論文 - 永田 賢治
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Molecular mechanisms of hereditary persistence of α-fetoprotein(AFP) in two Japanese families A hepatocyte nuclear factor-1 site mutation leads to induction of the AFP gene expression in adult livers 査読あり
坪内 佳子,井戸 章雄,宇都 浩文,沼田 政嗣,森内 昭博,金 一徳,蓮池 悟,永田 賢治,関屋 亮,林 克裕,坪内 博仁,日高 智徳
Hepatology Research 31 79 - 87 2005年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Usefulness of a new immuno-radiometric assay to detect hepatitis C core antigen in a community-based population 査読あり
林 克裕,蓮池 悟,楠元 寿典,井戸 章雄,永田 賢治,Kohara Michinori,Stuver O. Sherri,坪内 博仁
Journal of Viral Hepatitis 12 106 - 110 2005年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Hepatocyte growth factor facilitates the repair of large colonic ulcers in 2,4,6-Trinitrobenzene sulfonic acid-induced colitis in rats 査読あり
沼田 政嗣,井戸 章雄,森内 昭博,金 一徳,田原 良博,山本 章二朗,蓮池 悟,永田 賢治,宮田 義史,宇都 浩文,坪内 博仁
Inflamm Bowel Dis 11 ( 6 ) 551 - 558 2005年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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オステオアクチビンの肝線維化・発癌に及ぼす影響の解析
蓮池 悟,宇都 浩文,安倍 弘生,中西 千尋,中西 千尋,楠元 寿典,山本 章二朗,永田 賢治,森内 昭博,井戸 章雄,坪内 博仁
肝サイトスケルトン研究会誌 15 11 - 14 2005年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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The peroxisome proliferator-activated receptor-γ agonist, pioglitazone, inhibits fat accumulation and fibrosis in the livers of rats fed a choline-deficient, L-amino acid-defined diet 査読あり
宇都 浩文,中西 千尋,井戸 章雄,蓮池 悟,楠元 寿典,安倍 弘生,沼田 政嗣,永田 賢治,林 克裕,坪内 博仁
Hepatology Research 32 ( 4 ) 235 - 242 2005年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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HBV関連非代償生肝硬変に対する抗ウイルス剤による予後の工夫 査読あり
蓮池 悟,永田 賢治,宇都 浩文,井戸 章雄,林 克裕,坪内 博仁
消化器科 41 ( 4 ) 364 - 370 2005年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Ｃ型慢性肝炎に対するIFNβ先行IFNα2b+リバビリン併用療法の検討 査読あり
永田 賢治,林 克裕,黒木 穣二,楠元 寿典,蓮池 悟,宇都 浩文,村田 光宏,黒木 和男,中間 哲文,落合 俊雅,駒田 直人,加藤 順也,坪内 博仁
医学と薬学 54 ( 4 ) 519 - 523 2005年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Hepatocyte growth factor accelerates the proliferation of hepatic oval cells and possibly promotes the differentiation in a 2-acetylaminofluorene/partial hepatectomy model in rats 査読あり
蓮池 悟,井戸 章雄,宇都 浩文,森内 昭博,田原 良博,沼田 政嗣,永田 賢治,堀 剛,林 克裕,坪内 博仁
J Gastroenterol Hepatol 20 ( 11 ) 1753 - 1761 2005年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Development of a rapid semi-quantitative immunochromatographic assay for serum hepatocyte growth factor and its usefulness in acute liver failure 査読あり
宇都 浩文,井戸 章雄,楠元 寿典,蓮池 悟,永田 賢治,坪内 博仁
Hepatology Research 33 ( 4 ) 272 - 276 2005年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Reactivation of hepatitis C virus caused by steroid monotherapy for sudden deafness. 査読あり
Kaneko H, Ozono Y, Iwakiri H, Hatada H, Uchiyama N, Komaki Y, Nakamura K, Hasuike S, Nagata K, Kawakami H
Clinical journal of gastroenterology 17 ( 3 ) 505 - 510 2024年6月
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An autopsy case of an adult woman with Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHAD(NET)) syndrome developing nonalcoholic steatohepatitis and hepatocellular carcinoma: A case report. 査読あり
Hasuike S, Ozono Y, Uchida K, Ogawa S, Tamura H, Uchiyama N, Hatada H, Komaki Y, Nakamura K, Iwakiri H, Sueta M, Nagata K, Toyoki Nishimura, Matsuyama M, Sawada H, Oguri T, Sato Y, Kawakami H
Medicine 103 ( 22 ) e38383 2024年5月
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Clinical significances of several fibrotic markers for prognosis in hepatocellular carcinoma patients who underwent hepatectomy. 査読あり
Nanashima A, Hiyoshi M, Imamura N, Hamada T, Tsuchimochi Y, Shimizu I, Ochiai T, Nagata K, Hasuike S, Nakamura K, Iwakiri H, Kawakami H
Translational cancer research 13 ( 5 ) 2332 - 2345 2024年5月
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The successful posterior sectionectomy accompanied with caudate lobectomy for hepatocellular carcinoma located in segment 1 after LEN-TACE; a case report 査読あり
Atsushi Nanashima, Takeomi Hamada, Masahide HIyoshi, Naoya Imamura, Yuki Tsuchimochi, Ikko Shimizu, Kenji Nagata, Hiroshi Kawakami
Clinical Journal of Gastroenterology 17 ( 3 ) 490 - 496 2024年
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Performance evaluation of Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test for different diagnostic situations. 査読あり
Kuramitsu M, Momose H, Uchida Y, Ishitsuka K, Kubota R, Tokunaga M, Utsunomiya A, Umekita K, Hashikura Y, Nosaka K, Koh K-R, Nakamura H, Sagara Y, Sobata R, Satake M, Nagata K, Hasegawa Y, Sasaki D, Hasegawa H, Sato T, Yamano Y, Hiraga K, Tezuka K, Ikebe E, Matsuoka S, Okuma K, Watanabe T, Miura K, Hamaguchi I
Microbiology spectrum 11 ( 6 ) e0207823 2023年12月
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拠点病院以外の肝疾患専門医療機関における院内肝炎ウイルス陽性者対策調査
井上 泰輔, 井出 達也, 内田 義人, 小川 浩司, 井上 貴子, 末次 淳, 池上 正, 瀬戸山 博子, 井上 淳, 柿崎 暁, 榎本 大, 立木 佐知子, 遠藤 美月, 永田 賢治, 是永 匡紹
肝臓 64 ( 12 ) 649 - 652 2023年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本肝臓学会
This study was conducted in 2021, wherein we investigated in-hospital measures for patients positive for hepatitis virus in 288 hospitals specializing in liver diseases in 13 Japanese prefectures. Our results showed that even at specialty hospitals, the overall countermeasure implementation rate was low (56%). The rate was higher in hospitals that had a higher bed capacity (>400), more full-time hepatologists, and more hepatitis medical care coordinators. Of these three factors, implementation rate was most influenced by coordinator enrollment, with highest involvement by clinical laboratory technologists. Therefore, clinical laboratory technologists should be trained to improve countermeasure rates for both treatment of liver disease and safety management in hospitals. Furthermore, the improvement in the implementation rate of measures for patients positive for hepatitis virus will help in providing better treatment.
DOI： 10.2957/kanzo.64.649
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Hasuike S, Nagata K, Sasaki H, Hirata T, Suzuki S, Komaki Y, Ozono Y, Nakamura K, Miike T, Iwakiri H, Sueta M, Yamamoto S, Maekawa K, Kawakami H
Internal medicine (Tokyo, Japan) 62 ( 21 ) 3143 - 3149 2023年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本内科学会
We reported a notable case of inflammatory hepatocellular adenoma that grew during pregnancy, consequently changing its appearance on magnetic resonance imaging remarkably. A 5-months-pregnant 35-year-old woman presented with a 37-mm liver nodule that had been diagnosed as focal nodular hyperplasia 3 years earlier. She had never used oral contraceptives. After 2 months, the nodule grew to 57 mm. The patient delivered a full-term infant without complications. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging performed after delivery revealed markedly different findings compared with the first images. A liver biopsy was performed, and the tumor was diagnosed as inflammatory hepatocellular adenoma.
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Inflammatory Hepatocellular Adenoma Mimicking Focal Nodular Hyperplasia That Grew during Pregnancy and Changed Its Appearance on Magnetic Resonance Imaging after Delivery 査読あり
Satoru Hasuike, Kenji Nagata, Haruka Sasaki, Tomoya Hirata, Sho Suzuki, Yuri Komaki, Yoshinori Ozono, Kenichi Nakamura, Tadashi Miike, Hisayoshi Iwakiri, Mitsue Sueta, Shojiro Yamamoto, Kazuya Maekawa, Hiroshi Kawakami
Internal Medicine 62 ( 21 ) 3143 - 3149 2023年11月
記述言語：英語 掲載種別：症例報告
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肝疾患診療連携拠点病院における肝炎医療コーディネーターの現状（第2報）
磯田 広史, 榎本 大, 高橋 宏和, 大野 高嗣, 井上 泰輔, 池上 正, 井出 達也, 德本 良雄, 小川 浩司, 瀬戸山 博子, 内田 義人, 橋本 まさみ, 廣田 健一, 柿崎 暁, 立木 佐知子, 井上 貴子, 遠藤 美月, 島上 哲朗, 荒生 祥尚, 井上 淳, 末次 淳, 永田 賢治, 是永 匡紹
肝臓 64 ( 10 ) 510 - 513 2023年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本肝臓学会
Hepatitis medical care coordinators (HMCCs) in Japan are trained by local governments and regional core centers, and are expected to play an active role in various aspects of hepatitis countermeasures. A 2019 survey revealed varied activity statuses of HMCCs among facilities. This study surveyed the present status of HMCCs in 21 of the 72 regional core centers in the fiscal year 2021.A total of 951 HMCCs were trained at these 21 facilities. The 17 participating centers of the 2019 survey indicated a slight increase in the proportion of HMCCs who actively contributed to hepatitis patient care, from 84.2% to 85.8%.Despite the COVID-19 pandemic, HMCCs remained active in many facilities.
DOI： 10.2957/kanzo.64.510
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肝炎ウイルス陽性者に対する院内連携システムの構築とその成果 査読あり
小牧優里 大園芳範,中村憲一,岩切久芳,末田光恵,蓮池悟,和田徹也,永田賢治,河上洋
宮崎県医師会医学会誌 47 ( 2 ) 177 - 182 2023年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Klebsiella pneumoniaeによる侵襲性肝膿瘍症候群を発症し、眼内炎から失明に至った1例 査読あり
田村穂高 大園芳範,内山尚美,畑田紘志,中村憲一,岩切久芳,蓮池悟,永田賢治,河上洋
日本消化器病学会雑誌 120 ( 6 ) 500 - 507 2023年6月
記述言語：日本語 掲載種別：症例報告
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Tamura H, Ozono Y, Uchiyama N, Hatada H, Nakamura K, Iwakiri H, Hasuike S, Nagata K, Kawakami H
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 120 ( 6 ) 500 - 507 2023年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般財団法人 日本消化器病学会
症例は82歳，女性．両眼の視力低下を認め，近医眼科より当院紹介となった．精査により発症4日目に<i>Klebsiella pneumoniae</i>による侵襲性肝膿瘍症候群，両側眼内炎と診断した．抗菌薬の全身投与と硝子体内注射を行い，肝膿瘍は改善したが，両眼失明に至った．侵襲性肝膿瘍症候群は発熱を初発症状とする報告が多いが，本例では眼症状発症時に発熱がなく，診断が遅れ，視力予後が不良となった．
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Komaki Y., Ozono Y., Nakamura K., Iwakiri H., Hasuike S., Sueta M., Miike T., Yamamoto S., Uto H., Kusumoto K., Ochiai T., Kato J., Komada N., Kuroki K., Eto T., Shigehira M., Hirono S., Nagata K., Kawakami H.
BMC Gastroenterology 22 ( 1 ) 210 2022年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Gastroenterology
Background: It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years. Methods: This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group. Results: In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups. Conclusions: Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment.
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Trends in hepatocellular carcinoma incident cases in Japan between 1996 and 2019 査読あり
Nakano M., Yatsuhashi H., Bekki S., Takami Y., Tanaka Y., Yoshimaru Y., Honda K., Komorizono Y., Harada M., Shibata M., Sakisaka S., Shakado S., Nagata K., Yoshizumi T., Itoh S., Sohda T., Oeda S., Nakao K., Sasaki R., Yamashita T., Ido A., Mawatari S., Nakamuta M., Aratake Y., Matsumoto S., Maeshiro T., Goto T., Torimura T.
Scientific Reports 12 ( 1 ) 1517 2022年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996–2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60–69 years, 70–79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease.
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Uchida K., Ozono Y., Uchiyama N., Hatada H., Nakamura K., Komaki Y., Iwakiri H., Hasuike S., Nagata K., Sato Y., Kawakami H.
Medicine United States 101 ( 35 ) e30486 2022年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Medicine United States
Rationale: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer globally. Since 2020, combination treatment with atezolizumab and bevacizumab were approved in patients with unresectable HCC in Japan, and atezolizumab plus bevacizumab is the first-line treatment for unresectable HCC. Patient concerns: A 73-year-old Japanese man diagnosed with a large HCC was treated with atezolizumab plus bevacizumab. After 2 cycles, he had fever and fatigue and was admitted to the hospital. Diagnosis: Abdominal contrast-enhanced computed tomography revealed tumor necrosis in HCC with gas formation in the necrotic area. Laboratory examination revealed a white blood cell (WBC) count of 16,340/μL and C-reactive protein (CRP) level of 33.0 mg/dL. Based on the above findings, he was diagnosed with a liver abscess. Interventions: Percutaneous transhepatic liver abscess drainage and broad-spectrum antibiotics treatment were performed. Outcomes: Despite liver abscess drainage, persistent fever and no improvement in the WBC count or CRP level was observed. The patient's respiratory condition and renal function gradually worsened; The patient's general condition did not improve despite the ventilator support and continuous hemodiafiltration, and he died on day 37. Lessons: We report the first case of liver abscess after atezolizumab plus bevacizumab treatment for unresectable HCC.
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大園 芳範, 中村 憲一, 岩切 久芳, 蓮池 悟, 末田 光恵, 三池 忠, 山本 章二朗, 永田 賢治, 河上 洋
BMC Gastroenterology 22 ( 1 ) 210 2022年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Springer Nature
Background
It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years.
Methods
This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group.
Results
In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups.
Conclusions
Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment. -
NAKAMURA K., KUSUMOTO K., OZONO Y., KUROKI K., MATSUURA Y., MUKUDA T., OCHIAI T., TSUCHIMOCHI M., IWAKIRI H., HASUIKE S., SHIMODA K., NAGATA K.
Anticancer Research 41 ( 8 ) 4127 - 4131 2021年8月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Anticancer Research
Background/Aim: Direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection deliver higher cure rates and lower frequencies of adverse events than existing therapies, though DAA treatment costs $45,000-64,000 in Japan. The prognosis of patients who require new long-term care insurance (LTCI) certification is inferior to that of patients who do not. Here, we clarify the factors associated with new LTCI certification in elderly patients with HCV infection who undergo DAA therapy. Patients and Methods: We retrospectively surveyed 53 patients aged ≥70 years who were treated with DAAs, and evaluated the factors associated with new LTCI certification. Results: Of 53 patients, 10 required new LTCI certification. Age ≥85 years and a modified Japanese Cardiovascular Health Study index ≥2 were independently associated with new LTCI certification. Conclusion: In elderly HCV patients, poor frailty status strongly predicted new LTCI certification after DAA therapy.
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Ozono Y., Shide K., Kameda T., Kamiunten A., Tahira Y., Sekine M., Akizuki K., Nakamura K., Iwakiri H., Sueta M., Hidaka T., Kubuki Y., Yamamoto S., Hasuike S., Sawaguchi A., Nagata K., Shimoda K.
Leukemia 35 ( 2 ) 454 - 467 2021年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal myeloproliferation, progressive bone marrow (BM) fibrosis, splenomegaly, and anemia. BM fibrosis was previously thought to be a reactive phenomenon induced by mesenchymal stromal cells that are stimulated by the overproduction of cytokines such as transforming growth factor (TGF)-β1. However, the involvement of neoplastic fibrocytes in BM fibrosis was recently reported. In this study, we showed that the vast majority of collagen- and fibronectin-producing cells in the BM and spleens of Jak2V617F-induced myelofibrosis (MF) mice were fibrocytes derived from neoplastic hematopoietic cells. Neoplastic monocyte depletion eliminated collagen- and fibronectin-producing fibrocytes in BM and spleen, and ameliorated most characteristic MF features in Jak2V617F transgenic mice, including BM fibrosis, anemia, and splenomegaly, while had little effect on the elevated numbers of megakaryocytes and stem cells in BM, and leukothrombocytosis in peripheral blood. TGF-β1, which was produced by hematopoietic cells including fibrocytes, promoted the differentiation of neoplastic monocytes to fibrocytes, and elevated plasma TGF-β1 levels were normalized by monocyte depletion. Collectively, our data suggest that neoplastic fibrocytes are the major contributor to BM fibrosis in PMF, and TGF-β1 is required for their differentiation.
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肝疾患診療連携拠点病院における肝炎医療コーディネーターの現状 査読あり
Enomoto M., Hidaka I., Inoue T., Isoda H., Ide T., Arao Y., Uchida Y., Inoue T., Ikegami T., Kakizaki S., Setoyama H., Shimakami T., Ogawa K., Suetsugu A., Inoue J., Endo M., Nagata K., Korenaga M.
肝臓 62 ( 2 ) 96 - 98 2021年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Acta Hepatologica Japonica
In Japan, each prefecture in collaboration with regional core centers is required to train hepatitis medical care coordinators (HMCCs). In this study, we sur-veyed the present status of HMCCs in 17 of the 71 regional core centers. The findings indicated that the number of HMCCs varied from 8 to 77 per regional core center. The proportion of HMCCs who actively contributed to hepatitis patient care also varied from 7.9% to 100%. Among the HMCCs, 50% were nurses, 11% clinical laboratory technicians, 8.0% pharmacists, 8.0% registered dietitians, and 3.5% doctors. The results of the survey show that, in each regional core center, there is a substantial variety in the present status of HMCCs.
DOI： 10.2957/kanzo.62.96
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Shide K., Kameda T., Kamiunten A., Ozono Y., Tahira Y., Yokomizo-Nakano T., Kubota S., Ono M., Ikeda K., Sekine M., Akizuki K., Nakamura K., Hidaka T., Kubuki Y., Iwakiri H., Hasuike S., Nagata K., Sashida G., Shimoda K.
Blood 136 ( 1 ) 106 - 118 2020年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Blood
Mutations in JAK2, myeloproliferative leukemia virus (MPL), or calreticulin (CALR) occur in hematopoietic stem cells (HSCs) and are detected in more than 80% of patients with myeloproliferative neoplasms (MPNs). They are thought to play a driver role in MPN pathogenesis via autosomal activation of the JAK-STAT signaling cascade. Mutant CALR binds to MPL, activates downstream MPL signaling cascades, and induces essential thrombocythemia in mice. However, embryonic lethality of Calr-deficient mice precludes determination of a role for CALR in hematopoiesis. To clarify the role of CALR in normal hematopoiesis and MPN pathogenesis, we generated hematopoietic cell-specific Calr-deficient mice. CALR deficiency had little effect on the leukocyte count, hemoglobin levels, or platelet count in peripheral blood. However, Calr-deficient mice showed some hematopoietic properties of MPN, including decreased erythropoiesis and increased myeloid progenitor cells in the bone marrow and extramedullary hematopoiesis in the spleen. Transplantation experiments revealed that Calr haploinsufficiency promoted the self-renewal capacity of HSCs. We generated CALRdel52 mutant transgenic mice with Calr haploinsufficiency as a model that mimics human MPN patients and found that Calr haploinsufficiency restored the self-renewal capacity of HSCs damaged by CALR mutations. Only recipient mice transplanted with Lineage−Sca1+c-kit+ cells harboring both CALR mutation and Calr haploinsufficiency developed MPN in competitive conditions, showing that CALR haploinsufficiency was necessary for the onset of CALR-mutated MPNs. Key Points: • Calr deficiency induces reduction of erythropoiesis in the bone marrow and extramedullary hematopoiesis in the spleen. • CALR haploinsufficiency restores the self-renewal capacity of HSCs damaged by CALR del52 and is required for the development of MPN.
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Yamaji T, Shide K, Kameda T, Sekine M, Kamiunten A, Hidaka T, Kubuki Y, Shimoda H, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Shimoda K
Anticancer Research 37 ( 7 ) 3841 - 3847 2017年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Anticancer Research
Background/Aim: In myeloproliferative neoplasms (MPN), Janus kinase 2 (JAK2) is activated by mutations including JAK2V617F (JAK2VF). It is unclear whether JAK kinases [i.e. JAK1, JAK2, JAK3, or tyrosine kinase 2 (TYK2)] other than JAK2 have cooperative actions such as enhancement or suppression of JAK2. If other kinases enhance activation, therapies that co-target them could have a therapeutic efficacy. We examined the role of TYK2 in Jak2VF-induced murine MPN. Materials and Methods: We crossed Jak2VF transgenic mice and Tyk2-knockout (Tyk2KO) mice to generate Jak2VF/Tyk2KO mice. The disease severity and treatment effect with a JAK2 inhibitor was compared between Jak2VF and Jak2VF/Tyk2KO mice. Results: Both types of mice developed MPN, and there were no differences in peripheral blood counts, spleen weight, or survival period. Upon JAK2 inhibitor therapy, both types of mice had equally improved leukocytosis and splenomegaly. Conclusion: TYK2 does not have cooperative effects with JAK2VF upon MPN onset nor in the presence of a JAK2 inhibitor.
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Prediction of Sustained Virological Response to Telaprevir/Simeprevir-Based Triple Therapy in Patients with Genotype 1 Hepatitis C Virus Using Super-Early Viral Response within 2 Weeks. 査読あり
Ozono Y, Takaishi Y, Tsuchimochi M, Nakamura K, Abe H, Miike T, Kusumoto K, Iwakiri H, Sueta M, Tahara Y, Yamamoto S, Hasuike S, Nagata K, Shimoda K
Journal of Liver. 6 ( 6 ) 1 - 6 2017年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Shide K., Kameda T., Yamaji T., Sekine M., Inada N., Kamiunten A., Akizuki K., Nakamura K., Hidaka T., Kubuki Y., Shimoda H., Kitanaka A., Honda A., Sawaguchi A., Abe H., Miike T., Iwakiri H., Tahara Y., Sueta M., Hasuike S., Yamamoto S., Nagata K., Shimoda K.
Leukemia 31 ( 5 ) 1136 - 1144 2017年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Mutations of calreticulin (CALR) are detected in 25-30% of patients with essential thrombocythemia (ET) or primary myelofibrosis and cause frameshifts that result in proteins with a novel C-terminal. We demonstrate that CALR mutations activated signal tr ansducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic CMK11-5 cells and erythroleukemic F-36P-MPL cells with knocked-in CALR mutations showed increased growth and acquisition of cytokine-independent growth, respectively, accompanied by STAT5 phosphorylation. Transgenic mice expressing a human CALR mutation with a 52 bp deletion (CALRdel52-transgenic mice (TG)) developed ET, with an increase in platelet count, but not hemoglobin level or white blood cell count, in association with an increase in bone marrow (BM) mature megakaryocytes. CALRdel52 BM cells did not drive away wild-type (WT) BM cells in in vivo competitive serial transplantation assays, suggesting that the self-renewal capacity of CALRdel52 hematopoietic stem cells (HSCs) was comparable to that of WT HSCs. Therapy with the Janus kinase (JAK) inhibitor ruxolitinib ameliorated the thrombocytosis in TG mice and attenuated the increase in number of BM megakaryocytes and HSCs. Taken together, our study provides a model showing that the C-terminal of mutant CALR activated JAK-STAT signaling specifically downstream of MPL and may have a central role in CALR-induced myeloproliferative neoplasms.
DOI： 10.1038/leu.2016.308
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TET2 mutation in diffuse large B-cell lymphoma. 査読あり
Kubuki Y, Yamaji T, Hidaka T, Kameda T, Shide K, Sekine M, Kamiunten A, Akizuki K, Shimoda H, Tahira Y, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Kitanaka A, Shimoda K
Journal of clinical and experimental hematopathology 56 ( 3 ) 145 - 149 2017年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本リンパ網内系学会
<i>Ten-eleven translocation-2 (TET2)</i> mutation is frequently observed in myeloid malignancies, and loss-of-function of TET2 is essential for the initiation of malignant hematopoiesis. <i>TET2</i> mutation presents across disease entities and was reported in lymphoid malignancies. We investigated <i>TET2</i> mutations in 27 diffuse large B-cell lymphoma (DLBCL) patients and found a frameshift mutation in 1 case (3.7%). <i>TET2</i> mutation occurred in some populations of DLBCL patients and was likely involved in the pathogenesis of their malignancies.
DOI： 10.3960/jslrt.56.145
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Ito K., Yotsuyanagi H., Sugiyama M., Yatsuhashi H., Karino Y., Takikawa Y., Saito T., Arase Y., Imazeki F., Kurosaki M., Umemura T., Ichida T., Toyoda H., Yoneda M., Tanaka Y., Mita E., Yamamoto K., Michitaka K., Maeshiro T., Tanuma J., Korenaga M., Murata K., Masaki N., Koike K., Mizokami M., Imai Y., Yamada N., Takahashi H., Ishii K., Nomura H., Nishida J., Mikami S., Kitamura T., Tsubota A., Shimada N., Ishikawa T., Ueno Y., Ohno T., Orito E., Suzuki M., Kakizaki S., Takagi H., Tomita E., Takashi K., Mizuta T., Mine T., Kang J., Hirano K., Tsubouchi H., Nozaki A., Sakai A., Nishiguchi S., Tamori A., Hagiwara S., Nakazawa T., Sata M., Kamoshida T., Takahashi A., Kobayashi Y., Sasaki S., Ikegami T., Hiasa Y., Nagata K., Kubota T., Mitsui H., Yamamoto N., Tsuge M., Sato S., Ito Y., Sato W., Uchida S., Tada Y., Mizuochi T., Furusho N., Hige S., Yoshiyasu Karino, Kobayashi M., Hosho K., Yamagiwa S., Sakaida I., Nakane K.
Journal of Gastroenterology and Hepatology (Australia) 31 ( 1 ) 180 - 189 2016年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Gastroenterology and Hepatology (Australia)
© 2016 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd. Background and Aims: The prevalence of sexually transmitted acute infections of the genotype A hepatitis B virus (HBV) has been increasing in Japan. Genotype A HBV is associated with an increased risk of HBV progression to chronic infection after acute hepatitis B (AHB) in adults. A nationwide survey was conducted to evaluate the geographic distribution, clinical, and virologic characteristics of genotype A AHB and chronic hepatitis B (CHB) in Japan. Methods: Five hundred seventy AHB patients were recruited between 2005 and 2010, and 3682 CHB patients were recruited between 2010 and 2011. HBV genotypes were determined for 552 and 3619 AHB and CHB patients, respectively. Clinical characteristics were compared among different genotypes in AHB and CHB patients. Genomic characteristics of HBV genotype A were examined by molecular evolutionary analysis. Results: Hepatitis B virus genotype A was the predominant genotype for AHB between 2005 and 2010. Phylogenetic analysis showed that all strains in the AHB patients with genotype A were classified into subtype Ae. Among CHB patients, the occurrence of genotype A was 4.1%, and genotype A was spreading in young adults. In genotype A CHB patients, early stage liver diseases were predominant, although liver diseases progressed to cirrhosis or hepatocellular carcinoma in some patients. Conclusions: The distribution of HBV genotypes is quite different between AHB and CHB in Japanese patients. Genotype A infection is spreading in young adults of Japanese CHB patients. Sequences derived from Japanese AHB patients were identical to or closely resembled the sequences derived from other Japanese AHB patients.
DOI： 10.1111/jgh.13030
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Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer.
Miike T, Yamamoto S, Miyata Y, Hirata T, Noda Y, Noda T, Suzuki S, Takeda S, Natsuda S, Sakaguchi M, Maemura K, Hashimoto K, Yamaji T, Abe H, Iwakiri H, Tahara Y, Hasuike S, Nagata K, Kitanaka A, Shimoda K
Gastroenterology research and practice 2016 6527653 2016年
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Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer. (共著) 査読あり
Miike T, Yamamoto S, Miyata Y, Hirata T, Noda Y, Noda T, Suzuki Sho, Takeda S, Natsuda S, Sakaguchi M, Maemura K, Hashimoto K, Yamaji T, Abe H, Iwakiri H, Tahara Y, Hasuike S, Nagata K, Kitanaka A, Shimoda K:
Gastroenterology Research and Practice. 2015年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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TET2 Mutation in Adult T-Cell Leukemia/Lymphoma. (共著) 査読あり
Shimoda K, Shide K, Kameda T, Hidaka T, Kubuki Y, Kamiunten A, Sekine M, Akizuki K, Shimoda H, Yamaji T, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Kitanaka A:
J Clin Exp Hematop. 2015年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Kameda T., Shide K., Yamaji T., Kamiunten A., Sekine M., Taniguchi Y., Hidaka T., Kubuki Y., Shimoda H., Marutsuka K., Sashida G., Aoyama K., Yoshimitsu M., Harada T., Abe H., Miike T., Iwakiri H., Tahara Y., Sueta M., Yamamoto S., Hasuike S., Nagata K., Iwama A., Kitanaka A., Shimoda K.
Blood 125 ( 2 ) 304 - 315 2015年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Blood
© 2015 by The American Society of Hematology Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms (MPNs).We examined the individual and cooperative effects of these mutations onMPN development. Recipients of JAK2V617F cells developed primary myelofibrosis-like features; the addition of loss of TET2 worsened this JAK2V617F-induced disease, causing prolonged leukocytosis, splenomegaly, extramedullary hematopoiesis, and modestly shorter survival. Double-mutant (JAK2V617F plus loss of TET2) myeloid cells were more likely to be in a proliferative state than JAK2V617F single-mutant myeloid cells. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the second recipients, which did not develop MPNs. In marked contrast, cooperation between JAK2V617F and loss of TET2 developed and maintained MPNs in the second recipients by compensating for impaired hematopoietic stem cell (HSC) functioning. In-vitro sequential colony formation assays also supported the observation that JAK2V617F did not maintain HSC functioning over the long-term, but concurrent loss of TET2 mutation restored it. Transcriptional profiling revealed that loss of TET2 affected the expression of many HSC signature genes. We conclude that loss of TET2 has two different roles in MPNs: disease accelerator and disease initiator and sustainer in combination with JAK2V617F.
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Nakamura M., Kusumoto K., Ochiai T., Kawagoe T., Tai H., Matsuoka H., Nakano T., Nagata K., Shimoda K., Okamoto H.
Journal of Japanese Society of Gastroenterology 112 ( 8 ) 1533 - 1541 2015年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Japanese Society of Gastroenterology
We experienced two cases of acute hepatitis E in Miyazaki Prefecture in the same period. The patients were unknown to each other and did not have any clear causes or common risk factors of hepatitis E virus (HEV) infection. Nucleotide sequences of the HEV isolates revealed that the two isolates were closely related but with different HEV genotype 3 strains. The two cases appeared to be infected from unknown and different sources. Molecular phylogenetic analysis indicated that the strains were probably descendants of the strains which had been isolated from swine herd in Miyazaki Prefecture 12 years previously. This result indicates that the strains persisted in pig farms, in wild life, or in the natural environment in this region. The source should be identified, and efforts should be made to prevent of the spread of the infection. One of the cases had acute facial paralysis, which might be an extra-hepatic manifestation of HEV infection.
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12年前から宮崎県に存続している遺伝子型3型E型肝炎ウイルスによるE型急性肝炎の2症例 1例での急性末梢性顔面神経麻痺の合併(共著) 査読あり
Nakamura M, Kusumoto K, Ochiai T, Kawagoe T, Tai H, Matsuoka H, Nakano T, Nagata K, Shimoda K, Okamoto H:
日本消化器病学会雑誌 2015年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Kameda T., Shide K., Yamaji T., Kamiunten A., Sekine M., Hidaka T., Kubuki Y., Sashida G., Aoyama K., Yoshimitsu M., Abe H., Miike T., Iwakiri H., Tahara Y., Yamamoto S., Hasuike S., Nagata K., Iwama A., Kitanaka A., Shimoda K.
Genomics Data 4 102 - 108 2015年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Genomics Data
© 2015 The Authors. Myeloproliferative neoplasms (MPNs) are clinically characterized by the chronic overproduction of differentiated peripheral blood cells and the gradual expansion of malignant intramedullary/extramedullary hematopoiesis. In MPNs mutations in JAK2 MPL or CALR are detected mutually exclusive in more than 90% of cases [1,2]. Mutations in them lead to the abnormal activation of JAK/STAT signaling and the autonomous growth of differentiated cells therefore they are considered as "driver" gene mutations. In addition to the above driver gene mutations mutations in epigenetic regulators such as TET2 DNMT3A ASXL1 EZH2 or IDH1/2 are detected in about 5%-30% of cases respectively [3] . Mutations in TET2 DNMT3A EZH2 or IDH1/2 commonly confer the increased self-renewal capacity on normal hematopoietic stem cells (HSCs) but they do not lead to the autonomous growth of differentiated cells and only exhibit subtle clinical phenotypes [4,6-8,5]. It was unclear how mutations in such epigenetic regulators influenced abnormal HSCs with driver gene mutations how they influenced the disease phenotype or whether a single driver gene mutation was sufficient for the initiation of human MPNs. Therefore we focused on JAK2V617F and loss of TET2-the former as a representative of driver gene mutations and the latter as a representative of mutations in epigenetic regulators-and examined the influence of single or double mutations on HSCs (Lineage < sup > - < /sup > Sca-1 < sup > + < /sup > c-Kit < sup > + < /sup > cells (LSKs)) by functional analyses and microarray whole-genome expression analyses [9]. Gene expression profiling showed that the HSC fingerprint genes [10] was statistically equally enriched in TET2-knockdown-LSKs but negatively enriched in JAK2V617F-LSKs compared to that in wild-type-LSKs. Double-mutant-LSKs showed the same tendency as JAK2V617F-LSKs in terms of their HSC fingerprint genes but the expression of individual genes differed between the two groups. Among 245 HSC fingerprint genes 100 were more highly expressed in double-mutant-LSKs than in JAK2V617F-LSKs. These altered gene expressions might partly explain the mechanisms of initiation and progression of MPNs which was observed in the functional analyses [9]. Here we describe gene expression profiles deposited at the Gene Expression Omnibus (GEO) under the accession number GSE62302 including experimental methods and quality control analyses.
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インターフェロンによる精神症状発現の予測 気質・性格特性の関与 (共著) 査読あり
直野慶子、安部 博史、武田 龍一郎、岩切 久芳、蓮池 悟、永田 賢治、下田 和哉、石田 康：
精神医学 2015年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Gene expression profiling of loss of TET2 and/or JAK2V617F mutant hematopoietic stem cells from mouse models of myeloproliferative neoplasms. (共著) 査読あり
Kameda T, Shide K, Yamaji T, Kamiunten A, Sekine M, Hidaka T, Kubuki Y, Sashida G,Aoyama K, Yoshimitsu M, Abe H, Miike T, Iwakiri H, Tahara Y, Yamamoto S, Hasuike S, Nagata K, Iwama At, Kitanaka A, Shimoda K
Genomics Data. 2015年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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12年前から宮崎県に存続している遺伝子型3型E型肝炎ウイルスによるE型急性肝炎の2症例―1例での急性末梢性顔面神経麻痺の合併―
中村 仁彦, 楠元 寿典, 落合 俊雅, 川越 富夫, 田井 博, 松岡 均, 中野 達徳, 永田 賢治, 下田 和哉, 岡本 宏明
日本消化機病學會雜誌. 乙 112 ( 8 ) 1533 - 1541 2015年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：The Japanese Society of Gastroenterology
宮崎県内で同時期に2例のE型急性肝炎症例を経験した．2例に交友関係，共通の生活歴はなかった．両症例のE型肝炎ウイルス（HEV）株は，遺伝子配列の解析から近縁ではあるが同一株ではなく，感染源は異なると考えられた．2例のHEV株はともに12年前に同県内の飼育ブタから検出された遺伝子型3型株の子孫と考えられ，このウイルスが宮崎県内で存続していることが証明された．1例は急性末梢性顔面神経麻痺を合併した．
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Ito K., Yotsuyanagi H., Yatsuhashi H., Karino Y., Takikawa Y., Saito T., Arase Y., Imazeki F., Kurosaki M., Umemura T., Ichida T., Toyoda H., Yoneda M., Mita E., Yamamoto K., Michitaka K., Maeshiro T., Tanuma J., Tanaka Y., Sugiyama M., Murata K., Masaki N., Mizokami M., Imai Y., Yamada N., Takahashi H., Ishii K., Nomura H., Nishida J., Mikami S., Kitamura T., Tsubota A., Shimada N., Ishikawa T., Ueno Y., Ohno T., Orito E., Suzuki M., Takagi H., Tomita E., Takashi K., Mizuta T., Mine T., Kang J., Hirano K., Tsubouchi H., Nozaki A., Sakai A., Nishiguchi S., Tamori A., Hagiwara S., Nakazawa T., Sata M., Kamoshida T., Takahashi A., Kakizaki S., Kobayashi Y., Sasaki S., Ikegami T., Hiasa Y., Nagata K., Kubota T., Mitsui H., Yamamoto N., Tsuge M., Sato S., Ito Y., Sato W., Uchida S., Tada Y., Mizuochi T., Furusho N., Hige S.
Hepatology 59 ( 1 ) 89 - 97 2014年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Hepatology
© 2013 by the American Association for the Study of Liver Diseases. The proportion of patients who progress to chronicity following acute hepatitis B (AHB) varies widely worldwide. Moreover, the association between viral persistence after AHB and hepatitis B virus (HBV) genotypes in adults remains unclear. A nationwide multicenter study was conducted throughout Japan to evaluate the influence of clinical and virological factors on chronic outcomes in patients with AHB. For comparing factors between AHB patients with viral persistence and those with self-limited infection, 212 AHB patients without human immunodeficiency virus (HIV) coinfection were observed in 38 liver centers until serum hepatitis B surface antigen (HBsAg) disappeared or a minimum of 6 months in cases where HBsAg persisted. The time to disappearance of HBsAg was significantly longer for genotype A patients than that of patients infected with non-A genotypes. When chronicity was defined as the persistence of HBsAg positivity for more than 6 or 12 months, the rate of progression to chronicity was higher in patients with genotype A, although many cases caused by genotype A were prolonged cases of AHB, rather than chronic infection. Multivariate logistic regression analysis revealed only genotype A was independently associated with viral persistence following AHB. A higher peak level of HBV DNA and a lower peak of alanine aminotransferase (ALT) levels were characteristics of AHB caused by genotype A. Treatment with nucleotide analogs (NAs) did not prevent progression to chronic infection following AHB overall. Subanalysis suggested early NA initiation may enhance the viral clearance. Conclusion: Genotype A was an independent risk factor for progression to chronic infection following AHB. Our data will be useful in elucidating the association between viral persistence after AHB, host genetic factors, and treatment with NAs in future studies.
DOI： 10.1002/hep.26635
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KAWANO Noriaki, HASUIKE Satoru, IWAKIRI Hisayoshi, NAKAMURA Kenichi, OZONO Yoshinori, KUSUMOTO Hisanori, NAGATA Kenji, KIKUCHI Ikuko, YOSHIDA Shuro, KURIYAMA Takuro, YAMASHITA Kiyoshi, MURANAKA Takahiro, KAWAGUCHI Takumi, SATA Michio, OKAMURA Takashi, UEDA Akira, SHIMODA Kazuya
Journal of clinical and experimental hematopathology 53 ( 2 ) 151 - 155 2013年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：The Japanese Society for Lymphoreticular Tissue Research
Portal vein thrombosis is a rare, aggressive andlife-threatening complication of liver cirrhosis (LC). Eltrombopag is effective for the treatment of chronic hepatitis with thrombocytopenia, andportal vein thrombosis at this time has rarely been reported. We describe the case of a 78-year-old woman who suffered from LC due to hepatitis C viral infection. The patient developed immune thrombocytopenic purpura (ITP) that was diagnosed on the basis of nasal bleeding, progressive severe thrombocytopenia, elevation of platelet-associatedIgG (PAIgG), no response to the transfusion of platelets andno abnormal findings on bone marrow biopsy. Although we first administered prednisolone (0.5 mg/kg/day), there was no recovery of platelet function and the nasal bleeding persisted. Subsequently, we administered eltrombopag for refractory ITP at a dose of 12.5 mg/day, and the thrombocytopenia gradually improved. Fifty-four days after the start of eltrombopag therapy, she developedportal vein thrombosis. Eltrombopag was stoppedimmed iately, andantithrombin III was administeredfor prophylaxis against further portal vein thrombosis. Despite these treatments, there were subsequent deep vein and pulmonary artery thromboses. We then administered heparin for recanalization of the thrombi. One month after the initiation of heparin, there was recanalization as well as improvements of the portal vein, deep vein and pulmonary artery thromboses. There was no further thrombosis progression after switching from heparin to warfarin therapy. Our case suggests that eltrombopag may increase the risk of portal vein thrombosis ; therefore, this drug must be used carefully in the treatment of ITP in patients with LC due to hepatitis C viral infection. [<I>J Clin Exp Hematop 53(2) : 151-155, 2013</I>]
DOI： 10.3960/jslrt.53.151
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膜性腎症の治療経過中に発症した de novo B 型肝炎の1例
大園 芳範, 蓮池 悟, 永田 賢治, 山田 優里, 土持 舞衣, 中村 憲一, 白土 明美, 楠元 寿典, 岩切 久芳, 佐藤 祐二, 藤元 昭一, 北村 和雄, 鮫島 直樹, 下田 和哉
肝臓 54 ( 1 ) 74 - 80 2013年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：The Japan Society of Hepatology
症例は75歳，男性．特発性膜性腎症に対し免疫抑制療法を施行されていた．治療開始11カ月後に肝障害が出現し当科入院．膜性腎症診断時のHBs抗原陰性，HBs抗体陰性，HBc抗体陽性であり既往感染例と考えられたが，肝障害出現時にHBs抗原陽転化を認めたため，de novo B型肝炎と診断した．HBV-DNAは9.1 logcopies/mLと上昇しており，核酸アナログ製剤の内服を開始した．以後，トランスアミナーゼ，HBV-DNAともに漸減し，重症化・劇症化することなく経過した．de novo B型肝炎の基礎疾患として本症例のような腎疾患の報告は少なく，文献的考察を加えて報告する．<br>
DOI： 10.2957/kanzo.54.74
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TET2 is essential for survival and hematopoietic stem cell homeostasis
Shide K., Kameda T., Shimoda H., Yamaji T., Abe H., Kamiunten A., Sekine M., Hidaka T., Katayose K., Kubuki Y., Yamamoto S., Miike T., Iwakiri H., Hasuike S., Nagata K., Marutsuka K., Iwama A., Matsuda T., Kitanaka A., Shimoda K.
Leukemia 26 ( 10 ) 2216 - 2223 2012年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
Ten-Eleven-Translocation 2 (TET2) is an enzyme that catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5-hmC) and thereby alters the epigenetic state of DNA; somatic loss-of-function mutations of TET2 are frequently observed in patients with diverse myeloid malignancies. To study the function of TET2 in vivo, we analyzed Ayu17-449 (TET2 trap ) mice, in which a gene trap insertion in intron 2 of TET2 reduces TET2 mRNA levels to about 20% of that found in wild-type (WT) mice. TET2 trap/trap mice were born at Mendelian frequency but died at a high rate by postnatal day 3, indicating the essential role of TET2 for survival. Loss of TET2 results in an increase in the number of hematopoietic stem cells (HSCs)/progenitors in the fetal liver, and TET2 trap/trap HSCs exhibit an increased self-renewal ability in vivo. In competitive transplantation assays, TET2 trap/trap HSCs possess a competitive growth advantage over WT HSCs. These data indicate that TET2 has a critical role in survival and HSC homeostasis. © 2012 Macmillan Publishers Limited.
DOI： 10.1038/leu.2012.94
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Umekita K., Miyauchi S., Ueno S., Takajo I., Kusumoto K., Hasuike S., Umekita Y., Tanaka H., Nagata K., Nagatomo Y., Kataoka H., Shimoda K., Okayama A.
Internal Medicine 50 ( 11 ) 1245 - 1249 2011年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
We report a case of rheumatoid arthritis (RA) with autoimmune hepatitis (AIH) and Sjogren syndrome (SjS) that was treated with the tumor necrosis factor (TNF) inhibitor, etanercept (ETN). Both RA activity and transaminase levels improved as a result of treatment. Follow-up liver biopsy showed improvement of hepatitis. Although the efficacy of anti-TNF for RA patients with AIH remains controversial, this case suggests that treatment with ETN may result in a favorable clinical course in a certain subset of patients with RA and AIH. © 2011 The Japanese Society of Internal Medicine.
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KAWAGUCHI Takumi, KAKUMA Tatsuyuki, YATSUHASHI Hiroshi, WATANABE Hiroshi, SAITSU Hideki, NAKAO Kazuhiko, TAKETOMI Akinobu, OHTA Satoshi, TABARU Akinari, TAKENAKA Kenji, MIZUTA Toshihiko, NAGATA Kenji, KOMORIZONO Yasuji, FUKUIZUMI Kunitaka, SEIKE Masataka, MATSUMOTO Shuichi, MAESHIRO Tatsuji, TSUBOUCHI Hirohito, MURO Toyokichi, INOUE Osami, AKAHOSHI Motoo, SATA Michio
Hepatology research : the official journal of the Japan Society of Hepatology 41 ( 6 ) 564 - 571 2011年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Kawaguchi T., Kakuma T., Yatsuhashi H., Watanabe H., Saitsu H., Nakao K., Taketomi A., Ohta S., Tabaru A., Takenaka K., Mizuta T., Nagata K., Komorizono Y., Fukuizumi K., Seike M., Matsumoto S., Maeshiro T., Tsubouchi H., Muro T., Inoue O., Akahoshi M., Sata M.
Hepatology Research 41 ( 6 ) 564 - 571 2011年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Hepatology Research
Aim: Non-hepatitis B virus/non-hepatitis C virus-related hepatocellular carcinoma (NBNC-HCC) is often detected at an advanced stage, and the pathology associated with the staging of NBNC-HCC remains unclear. Data mining is a set of statistical techniques which uncovers interactions and meaningful patterns of factors from a large data collection. The aims of this study were to reveal complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC-HCC using data mining techniques. Methods: A database was created from 663 patients with NBNC-HCC at 20 institutions. The Milan criteria were used as staging of HCC. Complex associations of variables and clinical feature profiling with the Milan criteria were analyzed by graphical modeling and decision tree algorithm methods, respectively. Results: Graphical modeling identified six factors independently associated with the Milan criteria: diagnostic year of HCC; diagnosis of liver cirrhosis; serum aspartate aminotransferase (AST); alanine aminotransferase (ALT); α-fetoprotein (AFP); and des-γ-carboxy prothrombin (DCP) levels. The decision trees were created with five variables to classify six groups of patients. Sixty-nine percent of the patients were within the Milan criteria, when patients showed an AFP level of 200ng/mL or less, diagnosis of liver cirrhosis and an AST level of less than 93IU/mL. On the other hand, 18% of the patients were within the Milan criteria, when patients showed an AFP level of more than 200ng/mL and ALT level of 20IU/mL or more. Conclusion: Data mining disclosed complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC-HCC. © 2011 The Japan Society of Hepatology.
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急性膵炎を来した Henoch-Schonlein 紫斑病の1例
三池 忠, 田原 良博, 山本 章二朗, 橋本 神奈, 山路 卓巳, 安倍 弘生, 楠元 寿典, 蓮池 悟, 永田 賢治, 下田 和哉
日本消化器内視鏡学会雑誌 = Gastroenterological endoscopy 53 ( 5 ) 1465 - 1471 2011年5月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本消化器内視鏡学会
52歳，男性．両側下腿の紫斑，腹痛，血便を呈し，Henoch-Schönlein紫斑病と診断した．膵型優位の血清アミラーゼ，リパーゼの上昇が出現し，腹部CTでは軽度膵腫大を認め，急性膵炎を合併した．ステロイド，メシル酸ガベキサートを投与し，Henoch-Schönlein紫斑病，膵炎ともに軽快した．稀ではあるが，Henoch-Schönlein紫斑病に膵炎を合併することがあり，腹痛の原因として膵炎の可能性を念頭に，素早く適切な対応が必要である．
DOI： 10.11280/gee.53.1465
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A case of Henoch-Schönlein purpura associated with acute pancreatitis
Miike T., Tahara Y., Yamamoto S., Hashimoto K., Yamaji T., Abe H., Kusumoto K., Hasuike S., Nagata K., Shimoda K.
Gastroenterological Endoscopy 53 ( 5 ) 1465 - 1471 2011年5月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Gastroenterological Endoscopy
A 52 year old man presented with purpura on his lower limbs, abdominal pain, and melena. He was subsequently diagnosed as having Henoch-Schönlein purpura. Two days after admission, he was diagnosed as having acute pancreatitis-related complications based on the elevated serum levels of amylase and lipase, and slight pancreatic enlargement as seen on abdominal CT images. Following administration of predonisolone and gabexate mesylate the acute pancreatitis improved concomitantly with improvement of the Henoch- Schönlein purpura. As regarding the cause of abdominal pain, we should treat pancreatitis rapidly and adequately, because Henoch-Schönlein purpura is rarely associated with acute pancreatitis.
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Taura N., Fukushima N., Yatsuhashi H., Takami Y., Seike M., Watanabe H., Mizuta T., Sasaki Y., Nagata K., Tabara A., Komorizono Y., Taketomi A., Matsumoto S., Tamai T., Muro T., Nakao K., Fukuizumi K., Maeshiro T., Inoue O., Sata M.
Medical Science Monitor 17 ( 2 ) 2011年2月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Medical Science Monitor
Background: The incidence of hepatocellular carcinoma (HCC) in Japan has still been increasing. The aim of the present study was to analyze the epidemiological trend of HCC in the western area of Japan, Kyushu. Material/Methods: A total of 10,010 patients with HCC diagnosed between 1996 and 2008 in the Liver Cancer study group of Kyushu (LCSK), were recruited for this study. Cohorts of patients with HCC were categorized into five year intervals. The etiology of HCC was categorized to four groups as follows; B: HBsAg positive, HCVRNA negative, C: HCV-RNA positive, HBsAg negative, B+C: both of HBsAg and HCV-RNA positive, non- BC: both of HBsAg and HCV-RNA negative. Results: B was 14.8% (1,485 of 10,010), whereas 68.1% (6,819 of 10,010) had C, and 1.4% (140 of 10,010) had HCC associated with both viruses. The remaining 1,566 patients (15.6%) did not associate with both viruses. Cohorts of patients with HCC were divided into six-year intervals (1996-2001 and 2002-2007). The ratio of C cases decreased from 73.1% in 1996-2001 to 64.9% in 2002-2007. On the other hand, B and -nonBC cases increased significantly from 13.9% and 11.3% in 1996-2001 to 16.2% and 17.6% in 2002-2007, respectively. Conclusions: The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased after 2001 in Kyushu area. This change was due to the increase in the number and proportion of the HCC not only nonBC patients but also B patients. © Med Sci Monit.
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Automated external defibrillator (AED) の屋外使用時における音声指示の問題点 : 救命できた自験例をふまえて
長田 直人, 宮永 省三, 外山 勝浩, 松田 圭二, 永田 賢治, 新福 玄二, 成尾 浩明, 松田 俊太郎
日本集中治療医学会雑誌 = Journal of the Japanese Society of Intensive Care Medicine 18 ( 1 ) 113 - 114 2011年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：The Japanese Society of Intensive Care Medicine
DOI： 10.3918/jsicm.18.113
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Improvement of rheumatoid arthritis and autoimmune hepatitis in a patient treated with the tumor necrosis factor inhibitor, etanercept.
Umekita K, Miyauchi S, Ueno S, Takajo I, Kusumoto K, Hasuike S, Umekita Y, Tanaka H, Nagata K, Nagatomo Y, Kataoka H, Shimoda K, Okayama A
Internal medicine (Tokyo, Japan) 50 ( 11 ) 1245 - 9 2011年
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Absence of gain-of-function JAK1 and JAK3 mutations in adult T cell leukemia/lymphoma
KAMEDA T., SHIDE K., SHIMODA H. K., HIDAKA T., KUBUKI Y., KATAYOSE K., TANIGUCHI Y., SEKINE M., KAMIUNNTENN A., MAEDA K., NAGATA K., MATSUNAGA T., SHIMODA K.
International journal of hematology 92 ( 2 ) 320 - 325 2010年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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血栓性血小板減少性紫斑病との鑑別を要した自己免疫性溶血性貧血合併抗リン脂質抗体症候群
唐澤 直希, 谷口 康博, 日高 智徳, 片寄 恵子, 亀田 拓郎, 幣光 太郎, 下田 晴子, 永田 賢治, 久冨木 庸子, 松永 卓也, 下田 和哉
臨床血液 51 ( 4 ) 275 - 280 2010年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：「臨床血液」編集部
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KANMURA Shuji, UTO Hirofumi, SATO Yuko, KUMAGAI Koutarou, SASAKI Fumisato, MORIUCHI Akihiro, OKETANI Makoto, IDO Akio, NAGATA Kenji, HAYASHI Katsuhiro, STUVER Sherri O., TSUBOUCHI Hirohito
Journal of gastroenterology 45 ( 4 ) 459 - 467 2010年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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[Antiphospholipid syndrome with autoimmune hemolytic anemia which mimics thrombotic thrombocytopenic purpura].
Karasawa N, Taniguchi Y, Hidaka T, Katayose K, Kameda T, Side K, Shimoda H, Nagata K, Kubuki Y, Matsunaga T, Shimoda K
[Rinsho ketsueki] The Japanese journal of clinical hematology 51 ( 4 ) 275 - 80 2010年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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血栓性血小板減少性紫斑病との鑑別を要した自己免疫性溶血性貧血合併抗リン脂質抗体症候群
唐澤 直希, 谷口 康博, 日高 智徳, 片寄 恵子, 亀田 拓郎, 幣 光太郎, 下田 晴子, 永田 賢治, 久冨木 庸子, 松永 卓也, 下田 和哉
臨床血液 51 ( 4 ) 275 - 280 2010年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本血液学会
倦怠感を主訴に受診した67歳女性が，発熱，溶血性貧血，血小板減少，変動する意識障害等を呈した。直接クームス試験陽性，抗cardiolipin<i>β</i>2-glycoprotein I抗体，ループスアンチコアグラント陽性であり，autoimmune hemolytic anemia (AIHA)を合併したantiphospholipid syndromeと診断した。変動性意識障害，左右失認，失算，失書を認め，頭部MRIで多発性脳梗塞の所見を呈しており，優位大脳半球梗塞を合併していた。換気血流シンチで換気血流ミスマッチを認め肺梗塞を併発していた。下肢CTで両側下腿静脈，両側膝窩静脈，右大腿静脈に血栓を認め深部静脈血栓症を併発していた。臨床症状よりthrombotic thrombocytopenic purpuraとの鑑別を要したが，ADAMTS-13活性正常であることより否定的であった。AIHAに対しプレドニゾロン45 mg (1 mg/kg)，血栓症に対しワーファリン3 mg, 低分子ヘパリン3,500単位による抗凝固療法を開始し症状の改善を認めた。
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Uto H., Stuver S., Hayashi K., Kumagai K., Sasaki F., Kanmura S., Numata M., Moriuchi A., Hasegawa S., Oketani M., Ido A., Kusumoto K., Hasuike S., Nagata K., Kohara M., Tsubouchi H.
Hepatology 50 ( 2 ) 393 - 399 2009年11月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Hepatology
The overall mortality of patients infected with hepatitis C virus (HCV) has not been fully elucidated. This study analyzed mortality in subjects positive for antibody to HCV (anti-HCV) in a community-based, prospective cohort study conducted in an HCV hyperendemic area of Japan. During a 10-year period beginning in 1995, 1125 anti-HCV-seropositive residents of Town C were enrolled into the study and were followed for mortality through 2005. Cause of death was assessed by death certificates. Subjects with detectable HCV core antigen (HCVcAg) or HCV RNA were considered as having hepatitis C viremia and were classified as HCV carriers; subjects who were negative for both HCVcAg and HCV RNA (i.e., viremia-negative) were considered as having had a prior HCV infection and were classified as HCV noncarriers. Among the anti-HCV-positive subjects included in the analysis, 758 (67.4%) were HCV carriers, and 367 were noncarriers. A total of 231 deaths occurred in these subjects over a mean follow-up of 8.2 years: 176 deaths in the HCV carrier group and 55 in the noncarrier group. The overall mortality rate was higher in HCV carriers than in noncarriers, adjusted for age and sex (hazard ratio, 1.53; 95% confidence interval, 1.13-2.07). Although liver-related deaths occurred more frequently among the HCV carriers (hazard ratio, 5.94; 95% confidence interval, 2.58-13.7), the rates of other causes of death did not differ between HCV carriers and noncarriers. Among HCV carriers, a higher level of HCVcAg (≥100 pg/mL) and persistently elevated alanine aminotransferase levels were important predictors of liver-related mortality. Conclusion: The presence of viremia increases the rate of mortality, primarily due to liver-related death, among anti-HCV-seropositive persons in Japan. Copyright © 2009 by the American Association for the Study of Liver Diseases.
DOI： 10.1002/hep.23002
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Hidaka T., Shide K., Shimoda H., Kameda T., Toyama K., Katayose K., Kubuki Y., Nagata K., Takenaka K., Akashi K., Okamura T., Niho Y., Mizoguchi H., Omine M., Ozawa K., Harada M., Shimoda K.
European Journal of Haematology 83 ( 4 ) 328 - 333 2009年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：European Journal of Haematology
Cytogenetic abnormalities were often observed in primary myelofibrosis patients. The presence of specific cytogenetic abnormalities, such as sole abnormalities of chromosome 13q-, 20q-, or -7/7q-, is reported to have the influence on the prognosis of primary myelofibrosis. We analyzed the data from the prospective survey of Japanese primary myelofibrosis patients which was conducted from 1999 to clarify the impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis. A total of 202 primary myelofibrosis patients had the cytogenetic and the prognostic data. Eighty (40%) out of 202 cases had cytogenetic abnormalities, and an association was evident for platelet counts. Although the presence of an abnormal karyotype did not affect the prognosis, primary myelofibrosis patients with cytogenetic abnormalities other than 13q- and 20q- showed an inferior prognosis compared to patients with a normal karyotype or sole 13q- or 20q- abnormalities. Patients with an unfavorable cytogenetic profile (abnormal cytogenetics other than 13q- or 20q-) also had a greater tendency to transform to leukemia than patients with a favorable cytogenetic profile (normal cytogenetics, sole abnormalities of either chromosome 13q-, or 20q-). Abnormal cytogenetics other than 13q- or 20q- in primary myelofibrosis patients has the poor prognostic effect for both survival and the risk of leukemic transformation. © 2009 John Wiley & Sons A/S.
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食道静脈瘤上に発生し, 内視鏡的に治療しえた食道上皮内癌の1例
原田 拓, 山本 章二朗, 田原 良博, 三池 忠, 安倍 弘生, 山路 卓巳, 中村 憲一, 楠元 寿典, 岩切 久芳, 蓮池 悟, 永田 賢治, 下田 和哉
日本消化器内視鏡学会雑誌 = Gastroenterological endoscopy 51 ( 8 ) 1692 - 1699 2009年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japan Gastroenterological Endoscopy Society
69歳女性．B型+アルコール性肝硬変による食道静脈瘤上に不整発赤を認め，NBI（narrow band imaging）併用拡大内視鏡にて上皮内癌と診断した．静脈瘤の治療後（内視鏡的硬化療法，食道静脈瘤結紮術，クリッピング）に超音波内視鏡にて血管消失を確認し，癌病変の内視鏡的粘膜切除術を安全に施行できた．同様の症例では上述の非侵襲的検査を適切に組み合わせて用いることが非常に有用であると思われた．
DOI： 10.11280/gee.51.1692
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Harada T., Yamamoto S., Tahara Y., Miike T., Abe H., Yamaji T., Nakamura K., Kusumoto K., Iwakiri H., Hasuike S., Nagata K., Shimoda K.
Gastroenterological Endoscopy 51 ( 8 ) 1692 - 1699 2009年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Gastroenterological Endoscopy
We here report a case with esophageal cancer located on solely esophageal varices, requiring an endoscopic mucosal resection. A 69-year-old woman was referred to our hospital for further evaluation of the with an esophageal lesion suspected of being a superficial cancer. On upper gastrointestinal endoscopy, a slightly depressed, superficial, reddish lesion located solely on esophageal varices was found, it was diagnosed as a superficial esophageal cancer using special endoscopic techniques. Treatment was first performed for the esophageal varices using endoscopic procedures (endoscopic injection sclerotherapy (EIS), endoscopic variceal ligation (EVL), and endoscopic clipping). After eradication of the varices, the disappearance of vessels under the cancer was confirmed by endoscopic ultrasonography (EUS). Since then, endoscopic mucosal resection (EMR) of the cancer lesion was carried out without the occurence of any severe complications. On histopathology, the intraepithelial cancer, was found to have been completely resected without lymphatic or vascular permeation. The approach used in this patient is useful for the diagnosis and the treatment of superficial esophageal cancer located solely on varices.
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永田 賢治, 下田 和哉
臨床病理 57 ( 4 ) 357 - 364 2009年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本臨床検査医学会事務所
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Myeloproliferative diseases caused by JAK2 mutation
Nagata K., Shimoda K.
Rinsho byori. The Japanese journal of clinical pathology 57 ( 4 ) 357 - 364 2009年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Rinsho byori. The Japanese journal of clinical pathology
Polycythemia vera (PV), essential thrombocythemia(ET), and primary myelofibrosis (PMF) share common clinical features, being clonal disorders of multipotent progenitors. In 2005, a somatic activating mutation in JAK2 (V617F) was identified in most patients with PV and in about half of patients with ET or PMF. The JAK2 mutation causes the constitutive activation of the JAK-STAT signaling pathway, and leads to autonomous cell growth in a cytokine-independent manner. A higher expression of JAK2 V617F would favor erythrocytosis, and a lower one would favor thrombocytosis. This may suggest that the expression levels of JAK2 V617F directly determine which cell lineages increase, possibly leading to the diversity of myeloproliferative diseases. Although only V617F JAK2 may cause myeloproliferative disease (MPD), clonogenic assay, analysis of familial MPD patients, and examination of JAK2 mutation in acute leukemia patients transformed from MPD show that there are additional somatic mutations which contribute to the pathogenesis of V617F JAK2 positive PV, ET, and PMF.
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胃前庭部の嵌頓柿胃石に対してコーラによる溶解療法が奏功した1例
原田 拓, 井上 龍二, 有馬 志穂, 黒木 和男, 田原 良博, 三池 忠, 安倍 弘生, 山本 章二朗, 楠元 寿典, 蓮池 悟, 永田 賢治, 下田 和哉
日本消化器内視鏡学会雑誌 = Gastroenterological endoscopy 50 ( 12 ) 3033 - 3039 2008年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Takahama Y., Uto H., Kanmura S., Oketani M., Ido A., Kusumoto K., Hasuike S., Nagata K., Hayashi K., Stuver S., Okayama A., Tsubouchi H.
Journal of Gastroenterology 43 ( 12 ) 942 - 950 2008年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Gastroenterology
Background: The clinical course of chronic hepatitis C virus (HCV) infection is strongly associated with insulin resistance and obesity. The K121Q polymorphism in the ectonucleotide pyrophosphatase/ phosphodiesterase (ENPP)-1 gene and the rs7566605 genotype located near insulin-induced gene 2 have been shown to be associated with insulin resistance and obesity. This study examined whether the K121Q polymorphism in ENPP1 or the rs7566605 genotype is associated with the clinical course of HCV infection. Methods: The relationships between the clinical characteristics of 469 anti-HCV antibody-seropositive subjects (353 were positive for HCV core antigen or RNA, whereas 116 were negative for HCV RNA) and the polymorphisms were analyzed. Results: No significant differences in body mass index, plasma glucose level, serum insulin level, and other biochemical markers were observed between subgroups of subjects with different genotypes at the K121Q polymorphism or rs7566605. The frequency of the homozygous wild-type genotype at K121Q in HCV carriers, however, was significantly higher than that in subjects who were negative for HCV RNA (84.5% vs. 75.9%; P < 0.05). Moreover, in HCV carriers, HCV core antigen levels in subjects homozygous for the wild-type genotype at K121Q were significantly higher than in heterozygous carriers of K121Q (5358 fmol/l vs. 4002 fmol/l; P = 0.04). In contrast, the rs7566605 genotype was not associated with hepatitis C viremia or with the HCV core antigen level. Conclusions: The K121Q variant of ENPP1 may be associated with hepatitis C viremia and core antigen levels in HCV carriers. © Springer Japan 2008.
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Miike T., Tahara Y., Yamaguchi Y., Harada T., Abe H., Kusumoto K., Numata M., Hasuike S., Yamamoto S., Kodama M., Nagata K., Hayashi K., Shimoda K.
Japanese Journal of Gastroenterology 105 ( 9 ) 1362 - 1366 2008年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Gastroenterology
A 66-year-old man patient with chronic hepatitis (CH) C and complications from ulcerative colitis (UC) was treated with interferon-beta (IFN-β). Endoscopically, the UC disease activity was moderate before IFN-β treatment but was in remission eight week after treatment. However, a few months after stopping IFN treatment, endoscopy revealed that the UC disease activity had returned to moderate levels. This result shows that UC improved with IFN treatment.
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Harada T., Inoue R., Arima S., Kuroki K., Tahara Y., Miike T., Hiroo A., Yamamoto S., Kusumoto K., Hasuike S., Nagata K., Shimoda K.
Gastroenterological Endoscopy 50 ( 12 ) 3033 - 3039 2008年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Gastroenterological Endoscopy
We report a case of impacted diospyrobezoars in gastric antrum, which were treated successfully by dissolution therapy with Coca-Cola administration. An 87-year-old woman was admitted to our hospital because of abdominal pain and feeling of abdominal distension. Upper gastrointestinal endoscopy revealed two diospyrobezoars (each size was 7cm and 3cm in diameter) in the stomach, and one bezoar became impacted in gastric antrum at a later date. The endoscopic removal using forceps and polypectomy snare resulted in failure. Therefore, she received dissolution therapy with Coca-Cola. On the next day, the impacted bezoar was partially dissolved and turned to be softened, and that was safely-removed endoscopically. She took extra dose of Coca-Cola, and the next day, remaining bezoars were completely dissolved. The dissolution therapy with Coca-Cola may be useful in patients with diospyrobezoars resistant to endoscopic therapy.
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C型慢性肝炎に対するインターフェロンβ投与にて潰瘍性大腸炎が改善した1例
三池 忠, 田原 良博, 山口 由美, 原田 拓, 安倍 弘生, 楠元 寿典, 沼田 政嗣, 蓮池 悟, 山本 章二朗, 児玉 眞由美, 永田 賢治, 林 克裕, 下田 和哉
日本消化器病學會雜誌 = The Japanese journal of gastro-enterology 105 ( 9 ) 1362 - 1366 2008年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般財団法人 日本消化器病学会
症例は66歳男性．潰瘍性大腸炎(ulcerative colitis; UC）を合併したC型慢性肝炎(chronic hepatitis(C）; CH(C））に対して，インターフェロン(interferon; IFN）βの投与を行った．投与前の内視鏡的重症度は中等度であったが，投与開始後8週間で内視鏡的重症度は軽度となった．しかしIFN投与終了後は再び内視鏡的重症度は中等度となり，増悪を認めたため，IFN投与にて潰瘍性大腸炎が改善したと考えられた．<br>
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[A case study: interferon-beta-induced remission of ulcerative colitis in a patient with type C chronic hepatitis].
Miike T, Tahara Y, Yamaguchi Y, Harada T, Abe H, Kusumoto K, Numata M, Hasuike S, Yamamoto S, Kodama M, Nagata K, Hayashi K, Shimoda K
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 105 ( 9 ) 1362 - 6 2008年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Development of ET, primary myelofibrosis, and PV in mice expressing JAK2 V617F. 査読あり
Shide Kotaro,Shimoda K Haruko,Kumano Takashi , Karube Kennosuke, Kameda Takurou, Takenaka Katsuto, Abe H, Oku Seido, Katayose K Keiko, Kusumoto Kazunori, Hasuike Satoru, Tahara Yoshihiro, Nagata Kenji, Matsuda Tadashi, Ohshima Koichi, Hrada Mine,Shimoda Kazuya
Leukemia 22 ( 1 ) 87 - 95 2008年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F
Shide K., Shimoda H., Kumano T., Karube K., Kameda T., Takenaka K., Oku S., Abe H., Katayose K., Kubuki Y., Kusumoto K., Hasuike S., Tahara Y., Nagata K., Matsuda T., Ohshima K., Harada M., Shimoda K.
Leukemia 22 ( 1 ) 87 - 95 2008年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
An acquired JAK2 V617F mutation is found in most patients with polycythemia vera (PV), and about half of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Mice transplanted with bone marrow cells in which JAK2 V617F was retrovirally expressed developed PV-like features, but not ET or PMF. To address the contribution of this mutation to the pathogenesis of these three MPDs, we generated two lines of JAK2 V617F transgenic mice. One line showed granulocytosis after 4 months of age. Among 43 mice, 8 (19%) showed polycythemia and 15 (35%) showed thrombocythemia. The second line showed extreme leukocytosis and thromobocytosis. They showed anemia that means Hb value from 9 to 10g per 100ml when 1 month old. Myeloid cells and megakaryocytes were predominant in the bone marrow of these animals, and splenomegaly was observed. The expression of JAK2 V617F mRNA in bone marrow cells was 0.45 and 1.35 that of endogenous wild-type JAK2 in the two lines, respectively. In vitro analysis of bone marrow cells from both lines showed constitutive activation of ERK1/2, STAT5 and AKT, and augmentation of their phosphorylations by cytokine stimulation. We conclude that in vivo expression of JAK2 V617F results in ET-, PMF- and PV-like disease.
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Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats.
Abe H, Uto H, Takami Y, Takahama Y, Hasuike S, Kodama M, Nagata K, Moriuchi A, Numata M, Ido A, Tsubouchi H
Biochemical and biophysical research communications 356 ( 3 ) 610 - 5 2007年5月
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Early diagnostic potential for hepatocellular carcinoma using the SELDI proteinChip system. 査読あり
Kanmura Shuji,Uto Hirofumi, Kusumoto Kazunori, Ishida Yoichi, Hasuike Satoru, Nagata Kennji, Hayashi Katsuhiro, Ido Akio, Sherri Oliver Stuver, Tsubouchi Hirohito:
Hepatology 45 ( 4 ) 948 - 956 2007年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Early diagnostic potential for hepatocellular carcinoma using the SELDI ProteinChip system
Kanmura S., Uto H., Kusumoto K., Ishida Y., Hasuike S., Nagata K., Hayashi K., Ido A., Stuver S., Tsubouchi H.
Hepatology 45 ( 4 ) 948 - 956 2007年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Hepatology
Early detection of HCC increases the potential for curative treatment and improves survival. To facilitate early detection of HCC, this study sought to identify novel diagnostic markers of HCC using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS) ProteinChip technology. Serum samples were obtained from 153 patients with or without HCC, all of whom had been diagnosed with HCV-associated chronic liver disease. To identify proteins associated with HCC, serum samples were analyzed using SELDI-TOF/MS. We constructed an initial decision tree for the correct diagnosis of HCC using serum samples from patients with (n = 35) and without (n = 44) HCC. Six protein peaks were selected to construct a decision tree using this first group. The efficacy of the decision tree was then assessed using a second group of patients with (n = 29) and without (n = 33) HCC. The sensitivity and specificity of this decision tree for the diagnosis of HCC were 83% and 76%, respectively. For a third group, we analyzed sera from seven patients with HCC obtained before the diagnosis of HCC by ultrasonography (US) and from five patients free of HCC for the past 3 years. Use of these diagnostic markers predicted the diagnosis of HCC in six of these seven patients before HCC was clinically apparent without any false positives. Conclusion: Serum profiling using the SELDI ProteinChip system is useful for the early detection and prediction of HCC in patients with chronic HCV infection. Copyright © 2007 by the American Association for the Study of Liver Diseases.
DOI： 10.1002/hep.21598
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Shirado A., Uto H., Kusumoto K., Kurogi J., Sakamoto H., Hasuike S., Nagata K., Hayashi K., Iwamitsu A., Hori T., Ibusuki K., Ido A., Tsubouchi H.
Japanese Journal of Gastroenterology 103 ( 7 ) 827 - 832 2006年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Gastroenterology
A 28-year-old woman was given a diagnosis of gastric endocrine cell carcinoma with multiple liver metastases in 1997. Chemotherapy was administered for treatment after a distal gastrectomy and hepatic tumor resection, and she had shown no sign of relapse after 2002. In February 2004, she was in the third month of pregnancy, and experienced recurrent liver metastasis. Although the tumor grew rapidly from 3cm to 10cm during her pregnancy, its size was significantly reduced with systemic chemotherapy after delivery. This is a rare case in which a liver metastasis of a gastric endocrine cell carcinoma grew during the course of pregnancy.
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[A case of gastric endocrine cell carcinoma with liver metastasis showing rapid growth during pregnancy and marked reduction by systemic chemotherapy after delivery].
Shirado A, Uto H, Kusumoto K, Kurogi J, Sakamoto H, Hasuike S, Nagata K, Hayashi K, Iwamitsu A, Hori T, Ibusuki K, Ido A, Tsubouchi H
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 103 ( 7 ) 827 - 32 2006年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Effect of hepatocyte growth factor on endogenous hepatocarcinogenesis in rats fed a choline-deficient L-amino acid-defined diet.
Nakanishi C, Moriuchi A, Ido A, Numata M, Kim ID, Kusumoto K, Hasuike S, Abe H, Nagata K, Akiyama Y, Uto H, Kataoka H, Tsubouchi H
Oncology reports 16 ( 1 ) 25 - 31 2006年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Nakanishi C., Moriuchi A., Ido A., Numata M., Kim I., Kusumoto K., Hasuike S., Abe H., Nagata K., Akiyama Y., Uto H., Kataoka H., Tsubouchi H.
Oncology Reports 16 ( 1 ) 25 - 31 2006年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Oncology Reports
Hepatocyte growth factor (HGF) is a promising agent for the treatment of intractable liver disease, due to its mitogenic, anti-apoptotic, and anti-fibrotic effects. We investigated the effect of recombinant human HGF (rh-HGF) on the development of both hepatocellular carcinoma (HCC) and preneoplastic nodules in rats fed a choline-deficient L-amino acid-defined (CDAA) diet, an animal model of hepatocarcinogenesis resembling human development of HCC with cirrhosis. From weeks 13 to 48 of the CDAA diet, rh-HGF (0.1 or 0.5 mg/kg/day) was administered intravenously to rats in four-week cycles, with treatment for five consecutive days of each week for two weeks, followed by a two-week washout period. Treatment with rh-HGF significantly inhibited the development of preneoplastic nodules in a dose-dependent manner at 24 weeks. Although the numbers and areas of the preneoplastic nodules in rats treated with rh-HGF were equivalent to those in mock-treated rats by 60 weeks, the incidence of HCC was reduced by HGF treatment. Although one rat treated with low-dose rh-HGF exhibited a massive HCC, which occupied almost the whole liver, and lung metastases, HGF treatment did not increase the overall frequency of HCC. Administration of high-dose rh-HGF, however, induced an increase in the urinary excretion of albumin, leading to decreased serum albumin at 60 weeks. These results indicate that long-term administration of rh-HGF does not accelerate hepatocarcinogenesis in rats fed a CDAA diet. However, these findings do not completely exclude the potential of HGF-induced hepatocarcinogenesis; this issue must be resolved before rh-HGF can be used for patients with intractable liver diseases, especially those with cirrhosis.
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Effect of hepatocyte growth factor on endogenous hepatocarcinogenesis in rats fed a choline-deficient L-amino acid-defined diet（共著） 査読あり
Nakanishi Chihiro 他
Oncology Reports 16 25 - 31 2006年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats（共著） 査読あり
Kusumoto Kazunori 他
International Journal of Molecular Medicine 17 503 - 509 2006年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats.
Kusumoto K, Ido A, Moriuchi A, Katsura T, Kim I, Takahama Y, Numata M, Kodama M, Hasuike S, Nagata K, Uto H, Inui K, Tsubouchi H
International journal of molecular medicine 17 ( 3 ) 503 - 9 2006年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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UTO Hirofumi, HAYASHI Katsuhiro, KUSUMOTO Kazunori, HASUIKE Satoru, NAGATA Kenji, KODAMA Mayumi, IDO Akio, KOHARA Michinori, STUVER Sherri O., TSUBOUCHI Hirohito
Hepatology research : the official journal of the Japan Society of Hepatology 34 ( 1 ) 28 - 34 2006年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Spontaneous elimination of hepatitis C virus RNA in individuals with persistent infection in a hyperendemic area of Japan（共著） 査読あり
Uto hirofumi 他
Hepatology Research 34 28 - 34 2006年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Spontaneous elimination of hepatitis C virus RNA in individuals with persistent infection in a hyperendemic area of Japan.
Uto H, Hayashi K, Kusumoto K, Hasuike S, Nagata K, Kodama M, Ido A, Kohara M, Stuver SO, Tsubouchi H
Hepatology research : the official journal of the Japan Society of Hepatology 34 ( 1 ) 28 - 34 2006年1月
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UTO Hirofumi, IDO Akio, KUSUMOTO Kazunori, HASUIKE Satoru, NAGATA Kenji, HAYASHI Katsuhiro, YAMAGISHI Toshiya, GOHDA Eiichi, TSUBOUCHI Hirohito
Hepatology research : the official journal of the Japan Society of Hepatology 33 ( 4 ) 272 - 276 2005年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Uto H., Ido A., Kusumoto K., Hasuike S., Nagata K., Hayashi K., Yamagishi T., Gohda E., Tsubouchi H.
Hepatology Research 33 ( 4 ) 272 - 276 2005年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Hepatology Research
Measurement of serum human hepatocyte growth factor (HGF) by enzyme-linked immunosorbent assay (ELISA) is useful for the early diagnosis and prediction of prognosis of patients with acute liver failure (ALF). This ELISA methodology, however, is neither rapid nor convenient for use at the bedside. In this study, we have developed a rapid semi-quantitative immunochromatographic (IC) assay and evaluated its usefulness in assessing patients with acute hepatic injury. Only 100 μl of serum is required; the assay can be easily completed in 20 min. The values obtained using this novel assay correlated well with the values obtained using the standard ELISA protocol. In addition, the values obtained in the IC assay correlated with clinical course; increased serum HGF levels were associated with an increased frequency of ALF and death. These results indicate that this rapid semi-quantitative IC assay for HGF is useful for the early diagnosis of ALF and prediction of clinical outcome in acute hepatic injury. © 2005 Elsevier Ireland Ltd. All rights reserved.
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Hepatocyte growth factor accelerates the proliferation of hepatic oval cells and possibly promotes the differentiation in a 2-acetylaminofluorene/partial hepatectomy model in rats.
Hasuike S, Ido A, Uto H, Moriuchi A, Tahara Y, Numata M, Nagata K, Hori T, Hayashi K, Tsubouchi H
Journal of gastroenterology and hepatology 20 ( 11 ) 1753 - 61 2005年11月
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The peroxisome proliferator-activated receptor-gamma agonist, pioglitazone, inhibits fat accumulation and fibrosis in the livers of rats fed a choline-deficient, l-amino acid-defined diet.
Uto H, Nakanishi C, Ido A, Hasuike S, Kusumoto K, Abe H, Numata M, Nagata K, Hayashi K, Tsubouchi H
Hepatology research : the official journal of the Japan Society of Hepatology 32 ( 4 ) 235 - 42 2005年8月
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Hepatocyte growth factor facilitates the repair of large colonic ulcers in 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats.
Numata M, Ido A, Moriuchi A, Kim I, Tahara Y, Yamamoto S, Hasuike S, Nagata K, Miyata Y, Uto H, Tsubouchi H
Inflammatory bowel diseases 11 ( 6 ) 551 - 8 2005年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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NAGATA TSUBOUCHI Yoshiko, IDO Akio, UTO Hirofumi, NUMATA Masatsugu, MORIUCHI Akihiro, KIM Ildeok, HASUIKE Satoru, NAGATA Kenji, SEKIYA Toru, HAYASHI Katsuhiro, TSUBOUCHI Hirohito
Hepatology research : the official journal of the Japan Society of Hepatology 31 ( 2 ) 79 - 87 2005年2月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Molecular mechanisms of hereditary persistence of alpha-fetoprotein (AFP) in two Japanese families A hepatocyte nuclear factor-1 site mutation leads to induction of the AFP gene expression in adult livers.
Nagata-Tsubouchi Y, Ido A, Uto H, Numata M, Moriuchi A, Kim I, Hasuike S, Nagata K, Sekiya T, Hayashi K, Tsubouchi H
Hepatology research : the official journal of the Japan Society of Hepatology 31 ( 2 ) 79 - 87 2005年2月
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Hypermethylation of the wild-type ferrochelatase allele is closely associated with severe liver complication in a family with erythropoietic protoporphyria.
Onaga Y, Ido A, Uto H, Hasuike S, Kusumoto K, Moriuchi A, Numata M, Nagata K, Hori T, Hayashi K, Tsubouchi H
Biochemical and biophysical research communications 321 ( 4 ) 851 - 8 2004年9月
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Ido A., Uto H., Moriuchi A., Nagata K., Onaga Y., Onaga M., Hori T., Hirono S., Hayashi K., Tamaoki T., Tsubouchi H.
Cancer Research 61 ( 7 ) 3016 - 3021 2001年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Research
We previously reported that the retroviral vector expressing the herpes simplex virus-thymidine kinase gene under the control of 0.3-kb human α-fetoprotein (AFP) gene promoter (AF0.3) provided the cytotoxicity to ganciclovir (GCV) in high-AFP-producing human hepatoma cells but not in low-AFP-producing cells. Therefore, specific enhancement of AFP promoter activity is likely to be required to induce enough cytotoxicity in low-AFP-producing hepatoma cells. In this study, we constructed a hybrid promoter, [HRE] AF, in which a 0.4-kb fragment of human vascular endothelial growth factor 5′-flanking sequences containing hypoxia-responsive element (HRE) was fused to AF0.3 promoter. By means of the reporter gene transfection assay, hypoxia-inducible transcriptions that were mediated by [HRE] AF promoter were detected in low- and non-AFP-producing human hepatoma cells, but not in nonhepatoma cells. When the herpes simplex virus-thymidine kinase gene controlled by [HRE]AF promoter was transduced into hepatoma and nonhepatoma cells by a retroviral vector, the exposure to 1% O 2 induced GCV cytotoxicity specifically in the hepatoma cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors consisting of the virus-infected hepatoma cells gradually disappeared by GCV administration. These results indicate that the hypoxia-inducible enhancer of the human vascular endothelial growth factor gene, which is directly linked to human AFP promoter, involves selective and enhanced tumoricidal activity in gene therapy for hepatocellular carcinoma.