摘要:

AbstractThe livers of 33 captive woodchucks were examined histologically in 30 biopsy and 10 autopsy specimens and the findings were correlated with serum determinations for woodchuck hepatitis virus (WHV), surface antigen (WHsAg) and antibody (anti‐WHs), and WHV DNA and DNA polymerase. The liver appeared normal in all 3 serum‐negative animals, 7 of 16 with indeterminate WHV status, and 1 of 4 with anti‐WHs, but not in 10 animals with WHsAg, WHV DNA, and DNA polymerase. Mild hepatic inflammation was found in 7 woodchucks with indeterminate status, 4 with anti‐WHs, and 2 with each marker of WHV infection. Significant inflammation was found in 2 of indeterminate status and 4 with every marker, whereas more severe lesions (2 of chronic active type) occurred, almost always in autopsy specimens, in 8 animals with every marker. Eight of 10 animals with all markers had orcein‐positive inclusions (Shikata's technique) and 6 had hepatocellular carcinoma associated with acute and chronic hepatic inflammation and, usually, neoplastic nodules in the noncarcinomatous parenchyma. Features distinguishing the woodchuck lesion from human hepatitis B disease were: association of carcinoma with acute hepatic inflammation (but not with cirrhosis) and DNA polymerase in the serum; transition to carcinoma from neoplastic nodules; conspicuous plasma‐cellular reaction of hepatic inflammation, and hematopoietic cells in the tumor. Significant hepatic lesions in the woodchucks were regularly associated with serum WHsAg, WHV DNA, and DNA polymerase. In contrast to man, hepatocellular carcinoma in woodchucks was regularly associated with these markers of active viral replication. The nature of the orcein‐positive inclusions requires elucidation, although they may assist in screening for similar viruses in other species. The woodchuck may help in the study of the relation between hepatocellular carcinoma and hepatitis B, including the possibility of cocarcino

ISSN:0270-9139    

DOI:10.1002/hep.1840010202

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe normal rat hepatocyte divides approximately once per year but, following two thirds hepatectomy, rapid cellular replication occurs throughout the remaining liver remnant. Using a multiple indicator dilution technique, single‐pass transport of3H‐bilirubin and125I‐asialoorosomucoid was studied in isolated perfused liver from 6hr to 6d after two thirds hepatectomy or sham surgery. Influx (k1), efflux (k2), and sequestration (k3) rates were quantitated by computer analysis. k1for3H‐bilirubin fell by over 50% within 6hr after two thirds hepatectomy and returned to normal 4d later. k2progressively decreased with a nadir at 2d, and returned to normal by 4d. k3was transiently depressed, and became normal within 2d. Although hepatic uptake of asialoglycoproteins has been thought to be irreversible, the experimental data required k2and k3parameters for best fit. Similar to results for3H‐bilirubin, the k1of125I‐asialoorosomucoid was 20% of normal at 1d after two thirds hepatectomy, and returned to normal by 6d. Unlike results for3H‐bilirubin, there was a prolonged 50% reduction of k2and k3with return to normal by 6d. The transport changes during regeneration are independent of reduced liver mass or changes in hepatic spaces of distribution. The fact that influx of both compounds reaches a nadir at the time of greatest cellular proliferation with subsequent return to normal suggests a „maturation”︁ of liver cell function for restoration of these specific hepatocyte functions. Modulation of the hepatocyte receptor for desialylated glycoproteins may also be required for cellular recognition as a prerequisite for prol

ISSN:0270-9139    

DOI:10.1002/hep.1840010203

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe reticuloendothelial system has been implicated in galactosamine‐induced liver injury because of a correlation between phagocytic alterations induced by colloidal carbon or endotoxin, and development of liver necrosis. To evaluate this concept, the influence of galactosamine on liver function and histology was determined in rats in which the reticuloendothelial system was normal, stimulated, or depressed. Methyl palmitate was used as a reticuloendothelial system suppressant, and glucan was used as a reticuloendothelial system activating agent. Administration of galactosamine to control rats resulted in hypoglycemia and increased serum bilirubin concentration, elevated serum glutamic oxalacetic transaminase, lactic dehydrogenase and glutamic pyruvic transaminase activities, and retention of sodium sulfobromophthalein. Histological studies revealed hepatic necrosis, and a polymorphonuclear and lymphocytic cellular infiltrate in galactosamine‐treated rats. Pretreatment of rats with methyl palmitate inhibited galactosamine‐induced alterations in serum glucose concentration, glutamic oxalacetic transaminase and lactic dehydrogenase activities, and sodium sulfobromophthalein retention. Liver necrosis and inflammatory reactions were also reduced in methyl palmitate‐treated galactosamine‐injected animals. In contrast, activation of the reticuloendothelial system by glucan increased galactosamine‐induced alterations in serum bilirubin, glucose and cholesterol concentrations, glutamic oxalacetic transaminase, glutamic pyruvic transaminase and lactic dehydrogenase activities, and sodium sulfobromophthalein retention. Liver necrosis and inflammation were also increased. These findings suggest that the degree of galactosamine‐induced liver injury is directly correlated with macrophage function when specific macrophage‐modifying

