摘要:

AbstractThe cellular oncogene c‐jun is transiently expressed in cultured cells stimulated to proliferate but has not been identified in normal liver. Because partial hepatectomy results in coordinated cell proliferation in the remaining liver, we investigated c‐jun expression after partial hepatectomy in mice. Northern analysis of whole liver mRNA demonstrated a transient increased expression of c‐jun within half an hour of the operation. The related gene junB increased only 50%, whereas c‐jun expression increased 13‐fold compared with sham‐operated controls. To determine the cell of origin of the c‐jun transcript, bothin situhybridization and Northern analysis of mRNAs from parenchymal and nonparenchymal cell fractions were performed 2 hr after partial hepatectomy. C‐jun expression was found in both cell populations. To investigate the mechanism of increased c‐jun expression, cycloheximide was given to some animals preoperatively. C‐jun induction occurred with cycloheximide alone, but partial hepatectomy further increased c‐jun expression, indicating that new protein synthesis was not required for this effect. Furthermore, run‐on transcriptional assay demonstrated a twofold increase in c‐jun expression. Thus c‐jun expression increase after hepatectomy by transcriptional and posttranscriptional mechanisms. Because the extracellular matrixdegrading enzyme transin, which bears the recognition site for jun/AP‐1, showed sustained induction after hepatectomy, we speculate that an important function of c‐jun expression could be the remodeling of extracellular matrices to accommodate cell proliferatio

ISSN:0270-9139    

DOI:10.1002/hep.1840110602

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractA hypothesis has been proposed by this laboratory that endogenous gut‐derived lipopolysaccharide is responsible for systemic endotoxemia in animals with acute liver injury particularly after partial (67%) hepatectomy. Systemic lipopolysaccharide and possibly fibrin aggregates or tissue debris then elicit release of cytokines from phagocytizing macrophages and/or monocytes that may be essential for normal liver regeneration. To test this hypothesis liver regeneration was assessed in germ‐free euthymic mice that lack the gram‐negative bacterial source of lipopolysaccharide, as well as being deficient in lymphoid tissue and relatively resistant to endotoxin. To complement the germ‐free animals, conventional athymic nude BALB/c mice and conventional lipopolysaccharide‐resistant C3H/HeJ mice were also examined. Liver regeneration, quantified by [3H] thymidine incorporation into hepatic DNA after partial hepatectomy was performed on mice anesthetized with ether, was significantly depressed in germ‐free euthymic and conventional athymic BALB/c mice and delayed in conventional lipopolysaccharide‐resistant C3H/HeJ mice, as compared with conventional control BALB/c and C3H/HeN animals. Pretreatment of conventional euthymic control mice with lipopolysaccharide 24 hr before surgery significantly stimulated hepatic DNA synthesis after 67% liver resection. Germ‐free euthymic, conventional athymic, and conventional lipopolysaccharide‐resistant mice pretreated with endotoxin did not manifest significant stimulation of liver regeneration. Evidence is reviewed that cytokine release in response to endotoxin was depressed in germ‐free euthymic, conventional athymic, and conventional lipopolysaccharide‐resistant mice as compared with conventional euthymic controls. The inability to release cytokines in response to gut‐derived endotoxin in the three murine strains studied or the paucity of endogenous lipopolysaccharide in germ‐free animals may explain the significant depression or delay of liver regeneration as compared with conventional euthymic control mice.(HEP

ISSN:0270-9139    

DOI:10.1002/hep.1840110603

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to support the hypothesis that cytokines such as interleukin‐1, tumor necrosis factor and interleukin‐6 are released by macrophages or monocytes within 1 to 2 hr of phagocytosis of circulating, gut‐derived backterial lipopolysaccharide translocated by acute liver injury. Time courses of fever, neutrophilia and low blood‐zinc levels generally attributed to cytokines were quantified after partial (37%) hepatectomy of rats under ether anesthesia. These acute phase responses in hepatectomized rats were compared with those after intravenous injection of exogenous endotoxin and human natural interleukin‐1. Fever commenced 30 min after interleukin‐1 injection, 4 hr after exogenous lipopolysaccharide injection and 6 hr after 67% liver resection. Similarly, rectal temperatures were significantly elevated in recipient rats 30 min after intravenous administration of donor plasma from hepatectomized animals, indicating that cytokines, not lipopolysaccharide, elicited the febrile response. Neutrophilia was present 1, 2, and 4 hr after interleukin‐1 injection, lipopolysaccharide injection and hepatectomy, respectively. Furthermore, the reduction in plasma zinc, which depends on cellular metallothionein synthesis, occurred 4 hr after interleukin‐1 administration and 6 hr after lipopolysaccharide injection or partial hepatectomy. Donor plasma from hepatectomized rats also elicited neutrophilia at 1 hr and low blood‐zinc levels 4 hr after injection in recipient animals. The timing of these responses, just as for the fever, implies that cytokines and not lipopolysaccharide in the donated plasma elicited the neutrophilia and hypozincemia. Evidence was reviewed that interleukin‐1, tumor necrosis factor and interleukin‐6 function as hepatotrophic factors and have been identified in the circulation of humans with liver damage. This complements the conclusion of this study that unspecified cytokines are released after partial hepatectomy of rats.(HEPATOL

ISSN:0270-9139    

DOI:10.1002/hep.1840110604

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractLight microscopic, immunohistochemical and ultrastructural analysis of protocol before transplantation and after reperfusion biopsy specimens from 87 randomly selected patients was performed to assess the contribution of preservation and immunological injury to early graft failure. Most biopsy specimens were essentially normal by light microscopy before transplantatio, and no particular feature could be relied on to predict function after transplantation. Ultrastructural examination of biopsy specimens before transplantation demonstrated preferential degeneration of sinusoidal lining cells, but no strict correlation was seen between ultrastructural sinusoidal integrity before transplantation and function after transplantation. The presence of zonal or severe focal necrosis and a severe neutrophilic exudate in biopsy specimens after reperfusion presaged a poor early postoperative course in most, but not all, patients. The presence of preformed lymphocytotoxic antibodies had no effect on the early clinical course, but was associated with Kupffer cell hypertrophy in needle biopsy specimens taken after transplantation. No definite evidence was seen of hyperacute rejection as a result of preformed lymphocytotoxic antibodies as detected in conventional assays. These findings suggest that preservation injury accounts for only a subset of grafts that fail to function after transplantation. Other perioperative or “recipient” factors may be of equal or greater importance in early graft dysfunction or failure.(HEPATOLOGY 1990;11:932‐

ISSN:0270-9139    

DOI:10.1002/hep.1840110605

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractThis study was conducted to determine whether an amino acid solution enriched with branched‐chain amino acids altered protein catabolic rates and plasma ammonia in patients with cirrhosis. Nine stable subjects were given two peripheral intravenous infusions: a standard amino acid solution (solution A) and a branched‐chain‐enriched solution containing 97% more leucine (solution B). Each solution was given for separate 9‐day (group 1, n = 6) or 3‐day (group 2, n = 3) periods. Amino acid solutions delivered 0.7 gm protein kg−1day−1. Diets provided an additional 0.3 gm protein plus maintenance calories. Protein turnover was assessed by a primed continuous infusion of [1‐14C] leucine in six patients (three patients in group 1 and three patients in group 2). Nitrogen balance and urinary 3‐methyl histidine excretion were determined in group 1 patients. Compared with solution A, solution B increased leucine flux and leucine oxidation but had no significant effect on protein synthesis or catabolism based on the plasma specific activity of either leucine or α‐ketoisocaproic acid. The additional leucine infused with solution B was quantitatively oxidized. Nitrogen balance did not differ with the two solutions and there was also no difference in the urinary excretion of 3‐methyl histidine, suggesting that muscle protein catabolism was unchanged. Plasma ammonia concentration decreased significantly during the infusion of solution B and was associated with a slight fall in plasma glucagon concentration. The results indicated that a branched‐chain‐enriched amino acid solution did not alter protein synthesis or catabolism although it did lower the plasma ammonia when compared with a standard amino acid formula in stable cirrhotic patients.(HE

ISSN:0270-9139    

DOI:10.1002/hep.1840110606

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractThe disposition of oral oxazepam was investigated in seven patients with decompensated cirrhosis and encephalopathy and in nine healthy individuals to further examine the hypothesis of preservation of glucuronidation in liver disease. The patients showed a severe reduction in the quantitative liver function as assessed by estimation of the clearance of antipyrine; the median value was 9 ml. min−1and the range was 6 to 12 ml. min−1. Apparent clearance of oxazepam in cirrhotic patients was 0.55 ml. min−1. kg−1, with a range of 0.46 to 1.24 ml. min−1. kg−1, compared with 1.19 ml. min−1. kg−1and a range of 0.80 to 1.66 ml. min−1. kg−1in the controls (p<0.05). The unbound clearance of oxazepam in patients was 4.1 ml. min−1. kg−1, with a range of 3.4 to 5.5 ml. min−1. kg−1, compared with 25.4 ml. min−1. kg−1, and a range of 16.7 to 43.7 ml. min−1, kg−1, p<0.001, in the controls. In patients with liver disease, the unbound clearance of oxazepam correlated significantly with antiyprine clearance (r = 0.88; p<0.05). The results suggest a reduced capacity for glucuronidation in patients with decompensated liver disease and severe hepatic failure that corresponds to the general reduction in the quantitative liver fun

ISSN:0270-9139    

DOI:10.1002/hep.1840110607

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractSplanchnic and renal extraction of circulating aminoterminal propeptide of type III procollagen and related antigens were studied in 12 patients with normal liver function and in 19 patients with alcoholic cirrhosis during catheterization.Type III procollagen peptide in serum was measured in two assays: the Type III Procollagen Peptide Radioimmunoassay Kit, a new assay that selectively determines the intact propeptide (and larger type III propeptide‐holding antigens) and the Type III procollagen Fab assay that measures both the intact propeptide and the smaller fragments that quantitatively dominate in serum.A significant decrease in the concentration of the intact propeptide between the artery and the hepatic vein was found in the group with normal liver function (p<0.01) and in patients with cirrhosis (p<0.01). In patients with cirrhosis, however, the splanchnic extraction ratio of the intact propeptide (median = 0.04, range = ‐0.03 to 0.16) was significantly lower than in patients with normal liver function (median = 0.17, range = 0.05 to 0.36, p.<0.01). The concentration of the intact propeptide in the hepatic vein was positively correlated to hepatic pressure (n = 18, r = 0.51, p<0.05) and inversely correlated to indocyanine green clearance (n = 15, r = ‐0.61, p<0.05). No splanchnic extraction could be demonstrated in the Type III propeptide Fab assay.A significant renal extraction was found in the Fab assay, but not in Type III Procollagen Peptide Radioimmunoassay Kit. Similar extraction ratios were observed in both healthy patients (median = 0.11, range = 0.00 to 0.21) and cirrhotic patients (median = 0.14, range = 0.06 to 0.22).Thus intact circulating type III procollagen peptide is extracted in the liver, and the extraction ratio is decreased in alcoholic cirrhosis. Smaller type III procollagen peptide‐related antigens are extracted from the circulation by the kidneys.(HEPATOLOGY 1990;11:95

ISSN:0270-9139    

DOI:10.1002/hep.1840110608

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractVasopressin infusion and esophageal tamponade are still widely used to arrest variceal bleeding, but no objective evidence exists on the superiority of either of the two procedures. In this study, 108 cirrhotic patients bleeding from varices were included in a prospective, randomized trial to investigate the comparative effectiveness and safety of balloon tamponade (using the Sengstaken‐Blakemore tube for esophageal varices and the Linton‐Nachlas tube for gastric varices) (n = 52) and intravenous vasopressin infusion (0.4 to 0.8 μ/min) plus intravenous nitroglyeerin infusion (40 to 400 μg/min) (n = 56). Both treatments were maintained for 24‐hr. The hemostatic efficacy according to the intention to treat was 86.5% for tamponade and 66% for pharmacological therapy (p<0.01). No significant differences were found with respect to rebleeding during the first 72 hr after treatment, mortality rate or side effects. These results suggest that esophageal tamponade is more effective than vasopressin/nitroglycerin infusion in the treatment of variceal bleeding in cirrhotic patients.(HEPATOLOGY 1990;11:96

ISSN:0270-9139    

DOI:10.1002/hep.1840110609

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractWe describe four patients with hepatic vein thrombosis caused by Behçet's disease and review the 17 previously published cases. In addition, we compared these 21 cases of hepatic vein thrombosis to our 24 cases of hepatic vein thrombosis caused by primary myeloproliferative disorders. In patients with Behçet's disease, a male predominance (male/female ratio, 19:1) contrasted with the female predominance found in patients with hepatic vein thrombosis complicating primary myeloproliferative disorders (sex ratio = 1:3). The mean age at clinical onset was younger in patients with Behçet's disease than in those with primary myeloproliferative disorders (29 vs. 35 yr). Obstruction of the inferior vena cava was found in 90% of patients with hepatic vein thrombosis caused by Behçet's disease. Inferior vena caval thrombosis appears to be the main pathophysiological mechanism of hepatic vein thrombosis in patients with Behçet's disease. Unlike patients with primary myeloproliferative disorders who often had a progressive course, one third of patients with Behçet's disease had acute liver failure and died within 2 wk of clinical onset. These findings suggest that, in patients with Behçet's disease, hepatic vein thrombosis is a sudden event usually related to the extension of a caval thrombus to the ostium of the hepatic veins.(HEPATOLOGY 1990;11:969

ISSN:0270-9139    

DOI:10.1002/hep.1840110610

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY

摘要:

AbstractSera from patients with primary biliary cirrhosis contain autoantibodies that recognize mitochondrial proteins. Five of the target autoantigens have now been identified as enzymes of three related multienzyme complexes: the pyruvate dehydrogenase complex, the branched chain α‐ketoacid dehydrogenase complex and the α‐ketoglutarate dehydrogenase complex. Each complex consists of component enzymes designated E1, E2 and E3. In this report, we confirm that primary biliary cirrhosis sera react with dihydrolipoamide succinyltransferase, the E2 component of α‐ketoglutarate dehydrogenase complex. Seventy‐three of 188 (39%) primary biliary cirrhosis sera reacted with α‐ketoglutarate dehydrogenase complex‐E2 when immunoblotted against purified α‐ketoglutarate dehydrogenase complex; one of these sera also reacted with the E1 component. In addition, primary biliary cirrhosis sera possessing α‐ketoglutarate dehydrogenase complex‐E2 reactivity specifically inhibited enzyme function of α‐ketoglutarate dehydrogenase complex. Enzyme activity was not affected by primary biliary cirrhosis sera that contained autoantibodies to pyruvate dehydrogenase complex‐E2 and/or branched chain α‐ketoacid dehydrogenase complex‐E2, which lacked α‐ketoglutarate dehydrogenase complex‐E2 reactivity. Furthermore, affinity‐purified primary biliary cirrhosis sera against α‐ketoglutarate dehydrogenase complex‐E2 inhibited only α‐ketoglutarate dehydrogenase complex activity but did not alter enzyme activity of either pyruvate dehydrogenase complex or branched chain α‐ketoacid dehydrogenase complex. Finally, α‐ketoglutarate dehydrogenase complex‐E2 specific affinity‐purified antisera did not react on immunoblot with any component enzymes of pyruvate dehydrogenase complex or branched chain α‐ketoacid dehydrogenase complex. These data demonstrate that the E2 component of α‐ketoglutarate dehydrogenase complex is recognized by a distinct population of autoantibodies separate from autoantibodies that recognize pyruvate dehydrogenase complex‐E2 or branched chain α‐ketoacid dehydrogenase complex‐E2. Our data further suggest that these autoantibodies are directed

ISSN:0270-9139    

DOI:10.1002/hep.1840110611

出版商:W.B. Saunders    

年代:1990

数据来源: WILEY