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Biomedical subjects

G Gerken

Publications and source records attributed to G Gerken.

At least 217 records · Page 12Linked to original sources
PubMed1991

Chronic hepatitis delta virus (HDV) infection.

The Hepatitis Delta Virus (HDV) is a small RNA virus which replicates only in patients who are concurrently infected with hepatitis B virus (HBV). Delta hepatitis is endemic particularly in countries in the Mediterranean basin. In other parts of the world, HDV infection occurs among intravenous drug addicts and persons who receive multiple blood transfusion. HDV superinfection in a chronic HBV carrier often leads to severe chronic hepatitis and cirrhosis, whereas acute HDV and HBV co-infection is frequently associated with fulminant hepatitis. Diagnosis is usually based on the detection of HDV antigen in liver tissue and antibody to HDV (anti-HD) in serum. Nowadays, HDV antigen can also be detected in serum using immunoblot assay. The presence of HDV-RNA can now be confirmed by molecular biology techniques including polymerase chain reaction (PCR). Interestingly, up to 50% of patients with chronic HDV infection have in the serum autoantibodies against microsomal antigens of the human liver and kidney (LKM) and antibodies against the basal cell layer of the rat forestomach. Therapeutic approaches including interferon therapy and liver transplantation are still under discussion. This review discusses in detail some of the main features of chronic HDV infection.

Antigens, Viral↗
PubMed1990

Polymerase chain reaction to detect hepatitis B virus DNA and RNA sequences in primary liver cancers from patients negative for hepatitis B surface antigen.

BACKGROUND AND METHODS: The role of hepatitis B virus (HBV) in the course of patients with primary liver cancer who are negative for hepatitis B surface antigen has been debated. We used the polymerase chain reaction to evaluate 28 such patients for the presence of DNA and RNA sequences of the virus; 22 of these patients had associated cirrhosis. The patients were from areas with different prevalences of HBV infection (South Africa, Italy, France, and Japan). RESULTS: Antibodies to the surface and core antigens of HBV were detected in 10 of the 23 patients tested. HBV DNA sequences were detected in 17 of the 28 patients, including 8 of the 10 with HBV antibodies and 6 of 13 without HBV serologic markers. HBV RNA molecules were found in four of five tumors tested. CONCLUSIONS: Our investigation indicates that transcriptionally active HBV genomes are present in various geographic areas among patients with liver cancer who are negative for hepatitis B surface antigen. This observation is consistent with an etiologic role for the virus in the development of these tumors.

Adult↗
PubMed1990

Patients with type II autoimmune hepatitis express functionally intact cytochrome P-450 db1 that is inhibited by LKM-1 autoantibodies in vitro but not in vivo.

Liver-kidney microsomal-1 autoantibodies characterize a subgroup of autoimmune chronic active hepatitis. The liver antigen of liver-kidney microsomal-1 antibodies has been identified as cytochrome P450 db1, a microsomal enzyme catalyzing the oxidative metabolism of more than 20 drugs, including debrisoquine, sparteine and bufuralol. A genetic polymorphism (debrisoquin-sparteine polymorphism) is responsible for the lack of P450 db1 protein in the livers of 5% to 10% of Caucasians, leading to impaired drug metabolism and a distinct poor metabolizer phenotype. We investigated whether liver-kidney microsomal-1 positive autoimmune chronic active hepatitis patients express functionally intact P450 db1 in their livers. In four patients with liver-kidney microsomal-1 positive chronic active hepatitis, but not in five patients with various liver-kidney microsomal-1 negative liver diseases, the presence of circulating liver-kidney microsomal-1 antibodies was confirmed by immunofluorescence, radioimmunoassay and immunoblotting analysis using recombinant P450 db1. Moreover, only sera from liver-kidney microsomal-1 positive autoimmune chronic active hepatitis patients strongly inhibited the enzymatic activity of P450 db1 in human liver microsomes in vitro. Immunoblotting detected 50-kd P450 db1 protein in liver biopsy specimens from all patients. The in vivo function of P450 db1 was investigated by determining the metabolic ratio for sparteine and its 2-dehydro and 5-dehydro metabolites in 12-hr urine samples after oral administration of sparteine sulfate. In vivo P450 db1-mediated drug metabolism was of the extensive metabolizer phenotype and did not differ significantly between liver-kidney microsomal-1 positive (metabolic ratio = 1.15 +/- 0.32) and liver-kidney microsomal-1 negative (metabolic ratio = 1.18 +/- 0.48) patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Hepatic expression patterns of the large and middle hepatitis B virus surface proteins in viremic and nonviremic chronic hepatitis B.

The envelope of hepatitis B virus consists of large, middle, and small hepatitis B surface proteins. Recent data from in vitro studies suggest that intracellular expression and distribution of the three polypeptides may be variable. These observations in artificial expression systems prompted this analysis of the occurrence and distribution of the three hepatitis B surface proteins in the liver tissue of substantial viremic (hepatitis B virus DNA- and hepatitis B e antigen-positive) and low-viremic or nonviremic (hepatitis B virus DNA-negative, anti-hepatitis B e antigen-positive) carriers by specific monoclonal antibodies against large, middle, and small proteins. Patients with an active form of viral replication showed a prevalence of middle and small hepatitis B surface proteins in the liver. In nonviremic carriers, the large hepatitis B surface protein was the predominant intrahepatic antigen, a finding that was confirmed at the ultrastructural level by staining of the entire filaments of the viral envelope material in ground glass hepatocytes. The present data are thus consistent with observations in hepatitis B virus-transgenic mice and in transfected cell systems, suggesting that the different patterns of the envelope proteins in the liver may be due to different processing at the translational level.

Antibodies, Monoclonal↗
PubMed1990

Characterization of liver cytokeratin as a major target antigen of anti-SLA antibodies.

Anti-SLA antibodies characterize a newly defined subgroup of patients with autoimmune chronic active hepatitis. The aim of the present study was the immunochemical characterization of the target antigen(s) of anti-SLA antibodies. Anti-SLA-positive sera were found to contain high titres of anti-cytokeratin antibodies. In immunoblotting analyses with 100,000 x g supernatants of human liver homogenates (S-100) these sera recognized various proteins with a molecular mass of 40-60 kDa. These proteins were also recognized by monoclonal anti-cytokeratin antibodies. Two-dimensional co-electrophoresis and immunoblotting analysis of S-100 and liver cytokeratins showed that anti-SLA antibodies were primarily directed against cytokeratins, particularly against liver cytokeratin types 8 and 18. This was supported by affinity chromatography, immunofluorescence and absorption methods using anti-SLA sera.

Antibodies, Monoclonal↗
PubMed1990

[Echogenic splenic lesions--incidence and differential diagnosis].

In order to estimate the incidence and clinical relevance of echogenic focal lesions in the spleen, 121,372 ultrasound investigations from seven laboratories were evaluated. Ninety-two cases with echogenic lesions in the spleen were reviewed (incidence: 3.2 to 14.2 of 10,000 patients). Differential diagnosis included neoplastic tumors (17.4%; five metastases, three lymphomas, seven hemangiomas, one lymphangiomatosis), vascular disorders (17.4%: bleeding, infarct) and inflammatory focal lesions (8.7%; abscess, calcifications). Follow-up studies showed no change in size and pattern in a further 17.4% of the lesions, indicating benign disorders. Thirty patients suffered from a malignant condition with splenic metastasis or lymphomas in eight cases. In a further five patients, it was possible to confirm echogenic hemangiomas. There are no specific echographic patterns which differentiate hemangiomas from malignant tumors.

Diagnosis, Differential↗
PubMed1989

Treatment of chronic type B hepatitis with recombinant alpha-interferon induces autoantibodies not specific for autoimmune chronic hepatitis.

Recombinant human alpha-interferon is now under intensive investigation as therapy for chronic Type B hepatitis. Recent reports have suggested that prolonged alpha-interferon therapy may induce autoimmune reactions. We have evaluated the problem of autoimmunity related to alpha-interferon therapy by testing for 15 different antibodies in the sera of 31 patients treated with alpha-interferon. No patient had autoantibodies before treatment; 27 (87%) of 31 patients developed at least one autoantibody. Eleven patients had antinuclear antibodies and 21 had smooth muscle antibodies, both of which usually developed during alpha-interferon therapy. In contrast, antibodies to endocrine organs such as thyroid microsomal, thyroglobulin and parietal cell antibodies arose in 12 patients, but usually several months after alpha-interferon treatment. The appearance of these autoantibodies did not correlate with disease activity or response to alpha-interferon. No patient developed autoantibodies specifically associated with autoimmune liver diseases such as liver kidney microsomal antibodies, autoantibodies to soluble liver antigen and the primary biliary cirrhosis specific subtypes of antimitochondrial antibodies. These results suggest that prolonged alpha-interferon therapy can induce autoantibody production and, in susceptible patients, may lead to autoimmune disorders.

Antibody Specificity↗
PubMed1989

Immune blot analysis of viral surface proteins in serum and liver of patients with chronic hepatitis B virus infection.

The small and the middle surface proteins of hepatitis virus form either the virion or the 22 nm particle both of which are secreted. The large surface protein by itself remains cell bound in artificially transfected cell culture unless it is accompanied by an excess of the smaller protens. Its behavior in vivo is not yet well studied. Using specific monoclonal antibodies for immunoblotting, we found an abundance of small surface protein in the serum of chronic virus carriers and moderate amounts in the liver irrespective of viremia. The large surface protein was present in the serum and the liver of viremic carriers. In nonviremic carriers, the large protein was absent from serum, but in the liver a shorter form of the large protein was readily detectable. These findings suggest a complex regulatory mechanism of the viral surface protein depending on the expression of other viral gene products.

Adult↗
PubMed1989

Treatment of patients with chronic type B hepatitis and concurrent human immunodeficiency virus infection with a combination of interferon alpha and azidothymidine: a pilot study.

Six patients with chronic type B hepatitis and concurrent infection with the immunodeficiency virus were treated with 600 mg azidothymidine (AZT)/day and 3 X 10(6) units of interferon-alpha (IFN-alpha) every other day for a total of 4 months. None of the patients treated lost the hepatitis B virus (HBV). HBV-DNA concentrations were not significantly influenced by this treatment. Human immunodeficiency virus (HIV) infection was also not affected except for a transient rise in CD 4-positive cells in 2 individuals, who had initially low CD 4-positive cells. Treatment did not influence the presence of HIV-Ag in the serum. In conclusion, a combination therapy of IFN and AZT does not seem to be beneficial at the doses given and the time involved.

Adult↗
PubMed1988

Strategy for the characterization of autoantigens in autoimmune diseases. Investigation of the target antigens of antimitochondrial antibodies by radioimmunoassay, immunoblotting, monoclonal antibodies and affinity chromatography.

We present a strategy to characterize specific antigen/autoantibody systems using polyclonal sera from patients as a probe and crude antigenic preparations such as mitoplasts. Sera from patients with primary biliary cirrhosis (PBC) are characterized by at least one of two specific subtypes of antimitochondrial antibodies (AMA), anti-p48 or anti-p62. Immunoblotting of such sera with mitoplast preparations derived from human, rat and rabbit livers revealed three proteins of approximately 27, 48 and 68 kDa as target antigens. On the basis of the molecular weight of these antigens we were able to purify them by elution from preparative SDS gels. Immunization of NZB mice with the high molecular weight component (the 68 kDa antigen from human liver mitoplasts) elicited a monoclonal antibody. The 68 kDa protein was then isolated by affinity chromatography and may well represent the prime target antigen of anti-p62 antimitochondrial antibodies. This experimental approach could be applied to protein target antigens of other autoantibodies.

Animals↗
PubMed1988

Reactivation of chronic type B hepatitis: the effect on expression of serum HBV-DNA and pre-S encoded proteins.

Hepatitis B markers were studied in seven patients with reactivated liver disease. Reactivation of chronic type B hepatitis, as indicated by the reappearance of hepatitis B e antigen (HBeAg) in the serum, was characterised by the appearance of hepatitis B virus-DNA (HBV-DNA) in the serum. The expression of pre-S 1 encoded protein remained unchanged in five of seven patients, and poly-HSA as a marker for pre-S 2 encoded protein remained detectable in six of seven patients before and after reactivation of chronic hepatitis. The level of serum HBV-DNA correlated well with the level of liver enzymes, which rose from normal to various levels after reactivation of the liver disease. The data suggest that inflammatory activity of the liver disease is not related to the expression of pre-S encoded protein but to viral replication. Possibly pre-C and C-gene encoded antigens, which are produced together with viral nucleic acid and expressed on the surface of HBV-infected liver cells, play the key role in liver damage believed to be mediated by cytotoxic T cells.

Adolescent↗
PubMed1988

Immunochemical characterization of anti-acetylcholine receptor antibodies in primary biliary cirrhosis.

Although the presence of anti-mitochondrial antibodies is the main characteristic of primary biliary cirrhosis (PBC), other autoantibodies have been described in this disease. This study employs immunoblot methods to test whether the sera of PBC patients also contain antibodies directed against nicotinic acetylcholine receptors (AChR). We show that the majority of patients' sera indeed react with AChR just as sera of myasthenic patients do. In contrast, however, these anti-AChR antibodies do not lead to significant clinical symptoms of myasthenia. In all cases studied, PBC sera recognized a protein with the molecular weight of the alpha-chain of acetylcholine receptor (40 kDa). In addition, with both liver mitochondria and AChR-rich membranes as antigens, PBC sera reacted with proteins with apparent molecular weights around 68 kDa and the same pI values. This protein is not present in purified AChR preparations. These data suggest structural, if not functional, relationships between membrane components of liver mitochondria and muscle endplates.

Autoantibodies↗
PubMed1988

Expression of Pre-S-encoded proteins in sera of individuals chronically infected with hepatitis D virus.

The sera of 16 individuals chronically infected with the hepatitis D virus were analyzed for hepatitis B virus (HBV) markers. The majority of these patients had a non-replicative form of viral type B hepatitis as indicated by negative tests for HBeAg and HBV-DNA. Pre-S-encoded proteins were detected in 13/16 sera. Sera that were negative for polymerized serum albumin did also not contain pre-S1-encoded proteins. The presence of pre-S-encoded proteins is probably predominantly associated with 22-nm HBsAg forms present in large amounts in sera of individuals with chronic type D hepatitis.

Chronic Disease↗
PubMed1988

[Quantitative and qualitative findings of hepatitis B virus-associated antigens, receptors and antibodies in the course of the acute phase of hepatitis B infection].

UNLABELLED: Receptors for pHSA may be the links between HBV and hepatocytes. Therefore, we evaluated the correlation between serum binding activity for pHSA during the acute phase of hepatitis B in relation to the decrease of surface antigen concentration. METHODS: 130 sera from 22 patients with acute (HBeAg-positive) hepatitis B were obtained weekly during an average interval of 7 weeks after the onset of the disease. R-pHSA were tested by RIA in 4 titre steps (1:50, 1:500, 1:5000, 1:50,000). HBsAg was analysed quantitatively by RIA according to the standard serum of the Paul-Ehrlich-Institute.

Acute Disease↗
PubMed1988

[Detection of pre-S gene products in HBsAg carriers and in hepatitis B vaccines].

The immunogenicity and efficacy of different commercially available vaccines against hepatitis B virus (HBV) has been demonstrated in a number of controlled vaccination trials throughout the world. However, the significance of pre-S proteins in hepatitis B vaccines is still controversially discussed. Therefore, a radioimmunoassay (RIA) was developed to detect pre-S proteins in HBsAg-carriers as well as in different hepatitis B vaccines. This study confirmed the high amount of pre-S proteins as well as poly-albumin receptors in purified Dane particles and sera of patients with acute hepatitis B. The currently available plasma derived vaccine H-B-Vax and the recombinant hepatitis B vaccines Gen H-B-Vax and Engerix B yielded negative results in pre-S- and poly-albumin-receptor-RIAs. The plasma derived vaccine Hevac B Pasteur included pre-S encoded proteins. Future vaccination trials in man have to evaluate the role of pre-S antigens and antibodies in the pathogenesis and the protection of hepatitis B infection including recombinant pre-S vaccines which are under development.

Carrier State↗
PubMed1987

Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen.

Autoantibodies against a soluble liver antigen (SLA) were detected in 23 patients with HBsAg-negative chronic active hepatitis (CAH) but not in 502 patients with various other hepatic and non-hepatic disorders or 165 healthy blood donors. Anti-SLA-positive serum samples were negative for antinuclear and liver-kidney-microsomal antibodies, markers of two subgroups of autoimmune-type CAH, 6 anti-SLA-positive patients were negative for all autoantibodies sought. Most of the anti-SLA-positive patients were young women (2 men, 21 women; mean age 37 years) with hypergammaglobulinaemia (mean 3.2 g/l, range 1.8-5.3 g/l); 18 of the 23 patients had received immunosuppressive treatment and all responded well. Anti-SLA titres declined during therapy, corresponding to disease activity. Anti-SLA cannot be detected by immunofluorescence. SLA is not organ-specific or species-specific, but the highest concentrations were found in liver and kidney. Anti-SLA autoantibodies characterise a third subgroup of autoimmune-type CAH and will allow a better differentiation of HBsAg-negative CAH which has therapeutic consequences.

Adolescent↗