摘要:

AbstractDNA extracts from hepatocellular carcinomas of 13 patients from South Africa were examined for hepatitis B virus (HBV) DNA sequences by molecular hybridization using [32P]‐labeled recombinant, cloned, and purified HBV‐DNA. Eight patients were HBV carriers as demonstrated by the presence of hepatitis B surface antigen (HBsAg) in their serum, and each of these patients had HBV‐DNA sequences in hepatocellular carcinoma tissue. Five patients who were not HBsAg carriers, did not have HBV‐DNA in their tumors. In DNA extracts from all tumors of patients who were HBsAg‐positive, the HBV‐DNA was integrated into the host genome. The integration pattern was unique for each tumor, but HBV‐DNA bands of a given length were present in more than one specimen and in a human hepatocellular carcinoma cell line (PLC/PRF/5). These results suggest that integration of HBV‐DNA into the human genome occurs in conjunction with malignant

ISSN:0270-9139    

DOI:10.1002/hep.1840010102

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractA cytoskeleton fraction enriched in intermediate‐sized filaments and resistant to high and low salt buffer containing Triton X‐100 was prepared from dissociated mouse liver cells and mouse liver homogenates. One‐dimensional sodium dodecyl sulfate‐polyacrylamide gel electrophoresis revealed a family of polypeptides in the relative molecular weight (Mr) range from 41,000 to 55,000, with two polypeptides (component A, Mr55,000; component D, Mr48,000) as major constituents. Antibodies to isolated cytokeratin components of lower molecular weights (48,000 and 45,000 to 41,000) decorated, in indirect immunofluorescence microscopy, a distinct cytoplasmic filament meshwork in hepatocytes of various species whereas antibodies to higher molecular weight components were less or even not effective. The antibodies also reacted with cytokeratin filaments present in epithelial cells of various other organs and species, confirming the widespread occurrence of immunologically related cytokeratin filaments in epithelial tissues. The antibodies to higher molecular weight components showed a higher affinity to cytokeratin filaments of epidermis, stratified epithelia, and myoepithelial cells compared to epithelial cells of other organs, including small intestinal crypt epithelium and secretory cells of the submandibular gland. These observations further support the biochemical and immunologic heterogeneity in the cytokeratin family.Mallory bodies (MBs) present in murine and human livers specifically reacted not only with antibodies to lower molecular weight polypeptides, but also even more so with antibodies to higher molecular weight components, indicating (i) the relatedness of MB material to hepatocyte cytokeratin, and (ii) differences of exposed antigenic determinants of cytokeratin(s) during MB development. In polypeptide composition, MB material differed from hepatocyte cytokeratin by polypeptides of molecular weights in the range of 55,000 to 66,000, which is more reminiscent of the pattern of epidermal cytokeratin. The development of MBs was associated with severe derangement of the cytokeratin filament meshwork in the affected hepatocytes, as revealed by immunofluorescence microscopy, indicating that cytoskeletal material progressively coalesced and was incorporated into MBs. The results present the first demonstration of the hepatocyte cytokeratin meshwork and an example of a pathologic change of this structure. The observations suggest that liver disorders associated with MB development can be regarded as cytoskeleton d

ISSN:0270-9139    

DOI:10.1002/hep.1840010103

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractOral administration to mice of high doses of 4‐isothiocyano‐4′nitrodiphenylamine (amoscanate), a potent antischistosomal drug, produced focal necrotizing lesions of the large intrahepatic and extrahepatic bile ducts and the gallbladder. Coadministration of erythromycin and, to a somewhat lesser degree, of paromomycin, markedly reduced the effects of amoscanate on the biliary tract. These results suggest that amoscanate may be converted to a cholangiotoxic product by one or several constituents of the enteric bacterial flora. Since erythromycin does not affect the antischistosomal activity of amoscanate, coadministration of an antibacterial agent can reduce toxic effects of a drug while full chemotherapeutic activity is maintained. The possibility of toxic effects of metabolites of xenobioties produced by intestinal bacteria deserves attention and the experimental production of focal intrahepatic and extrahepatic cholangitis by such drug metabolites suggests a possible mechanism in human bile dis

ISSN:0270-9139    

DOI:10.1002/hep.1840010104

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractProline, a critical substrate for collagen synthesis, is increased in liver undergoing fibrosis. In mice with schistosomiasis, the incorporation of proline into collagen occurs within liver granulomas. To study the interaction of liver cells and granulomas in the development of fibrosis, we assayed the enzymes that catalyze the formation and degradation of proline in isolated granulomas and liver.Two sequential enzymes involved in the formation of proline from arginine are ornithine‐δ‐aminotransferase and Δ1‐pyrroline‐5‐carboxylate (P5C) reductase. Activities of both these enzymes in granulomas were approximately 10% of those in liver, expressed on the basis of DNA content.The enzymes involved in degradation of proline are proline oxidase and P5C dehydrogenase; both are present in liver cells. In isolated granulomas, activity of proline oxidase was minimal, and P5C dehydrogenase activity was absent. These findings suggest that the metabolism of proline within granulomas differs greatly from that in liver cells. Earlier studies showed that exogenous proline enters granulomas and is rapidly incorporated into collagen. The combined findings raise the possibility that granulomas serve as a proline trap. Proline can enter this compartment and can be incorporated into collagen; however, proline within granulomas cannot readily be diverted into other pathways by

ISSN:0270-9139    

DOI:10.1002/hep.1840010105

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractAcute ethanol administration results in increased hepatic NADH/NAD+ratio and inhibition of galactose elimination, tricarboxylic acid cycle activity, and fatty acid oxidation. To determine how this redox change is affected by chronic alcohol consumption and to assess the resulting metabolic consequences, we studied baboons which were fed alcohol as 50% of their total calories. Redox changes were evaluated through measurement of galactose eliminationin vivoand lactate/pyruvate ratios in liver slicesin vitro. The metabolic consequences of these changes were assessed through measurement of CO2production and fatty acid oxidation in liver slices and hepatic lipid accumulation. Chronic alcohol feeding resulted in attenuation of inhibition of galactose elimination, increase in the lactate/pyruvate ratio, and decrease in fatty acid oxidation which were caused by acute ethanol administration. These metabolic adaptations were associated with reduced accumulation of hepatic fat.

ISSN:0270-9139    

DOI:10.1002/hep.1840010106

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe hypothalamic‐pituitary‐gonadal axis was evaluated in two groups of age‐matched men with documented biochemical and histologic liver disease and compared to that of age‐matched normal controls. Basal testosterone levels (p<0.05), spermatozoa concentrations (p<0.01), and seminal plasma volume (p<0.01) were reduced in the alcoholics studied with liver disease, but not the hemophiliacs with liver disease when compared to the normal controls. No difference in estradiol levels was noted between groups. Basal follicle‐stimulating hormone and luteinizing hormone (LH) concentrations were increased (both p<0.01) in the alcoholics while only LH concentrations were increased (p<0.01) in the hemophiliacs compared to the normal controls. Gonadotropins (folliclestimulating hormone and LH) and testosterone responses to clomiphene and to luteinizing hormone‐releasing factor (LH only) in the alcoholic population studied, further distinguished the alcoholics from the hemophiliacs and the normal controls. The basal levels of the other anterior pituitary hormones (growth hormone and thyroid‐stimulating hormone) as well as their provocative responses to thyrotropin‐releasing hormone also distinguished the alcoholics from the hemophiliac population. Based upon these results, we propose that factors other than the liver diseaseper seare responsible for the disturbances of hypothalamic‐pituitary‐gonadal function observed in men with biochemically as well as histologically advanced s

