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C Brechot

Publications and source records attributed to C Brechot.

At least 109 records · Page 6Linked to original sources

Expression of insulin-like growth factor II and receptors for insulin-like growth factor II, insulin-like growth factor I and insulin in isolated and cultured rat hepatocytes.

Insulin-like growth factor II is believed to play an important role in fetal growth and development. The insulin-like growth factor II gene expression is tissue specific and developmentally regulated. We have previously shown an enhanced level of insulin-like growth factor II messenger RNA and protein in human hepatocellular carcinomas. This led to the suggestion that hepatocytes might be involved in insulin-like growth factor II expression. However, previous studies based on in situ hybridization only showed insulin-like growth factor II messenger RNA in liver sinusoidal cells. This paper reports on the analysis of the expression of insulin-like growth factor II and insulin-like growth factor II, insulin-like growth factor I and insulin receptor messenger RNAs in vivo in isolated rat hepatocytes at various stages of development and in vitro in adult rat hepatocytes primary culture. Our study indicates that isolated rat hepatocytes synthesize insulin-like growth factor II messenger RNA with a switch between fetal and adult messenger RNA profiles occurring 21 days after birth. In addition, adult rat hepatocytes in culture expressed insulin-like growth factor II messenger RNA and protein. Insulin-like growth factor II, insulin-like growth factor I and insulin receptor messenger RNAs were also detected. Therefore these results are consistent with the hypothesis that insulin-like growth factor II acts as an autocrine growth factor for hepatocytes in addition to having a paracrine effect. They also indicate that primary culture of hepatocytes is a good model for further studies on insulin-like growth factor II gene regulation.

Animals↗

[Significance of isolated anti-HBs antibodies in subjects not vaccinated against hepatitis B viruses].

The significance of isolated anti-HBs antibodies in subjects not vaccinated against the hepatitis B virus (HBV) was investigated in 13 healthy blood donors. All were European and none had any risk factor for hepatitis B infection. Serological assays included HBV-DNA and anti-preS 2 antibody determinations which were all negative. After injection with hepatitis B vaccine (Hevac B), only one out of the 13 subjects exhibited an anamnestic response in favor of secondary immunization. Neutralization tests for serum anti-HBs antibody were positive in only 6 subjects. Our data suggest that in most cases isolated anti-HBs positivity does not correspond to true antibody; booster injection of HBV vaccine seems to be the best way of verifying that antibodies are really protective.

Adult↗

Is hepatitis C virus involved in hepatitis-associated aplastic anemia?

OBJECTIVE: To determine whether hepatitis C virus is involved in hepatitis-associated aplastic anemia. DESIGN: Retrospective analysis. SETTING: Bone marrow transplantation unit. PATIENTS: One hundred and eighteen patients with severe aplastic anemia, including 19 with hepatitis-associated aplasia, 61 with aplastic anemia of undetermined cause, and 38 with aplastic anemia related to an inherited syndrome or an acquired etiology. MEASUREMENTS AND MAIN RESULTS: There was no statistically significant difference in antihepatitis C virus antibodies between hepatitis-related aplastic anemia (15.8%; 95% CI, 4% to 36%) and aplasia of unknown (9.8%; CI, 5% to 22%) or known (7.9%; CI, 2% to 22%) cause. The antihepatitis C virus levels did not differ according to the cause of aplastic anemia. There was no relation between hepatitis C and hepatitis B virus serologies, regardless of cause. CONCLUSIONS: Hepatitis C virus is not a frequent cause of non-A, non-B hepatitis-associated aplastic anemia. Either a non-A, non-B, non-C hepatitis virus is involved in non-A, non-B hepatitis-related aplasia or hepatitis C virus prevalence is underestimated in patients with hepatitis-related aplasia, possibly as a result of immunologic defects.

Anemia, Aplastic↗

Chronic hepatitis in kidney allograft recipients.

98 HBsAg-positive and 31 HBsAg-negative kidney recipients were compared to assess the effect of renal transplantation on chronic liver disease and vice versa. Diagnosis was based on analysis of liver biopsy specimens including semiquantitative evaluation of histological features of chronic hepatitis. Serial specimens were examined: chronic liver disease occurred in 88% of HBsAg-positive patients and 4% of HBsAg-negative patients with normal liver at the time of transplantation. Liver abnormalities in the former were chronic persistent hepatitis (32%), chronic active hepatitis (51%), and cirrhosis (17%). Actuarial patient survival was similar in HBsAg-positive (78%) and HBsAg-negative (87%) patients, as was allograft survival (64% and 71%, respectively). In both HBsAg-positive and HBsAg-negative patients chronic alcohol consumption was more frequent in those with chronic liver disease than those without. These data suggest that renal transplantation may be appropriate for haemodialysis patients with chronic hepatitis whatever their HBV status.

Actuarial Analysis↗

Expression of insulin-like growth factor II (IGF-II) in human primary liver cancer: mRNA and protein analysis.

Insulin-like growth factor II (IGF-II) is a polypeptide growth factor thought to be involved in fetal tissue development. We previously showed an increased expression of IGF-II mRNA in human primary liver cancer. The present investigation was undertaken to characterize the overexpressed IGF-II transcripts and to determine whether they are translated into protein. Two cDNAs with distinct 5' untranslated regions, corresponding to IGF-II transcripts expressed in fetal liver, were isolated from a primary liver cancer. Complete nucleotide sequence analysis showed an identical open reading frame of 540 bp, encoding a predicted polypeptide identical to the IGF-II isolated from serum. An increased synthesis of IGF-II protein was demonstrated by a protein-binding assay in tumorous liver samples, the highest levels being found in primary liver cancers with the highest IGF-II steady state level. By contrast, serum IGF-II content was low in most of primary liver cancer cases analyzed. Altogether, the results indicate reexpression of IGF-II both at the mRNA and protein levels in primary liver cancer. This finding is consistent with IGF-II being a marker of liver cell differentiation. In addition, this growth factor might be involved in liver cancer progression by an autocrine and/or paracrine mechanism.

Adenoma, Bile Duct↗

Persistent hepatitis B virus infection of mononuclear blood cells without concomitant liver infection. The liver transplantation model.

We have investigated the recurrence of Hepatitis B virus (HBV) in 30 patients treated by orthotopic liver transplantation and given high doses of anti-HBs immunoglobulin. The polymerase chain reaction (PCR) assay showed no evidence of HBV DNA sequences in the liver of 23/24 patients who remained serum HBsAg-negative during a mean follow-up of 13 months (2-24 months) after OLT. However, the liver scored positive in all the 6 individuals in whom HBsAG reappeared. The PCR assay identified HBV DNA sequences in the peripheral blood mononuclear cells of 7 of 11 subjects who were serum HBsAG-negative and liver HBV DNA-negative by PCR. Therefore, this application of the sensitive PCR assay demonstrates persistent infection of PBMC in the absence of liver HBV--thus OLT provides a model for studying the interaction between HBV, PBMC, and the liver.

DNA, Viral↗

The polymerase chain reaction in the human immunodeficiency virus diagnosis.

The PCR technique detects HIV1 and HIV2 DNA and RNA sequences in mononuclear cells with high sensitivity. It allows therefore to analyse the mother to child HIV1 transmission. Moreover, in the near future, the quantification of the PCR products could allow the follow-up of the patients treated for HIV infection.

Child↗

Randomized controlled trial of adenine arabinoside 5'-monophosphate in chronic active hepatitis B: comparison of the efficacy in heterosexual and homosexual patients.

Twenty-two heterosexuals and 21 homosexuals with chronic active hepatitis B and who had HBsAg, HBeAg and hepatitis B virus DNA in serum were randomized separately to receive adenine arabinoside monophosphate or placebo. In the 10 heterosexuals and nine homosexuals who received placebo, no change in hepatitis B virus DNA level and HBeAg was observed. Among the patients who received adenine arabinoside monophosphate, seven of the 12 heterosexuals and five of the 12 homosexuals lost hepatitis B virus DNA; five heterosexuals and three homosexuals also lost HBeAg; one homosexual lost HBsAg. There was no significant differences in response between heterosexual and homosexual patients. When results were pooled, there was a significant effect of adenine arabinoside monophosphate on hepatitis B virus replication. None of the 19 patients who received placebo but 50% of the 24 patients who received adenine arabinoside monophosphate were negative for serum hepatitis B virus DNA at 10 months after treatment (p less than 0.001) and none of the 19 patients who received placebo and 33% of the 24 patients who received adenine arabinoside monophosphate were negative for HBeAg in serum (p less than 0.005). Retrospective analysis showed that disappearance of hepatitis B virus DNA after administration of adenine arabinoside monophosphate was more common (i) in patients with a low pretreatment hepatitis B virus DNA level than in patients with a high pretreatment hepatitis B virus DNA level (8/11 vs. 4/13, p less than 0.05); (ii) in patients with a high pretreatment ALT level than in patients with a low pretreatment ALT level (10/14 vs. 2/10, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hepatitis delta virus infection in French male HBsAg-positive homosexuals.

The prevalence and serological features of hepatitis delta virus infections were studied in a French population of chronic, non-drug addict, hepatitis B surface antigen carriers: 42 male homosexual patients were compared to 30 nonhomosexuals (20 who evidently had not been exposed to any of the usual hepatitis B virus-hepatitis delta virus risk factors and 10 hemodialyzed patients or kidney allograft recipients). Six of the 42 male homosexuals (14.3%) had at least one serological marker of hepatitis delta virus infection (hepatitis delta antigen, total and/or IgM anti-hepatitis delta antibodies). Serological follow-up was obtained for five of these patients over several months and confirmed the chronicity of the delta infection in at least four of the five subjects. Hepatitis delta antigen and hepatitis delta virus RNA were found in the liver and in the serum, respectively, of four of the five tested patients. Hepatitis B virus DNA was negative in the serum of five of the six hepatitis delta virus-positive homosexuals vs. only eight of 35 hepatitis delta virus-negative homosexuals (p less than 0.02). Human immunodeficiency virus was negative in all of the nonhomosexuals; its prevalence did not differ between the hepatitis delta virus-positive and -negative homosexuals: three were human immunodeficiency virus-positive among the six former vs. 15 among the 36 latter. Human immunodeficiency virus positivity was without obvious influence on hepatitis B virus replication, since among 35 hepatitis delta virus-negative homosexuals hepatitis B virus DNA was found in 80% of the human immunodeficiency virus-positive individuals and 70% of those who were human immunodeficiency virus-negative.

Adult↗

Liver collagen mRNA and serum amino-terminal peptide of type III procollagen (PIIINP) levels in patients with alcoholic liver disease.

We have investigated the alpha 1 (I), alpha 2 (I) and alpha 1 (III) liver collagen mRNA levels in 38 patients with alcoholic liver disease. The patients were divided into 3 groups according to the severity of their liver disease. Liver collagen mRNA levels were estimated by densitometric analysis after hybridization with the corresponding cDNA. Serum amino-terminal peptide of type III procollagen (PIIINP) was determined by radioimmunoassay in 30 patients. The results indicated that there was no increase but rather a decrease in the liver alpha 1 (I), alpha 2 (I) and alpha 1 (III) collagen mRNA in patients with the most severe liver lesions as compared to those with minimal changes. This decrease was significant for alpha 2 (I) and alpha 1 (III) cDNA probes. In contrast, serum PIIINP levels showed a positive correlation with the severity of the disease. Thus this study indicates that collagen accumulation in the liver as well as elevation of the serum PIIINP during the development of alcoholic liver disease probably reflects posttranscriptional events in collagen synthesis.

Collagen↗

Comparison of a non-radioactive hybridization assay for detection of hepatitis B virus DNA with the radioactive method.

Biotin and 32P-labelled HBV probes were compared in 150 sera analysed with a spot hybridization test. In 144 cases (96%) results were concordant. The non-isotopic procedure was therefore not only simple and rapid to perform, but also sensitive and specific. Since it overcame the problems associated with 32P, it allowed more diagnostic applications of HBV-DNA determination in serum.

Biotin↗

Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma.

Primary hepatocellular carcinoma (PHC), epidemiologically associated with chronic hepatitis B virus (HBV) infection, has historically been felt to be caused by the activation or introduction of an oncogene. However, transforming sequences from human PHC have not been reproducibly isolated. In this paper, evidence is presented that suggests PHC may result instead from the loss of an anti-oncogene. Seven of 12 human primary liver tumors tested against a panel of restriction fragment length polymorphisms (RFLPs) demonstrated loss of constitutional heterozygosity for markers on chromosome 4. Tumor and nontumor liver tissue were typed for 11 chromosome 4 RFLPs. In addition, at least one RFLP on nine other chromosomes (1, 2, 6, 7, 9, 11, 13, 14, and 17) was tested for allelic loss. Seven of nine tumors constitutionally heterozygous for chromosome 4q markers showed allele loss in tumor tissue. Six of the seven samples were jointly informative for both 4p and 4q markers. Five of the six demonstrated loss for only 4q RFLPs. In one individual, in which two samples were taken from distant locations within the same tumor, both samples showed loss of the same alleles. Among the other chromosomes informative for allele loss, one tumor showed changes on 13q. No other changes were observed in RFLPs located on the eight other chromosomes tested. These results indicate that an anti-oncogene may be located on 4q and suggest a mechanism for PHC and other cancers seroepidemiologically related to virus infection. Liver cancer caused by chronic HBV infection or other environmental agents may be linked through genetic events responsible for the loss of a tumor suppressor locus (anti-oncogene) located on chromosome 4.

Carcinoma, Hepatocellular↗

An epidemiological and clinical study of transaminase levels and hepatitis B antibodies in 1,100 blood donors.

In order to provide epidemiological and clinical information on surrogate testing of blood donations, the respective prevalences of serum hepatitis B virus (HBV) markers and elevated transaminase levels were studied in 1,100 blood donors according to their geographic origin and socioeconomic level. The frequency of serum HBV markers varied as a function of HBV endemicity in the country of origin; however, it was inversely correlated (p less than 0.05) to the socioeconomic level of the donors, even in those originating from countries of low HBV endemicity. There was no association between serum HBV markers and the increased transaminase level which was observed in 48 (4.3%) donors. Twenty-five of these accepted further clinical evaluation. A diagnosis appeared probable in 12 of the 25: alcohol in 5; drugs in 6; non-A, non-B hepatitis in 1. Seven of the remaining 13 subjects were more than 25% above ideal body weight. Transaminase activities determined at the time of clinical assessment were normal in 14. In addition, serum HBV DNA was found in 5 of 247 donors, even in the absence of any usual HBV marker and/or hypertransaminasemia. This could account for the few cases of B and B-like posttransfusion hepatitis which are known to still occur despite careful HBsAg screening of blood donors.

Biomarkers↗

[Prevalence of HBs antigen carriers and markers of B virus replication in a population of pregnant women, in France].

To assess the risk of perinatal B virus transmission in a population of French and immigrant women, 1,923 women were tested for HBs antigen and serological markers of B virus replication, i. e. HBe antigen and HBV DNA, during the last trimester of their pregnancy. The patients included in this study were French (n = 1,295 (67.3 per cent] and immigrant women (n = 628 (32.7 per cent] attending consultation in four public Parisian suburb hospitals. The immigrant population was composed of natives of the Mediterranean area or Portugal (64 per cent), West Africa (23 per cent), and South-East Asia (13 per cent). Serum HBsAg was tested by conventional radioimmunoassay. When present, HBeAg and antiHBe were tested by radioimmunoassay, and HBV DNA by the hybridization procedure. The overall HBsAg prevalence was 1.56 per cent. This high prevalence was in part explained by the large proportion of immigrants in whom it varied from 0.8 to 7.5 per cent according to their origin. Prevalence was 0.85 per cent in French women, higher than that usually admitted in France. Serological markers of viral replication (HBeAg and/or HBV-DNA) were more often present in the immigrants (4 out of 19) than in the French women (1 out of 11). Discrepancies between HBe status and HBV DNA were present in 4 out of the 30 HBs antigen positive women. Due to the possible high prevalence of HBV carriage in pregnant women, routine antenatal HBs antigen screening should be recommended in France. Such screening, associated with immunoprophylaxis of newborns at risk of contamination, can help in the prevention of perinatal transmission of hepatitis B virus.

Adolescent↗