摘要:

AbstractTwenty‐one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given α‐interferon for chronic hepatitis B virus infection. In those patients who had received a minimum of 90 million units per m2total dose over 12 weeks, a negative anti‐human immunodeficiency virus antibody status (p<0.001), chronic active hepatitis on liver biopsy (p<0.005), high AST level (p<0.001), low hepatitis B virus DNA level (p<0.001) and a history of acute hepatitis (p<0.005) were all associated with an increased likelihood of response on univariate analysis. On stepwise logistic regression analysis, hepatitis B virus DNA, AST and a history of acute hepatitis predicted response independently (p85 IU per liter, which predicted response in 77% with a specificity of 79% (p<0.001). The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of<2 years duration (

ISSN:0270-9139    

DOI:10.1002/hep.1840100502

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractWe previously described a cytoplasmic antigen, detected by monoclonal antibodies, in hepatocytes of chimpanzees experimentally infected with the parenterally transmitted form of non‐A, non‐B hepatitis virus or with the hepatitis delta virus. The expression of this antigen appears to be a host‐specified response to infection with these two hepatitis viruses but not with hepatitis A virus, hepatitis B virus or enterically transmitted non‐A, non‐B hepatitis virus. To determine whether this antigen, found in parallel with the hepatocyte cytoplasmic structures described previously, is associated with interferon, as suggested by others, we studied by immunofluorescence liver biopsies from chimpanzees treated with an interferon inducer or exogenous interferon for the presence of the antigen. In two hepatitis B virus carrier chimpanzees and one normal chimpanzee treated with the interferon inducer polyinosinic‐poly‐ribocytidylic acid‐poly‐l‐lysine carboxymethylcellulose, the antigen became detectable in hepatocytes within 2 weeks of initiation of the treatment, remained detectable throughout the treatment and disappeared within 4 weeks after treatment was terminated. Electron microscopy revealed that the biopsies positive for the antigen exhibited the hepatocyte cytoplasmic changes; convoluted membranes and microtubular aggregates, identical to those described originally for chimpanzees infected with non‐A, non‐B hepatitis virus. The antigen was not detected in any of the biopsies from a control chimpanzee that received only the carboxymethylcellulose used to stabilize the interferon inducer. In addition, liver biopsies obtained from a hepatitis B virus carrier chimpanzee during treatment with exogenous human leukocyte interferon were found to be positive for the antigen as well. It is likely that expression of this antigen and induction of the hepatocyte cytoplasmic structures are a host response to interferon induced by non‐A, non‐B hepatitis virus and hepat

ISSN:0270-9139    

DOI:10.1002/hep.1840100503

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractWe investigated the production of tumor necrosis factor α by peripheral blood mononuclear cells of patients with chronic liver disease and its association with hepatitis activity. Tumor necrosis factor α production was measured with an enzyme‐linked immunosorbent assay. Tumor necrosis factor α production by peripheral blood mononuclear cells stimulated with recombinant γ‐interferon of patients with chronic active hepatitis (5.8 ± 4.0 units per ml, p<0.05) and patients with cirrhosis (4.1 ± 2.1 units per ml, p<0.05) was significantly increased when compared with controls (2.5 ± 1.6 units per ml). Tumor necrosis factor α production by peripheral blood mononuclear cells stimulated with a combination of recombinant γ‐interferon and recombinant interleukin 2 of patients with chronic persistent hepatitis (5.8 ± 3.8 units per ml, p<0.05), patients with chronic active hepatitis (8.9 ± 3.0 units per ml, p<0.001) and patients with cirrhosis (6.7 ± 3.2 units per ml, p<0.05) was significantly increased in comparison with controls (3.3 ± 1.8 units per ml). Tumor necrosis factor α production of patients with chronic active hepatitis was significantly higher than that of patients with chronic persistent hepatitis ( p<0.05). There was a significant correlation (r = 0.5699, p<0.005) between tumor necrosis factor α production and histologic activity index in patients with chronic persistent hepatitis or chronic active hepatitis. These findings show that tumor necrosis factor α production is increased in chronic liver disease and that the increased tumor necrosis factor α production is related

ISSN:0270-9139    

DOI:10.1002/hep.1840100504

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractLiver needle biopsies from patients with non‐A, non‐B chronic active hepatitis and so‐called abnormal bile duct epithelium were studied with a three‐dimensional method. Photographs of bile duct structures in serial sections were transferred to acrylic plates. Five bile duct lesions of a not previously described diverticular type were revealed. The diverticuli were of varying shape with a diameter of 30 to 110 μ and a length of 75 to 150μm budding from small (12 to 25μm), slightly ectatic bile ducts. The diverticular epithelium was disordered. Some cells appeared as bile duct cells, but most were larger, with rounded nuclei, prominent nucleoli and abundant eosinophilic cytoplasm, sometimes with periodic acid‐Schiff‐positive, diastase‐resistant granules. The lesions were only partly surrounded by a basement membrane. They were all embedded in a tight mononuclear inflammatory infiltrate associated with pronounced periportal piecemeal necrosis. In two cases, a germinal center was adjacent to the epithelium.The pathogenesis of the diverticular bile duct lesion is unknown, but the diverticuli probably represent Hering ducts and groups of periportal liver cells which have escaped the pi

ISSN:0270-9139    

DOI:10.1002/hep.1840100505

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractIn preparation for studies using gene transfer, we have identified transcriptional control elements which are active in primary rat hepatocytes. We used plasmids which were constructed so that the promoter or enhancer of interest initiated transcription of the bacterial chloramphenicol acetyltransferase (CAT) gene. Plasmids were introduced into primary rat hepatocytes in culture, into Hep G2 cells and other human and animal cell lines and into bone marrow stromal cells, and CAT activity was assayed after 48 hr.In primary rat hepatocytes, the highest CAT activity was obtained with plasmids carrying the Rous sarcoma virus long terminal repeat (pRSVCAT), or the SV40 early region promoter and enhancer (pSV2CAT). Hepatocytes carrying the murine cytomegalovirus immediate early promoter (pUCRNmCMVX/HCAT) also had appreciable CAT activity. No CAT activity was detected in rat hepatocytes carrying pSVOCAT (a promoterless construct), pUCRNtKCAT (herpes simplex thymidine kinase gene promoter), pLPVCAT (lymphocytotrophic papovavirus promoter) and pHBV1CAT (hepatitis B virus enhancer and core gene promoter). Therefore, for future studies of gene transfer in primary rat hepatocytes, the Rous sarcoma virus long terminal repeat or the SV40 early region promoter and enhancer can be effectively used to drive gene expression.Hep G2 cells carrying pHBV1CAT had high CAT activity. Hep G2 cells carrying pHBV2CAT (similar to pHBV1CAT, but with the hepatitis B virus sequences in reverse orientation with respect to the CAT sequences) and pHBV3CAT (similar to pHBV2CAT, but hepatitis B virus sequences are separated from the CAT sequences by about 700 bases) also expressed CAT activity, but not as strongly as with pHBV1CAT. The hepatitis B virus enhancer and core gene promoter were also active in human nonliver cell lines but were virtually inactive in nonhuman cell lines.

ISSN:0270-9139    

DOI:10.1002/hep.1840100506

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractSystemic endotoxemia has been observed in patients with acute and chronic liver failure, and bacterial endotoxin is known to increase vascular permeability. We investigated in the normal rat the effects of intraportal endotoxin administration and the possible mediation of these effects by platelet‐activating factor. Injection of endotoxin lipopolysaccharide (10 and 25 mg per kg) in the rat resulted in rapid ascites formation, as well as systemic hypotension, hemoconcentration and acute erosions of the gastrointestinal mucosa. These effects were significantly attenuated by pretreatment with L652,731 and CF‐3988, specific platelet‐activating factor antagonists. Administration of 25 mg per kg endotoxin also resulted in significant elevations of plateletactivating factor biosynthesisin vitroby samples of duodenum, liver and lung. The effects of endotoxin were mimicked by intraportal infusion of platelet‐activating factor (50 ng per kg per min), which induced ascites and gastrointestinal lesions. Platelet‐activating factor reduced circulating plasma volume and increased peritoneal permeability to albumin as assessed by the ascites to plasma ratio of labeled albumin. These results, therefore, support a role for platelet‐activating factor in mediating endotoxin‐induced ascites and gastrointest

ISSN:0270-9139    

DOI:10.1002/hep.1840100507

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractSince interferons have been shown to affect the synthesis of matrix proteins such as collagen in severalin vitrosystems, the potential role of γ‐interferon in inhibiting hepatic fibrosis was investigated. Hepatic cells, consisting primarily of hepatocytes, were treated with recombinant γ‐interferon for 24 hr. Northern blot hybridization showed that γ‐interferon treatment caused a profound decrease in pro‐α2(I)collagen mRNA levels but an increase in β‐actin mRNA content. The effects of γ‐interferon were then studied in anin vivomodel of hepatic fibrogenesis, murine schistosomiasis.Schistosoma‐infected mice were treated with daily i.m. injections of γ‐interferon for a 4‐week period starting 4 weeks after the initial infection. γ‐Interferon treatment decreased collagen deposition as determined by histologic evaluation and measurement of total liver collagen content. Northern blots showed Types I and III procollagen mRNA levels for treated, infected animals to be only 32 and 29% that of infected controls, but β‐actin mRNA levels were significantly elevated. These results indicate a potential role for γ‐interferon

ISSN:0270-9139    

DOI:10.1002/hep.1840100508

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractTo determine whether a serum parameter of collagen metabolism, serum procollagen type III peptide, correlated with hepatic collagen in a model of diet‐induced fibrosis, rats were fed a control or cirrhogenic diet for 6 months and treated with either subcutaneous vehicle or the hepatoprotective prostaglandin 16,16‐dimethyl prostaglandin E2 (100 μg per kg) twice daily. Pair‐fed rats from each group were killed after 2, 4 or 6 months. The value of serum procollagen type III peptide to body weight integrated over time (Kt) correlated linearly with hepatic hydroxyproline content (r = 0.97) at killing time t. Good correlations were also seen between Ktand histopathological assessment of aniline blue‐stainable collagen (r = 0.93) and between the histopathology and hydroxyproline content (r = 0.97). Rats receiving 16,16‐dimethyl prostaglandin E2had lower values of all three parameters compared to rats receiving vehicle, confirming the previously demonstrated hepatoprotective effect of 16,16‐dimethyl prostaglandin E2. The excellent correlation between Ktand the two other traditional parameters of hepatic collagen suggest that sequential measurements of serum procollagen type III peptide can be used to predict alterations in liver collagen deposi

ISSN:0270-9139    

DOI:10.1002/hep.1840100509

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractWe have previously reported the detection of a 37 kD liver protein‐acetaldehyde adduct in rats fed alcohol chronically with the AIN'76 diet. It was surprising that only one liver protein‐acetaldehyde adduct was found. In this report, we have tried to detect additional protein‐acetaldehyde adducts by electroimmunotransblot with rabbit anti‐hemocyanin‐acetaldehyde adduct IgG and to further characterize the 37 kD liver protein‐acetaldehyde adduct. Sensitivity of electroimmunotransblot increased 10‐to 20‐fold when alkaline phosphatase‐linked antibody was used in place of horseradish peroxidase, but only one protein‐acetaldehyde adduct band was detected in liver. Feeding rats the Lieber‐DeCarli alcohol diet also did not produce more protein‐acetaldehyde adduct bands in electroimmunotransblot. Addition of cyanamide, an aldehyde dehydrogenase inhibitor, to the AIN'76 alcohol diet greatly increased the intensity of the 37‐kD protein‐acetaldehyde adduct band on electroimmunotransblot but did not produce other bands. The 37 kD protein‐acetaldehyde adduct decayedin vivowith a half‐life of 4 days when alcohol was removed from the diet. The 37 kD protein‐acetaldehyde adduct in liver is cytosolic. Its interaction with anti‐hemocyanin‐acetaldehyde adduct IgG was blocked by polylysine‐acetaldehyde adduct and polytyrosine‐acetaldehyde adduct. It could be removed by immunosorption with anti‐hemocyanin‐acetaldehyde adduct IgG‐bound immunoresin. When immunoblotted with anti‐alcohol dehydrogenase and anti‐aldehyde dehydrogenase antibodies, the alcohol dehydrogenase and aldehyde dehydrogenase bands in liver of alcoholfed rats showed identical intensities before and after immunosorption. These data indicate that: (i) the 37 kD protein‐acetaldehyde adduct is neither alcohol dehydrogenase nor aldehyde dehydrogenase; (ii) its interaction with anti‐hemocyanin‐acetaldehyde adduct IgG is by way of acetaldehyde adducts of ϵ‐ and/or α‐amino groups; (iii) its formation and decay in

ISSN:0270-9139    

DOI:10.1002/hep.1840100510

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractThe effects of chronic ethanol feeding on hepatic lipid peroxidation, ascorbic acid, glutathione and vitamin E levels were investigated in rats fed low or adequate amounts of dietary vitamin E. Hepatic lipid peroxidation was significantly increased after chronic ethanol feeding in rats receiving a low‐vitamin E diet, indicating that dietary vitamin E is an important determinant of hepatic lipid peroxidation induced by chronic ethanol feeding. No significant change was observed in hepatic non‐heme iron content, but hepatic content of ascorbic acid and glutathione was increased by ethanol feeding. Both low dietary vitamin E and ethanol feeding significantly reduced hepatic α‐tocopherol content, and the lowest hepatic α‐tocopherol was found in rats receiving a combination of low vitamin E and ethanol. Plasma α‐tocopherol was elevated after ethanol feeding, probably because of the associated hyperlipemia. Both the ratio of plasma α‐tocopherol/plasma lipid and the red blood cell α‐tocopherol were reduced by ethanol feeding. Furthermore, ethanol feeding caused a marked increase of hepatic α‐tocopheryl quinone, a metabolite of α‐tocopherol by free radical reactions. Ethanol feeding caused little changes of α‐tocopherol and α‐tocopheryl quinone content in mitochondria, whereas a striking increase in α‐tocopheryl quinone was observed in microsomes. These data suggest that ethanol feeding causes a marked alteration of vitamin E metabolism in the liver and that the combination of ethanol with a low‐vitamin E intake results in a decrease of hepatic α‐tocopherol content which renders the liver m

ISSN:0270-9139    

DOI:10.1002/hep.1840100511

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY