摘要:

AbstractThe occurrence and pathogenetic role of intrahepatic deposits of immunoglobulins in experimental viral infection have been evaluated by determining with immunofluorescence their capacity to fix complementin vitro[in vitrocomplement fixation (VCF)]. Liver biopsies from chimpanzees chronically or acutely infected with hepatitis B virus or the hepatitis B surface antigen (HBsAg)‐associated δ agent were used in the study. VCF was observed in each animal expressing hepatitis B core antigen (HBcAg) or δ antigen in the liver and concurrently circulating the homologous antibody in the blood. In acutely infected animals, VCF appeared at the same time that the homologous serum antibody appeared, and the intensity of VCF staining was proportional to the antibody titer in the serum. In animals expressing sequentially the HBcAg/antibody system and then δ antigen and antibody to δ, VCF was first observed in HBcAg‐containing nuclei and then in nuclei expressing δ antigen. There was no relationship between VCF and intrahepatic expression of HBsAg or serologic expression of hepatitis B e antigen (HBeAg).A positive VCF reaction appears related to the formation of intrahepatic immune complexes between HBcAg or δ antigen and the homologous antibody. Although acute hepatitis developed in parallel with the occurrence of VCF in two animals, strong VCF fluorescence was also observed in each of the asymptomatic carriers of HBsAg, and, in one of them, preexisting VCF staining of HBcAg disappeared in parallel with development of acute hepatitis.In experimentally infected chimpanzees, the finding in liver biopsies of immune complexes detectable by VCF appears to be a common epiphenomenon without pathogenic sig

ISSN:0270-9139    

DOI:10.1002/hep.1840010602

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractLiver biopsies from five patients with chronic non‐A, non‐B (NANB) hepatitis were examined by electron microscopy for hepatocellular alterations. Circular fused membranes were observed within the cytoplasm of hepatocytes of four of the patients. Aggregates of intranuclear particles, measuring 22 ± 2 nm in diameter, were also seen in two of the biopsies in which fused membranes were identified. Sera of all five patients formed precipitin lines detectable by counterimmunoelectrophoresis when reacted with serum from an individual convalescent from posttransfusion NANB hepatitis. Using this convalescent serum as an antibody source, complexes of 22 ± 2 nm particles were identified in three of the chronic patient sera by immunoelectron microscopy. These observations suggest that at least one of the agents responsible for NANB hepatitis elicits both nuclear and cytoplasmic modifications. Furthermore, the 22 ± 2 nm particles circulating in the sera of the chronic NANB patients may represent components related to NANB hepatitis

ISSN:0270-9139    

DOI:10.1002/hep.1840010603

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractFifty patients with chronic HBs antigenemia and Dane particle‐associated DNA polymerase and HBeAg in their serum were contrasted to 46 HBsAg positive patients who had neither serum DNA polymerase or HBeAg. The time from acute onset and the duration of antigenemia were longer in patients who were DNA polymerase and HBeAg negative than in those who had both serum markers. Cirrhosis, hypoalbuminemia, and sequelae of chronic liver disease were more common in DNA polymerase, HBeAg negative patients than in those who were positive. These findings are consistent with the hypothesis that active viral replication is an early, albeit prolonged stage in the development of advanced HBsAg‐associated liver dise

ISSN:0270-9139    

DOI:10.1002/hep.1840010604

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractSeven patients are described in whom HBsAg persisted for 13 to 98 months after acute viral hepatitis B and then became nondetectable. All patients subsequently developed anti‐HBs. During the period of HBs‐antigenemia, liver biopsies in five patients showed persistent viral hepatitis. Retrospectively, impending negativity of HBsAg was predictable in five patients by a decrease in HBsAg titer, and in four patients by persistent normalization of serum alanine aminotransferase. Although delayed clearance of HBsAg in patients with chronic hepatitis B virus infection is uncommon, it appears to be predicta

ISSN:0270-9139    

DOI:10.1002/hep.1840010605

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe effects of ethanol on the synthesis and secretion of serum glycoproteins and albumin, a nonglycosylated protein, were studied in rat liver slices. Serum glycoproteins and albumin were determined by immunoprecipitation from either the incubation medium or from the washed slices. When ethanol (10 mM) was present in the incubation medium, [14C]glucosamine incorporation in secretory glycoproteins was decreased. This inhibitory effect was, however, much greater in the secretory proteins released into the medium than in those retained in the liver slices. Similar inhibitions by ethanol were also observed when leucine or valine were used as a label for either total export proteins or albumin. Since ethanol impaired protein synthesis, an inhibitor of protein synthesis, cycloheximide, was used so that both the control and ethanol‐treated slices had identical pools of protein acceptors available for glycosylation. When cycloheximide alone was added to the slices, glucosamine radioactivity of secretory glycoproteins was equally reduced in both the medium and the liver. When cycloheximide and ethanol were both present, decreased appearance of glucosamine‐labeled proteins in the medium was observed when compared to the slices containing cycloheximide alone; however, radioactivity of secretory glycoproteins retained in the liver was elevated. Ethanol also decreased the appearance of fucose‐labeled glycoproteins in the medium without altering fucose incorporation into the total pool of secretory glycoproteins. The effects of ethanol on hepatic protein secretion independent of its effect on synthesis were further determined by prelabeling proteins with either [14C]leucine or [14C]fucose. Ethanol impaired the secretion of these prelabeled proteins into the medium. The results of this study show that ethanol impairs both the synthesis and secretion of secretory glycoproteins and al

ISSN:0270-9139    

DOI:10.1002/hep.1840010606

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractInterrelationships among histologic features of alcoholic liver disease were studied in 24 chronic alcoholics who took part in a double‐blind, controlled trial of prednisolone vs. placebo therapy. Each patient underwent liver biopsy at the start and upon completion of the 1‐month study. Although all patients had a clinical diagnosis of alcoholic hepatitis and had at least mild alcoholic hepatitis with alcoholic hyalin in their initial liver biopsy specimens, each of the histologic features studied (fat accumulation, bile stasis, alcoholic hyalin, acute inflammation, active intralobular fibrosis, chronic inflammation, bile duct proliferation, established fibrosis, and parenchymal nodularity) covered a wide spectrum of severity.Relationships of the severities of the individual histologic features were studied within the initial biopsy specimens and between the pre‐ and posttreatment biopsies. Four major histopathologic categories were evident in the correlation patterns: fat accumulation; cholestasis; alcoholic hepatitis, and cirrhosis. While having common pathogenetic ties and thus often occurring together, the severities of these categories in a given patient at a given time were little related and they are best considered as separate features of alcoholic liver disease. The amount of alcoholic hyalin appeared to be the best single indicator of the severity of alcoholic hepatitis in these patients and was the best predictor in the pretreatment biopsies of the amounts of hepatocellular injury, active fibrosis, acute inflammation, and total inflammation in the posttreatment biopsy specimens. Active fibrosis and hepatocellular injury in turn appeared to be the most immediate precursors of established fibrosis and parenchymal nodularity. Bile duct proliferation was, in part, a reflection of cholestatic disease and, in part, a more nonspecific reflection of chronic alcoholic liver injury, correlating with the amount of established fibrosis. The relationship of chronic inflammation to other histologic features was complex, but probably included an intralobular component related to the severity and stage of alcoholic hepatitis and another, more nonspecific, component related to the amount of established fibrosis or bile duct proliferation.One month of prednisolone therapy (40 mg per day) significantly decreased the amount of inflammation, but did not have a comparable effect on hepatic fibrosis.The statistical methods used in this study to investigate the multiple interrelationships among histologic features are useful in evaluating potential pathogenetic relationships and are quite helpful in assessing the effects of trea

ISSN:0270-9139    

DOI:10.1002/hep.1840010607

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractWe have shown that serum bile acid concentrations are elevated in human infants reflecting physiologic immaturity of the enterohepatic circulation. To define further the ontogeny of bile acid metabolism in mammals, we examined maturational changes in the serum concentration of total cholate conjugates by radioimmunoassay in fetal, neonatal, suckling, and mature Sprague‐Dawley rats. Fetal (21st day) levels were low (1.4 ± 0.23 μM; X̄ ± S.E.), possibly due to minimal enterohepatic cyclingin utero.The concentrations in samples obtained minutes after birth, prior to suckling were significantly elevated (12.6 ± 2.37; p<0.001 vs. fetal); these high values persisted after feeding was initiated (6 hr = 13.5 ± 0.99), but fell at 12 hr (5.2 ± 0.81) and remained unchanged for the duration of the first day. Serum values fluctuated briefly, being 9.6 ± 0.73 on Day 4, and then rose progressively through the suckling period (Day 10 = 7.2 ± 0.57; Day 14 = 10.4 ± 1.70; Day 21 = 16.8 ± 1.93); there was a dramatic peak after weaning (Day 28 = 21.8 ± 1.53). The serum concentration of cholate conjugates then fell (5.6 ± 0.68 on Day 42) to achieve adult levels by 56 days (4.0 ± 0.55), a value substantially different from that of all developing animals (p<0.025). These data corroborate studies which suggest that a period of physiologic cholestasis occurs in the developing rat. Serum cholate conjugate concentrations likely reflect interrelated morphologic alterations (bile canalicular structure and portal blood flow) and physiologic changes (bile acid synthesis, pool size, and transport) occurring in the enterohepatic circulation du

ISSN:0270-9139    

DOI:10.1002/hep.1840010608

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractIn order to determine if the delayed clearance of organic anions observedin vivoafter fasting can be related to an alteration of cell membrane carriers, kinetics of sulfobromophthalein (BSP) uptake were determined in isolated rat liver cells obtained from 48‐hr starved rats. Surprisingly, in fasted rats the existence of two carriers can be directly revealed by classical kinetic plots. The high‐affinity component, inhibited by Na+‐taurocholate, has a Kmof 0.5 ± 0.2 μMand a Vmaxof 0.2 ± 0.1 nmole per min per 106cells; the low‐affinity component, which is not sensitive to Na+‐taurocholate, has a Kmof 21.2 ± 3.2 μMand a Vmaxof 4.8 ± 0.9 nmoles per min per 106cells. Comparison with control cells shows that fasting does not modify the total capacity of the liver cell membrane carriers to take up BSP. However, alterations in the kinetic parameters of the two uptake components were observed: a 53% decrease in the affinity of the low‐affinity component and a 50% reduction in the capacity of the high‐affinity uptake. These alterations, together with the observed decrease in hepatic blood flow and/or the increase in BSP efflux from the hepatocytes, could be involved in the delayed clearance of BSP and other anionic compounds occurringi

ISSN:0270-9139    

DOI:10.1002/hep.1840010609

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractBilirubin diglucuronide, the major pigment in human bile is formed in two steps. Bilirubin is converted to bilirubin monoglucuronide by transfer of the glucuronosyl moiety of uridine diphosphoglucuronic acid catalyzed by the microsomal enzyme, uridine diphosphoglucuronate glucuronosyl transferase (UDP glucuronyl transferase, EC 2.4.1.17). Bilirubin monoglucuronide is converted to bilirubin diglucuronidein vitroby two enzymatic mechanisms: (a) UDP glucuronyl transferase‐mediated transfer of a second mole of glucuronic acid form UDP‐glucuronic acid to bilirubin monoglucuronide; (b) dismutation of 2 moles of bilirubin monoglucuronide to 1 mole of bilirubin diglucuronide and 1 mole of unconjugated bilirubin, catalyzed by bilirubin monoglucuronide dismutase (bilirubin glucuronoside glucuronosyl transferase EC 2.4.1.95). Assay methods for the three enzymatic mechanisms in human liver homogenate by high‐pressure liquid chromatography analysis of underivatized bilirubin tetrapyrroles have been developed. UDP glucuronyl transferase was activated in five human liver homogenates with digitonin, Triton X‐100, or UDP‐N‐acetylglucosamine. Greatest activation was observed with Triton X‐100. The pH optimum for conversion of bilirubin to bilirubin monoglucuronide was 7.4, and UDP glucuronyl transferase activity was 625 ± 51 nmoles per 20 min per gm liver. At high initial bilirubin concentrations (342 μM), the product of UDP glucuronyl transferase assay with bilirubin as substrate was predominantly bilirubin monoglucuronide. At lower initial bilirubin concentrations (6.5 to 34 μM), up to 15% bilirubin diglucuronide was formed. Glucuronyl transferase‐mediated UDP glucuronic acid‐dependent conversion of bilirubin monoglucuronide to diglucuronide was assayed using UDP‐14‐C‐glucuronic acid. The pH optimum was 7.4, and the rate was 21 ± 7 nmoles per gm liver per 20 min. The rate of bilirubin diglucuronide formation by enzymatic dismutation of bilirubin monoglucuronide was 470 ± 112 nmoles per gm liver per min. The pH optimum was 6.6. The products of enzymatic dismutation w

ISSN:0270-9139    

DOI:10.1002/hep.1840010610

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

Abstractα‐1‐Antitrypsin deficiency due to homozygous Pi ZZ state is reported to be associated with cirrhosis and hepatocellular carcinoma (HCC); however, the role of heterozygous Pi Z state is not definitively known. In order to investigate the possible association, we studied the phenotypic distribution of α‐1‐antitrypsin variants (Pi) in 124 cases of HCC. Two thousand ten normal American Red Cross blood donors were studied as controls. Twelve patients with HCC had aberrant pheno‐types, an incidence of 9.67% as compared to 8.36% among normal controls. Nine of 12 patients with HCC with aberrant Pi type had cirrhosis; 5 of the 9 had cirrhosis due to hepatitis B virus; 2 of the 9 had alcoholic liver disease with cirrhosis, and 2 had cryptogenic cirrhosis. The three patients with HCC arising in noncirrhotic livers who also had aberrant Pi phenotypes, had a relatively rare variety of HCC called fibrolamellar type. Z gene was found in five patients: all five were MZ. Incidence of MZ phenotype in HCC was similar to that of the normal control population (4.0% in HCC and 2.9% in the controls). However, 3 of 5 MZ were associated with fibrolamellar HCC. Another aberrant phenotype found among the patients with HCC was MF (fast moving) which occurred with an incidence of 2.41% as compared to none in the control group. In conclusion, we found no significant increase in the incidence of Z gene among 124 patients with HCC as compared to the normal

ISSN:0270-9139    

DOI:10.1002/hep.1840010611

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY