摘要:

AbstractA new complement‐fixing antimitochondrial antibody–anti‐M8–was detected in patients with primary biliary cirrhosis. Anti‐M8 was only found in association with anti‐M2, however, not all anti‐M2 positive patients had anti‐M8. Thus, among 66 anti‐M2 positive patients, 29 were also positive for anti‐M8, whereas sera from patients who had the complement‐fixing anti‐M2 and anti‐M4 antibodies in parallel always strongly reacted with the M8 antigen. This group was previously described as mixed form. The M8 antigen was isolated either from human liver mitochondria or pig kidney microsomes and could be clearly distinguished from the M4 antigen. In contrast to M4, M8 was trypsin sensitive and banded at sucrose densities from 1.16 to 1.24, while M4 was found at densities from 1.08 to 1.14. Like M4, the M8 antigen also co‐purified with outer mitochondrial membranes.Fifty‐three patients with primary biliary cirrhosis have been followed over a period of up to 16 years and were classified according to their complement‐fixing antimitochondrial antibody profile. At the time of the first diagnosis, 95% of 31 patients being anti‐M2 positive, but anti‐M8 negative (antimitochondrial antibody Profile I) were in Stage I or II. In contrast, only 61% of 13 patients being anti‐M2 and anti‐M8 positive (antimitochondrial antibody Profile II) and 44% of 9 patients with anti‐M2, anti‐M8 and anti‐M4 in parallel (antimitochondrial antibody Profile III) belonged to Stage I or II. At the end of the observation period, only 24% of patients with antimitochondrial antibody Profile I (anti‐M8 negative) had reached Stage III or IV, while 75% of patients with antimitochondrial antibody Profile II or III (anti‐M8 positive) had a progression to Stage III or IV.It is concluded that the presence of complement‐fixing anti‐M8 antibody may herald a

ISSN:0270-9139    

DOI:10.1002/hep.1840060402

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractWe studied intrahepatic bile ducts of five patients with chronic ulcerative colitis and primary sclerosing cholangitis. The livers had been obtained at the time of orthotopic liver transplantation. After specimen cholangiography and perfusion fixation, sequential blocks and sections from portal tracts were studied, combining light microscopy with scanning electron microscopy.In vivocholangiograms were studied also. The specimens revealed: (i) absence of normal bile ducts; (ii) presence of thin‐walled tubular or saccular cholangiectases with semicircular and annular fibrous crests, without evidence of superinfection; (iii) cholangiectases with secondary acute or chronic‐cellular cholangitis, with or without cholangitic abscesses; (iv) fibrous cholangitis without ductal dilatation; (v) transformation of bile ducts into fibrous cords which were either solid or contained remnants of bile duct epithelium, and (vi) complete loss of bile ducts. The shape and distribution of the cholangiectases suggested that these lesions were manifestations of the disease process and not passively dilated normal ducts. Fibrous‐obliterative cholangitis with formation of fibrous cords was found not only at the level of interlobular and adjacent septal bile ducts but also at the level of segmental bile ducts that normally would have been demonstrable in cholangiograms. The “pruned‐tree” appearance in cholangiograms appears to result from the transition between patent and often cholangiectatic ducts, and duct obliteration. At present, intrahepatic cholangiectases in association with duct obliteration can be considered pathognomonic morphologic features of primary sclerosing

ISSN:0270-9139    

DOI:10.1002/hep.1840060403

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to examine the role of calcium ions in gallbladder glycoprotein secretion in cultured guinea pig gallbladder explants. The calcium ionophore A23187 showed a threshold of 2 μg per ml medium for stimulation of secretion of [3H]glucosamine‐labeled glycoproteins over a 30 min incubation period. The ionophore at 3 and 5 μg per ml medium resulted in a 3‐ to 4‐fold increase in secretion of [3H]glucosamine‐labeled glycoproteins. Ionophore‐induced stimulation of glycoprotein secretion was abolished by the addition of 0.01 mMverapamil to the medium. To study the effect of changes in extracellular calcium on basal glycoprotein secretion, explants were cultured for 24 hr in media with 0.007, 0.5 or 2.0 mMcalcium; no differences in basal glycoprotein secretion were observed. When cultured in medium with 1.0 mMEGTA, basal secretion decreased significantly vs. controls in 0.007 mMtotal calcium medium. Total [3H]glucosamine incorporation by explants in medium with EGTA was unaltered, however, suggesting that the low level of calcium in the medium was selectively impairing the secretory process. These findings indicate that calcium ions are important in the regulation of gallbladder glycoprotei

ISSN:0270-9139    

DOI:10.1002/hep.1840060404

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractGallbladder disease is more prevalent in women than men. Estrogen therapy has been associated with an increased incidence of gallbladder disease in both sexes. Further, increased progesterone levels have been implicated in impairment of gallbladder motility in pregnancy. Because sex hormones often exert their action through specific receptors, we investigated whether human gallbladder contains receptors for estrogen and progesterone. Binding of radiolabeled hormones in cytosol and nuclei prepared from human gallbladder of both sexes is indicative of the presence of receptors for both estrogen and progesterone. The binding is saturable, of high affinity and highly specific for its particular type of hormone but not other steroids. Fractionation of sodium molybdate‐stabilized gallbladder cytosol on Sephadex G‐100 demonstrates that the labeled hormones are not bound to defined proteins such as sex steroid binding globulin or albumin. These studies indicate that human gallbladder contains both estrogen and progesterone receptors, that the presence of these receptors may explain the sensitivity of gallbladder tissue to these hormones and that certain aspects of gallbladder function may be mediated by the interaction of steroid hormones with these recept

ISSN:0270-9139    

DOI:10.1002/hep.1840060405

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractA monoclonal antibody, PK1B, directed against rat liver bile acid sulfotransferase was used for the purification and characterization of the enzyme. Incubation of rat liver supernatant with the antibody followed by immunoprecipitation withStaphylococcus aureuscells demonstrated that PK1B reacted with 90% of the enzymatic activity present in the liver supernatant from female rats and 40 to 50% of the activity in male liver preparations. Immunoadsorption chromatography with PK1B bound to Sepharose isolated active enzyme which was purified greater than 75‐fold. Sodium dodecyl sulfate‐polyacrylamide gel electrophoretic analysis of this preparation in the presence of 2‐mercaptoethanol demonstrated three polypeptides: Mr29,500; 32,500, and 34,000. Western blot analysis indicated that PK1B recognized an epitope which was found only on the Mr29,500 polypeptide. Two‐dimensional gel electrophoresis associated the enzymatic activity with this Mr29,500 band. High‐pressure liquid chromatographic analysis of immunopurified enzyme defined three distinct, enzymatically active protein populations: I (Mr400,000 to 170,000); II (Mr130,000), and III (Mr43,000). An Mr29,500 polypeptide was the sole constituent of Peaks I and III and a major constituent of Peak II. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis in the presence and absence of 2‐mercaptoethanol indicated that in Peak II, catalytically active Mr29,500 protein is associated with the other two polypeptides by disulfide bonds. In contrast, Peak I consists of a polymer of Mr29,500 polypeptide which is independent of disulfid

ISSN:0270-9139    

DOI:10.1002/hep.1840060406

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractEmploying thein situperfused rat liver, we examined the origins and mechanisms of transport of proteins into bile. First, utilizing polyacrylamide gels, we noted that many biliary proteins co‐migrated with dominant serum proteins. Upon liver perfusion with serum‐free medium, most proteins disappeared from the biliary profile; one major biliary protein that was not present in serum, identified as secretory component, remained. Kinetic analysis of the disappearance half‐lives of the biliary proteins suggested that some serum proteins enter bile by a slow (20 to 30 min; transcellular) route, while others utilize both slow and rapid (5 min; paracellular) routes. In biosynthetic labeling experiments, secretion of newly synthesized proteins into bile was delayed about 20 min when compared with secretion of proteins into the perfusion medium and comprised less than 1% of the total secreted proteins. When a new liver was inserted into the perfusion medium containing newly synthesized secreted proteins, only two proteins, hemopexin and an unidentified protein, were transported into the bile from the perfusion medium; other biliary proteins were presumed to come directly from the hepatocyte. This latter group included some proteins that were secreted into the perfusion medium as well as into bile, and others, e.g., secretory component, that were secreted only into bile. Based on our results we have defined six pathways for entry of proteins into

ISSN:0270-9139    

DOI:10.1002/hep.1840060407

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractVascular instability as defined by systemic hypotension and unresponsiveness to endogenous or exogenous vasoactive substances is a feature of both patients and experimental animals with obstructive jaundice. In this study, we have attempted to dissect the possible mechanisms for these abnormalities using bothin vivoandin vitromethods.In vivocumulative pressor responses (Rmax) to intravenous and intraarterial infusions of norepinephrine and angiotensin II and to intravenous infusion of angiotensin I were studied pre‐ and postoperatively in chronic bile duct‐ligated dogs and compared to sham‐operated dogs. Preoperatively, the pressor responses to the cumulative infusion of six doses of vasoactive substances in the pre‐sham operated and prechronic bile duct‐ligated dogs were not significantly different. Postoperatively, in the sham‐operated dogs, there was no significant change in systemic blood pressure at 1 and 3 weeks, and only in isolated instances were significantly different pressor responses found compared to the preoperative result. In chronic bile duct‐ligated dogs, the mean systemic blood pressure fell significantly from 117.2 ± 3.1 to 107.2 ± 3.0 mm Hg (p<0.01) at 1 week and remained significantly lower at 3 weeks [109.7 ± 2.6 mm Hg (p<0.05)]. The Rmaxto intravenous, but not intraarterial norepinephrine, was significantly decreased. In contrast, the Rmaxto both intravenous and intraarterial angiotensin II infusions were significantly depressed at both 1 and 3 weeks. Similarly, the response to intravenous angiotensin I was significantly depressed.Cardiac output rose moderately in two sham‐operated dogs from an average of 3.1 to 3.5 liters per min by 3 weeks associated with a decrease of 14.8% in peripheral vascular resistance. In chronic bile duct‐ligated dogs, it rose from 2.9 to 3.6 liters per min associated with a 33% drop in peripheral vascular resistance. There was no evidence of a metabolic acidosis or hypovolemia in the chronic bile duct‐ligated dogs.In vitro, using isolated helically cut arterial strips, we found that in chronic bile duct‐ligated dogs, the mean cumulative contractile response (Rmax) to the addition of angiotensin II to the organ bath (1,571 ± 695 mg) was significantly lower than that from sham‐operated controls (3,683 ± 380 mg). In contrast with norepinephrine, there was no significant difference between arterial strips from chronic bile duct‐ligated and sham‐operated dogs, thus confirming thein vivoresults.In conclusion, the reduced pressor responsiveness to vasoactive substances in this animal model of chronic liver disease is associated with evidence of systemic vasodilation and appears to be multifactorial in origin. With angiotensin II, there is a peripheral and possibly a central defect, whereas with norepinephrine it appears to be a central or cardiopulmonary effect. A better understanding of the mechanism of these changes may help in the management of circulatory abnormalities in pa

ISSN:0270-9139    

DOI:10.1002/hep.1840060408

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractBiliary copper excretion was studied in male, bilecannulated rats of the inbred strains Fischer, Brown Norway, WAG/Rij and Lewis. After intravenous injection of 10, 30 and 50 μg copper per 100 gm body weight, two patterns of copper excretion were observed; their profiles varied with the copper dose and the strain of the rats used. The lowest amounts of copper were excreted by Fischer rats, the highest by WAG/Rij rats; this was related to the effect of the copper dose on both patterns. The subcellular distribution of copper in the liver was studied in Fischer and Brown Norway rats after doses of 50, 100, and 200 μg per 100 gm body weight. Brown Norway rats accumulated more copper in the liver, although the copper concentration was the same in both strains 1 hr after injection of all doses. Fischer rats accumulated proportionally more copper in lysosomal and nuclear mitochondrial fractions whereas Brown Norway rats accumulated proportionally more copper in the cytosol.Gel filtration of liver supernatants revealed that the amount of copper accumulating in the protein presumed to be metallothionein was 2 to 3 times higher in Brown Norway rats, whereas in the Fischer rats more copper eluted in the void volume fraction. We conclude that both biliary copper excretion and copper distribution in the liver are under genetic control. Because of its low copper excretion and reduced binding of copper to metallothionein the Fischer rat, compared to other strains, may be a suitable model for studying the involvement of the liver in copper intoxicatio

ISSN:0270-9139    

DOI:10.1002/hep.1840060409

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractSerum mitochondrial aspartate aminotransferase activity was measured using an immunochemical method in 251 subjects, of whom 140 were chronic alcoholics. The alcoholic patients included 37 with normal liver routine tests (Group I), 61 with noncirrhotic alcoholic liver disease (Group II) and 42 with cirrhosis (Group III), of whom 21 had been abstainers for at least 2 months. All of the remaining 111 subjects were nonalcoholic: 61 had various types of liver disease (Group IV) and 50 were healthy controls. A second assay of serum mitochondrial aspartate aminotransferase activity was performed in 76 alcoholics after a period of abstinence of about 7 days. In addition, serial mitochondrial aspartate aminotransferase determinations were performed in four nonalcoholic volunteers prior to, during and following an alcohol bout.Mean mitochondrial aspartate aminotransferase and mitochondrial aspartate aminotransferase/total aspartate aminotransferase ratio were significantly increased in the alcoholics whatever their liver status, with a sensitivity of the ratio of 81, 85 and 66% for Group I, Group II and the 21 drinkers of Group III, respectively. Only 1 of the 21 cirrhotic abstainers had an increased ratio. Among the 61 nonalcoholic patients with liver disease, 11 had an increased mitochondrial aspartate aminotransferase/total aspartate aminotransferase ratio, specificity of which was 82%. After drinking had been stopped for about 1 week, mitochondrial aspartate aminotransferase decreased by more than 50% and therefore appears as a reliable tool to assess abstinence. In the four cases of alcohol bouts, no significant modifications in mitochondrial aspartate aminotransferase serum values were observed, thus suggesting that mitochondrial aspartate aminotransferase is indeed a marker of chronic, but not of acute, alcohol intake.

ISSN:0270-9139    

DOI:10.1002/hep.1840060410

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY

摘要:

AbstractThis study was designed to determine whether chronic moderate ethanol ingestion alters the levels of vitamin A of liver and esophageal epithelium and if this is dependent on zinc nutriture. Forty male Sprague‐Dawley 4‐week‐old rats were divided into five groups: zinc‐deficient (0.9 ppm), ethanol‐fed; zinc‐deficient; zinc‐adequate (25 ppm); zinc‐adequate (25 ppm), ethanol‐fed; and zinc‐supplemented (50 ppm), ethanol‐fed. All rats received liquid Lieber‐DeCarli diet containing 4,000 IU per liter of vitamin A for 5 weeks. Zinc‐deficient, ethanol‐fed rats and zinc‐adequate, ethanol‐fed rats and zinc‐supplemented, ethanol‐fed rats received 15.5% of the caloric intake as ethanol while zinc‐deficient and zinc‐adequate rats received isocaloric amounts of maltose dextrin. All groups were pair‐fed to zinc‐deficient, ethanol‐fed rats. In addition, a group of eight rats designated as weight‐restricted controls were fed a diet similar to the one given to zinc‐adequate rats but in the amount to obtain a final weight as in the zinc‐deficient group. After 35 days, the liver histology was normal in all rats, and no fat accumulation was noted. Hepatic vitamin A concentration was significantly decreased in zinc‐adequate, ethanol‐fed rats (41 ± 10 μg per gm) and further in zinc‐supplemented, ethanol‐fed rats (12 ± 5 μg per gm) as compared to controls (137 ± 49). A highly significant negative correlation between serum zinc and liver vitamin A was found in ethanol‐fed animals. In zinc‐deficient, ethanol‐fed rats, ethanol did not induce mobilization of liver vitamin A, however, it caused a significant reduction in the ratio of retinyl ester to retinol (53 ± 16%) as compared to controls. Zinc deficiency in the absence of alcohol caused a reduction of hepatic vitamin A concentration and total content, and this effect was not secondary to protein‐caloric malnutrition as values were unaffected in weight‐restricted controls. In esophageal epithelium, a significant reduction of vitamin A stores was noted in zinc‐supplemented, ethanol‐fed rats (0.67 ± 0.7 μg per gm) as compared to controls (3.3 ± 1.0, p<0.01), and a significant negative correlation was seen between serum zinc and esophageal vitamin A levels of ethanol‐fed rats. These results demonstrate that ethanol in moderate quantities causes profound alterations of the vitamin A status of t

ISSN:0270-9139    

DOI:10.1002/hep.1840060411

出版商:W.B. Saunders    

年代:1986

数据来源: WILEY