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C Pichoud

Publications and source records attributed to C Pichoud.

50 records · Page 3Linked to original sources

[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↗

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↗

Immunopathologic aspects of woodchuck hepatitis.

The natural history of infection with woodchuck hepatitis virus (WHV) has been studied in a colony of 38 Marmota monax. Besides serologic assessment for WHV markers, light-microscopic findings of 61 liver biopsies were correlated with the results of immunofluorescence analysis for nucleocapsid (WHcAg) and surface (WHsAg) antigens. Twenty-four chronic WHsAg carriers all featured signs of continuous viral replication. Two major immunomorphologic patterns were observed in their livers: 1) portal hepatitis in which WHcAg accumulated in the cytoplasm and WHsAg was associated with the hepatocyte membrane and 2) periportal hepatitis in which WHcAg shifted toward nuclear localization and WHsAg became mostly intracytoplasmic. Progression from portal to periportal hepatitis, observed in 7 woodchucks, appeared to be induced by a partial recovery of specific immune reactivity to WHV, insufficient, however, to interrupt WHV replication. Deposits of WHsAg and immunoglobulins were present in the kidney and spleen of animals with severe hepatitis.

Animals↗

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↗

Identification and detection of long incubation non-A, non-B hepatitis virus and associated antigens or antibodies.

Three distinct antigen/antibody systems supposedly associated with an HBV-like virus of non-A, non-B hepatitis have been identified. Because of previously demonstrated cross-reactivity with HBe/3 and HBc antigens and other analogies the following terminology is tentatively used. 1. The previously reported serum antigen has been redesignated non-A, non-B e antigen, since it is equivalent to HBe/3 Ag and cross-reacts with it. Non-A, non-BeAg or Ab were detected in 51/62 post-transfusion and 11/56 sporadic acute non-A, non-B hepatitis cases, and in 12/14 cases affecting staff members. In non-A, non-B chronic persistent or active hepatitis and cryptogenic cirrhosis, the prevalence was similarly high: 14/18, 22/48 and 12/18 respectively. Ten out of 26 implicated blood donors were found positive for non-A, non-BeAg accounting for 7 out of 8 post-transfusion cases. A high prevalence of non-A, non-BeAg was also found in haemophiliacs (11/48) and haemodialysed patients (6/42), whereas anti-non-A, non-Be was respectively detected in 4/48 and 6/42 of these cases. 2. Using immunofluorescence, a second antigen termed non-A, non-BcAg has been identified in liver biopsies from 55/84 non-A, non-B chronic hepatitis or cryptogenic cirrhosis cases. All 8 positive biopsies examined by electron microscopy revealed clusters of 22--25 nm intranuclear particles identical to those described in chimpanzees. Anti-non-A, non-Bc detectable by counter-electrophoresis and indirect immunofluorescence was found in the serum of all patients of which biopsy was positive for non-A, non-BcAg. Anti-non-A, non-Bc was also detected in 5/5 non-A, non-BeAg positive cases of post-transfusion hepatitis, 2--6 weeks after onset end remained positive for the 6 month follow-up period. 3. A third antigen, tentatively designated non-A, non-BsAg, has been found less frequently than non-A, non-BeAg in serum. However, it was detectable in 3/18 and 2/12 washed ultracentrifugation pellets of sera positive for non-A, non-BeAg or anti-non-A, non-Be, respectively.

Antibodies, Viral↗

[Identification of a virus similar to hepatitis B virus in non-A non-B hepatitis].

Hepatitis B virus-like particles (including DANE particles) with DNA polymerase activity but negative for HBs Ag have been identified in NON-A, NON-B hepatitis sera positive for HC Ag. Although specifically associated with the particles, HC Ag is not a surface antigen of the hepatitis C virus identified here for the first time. The relationship of this agent with HBV seems obvious, and deserves further study.

Hepatitis B virus↗

[Demonstration of a serum and liver antigen in acute or chronic non A-non B viral hepatitis].

A new precipitating antigen-antibody system possibly was demonstrated by immuno-diffusion in the serum of patients suffering from non A-non B hepatitis. The antigen appears during the first four weeks of transaminases elevation. In acute cases was transient antigenemia (average 3 weeks). Antibodies appeared rapidly after the disappearance of antigen. The same antigen was also detected, by immunodiffusion and by immunofluorescence, in the liver nuclei of infected hepatocytes. This antigen specific appears for non A-non B hepatitis since it is neither found in the serum of normal subjects nor in that of patients with cirrhosis toxic or viral that hepatitis A or B. The hypothesis of a virus associated antigen is the most likely explanation.

Acute Disease↗

Anti-HBc screening for the prevention of perinatal transmission of hepatitis B virus in France.

As anti-HBc screening has been proposed for blood donor testing, we investigated its effectiveness during pregnancy. Among 4,023 successive pregnant women screened for anti-HBc, 539 (13.4%) were positive and further tested for HBsAg and anti-HBs. HBsAg was found in 73 (1.81%) and anti-HBc only was positive in 66 (1.64%). Among the 73 women positive for HBsAg, HBV DNA was found in the serum of seven, the cord blood of two, the placenta of three. Of the 58 infants given HBV immunoglobulins and vaccine, only four had transient HBsAg. None of the 66 women positive for anti-HBc only had anti-HBc IgM, HBeAg, or HBV DNA in serum, cord blood or placenta but five women became HBsAg positive before, at, or after delivery. Among the infants born of these 66 mothers, three had high ALT, two had HBsAg and one HBV DNA without HBsAg. Screening for anti-HBc may be cost effective, at least in low HBV prevalence areas, since there is evidence for infectivity of pregnant women positive for anti-HBc only.

Carrier State↗

Analysis of a hepatitis delta virus isolate from the Central African Republic.

Based on the analysis of HDV genomes from different areas of the world, three genotypes of HDV have been identified. Genotype I is the most prevalent and widespread. Genotype II is represented by two isolates from Japan and Taiwan. Genotype III has been found only in the Amazonian basin where it is associated with a history of severe disease, fulminant hepatitis with microvesicular steatosis (spongiocytosis). We report here the cloning and the analysis of the complete viral genome from woodchuck serum-derived HDV RNA after transmission from Central African Republic (RCA) patients with fulminant spongiocytic delta hepatitis. Two overlapping cDNA fragments, covering the entire HDV genome, were generated by RT-PCR and cloned. Three clones obtained from each fragment were fully sequenced. A complete consensus RCA HDV genome was reconstituted. The individual and the consensus nucleotide sequences were compared with those of 16 other fully sequenced isolates belonging to the three genotypes. Phylogenetic trees generated by the neighbour joining method firmly place our isolate in genotype I, and show that this RCA isolate differs significantly from the east African isolates previously analysed. Transfection experiments showed that the isolate is replication-competent, but less so than the control "wild-type" strain. Two novel mutations encountered in this work, one in the antigenomic ribozyme sequence and one affecting delta antigen, were studied.

Amino Acid Sequence↗

Transmission of serologically silent hepatitis B virus along with hepatitis C virus in two cases of posttransfusion hepatitis.

The polymerase chain reaction (PCR) was used to investigate the presence of hepatitis B virus (HBV)-related DNA sequences in blood from three blood donors and two transfusion recipients who developed posttransfusion non-A, non-B hepatitis (NANBH). In the first case, the sole donor was positive for antibody to hepatitis B surface (HBs) and core (HBc) antigens and had elevated alanine aminotransferase (ALT) levels, while the recipient had no HBV serologic markers. Both the donor and the recipient had serologic markers of hepatitis C virus (HCV) and were found positive for HBV DNA and HCV RNA sequences by PCR. The second case involved two donors and one recipient. Serologic tests for conventional HBV markers were negative in all three individuals, but one of the donors had elevated ALT. HBV DNA sequences were detected by PCR in the serum of the recipient and of the donor with high ALT, but not in the serum of the donor with normal ALT. Anti-HCV was detected in the serum of the recipient and of the suspect donor but not in that of the donor with normal ALT. The sequences amplified in the S region and determined after cloning of PCR products for both donor-recipient pairs were indistinguishable from each other and identical to the sequence of the major HBV subtype of adw in the first case and ayw in the second case. Furthermore, for the second case, an identical single-point mutation was found in both the donor and the recipient. These data confirm the transmission of conserved HBV sequences together with HCV in posttransfusion NANBH.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

[Hepatitis B virus reactivation after allogeneic bone marrow transplantation in a patient previously cured of hepatitis B].

The presence of antibodies to HBs and HBc antigens indicates previous infection with hepatitis B virus but does not necessarily reflect viral clearance. Immunosuppression such as that observed in patients with bone marrow transplantation may be responsible for viral reactivation followed by acute exacerbation after withdrawal of immunosuppressive therapy. We report a case in a patient with natural immunity to hepatitis B who had undergone allogenic bone marrow transplantation with an identical sibling donor one year before for the chronic myelogenous leukemia in the first chronic phase. Ganciclovir treatment resulted in control of hepatitis virus B replication and in biochemical remission. We suggest that prevention relies on serological evaluation and therapy with active or passive immunisation or antiviral drugs in case of a rapid decline of anti-HBs Ab titers to undetectable levels.

Adult↗

[Prevalence of viral hepatitis B markers in the region of Tataouine (southern Tunisia)].

Tataouine (South Tunisia) has been subject to several viral hepatitis epidemics during these last years. Prospective study has been conducted to define the prevalence of HVB infection. It has examined 511 cases, the age of whom was between 1 month and 70 years, reported in groups through the OMS recommendations, taking into account the number of inhabitants in each area. The global prevalence was 6.2% for HBs Ag and 18.5% for HBs antibody. These results were not different from the frequencies observed within the Tunisian population in general. The analysis of this study according to these groups, shows that in three areas (Ras El Oued, Bir 30, Dhibet) 60 to 80% of cases have at least one of HVB marquers, whereas the prevalence in other areas (Rogba) was very weak. The geographic repartition of HVB infection corresponds approximatively to areas that have been the most infected by the last hepatitis epidemics. A second study has completed and confirmed the results of the first one, taking into consideration a more important number of cases from areas of strong and weak endemicity. 596 sera have been examined in Rogba which counts 2000 inhabitants and is a weak endemicity area. 528 sera have been examined in the three areas of strong endemicity: 199 in Bir 30, 201 in Dhibet and 128 in Ras El Oued, which count around 2000 inhabitants, too. The percentage of cases presenting at least one of HVB serological marquers reaches 84 in Dhibet, 70 in Ras El Oued, 50 in Bir 30 and 24 in Rogba. This HBs Ag frequency is 3.8% in Rogba, 15% in Bir 30, 24% in Ras El Oued and 26.3% in Dhibet. It seems that the HVB is the virus of hepatitis epidemics observed in Tataouine at least in the three strong endemicity areas.

Adolescent↗

[Significance of the expression of pre-S proteins in mononuclear blood cells in chronic hepatitis caused by the hepatitis B virus].

In chronic viral type B hepatitis, the presence in the serum of pre-S proteins of hepatitis B virus (HBV) envelope reflects viral replication. As peripheral blood mononuclear cells (PBMC) are known to be target cells for HBV replication, the aim of our study was to investigate the clinical relevance of pre-S protein expression in PBMC. Fifty-seven patients with chronic type B hepatitis and HBs antigenemia were studied. Following separation using the Ficoll gradient, the PBMC were lysed and studied for pre-S proteins by Western blot. HBs Ag and HBc/e Ag were assayed in parallel by radioimmunoassay. HBs Ag was detected in PBMC in 86 percent of cases, HBc/e Ag in 28 percent of cases and pre-S proteins in 34 percent of cases. A statistically significant association was found between the presence of HBc/e Ag in PBMC and both the serum HBe Ag (chi 2 test, p less than 0.01) and the serum viral DNA/DNA polymerase (t test, p = 2.10(-4)). The pre-S protein expression in PBMC was significantly associated with higher levels of DNA/DNA polymerase activity (chi 2 test, p less than 0.05). The expression of pre-S proteins in PBMC appears therefore to correlate with the HBV viral replication phase. The HBc/e Ag and pre-S protein detection in PBMC therefore offers a reliable non invasive approach to tissular viral replication. The clinical relevance of pre-S testing in PBMC was illustrated by the study of 12 cases of chronic active hepatitis positive for anti-HBe but with no or low level of serum DNA polymerase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