ISSN:0270-9139    

DOI:10.1002/hep.1840010204

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractIsolated rat hepatocytes accumulate iron from iron‐transferrin by a process which is dependent on the temperature and on the transferrin concentration, and which is diminished by treatment of the cells with a proteolytic enzyme. These observations are consistent with a mechanism for iron uptake into hepatocytes involving the binding of iron‐transferrin to a specific cell‐surface receptor.Apotransferrin is also able to bind to the hepatocyte but the apparent binding constant is about 35 times lower than that observed for the binding of iron‐transferrin. The binding of apotransferrin to the cells is completely abolished by a low concentration of iron‐transferrin. This suggests that the apotransferrin is binding weakly to the same receptor to which iron‐transferrin binds and that there are no receptors on the surface of the hepatocyte specific for apotransferrin. In the absence of such specific‐binding sites, apotransferrin may act as a passive acceptor of iron released from t

ISSN:0270-9139    

DOI:10.1002/hep.1840010205

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractIn a study of 20 families with idiopathic hemochromatosis, relatives of probands were classified as either homozygous, heterozygous, or normal according to their HLA phenotype. An abnormality in the serum iron concentration, total iron‐binding capacity, or serum ferritin concentration was present in all homozygotes and in 25% of heterozygotes. In heterozygotes, the mean total iron‐binding capacity was significantly decreased, and the mean hepatic iron concentration was significantly increased compared to normals. However, in contrast to homozygotes, clinical evidence of iron overload was not observed in heterozygotes, and there was no biochemical or histological evidence of liver disease resulting from excessive iron stores. Progressive iron overload did not develop in 44 heterozygotes who were studied for up to 16

ISSN:0270-9139    

DOI:10.1002/hep.1840010206

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe hepatitis B virus‐associated delta antigen was detected in the serum of a young female drug addict with acute hepatitis and a previous history of hepatitis B surface antigen carrier. Delta antigen was associated with a 35‐ to 37‐nm subpopulation of hepatitis B surface antigen particles which banded at a density of 1.25 gm per cm3of CsCl and contained a small RNA of approximately 5.5 × 105molecular weight. This report demonstrates that delta antigen is associated with a unique subpopulation of hepatitis B surface antigen particles and small RNA in human

ISSN:0270-9139    

DOI:10.1002/hep.1840010207

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractRecent evidence suggests that hepatitis B virions (HBV) and HBsAg particles contain receptors for polymerized human serum albumin (pHSA). We studied, by immunohistochemical techniques, the relationship between HBsAg and pHSA receptors in liver tissue from eight patients with chronic HBV infection and in a human hepatocellular carcinoma cell line (PLC/PRF/5) producing HBsAg. Both parallel sections and double fluorescent antibody staining of liver tissue demonstrated that only HBsAg‐containing hepatocytes expressed pHSA receptors. The receptors could not be demonstrated in eight HBsAg negative livers. Sequential studies of PLC/PRF/5 cells revealed that pHSA and HBsAg emerged simultaneously in the cytoplasm, on the cell surface, and in the supernatant culture media. These findings indicate that pHSA receptors are closely associated with HBsAg during its synthesis and secretion by hepatocytes and suggest that the receptors are HBV‐speci

ISSN:0270-9139    

DOI:10.1002/hep.1840010208

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractConsiderable evidence suggests that liver plasma membrane (LPM) NaK‐ATPase [(Na++ K+)‐dependent adenosinetriphosphatase] and Mg‐ATPase (Mg2+‐dependent adenosinetriphosphatase) activity and lipid fluidity are important in liver cell functions such as bile formation. However, little is known regarding factors which might alter these membrane propertiesin vivo.Bile salts are actively concentrated by liver cells under normal conditions and reach even higher tissue concentrations in cholestasis. Since current methodology does not permit investigation of the effect of bile salts on LPMin vivo, we have examined the effects of bile saltsin vitroon isolated rat LPM essentially free of organelle contamination and enriched 52.9‐, 23.8‐, and 27.8‐fold in NaK‐ATPase, 5′‐nucleotidase, and alkaline phosphatase, respectively, compared with homogenate. We found that taurocholate (0.5 to 4.0 mM), taurochenodeoxycholate (0.25 to 4.0 mM), deoxycholate (0.25 to 4.0 mM), but not dehydrocholate (0.25 to 4.0 mM) caused immediate, concentration‐dependent inhibition of LPM Mg‐ and NaK‐ATPase which at low bile salt concentration (1.0 mM) was reversible. By contrast, taurocholate (1 to 4 mM) had no effect on LPM 5′‐nucleotidase activity. Both 1 mMtaurocholate and taurochenodeoxycholate caused a decrease in the apparent Kmfor ATP of NaK‐ATPase, but not of Mg‐ATPase, and 1 mMtaurochenodeoxycholate caused no significant change in the activation of either Mg‐ or NaK‐ATPase by cations. Finally, LPM lipid fluidity measured by fluorescence polarization using 1,6‐diphenyl‐1,3,5‐hexatriene as a probe was reversibly increased by taurocholate, taurochenodeoxycholate, and deoxycholate, but not dehydrocholate; the effect of taurochenodeoxycholate on lipid fluidity was confirmed by electron spin resonance using 5‐(2,2‐dimethyl‐N‐oxyl‐oxayalidine)‐stearic acid as a probe. However, by both techniques, the effect of low concentrations of these bile salts on ATPase activity was independent of detectable changes in fluidity.These findings indicate that at concentrations comparable to those reported for liver tissue endogenous, micelle‐forming bile salts reversibly inhibit LPM ATPases and reversibly increase LPM lipid fluidityin vitro; these two effects being dissociable at low bile salt concentrations. It is possible that bile salts may have similar

ISSN:0270-9139    

DOI:10.1002/hep.1840010209

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractThe present report has been directed toward providing additional information on the major defects in the bile acid pathways present in patients with cirrhosis and its relevance to the problem of how bile acid synthesis is regulated in man. An unusual patient with severe liver disease and a completely broken enterohepatic circuit was studied. The synthesis of cholic and chenodeoxycholic acids was examined over a 5‐d period. The secretion rates and the incorporation of [3H]7α‐hydroxycholesterol and [3H]26‐hydroxycholesterol into both primary bile acids in the cirrhotic bile fistula patient was cross compared to earlier data obtained on patients with and without liver disease and an intact enterohepatic circuit and patients with no liver disease and a bile fistula. The daily synthesis rate of cholic acid increased 7‐fold and chenodeoxycholic acid 2‐fold in the cirrhotic bile fistula patient. The incorporation of [3H]7α‐hydroxycholesterol into bile acids in the cirrhotic bile fistula patient was efficient (75%) and equal to bile fistula patients with no cirrhosis (76%); chenodeoxycholic acid synthesis was favored over cholic acid particularly in the cirrhotic patient. [3H]26‐hydroxycholesterol was poorly incorporated in patients with no cirrhosis (25%) and the cirrhotic patient (20%); chenodeoxycholic acid was favored by a wide margin. It is concluded from this and previous reports that the profound reduction in bile acid synthesis present in patients with cirrhosis is not caused singly by a failure in the metabolic pathways from 7α‐hydroxycholesterol to cholic and chenodeoxycholic acid (i.e., 12α‐hydroxylation step), but rather due to a defect in the feedback control regulatin

ISSN:0270-9139    

DOI:10.1002/hep.1840010210

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY

摘要:

AbstractA prospective controlled comparison of portal‐systemic (PSS) and distal splenorenal shunts (DSRS) in cirrhotic patients who had survived hemorrhage from esophagogastric varices was undertaken 5 yr ago at five hospitals by the Boston‐New Haven Collaborative Liver Group. The clinical and endoscopic criteria for massive hemorrhage were satisfied in 155 patients. Thirty‐four patients were excluded, primarily because of uncontrolled hemorrhage. Thirty‐four were rejected because they were poor operative risks and 21 because they did not satisfy criteria. Thirteen patients refused to participate; the remaining 53 were randomized; 29 to receive PSS and 24, DSRS. The two groups were similar in clinical, laboratory, and manometric characteristics. The DSRS group was older and tended to have had more previous hemorrhages. Followup ranged from1to56months (mean21). After PSS, which was performed by 10 different surgeons, 6 patients died during the hospital admission (21%) compared to 2 after DSRS (12%). There were 6 late deaths in the PSS group and 4 in the DSRS group. Portal‐systemic encephalopathy occurred in 5 of the 23 survivors of PSS (23%), and in 6 of the 19 who survived DSRS (32%). Two patients in the PSS group bled (9%), 1 after thrombosis and 1 after stenosis of the shunt. Three patients in the DSRS group bled (16%) and all had thrombosis of the shunt. PSS was associated with an unexplained but inordinately high operative mortality.Although the DSRS was accomplished with an acceptably low operative mortality, it was associated with frequent portal‐systemic encephalopathy, shunt occlusion, and recurrent hemorrhage. Similar incidences of portal‐systemic encephalopathy, shunt occlusion, and recurrent hemorrhage were observed in the PSS group. More patients and longer followup are necessary to determine which of these portal decompressive procedure

ISSN:0270-9139    

DOI:10.1002/hep.1840010211

出版商:W.B. Saunders    

年代:1981

数据来源: WILEY