摘要:

AbstractCalcium salts are often present in the center of all types of gallstones. Matrix proteins are known to be essential for biomineralization and may therefore also be important in the formation and growth of gallstones. Other researchers have described an anionic peptide fraction of a biliary lipoprotein complex in bile and a low—molecular weight acidic glycoprotein present in gallstones. Our goal was to determine whether such a protein was present in bile and whether this protein has any calcium‐binding properties. We identified a pigment‐associated, highly acidic protein that precipitates from bile on addition of CaCl20.5 mol/L. In addition, the protein is selectively concentrated in cholesterol and pigment stones. We have, therefore, confirmed the findings of these other researchers, and we have extended the study of this protein's interactions with calcium. Sodium dodecylsulfate—polyacrylamide gel electrophoresis demonstrates a single band (molecular weight ≤ 14 kD) that reacts positively with cationic stains. The protein was shown to inhibit the precipitation of CaCO3from a supersaturated solution. The capacity to bind calcium was further confirmed by autoradiography with45Ca++and by a membrane adsorption—binding assay. Calcium‐induced aggregation was demonstrated by equilibrium dialysis and by quasielastic light scattering studies. Protein measured by Lowry's assay method and amino acid analysis constitutes only 2% to 4% of the harvested material. We speculate that a substantial lipid component may also be present. The presence of this material in bile, its ability to bind pigment and calcium, its presumed lipid content, its self‐aggregation in the presence of calcium and its selective incorporation into gallstones suggest that it may play a functional role in the pathogenesi

ISSN:0270-9139    

DOI:10.1002/hep.1840160602

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractPorphyria cutanea tarda in human beings is believed to be due to reduced hepatic uroporphyrinogen decarboxylase activity. However, extrinsic factors such as alcohol abuse and drug intake are required for clinical manifestation of the disease. In addition to typical cutaneous lesions, patients with porphyria cutanea tarda usually have chronic liver disease and moderate iron overload. Of 74 Italian patients with porphyria cutanea tarda, hepatitis C virus antibodies were detected in 76% by enzyme‐linked immunoassay and in 82% by recombinant immunoblot assay. Viral genome, studied with nested polymerase chain reaction, was found in the sera of 49 subjects—47 positive and 2 indeterminate on recombinant immunoblot assay. Five percent of the patients were HBsAg‐positive, and about 40% had had past hepatitis B contacts. Alcohol abuse was present in 38%. Liver biopsies performed in 42 patients showed chronic persistent hepatitis in 7 patients, chronic active hepatitis in 22 patients, fibrosis in three patients and cirrhosis in 10 patients. Hepatitis C virus antibody was detected in 100% of patients with chronic active hepatitis and in about 80% of all other groups. Alcohol abuse was more frequent in patients with cirrhosis (80%) than in the other groups. In Italian patients with porphyria cutanea tarda, the prevalence of hepatitis C virus infection was very high, comparable to that in non‐A, non‐B hepatitis and high‐risk patient groups. Hepatitis C virus is probably the main pothogenetic factor of the liver disease of patients with porphyria cu

ISSN:0270-9139    

DOI:10.1002/hep.1840160603

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractProliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and α‐fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus—positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross‐reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in α‐fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of α‐fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval‐type cells may partly account for the elevation of serum α‐fetoprotein frequently seen in precancerous stages of hepatitis B virus—associated human hepat

ISSN:0270-9139    

DOI:10.1002/hep.1840160604

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe natural history of chronic hepatitis B patients who spontaneously cleared serum HBsAg was investigated. A total of 351 patients with chronic hepatitis B were observed in our hospital for at least 3 yr. Seven of these patients became HBsAg negative during the follow‐up period. HBsAg disappeared within 6 mo (range = 11 to 169 days, mean = 70 days) after acute elevation of ALT. ALT levels as high as 500 IU were found in three patients, whereas such elevation was not demonstrated in the other four patients. After the disappearance of HBsAg, ALT levels returned to normal in all patients. With one exception, all patients seroconverted to antibody to HBsAg; however, hepatitis B virus DNA remained detectable in serum using the polymerase chain reaction in five patients. The titer of percent inhibition of antibody to HBcAg gradually decreased to less than 70% when a 1:200 dilution of the serum of six patients was used. Four of the patients had active liver disease develop: two had chronic active hepatitis and two had cirrhosis. Three of these four patients subsequently had hepatocellular carcinoma develop. These findings suggest that patients may suffer complications of chronic hepatitis even after normalization of transaminase activities and after the clearance of HBsAg. Thus hepatitis B virus should be considered as a possible factor associated with hepatocellular carcinoma even in the absence of HBsAg, particularly if serum hepatitis B virus DNA persist

ISSN:0270-9139    

DOI:10.1002/hep.1840160605

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractHepatitis B virus carriers in Israel are mostly HBeAg negative, of whom 5% to 10% have circulating hepatitis B virus. Recently, a hepatitis B virus variant with a stop codon in the precore region was identified, and it was suggested that specific mutations are associated with fulminant or severe chronic active hepatitis. We have analyzed serum samples from HBeAg‐positive and HBeAg‐negative patients by polymerase chain reaction, using primers spanning the precore/core region. Nucleotide sequence analysis (by direct sequencing) from amplified hepatitis B virus DNA demonstrated that viral genomes from all HBeAg‐negative patients contain G to A mutation (nucleotide 1896), leading to the formation of a stop codon. An additional G to A mutation was identified three nucleotides downstream (nucleotide 1899). These patients are of various ethnic origins, with no unique clinical characteristics and with normal liver histology, chronic hepatitis or cirrhosis. No mutation at the precore/core region was observed in the HBeAg‐positive patients. In conclusion, the precore mutations identified in hepatitis B virus carriers in Israel are identical regardless of the carrier's ethnic origin and are associated with mild‐to‐severe li

ISSN:0270-9139    

DOI:10.1002/hep.1840160606

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractTo determine the prevalence and natural history of gastric varices, we prospectively studied 568 patients (393 bleeders and 175 nonbleeders) with portal hypertension (cirrhosis in 301 patients, noncirrhotic portal fibrosis in 115 patients, extrahepatic portal vein obstruction in 117 patients and hepatic venous outflow obstruction in 35 patients). Primary (present at initial examination) gastric varices were seen in 114 (20%) patients more were present in bleeders than in nonbleeders (27% vs. 4%, respectively; p<0.001). Secondary (occurring after obliteration of esophageal varices) gastric varices developed in 33 (9%) patients during follow‐up of 24.6 ± 5.3 mo. Gastric varices (compared with esophageal varices) bled in significantly fewer patients (25% vs. 64%, respectively). Gastric varices had a lower bleeding risk factor than did esophageal varices (2.0 ± 0.5 vs. 4.3 ± 0.4, respectively) but bled more severely (4.8 ± 0.6 vs. 2.9 ± 0.3 transfusion units per patient, respectively). Once a varix bled, mortality was more likely (45%) in gastric varix patients. Gastric varices were classified as gastroesophageal or isolated gastric varices. Type 1 gastroesophageal varices (lesser curve varices) were the most common (75%). After obliteration of esophageal varices, type 1 gastroesophageal varices disappeared in 59% of pateints and persisted in the remainder; bleeding from perisistent gastroesophageal varices was more common than it was from gastroesophageal varices that were obliterated (28% vs. 2%, respectively; p<0.001). Type 2 gastroesophageal varices, which extend to greater curvature, bled often (55%) and were associated with high mortality. Type 1 isolated gastric varices patients had only fundal varices, with a high (78%) incidence of bleeding. Type 2 isolated gastric varices were mainly (86%) ectopic, secondary gastric varices that bled only rarely (9%). Sclerotherapy was more effective in controlling acute bleeding and obliterating varices in gastroesophagael varices than in isolated gastric varices; the latter often required surgery. In conclusion, gastric varices are a common and serious complication of portal hypertension. Our classification was helpful in understanding the natural history and management of gastric v

ISSN:0270-9139    

DOI:10.1002/hep.1840160607

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe influence of lactulose on organic acid fermentation, nitrogen metabolism and excretion in the colonassociated with its mechanism of action on hepatic encephalopathy was investigated. Orally administered lactulose in increasing amounts (0 to 20 to 40 to 80 to 160 gm/day) to 12 healthy volunteers decreased ammonia production in 16.6% fecal homogenates incubated 6 hr and 24 hr at 37° C (mean ± S.E.M.:from 7 ± 1 to 0 ± 0 and from 13 ± 2 to 0 ± 0 mmol/L, respectively). Every dose of lactulose was given for 3 days with intervals of 1 to 2 wk, and 24‐hr stools were collected on day 3. Fecal concentrations of ammonia decreased (from 50 ± 9 to 11 ± 3 mmol/L), but ammonia excretions increased (from 6 ± 2 to 17 ± 4 mmol/24 hr). Total fecal concentrations of nitrogen decreased (from 1,043 ± 78 to 300 ± 136 mmol/L), but excretions of nitrogen increased fourfold (from 111 ± 21 to 457 ± 113 mmoL/24 hr) because of the increase in stool mass. Fecal pH declined (from 6.9 ± 0.1 to 4.9 ± 0.1), but total organic acids (short‐chain fatty acids and DL‐lactate; range = 105 to 148 mmol/L) and osmolality in feces (417 to 450 mOsm/L) did not change, although the colonic fermentation of lactulose had a major impact on the proportions between the nontoxic acetate (increased from 65% ± 2% to 89% ± 3%) and the potentially neurotoxic 3‐6‐carbon fatty acids (decreased from 35% ± 2% to 11% ± 2%). The effects of lactulose on bacterial ammonia assimilation, protein degradation and fermentation in the colonic contentsin vivoare central in the mechanism of action for the increased excretion of nitrogen. However, ammonia excretionper seis not important because it only constitut

ISSN:0270-9139    

DOI:10.1002/hep.1840160608

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractWe observed life‐threatening intrapulmonary hemorrhages and focal proliferative glomerulonephritis in a 41‐yr‐old woman with primary biliary cirrhosis. The severity of the symptoms necessitated blood transfusions and mechanical ventilation; the patient improved with the help of corticosteroid therapy. No formal evidence of either Goodpasture's syndrome or any other well‐defined systemic vasculitis could be found. Neutrophil cytoplasmic antibodies were initially positive and became undetectable after 3 mo of immunosuppressive treatment without relapse. This association has not been described previously and may be added to the list of extrahepatic immune‐mediated conditions associated with primary biliary

ISSN:0270-9139    

DOI:10.1002/hep.1840160609

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractHuman hepatocellular carcinomas from patients in Britain, an area of low prevalence of hepatocellular carcinoma and low dietary exposure to aflatoxin B1, were analyzed for mutations in the p53 tumorsuppressor gene. Abnormalities in the p53 gene were detected in 2 of 19 hepatocellular carcinomas by polymerase chain reaction—single‐stranded conformation polymorphism. Direct sequencing of the evolutionarily conserved regions of p53 (exons 5,6,7 and 8), where mutations have been commonly found in a variety of tumors, confirmed that only two hepatocellular carcinomas had mutations in p53, one a 6‐bp deletion of codons 158 and 159 (exon 5) and the other a G to A transition at codon 286 (exon 8). No mutations were found in any hepatocellular carcinoma in exons 6 and 7; in particular all tumors had wild‐type sequence at codon 249, which has been reported to be a mutational hot spot in the p53 gene in hepatocellular carcinomas from high incidence areas such as China and southern Africa. Abnormalities in p53 expression were examined by immunohistochemistry and found in 1 of the 19 hepatocellular carcinomas. These findings show that p53 mutations are infrequently involved in the malignant transformation of hepatocytes in an area of low hepatocellular carcinoma prevalence. They support the suggestion of a possible link between dietary exposure to aflatoxin and selective G to T mutations at codon 249 of the p53 gene. Our observations also indicate that hepatitis B virus infection alone, present in six of the hepatocellular carcinomas examined, does not account for the specificity for codon 249 mutations reported from endemi

ISSN:0270-9139    

DOI:10.1002/hep.1840160610

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractA total of 238 patients who received curative hepatic resections during the last 10 yr were observed to search for the risk factors linked to early tumor recurrence of human hepatocellular carcinoma after hepatectomy. The results revealed that tumor size, tumor appearance and DNA ploidy were the factors in predicting tumor recurrence after resection for hepatocellular carcinoma. Patients with a tumor size less than or equal to 5 cm or a tumor appearance of the solitary type had better disease‐free survival than did those with a tumor size greater than 5 cm or a tumor appearance of multiple/daughter nodule types (p<0.05). Although patients with pattern III (aneuploid with ≥ 2 G0/G1 peaks) hepatoma had fewer statistically significant differences (p = 019) than did those with pattern I (diploid) or pattern II (aneuploid with single G0/G1 peak) tumors in predicting tumor recurrence, they did have poorer results in terms of the overall survival rate (p<0.05). We conclude that patients with hepatocellular carcinoma having the aforementioned risk factors should be observed clos

ISSN:0270-9139    

DOI:10.1002/hep.1840160611

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY