摘要:

AbstractWe have taken advantage of the presence of hepatic receptors for galactose‐terminal (asialo‐)glycoproteins to achieve targeted rescue of differentiated hepatocytes from acetaminophen‐induced toxicityin vitro. To accomplish this, a conjugate was formed by covalent coupling ofN‐acetylcysteine (an acetaminophen antagonist) to galactose‐terminal (asialo‐)fetuin. We used two human hepatocyte‐derived cell lines to test our targeted‐rescue method: Hep G2 cells are capable of receptor‐mediated endocytosis of galactose‐terminal glycoproteins and PLC/PRF/5 cells are not. In the presence of acetaminophen alone, both cell lines demonstrated a similar concentration‐dependent sensitivity. Growth rates of both cell lines became normal whenN‐acetylcysteine was administered in equimolar quantities with acetaminophen indicating that both cell lines had the potential of responding to the antagonist. When asialofetuin‐N‐acetylcysteine conjugate was given to both cell lines in the presence of acetaminophen, PLC/PRF/5, receptor (−) cells failed to respond. However, Hep G2, receptor (+) cells treated with asialofetuin‐N‐acetylcysteine conjugate under identical conditions, increased their populations and eventually reached confluence. Control conjugate fetuin‐N‐acetylcysteine as well as asialofetuin al

ISSN:0270-9139    

DOI:10.1002/hep.1840050502

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY

摘要:

AbstractThe metabolism of transferrin was studied using purified125I‐labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group.There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 ± 0.3 gm per liter vs. 2.9 ± 0.2; p<0.01), resulting from diminished total body synthesis (0.9 ± 0.2 mg per kg per hr vs. 1.8 ± 0.2; p<0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 ± 0.3 mg per kg per hr) was significantly increased when compared with controls (p<0.05).For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = +0.70; p<0.01) but the serum iron did not.These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accel

ISSN:0270-9139    

DOI:10.1002/hep.1840050503

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY

摘要:

AbstractA study from five hepatology units documenting 157 cases of drug‐induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug‐induced hepatitis. In drug‐induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug‐induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin‐induced hepatitis. The third group included drug‐induced hepatitis with special antibody:iproniazid‐induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)‐induced hepatitis with antiliver/kidney microsome antibody 2 (anti‐LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid‐induced hepatitis and 67 cases of tienilic acid‐induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane‐induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug‐induced hepatitis of the second group and lupoïd hepatitis suggest that drugs may reveal this spontaneous disorder. The specific antibody found in iproniazid and tienilic acid‐induced hepatitis may suggest the site where the drug attachesin vivo. Immunoallergic hypersensitivity seems to be the mechanism involved in halothane‐induced hepatitis; autoimmune phenomenon may play a role in liver

ISSN:0270-9139    

DOI:10.1002/hep.1840050504

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY

摘要:

AbstractTwenty patients with HBeAg‐positive chronic liver disease were given large doses of recombinant leukocyte interferon for 4 weeks. Changes of hepatitis B virus DNA in livers and sera were analyzed by the molecular hybridization technique in paired biopsies obtained before and 2 weeks after treatment. Serum hepatitis B virus DNA was examined before, during and after the treatment until 4 weeks post‐interferon.Analysis of hepatic hepatitis B virus DNA revealed species that appeared to represent various forms of replicative hepatitis B virus DNA, i.e., relaxed circular, linear, supercoiled and single‐stranded hepatitis B virus DNA, respectively. No evidence of integration of hepatitis B virus DNA in genomic DNA was obtained. Of 15 cases which were positive for hepatic hepatitis B virus DNA before treatment and in which paired biopsies were obtained, hepatic hepatitis B virus DNA became negative in 4, decreased in 5 and unchanged in 6. Among several types of replicative viral DNA in liver tissue, supercoiled hepatitis B virus DNA tended to remain after other forms were reduced.A close correlation between hepatic and serum hepatitis B virus DNA was found in 37 liver biopsy samples and corresponding sera.These results indicate that interferon treatment reduces serum hepatitis B virus levels by inhibiting viral replication in the liver and that persistence or reappearance of hepatitis B virus in serum after interferon is associated with replic

ISSN:0270-9139    

DOI:10.1002/hep.1840050505

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY

摘要:

