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論文 |
論文
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Kobayashi, Mio ; Kakuda, Yuko ; Harada, Kenichi ; Sato, Yasunori ; Sasaki, Motoko ; Ikeda, Hiroko ; Terada, Mitsuhiro ; Mukai, Munenori ; Kaneko, Shuichi ; Nakanuma, Yasuni ; 小林, 水緒 ; 原田, 憲一 ; 佐藤, 保則 ; 佐々木, 素子 ; 池田, 博子 ; 金子, 周一 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />AIM: To investigate histological and immunohistochemical differences in hepatitis between autoimmune
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hepatitis (AIH) and primary biliary cirrhosis (PBC) with AIH features. METHODS: Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined. The activity of periportal and lobular inflammation was scored 0 (none or minimal activity) to 4 (severe), and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3. The infiltration of mononuclear cells positive for CD20, CD38, CD3, CD4, and CD8 and positive for immunoglobulins (IgG, IgM, and IgA) at the periportal areas (interface hepatitis) and in the hepatic lobules (lobular hepatitis) were semiquantitatively scored in immunostained liver sections (score 0-6). Serum aspartate aminotransferase (AST), immunoglobulins, and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions. RESULTS: Lobular hepatitis, hepatitic rosette formation, and emperipolesis were more extensive and frequent in AIH than in PBC. CD3+, CD4+, and CD8+ cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC. The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC, but to a lesser degree in AIH. CD20+ cells were mainly found in the portal tracts and, occasionally, at the interface in both diseases. Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration, specifically CD38+ cells in PBC. No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH. While most AIH cases were IgG-predominant at the interface, PBC cases were divided into IgM-predominant, IgM/IgGequal, and IgG-predominant types, with the latter sharing several features with AIH. CONCLUSION: These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
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論文 |
論文
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Sasaki, Motoko ; Ikeda, Hiroko ; Nakanuma, Yasuni ; 佐々木, 素子 ; 中沼, 安二
概要:
金沢大学大学院医学系研究科がん細胞学<br />Mucin secreted by mucosal epithelial cells plays a role in the protection of the mucosal surface
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and also is involved in pathological processes. So far, MUC1-4, 5AC, 5B, 6-8, 11-13 and 15-17 genes coding the backbone mucin core protein have been identified in humans. Their diverse physiological distribution and pathological alterations have been reported. We have studied the expression profiles of MUC genes in the intrahepatic biliary system in developmental, normal and diseased livers using immunohistochemistry and in situ hybridization. Fetal intrahepatic bile ducts and ductal plates frequently express MUC1, while intrahepatic large bile ducts after birth express mainly MUC3 mucin. In hepatolithiasis, MUC5AC (gastric foveolar epithelial type) and MUC6 (pyloric gland type) mucins are newly expressed in surface epithelial cells and proliferated peribiliary glands, respectively, and the expression of gel-forming mucin may play a role in lithogenesis. Most biliary epithelial dysplasias and cholangiocarcinomas associated with hepatolithiasis expressed MUC5AC, suggesting that intrahepatic bile ducts express the gastric foveolar phenotype during carcinogenesis. In addition, intestinal metaplasia, intraductal papillary tumor and mucinous carcinoma, characterized by MUC2 expression, are occasionally associated with hepatolithiasis in a CDX2 homeobox gene-dependent manner. These findings may suggest the presence of intestinal metaplasia-related carcinogenesis in the intrahepatic biliary system as in the stomach.
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