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F Lemonnier - One of the best experts on this subject based on the ideXlab platform.

  • fatty acid content in lymphocytes from children with syndromic paucity of Interlobular Bile Ducts alagille syndrome
    Journal of Inherited Metabolic Disease, 1995
    Co-Authors: P Pina, Martine Couturier, F Lemonnier
    Abstract:

    Fatty acid (FA) concentrations were studied in lymphocytes isolated from children with syndromic paucity of Interlobular Bile Ducts (PILBD), Alagille syndrome. The aim of this study was to assess whether the specific FA changes previously observed in fibroblast cultures from such patients were also present in other tissues. Lymphocyte FA, obtained both from controls and patients were studied under two experimental conditions, either after separation of the mononuclear cells or after 48 hours of culture. Freshly isolated lymphocytes from patients presented few FA changes compared to the controls. However, when patient lymphocytes were placed in culture medium for 47 hours, FA changes were amplified compared to those observed in controls; the decrease in the sum of saturated andn-6 polyunsaturated FA of total lipids was significant only in patients, and then-3 FA of phospholipids was strikingly increased in patients (p≤0.001), compared to controls. These results are related to those previously observed in fibroblast cultures and suggest that placing cells in culture could reveal a pre-existing cellular abnormality in patients with PILBD.

  • 2 deoxy d glucose uptake and fatty acid content in fibroblast cultures from children with syndromic paucity of Interlobular Bile Ducts alagille syndrome
    Journal of Inherited Metabolic Disease, 1991
    Co-Authors: Martine Couturier, F Lemonnier
    Abstract:

    2-Deoxy-d-glucose (2-DOG) uptake was studied in skin fibroblast cultures from control children and children with Alagille syndrome or syndromic paucity of Interlobular Bile Ducts (PILBD). No significant differences in uptake were observed between patients and controls. However, as the scatter of the results was larger in the fibroblasts from patients, we attempted to establish for these patients a relationship between 2-DOG uptake and some biochemical parameters. We observed an inverse relationship between this uptake and the levels of plasma cholesterol and phospholipids (r=−0.85). Compared to controls, 2-DOG uptake was significantly lower in cultures from patients who had very high levels of cholesterol (P2 group), but not in cultures from patients with moderately increased levels of cholesterol (P1 group). The level of total cellular cholesterol in cultured cells from the P1 and P2 groups was not significantly different from the control level, but we found marked differences between the concentrations of fatty acids. In the cultures from patients (especially the P2 group), we observed a significant increase in total fatty acids; among the saturated fatty acids, this increase chiefly concerned the 18:0 (14%) and among the polyunsaturated then −3 fatty acids (55%). The high concentrations of 20:5, 22:5 and 22:6, which enhance membrane fluidity, might explain the decrease in 2-DOG uptake found in the cultures from patients (P2 group) with PILBD. The nature of these abnormalities might be connected with the genetic origin of Alagille syndrome

Joan Rodes - One of the best experts on this subject based on the ideXlab platform.

  • nonsyndromic paucity of intrahepatic Bile Ducts in infancy and idiopathic ductopenia in adulthood the same syndrome
    Hepatology, 1992
    Co-Authors: M Bruguera, Josep Llach, Joan Rodes
    Abstract:

    Eleven patients with chronic intrahepatic cholestasis in whom a liver biopsy specimen showed unexplained Bile duct paucity were investigated. Cholestasis developed during the neonatal period in three, at infancy (before 14 yr) in four and after 14 yr in the remaining four patients. In all patients other conditions characterized by chronic cholestasis associated with ductopenia such as primary biliary cirrhosis, primary sclerosing cholangitis, drug-induced liver disease, sarcoidosis or graft-vs.-host disease were excluded. Cardiovascular abnormalities in the three patients who had neonatal cholestasis permitted diagnosis of Alagille's syndrome. Clinical, biochemical and histological features were similar in the remaining eight patients, independent of the age at which the disease appeared. Idiopathic adulthood ductopenia may be a late-onset form of the nonsyndromic paucity of Interlobular Bile Ducts seen in children, or it may be due to a still-unidentified cause that strikes later in life.

  • nonsyndromic paucity of intrahepatic Bile Ducts in infancy and idiopathic ductopenia in adulthood the same syndrome
    Hepatology, 1992
    Co-Authors: M Bruguera, Josep Llach, Joan Rodes
    Abstract:

    Eleven patients with chronic intrahepatic cholestasis in whom a liver biopsy specimen showed unexplained Bile duct paucity were investigated. Cholestasis developed during the neonatal period in three, at infancy (before 14 yr) in four and after 14 yr in the remaining four patients. In all patients other conditions characterized by chronic cholestasis associated with ductopenia such as primary biliary cirrhosis, primary sclerosing cholangitis, drug-induced liver disease, sarcoidosis or graft-vs.-host disease were excluded. Cardiovascular abnormalities in the three patients who had neonatal cholestasis permitted diagnosis of Alagille's syndrome. Clinical, biochemical and histological features were similar in the remaining eight patients, independent of the age at which the disease appeared. Idiopathic adulthood ductopenia may be a late-onset form of the nonsyndromic paucity of Interlobular Bile Ducts seen in children, or it may be due to a still-unidentified cause that strikes later in life. (HEPATOLOGY 1992;15:830–834).

Yasuni Nakanuma - One of the best experts on this subject based on the ideXlab platform.

  • Immunohistochemical analysis of the the liver and kidney of the PCK rat treated with NVP-BEZ235.
    2014
    Co-Authors: Xiang Shan Ren, Yasunori Sato, Shinichi Furubo, Kenichi Harada, Motoko Sasaki, Jing Yu Song, Yasuni Nakanuma
    Abstract:

    Treatment with NVP-BEZ235 reduced the expression of p-Akt (Ser473), p-mTOR (Ser2448) and p-S6 in Bile duct epithelium of the PCK rat (A). The treatment increased immunohistochemical expression of LC3 in Bile duct epithelium of the PCK rat (B). In the kidney, the expression of p-Akt (Ser473), p-mTOR (Ser2448) and p-S6 was increased in collecting tubule-derived cyst epithelium of the PCK rat without NVP-BEZ235 treatment compared to those in the renal tubules of normal rat, and their expression appeared to be reduced in the kidney of the PCK rat following the treatment (C). Arrows indicate Interlobular Bile Ducts of the normal liver. Original magnifications; x400 (A–C).

  • Overexpression of p-mTOR, p-Akt, p-S6, and PI3K in PCK cholangiocytes.
    2014
    Co-Authors: Xiang Shan Ren, Yasunori Sato, Shinichi Furubo, Kenichi Harada, Motoko Sasaki, Jing Yu Song, Yasuni Nakanuma
    Abstract:

    The immunohistochemical expression of p-mTOR (Ser2448) and p-Akt (Ser473) was examined using liver sections of 10-month-old rats. Increased expression of p-mTOR (Ser2448) and p-Akt (Ser473) was observed in Bile duct epithelium of the PCK liver compared to that of the normal liver (A). Western blot analysis using protein extracts from cultured cholangiocytes showed that the expression p-mTOR (Ser2448), p-mTOR (Ser2481), p-Akt (Ser473), p-S6, PI3K p110α, and PI3K p85 was increased in PCK cholangiocytes compared to normal cholangiocytes (B). The results of the semiquantitative analysis of Western blotting are shown in C. Arrows indicate Interlobular Bile Ducts of the normal liver. *, p

  • scavenger cells with gram positive bacterial lipoteichoic acid infiltrate around the damaged Interlobular Bile Ducts of primary biliary cirrhosis
    Journal of Hepatology, 2001
    Co-Authors: Koichi Tsuneyama, Kenichi Harada, Naoko Kono, Katsushi Hiramatsu, Yoh Zen, Yoshiko Sudo, Eric M Gershwin, Mamoru Ikemoto, Hiroyuki Arai, Yasuni Nakanuma
    Abstract:

    Abstract Background/Aims : Gram-positive bacterial DNA is frequently detectable in gallbladder Bile of primary biliary cirrhosis (PBC) patients. To advance these findings, lipoteichoic acid (LTA) of Gram-positive bacteria with high antigenicity was examined in liver specimens and Bile from PBC patients and controls. Methods : LTA was examined by Western blotting in the gallbladder Bile from 15 PBC, 11 cholecystolithiasis and six normal subjects, and by immunohistochemistry in liver specimens from 16 PBC, six primary sclerosing cholangitis (PSC), eight chronic viral hepatitis C (CVH-C) and five normal subjects. Results : In the gallbladder Bile, there was no significant difference in the positive rate of LTA between PBC and controls. LTA-containing mononuclear cells were frequently detected in the portal tracts, particularly around the Bile Ducts and in hepatic sinusoids in PBC, while they were infrequent or occasional in control livers. These LTA-containing cells were sinusoidal endothelial cells and Kupffer cells, and portal monocytes, which frequently expressed scavenger receptor class B type 1. Conclusions : LTA derived from bacterial fragments may reach the Bile, not only in the diseased state but also under normal conditions. Such LTA may be involved in the development and progression of portal tract lesions, particularly Bile duct lesions, in PBC.

  • b7 2 positive cells around Interlobular Bile Ducts in primary biliary cirrhosis and chronic hepatitis c
    Journal of Gastroenterology and Hepatology, 1997
    Co-Authors: Kyosuke Kaji, Yasuni Nakanuma, Kenichi Harada, Motoko Sasaki, Koichi Tsuneyama, Shuichi Kaneko, Kenichi Kobayashi
    Abstract:

    Bile duct damage in patients with chronic hepatitis C (hepatitis-associated Bile duct lesion) as well as that in patients with primary biliary cirrhosis (PBC; chronic non-suppurative destructive cholangitis), may be causally related to immunological assaults. Efficient antigen presentation is known to require the provision of a costimulatory signal which is dependent on the CD28 on T cell surfaces, and that at least two molecules, B7-1 and B7-2, work as costimulatory ligands for CD28. In this study, we examined immunohistochemically, the expression of B7-2 in portal tracts of liver biopsy specimens obtained from 75 patients with chronic hepatitis C who had hepatitis-associated Bile duct lesions, and from 63 PBC patients with chronic non-suppurative destructive cholangitis. B7-2 positive cells were recognizable as large mononuclear cells scattered in portal tracts. Some of these cells showed a dendritic cell-like appearance. B7-2 positive cells were observed more frequently (41%) in PBC liver specimens than in chronic hepatitis C specimens (17%, P < 0.05). In PBC livers, such cells were preferentially observed around the damaged Bile duct with a few located in the biliary epithelial layer. There was no such finding in chronic hepatitis C livers. The frequency and density of B7-2 positive cells in the liver specimens tended to decrease according to the stage of PBC (45% in stages 1 and 2, and 33% in stages 3 and 4; P = 0.10), whereas with chronic hepatitis C, no such tendency was observed. These findings suggest that B7-2 positive cells may play a role in the Bile duct lesions that appear in the early histological stages of PBC and that the immunological mechanisms of Bile duct damage, particularly of antigen presentation and B7-2 expression, differ between PBC and chronic hepatitis C.

  • expression of vimentin in proliferating and damaged Bile ductules and Interlobular Bile Ducts in nonneoplastic hepatobiliary diseases
    Modern Pathology, 1992
    Co-Authors: Yasuni Nakanuma, N Kono
    Abstract:

    Biliary epithelial cells express characteristically cytokeratin in their cytoplasm in normal and diseased livers. The present study disclosed that vimentin was frequently expressed in the cytoplasm of proliferating and damaged Bile ductules and Interlobular Bile Ducts, while their normal counterparts were negative for vimentin. Although this expression itself seemed nonspecific to any of the hepatobiliary diseases examined, Bile ductules and Interlobular Bile Ducts were frequently positive in chronic cholestatic and necroinflammatory liver diseases. In biliary epithelial cells, vimentin was localized around the nucleus or in the subnuclear regions, when present. Immunoelectron microscopically, reaction proDucts for vimentin and for cytokeratin were found on bundles of intermediate filaments in the cytoplasm of biliary epithelial cells. The former was found mostly in the paranuclear and subnuclear regions, while the latter detected around the desmosomes, in addition to the paranuclear cytoplasm. Vimentin and cytokeratin were also seen together under immunoelectron microscopy on the same intermediate filaments. It seems likely that aberrant expression of vimentin in Bile ductules and Interlobular Bile Ducts and heterogeneous antigenic expression of intermediate filaments in the same biliary epithelial cells may be related to proliferation of, reorganization of, or damage to the ductular and ductal biliary cells in a variety of hepatobiliary diseases.

Paul G Killenberg - One of the best experts on this subject based on the ideXlab platform.

  • peribiliary vascular plexus in primary sclerosing cholangitis and primary biliary cirrhosis
    Human Pathology, 1997
    Co-Authors: Kay Washington, Pierrealain Clavien, Paul G Killenberg
    Abstract:

    The peribiliary vascular plexus plays an important role in physiology of Bile flow. Disturbance of the microcirculation may contribute to ductal injury, but little is known about alterations in the vascular supply of small Bile Ducts in liver disease. Immunoperoxidase stains for vascular endothelium (Ulex europaeus, factor VIII-related antigen, CD34) were used to study the peribiliary vascular plexus in 20 cases of primary sclerosing cholangitis (PSC) and 27 cases of primary biliary cirrhosis (PBC), two diseases characterized by Bile duct destruction. Normal liver from 10 autopsy cases of sudden cardiac death was used as a control. Interlobular Bile Ducts (20- to 80-microm diameter) were identified on AE1/AE3 immunostain; vessels adjacent to the basement membrane of these Ducts were counted. Normal Interlobular Bile Ducts had an average of 2.15 vessels per duct (range, 1.68 to 2.71). Few PBC or PSC cases had a normal number of peribiliary vessels. There was a trend toward vasopenia at higher stage, although vascular loss was noted in early stages as well. The pattern of vascular loss was different for the two diseases; in PSC, the periductal capillaries were often preserved but were pushed away from the basement membrane by concentric deposits of collagen. Small residual vessels could be identified within fibrous scars of obliterated Bile Ducts in PSC. In 4 stage 3 or 4 PSC cases with little Bile duct injury, vessel/duct ratio approached normal levels. In PBC, vessels were obliterated in areas of granulomatous inflammation and heavy lymphocytic infiltrate around Bile Ducts. In conclusion, loss of peribiliary vessels is common in PSC and PBC. Vessel loss is seen in early stages and may contribute an element of ischemia to continued small Bile duct loss but is probably secondary to the inflammatory process.

Martine Couturier - One of the best experts on this subject based on the ideXlab platform.

  • fatty acid content in lymphocytes from children with syndromic paucity of Interlobular Bile Ducts alagille syndrome
    Journal of Inherited Metabolic Disease, 1995
    Co-Authors: P Pina, Martine Couturier, F Lemonnier
    Abstract:

    Fatty acid (FA) concentrations were studied in lymphocytes isolated from children with syndromic paucity of Interlobular Bile Ducts (PILBD), Alagille syndrome. The aim of this study was to assess whether the specific FA changes previously observed in fibroblast cultures from such patients were also present in other tissues. Lymphocyte FA, obtained both from controls and patients were studied under two experimental conditions, either after separation of the mononuclear cells or after 48 hours of culture. Freshly isolated lymphocytes from patients presented few FA changes compared to the controls. However, when patient lymphocytes were placed in culture medium for 47 hours, FA changes were amplified compared to those observed in controls; the decrease in the sum of saturated andn-6 polyunsaturated FA of total lipids was significant only in patients, and then-3 FA of phospholipids was strikingly increased in patients (p≤0.001), compared to controls. These results are related to those previously observed in fibroblast cultures and suggest that placing cells in culture could reveal a pre-existing cellular abnormality in patients with PILBD.

  • 2 deoxy d glucose uptake and fatty acid content in fibroblast cultures from children with syndromic paucity of Interlobular Bile Ducts alagille syndrome
    Journal of Inherited Metabolic Disease, 1991
    Co-Authors: Martine Couturier, F Lemonnier
    Abstract:

    2-Deoxy-d-glucose (2-DOG) uptake was studied in skin fibroblast cultures from control children and children with Alagille syndrome or syndromic paucity of Interlobular Bile Ducts (PILBD). No significant differences in uptake were observed between patients and controls. However, as the scatter of the results was larger in the fibroblasts from patients, we attempted to establish for these patients a relationship between 2-DOG uptake and some biochemical parameters. We observed an inverse relationship between this uptake and the levels of plasma cholesterol and phospholipids (r=−0.85). Compared to controls, 2-DOG uptake was significantly lower in cultures from patients who had very high levels of cholesterol (P2 group), but not in cultures from patients with moderately increased levels of cholesterol (P1 group). The level of total cellular cholesterol in cultured cells from the P1 and P2 groups was not significantly different from the control level, but we found marked differences between the concentrations of fatty acids. In the cultures from patients (especially the P2 group), we observed a significant increase in total fatty acids; among the saturated fatty acids, this increase chiefly concerned the 18:0 (14%) and among the polyunsaturated then −3 fatty acids (55%). The high concentrations of 20:5, 22:5 and 22:6, which enhance membrane fluidity, might explain the decrease in 2-DOG uptake found in the cultures from patients (P2 group) with PILBD. The nature of these abnormalities might be connected with the genetic origin of Alagille syndrome