AbstractBy manipulating dietary sugar intake and perfusate glucose concentration, we have identified two independent hepatic immunoregulatory molecules produced by the perfused rat liver. The first is released by injured hepatocytes, appears in perfusates together with hepatocellular glutamic pyruvic transaminase, is quantitatively inhibited by exogenous L‐arginine and coelutes with arginase on high‐pressure liquid chromatography. Based on these findings, we conclude that this activity is due to the release of cytoplasmic arginase from injured hepatocytes. Since supplementation studies reveal that lymphocyte proliferation is exquisitely arginine‐dependent, it is conceivable that arginase released by injured hepatocytes might influence lymphocyte functionin vivoby local arginine depletion. The second immunoregulatory molecule is released by noninjured hepatocytes following induction by sugar, particularly glucose, bothin vivoorin vitro. This inducible activity is arginase‐independent, triglyceride‐rich and floats at a density less than 1.006 gm per ml upon ultracentrifugation. Based on these characteristics, we tentatively ascribe this activity to hepatic very low density lipoprotein, the serum counterpart of which is known to express many immunoregulatory properties. These results directly illustrate for the first time the pathophysiological conditions required for the secretion and release of these distinct and independent hepatic immunoregulatory molecules, and they suggest possible routes by which they may influence immunological homeostasis and immunologically mediated live

ISSN:0270-9139    

DOI:10.1002/hep.1840050506

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY

摘要:

AbstractThe role of accessory cells (antigen‐presenting cells) in binding HBsAg in the response of human T cells to this antigen was studied. Antibodies to HBsAg of IgG class increased significantly the amount of HBsAg that was captured and internalized by accessory cellsin vitro. On the other hand, antibodies to HBsAg of IgM class or the F(ab‐)2and Fab fragments of antibodies to HBsAg of IgG class did not modify the amount of HBsAg associated to these cells. HBsAg that was subjected to various denaturing treatments (acid, organic solvents, urea and heat) was compared for its capacity to react with antibody to HBsAg and stimulate the response of helper T lymphocytes. Results presented here indicate that HBsAg denatured by treatment with formic acid was captured by accessory cells and presented to the T cells much more efficiently than the native HBsAg. These results suggest that the response of helper T lymphocytes to some antigens such as HBsAg can be affected greatly by the presence of antibodies or the antigens‐ conform

ISSN:0270-9139    

DOI:10.1002/hep.1840050507

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY

摘要:

AbstractStudies were undertaken to evaluate whether antiidiotypic antibody against antiliver‐specific membrane lipoprotein is related to the disease activity of patients with hepatitis. Sera from normal individuals, patients with viral hepatitis and medical staffs were depleted of antiliver‐specific membrane lipoprotein antibody by absorbing with liver‐specific membrane lipoprotein‐bearing cell line SK‐Hep‐1. Anti‐antiliver‐specific membrane lipoprotein was detected by binding activity to antihuman liver‐specific membrane lipoprotein monoclonal antibody using solid‐phase radioimmunoassay and by inhibitory activity for binding of antiliver‐specific membrane lipoprotein monoclonal antibody to SK‐Hep‐1 using competitive radioimmunoassay. The results obtained by the two assays were equivalent for detecting anti‐antiliver‐specific membrane lipoprotein. Sera from patients with acute viral hepatitis during recovery phase (n = 6) and chronic persistent hepatitis (n = 12), respectively, showed significantly increased anti‐antiliver‐specific membrane lipoprotein activity (p<0.01) when compared to those from normal individuals (n = 10), whereas sera from patients with chronic active liver disease (n = 12) did not reveal significantly different values from controls. Sera from the medical staff (n = 11) who had contact with hepatitis patients also demonstrated increased anti‐antiliver‐specific membrane lipoprotein activity (p<0.05). Inhibitory activity of anti‐antiliver‐specific membrane lipoprotein in the serum appeared localized within the F(ab‐)2fragments of immunoglobulin G fraction by competitive radioimmunoassay. The specificity of the inhibitory activity of the serum was confirmed by its inability to block unrelated antigen‐antibody reactions. These findings suggest that the presence of antibody against antiliver‐specific membrane lipoproteins is related to the dise

ISSN:0270-9139    

DOI:10.1002/hep.1840050508

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY

摘要:

AbstractAn IgM‐specific anti‐[anti‐HBs] antibody was detected by radioimmunoassay using anti‐IgM‐coated beads and125I‐labeled anti‐HBs. This antiidiotype was found only in the sera of hepatitis B virus‐infected patients, both acute and chronic. However, not all HBsAg‐positive patients exhibited this reaction, and activity was correlated with the presence of HBeAg. Approximately 93% of sera that contained antiidiotype activity also contained HBeAg. Conversely, 70% of the sera positive for HBeAg reacted in the IgM assay. No correlation was observed between the presence of antiidiotype and rheumatoid factor or elevated SGPT levels.Two approaches were used to determine whether the reactive moiety was an IgM anti‐[anti‐HBs] as postulated or an IgM anti‐HBs/HBsAg complex. It was shown that chicken anti‐HBs sera, which does not share the common idiotype of human and other mammalian anti‐HBs, did not block a positive reaction in this radioimmunoassay even though it specifically bound HBsAg. It was also demonstrated that treatment with polyethylene gylcol, which will precipitate IgM anti‐HBs/HBsAg activity, did not precipitate the reactive moiety in 6 of 7 sera tested, lending further evidence to the existence of an IgM antiidiotype in these patients.It is suggested that this antiidiotype directed against anti‐HBs may be involved in a defective feedback mechanism resulting in the suppression of production of anti‐HBs and

ISSN:0270-9139    

DOI:10.1002/hep.1840050509

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY

摘要:

AbstractSera from patients with primary biliary cirrhosis reacted with four major bands in beef heart mitochondria and ATPase extract when analyzed by immunoblot after sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. These four immunologically reactive bands corresponded to protein bands with molecular weights of about (a) 80,000; (b) 63,000; (c) 56,000; and (d) 43,000 to 46,000. An additional immunoreactive band was found with some high‐titered primary biliary cirrhosis sera at 36,000. No association with any ATPase subunits was found, except for band c which migrated between the α‐ and β‐subunit of ATPase. Most ATPase fractions did not contain this band c, indicating that M2 determinants, as defined by immunoblot, are not identical with any ATPase subunit.Species and nonspecies‐specific determinants of M2 were identified using mitochondria from rat liver and human heart and liver. Antigenic bands a, c and d were nonspecies‐specific. Band b and e occurred only in beef heart. An additional determinant at about 38,000 was detected using human heart and liver mitochondria. Primary biliary cirrhosis sera showed a typical reaction with two protein bands ofEscherichia coli, one at about 85,000 to 90,000 and the other at 60,000. Antibodies against both determinants could be absorbed with submitochondrial particles of beef heart showing thatE. colishares cross‐reacting determinants with mitochondria.Sera from 56 primary biliary cirrhosis patients were tested using beef heart mitochondria. Fifty‐four sera reacted positively with the M2 antigen in the ELISA, and these sera reacted with at least 1 of the 4 major antigenic bands: 85% were positive with band a and/or band b; 15% detected exclusively band c and none of the latter fixed complement. Antimitochondrial antibodypositive sera possessing other specificities (anti−M1, −M3, −M5, −M6 and −M7) were negative. A correlation with the precipitating antimitochondrial an

ISSN:0270-9139    

DOI:10.1002/hep.1840050510

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY

摘要:

AbstractSpleen cells obtained from C57BL/6 (B6) mice with an experimental autoimmune hepatitis were transferred to normal C57BL/6 recipient mice. Most prominent liver damages occurred in the recipient mice injected with sensitized nylon wool column‐adherent spleen cells from the donor mice. Production of such liver damage was blocked by treatment of the sensitized adherent spleen cells with anti‐Thy 1,2 monoclonal antibody and complement before injection. Based on thesein vivoresults, a microcytotoxicity assay was performed using isolated C57BL/6 hepatocytes as target cells and sensitized spleen cells obtained from hepatitis donor mice as effector cells. The fraction of sensitized nylon wool‐adherent spleen cells demonstrated a high cytotoxic activity against isolated syngeneic hepatocytes, although the other fractions and spleen cells of control animals showed no such effect. The cytotoxic activity of sensitized‐adherent spleen cells against target hepatocytes was significantly reduced after treatment with anti‐Thy 1,2 antibody and complement, but it increased after depletion of B cells and Fc receptor‐bearing T‐cells. Although these sensitized nylon wool‐adherent spleen cells showed high cytotoxic activities against syngeneic hepatocytes, their cytotoxicity against allogeneic hepatocytes was lower. They exerted no cytotoxic activity against syngeneic renal glomerular cells and EL‐4 thymoma cells. These results suggest that sensitized T‐cells in the nylon wool column‐adherent fraction play the role of cytotoxic killer cells against targe

ISSN:0270-9139    

DOI:10.1002/hep.1840050511

出版商:W.B. Saunders    

年代:1985

数据来源: WILEY