摘要:

AbstractChronic nutritional injury was induced in rats by a high‐fat, lipotrope‐deficient diet. The hepatoprotective effect of 16,16‐dimethyl prostaglandin E2on the deposition of collagen and fat was assessed by histological evaluation and measurement of hydroxyproline. Dose‐response studies established that optimal protection was achieved by the twice daily administration of 16,16‐dimethyl prostaglandin E2at 100 μg per kg (subcutaneous) or 250 μg per kg (oral). 16,16‐Dimethyl prostaglandin E2and a crystalline analog [(p‐acetami‐dobenzamido)phenyl ester of 16,16‐dimethyl prostaglandin E2significantly delayed both the deposition of collagen and the increase in hepatic hydroxyproline content. There was an excellent correlation between the histological assessment of collagen and the biochemical measurement of hydroxyproline. These data provide a rationale for the evaluation of prostaglandins in the treatment of

ISSN:0270-9139    

DOI:10.1002/hep.1840080112

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractWe have measured the activityS‐adenosyl‐L‐methio‐nine synthetase in liver biopsies from a group of controls (n = 17) and in 26 cirrhotics (12 alcoholic and 14 posthepatitic). The activity of this enzyme was markedly reduced in the group of cirrhotics (285 ± 32 pmoles per min per mg protein) when compared with that observed in controls (505 ± 37 pmoles per min per mg protein). No differences inS‐adenosyl‐L‐methionine synthetase was observed between both groups of cirrhotics. Similarly, a marked reduction in the activity phospholipid methyltransferase was also observed in liver biopsies from the same group of cirrhotics (105 ± 12 pmoles per min per mg protein) when compared with the control subjects (241 ± 13 pmoles per min per mg protein). Again, no difference in the activity of this enzyme was observed between both groups of cirrhotics. These results indicated a marked deficiency in the metabolism ofS‐adenosyl‐L‐

ISSN:0270-9139    

DOI:10.1002/hep.1840080113

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractSera of patients with hepatic encephalopathy strongly inhibit the specific binding of γ‐aminobutyric acid to synaptic membranes. In a previous study, this inhibition of specific γ‐aminobutyric acid binding was attributed to γ‐aminobutyric acid itself, and it was assumed that serum γ‐aminobutyric acid is increased 5‐ to 30‐fold in patients with hepatic encephalopathy. The findings of that study, however, were not confirmed by other analytical methods. Therefore, the validity of the γ‐aminobutyric acid‐radioreceptor assay was tested. In view of the increased serum concentrations of several amino acids in hepatic encephalopathy, the effects of L‐α‐amino acids on the assay were studied. Five amino acids inhibited specific γ‐aminobutyric acid binding at a concentration of 0.5 mMor lower: glutamine; glutamate; taurine; proline, and OH‐proline. Equimolar amounts of amino‐oxyacetate prevented the inhibition of specific γ‐aminobutyric acid binding by glutamine and glutamate but had no effect on that of γ‐aminobutyric acid, taurine, proline and OH‐proline. Aminooxyacetate had no effect on specific γ‐aminobutyric acid binding itself. The inhibitory activity of a serum sample from a patient with hepatic encephalopathy was inhibited by 0.5 mMaminooxyacetate. The γ‐aminobutyric acid binding inhibitory activity of a serum sample of a patient with hepatic encephalopathy was purified by gel chromatography and contained several amino acids at concentrations of about 0.1 mM, 3.5 mMglutamine but no detectable γ‐aminobutyric acid. Accordingly, the γ‐aminobutyric acid binding inhibitory activity is not mediated by γ‐aminobutyric acid alone and is most likely due to glutamine. Thus, using the γ‐aminobutyric acid‐radioreceptor assay serum, “true γ‐aminobutyric acid” concen

ISSN:0270-9139    

DOI:10.1002/hep.1840080114

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractSystolic and diastolic blood pressures were recorded in 176 ambulant patients with chronic liver disease, including 36 patients with compensated cirrhosis (Group I), 119 patients with noncirrhotic chronic liver disease (Group II) and 21 patients with benign structural or functional liver disease (Group III). Group I patients had significantly lower systolic (113.0 ± 2.2 mm Hg, mean ± S.E.) and diastolic (65.3 ± 1.7 mm Hg) pressures than Group II patients (125.8 ± 3.5 and 76.6 ± 1.5 mm Hg, respectively (p<0.0001) or Group III patients (125.1 ± 3.4 and 77.5 ± 2.4 mm Hg, respectively) (p<0.0001). Serum levels of GABA, a potent amino acid neurotransmitter with known vasodilatory effectsin vitro, were higher in Group I patients (1.12 ± 0.26 μM, mean ± S.E.) than in Group II patients (0.41 ± 0.05 μM) (p<0.005) or Group III patients (0.34 ± 0.03 mM) (p<0.05). A constant infusion of GABA into the systemic circulation of six adult dogs, at rates required to achieve serum GABA levels within one order of magnitude of those observed in humans with cirrhosis, resulted in a 17.0 ± 4.3 mm Hg decrease in systolic pressure (p<0.05) and a 10.8 ± 3.7 mm Hg decrease in diastolic pressure (p<0.05). Control amino acids were not vas‐oactive. The results of this study suggest that, in addition to other vasoactive compounds, a GABA‐mediated process might contribute to the hypotension observed in patients with com

ISSN:0270-9139    

DOI:10.1002/hep.1840080115

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractA 40‐yr‐old man presented with encephalopathy and was found to have hepatocellular carcinoma without cirrhosis. A large vascular hepatic mass was defined by CT scan and angiography; laparoscopy with biopsy confirmed the absence of chronic liver disease. A definitive tissue diagnosis of hepatocellular carcinoma was made at laparotomy; the tumor was unresectable. Peripheral arterial and selective portal and hepatic venous ammonia levels were high, and this finding suggested that the encephalopathy was nitrogenous and hepatic in origin. The proposed mechanisms of the encephalopathy are generation of ammonia from tumor breakdown and por‐tosystemic shunting, a result of partial tumor occlusion of the hepatic veins. An unusually high urinary excretion of orotic acid was found similar to that seen in hereditary orotic aci

ISSN:0270-9139    

DOI:10.1002/hep.1840080116

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractThe entire surface protein of hepatitis B virus sero‐typeaywcontaining the preS (preS1+preS2) and S domains has been expressed in the yeastSaccharomyces cerevisiae. Yeast containing a recombinant plasmid utilizing a constitutive promoter did not express this gene successfully due to the toxicity of the protein. A plasmid using a regulatable promoter directed expression which initiated late in the exponential phase of growth and resulted in the accumulation of high intracellular levels of the complete surface protein. The purified polypeptide aggregates into a form which, although not comprised of typical 20 nm particles, displays antigenic determinants encoded by the preS1, preS2 and S domains. Immunization of rabbits elicited the formation of antibodies directed against all three domains. This candidate vaccine will be useful for studying the contributions to viral immunity of the host response to the preS1 and preS2 domain

ISSN:0270-9139    

DOI:10.1002/hep.1840080117

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractLocalization of woodchuck hepatitis virus in liver tissue from 10 infected woodchucks was investigated immunohistochemically and ultrastructurally. Woodchuck hepatitis virus surface antigen was detected by immunoperoxidase methods in the cytoplasm of hepato‐cytes with a fine granular and/or inclusion body appearance. Woodchuck hepatitis virus surface antigen positive hepatocytes were often found in the peripheral zone of hepatic lobules. In contrast to human hepatitis B core antigen, woodchuck hepatitis virus core antigen was observed only in the cytoplasm of hepatocytes, but not in the nuclei. In hyperplastic foci, woodchuck hepatitis virus antigen‐positive hepatocytes were found in 3 of 8 animals. Furthermore, in 1 of 5 animals with hepatocel‐lular carcinoma, woodchuck hepatitis virus surface antigen and woodchuck hepatitis virus core antigen were present in carcinoma cells. Electron microscopic examination revealed many filamentous structures (18 to 20 nm in diameter) in the cisternae of the endoplasmic reticulum. Noncoated core particles (18 to 20 nm in diameter) were found in the cytoplasm of the hepatocytes, but not in the nuclei. The coated particles (42 to 45 nm in diameter) were observed in the cisternae of the endoplasmic reticulum. These coated particles were shown to be morphologically identical to the virus particles in serum. These results indicate that woodchuck hepatitis virus core antigen is produced and assembled mainly in the cytoplasm of hepatocytes, and seems to be rapidly assembled into virion. The similarity of woodchuck hepatitis virus infection to human hepatitis B virus infection makes the woodchuck an excellent experimental model for the study of hepadna virus onco‐

ISSN:0270-9139    

DOI:10.1002/hep.1840080118

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractThe levels of endogenous serum digoxin‐like immunoreactive substances were investigated during development of encephalopathy in patients with fulminant hepatic failure. The 67 patients studied had varying degrees of hepatic failure as a result of viral hepatitis or paracetamol overdose. Serum levels of digoxin‐like immunoreactive substances were significantly increased in both viral hepatitis and paracetamol overdose, with mean values of 0.42 ± S.D. 0.25 ng per ml (n = 36) and 0.53 ± 0.19 ng per ml (n = 31), respectively, as compared to normal control subjects with mean values of 0.01 ± 0.02 ng per ml (n = 21, p<0.001). A statistically significant correlation was found between serum digoxin‐like immunoreactive substances and the degree of encephalopathy in the viral hepatitis patients and with the serum creatinine in the paracetamol overdose patients where renal failure was more severe. No correlation was found with liver damage as assessed by the prolongation of the prothrombin time, serum AST or bilirubin values. Experiments with ultrafiltration and heating showed that both free nonprotein‐bound digoxin‐like immunoreactive substances and the total digoxin‐like immunoreactive substances measured were increased. Column chromatography of ultrafiltrates of fulminant hepatic failure serum on Sephadex G‐25 demonstrated at least two peaks with digoxin‐like immunoreactive activity. Reduced renal function is an important factor in the increased serum level of digoxin‐like digoxin‐like immunoreactive substances, but their presence due to liver failure, where there is increased permeability of the blood‐brain barrier, could be relevant to the development o

ISSN:0270-9139    

DOI:10.1002/hep.1840080119

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractA numerical scoring system was applied and compared with conventional histological classification to assess the histological outcome in 42 patients with chronic hepatitis B followed for 16 to 162 months (mean = 75 months). Four histological categories in the biopsies were assessed and scored: (i) piecemeal necrosis; (ii) lobular necrosis; (iii) portal inflammation, and (iv) fibrosis and cirrhosis. The sum of all four categories was defined as the “Histological Activity Index.” Altogether, 102 liver specimens, including 2 to 4 repeats from each patient, were investigated. A good correlation was noted between a high value of the Histological Activity Index score and several liver histology as monitored by conventional terminology for chronic hepatitis. Among patients, with HBeAg persistence, 8 of 14 (57%) deteriorated during follow‐up as judged by an increase in the Histological Activity Index score compared to 3 of 13 (23%) of the patients with HBeAg seroconversion (0.5

ISSN:0270-9139    

DOI:10.1002/hep.1840080120

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY

摘要:

AbstractA new cell line derived from a woodchuck hepatitis surface antigen‐positive woodchuck hepatocellular carcinoma has been established and named T3‐HEP‐W1. This new cell line was established directly from a primary woodchuck hepatocellular carcinoma. Adaptation of the cells to thein vitroculture condition was completed after 3 months, with the doubling time of 24 hr. The morphologic features of the cell by light microscopy were of an epithelial type. The modal chromosome number was 100. Ornithine and tyrosine aminotransferase activities were detected. Production of albumin was negative. Integration of woodchuck hepatitis virus DNA was demonstrated by Southern blot analysis, although the secretion of woodchuck hepatitis surface antigen was not detected. T3‐HEP‐W1 is quite different from the previously reported WH257GE10 cell line and provides anotherin vitromodel for the study of human hepatocellular carcinoma related to hepatiti

ISSN:0270-9139    

DOI:10.1002/hep.1840080121

出版商:W.B. Saunders    

年代:1988

数据来源: WILEY