摘要:

Abstract:Although it has been known for many years that the liver receives a nerve supply, it is only with the advent of immunohistochemistry that this innervation has been analysed in depth. It is now appreciated not only that many different nerve types are present, but also that there are significant differences between species, especially in the degree of parenchymal innervation. This has stimulated more detailed investigation of the innervation of the human liver in both health and disease. At the same time, functional studies have been underlining the important roles that these nerves play in processes as diverse as osmoreception and liver regeneration. This article briefly reviews current understanding of the morphology and functions of the hepatic nerve supply.

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00721.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Although autoantibodies have been found in the serum of patients with chronic hepatitis C virus (HCV) there has been no convincing evidence of the presence of antimitochondrial antibodies, until now. Sera from 460 untreated patients with chronic hepatitis C were tested for antimitochondrial antibodies, using an indirect immunofluorescence technique; and if they tested positive for the antibodies (titer more than 1:50), they also were treated by Western blot analysis. Seven (1.5%) sera were positive. None of the patients had biological or histological evidence of primary biliary cirrhosis. Antimitochondrial antibodies recognized one of the oxo‐dehydrogenase multienzyme complexe's epitopes by Western blot assay in three patients only. All seven patients were then treated by interferon alpha for six months. None showed exacerbation of liver disease during treatment. HCV‐RNA disappeared from the serum in one patient who became negative for anti‐M2 antibodies. The four patients who did not respond to interferon‐alpha therapy, and the two who relapsed after treatment withdrawal, had sustained positive antimitochondrial antibodies. These data suggest that: 1) antimitochondrial antibodies present in patients with chronic hepatitis C do not always recognize the same epitopes as in primary biliary cirrhosis; 2) these antibodies may disappear after eradication of HCV, suggesting that the production of antimitochondrial antibodies is linked to the presence of the virus and 3) the clinical and biological course of chronic hepatitis C, and the response to interferon‐alpha therapy, does not seem to be different in patients who are positive for antimitochondrial a

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00722.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The distribution of glutamine synthetase (GS) in a mammalian liver is restricted to a small zone of hepatocytes surrounding the central veins. The determination of the size of the GS+ zone in rats by immunohistochemistry revealed that it differed between rat strains and was larger in males than in females of each strain. Accordingly, the means of the relative mean width (RMW) values that characterize the size of the GS+ zone were 19%, 26%, and 39% lower in females than in males of Sprague‐Dawley, Wistar, and Fischer rats, respectively. Upon orchidectomy of male rats, the size of the GS+ zone diminished towards the value found in females, while ovariectomy was without effect. This orchidectomy‐induced reduction was reflected in corresponding changes of the RMW values as well as in the number of GS+ cells per pericentral field and was not due to the slightly smaller size of the GS+ hepatocytes in the orchidectomized males. No such sex difference was found in M775 mice. Biochemical GS activity was higher in the male rats than in the female rats and changed correspondingly to the distribution after gonadectomy. In the mice, only the specific activity of GS dropped after orchidectomy. In primary cultures of rat hepatocytes, no influence of testosterone or estrogen on GS activity and cellular distribution was observed, even after stimulation of GS activity with dexamethasone and growth hormone. Both sex hormones, however, were able to affect the activity of glucose‐6‐phosphate dehydrogenase (G6PD). The observed sex differences in the activity and distribution of GS in rat livers suggest that sex hormones not only modulate the level of this enzyme but are at least partially involved in the determination of the size of the compartment of GS expression. According to the results in the cell cultures, the effects of the sex hormones appear indirect rather than

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00723.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The aim was to assess the specificity and functional significance of liver‐infiltrating and peripheral blood T cells in chronic hepatitis C. Peripheral blood mononuclear cells hepatitis C virus from 50 of 58 (86.2%) patients with chronic hepatitis C virus infection and 6 of 28 (21.4%) controls showed a proliferative T cell response to at least one of 16 synthetic peptides covering highly conserved regions of the core, envelope (El) and non‐structural regions (NS4) of hepatitis C virus. However, six immunodominant peptides were exclusively recognized by the proliferating blood mononuclear cells from 46 patients with chronic hepatitis C virus infection (79.3%). Fine specificity and HLA‐restriction were studied with 15 peptide‐specific CD4+ T cell lines and 23 T cell clones isolated from liver tissue and peripheral blood of 12 patients with chronic hepatitis C. It was demonstrated that the peptide‐specific response of CD4+ T cells was restricted to the presence of autologous accessory cells and HLA‐DR and ‐DP molecules. Eight peptide‐specific T cell lines and five T cell clones derived from liver tissue and peripheral blood, released interferon‐γ (200–6600 pg/ml) and tumor necrosis factor‐α (100–400 pg/ml) and no or little interleukin‐4 (<140 pg/ml) after peptide‐specific or mitogeneic stimulation, thus resembling a Th1‐like cytokine profile. Patients with active liver disease showed significantly higher proliferative responses to hepatitis C virus core peptides than asymptomatic hepatitis C virus carriers or complete responders to interferon therapy. In conclusion, class II‐restricted CD4+ T cell responses to some immunodominant epitopes within the hepatitis core region correlated with disease activity in chronic hepatitis C virus infection. Functionally, liver‐infiltrating and peripheral blood T cells released Th1‐like cytokines in response to the specific stimulus. Thus, it can be suggested that CD4+ T cells can mediate the pathogenesis of chronic he

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00724.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The present study was undertaken in rats to clarify the role of sinusoidal circulatory disturbances due to fibrin thrombi in the development of focal and random hepatocellular necrosis in endotoxemia. Sinusoidal circulation was examined microscopicallyin vivoin rats injected with endotoxin or heparin, or both. The sinusoids in places were occluded by adherent fibrin and neutrophils soon after endotoxin injection, and subsequently the sinusoidal blood flow stagnated, reversed, or detoured. Most of these sinusoidal circulatory disturbances recovered in a few hours. However, when the sinusoidal occlusion developed simultaneously in clusters of adjacent sinusoids, the sinusoidal circulatory disturbance persisted and induced ischemic foci and then hepatocellular coagulative necrosis. Pretreatment with heparin definitely prevented the adherence of fibrin and neutrophils to the sinusoidal walls, and focal hepatocellular necrosis did not appear. These results suggest that focal and random hepatocellular necrosis in endotoxemia is caused by circulatory disturbances due to fibrin thrombi in clusters of adjacent sinusoids.

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00725.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:In the present study, we investigated the role of the spleen in experimental hepatic ischemia/reperfusion in the rat. After a 90‐min period of ischemia in the left and middle hepatic lobes, the ischemia was released and the liver was reperfused for up to 24 h. Plasma alanine aminotransferase reached a peak 3 h after the onset of reperfusion, and gradually decreased thereafter. A histological examination revealed evidence of hepatocellular necrosis and degeneration, especially 24 h after the onset of reperfusion. In addition, there was a noticeable accumulation of polymorphonuclear cells in the liver following ischemia/reperfusion. A splenectomy performed just prior to ischemia/reperfusion reduced both biochemical and histological hepatocellular injury. The number of polymorphonuclear cells in the liver following ischemia/reperfusion was significantly reduced in rats subjected to splenectomy, suggesting that the increase in polymorphonuclear cells may contribute to liver injury. The number of mononuclear cells also increased in the marginal zones of the spleen following ischemia/reperfusion, and appeared to be derived from the splenic monocyte/macrophage population, based on immunohistochemical studies. The spleen plays an important role in the pathogenesis of hepatic ischemia/reperfusion injury and the splenic monocyte/macrophage population contributes to liver damag

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00726.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The right part of the median lobe of the liver of female Wistar rats was irradiated, 12.5 or 25 Gy, at a field size of 15×20 mm. The central part of the irradiated liver lobe was fixed and used for the estimation of the collagen protein ratio by means of the Sirius Red‐Fast Green extraction method, immediately, 8, 16 or 32 weeks after irradiation. No significant increase in collagen content could be demonstrated in this time range, both after irradiation at 12.5 Gy and at 25 Gy. Partial hepatectomy according to Higgins led to rapid regrowfh of the remaining liver lobes. The right lobe grew out rapidly to replace the median lobe. Two days after partial hepatectomy the right lobe was irradiated at the same field size. Measurement of the collagen protein ratio in this experiment did not show a significant increase 8, 16 or 32 weeks after irradiation. However, the 25 Gy group did not survive long enough to obtain data at 16 or 32 weeks. The animals in this latter experiment suffered from ascites before dying. Experimentally induced cholestasis was obtained by ligation and partial resection of the common bile duct. After two weeks of cholestasis the bile flow was restored by Roux‐en‐Y choledochojejunostomy. The effect of irradiation 2 days after repair surgery was studied. Without irradiation the collagen protein ratio is increased. Irradiation of the right part of the median lobe led to a relatively enhanced collagen content in this lobe. Our results indicate that radiation itself does not lead to a significantly enhanced degree of fibrosis in the liver. However when an increase in collagen content was induced by cholestasis, the partial “dilution” of enhanced fibrosis as a result of proliferation of liver parenchyma cells following repair surgery was inhibited by i

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00727.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The effectiveness of second‐generation anti‐hepatitis C virus antibody (anti‐HCV) screening of blood donations for the prevention of non‐A, non‐B post‐transfusion hepatitis (NANB PTH) was assessed. A prospective study of 192 transfusion recipients was performed to compare the incidence of NANB PTH after the introduction of the second‐generation anti‐HCV test with the incidence before its introduction. We used a polymerase chain reaction to detect HCV‐RNA and HBV‐DNA in the sera of patients with NANB PTH. The incidence of acute post‐transfusion hepatitis C was 11% (8 of 71) before the screening for anti‐HCV as compared with 2.5% (3 of 121) after the screening (p<0.05). Viremia was detected within the first five weeks of infection in 10 patients with acute post‐transfusion hepatitis C. However, there was no significant difference in the incidence of non‐A, non‐B, non‐C (NANBNC) PTH before screening (3 of 71, 4.2%) compared with after screening (3 of 121, 2.5%). Usually, NANBNC PTH was not clinically important. Anti‐HCV screening of blood donors significantly reduces the incidence of post‐transfusion hepatitis C,

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00728.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:A randomized, double‐blind, placebo‐controlled trial was performed to evaluate the efficacy and safety of thymosin alphal (α1) in treating chronic hepatitis C. Nineteen Italian patients with chronic active hepatitis C, proven by biopsy were randomly assigned to receive a six month course of thymosin α1(900 μg/m2of body surface area twice weekly) or a placebo. All had HCV‐RNA in their serum (by PCR), with serum ALT levels more than double the upper limit of the normal range for at least six months before enrollment. After treatment, patients were followed for an additional six months. All patients completed the trial. One patient treated with thymosin α1, but no patient in the placebo group, normalized serum ALT levels by the end of the treatment. This patient, however, relapsed at the sixth month of the follow‐up. Overall, there were no significant changes in mean serum ALT levels in either group during the treatment or follow‐up period. No patient cleared HCV‐RNA. No side effects were reported except for local discomfort at the injection sites, reported by some patients treated with thymosin α1. In conclusion, this regimen of thymosin α1is not effective in the treatment of ch

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00729.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:In a 58‐year‐old woman with erythropoietic protoporphyria, asymptomatic liver involvement had been diagnosed 12 years earlier. For more than 20 years the patient had been known to have symptomatic gallstones. A mild polyneuropathy of the lower limbs had been diagnosed several years ago. In December 1992, she presented with colicky upper abdominal pain, dyspepsia and mild jaundice. Diagnosis of beginning cholestasis in erythrohepatic protoporphyria and coincidental choledocholithiasis was made. A causal relation between choledocholithiasis and deterioration of liver function was assumed. Endoscopic extraction of the bile duct stones, however, could not prevent the development of terminal hepatic failure. Biochemically, an excessive protoporphyrinemia and coproporphyrinuria were found. Five weeks after presentation, the patient underwent orthotopic liver transplantation. Immediately after the operation she developed a severe axonal neuropathy with cranial nerve involvement. One year after transplantation, her general condition has markedly improved, but there is still a disabling polyneuropathy. Recently, there were single reports on patients with very similar neurological symptoms following liver transplantation in erythropoietic protoporphyria. This case supports the assumption of a distinct protoporphyrin‐induced neural damage in severe hepatic fa

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00730.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY