摘要:

AbstractBiosynthesis of the polyamines, putrescine, spermidine and spermine, is required for DNA synthesis and liver regeneration after partial hepatectomy. Chronic ethanol consumption impairs polyamine synthesis during the prereplicative phase after partial hepatectomy. To determine whether this delay in polyamine synthesis contributes to ethanol's inhibition of liver regeneration, the ability of supplemental putrescine to improve regeneration in ethanol‐fed rats was tested. Chronically ethanol‐fed rats and isocalorically maintained controls underwent partial hepatectomy and were injected intraperitoneally with saline or putrescine (0.03 or 0.30 mmol/kg) at 0, 4, 8 and 12 hr after partial hepatectomy. Rats were killed at 24, 48 or 72 hr, 1 hr after exposure to [3H]thymidine, so that DNA synthesis could be estimated. DNA synthesis was significantly inhibited in ethanol‐fed rats treated with saline compared with saline‐treated pair‐fed controls. Supplemental putrescine did not affect DNA synthesis in pair‐fed rats. In contrast, putrescine significantly improved [3H]thymidine incorporation 24 to 72 hr after partial hepatectomy in ethanol‐fed rats. Intraperitoneal injection of putrescine (1.2 mmol/kg) at the time of partial hepatectomy increased hepatic polyamine concentrations for the first 6 hr after partial hepatectomy despite significantly inhibiting the activity of ornithine decarboxylase, the rate‐limiting enzyme for polyamine synthesis, in both groups. Hepatic polyamine levels after putrescine injection were greater in ethanol‐fed rats than in similarly treated controls. These data suggest that putrescine treatment triggers events that normalize DNA synthesis in ethanol‐fed rats. These results confirm the hypothesis that ethanol's antiregenerative mechanism intimately involves inhibition of putrescine synthesis. (HEPATOLO

ISSN:0270-9139    

DOI:10.1002/hep.1840120402

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractRecent observations in children with rotavirus gastroenteritis and in infant mice given rotavirus vaccine by oral administration suggest that this well‐known gastrointestinal pathogen may infect the liver. To examine this possibility, the susceptibility of Hep G2 cells to infection with a variety of rotavirus strains was tested. These cells were used because they are considered to be well differentiated and exhibit many liver‐specific functions. The Hep G2 cells supported the growth of the simian strain rhesus rotavirus (MMU 18006), a strain currently being used in vaccine trials, but did not support the growth of any human strain (D, DS1, Price or ST3). The rhesus rotavirus infection was cytopathic and resulted in release of lactate dehydrogenase. Rhesus rotavirus growth in Hep G2 cells displayed trypsin‐enhanced infectivity and was inhibited by pretreatment of cells withArthrobacter ureafaciensneuraminidase but not with neuraminidase fromClostridium perfringens. Hep G2 cells were also permissive for another simian strain (SA11), a bovine strain (UK) and single gene substitution reassortants containing VP7 (the major outer capsid neutralization protein) from a human rotavirus strain and the remaining 10 genes from either rhesus rotavirus or UK. In general, UK and its reassortants produced lower levels of antigen than did rhesus rotavirus and its reassortants. Hep G2 cells and other hepatic cell lines may prove to be useful tools to explore the hepatotropic potential of wild‐type rotaviruses and candidate vaccine strains. (HEPATOLOGY 1990;12:6

ISSN:0270-9139    

DOI:10.1002/hep.1840120403

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractMurine lymphokine‐activated‐killer cell activity was readily induced by culturing spleen cells with 10 U/ml of interleukin‐2 for 4 days. In contrast, very little activity was generated under the same culture conditions when nonparenchymal liver cells were used as the responding cells. It was concluded that Kupffer cells produced prostaglandin and interferon α/β, which suppressed lymphokine‐activated‐killer induction because (a) induction of lymphokine‐activated‐killer activity from nonparenchymal liver cells was observed in the presence of indomethacin and anti‐interferon α/β antibody; (b) when adherent nonparenchymal liver cells, primarily Kupffer cells, were removed, lymphokine‐activated‐killer activity could be obtained with interleukin‐2 alone; (c) coculture of Kupffer cells with nonadherent nonparenchymal liver cells in a two‐chambered system inhibited lymphokineactivated killer cell induction in a dose‐dependent manner; (d) exogenous prostaglandin E2and interferon α/β added at the start of culture inhibited interleukin‐2—induced cytotoxicity and proliferation, whereas the other major prostaglandin species in the liver, prostaglandin D2, had little effect. These findings are distinctive with Kupffer cells because splenic macrophages did not exert such inhibition in parallel experiments. Moreover, the supernatant collected from the 24‐hr culture of nonparenchymal liver cells contained greater than 20‐fold more prostaglandin E2and interferon α/β than that from culture of spleen cells. In subsequentin vivoexperiments, when interleukin‐2 was given intraperitoneally to mice, the combination of indomethacin and anti‐interferon α/β antibody significantly enhanced lymphokine‐activated‐killer activity recovered from the liver. Besides Kupffer cells, it was found that hepatocytes, the major cellular component of the liver, also played an inhibitory role on lymphokine‐activated‐killer cell generation. A cell‐free liver cytosolic extract had even more potent suppressive effect, which was partially reversed by supplementation of arginine, indicating that arginase may be one of the hepatocy

ISSN:0270-9139    

DOI:10.1002/hep.1840120404

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractSerum samples from 62 women, inadvertently infected with hepatitis B virus in anin vitrofertilization program, were tested for the presence of hepatitis B virus‐DNA using the polymerase chain reaction. Under conditions of a strict spatial separation of DNA extraction, amplification and product analysis, we succeeded in detection of as few as 360 hepatitis B virus particles per milliliter. Hepatitis B virus‐DNA was detected with a high frequency during HBsAg and HBeAg antigenemia (98.5%) but also in the convalescent phase after appearance of antibody to HBsAg (18.2%). However, all patients with hepatitis B virus‐DNA in convalescent sera were hepatitis B virus‐DNA negative 3 to 6 mo later. All patients with HBeAg‐positive samples showed hepatitis B virus‐DNA positivity by polymerase chain reaction. For acute hepatitis, gene amplification restores the relationship between HBeAg and hepatitis B virus‐DNA observed in serum from chronic hepatitis B patients and calls attention to the prolonged presence of hepatitis B virus‐DNA in serum after generally accepted criteria for resolution of the infection have been reached. (HEPATOLOGY 1

ISSN:0270-9139    

DOI:10.1002/hep.1840120405

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractDuring a follow‐up period of 3.2 ± 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(−) serum (60%), HBeAg(−)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(−)/hepatitis B virus DNA(−) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level ≤ 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level>1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow‐up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion. This study also demonstrated that (a) serum ALT elevations in HBsAg carrier children were usually mild in degree and infrequently exceeded 100 IU/L, (b) hepatitis B virus DNA was detectable in only 1% (4 of 352) of the anti‐HBe(+) sera and all showed normal ALT levels. These findings are in contrast to the adult carriers and denote some unique features of HBsAg carrier children. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840120406

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractPatients undergoing long‐term hemodialysis are at high risk of acquiring hepatitis B yet tend to have poor rates of response to hepatitis B vaccine. The effect of recombinant human γ‐interferon (2 million units/m2) on the response to a recombinant hepatitis B vaccine was evaluated in a prospective, randomized controlled trial in 81 hemodialysis patients. A similar proportion of both groups of vaccinees ultimately developed antibody to HBsAg including 81% of the 41 recipients of vaccine alone (group I) and 89% of the 40 recipients of vaccine with γ‐interferon (group II). However, the antibody to HBsAg response occurred earlier in recipients of vaccine with γ‐interferon, so that at 4 mo 63% of group I and 88% of group II had antibody to HBsAg (p<0.025). Furthermore, titers of antibody to HBsAg tended to be higher in the vaccinees given interferon; the final geometric mean titers were 232 IU/L in group I and 330 IU/L in group II (p = not significant). Retrospective testing for antibody to hepatitis C virus revealed that 21 (26%) hemodialysis patients were seropositive at entry into this trial, but the presence of antibody to hepatitis C virus did not appear to affect the response rate to the hepatitis B vaccine. These results suggest that the effects of γ‐interferon as an adjuvant in increasing the response rate to hepatitis B vaccination deserve further evaluation perhaps most appropriately in persons who have not responded to an initial course of vaccine. (HEPATOLOGY 199

ISSN:0270-9139    

DOI:10.1002/hep.1840120407

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractSera from patients with autoimmune chronic active hepatitis were found to contain IgG‐class antibody to the acidic glycosphingolipid fraction from rabbit hepatocyte plasma membrane by solid‐phase enzyme‐linked immunosorbent assay. Using serum positive for the antibody as a probe, we isolated the target antigen by Iatrobeads column chromatography. Analysis by thinlayer chromatography and negative ion fast atombombardment mass spectrometry revealed that the antigen was sulfatide. The presence of antisulfatide antibody was also confirmed by immunoblotting. The reactivity of the serum with sulfatide was diminished by preincubation of the serum with galactosylceramide‐6‐sulfate and sulfatide, indicating that the antibody reacted with sulfated galactosylceramide regardless of the position of the sulfate residue. The antibody was found in 92.3%, 42.9%, 15.8%, 14.2%, 0% and 0%, respectively, of patients with autoimmune chronic active hepatitis, primary biliary cirrhosis, cirrhosis, systemic lupus erythematosus, chronic active hepatitis and chronic persistent hepatitis. Thus antisulfatide antibody was characteristic of autoimmune‐type chronic liver diseases. Antisulfatide antibody was absorbed by rabbit hepatocyte plasma membrane. Preincubation of sera with sulfatide immobilized on Sepharose decreased their reactivities with not only sulfatide but also rabbit plasma membrane and rat hepatocytes. Therefore sulfatide may be a target antigen of the antibody to hepatocyte surface membrane. (HEPATOLOGY 1990;

ISSN:0270-9139    

DOI:10.1002/hep.1840120408

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractTo clarify the relationship between hepatitis C virus infection and the development of hepatocellular carcinoma as sequelae of non‐A, non‐B posttransfusion hepatitis, 231 patients with chronic non‐A, non‐B hepatitis (96 with chronic hepatitis, 81 with cirrhosis and 54 with hepatocellular carcinoma) were analyzed for antibody to hepatitis C virus and were compared with 125 patients with chronic hepatitis B (50 with chronic hepatitis, 46 with cirrhosis and 29 with hepatocellular carcinoma). Antibody to hepatitis C virus was detected in 89.6%, 86.4% and 94.4% of patients with non‐A, non‐B hepatitis‐related chronic hepatitis, cirrhosis and hepatocellular carcinoma, respectively, compared with 6%, 17.4% and 34.5% with similar diseases related to hepatitis B. A history of transfusion was documented in 52%, 33% and 42% of anti‐hepatitis C virus‐positive cases of chronic hepatitis, cirrhosis and hepatocellular carcinoma. The mean intervals between the date of transfusion and the date of diagnosis of anti‐hepatitis C virus—positive chronic hepatitis, cirrhosis and hepatocellular carcinoma were 10, 21.2 and 29 yr, respectively. In 21 patients with transfusion‐associated hepatocellular carcinoma, anti‐hepatitis C virus was present in each serial sample available for testing, including samples obtained up to 14 yr before the diagnosis of hepatocellular carcinoma. These data suggest the slow, sequential progression from acute hepatitis C virus—related non‐A, non‐B hepatitis through chronic hepatitis and cirrhosis to hepatocellular carcinoma and support a causal association between hepatitis C virus and hepatocellular carcinoma

ISSN:0270-9139    

DOI:10.1002/hep.1840120409

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractOne patient with the fibrolamellar variant of hepatocellular carcinoma was found to be seropositive for HBsAg and anti‐HBe. DNA from tumor and nontumor areas of the liver was examined by molecular hybridization for hepatitis B virus DNA sequences. Undigested DNA from the tumor gave a high‐molecular‐weight smear, and restriction‐enzyme analysis indicated a single instance of integration. Nontumor liver tissue was analyzed from three separate areas. Hepatitis B virus DNA was detected in two of these; restriction‐enzyme digestion suggested they contained different sites of viral integration.As with the typical hepatitis B virus—related hepatocellular carcinoma, analysis of hepatitis B virus DNA from nontumorous liver yielded a different pattern of high‐molecular‐weight bands, indicating that the virus genome had integrated at different chromosomal locations than that seen in the tumor. The finding of integrated hepatitis B virus DNA, especially in tumorous but also in nontumorous liver, would be consistent with an oncogenic role for hepatitis B virus in certain instances of fibrolamellar tumors and in the more typical hepatitis B virus—related hepatocellular carcinoma. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840120410

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractWe prospectively monitored 140 cirrhotic patients for the development of hepatocellular carcinoma for 6 yr, using periodical screening by high‐resolution convex‐array ultrasonography and α‐fetoprotein. Twenty‐eight patients were positive for HBs antigen, 26 patients had received blood transfusions and were negative for HBs antigen and 26 patients had a history of heavy drinking. We detected hepatocellular carcinoma in 40 patients during this period. The overall cumulative incidence of hepatocellular carcinoma in the 6 yr was 39%; the cumulative incidence was 59% in patients with HBsAg, 53% in patients who had had blood transfusions and were negative for HBsAg and 22% in patients who had a history of heavy drinking and who were without HBsAg. Detection of the carcinoma in 85% of these 40 patients was based on results of ultrasonography. Twenty‐six of the patients (65%) had a small hepatocellular carcinoma of 2 cm or less. α‐Fetoprotein levels were lower than 100 ng/ml in 56% of these 40 patients. Patients with cirrhosis are at high risk of developing hepatocellular carcinoma, especially patients with HBsAg or with a history of blood transfusion who are negative for HBsAg. Periodic monitoring by use of ultrasonography in particular is recommended for early detection of hepatocellular carcinoma. (HEPATOLOGY 199

ISSN:0270-9139    

DOI:10.1002/hep.1840120411

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY