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J Reichen

Publications and source records attributed to J Reichen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Dynamic phosphorus-31 spectroscopy after fructose load in experimental biliary liver cirrhosis.

RATIONALE AND OBJECTIVES: The authors investigated the usefulness of dynamic phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of hepatic function by studying the effect of a fructose load on a rat model of liver cirrhosis. METHODS: In vivo P-31 MR liver spectra of eight rats with bile duct ligature and 10 control rats were obtained every 4.6 minutes before and after intraperitoneal fructose load (10 mmol per kilogram of body weight). RESULTS: In the basal spectra of the experimental group, the phosphomonoester peak was higher than in the control group (P = .026). After the fructose load, the phosphomonoester peak increase and the inorganic phosphate peak decrease were significantly less marked in the experimental group (P = .003). There was a linear correlation between the serum level of bilirubin and the phosphomonoester increase (r = .61, P < .001). CONCLUSION: Dynamic P-31 MR spectroscopy may be useful in the assessment of hepatic function in chronic liver disease.

Analysis of Variance↗
PubMed1997

Carnitine metabolism in patients with chronic liver disease.

Carnitine metabolism was studied in 79 patients with chronic liver disease, including 22 patients with noncirrhotic liver disease and 57 patients with different types of cirrhosis (22 patients with hepatitis B- or C-associated cirrhosis, 15 patients with alcohol-induced cirrhosis, 15 patients with primary biliary cirrhosis [PBC], and 5 patients with cryptogenic cirrhosis), and compared with 28 control subjects. In comparison with control subjects, patients with noncirrhotic liver disease showed no change in the plasma carnitine pool, whereas patients with cirrhosis had a 29% increase in the long-chain acylcarnitine concentration. Analysis of subgroups of patients with cirrhosis showed that patients with alcohol-induced cirrhosis had an increase in the total plasma carnitine concentration (67.8 +/- 29.5 vs. 55.2 +/- 9.9 micromol/L in control subjects), resulting from increases in both the short-chain and long-chain acylcarnitine concentration. In this group of patients, the acylcarnitine concentrations showed a close correlation with the total carnitine concentration, and the total carnitine concentration with the serum bilirubin concentration. Urinary excretion of carnitine was not different between patients with noncirrhotic or cirrhotic liver disease and control patients. However, patients with PBC showed an increased urinary excretion of total carnitine (52.5 +/- 40.0 vs. 28.0 +/- 16.7 micromol carnitine/mmol creatinine), resulting from an increase in the fractional excretion of both free carnitine and short-chain acylcarnitine. The current studies show that patients with cirrhosis are normally not carnitine deficient. Patients with alcohol-induced cirrhosis have increased plasma carnitine concentrations, which may result from increased carnitine biosynthesis because of increased skeletal muscle protein turnover. The increase in the fractional carnitine excretion in patients with primary biliary cirrhosis may result from competition of bile acids and/or bilirubin with tubular carnitine reabsorption and/or from a reduced activity of the carnitine transporter located in the proximal tubule.

Adult↗
PubMed1997

Benzoic acid metabolism reflects hepatic mitochondrial function in rats with long-term extrahepatic cholestasis.

Benzoic acid metabolism, which is primarily a function of liver mitochondria, depending on the concentration of adenosine triphosphate (ATP), coenzyme A (CoA), and glycine in the mitochondrial matrix, was investigated in both rats with long-term cholestasis caused by bile duct ligation (BDL) and sham-operated control rats. In isolated liver mitochondria, hippurate production from benzoate in the presence of saturating glycine concentrations was reduced in BDL rats by 36% with L-glutamate as a source for ATP, by 21% in the presence of succinate, and by 31% in the presence of ATP plus oligomycine. This reduction in benzoate metabolism is in the same range as the previously observed reduction in the activity of the electron transport chain in liver mitochondria from BDL rats. The mitochondrial CoA pool, which can be rate-limiting for benzoic acid metabolism, was not different between BDL and control rats. The activity of benzoyl-CoA synthase, the enzyme catalyzing the rate-limiting step in benzoate metabolism, was reduced by 25%, and the activity of benzoyl-CoA:glycine N-transferase was reduced by 66% in BDL rats. The activity of benzoyl-CoA synthase was significantly inhibited by lithocholate, suggesting that hepatic accumulation of hydrophobic bile acids could contribute to the observed reduction of benzoate metabolism in BDL rats. Benzoate metabolism was also studied in vivo by monitoring the urinary hippurate excretion after intraperitoneal administration of benzoate (100 micromol/100 g of body weight). The time course of hippurate excretion was not different between BDL and control rats. Hippurate excretion over 24 hours after benzoate administration averaged 89.7 +/- 4.0% of the administered dose in BDL and 74.4 +/- 6.9% (mean +/- SEM, difference not significant) in control rats. This finding could be explained by an increase in mitochondrial protein in BDL rats, averaging 2.34 +/- 0.29 g per liver in BDL and 1.35 +/- 0.07 g per liver in control rats (mean +/- SEM, p < .05). Thus, the studies show that benzoate metabolism reflects mitochondrial function in BDL rats both in vivo and in vitro, and that mitochondrial proliferation compensates for the observed decrease in benzoic acid metabolism in isolated mitochondria in vitro.

Animals↗
PubMed1997

Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study.

The objectives were to determine quantitative liver function prospectively in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitative liver function and to assess the relationship between quantitative liver function and histological staging. A total of 117 patients with RA (ACR criteria, 85 women, mean age 59 yr) had measurements of galactose elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids, bilirubin, albumin] before treatment with weekly i.m. MTX injections and every year thereafter. In 16 patients, liver biopsies were performed. Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th percentile (5-95 PC) 5.1-8.5; reference range 6.0-9.1] and mean ABT was 0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC (-0.12 mg/min/kg per year. t = 3.30, P < 0.002) and ABT (-0.06% kg/mmol per year, t = 4.81, P < 0.001) were observed. Negative correlations were found between the annual change in GEC and GEC at baseline (Rs = -0.40, P < 0.0001), and the annual change in ABT and ABT at baseline (Rs = -0.43, P < 0.0001). No correlations were found between the annual change in GEC or ABT and weekly MTX dose, age or percentage of increased liver enzymes, and no effect of a history of alcohol consumption > 30 g/week became evident. Two patients with Roenigk grade III had impaired quantitative liver function, while 14 patients with Roenigk grades I and II exhibited a high variability of GEC and ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatment. Patients with a low GEC or ABT at baseline seem not to be at increased risk for a further loss of quantitative liver function. An impaired GEC or ABT does not necessarily concur with hepatic fibrosis on histological examination.

Alanine Transaminase↗
PubMed1997

Targeting naproxen to non-parenchymal liver cells protects against endotoxin induced liver damage.

Non-steroidal anti-inflammatory drugs (NSAID's) could be of value in the treatment of liver disease; however, their use in this situation is limited by renal side effects. Therefore, we explored whether naproxen covalently bound to human serum albumin NAP-HSA) was able to reduce toxicity in an acute model of liver disease induced by endotoxin in rats pretreated with Corynebacterium parvum. In the isolated perfused liver of such animals endotoxin induced cholestasis (0.62 +/- 0.05 vs. 0.24 +/- 0.09 microliter.min-1.g liver-1; p < 0.05), increased vascular resistance (11300 +/- 400 vs. 311000 +/- 2000 dyn.s.cm-5; p < 0.05) and alanine aminotransferase release (22 +/- 9 vs. 149 +/- IU/l; p < 0.05). At the highest dose tested (22 mg/kg, corresponding to 6.0 mumoles naproxen), NAP-HSA normalized ALT release (21 +/- 10 IU/l: p < 0.05) while an equimolar amount of non-targeted naproxen was only partially effective (56 +/- 19 IU/l). A conventional dose of naproxen similarly prevented transaminase release. Cholestasis and increased vascular resistance were also prevented by NAP-HSA. Drug targeting by linking drugs to proteins is a potentially useful approach to maximizing drug effect while minimizing adverse events; this could be particularly useful for compounds with potentially serious adverse effects in patients with chronic liver disease such as the nonsteroidal anti-inflammatory agents used in the present study.

Animals↗
PubMed1997

[Liver transplantation at the Bern Island Hospital: results from the last 5 years].

Today, orthotopic liver transplantation (OLT) is the treatment of choice for the endstage of various liver diseases, a 1-year survival rate of 80% and a 5-year survival rate of 70% in elective patients without tumor is reported in international surveys. The liver transplant program of the Inselspital Bern is very small compared with international centers, and this may raise questions about the (long-term) results and the justification for such a program. During the last 63 months, 59 liver transplantations (including two retransplants) have been performed in 57 patients at the Inselspital. The 30-day mortality was 3.5% and the 2.5-year overall survival rate was 82% and 93% for elective cases without tumor. After a median follow-up of 29 months, 67% of all patients were reintegrated fully or part-time in their profession and 81% were independent of others' help. We conclude that even a small liver transplant program based on routine resources only can achieve results which are comparable to international standards.

Adult↗
PubMed1997

Differentiation between naproxen, naproxen-protein conjugates, and naproxen-lysine in plasma via micellar electrokinetic capillary chromatography--a new approach in the bioanalysis of drug targeting preparations.

Pharmacotherapy through the targeting of drugs is a promising new approach that requires adequate analytical methods capable of differentiating between the free drug, the drug carrier, and metabolites. Using micellar electrokinetic capillary chromatography (MECC), we report the separation of naproxen (NAP) from NAP covalently coupled to human serum albumin or to mannosylated serum albumin and the metabolite naproxen-lysine. An assay for selective analysis of the different forms of NAP by direct plasma injection was developed with salicylate as internal standard and solute detection by laser-induced fluorescence. Compared with previously applied techniques, including HPLC and total plasma fluorescence, MECC offers the advantage that free and covalently bound NAP can be differentiated in one run and can be accurately monitored in microliter quantities of plasma. Summation of all NAP equivalents determined by MECC revealed data that compare well with those produced by total plasma fluorescence and HPLC.

Animals↗
PubMed1996

Application of mRNA differential display to liver cirrhosis: reduced fetuin expression in biliary cirrhosis in the rat.

We here show the application of mRNA differential display to investigate changes in gene expression in rat liver cirrhosis and address problems inherent in the technique when applied to this complex disease model. A number of differentially expressed mRNA species could be identified and two were analyzed in more detail here. One was found to derive from a new gene while the other corresponded to fetuin, a 41 kDa N-glycoprotein that specifically inhibits tyrosine kinase activity of the insulin receptor when phosphorylated. Fetuin expression was reduced by 45% in liver cirrhosis induced by bile duct ligation, but not in cirrhosis induced by carbon tetrachloride/Phenobarbital, as compared to controls. Our results raise the possibility that fetuin plays a regulatory role in the proliferation of parenchymal liver cells.

Animals↗
PubMed1996

Liver cirrhosis induces renal and liver phospholipase A2 activity in rats.

Maintenance of renal function in liver cirrhosis requires increased synthesis of arachidonic acid derived prostaglandin metabolites. Arachidonate metabolites have been reported to be involved in modulation of liver damage. The purpose of the present study was to establish whether the first enzyme of the prostaglandin cascade synthesis, the phospholipase A2(PLA2) is altered in liver cirrhosis induced by bile duct excision. The mRNA of PLA2(group I and II) and annexin-I a presumptive inhibitor of PLA2 enzyme was measured by PCR using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an internal standard. The mean mRNA ratio of group II PLA2/GAPDH was increased in liver tissue by 126% (P < 0.001) and in kidney tissue by 263% (P < 0.006) following induction of liver cirrhosis. The increase in group II PLA2 mRNA in cirrhotic animals was reflected by an increase in PLA2 protein and enzyme activity in both liver and kidney tissues. Since the mRNA of group I PLA2 was not detectable and Group IV PLA2 activity measured in liver and kidney tissue samples was very low and not changed following induction of cirrhosis, it is likely that the major PLA2 activity measured in liver and kidney corresponds to group II PLA2 enzyme. The mean mRNA ratio of annexin-I/GAPDH was increased in liver tissue by 115% (P < 0.05) but unchanged in kidney tissue following induction of cirrhosis. The protein content of annexin-I and -V were not affected by bile duct excision in liver and kidney tissue indicating that upregulation of group II PLA2 activity was not due to downregulation of annexin-I or -V. Group II PLA2 activity of glomerular mesangial cells stimulated by interleukin-1 beta was enhanced by bile juice and various bile salts. In conclusion, activity of group II PLA2 is upregulated partly due to enhanced transcription and translation in cirrhosis and is furthermore augmented by elevated levels of bile salts.

Animals↗
PubMed1996

Albumin but not fibrinogen synthesis correlates with galactose elimination capacity in patients with cirrhosis of the liver.

Albumin and fibrinogen synthesis rates were measured in 15 subjects with different clinical stages of postviral cirrhosis and compared with galactose elimination capacity and aminopyrin breath test. Forty-three mg per kg body weight [2H5ring]phenylalanine with an isotopic enrichment of 10 atom% were intravenously injected. [2H5ring]phenylalanine enrichments in the plasma-free phenylalanine and the albumin and fibrinogen isolates were measured by gas chromatography-mass spectrometry. Fractional synthesis rates of albumin were normal in Child A cirrhosis (7.6 +/- 2.2%d), but were lower in both Child B (3.5 +/- 0.8%d) and C (4.5 +/- 2.8%d). Absolute rates of albumin synthesis were (103 +/- 30 mg/kg/d) in the child A group and substantially lower in the Child B (50 +/- 3 mg/kg/d) and C (36 +/- 20 mg/kg/d) group. The average fractional synthesis rate of fibrinogen was 16.7 +/- 7.5%d and the absolute synthesis rate 11.6 +/- 6.4 mg/kg/d. The values of the galactose elimination capacity and the aminopyrin breath test were below the normal range in all patients, gradually decreasing with an increase in the severity of the clinical stage of cirrhosis. Albumin synthesis rates significantly correlated with the Child scores, the galactose elimination capacity, and the aminopyrin breath test, whereas fibrinogen synthesis rates showed no such correlations.

Adult↗
PubMed1996

Fixed versus titrated interferon-alpha 2B in chronic hepatitis C. A randomized controlled multicenter trial. The Swiss Association for the Study of the Liver.

BACKGROUND/AIM: Interferon has become the mainstay of treatment of chronic hepatitis C; however, duration of treatment and dose remain unresolved questions. The present study aimed to compare standard dose interferon with a titrated dose regimen carried out for 1 year. METHODS: This was a randomized, controlled multicenter trial. Patients with chronic hepatitis C were randomly allocated to a control group (n = 30), to a fixed dose group (n = 31) where interferon-alpha 2b 3 MU thrice weekly was given for 1 year or a titrated group (n = 34) where interferon was titrated starting at 5 MU thrice weekly to the lowest dose keeping the patient in remission as assessed by a normal ALT value. Liver biopsies were obtained before and at the end of treatment; in addition, galactose elimination capacity was measured as a measure of cytosolic function. RESULTS: In the control, fixed and titrated groups a complete response was achieved in 2/29, 10/28 and 15/31, respectively (p < 0.001 in favor of treatment, p = n.s. for the two treatments). The corresponding figure for sustained response was 1/29, 5/28 and 6/ 31 (p = n.s). In the titrated group, a complete (sustained) response was achieved with 5 MU in 2 (2), with 4 MU in 1 (0), with 3 MU in 4 (0), with 2 MU in 3 (0) and with 1 MU in 5 (4). Liver biopsy score and galactose elimination capacity improved significantly in responders but not in treatment failures. CONCLUSIONS: Both fixed and titrated dosing of interferon given for 1 year induced virus clearance in only a minority of treated patients. However, in a small number of patients, a complete and sustained response can be achieved with low doses of interferon. Dose titration could be an interesting approach to decreasing the cost and side effects in the treatment of chronic hepatitis C.

Adult↗
PubMed1996

Differential expression of Na+,H(+)-antiporter mRNA in biliary epithelial cells and in hepatocytes.

BACKGROUND/AIMS: Amiloride inhibitable Na+,H(+)-exchange has recently been identified and characterized in rat biliary epithelial cells where its activity at low intracellular pH is significantly higher than in hepatocytes. METHODS: Northern blot and reverse transcription-polymerase chain reaction were used to study the expression of the different Na+,H(+)-antiporter isoforms in isolated biliary epithelial cells and hepatocytes. RESULTS: The present study demonstrates for the first time the expression of Na+,H(+)-antiporter isoform 1 mRNA in rat biliary epithelial cells. Moreover, steady-state levels of this message were several-fold higher in biliary epithelial cells than in hepatocytes. In addition, the expression of Na+,H(+)-antiporter isoform 2 in bile duct epithelial cell but not hepatocytes could be demonstrated by reverse transcription-polymerase chain reaction. CONCLUSIONS: The higher expression of Na+,H(+)-antiporter isoform 1 mRNA may indicate a higher rate of synthesis and therefore a higher Na+,H(+)-exchange activity in biliary epithelial cells than in hepatocytes and is entirely compatible with the results of the previous functional studies.

Animals↗
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↗