beta-D-arabinofuranosyladenine-5'-triphosphate, 1-beta-D-arabinofuranosylcytosine-5'-triphosphate, 1-beta-D-arabinofuranosylthymine-5'-triphosphate) and dideoxythymidine triphosphate, whereas no effect was obtained with corresponding nucleosides. The therapeutic significance of these results and the relevance of the woodchuck as an experimental animal model for the study of human hepatitis B virus infections are discussed.

Animals↗

[Neuropathy following treatment of chronic active hepatitis with vidarabine].

In a patient with chronic active hepatitis (CAH) due to B-virus, a polyneuropathy developed following a cure of vidarabine. The pathophysiology of this neuropathy remains unclear as it appears not to occur in patients with diseases other than CAH. Muscular pains and paresthesias reported in such patients treated with vidarabine could be the consequence of peripheral nerve involvement.

Adult↗

[Immunopathological mechanisms responsible for hepatic lesions caused by B virus].

Clinical and experimental observations suggested that liver lesions related to Hepatitis B Virus infection were the result of an immunological process similar to that observed in graft rejection. Virus-antigens (Ag) and particularly, HBsAg expressed on the hepatocyte-membrane are the best candidates as target-Ag. Constituents of the hepatocyte membrane itself and particularly Liver Specific Protein (LSP) are also susceptible to represent targets for an auto-immune attack. Humoral immunity does not seem to be involved in the pathogenesis of the liver lesions; specific antibodies have a protective more than an aggressive role in hepatitis, and immune-complexes are responsible for extra-hepatic lesions. In vitro studies of lymphocytotoxicity against autologous liver cells or rabbit hepatocytes have demonstrated the predominant role of T-lymphocytes in acute hepatitis and that of K lymphocytes in HBsAg positive chronic active hepatitis. The role of Natural Killer cells has not been clearly precised up to now. Analysis of the experimental data has to be cautious because of the diversity of in vitro models and difficulty in interpretation of the results. A better understanding of the immune mechanisms involved in the progression of the disease to chronicity, cirrhosis and hepatocellular carcinoma could allow more suitable treatments according to immunological status of the patients and virus-markers in the serum and the liver.

Animals↗

Detection of immune complexes by their complement-dependent binding to bovine conglutinin: technical aspects of a solid-phase immunoenzyme microassay and its application to normal and pathological sera.

A micromethod for the solid-phase conglutinin binding assay (Con BA) for the detection of circulating immune complexes (CIC) is described, in which the use of microplates, glucose oxidase-coupled anti-human immunoglobulins and automatic OD recorder contributed to the speed and low cost of this reproducible and sensitive test. The Con BA values of a large population of healthy blood donors had a wide distribution which in our series of 189 appeared to be trimodal. The Con BA values clearly reflected the levels of the main Ig classes (M, G, and A). This was confirmed by follow up of 6 individuals with high initial Con BA values. For 4 of them, a parallel decrease in Con BA value and IgG concentration was observed. In the 2 others, the sustained high level of Con BA remained unexplained. Complement components and activity of these sera were within normal limits. Because of fluctuation in the aggregated human gamma-globulins (AHG) reference curve, expression of results was based upon the standard deviation of 6 normal sera. In view of the above results, these sera were selected from those with the lowest Con BA values. On the basis that Con BA and C1q BA may detect CIC differing in their ag/ab ratio, sera from rheumatoid arthritis and chronic active B hepatitis patients with or without conventional rheumatoid factors (RF) were analyzed by both Con BA and C1q BA. RF-containing sera, likely to contain CIC in antigen excess, contributed exclusively to the highest C1q BA and lowest Con BA values. In contrast C1q BA-Con BA+ sera were preferentially RF negative. It is proposed that the complexes thus detected may be of idiotype-anti-idiotype nature.

Antigen-Antibody Complex↗

Use of the cross-reactivity with hepatitis B virus antigens and antibodies for the demonstration of a woodchuck hepatitis virus 'e' antigen-antibody system.

Woodchucks hepatitis virus (WHV)-associated antigens and antibodies were studied using current sensitive radio- or enzyme immunoassays (RIA, EIA). A significant cross-reactivity was observed between hepatitis B surface antigen (HBsAg) and woodchuck hepatitis surface antigen (WHsAg) using RIA or EIA (Abbott Laboratories, North Chicago, Ill., U.S.A.) although not with two other commercial EIA tested (Organon Technika, Oss, The Netherlands; Behringwerke AG, Marburg, F.R.G.). A weak but significant reactivity was also found when woodchuck sera positive for WHsAg or anti-WHs by immunodiffusion were tested for HBeAg and anti-HBe by RIA, suggesting the existence of a WHeAg-anti-WHe system in infected woodchucks. The specificity of this e-anti-e reactivity in the woodchuck was further confirmed by successful absorption experiments. WHsAg and WHeAg could be distinguished serologically by immunodiffusion and separated from each other by ultracentrifugation and ammonium sulphate precipitation. A WHeAg preparation was used to boost the presumed natural antibody activity of an immune woodchuck. The specific anti-HBe response detected by RIA during the immunization experiments demonstrated the existence of a soluble WHeAg cross-reacting with the human HBe-anti-HBe system. This was confirmed in immunodiffusion by a partial identity between the precipitin lines formed by the WHeAg-anti-Whe and HBeAg-anti-HBe reaction. Whether the WHe-Ag-anti-WHe system wil mimick HBeAg and anti-HBe in all their clinico-pathological correlations, deserves further study.

Animals↗