摘要:

Abstract:Understanding of the possible toxicity associated with hypervitaminosis A becomes increasingly important in view of the popularity of vitamin A supplementation. Hypervitaminosis A for many years may eventually lead to hepatocellular damage. In the present study, rats were treated for 7 days with high doses of retinol to study the early effects on the metabolism of different types of liver cells using (enzyme) histochemistry, immunohistochemistry and electron microscopy. Excessive intake of vitamin A activates Kupffer cells and induces accumulation of lipid droplets in fat‐storing cells as well as proliferation of these cells. Moreover, it affects the metabolic heterogeneity in the liver lobules, but does not lead to apparent cell damage. Based on the changes in marker enzymes for different metabolic processes, it is concluded that the capacity for breakdown of purines, the antioxidant capacity, the potential for phagocytosis and the regulation of ammonia levels were largely decreased. Increased alkaline phosphatase activity in hepatocytes pointed to an activated process of transport of retinol esters over the bile canalicular membrane. The possible causes of these metabolic changes have been described in the discussio

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00696.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Rats with portal hypertension and experimental liver disease may exhibit increased susceptibility of the gastric mucosa to damage by noxious agents, and increased bacterial translocation through the bowel wall. The aim of this study was to determine mucosal gastric and colonic generation of vasoactive substances, because they may contribute to the altered mucosal function. Rats with partial vein ligation (n=7), complete bile duct ligation (n=6) and sham‐operated rats (n=10) were studied. Three weeks following surgery rats were anesthetized, splenic pulp pressure was measured, stomachs and colons were removed and mucosa was extracted for determination of prostaglandin E2, thromboxane B2, leukotriene B4, leukotriene C4and endothelin‐l by radioimmunoassay (ng/g) and platelet activating factor activity (pg/10 mg) by platelet aggregation. Pulp pressure was>13 mmHg in partial vein ligated rats and bile duct ligated rats and 6 mmHg in sham‐operated rats. No macroscopic or microscopic lesions were seen any of the removed tissues. Gastric mucosal prostaglandin E2and thromboxane B2generation were decreased by 35% and 7%, respectively, in bile duct ligated rats (bile duct ligated versus sham‐operated, p>0.05 for prostaglandin E2and thromboxane B2). Gastric leukotriene B4and C4generation, platelet activating factor activity and endothelin‐l content did not differ significantly among the three groups. A different pattern of changes was observed in the colon. Colonic leukotriene B4generation and endothelin‐1 content were increased in bile duct ligated rats by 105% and 210%, respectively (bile duct ligated versus sham‐operated, p>0.05 for leukotriene B4and endothelin‐l). The decreased gastric mucosal prostaglandin E2generation of bile duct ligated rats may render the gut mucosa of these animals relatively ischemic and vulnerable to damage by noxious agents. The increased colonic leukotriene B4generation and the increased endothelin‐l content of the colonic mucosa of bile duct ligated rats may promote inflammatory and ischemic changes in the colonic mucosa and may enable bacter

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00697.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The results of various biochemical examinations in 14 patients with cirrhosis (6 males and 8 females) with muscle atrophy at the thenar and hypothenar eminence (muscle atrophy group; mAG) were compared with those in 13 patients (8 males and 5 females) with cirrhosis without muscle atrophy at these sites (non‐muscle atrophy group; NmAG). All patients were elderly men and women (mAG and NmAG, mean age, 69±3 years and 60±7, respectively). In most mAG patients, muscle atrophy was accompanied by palmar erythema. Muscle atrophy was histologically demonstrated by biopsy. Furthermore, electromyography and magnetic resonance study of the cervical spinal cord revealed that the atrophy was of myogenic rather than neurogenic origin. The Child‐Pugh score, body mass index and sex hormone level in urine (total 24 h) in the two groups were compared along with the biochemical results. There were no significant differences between the two groups in urine estrogen and testosterone levels. The urinary creatinine excretion was significantly reduced in mAG. The creatine phosphokinese, lactate dehydrogenase isoenzyme and aldolase levels in serum did not differ significantly in the two groups, whereas the serum albumin level was significantly increased in NmAG. Significant differences were observed only for the serum albumin level, age and body mass index. Thus, we consider that palmar muscle atrophy in patients with cirrhosis is not due to hormonal excess in serum, but may be attributable to advanced age and diminished physical str

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00698.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:To determine whether pretreatment HCV‐RNA level, hepatitis C virus genotypes, alanine aminotransferase and histology correlate with subsequent response to interferon‐α therapy or not, serum HCV‐RNA levels and genotype were determined by branched DNA signal amplification assay and genotype‐specific polymerase chain reaction in 43 patients with chronic active hepatitis C. Response to recombinant interferon‐α 2α (504 million units in total) was defined as complete and sustained CR→SR, n=12), complete response followed by relapse (CR→Rel, n=17), and no response (NR, n=10), excluding dropouts (n=4). Patients who showed CR→SR had a lower HCV‐RNA level (0.438 × 106eq/ml) compared to CR→Rel (2.452 × 106eq/ml, p=0.008) and NR (4.882 × 106eq/ml, p=0.009). A higher proportion of patients with CR→SR had type 2a HCV (67%) compared to the CR→Rel (28%) and the NR (0%). There was a trend for type 1b hepatitis C virus infection to have higher serum HCV‐RNA levels. There was no correlation between pretreatment HCV‐RNA level and alanine aminotransferase. However, no relation between pretreatment HCV‐RNA level and liver histology was observed; a high proportion of patients with CAH2a showed CR→SR, compared to those with CAH2b (p=0.001). Moreover, the patients with CAH2b who had low level hepatitis C virus viremia did not show CR→SR. These data indicate that pre‐treatment serum HCV‐RNA levels, genotype and liver histology are good predictors of subsequent response to interferon‐α therapy in Japanese pat

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00699.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Perinuclear antineutrophil cytoplasmic autoantibodies have been described in inflammatory bowel diseases and in primary sclerosing cholangitis. Because the data concerning their occurrence are conflicting, we have used indirect immunofluorescence on ethanol‐fixed neutrophils to test the sera from a large population of 382 patients with various liver and digestive diseases: in particular, from 27 patients with primary sclerosing cholangitis, 105 patients with autoimmune chronic active hepatitis, 30 patients with primary biliary cirrhosis and 124 patients with inflammatory bowel disease. The prevalence of the perinuclear antineutrophil cytoplasmic autoantibodies was 37% in ulcerative colitis and 15% in Crohn's disease. They would not be helpful in the differential diagnosis between these two inflammatory bowel diseases. Within the group of autoimmune liver diseases, perinuclear antineutrophil cytoplasmic autoantibodies were detected in 44% of sera from patients with primary sclerosing cholangitis and in 36% of sera from patients with type I autoimmune active hepatitis, but not in primary biliary cirrhosis. When primary sclerosing cholangitis was associated with an inflammatory bowel disease, the prevalence of these autoantibodies was 60%. They were 88% specific for primary sclerosing cholangitis and 86% specific for type I autoimmune active hepatitis. Despite their moderate sensitivity and specificity in primary sclerosing cholangitis, they remain the only serologic marker of this autoimmune liver disease. Moreover, they turned out to be a more sensitive marker for inflammatory bowel disease with associated primary sclerosing cholangit

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00700.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Diethylmaleate is an organic anion secreted into bile as a glutathione conjugate. Its transport by the hepatocyte is associated with dilatation of the Golgi apparatus and the appearance of small vesicles in the pericanalicular area. It has been speculated that the Golgi apparatus could play a role in the intracellular transport and/or the biliary canalicular secretion of diethylmaleate. The purpose of this work was to determine whether the alterations in the Golgi apparatus and the pericanalicular vesicles could mediate the canalicular secretion of diethylmaleate. Diethylmaleate biliary secretion and diethylmaleate‐induced bile flow were measured in Sprague‐Dawley rats, and in TR‐rats which have an inherited defect in the excretion into bile of organic anions, including glutathione conjugates. Livers of both Sprague‐Dawley and TR‐rats were examined by electron microscopy, to characterize the changes in intracellular organelles. In Sprague‐Dawley rats, as previously described, diethylmaleate administration was associated with an increase in bile flow, which was parallel in time to the secretion into bile of diethylmaleate conjugates. Electron microscopic examination of the liver after diethylmaleate administration showed dilatation of the Golgi saccules. In contrast, in TR‐rats, the increase in bile flow and the secretion of diethylmaleate conjugates were nearly absent. Nevertheless, electron microscopic examination showed a dilatation of the Golgi saccules similar to that observed in Sprague‐Dawley rats. TR‐rats, in addition to the changes in the Golgi apparatus, had marked dilatation of the endoplasmic reticulum. These results show that biliary secretion of diethylmaleate conjugates was severely impaired in TR‐rats, in spite of a dilatation of the Golgi apparatus and of the endoplasmic reticulum. We conclude that it is unlikely that the alterations in the Golgi apparatus (and the endoplasmic reticulum) induced by diethylmaleate play a role in the canalicular secretion of diethylmaleate. We do not exclude the possibility that these organelles could play a role in intracellular transport of this compound. Alternatively, these alterations could be due to a “toxic” effect of diethylmaleate accu

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00701.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Although eosinophil infiltrate has been recognized in hepatic graft‐versus‐host disease, its significance in relation to hepatic graft‐versus‐host disease lesions is unknown. In the present study, we analyzed hepatic eosinophil infiltration in relation to bile duct damage in experimental mouse graft‐versus‐host disease across minor histocompatibility barriers up to 14 months after transplantation. Portal eosinophil infiltration was found from 1 week after transplantation throughout the entire 14‐month observation period. It was most striking during the early chronic stage of hepatic graft‐versus‐host disease between 2 to 7 months, with a peak at 5 months after transplantation. Microscopic and electron microscopic study revealed eosinophils infiltrated around the bile duct as well as in the bile duct epithelial layer. They were commonly found together with lymphocytes but were also occasionally found singly around the bile duct and in the bile duct epithelial layer. Bile duct epithelial cells in contact with and in the vicinity of eosinophils showed a variety of degenerative changes, occasionally associated with the presence of extracellular eosinophil granules. Bile duct epithelial cells with eosinophil infiltration just beneath the basement membrane frequently showed further characteristic severe degenerative changes with shedding or dropping‐off into the lumen, which features were quite similar to those seen in the bronchial epithelium in asthma patients. These results indicate that not only lymphocytes but also eosinophils may be involved in the production of the bile duct injury in hepatic graft‐versus‐host disease, especially in

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00702.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The principal cause of primary non‐function in orthotopic liver transplantation is thought to be preservation injury to the microvasculature. We, therefore, evaluated if effluent levels of hyaluronate, whose uptake is an endothelial cell marker, could predict early graft function and ultimate graft outcome in orthotopic liver transplantation. A total of 102 cases were studied in two phases. In the first phase, we attempted to determine if a correlation existed between effluent hyaluronate levels, early graft function and ultimate graft outcome. This phase of the study was also used to determine hypothetical cut‐off values for hyaluronate which could discriminate between good and bad livers. Thirty‐two livers orthotopically transplanted to randomly selected primary recipients were studied. After varying periods of static cold storage (4°C) in University of Wisconsin solution, the livers were reinfused with cold (4°C) lactated Ringer's solution. The first 50 ml of the reperfusion effluent was collected from the infrahepatic vena cava. Effluent samples were analyzed for hyaluronate. Linear regression analysis demonstrated a significant correlation between effluent hyaluronate levels and post‐operative aspartate and alanine aminotransferase levels (p>0.001 for both). Logistic regression demonstrated a highly significant correlation (p=0.0056) between effluent hyaluronate levels and ultimate graft outcome. Generation of Receiver Characteristics Curves indicated that a level between 400 and 430 μg l‐1could possibly discriminate between good livers and those at risk of early graft failure. The authenticity of this hyaluronate cut‐off level was further confirmed in the second phase of the study where 70 consecutive primary crossmatch‐negative transplants were performed. A highly significant difference was observed in peak aspartate and alanine aminotransferase levels in the first week (p>0.0006 and p>0.0005, respectively) between livers with effluent hyaluronate levels 400 μg · l‐1and livers with hyaluronate levels higher than 400 μg l‐1. Logistic regression revealed a highly significant correlation between effluent hyaluronate levels and graft success (p=0.0001). Since hyaluronate uptake by the microvascular endothelial cell is significantly greater than production, high hyaluronate effluent levels in failed livers would be due to decreased hyaluronate uptake by the injured microvascular endothelial cell. We therefore conclude that effluent hyaluronate levels may prove to be a reliable preoperative test to assess early graft function and outcome in clinical orthotopi

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00703.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:To investigate a cellular mode of HCV‐infection in the liver and its pathological implications in relation to histopathological changes or clinical data, we studied the distribution of HCV‐RNA in the livers of 21 patients with HCV‐related chronic liver disease (chronic active hepatitis, 14 cases; cirrhosis, 7 cases) using thein situhybridization technique.In situhybridization was performed on 4% paraformaldehyde‐fixed frozen sections with digoxigenin‐labeled DNA probe deduced from the core region of HC–J4.In situhybridization showed positive signals in the liver specimens of 20/21 cases. The signals were localized in the cytoplasm of hepatocytes. The distribution pattern of positive cells was individually different, whereas the pattern was identical in the right and left lobes. There were no correlations of the HCV‐positive cell number with serum aminotransferase levels at biopsy or with genotypes of HCV. The positive hepatocytes were occasionally associated with infiltrating mononuclear cells, and they were sparsely distributed in the area of piecemeal necrosis. These findings suggest that factors such as host immunoreaction to the virus may be more important than its direct cytopathy in the pathogenesis of chronic hepatitis C vi

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00704.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Spheroids of adult rat hepatocytes are spherical cell aggregates which retain three‐dimensional architecture and hepatocyte specific functions. In this study, we investigated the detailed structure and function of bile canaliculi in spheroids. Hepatocytes were prepared from adult rat liver and cultured with epidermal growth factor (50 ng/ml). Hepatocytes formed floating spheroids 4 days after inoculation. The morphology of hepatocyte spheroids was investigated after fluorescent staining for actin using confocal laser scanning microscopy and electron microscopy. To study the function of bile canaliculi, the transcellular transport of fluorescein diacetate was observed. These experiments were performed in a control group and in a group treated with the actin inhibitor cytochalasin B. In a control group, spheroids contained bile canalicular structures which were surrounded by actin filaments. Added fluorescent dye was secreted and pooled in bile canaliculi. Cytochalasin B caused marked distention of bile canaliculi and prominent accumulation of secreted fluorescent dye in dilated bile canaliculi. This phenomenon was based on the impairment of contractile movement of bile canaliculi. These results demonstrate that hepatocyte spheroids maintain functional and morphological peculiarity, and therefore this model may be useful in investigation of the mechanism of bile formation and intrahepatic cholestasi

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00705.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY