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J Reichen

Publications and source records attributed to J Reichen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Progressive decrease in tissue glycogen content in rats with long-term cholestasis.

Liver and skeletal muscle glycogen metabolism were investigated in rats 1 and 4 weeks after bile duct ligation (BDL) and in pair-fed, sham-operated control rats. Livers were subjected to morphometric analysis to express glycogen content and enzyme activities per mL hepatocytes. One week after BDL, the hepatic glycogen content was 28.8 +/- 13.8 versus 38.6 +/- 16.4 mg/mL hepatocyte in BDL and control rats, respectively. Total activity of glycogen synthase (50.2 +/- 7.0 vs. 63.5 +/- 9.4 mU/mL hepatocytes) and glycogen phosphorylase (59.4 +/- 12.9 vs. 90.8 +/- 18.9 U/mL) were significantly reduced in BDL whereas the active fraction of glycogen synthase (27 +/- 6 vs. 38 +/- 5%) but not of glycogen phosphorylase was reduced. The skeletal muscle glycogen content was not different between BDL and control rats. Four weeks after BDL, hepatic glycogen content was further reduced (20.5 +/- 14.2 vs. 52.9 +/- 6.4 mg/mL). Total activity of glycogen synthase (38.8 +/- 12.1 vs. 60.1 +/- 4.6 mU/mL hepatocytes) and glycogen phosphorylase (127 +/- 19 vs. 178 +/- 33 U/mL hepatocytes) were both reduced in BDL rats as were their corresponding active fractions (30 +/- 18 vs. 66 +/- 8% and 58 +/- 10 vs. 76 +/- 10). At this time point, the glycogen content in soleus muscle was decreased by 64% in BDL. The glucagon plasma concentration was increased in BDL rats at both time points. There were positive correlations between the volume fraction and both hepatic glycogen content and total activity of hepatic glycogen synthase. Plasma glucagon and the active fraction of hepatic glycogen synthase were negatively correlated. The current studies show a progressive decrease in the hepatic and skeletal muscle glycogen content in BDL rats. The observed decrease in the activities of glycogen synthase and phosphorylase suggest that reduced glycogen synthesis is the major mechanism leading to the reduction in the hepatic glycogen content in BDL rats.

Animals↗
PubMed1995

[Does serum HCV-RNA-positive hepatitis C differ from serum HCV-RNA-negative hepatitis C?].

Viral RNA is detectable in the serum of the majority but not all patients with chronic hepatitis C. Whether the viremic form differs from the non-viremic form of the disease is unknown. We therefore compared histology (modified Knodell score) and liver function (conventional liver function tests, galactose elimination capacity and aminopyrin breath test) of viremic (n = 45) and non-viremic (n = 37) patients with chronic hepatitis C. Neither the total histologic score, nor any of the individual histologic parameters assessed differed significantly in serum HCV RNA positive and negative patients. Compared to non-viremic subjects, patients with detectable HCV RNA in serum had slightly higher transaminases (p = ns), lower serum albumin (p < 0.05) and decreased galactose elimination capacity (p < 0.05). This trend towards more severe functional hepatic impairment in serum HCV RNA positive patients persisted when cirrhotics and non-cirrhotics were analyzed separately; it fell just short of reaching statistical significance, however, most probably due to the small number of subjects per patient group. The median age of serum HCV RNA positive cirrhotics was 17 years, and that of serum HCV RNA negative cirrhotics 22 years higher than that of the respective non-cirrhotics. Biochemical (transaminases) and histological (intralobular and piece-meal necrosis) markers of disease activity, as well as metabolic functional reserve (aminopyrin breath test, galactose elimination capacity) and histologic severity of fibrosis correlated only loosely (Rs = 0.24-0.56), albeit significantly (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Solvent isotope effect on bile formation in the rat.

2H2O affects many membrane transport processes by solvent and kinetic isotope effects. Since bile formation is a process of osmotic filtration where such effects could be important, we investigated the effects of 2H2O on bile formation in the in situ perfused rat liver. Dose finding experiments showed that at high concentrations, 2H2O increased vascular resistance and induced cholestasis; at 60% 2H2O however, a clear dissociation between the vascular and biliary effects was observed. Therefore, further experiments were carried out at this concentration. The main finding was a reduction in bile salt-independent bile flow from 0.99 +/- 0.04 to 0.66 +/- 0.04 microliters.min-1.g-1 (P < 0.001). This was associated with a 40% reduction in biliary bicarbonate concentration (P < 0.001). Choleretic response to neither taurocholate nor ursodeoxycholate was altered by 2H2O; in particular, there was a similar stimulation of bicarbonate secretion by ursodeoxycholate in the presence of 60% 2H2O. To further elucidate this phenomenon, the effect of 2H2O on three proteins potentially involved in biliary bicarbonate secretion was studied in vitro. 2H2O slightly inhibited cytosolic carboanhydrase and leukocyte Na+/H(+)-exchange, these effects reached statistical significance at 100% 2H2O only, however. In contrast, Cl-/HCO(3-)-exchange in canalicular membrane vesicles was already inhibited by 50% (P < 0.001) at 60% 2H2O. Finally, there was a slight reduction in biliary glutathione secretion while that of the disulphide was not affected. Our results are compatible with an inhibition of canalicular Cl-/HCO(3-)-exchange by 2H2O. Whether this is due to altered hydration of the exchanger and/or of the transported bicarbonate remains to be determined.

Animals↗
PubMed1995

Reduced antioxidative capacity in liver mitochondria from bile duct ligated rats.

Lipid peroxidation and antioxidative mechanisms were investigated in liver mitochondria from bile duct ligated rats (BDL rats) and correlated with the activity of enzyme complexes of the electron transport chain. In comparison to pair-fed control rats, BDL rats had increased concentrations of thiobarbituric acid reacting substances (TBARS) per gram of liver and per milligram of mitochondrial protein 3, 7, 14, and 28 days after surgery. The hepatic glutathione (GSH) content was decreased in BDL rats 28 days after surgery when expressed per gram of liver but equal between BDL and control rats when expressed per liver. The mitochondrial GSH content was decreased in BDL rats by 20% to 33% from day 7 after surgery. The concentrations of ubiquinone-9 and ubiquinone-10, substances involved in electron transport and efficient antioxidants, were both decreased in BDL rats 14 and 28 days after surgery per gram of liver and per milligram of mitochondrial protein. When expressed per liver, ubiquinone-9 was decreased in BDL rats from day 7 after surgery. In comparison with controls, the decrease in total mitochondrial ubiquinone content in BDL rats averaged 52% 14 days and 38% 28 days after surgery. The activity of the succinate:ferricytochrome c oxidoreductase (complexes II and III of the electron transport chain) was decreased in BDL rats at days 7, 14, and 28 after surgery, and the activity of the ferrocytochrome c:oxygen oxidoreductase (complex IV) was reduced at 14 and 28 days after surgery. The mitochondrial concentration of TBARS showed a negative and the concentrations of GSH and ubiquinone a positive correlation with the activity of the succinate:ferricytochrome c oxidoreductase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The overexpression of proliferating cell nuclear antigen in biliary cirrhosis in the rat and its relationship with epidermal growth factor receptor.

Chronic bile duct obstruction in the rat leads to biliary cirrhosis but maintained hepatocellular mass. We have previously demonstrated translocation of epidermal growth factor receptor to nuclei. It remained unclear, however, whether this was due to hepatocyte proliferation and/or altered handling of epidermal growth factor receptor. Therefore, in the present investigation we stereologically estimated expression of proliferating cell nuclear antigen, a marker of the S phase of teh cell cycle at 1, 2, 3, 7, 14, 21 and 28 days after bile duct ligation. Proliferating cell nuclear antigen positive hepatocytes averaged 2.1 +/- 3.6% in sham-operated control animals. This increased to 20.7 +/- 6.4, 26.8 +/- 18.7, 31.3 +/- 23.9, 42.3 +/- 16.6 and 24.7 +/- 28.0% 3, 7, 14, 21 and 28 days after bile duct ligation, respectively (p<0.005 by ANOVA). This was correlated with the number of epidermal growth factor receptor positive nuclei (rs = 0.737) and inversely with the maximal binding capacity of epidermal growth factor to a crude plasma membrane fraction (rs = 0.697) reported previously. We conclude that bile duct ligation in the rat induces a significant hepatocellular proliferation as assessed by proliferating cell nuclear antigen expression and that this process could, at least in part, be related to increased nuclear expression of the epidermal growth factor receptor.

Analysis of Variance↗
PubMed1994

[Can the quality of a modest liver transplantation program compare to international standards? Results in Inselspital Berne].

Today, orthotopic liver transplantation is the treatment of choice for the endstage of various liver diseases, and a 1-year survival rate of over 80% is reported in international surveys. The liver transplant program of the Inselspital is very small compared to international centers and this may raise questions about the results and the justification for such a program. In a 24-month period, 20 liver transplants (including 2 retransplants) have been performed in 18 patients at the Inselspital. 2 patients (11%) died 20 and 268 days respectively after transplantation. 2 patients (11%) had significant morbidity 502 and 529 days respectively after transplantation. After a median follow-up of 11.5 months postoperatively, 14 (80% of all patients) lived an independent life. 9 (50%) were fully reintegrated in the household or in their profession and 5 others (30%) were working part time. We conclude that even a small liver transplant program based only on routine resources can achieve results comparable to international standards.

Adult↗
PubMed1994

[Reactivation of hepatitis B following withdrawal of chloroquine].

A severe flare-up of chronic hepatitis B infection with liver cell insufficiency has been observed in two patients after discontinuation of chloroquine administered either as malaria prophylaxis or as treatment of presumed rheumatoid arthritis. Chloroquine is known to inhibit the association of the major histocompatibility complex type II with hepatitis B virus antigens, thereby inhibiting T-cell mediated lysis of infected cells. Furthermore, it inhibits uptake of duck hepatitis B virus by duck liver cells. These in vitro studies and our clinical observations suggest that chloroquine inhibits the lysis of hepatitis B virus infected hepatocytes. Withdrawal of chloroquine in patients with chronic hepatitis B virus infection can lead to a rebound immune response manifesting as a reactivation of hepatitis B, similar to that observed after steroid withdrawal.

Adult↗
PubMed1994

Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria.

The toxicity of hydrophilic (cholate) and lipophilic (deoxycholate, chenodeoxycholate, and lithocholate) bile acids on the function of the electron transport chain was investigated in intact and disrupted rat liver mitochondria. In intact mitochondria, lipophilic bile acids used at a concentration of 100 mumol/L (0.1 mumol/mg protein) inhibited state 3 and state 3u (dinitrophenol-uncoupled) oxidation rates for L-glutamate, succinate, duroquinol or ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine as substrates. In contrast, state 4 oxidation rates and ADP/oxygen ratios were not significantly affected. At a bile acid concentration of 10 mumol/L (0.01 mumol/mg protein), the state 3 oxidation rate for L-glutamate was decreased in the presence of deoxycholate, chenodeoxycholate or lithocholate, whereas only lithocholate inhibited state 3 oxidation for succinate or duroquinol. In broken mitochondria, inhibition of oxidative metabolism was found for NADH or duroquinol as substrate in the presence of 100 mumol/L lithocholate (0.2 mumol/mg protein) and for duroquinol in the presence of 100 mumol/L chenodeoxycholate. Direct assessment of the activities of the enzyme complexes of the electron transport chain revealed decreased activities of complex I and complex III in the presence of 100 mumol/L deoxycholate or chenodeoxycholate or 10 mumol/L lithocholate. Inhibition of complex IV required higher bile acid concentrations (300 mumol/L for chenodeoxycholate or 30 mumol/L for lithocholate), and complex II was not affected. Both chenodeoxycholate and lithocholate were incorporated into mitochondrial membranes. The phospholipid content of mitochondrial membranes decreased in incubations containing 100 mumol/L (0.1 mumol/mg protein) chenodeoxycholate but was not affected in the presence of 100 mumol/L lithocholate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Mechanisms of impaired hepatic fatty acid metabolism in rats with long-term bile duct ligation.

Hepatic metabolism of fatty acids is impaired in experimental animals with long-term bile duct ligation. To characterize the underlying defects, fatty acid metabolism was investigated in isolated hepatocytes and isolated liver mitochondria from rats subjected to long-term bile duct ligation or sham surgery. After starvation for 24 hr, the plasma beta-hydroxybutyrate concentration was decreased in rats with bile duct ligation as compared with control rats. Production of beta-hydroxybutyrate from butyrate, octanoate and palmitate by hepatocytes isolated from rats subjected to bile duct ligation was also decreased. Liver mitochondria from rats subjected to bile duct ligation showed decreased state 3 oxidation rates for L-glutamate, succinate, duroquinone, and fatty acids but not for ascorbate as substrate. State 3u oxidation rates (uncoupling with dinitrophenol) and activities of mitochondrial oxidases were also decreased in mitochondria from rats subjected to bile duct ligation. Direct assessment of the activities of the subunits of the electron transport chain revealed reduced activities of complex I, complex II and complex III in mitochondria from rats subjected to bile duct ligation. Activities of the beta-oxidation enzymes specific for short-chain fatty acids were all reduced in rats subjected to bile duct ligation. Mitochondrial protein content per hepatocyte was increased by 32% in rats subjected to bile duct ligation compared with control rats. Thus the studies directly demonstrate mitochondrial defects in fatty acid oxidation in rats subjected to bile duct ligation, which explain decreased ketosis during starvation.

3-Hydroxybutyric Acid↗
PubMed1994

Ursodeoxycholate-induced hypercholeresis in cirrhotic rats: further evidence for cholehepatic shunting.

The aim of the investigation was to explore whether ursodeoxycholate, a tertiary bile acid with potential for treatment of chronic cholestasis in cirrhotic liver disease, has the same physiological effects in cirrhotic as in normal rats. Furthermore, we wanted to investigate whether ductular proliferation, as it occurred in this situation, increases the bicarbonate stimulatory effect of ursodeoxycholate. Rats (n = 16) were rendered cirrhotic by continuous exposure to phenobarbital-carbon tetrachloride; untreated animals (n = 13) served as controls. In cirrhotic rats in vivo, ursodeoxycholate (20 mumoles/min/kg) stimulated bile salt secretion and bile flow less than in controls. Nevertheless, the increment in ursodeoxycholate-induced biliary bicarbonate--the bicarbonate stimulatory potency--was increased by 29% in cirrhotic animals (0.55 +/- 0.08 mmol vs. 0.71 +/- 0.11 mmol; p < 0.05). This finding could be related to ductular proliferation because the volume fraction of bile ductules, determined stereologically, increased from 0.3% +/- 0.1% to 2.7% +/- 0.6% in cirrhotic rats (p < 0.005). To explore further the behavior of ductules during ursodeoxycholate stimulation, we carried out experiments in the in situ perfused rat liver. In the portally perfused organ, replacement of bicarbonate by tricine-acetate abolished ursodeoxycholate-induced hypercholeresis. In the dually perfused organ (perfusion of both portal vein and hepatic artery) perfusion of the hepatic artery with bicarbonate-containing buffer, ursodeoxycholate had a similar stimulatory effect as in vivo in both control and cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Ursodeoxycholate protects oxidative mitochondrial metabolism from bile acid toxicity: dose-response study in isolated rat liver mitochondria.

The effect of ursodeoxycholate and tauroursodeoxycholate on the toxicity of lipophilic bile acids (chenodeoxycholate and lithocholate) on the function of the electron transport chain was investigated in isolated rat liver mitochondria. At a concentration of 30 mumol/L, both chenodeoxycholate and lithocholate reduced state 3 oxidation rates and respiratory control ratios of L-glutamate, succinate and duroquinol. In contrast, ADP/O ratios of these substrates and oxidative metabolism of ascorbate were not significantly affected. Ursodeoxycholate did not impair mitochondrial oxidative metabolism up to concentrations of 100 mumol/L; at 300 mumol/L, however, it decreased state 3 oxidation rates and respiratory control ratios of L-glutamate, succinate and duroquinol. Tauroursodeoxycholate had no significant inhibitory effect on state 3 oxidation rates of L-glutamate and succinate at concentrations up to 300 mumol/L. When ursodeoxycholate (final concentration, 30 mumol/L or 100 mumol/L) was added to mitochondrial incubations containing chenodeoxycholate or lithocholate, the toxic effects of lipophilic bile acids on mitochondrial oxidative metabolism were partially reversed. However, 300 mumol/L ursodeoxycholate, in combination with chenodeoxycholate or lithocholate, exhibited greater toxicity compared with incubations containing only the individual bile acids. In contrast to ursodeoxycholate, tauroursodeoxycholate did not reduce the toxic effects of chenodeoxycholate or lithocholate on mitochondrial metabolism. Ursodeoxycholate (100 mumol/L) significantly decreased the incorporation of chenodeoxycholate into mitochondrial membranes, whereas the decrease in lithocholate incorporation was not statistically significant. These studies demonstrate that ursodeoxycholate, but not tauroursodeoxycholate, decreases the toxicity of lipophilic bile acids on the function of the electron but increases bile acid-induced mitochondrial toxicity at higher concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Hepatocellular Na+/H+ exchange is activated at transcriptional and posttranscriptional levels in rat biliary cirrhosis.

BACKGROUND/AIMS: Rat hepatocyte Na+/H+ exchange is activated in vitro by growth factors and in vivo following partial hepatectomy. This study explored by which mechanism(s) it is activated in a cirrhosis model characterized by chronic stimulation of hepatocyte proliferation. METHODS: Rat hepatocytes were isolated 4 weeks after bile duct ligation or sham operation. Intracellular pH (pHi) was fluorimetrically determined, and plasma membranes and messenger RNA (mRNA) were prepared from isolated hepatocytes by standard methods. RESULTS: Resting pHi was higher in bile duct-ligated than in control rats (7.42 +/- 0.03 vs. 7.06 +/- 0.04; P < 0.001). Although plasma membrane lipid composition and intracellular buffering capacity were similar, initial Na+/H+ exchange-mediated rates of pHi recovery following acid loading were higher in bile duct-ligated than in control rats (0.098 +/- 0.011 vs. 0.055 +/- 0.005 pH units/min; P < 0.05). The antiporter's set point was shifted approximately 0.3 pH units towards more alkaline values and its steady-state mRNA levels were doubled after bile duct ligation. CONCLUSIONS: Hepatocellular Na+/H+ exchange is transcriptionally and posttranscriptionally activated in rat biliary cirrhosis further supporting a relationship between hepatocyte proliferation and Na+/H+ exchange activation.

Animals↗
PubMed1994

Efficacy of steroid withdrawal and low-dose interferon treatment in chronic active hepatitis B. Results of a randomized multicenter trial. Swiss Association for the Study of the Liver.

Fifty-six patients with biopsy-proven, chronic active hepatitis B were included in a multi-center, randomized trial comparing steroid withdrawal followed by 1.5 MU recombinant interferon alpha 2b (Intron) with placebo withdrawal followed by either 1.5 or 5 MU interferon. The patients were equally distributed between the treatment groups with respect to biochemical and histologic activity as well as with respect to DNA levels and quantitative liver function tests. One patient was lost to follow up. After 1 year of treatment, 10/18, 13/19 and 11/18 patients had lost hepatitis B virus DNA in the three groups, respectively (non-significant). Transaminase levels were normal in 27/34 of the responders but in only 4/21 of the non-responders (p < 0.0001). Both galactose elimination capacity and aminopyrine breath test improved significantly in responders, but either did not change (aminopyrine breath test) or deteriorated in non-responders (galactose elimination capacity). Biopsy score improved in both groups but this reached statistical significance only in responders. This effect was due to improvements in both inflammatory and fibrotic activity. Side effects included almost universally a flu-like syndrome, granulocytopenia (1), depression (3) and thyroid dysfunction (2). Two deaths occurred, one due to hepatocellular cancer, and the other to hepatorenal syndrome after spontaneous bacterial peritonitis. A severe cytolytic episode was observed in three patients in the steroid withdrawal group. We conclude that in patients with marked histologic activity, lower doses of interferon may be as effective as the standard dose of 5 MU.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effect of development on the functional and histological changes induced by bile-duct ligation in the rat.

Secondary biliary cirrhosis in the rat can be induced by bile duct ligation; the aim of the present study was to investigate whether susceptibility to this injury depends on development. Rats aged 4, 7, 14 and 22 weeks were bile-duct ligated or sham operated. Four weeks later, stereologic analysis of the liver was performed and the volume fraction of parenchyma, bile ducts and connective tissue was determined. Microsomal function was assessed in vivo by the aminopyrine breath test and in vitro by determining the microsomal cytochrome P450 content and microsomal lipid composition. In addition, portal pressure was measured. The volume fraction of parenchyma decreased in an age-dependent fashion in bile-duct ligated rats from 64.0 +/- 11.2% in the youngest to 46.4 +/- 8.4% in the oldest age group. This decrease was compensated by an age-dependent increase in both ductular proliferation and fibrosis. Microsomal function both in vivo and in vitro showed an age-dependent deterioration. Microsomal cholesterol and some individual phospholipids showed age-dependent changes. Portal hypertension developed in all bile-duct ligated groups, but portal pressure was significantly lower in the oldest bile-duct ligated groups (16.0 +/- 2.6 cmH2O) compared with other bile-duct ligated groups (around 21 cmH2O). We conclude that susceptibility to the sequelae of chronic cholestasis depends on the stage of development in rats. In experiments using this model, the age of the rats should be explicitly stated.

Age Factors↗
PubMed1994

Increased hepatic lysosomal activity in biliary cirrhosis originates from hepatocytes rather than from macrophages.

To investigate the potential role of lysosomes in cirrhosis, the activity of lysosomal enzymes was analyzed in rats with cirrhosis induced by bile-duct ligation. Twenty-eight days after surgery, the activity of lysosomal enzymes was markedly increased in the homogenate of cirrhotic livers (e.g. arylsulfatase 7 +/- SD 1 vs 17 +/- 3 nmol.min-1.mg-1 in controls and cirrhotics, respectively; p < 0.001). The corresponding plasma levels were also increased (arylsulfatase: 10 +/- 1 vs 25 +/- 9 pmol.min-1.mg-1; p < 0.01). In contrast, the activities of these enzymes in lysosomal fractions did not differ, suggesting an increase in number of lysosomes. The increased lysosomal activity correlated with severity of cirrhosis as assessed by the aminopyrine breath test and with cholestatic parameters but less with transaminases. Since macrophages, cells which are rich in lysosomes, could contribute to the increase in lysosomal enzyme content, these cells were estimated stereologically after being marked immunohistochemically with a monoclonal antibody against the rat macrophage membrane antigen ED2. ED2 positive cells were increased 2.7-fold in cirrhotic livers. This increase cannot account for the observed increase in hepatic lysosomal enzyme content. Furthermore, 1 week after bile-duct ligation, when there was cholestasis but not yet cirrhosis, lysosomal enzyme activities were already increased. These data support the idea that the increased hepatic lysosomal activity in biliary cirrhosis is of hepatocyte rather than of macrophage origin, and is presumably related to cholestasis.

Animals↗
PubMed1994

Differential effect of micronodular and biliary cirrhosis on epidermal growth factor receptor expression in the rat.

Cirrhosis is characterized by fibrogenesis, hepatocyte necrosis and the formation of regenerative nodules. Modulation of the epidermal growth factor receptor is an early event during regeneration. We have recently demonstrated alterations in the epidermal growth factor receptor during the development of biliary cirrhosis. The aim of the present study was to compare epidermal growth factor receptor distribution, expression and binding in biliary cirrhosis to that occurring in micronodular cirrhosis induced by phenobarbital/CCl4 exposition. Biliary cirrhosis and micronodular cirrhosis had similar functional impairment as assessed by the aminopyrine breath test. Epidermal growth factor receptor binding capacity was reduced in both models (control vs micronodular cirrhosis vs biliary cirrhosis: (mean +/- 1 SD) 60 +/- 22 vs 16 +/- 12 vs 27 +/- 9 fmol/mg protein, p < 0.05), while the binding constant was increased in biliary cirrhosis only. The receptor mass in plasma membrane, determined by Western blotting, was not changed. Distribution of epidermal growth factor receptor was assessed immunohistochemically on tissue sections. In both models, cytoplasmic staining was decreased and basolateral plasma membrane labeling was maintained. Nuclear localization was found in biliary cirrhosis only. In conclusion, in both models, cirrhosis induces an alteration in the binding properties, but not in the number of epidermal growth factor receptors in the plasma membrane. The loss of cytoplasmic epidermal growth factor receptor could reflect alterations in expression and/or in intracellular trafficking. This is supported by the reduced mRNA steady state levels for epidermal growth factor receptor which were found in both models, presumably representing down-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