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Hepatic Lobules (hepatic + lobule)
Selected AbstractsTroglitazone prevents fatty changes of the liver in obese diabetic ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2000Dong Mei Jia Abstract Background and Aims: Troglitazone is a newly developed antidiabetic drug and is indicated to be useful for the treatment of patients with type II diabetes mellitus. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. In addition, a relationship between the activation of the peroxisome proliferator-activated receptor gamma receptor by troglitazone and colon tumorigenesis has been suggested. The present study was undertaken to examine the effects of long-term administration of troglitazone on the liver and intestine in genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) and control Long-Evans Tokushima Otsuka (LETO) rats. Methods: A troglitazone-rich diet (200 mg/100 g normal chow) or a standard rat chow, free of troglitazone (control), was given to OLETF and LETO rats from 12 or 28 weeks of age until 72 weeks of age. Serum levels of glucose, insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined at several time points. In addition, histology of the liver and intestine and serum levels of cholesterol and triglycerides were examined at 72 weeks of age. Results: Troglitazone prevented age-related increases in fasting glucose and insulin concentrations in OLETF rats, but had no significant influences on serum levels of AST and ALT in both strains of rats. The liver weights in the control OLETF rats were significantly heavier than in the LETO rats. Troglitazone significantly reduced serum cholesterol and triglyceride levels and the liver weight. However, it had no influence on the large intestine weight and the number of colonic polyps in both OLETF and LETO rats. Sections of the liver from the untreated OLETF rats showed mild fatty changes in the central zone of the hepatic lobule, whereas those from the troglitazone-treated OLETF rats appeared normal with no fat deposition in the hepatocytes. Troglitazone in LETO rats also caused no significant histopathologic changes of the liver tissue. Conclusion: Our present study demonstrated that long-term administration of troglitazone prevents the progress of the metabolic derangement and fatty changes of the liver in genetically determined obese diabetes. [source] A mouse model for cystic biliary dysgenesis in autosomal recessive polycystic kidney disease (ARPKD),HEPATOLOGY, Issue 5 2005Markus Moser Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of liver- and renal-related morbidity and mortality in childhood. Recently, PKHD1, the gene encoding the transmembrane protein polyductin, was shown to be mutated in ARPKD patients. We here describe the first mouse strain, generated by targeted mutation of Pkhd1. Due to exon skipping, Pkhd1ex40 mice express a modified Pkhd1 transcript and develop severe malformations of intrahepatic bile ducts. Cholangiocytes maintain a proliferative phenotype and continuously synthesize TGF-,1. Subsequently, mesenchymal cells within the hepatic portal tracts continue to synthesize collagen, resulting in progressive portal fibrosis and portal hypertension. Fibrosis did not involve the hepatic lobules, and we did not observe any pathological changes in morphology or function of hepatocytes. Surprisingly and in contrast to human ARPKD individuals, Pkhd1ex40 mice develop morphologically and functionally normal kidneys. In conclusion,our data indicate that subsequent to formation of the embryonic ductal plate, dysgenesis of terminally differentiated bile ducts occurs in response to the Pkhd1ex40 mutation. The role of polyductin in liver and kidney may be functionally divergent, because protein domains essential for bile duct development do not affect nephrogenesis in our mouse model. Supplementary material for this article can be found on the HEPATOLOGYwebsite (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005.) [source] Enhanced expression of B7-1, B7-2, and intercellular adhesion molecule 1 in sinusoidal endothelial cells by warm ischemia/reperfusion injury in rat liverHEPATOLOGY, Issue 4 2001Naosuke Kojima To elucidate a role of costimulatory molecule and cell adhesion molecule in hepatic ischemia/reperfusion injury, we examined an alteration in B7-1 (CD80), B7-2 (CD86), and intercellular adhesion molecule 1 (ICAM-1; CD54) expression in the rat liver after warm ischemia/reperfusion injury. To induce hepatic warm ischemia in a rat model, both portal vein and hepatic artery entering the left-lateral and median lobes were occluded by clamping for 30 minutes or 60 minutes, and then reperfused for 24 hours. B7-1, B7-2, and ICAM-1 expressions in the liver were analyzed by immunofluorescence staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Although B7-1 and B7-2 expressions were at very low levels in the liver tissues from normal or sham-operated control rats, both B7-1 and B7-2 expressions were enhanced at protein and messenger RNA (mRNA) levels in the affected, left lobes after warm ischemia/reperfusion. ICAM-1 protein and mRNA were constitutively expressed in the liver of normal and sham-operated control rats, and further up-regulated after warm ischemia/reperfusion. Localization of increased B7-1, B7-2, and ICAM-1 proteins, as well as von Willebrand factor as a marker protein for endothelial cells, was confined by immunofluorescence staining to sinusoidal endothelial cells in hepatic lobules. Data from quantitative real-time RT-PCR analysis revealed that B7-1 and B7-2 mRNA levels were elevated in hepatic lobes after warm ischemia/reperfusion (5.13- and 52.9-fold increase, respectively), whereas ICAM-1 mRNA expression was rather constitutive but further enhanced by warm ischemia/reperfusion (4.24-fold increase). These results suggest that hepatic sinusoidal endothelial cells play a pivotal role as antigen-presenting cells by expressing B7-1 and B7-2 in warm hepatic ischemia/reperfusion injury, and that B7-1 and/or B7-2 might be the primary target to prevent early rejection and inflammatory reactions after hepatic ischemia/reperfusion injury associated with liver transplantation. [source] Liver-infiltrating CD56 positive T lymphocytes in hepatitis C virus infectionLIVER INTERNATIONAL, Issue 5 2000Kenji Yonekura Abstract:Aim: Hepatitis C virus (HCV) is a major cause of post-transfusional and sporadic hepatitis, and leads to chronic liver disease. It has been suggested that virus-specific cytotoxic T lymphocytes are responsible for liver injuries that occur in HCV-infected patients. However, the detailed characteristics of these lymphocytes have not yet been defined. We have previously reported that CD56+ T lymphocytes, as intermediates between natural killer cell and T lymphocytes, predominantly infiltrated the liver and were increased in patients with chronic hepatitis related to HCV (CH-C). Material and Methods: We obtained peripheral blood and liver tissues from 32 patients diagnosed as having CH-C, and 10 other liver disease patients (5 chronic hepatitis related to HBV, 5 alcoholics), and analyzed peripheral blood and liver-infiltrating lymphocytes using flow cytometric and immunohistochemical techniques. Results: The CD56+ T lymphocyte ratio in the liver of patients with a high histology activity index (HAI) score for chronic hepatitis was higher than that of patients with a low HAI score and patients with other liver diseases. In addition, T lymphocytes from patients with chronic hepatitis with a high HAI score carried mostly ,,-TCR. There was a correlation between the ratio of CH-C and serum alanine aminotransferase, category I (periportal inflammation and necrosis), and IV (fibrosis) of the HAI scoring system. The ratio was highest in zone 1 of the hepatic lobules. Conclusion: The correlation between CD56+ T lymphocyte ratios and hepatocellular damage was examined. These findings suggest strongly that liver-infiltrating CD56+ T lymphocytes play an important pathologic role in hepatocellular injury in CH-C. [source] | ||||||||||