摘要:

AbstractAntibodies reacting in immunofluorescence with the basal cell layer of rat forestomach (BCLA) have been detected in 36 of 121 (30%) hepatitis B virus (HBV)‐mediated chronic liver disease (CLD), in 1 of 30 (3%) HBV‐negative CLD, in 3 of 36 (8%) alcoholic liver disease (with no correlation with serum HBV markers), in 1 of 25 (4%) primary biliary cirrhosis, in none of 19 HBV‐related HBsAg‐negative CLD and 60 healthy blood donors. Of 352 hospitalized patients with miscellaneous diseases (including immunological conditions), the antibodies were found in four (1%).In the 36 BCLA positive cases from HBV‐mediated CLD, evidence of chronic delta infection was found in 34. The overall prevalence of BCLA in 68 delta cases was 50% (58% in chronic active hepatitis, 46% in cirrhosis), and in 28 delta negative cases was 4% (p1:640).The high titer BCLA has to be considered a marker of chronic delta infection in

ISSN:0270-9139    

DOI:10.1002/hep.1840040601

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThe A, B, C and DR locus specificities of the human leukocyte antigens system (HLA) were determined in 45 delta‐positive and 44 delta‐negative Italian patients, all with HBsAg‐positive chronic active liver disease; controls were 526 healthy Italian blood donors matched for age, sex and geographical origin. HLA‐A, B, C gene frequencies were not significantly changed. In delta‐positive patients, the frequencies of the DR locus specificities were: DR2, 37.8%; DR3, 20%; DR4, 11.1%. In the delta‐negative patients, the frequencies were: DR2, 13.6%; DR3, 36.4%; DR4, 0%. Control frequencies were: DR2, 19.4%; DR3, 17.1%; DR4, 18.5%. The corrected p values of the differences between controls and delta‐positive patients were: DR2, pc= 0.046; DR3, pc= NS (not significant); DR4, pc= NS. The corrected p values of the differences between controls and delta‐negative patients were: DR2, pc= NS; DR3, pc= 0.03; DR4, pc= 0.002. These findings show that: (a) DR3, a genetic marker of autoimmunity, might assist the establishment of chronic HBsAg liver disease in the absence of delta superinfection; (b) DR2 is linked with failure to clear the delta agent, and (c) DR4 may protect from virus B persistence. Identification of adventitious factors such as delta may help uncover a subgroup of HBsAg carriers who are genetically predisposed to develop chroni

ISSN:0270-9139    

DOI:10.1002/hep.1840040602

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractHepatitis B virus and hepatitis delta virus co‐infection in drug addicts has been well described in Europe, the latter agent appearing to have been introduced there in the mid‐1970's. Currently, similar data are scanty among United States addicts. We therefore reevaluated 99 drug addicts from three different geographic locations in the United States who had participated in a Veterans Administration Cooperative Study between 1972 and 1975. Almost all were asymptomatic, and all had been subjected to liver biopsy because of prolonged aminotransferase abnormalities. Stored sera were tested for antibody to hepatitis delta antigen (anti‐HD) by radioimmunoassay and available liver biopsies examined for hepatitis delta antigen (HDAg) by immunofluorescence.Overall, 19.2% were HBsAg positive, 9.1% HBeAg positive, 90% anti‐HBc positive and 10.1%, positive for anti‐HD. Anti‐HD was identified in 42.1% of addicts who were HBsAg positive and in 3.3% who were anti‐HBs positive. No correlation was found between HBeAg and anti‐HD, but anti‐HD was present significantly more frequently in those with chronic active hepatitis than in those with chronic persistent hepatitis. We conclude that hepatitis delta virus infection is common in HBsAg‐positive drug addicts in the United States dating back to at least 1972 a

ISSN:0270-9139    

DOI:10.1002/hep.1840040603

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractHBsAg from plasma of chronic hepatitis B carriers was purified by affinity chomatography using a mouse monoclonal antibody specific for HBsAg. Elution with buffer at two different pH values separated HBsAg into two fractions: one contained high amounts of immune complexes associated with HBsAg; the other contained larger quantities of the HBsAg polypeptides P24 and GP27 and only small amounts of immunoglobulin. When compared for effects on stimulating the proliferative response of freshly isolated lymphocytes and an HBsAg‐specific T cell clone, the HBsAg fraction containing a high proportion of immunoglobulin was much more potent than HBsAg with low amounts of immunoglobulins or pure HBsAg, which was isolated from the culture supernatant of the human hepatoma cell line (PLC/PRF/5). The plasma‐derived HBsAg with low amounts of complexed immunoglobulins became more immunogenic in the presence of an anti‐HBsAg monoclonal IgG. The present results, combined with earlier findings, suggest that HBsAg associated with immune complexes is a more potent stimulator of T cells than purer HBsAg preparations due to an increase in the efficiency of monocytes to capture the antigen through binding to immune complexes for subsequent processing and presentation of the antigen. These observations could be of relevance for the preparation of effective hepatitis B vaccines from recombinant DNA and peptide synthesis technol

ISSN:0270-9139    

DOI:10.1002/hep.1840040604

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractLiver sections were stained with orcein, and duck hepatitis B virus was identified in sera and livers by the hybridization technique in 106 ducks (44 Chinese ducks, 15 Japanese ducks and 47 Japanese ducklings). Orcein‐positive hepatocytes were found in 18 of 38 (47%) duck hepatitis B virus DNA seropositive ducks, and only in 3 of 68 (4%) seronegative ducks. The three ducks were all from a heavily infected flock in southern China.Serial analyses of viral DNA by Southern blot and spot hybridizations in experimentally infected Japanese ducklings revealed a dissociation or a time gap between the amount of viral DNA in serum and the emergence of orcein positive hepatocytes. Orcein‐positive hepatocytes were generally associated with prolonged presence of viral infection for at least 4 to 6 months. These findings support the clinical hypothesis that the presence of orcein‐positive hepatocytes indicates persistent rather than acute infection.Since orcein‐positive hepatocytes have been seen in infection with hepatitis B, woodchuck hepatitis, ground squirrel and duck hepatitis B viruses, accumulation of orcein‐positive material in liver cells may be one of the common properties these viruses share. This stain may be utilized for screening new hepatitis B virus‐l

ISSN:0270-9139    

DOI:10.1002/hep.1840040605

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThe effect of a short course of prednisone therapy on serum IgM type antibody to the hepatitis B core antigen (anti‐HBc IgM) was studied in 14 male patients with chronic active type B hepatitis. Eleven patients (78.5%) became positive for serum anti‐HBc IgM either during or shortly after prednisone withdrawal. Detection of anti‐HBc IgM correlated with an increase in hepatitis B virus specific DNA‐polymerase activity and was followed by a rise in serum transaminase levels. Six patients with histologic evidence of cirrhosis developed anti‐HBc IgM which lasted six or more months after prednisone therapy and had a rapid onset of hepatic decompensation manifested by encephalopathy with ascites and/or variceal bleeding. In 17 untreated chronic active type B hepatitis patients who served as controls, anti‐HBc IgM was detected at low levels in only a single serum sample from each of two patients during the same observa

ISSN:0270-9139    

DOI:10.1002/hep.1840040606

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThe effect of 4–(3,7,ll,15‐tetramethyl‐6,10,14‐hexadecatrienoyl)morpholine (E‐0712), a new synthetic compound, on liver injury induced by two hepatotoxins in rats was studied. Oral doses of E‐0712 four times at 0, 6, 12 and 18 hr significantly attenuated elevated SGPT values and prolonged prothrombin time (PT) at 24, 36, 48, 60 and 72 hr in rats with a single s.c. dose of D‐galactosamine in which SGPT values and PT reached the peak within 48 hr. In cases in which a dose of carbon tetrachloride (i.p.) produced peak SGPT values and PT within 36 hr attenuation occurred likewise at 24, 36 and 60 hr. In the control and E‐0712‐treated rats dosed with D‐galactosamine or carbon tetrachloride, SGPT values were positively correlated with PT at 24 hr. In addition, morphological degrees of acidophilic body formation or centrizonal necrosis were significantly reduced by E‐0712. These results suggest that E‐0712 protects against liver injury, particularly hepatocellular necrosis, induced by D‐galactosamine and car

ISSN:0270-9139    

DOI:10.1002/hep.1840040607

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThis report describes immunocytochemical and ultrastructural methods which led to the identification of Reovirus type 3 (Reo‐3) in the porta hepatis of a patient with extrahepatic biliary atresia. The study indicates that Reo‐3 antigenic sites are demonstrable by the avidin‐biotinylated complex peroxidase method following formalin fixation and paraffin embedding, but are destroyed by freezing and thawing prior to fixation. Deparaffinization of the block and subsequent rembed‐ding in epon‐araldite did not alter immunoperoxidase staining. This procedure offered the advantage of higher light microscopic resolution of semithin (1 jtm) sections and assisted in the selection of specific areas for ultrastructural studies.Localization of Reo‐3 in extrahepatic biliary atresia was confined to a biliary remnant in which there were acutely inflammed, partially necrotic microscopic ducts. Electron microscopic examination of the immunoreactive sites revealed virus‐like particles similar in appearance to Reo‐3 particles in infected tissue culture cells. The observations presented here support previously reported serologic data which have shown an association between Reo‐3 infection and extrahepati

ISSN:0270-9139    

DOI:10.1002/hep.1840040608

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractValproic acid (VPA), its unsaturated metabolites and pent‐4‐enoate (4‐PA) were studied for potential hepatotoxicity in rats. 4‐PA, 4‐en‐VPA and 2,4‐dien‐VPA were potent inducers of microvesicular steatosis in young rats. Microvesicular steatosis induced by the 4‐en‐VPA was accompanied by ultrastructural changes characterized by myeloid bodies, lipid vacuoles and mitochondrial abnormalities. Myeloid bodies and lipid vacuoles were seen to a lesser extent in 2,4‐dien‐VPA and 4‐PA‐treated rats. VPA failed to induce discernible liver lesions in young rats even at near lethal doses of 700 mg per kg per day. The drug did, however, induce hepatic lipid accumulation in mature rats and in young rats dosed concomitantly with phenobarbital. β‐oxidation inhibition and several other biochemical alterations were observed in rats dosed with VPA, its unsaturated metabolites and 4‐PA. It was suggested that β‐oxidation inhibition observed in both VPA and en‐metabolite‐treated rats occurred by different mechanisms. VPA inhibits by a transient sequestering of CoA while the CoA esters of some en‐V,PA‐metabolites, particularly 4‐en‐VPA, inhibit

ISSN:0270-9139    

DOI:10.1002/hep.1840040609

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY

摘要:

AbstractThe role of metabolites in valproic acid (VPA)‐associated hepatotoxicity was studied in rats. The most steatogenic mono‐unsaturated metabolite, 4‐en‐VPA, caused the greatest changes in indicators of β‐oxidation inhibition (dicarboxylic aciduria, β‐hydroxybutyrate reduction); however, the biochemical effects were much less pronounced than those reported for hypoglycin. Steatosis in VPA‐treated rats occurred only at nearly lethal doses. Phenobarbital induction was confirmed as a predisposing factor; however, it appeared not to greatly enhance production of 4‐en‐VPA or its recognized metabolites, which collectively comprised only 0.5% of the dose. Elevated oxo‐VPA metabolites in serum and 2‐propylglutarate in liver were associated with toxicity. Among the newly discovered minor metabolites with possible biologic effects were diols (suggesting epoxide precursors) and a series of dienes and trienes. The rarity of severe human hepatotoxicity indicates that, normally, β‐oxidation inhibition is compensated, and cellular defense mechanisms prevail over reactive metabolites. This requires adequate nutrition; on the other hand, severe glycogen depletion may promote toxicity by compromising glucuronidation, the major clearance route. Other literature comments are also supported: (i) caution is indicated for patients with various unusual congenital disorders (e.g., organic acidurias or other mitochondrial defects), and (ii) monotherapy obviates both the predisposition to toxicity and the requirement of large doses to

ISSN:0270-9139    

DOI:10.1002/hep.1840040610

出版商:W.B. Saunders    

年代:1984

数据来源: WILEY