1.

その他

その他
佐々木, 素子 ; Sasaki, Motoko
出版情報: 博士学位論文要旨 論文内容の要旨および論文審査結果の要旨/金沢大学大学院医学研究科.  平成8年7月  1996-07-01.  金沢大学
URL: http://hdl.handle.net/2297/15389
概要: 取得学位:博士(医学),報告番号:乙第1437号,学位授与年月日:平成7年5月17日,学位授与年:1995
2.

論文

論文
佐々木, 素子 ; Sasaki, Motoko
出版情報: 平成29(2017)年度 科学研究費補助金 基盤研究(C) 研究成果報告書.  2015-04-01 - 2018-03-31  pp.5p.-,  2018-05-25.  金沢大学医薬保健研究域医学系
URL: http://hdl.handle.net/2297/00050993
概要: 本研究では, オートファジー異常と自己抗原異常表出の関連を中心に, 原発性胆汁性胆管炎/肝硬変(PBC)の病態解明と新たな治療法の分子基盤の確立, オートファジー異常検出による新しいPBCの病理診断マーカーの開発を目ざした。肝移植後肝生検や 原因不明肝硬変においても, PBC特異的なオートファジー異常とミトコンドリア抗原異常発現はPBCの病理診断に有用であることが示された。さらに, PBCの胆管病変におけるオートファジー異常, ミトコンドリア抗原異常発現, 細胞老化の発生機構には, 胆管保護に重要な役割を持つAnion Exchanger 2 (AE2)の発現低下が関与することが示唆された。<br />研究課題/領域番号:15K08341, 研究期間(年度):2015-04-01 - 2018-03-31 続きを見る
3.

論文

論文
Kakuda, Yuko ; Harada, Kenichi ; Sawada-Kitamura, Seiko ; Ikeda, Hiroko ; Sato, Yasunori ; Sasaki, Motoko ; Okafuji, Hirofumi ; Mizukoshi, Eishiro ; Terasaki, Shuichi ; Ohta, Hajime ; Kasashima, Satomi ; Kawashima, Atsuhiro ; Kaizaki, Yasuharu ; Kaneko, Shuichi ; Nakanuma, Yasuni
出版情報: Human Pathology.  44  pp.1107-1117,  2013-06-01.  Elsevier
URL: http://hdl.handle.net/2297/33483
概要: Recently, our research team proposed a new histologic staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histologic heterogeneity. The present study aimed to confirm the usefulness of the new evaluation system. A total of 152 liver biopsy specimens and clinical data (including outcomes in patients with PBC before treatment with ursodeoxycholic acid) were analyzed with respect to the new system. Staging was evaluated on the basis of 3 histologic components (fibrosis, bile duct loss, and deposition of orcein-positive granules), and grading was assessed on the basis of chronic cholangitis activity and hepatitis activity. Concurrently, the classical systems, that is, the Scheuer and Ludwig staging systems, were also assessed and compared with our new system. PBC cases showed different distributions in each stage of the 3 systems. The new staging and grading system reflected liver dysfunctions before specific treatment. This was on a par with the results obtained using the classical systems. Development of cirrhosis-related conditions correlated well with the new staging system compared with the 2 classical staging systems, and in particular, the amount of deposition of orcein-positive granules could reflect development of cirrhosis-related conditions (scores 0-1 versus scores 2-3 groups, P < .0001). In conclusion, the new PBC staging system was demonstrated to reflect clinicolaboratory features, and its progression was associated with the development of cirrhosis-related conditions. © 2013 Elsevier Inc. All rights reserved. 続きを見る
4.

論文

論文
Sasaki, Motoko ; Miyakoshi, Masami ; Sato, Yasunori ; Nakanuma, Yasuni
出版情報: Digestive Diseases and Sciences.  57  pp.660-666,  2012-03-01.  Springer Science+Business Media, LLC
URL: http://hdl.handle.net/2297/29481
概要: Background and Aim: Recent studies disclosed that autophagy facilitates the process of senescence. Given that cellular senescence is involved in the pathophysiology of ductular reaction (DR) in primary biliary cirrhosis (PBC), we examined an involvement of autophagy in DRs in PBC and control livers. Methods: We examined immunohistochemically the expression of microtubule-associated proteins light chain 3β (LC3) as autophagy marker, p62/sequestosome-1 (p62) as autophagy-related marker in bile ductular cells in livers taken from the patients with PBC (n = 42), and control livers (n = 100). The expression of senescent markers (p16INK4a and p21WAF1/Cip1) in bile ductular cells and their correlation with autophagy was also evaluated. Results: The expression of LC3 was seen in coarse vesicles in the cytoplasm of bile ductular cells and significantly more frequently in PBC of both early and advanced stages when compared to control livers (p < 0.01). The expression of p62 was seen as intracytoplasmic aggregates and significantly more frequently in PBC when compared to control livers (p < 0.05). The expression of LC3 and p62 significantly correlated with each other (p < 0.01). The expression of LC3 and p62 significantly correlated with the expression of p16INK4a, p21WAF1/Cip1 (p < 0.05). Conclusions: Autophagy is frequently seen in bile ductular cells in DRs in PBC. Since cellular senescence of bile ductular cells is rather frequent in the advanced stage of PBC, autophagy may precede cellular senescence of bile ductular cells in DRs in PBC. © 2011 Springer Science+Business Media, LLC. 続きを見る
5.

論文

論文
Sasaki, Motoko ; Nakanuma, Yasuni
出版情報: International Journal of Hepatology.  2010  pp.205128-,  2010-01-01.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/31484
概要: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized serologically by the high prevalence of anti-mitochondrial autoantibodies (AMAs) and histologically by the cholangitis of small bile ducts, eventually followed by extensive loss of the small bile duct. An autoimmune pathogenesis is suggested by clinical and experimental studies, but there remain issues regarding the etiology, the significance of AMAs in the pathogenesis of bile duct lesions, and so on. The unique properties of apoptosis in biliary epithelial cells (BECs), in which there is exposure of autoantigen to the effectors of the immune system, are proposed to be a cause of bile duct lesions in PBC. Recent progress disclosed that cellular senescence and autophagy are involved in bile duct lesions in PBC. Senescent BECs may modulate the periductal microenvironment by expressing senescence-associated secretory phenotypes, including various chemokines, and contribute to the pathogenesis of bile duct lesions in PBC. 続きを見る
6.

論文

論文
Sasaki, Motoko ; Nakanuma, Yasuni
出版情報: International Journal of Hepatology.  2012  pp.452143-,  2012-01-01.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/31480
概要: Primary biliary cirrhosis (PBC) is characterized by antimitochondrial autoantibodies (AMAs) in patients' sera and histologically by chronic nonsuppurative destructive cholangitis in small bile ducts, eventually followed by extensive bile duct loss and biliary cirrhosis. The autoimmune-mediated pathogenesis of bile duct lesions, including the significance of AMAs, triggers of the autoimmune process, and so on remain unclear. We have reported that cellular senescence in biliary epithelial cells (BECs) may be involved in bile duct lesions and that autophagy may precede the process of biliary epithelial senescence in PBC. Interestingly, BECs in damaged bile ducts show characteristicsof cellular senescence and autophagy in PBC. A suspected causative factor of biliary epithelial senescence is oxidative stress. Furthermore, senescent BECs may modulate the microenvironment around bile ducts by expressing various chemokines and cytokines called senescence-associated secretory phenotypes and contribute to the pathogenesis in PBC. 続きを見る
7.

論文

論文
Sasaki, Motoko ; Allina, Jorge Joseph ; Odin, A. ; Thung, Swan N. ; Coppel, Ross ; Nakanuma, Yasuni ; Gershwin, Eric M.
出版情報: Developmental Immunology.  9  pp.103-111,  2002-01-01.  Hindawi Publishing Corporation
URL: http://hdl.handle.net/2297/31500
概要: Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by intrahepatic bile duct destruction and the production of anti-mitochondrial antibodies (AMA). The absence of an animal model has been a striking impedance in defining the molecular basis of disease. Previous work has suggested that SJL/J mice immunize with the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC, leads to the development of lymphoid cell infiltration in portal tracts and a model system coined autoimmune cholangitis. We hypothesized that this pathology would be augmented if immunization occurred in the presence of IFN-γ injections. Accordingly, SJL/J mice were immunized with PDC-E2 and, for purpose of control, α-casein. Subgroups of mice were also treated with exogenous IFN-γ. As expected, mice immunized with PDC-E2, with or without IFN-γ, developed high titer AMAs. In contrast, mice immunized with α-casein, develop antinuclear antibodies. More importantly, the livers from mice immunized with PDC-E2 and/or those immunized with α-casein all displayed lymphoid cell infiltration to the portal tracts, irrespective of bile duct size. Indeed, there was no significant difference between the experimental and the control groups by histologic analysis. Thus, autoimmune cholangitis in these mice is antigen non-specific. 続きを見る
8.

論文

論文
Mochizuki, Kanako ; Kondo, Yukio ; Hosokawa, Kohei ; Ohata, Kinya ; Yamazaki, Hirohito ; Takami, Akiyoshi ; Sasaki, Motoko ; Sato, Yasunori ; Nakanuma, Yasuni ; Nakao, Shinji
出版情報: Internal Medicine.  53  pp.499-503,  2014-01-01.  The Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/37592
概要: Adenoviruses are increasingly recognized as important pathogens following allogeneic stem cell transplantation. We herein report two cases of disseminated adenovirus infection that presented with nodular shadows on chest X-ray after allogeneic bone marrow transplantation from unrelated donors. Both patients died of respiratory failure. Autopsies revealed adenovirus infection of multiple organs. Adenovirus infection should be suspected when nodular lung lesions of unknown origin appear in allogeneic stem cell transplant recipients. © 2014 The Japanese Society of Internal Medicine. 続きを見る
9.

論文

論文
Ikeda, Hiroko ; Katayanagi, Kazuyoshi ; Kurumaya, Hiroshi ; Harada, Kenichi ; Sato, Yasunori ; Sasaki, Motoko ; Nakanuma, Yasuni
出版情報: Gastroenterology Research, bimonthly.  4  pp.168-173,  2011-08-01.  Elmer Press
URL: http://hdl.handle.net/2297/34940
概要: Hypereosinophilic syndrome (HES) is defi ned by elevation more than 1.5×109/L of presence of a peripheral blood count, evidence of organ involvement, and exclusion of secondary eosinophilia such as allergic, vasculitis, drugs, or parasite infection and also clonal eosinophilia. We present the HES case with hepatic involvement. The patient is 70-year-old male. He complained fever and back pain. Blood examination showed marked peripheral eosinophilia, elevation of transaminase and biliary enzymes. Multiple irregular mass lesions of the liver were pointed out by CT and MRI. The liver biopsy was done for differentiation from malignancy. In parenchyma, hepatic necrotic lesion was observed accompanying severe eosinophilic infi ltration with Charcot-Leyden’s crystals. There was granulomatous reaction. He was diagnosed as HES and got recovery due to steroid therapy. From the review of HES article, the hepatic histology is categorized into four types as below: 1) cholangitis type; 2) chronic active hepatitis type; 3) vasculopathic type, 4) hepatic necrosis type. Our case is classifi ed in hepatic necrosis type. This type seems to be important to distinguish malignant tumor and also visceral larva migrans by liver biopsy. 続きを見る
10.

論文

論文
Yamaguchi, Junpei ; Sasaki, Motoko ; Sato, Yasunori ; Itatsu, Keita ; Harada, Kenichi ; Zen, Yoh ; Ikeda, Hiroko ; Nimura, Yuji ; Nagino, Masato ; Nakanuma, Yasuni
出版情報: Cancer Science.  101  pp.355-362,  2010-02-01.  Japanese Cancer Association / Blackwell Publishing Ltd
URL: http://hdl.handle.net/2297/45959
概要: 医薬保健研究域医学系<br />Polycomb group protein EZH2, frequently overexpressed in malignant tumors, is the catalytic subuni t of polycomb repressive complex 2 (PRC2). PRC2 interacts with HDACs in transcriptional silencing and relates to tumor suppressor loss. We examined the expression of HDAC isoforms (HDAC 1 and 2) and EZH2, and evaluated the possible use of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and EZH2 repressor for gallbladder carcinoma. We used 48 surgically resected gallbladders and cultures of human gallbladder epithelial cells (HGECs), gallbladder carcinoma (TGBC2TKB), and cholangiocarcinoma (HuCCT-1 and TFK-1) cell lines for examination. Immunohistochemically, EZH2 was overexpressed in gallbladder carcinoma, especially poorly differentiated carcinoma, but not in normal epithelium. In contrast, HDAC1/2 were expressed in both carcinoma and normal epithelium in vivo. This pattern was verified in cultured cells; EZH2 was highly expressed only in TGBC2TKB, whereas HDAC1/2 were expressed in HGECs and TGBC2TKB. Interestingly, SAHA treatment caused significant cell number decline in three carcinoma cells, and this effect was synergized with EZH2 siRNA treatment; however, HGECs were resistant to SAHA. In TGBC2TKB cells, the expression of EZH2 and HDAC1/2 were decreased by SAHA treatment, and p16INK4a, E-cadherin, and p21were simultaneously activated; however, no such findings were obtained in HGECs, suggesting that the effect of SAHA depends on the EZH2-mediated tumor suppressor loss. In conclusion, this study suggests a possible mechanism by which carcinoma cells but not normal cells are sensitive to SAHA and indicates the efficacy of this new anticancer agent in combination with EZH2 repression in gallbladder carcinoma. © 2009 Japanese Cancer Association. 続きを見る