ISSN:0270-9139    

DOI:10.1002/hep.1840010107

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe disposition of chlordiazepoxide (Librium®) and diazepam (Valium®), compounds which are initially degraded by oxidative processes, differs from that of oxazepam (Serax®) and lorazepam (Ativan®), drugs which are inactivated by conjugation with glucuronic acid. Liver disease and cimetidine impair the elimination of the former agents, but not the latter two benzodiazepines. In addition, ethanol inhibits the metabolism of chlordiazepoxide and diazepam. The present studies were performed to determine the effect of short‐term ethanol administration on glucuronidation and elimination of lorazepam in dogs and humans. Because, in dogs, lorazepam has a high extraction ratio (approximately 0.9) with an anticipated large presystemic elimination, the influence of ethanol on the presystemic (first‐pass) elimination of lorazepam was determined. Administration of p.o. lorazepam to five healthy dogs 1 hr after i.v. saline or ethanol (3 gm/kg) reduced the presystemic elimination of lorazepam by 52% (p<0.05). In man, lorazepam has a low (approximately 0.05) extraction ratio and only a small first‐pass effect. Short‐term administration of ethanol (0.8 gm/kg followed by 0.5 gm/kg p.o. every 5 hr for four doses) reduced i.v. lorazepam clearance by 18% (p<0.03). In dogs and man, ethanol did not significantly alter lorazepam t½, plasma protein binding, or distribution volume (Vdβ). The results suggest that short‐term ethanol administration impairs the conjugation of lorazepam

ISSN:0270-9139    

DOI:10.1002/hep.1840010108

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractIn our double‐blind randomized trial of methylprednisolone vs. placebo in severe viral hepatitis, 16 patients with hepatitis B (8 on steroid, 8 on placebo) were followed for at least 4 weeks. Four of the eight patients receiving methylprednisolone eventually died and all patients on placebo survived. Despite marked reduction in serum IgG in steroid‐treated patients, the decline in HBsAg titer and disappearance of Dane particle markers was the same in both treatment groups. A nonspecific depression of anti‐HBc was noted in patients given steroid. There is no evidence that corticosteroid therapy accelerates viral replication when the acute hepatitis is s

ISSN:0270-9139    

DOI:10.1002/hep.1840010109

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractAutopsy studies of two infants, one a newborn, the other 4 months old, revealed massive amounts of iron in lysosomes of hepatocytes and pancreatic acinar cells. Iron, which had been transported across the placenta, accumulated in the same cell types as in adults with primary and secondary hemochromatosis. Hemosiderin was found in cardiac muscle cells, gastric and intestinal glands, and endocrine and exocrine organs including pituitary, thyroid, adrenals, islets of Langerhans, and sublingual and sweat glands. The liver was the most affected organ and the normal hepatic architecture was replaced by hepatocytes which were arranged in clusters, pseudoacinar structures, and multinucleated giant cells embedded in a collagen matrix. The islets of Langerhans were hyperplastic and hypertrophic. Ten similar cases, in five families, have been described; no patients lived longer than 4 months. Neonatal iron storage disease is clinically and pathologically distinct from Zellweger's cerebrohepatorenal syndrome and hypermethioninemia (tyrosinemia) neonatal diseases in which large stores of iron are present in hepatocytes. No abnormalities in serum iron, ferritin, or transferrin concentrations were detected in five parents of the affected children.

ISSN:0270-9139    

DOI:10.1002/hep.1840010110

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe liver histopathology in 40 liver biopsies from 24 patients with verified chronic common bile duct stenosis due to chronic alcoholic pancreatitis has been reviewed code‐blinded. This represents an 8% prevalence of this complication in approximately 300 patients with alcoholic pancreatitis screened biochemically for alkaline phosphatase>two‐fold for>1 month. The majority were anicteric with no symptoms other than from acute exacerbations of chronic pancreatitis. Biliary obstructive liver histopathology of varying severity was diagnosed in 19 patients (79%), seven of whom (29%) had secondary biliary cirrhosis. In 3 of these 7 cases, progression to biliary cirrhosis was documented with sequential biopsies. The remainder demonstrated this histologic picture when first diagnosed, supporting the insidious nature of this process. Stromal edema of the portal tracts, increased portal connective tissue, and marked proliferation of interlobular bile ducts and ductules were the most striking histologic features. Histologic cholangitis, although frequent, was generally mild or absent, reflecting the incomplete nature of the duct obstruction. Features of alcoholic liver disease were observed in only two cases. The results indicate that (1) chronic alcoholic pancreatitis with incomplete duct obstruction frequently causes secondary biliary cirrhosis, (2) significant alcoholic liver disease very infrequently coexists with persistent common bile duct stricture from alcoholic pancreatitis, and (3) surgical biliary decompression should be considered in any patient with documentedpersistentcommon bile duct stenosis from alcoholic pancreati

ISSN:0270-9139    

DOI:10.1002/hep.1840010111

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY