摘要:

AbstractPatients with overt alcoholic liver disease who had participated in a multicenter therapeutic trial and subgroups of controls (i.e., alcoholic patients without liver disease and patients with neither alcoholism nor liver disease) were tested for hepatitis B virus and hepatitis C virus antibodies to determine the prevalence of these antibodies and any clinical association in the progression and outcome of alcoholic liver disease. Antibodies to hepatitis B (anti–HBs and/or anti‐HBc) were found in 29.2% of patients with alcoholic liver disease, in 26.1% of hospitalized alcoholic patients without liver disease and in 24.2% of hospitalized nonalcoholic patients without liver disease; frequencies were not significantly different from one another. HBsAg was not evaluated because HBsAg+ patients had been excluded from the original trial. The presence of these antibody markers correlated with ethnic origin of and immunoglobulin levels in the patients. In contrast, antibody to hepatitis C, as detected by enzyme immunoassay, was positive in 27.1%, 4.8% and 3.0% of the three groups, respectively, the first differing significantly from the other two. Antibody to hepatitis C virus positivity correlated significantly with clinical severity of the disease and with the presence of histological features that imply chronic viral infection (periportal inflammation, cirrhosis), despite the fact that the supplementary assay for antibody to hepatitis C virus, using recombinant immunoblot assay, reduced the positive rate by 79%. Although the presence of hepatitis B antibodies did not correlate with patient survival, some categories of patients with antibody to hepatitis C virus did; the survival of those with antibody to hepatitis C virus and recombinant immunoblot assay reactivity was 67%; for those with antibody to hepatitis C virus positivity but recombinant immunoblot assay negativity the survival was 29% (p<0.01). The reason for the poor prognosis for those with antibody to hepatitis C virus positivity and recombinant immunoblot assay negativity is not clear, although some theories are offered. (HEPATOLOGY1991;14:581

ISSN:0270-9139    

DOI:10.1002/hep.1840140402

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractIn anesthetized male rats, infusion of glutamine (2 μmol/min) into the superior mesenteric vein at a rate known to induce liver cell swelling leads to marked decreases in renal glomerular filtration rate, renal para‐aminohippurate clearance and urinary flow rate. Glutamine infused at identical rates into the jugular vein does not elicit any of these effects. The effect of glutamine is mimicked by serine but not by glutamate. Spinal transection, renal denervation or section of the vagal hepatic nerves abolishes the effect of mesenteric venous glutamine infusion. Mesenteric application of glucagon (1 ng/min) or of both glutamine and glucagon enhances glomerular filtration rate and urinary flow rate. Infusion of 1 ng/min glucagon through the jugular vein does not significantly alter glomerular filtration rate or urinary flow rate. The data disclose a powerful liver‐borne mechanism regulating kidney function that is mediated by the hepatorenal innervation. (HEPATOLOGY1991;14:590

ISSN:0270-9139    

DOI:10.1002/hep.1840140403

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractThree oligonucleotide primer combinations selected from the 5′ noncoding, the nucleocapsid and the putative nonstructural regions of the hepatitis C virus genome were compared in a nested polymerase chain reaction assay with respect to sensitivity and specificity for the detection of viral RNA in chimpanzeeinfected and human‐infected sera. Sera from both the acute and the chronic phase of the infection were obtained from 13 animals inoculated with five different non‐A, non‐B hepatitis strains and from seven cardiac surgery patients who had non‐A, non‐B hepatitis develop after transfusion and who had been tested in parallel for the presence of hepatitis C virus RNA and anti‐C100‐3. A total of 90% of the acute‐phase and 100% of the chronic‐phase sera tested positive for hepatitis C virus RNA when the 5′ noncoding–derived or the nucleocapsid‐derived combinations were used; only 58% and 56%, respectively, gave positive results with the putative nonstructural primers, whereas 33% and 71%, respectively, scored positive for C100‐3. Thus polymerase chain reaction primers selected from either the highly conserved 5′ noncoding or nucleocapsid‐regions appear to provide the sensitivity and the specificity necessary to detect low levels of hepatitis C virus RNA in both chimpanzee‐infected and human‐infecte

ISSN:0270-9139    

DOI:10.1002/hep.1840140404

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractPatients with cirrhosis and ascites show sodium retention and normal or increased plasma levels of atrial natriuretic factor, a peptide with powerful natriuretic activity. To investigate whether this paradoxical observation could be related to a dysregulation in the process of synthesis and maturation of atrial natriuretic factor leading to abnormal molecular forms lacking biological activity, the chromatographic patterns of atrial natriuretic factor contained in plasma extracts from 10 patients with cirrhosis and ascites and 6 healthy subjects were compared. Atrial natriuretic factor from cirrhotic patients was also tested in two different radioreceptor assays, which detect the biologically active form(s) of this peptide. Patients with cirrhosis and ascites had higher plasma levels of atrial natriuretic factor (81.3 ± 8.5 pg/ml, p<0.001) than control subjects (29.8 ± 3.2 pg/ml). High‐performance liquid chromatography analysis of atrial natriuretic factor showed an identical chromatographic pattern in cirrhotic patients and control subjects. Three peaks related to the atrial natriuretic factor prohormone were observed in cirrhotic patients and control subjects, accounting for 64%, 23% and 11% of the total atrial natriuretic factor in cirrhotic patients and 63%, 18% and 8% of the total atrial natriuretic factor in control subjects. The main peak eluted at the same position of synthetic human atrial natriuretic factor (Ser 99‐Tyr 126), which represents the major active form of the circulating hormone. Cirrhotic atrial natriuretic factor displayed the same ability to inhibit the binding of125I‐atrial natriuretic factor to rat glomerular and bovine adrenal membrane receptors as synthetic human atrial natriuretic factor. In conclusion this study demonstrates that atrial natriuretic factor of patients with cirrhosis and ascites has an equipotent binding activity to its receptor as to that of synthetic human atrial natriuretic factor and possesses the same molecular weight and biologically active forms as atrial natriuretic factor of normal subjects. These data indicate that in cirrhosis there is no dysregulation in the atrial natriuretic factor maturation process. (HEPATOLOGY1991;14:6

ISSN:0270-9139    

DOI:10.1002/hep.1840140405

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractCytosolic receptors for estrogen and progesterone were assayed in 50 gallbladders from 29 women and 21 men who had cholecystectomies because of choleithiasis. High‐affinity (equilibrium dissociation constant, KD= 0.46 ± 0.23 nmol/L of 24 cases) estrogen receptors were detected in 20 of 29 gallbladders from women (range = 1.6 to 32 fmol/mg protein; mean ± S.D. = 10.9 ± 8.1), whereas in men only 4 of 21 specimens contained detectable estrogen receptors. High‐affinity (KD= 0.45 ± 0.17 nmol/L; mean ± S.D. of 41 cases) progesterone receptors were found in 25 of 29 gallbladders of women (range = 2 to 62 fmol/mg protein; mean ± S.D. = 19.2 ± 14.4) and in 16 of 21 gallbladders of men (range = 4 to 36 fmol/mg protein; mean ± S.D. = 12.5 ± 8.5). There is a statistically significant difference between men and women in the proportion of estrogen receptor–positive gallbladders, 19% and 69% for men and women, respectively. Progesterone receptors are present in similar proportion in the gallbladders of men (72.2%) and women (86.2%). In women a positive correlation between estrogen and progesterone receptors was found. Even in the absence of estrogen receptors, the gallbladders of men express progesterone receptors at levels similar to those observed in women. At least in cholelithiasic gallbladders, this suggests that a sex difference exists in the coexpression of estrogen and progesterone receptors. Such a difference could be related with the higher gallstone incidence in women than in men. (HEPATOLOGY19

ISSN:0270-9139    

DOI:10.1002/hep.1840140406

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractWe studied 35 adult patients (mean age = 43 yr) referred for orthotopic liver transplantation. Spinal bone mineral density was measured by quantitative computed tomography scanning before transplantation (n = 35) and at 3 mo (n = 21) and 12 mo (n = 11) after orthotopic liver transplantation. The readings were corrected to age 50 yr, using the regression equations derived from normal control subjects. Quantitative bone histological studies were performed in 17 patients before orthotopic liver transplantation and 3 mo after orthotopic liver transplantation. Before orthotopic liver transplantation, the corrected spinal bone mineral density in men was 108 ± 20 mg/cm3, less than in male control subjects (129 ± 22 mg/cm3, p<0.005). In women patients the value was 117 ± 27 mg/cm3, and in female control subjects 126 ± 19 mg/cm3(NS). However, women patients with primary biliary cirrhosis had lower spinal bone mineral density (106.5 ± 14.8) than female control subjects (p<0.005). Histologically, the resorbing surface was near the normal mean, whereas the osteoblast surface, tetracycline surface and bone formation rate was lower in men (p<0.05) but not women. Spinal bone mineral density decreased by 24% in the first 3 mo after orthotopic liver transplantation with no further decrease at 12 mo. Five patients had vertebral fractures within 6 mo of orthotopic liver transplantation. One patient fractured a wrist and three had osteonecrosis of the hip or knee. Bone histological studies 3 mo after orthotopic liver transplantation showed no change in resorbing surface but an increase in osteoblast surface from 2.1% ± 3.0% to 6.0% ± 7.0% (p<0.05), increased bone formation in men (21 ± 31 to 80 ± 96 μm2/mm2p<0.05) and serum osteocalcin increased from 2.3 ± 0.3 pg/ml before transplantation to 5.9 ± 1.8 pg/ml (p<0.05). Bone loss was related to the number of hospital days after orthotopic liver transplantation (r = 0.79, p<0.001) but not to any other factor, including prednisone and cyclosporin dose.The study shows that bone mass is reduced in men with end‐stage liver failure and that considerable bone loss occurs in the first 3 mo after orthotopic liver transplantation, frequently resulting in vertebral fractures. The exact cause of the bone loss is not clear, although immobilization appears to be important, probably in combination with corticosteroid therapy. The cellular changes causing this bone loss must occur very early after orthotopic liver transplantation because by 3 mo after transplantation, increased bone formation had begun to occur. (HEPATOLOGY199

ISSN:0270-9139    

DOI:10.1002/hep.1840140407

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractIn liver and serum, AST activity is dependent on two isoenzymes, which are mitochondrial and cytosolic in nature. In an attempt to explain the well‐known increase of serum mitochondrial AST‐to‐total AST ratio in chronic alcoholism (which is due to a specific increase of the mitochondrial isoenzyme), we analyzed: (a) liver and serum AST, ALT and glutamate dehydrogenase activities in 23 active drinkers with minimal liver changes, 11 alcoholic patients with cirrhosis who had stopped drinking, 18 nonalcoholic patients with viral chronic hepatitis and 11 subjects with normal livers; and (b) the expression of messenger RNAs for AST isoenzymes in the corresponding liver samples.Enzymatic activities were decreased in the liver irrespective of the origin of the liver disease. In patients with viral chronic hepatitis (or in those with alcoholic cirrhosis when abstinent), variations in liver proteins and messenger RNAs paralleled significant decreases in mitochondrial AST, ALT and glutamate dehydrogenase and a nonsignificant decrease of cytosolic AST. In alcoholic patients with minimal liver changes, the significant decrease of hepatic cytosolic AST, ALT and glutamate dehydrogenase activities contrasted with a close‐to‐normal liver mitochondrial AST activity; the increased amounts of mitochondrial AST messenger RNA give evidence for a pretranslational mechanism of regulation, indicating a possible increase in the total production of mitochondrial AST in the liver. The decrease of hepatic cytosolic AST activity was statistically significant only in alcoholic patients without cirrhosis who had a normal cytosolic AST mRNA level, thus suggesting a contributory role of translational or posttranslational regulation. In conclusion, regulation of AST isozymes during liver disease is complex, including differential, pretranslational and translational or posttranslational mechanisms. (HEPATOLOGY1991;14

ISSN:0270-9139    

DOI:10.1002/hep.1840140408

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractThe objective of this study was to determine the relationship between cytosolic pH and vesicular pH during ATP depletion. Using digitized video microscopy and single, cultured rat hepatocytes, cytosolic pH and vesicular pH were quantitated by ratio imaging of BCECF (2′, 7′ biscarboxyethyl‐5, 6‐carboxyfluorescein) fluorescence and fluoresceindextran fluorescence, respectively. Basal value for cytosolic pH was 7.26 and basal value for vesicular pH was 4.86. During ATP depletion by metabolic inhibition with KCN plus iodoacetic acid or antimycin A, cytosolic pH decreased 0.71 units to 6.55. In separate experiments under identical conditions, vesicular pH increased 1.59 units to 6.45, suggesting that protons were leaking from acidic vesicles during ATP depletion. Fluorescein‐dextran fluorescence remained punctate, indicating that the rise in vesicular pH was due to an efflux of protons from vesicles and not loss of vesicle integrity. To determine whether efflux of protons from acidic vesicles can acidify cytosolic pH, we used two maneuvers that result in leakage of protons from acidic vesicles without significantly decreasing cellular ATP: (a) hypotonic stress in K+free media and (b) exposure of the cells to the H+‐ATPase inhibitor NBD‐Cl. Both hypotonic stress and NBD‐Cl decreased cytosolic pH 0.4 units to 6.86 and increased vesicular pH 2.0 units to 6.76, resulting in near‐equilibration of cytosolic pH and vesicular pH. Thus an efflux of protons from intracellular compartments will acidify cytosolic pH of hepatocytes (pH 6.86), but not to the same degree as ATP depletion (pH 6.55). Calculations based on buffering capacities and relative volumes of the cytosol and acidic compartments suggest that efflux of protons from acidic compartments into the cytosol may account for up to 20% of the decrease of cytosolic pH during the ATP depletion of anoxia observed in hepatocytes. (HEPATOLOG

ISSN:0270-9139    

DOI:10.1002/hep.1840140409

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractA quantitative histochemical method was developed for the demonstration in rat liver of the activity of phosphofructokinase, one of the enzymes assumed to be rate‐limiting for glycolysis. The procedure was based on the reduction of a tetrazolium salt as final electron acceptor and a multistep reaction using the exogenous or endogenous auxiliary enzymes aldolase, triosephosphate isomerase and glyceraldehyde‐3‐phosphate dehydrogenase. The highest activity was found in unfixed cryostat sections of rat liver when the incubation medium contained 17% (wt/vol) polyvinyl alcohol, 100 mmol/L Tris‐maleate buffer (pH 8.4), 20 mmol/L fructose‐6‐phosphate, 2 mmol/L ATP, 2 mmol/L MgCl2, 5.9 mmol/L NAD+, 0.47 mmol/L 1‐methoxyphenazine methosulfate, 5 mmol/L sodium azide and 5 mmol/L Nitro BT. The addition of auxiliary enzymes was not necessary to demonstrate maximum activity in rat liver. The specificity of the reaction was proven by the absence of any specific (test minus control) reaction when the incubation was performed in the presence of 25 mmol/L phosphoenolpyruvate, a competitive inhibitor of phosphofructokinase. Cytophotometric analysis revealed that linear relationships exist between the amount of specific reaction product formed and incubation time and the section thickness. The Kmvalues for fructose‐6‐phosphate and the Vmaxvalues were not significantly different in periportal and pericentral areas of livers from either normally fed or 24‐hr‐fasted rats. The homogeneous distribution of phosphofructokinase activity in the liver acinus is in line with biochemical findings using hepatocytes isolated from the two different areas showing that these cells contained similar amounts of enzyme activity. It indicates that either phosphofructokinase is not a rate‐limiting enzyme of glycolysis or the capacity for glycolysis is not different in periportal and pericentral areas of the rat liver acinus. (HEP

ISSN:0270-9139    

DOI:10.1002/hep.1840140410

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractBile‐canaliculus contraction in rat hepatocyte doublets is postulated to involve activation of an actinmyosin system. We examined this hypothesis by determining the relationship between canalicular contraction and cystolic free Ca2+([Ca2+]i) concentration after extracellular addition of ATP or microdialysis of myosin light chain kinase or its Ca2+‐independent fragment, which retains catalytic activity. After incubation of doublets with 200 μmol/L ATP in the absence of extracellular Ca2+, [Ca2+]ipeaked at 40 sec and 71% of canaliculi contracted within 4 min. Decreasing effects were observed with equimolar ADP, AMP and nonhydrolyzable ATP, but no effect was observed with adenosine. The effect of extracellular ATP on [Ca2+]iand canalicular contraction was dose dependent. Addition of extracellular Ca2+and ATP resulted in a plateau level of [Ca2+]i. Cytochalasin D, which depolymerizes actin filaments, inhibited ATP‐induced canalicular contraction, but not the increase in [Ca2+Microdialysis of myosin light chain kinase and its Ca2+‐independent fragment (but not the heatdenatured fragment, albumin, trypsin plus soybean inhibitor or buffer) into one hepatocyte of a doublet resulted in canalicular contraction in 86% of doublets. Injection of myosin light chain kinase or its Ca2+‐independent fragment did not increase [Ca2+]iwithin 5 min. These results indicate that (a) the basolateral plasma membrane of hepatocytes has a P2Y‐class purinoceptor, (b) increased [Ca2+]iafter incubation with ATP is initially due to mobilization from internal sites and (c) canalicular contraction is directly related to [Ca2+]iand activation of an actin‐myosin system. The physiological role of extracellular ATP in canalicular contraction is uncertain. (HEPATOLOGY19

ISSN:0270-9139    

DOI:10.1002/hep.1840140411

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY