2021/10/25 更新

写真a

タナカ モトツグ
田中 基嗣
TANAKA Mototsugu
所属
医歯学総合病院 臨床研究推進センター 准教授
職名
准教授
連絡先
メールアドレス
外部リンク

学位

  • 博士(医学) ( 2015年3月 )

研究キーワード

  • 細菌学

  • レギュラトリーサイエンス

  • 臨床薬学

  • 腎臓病学

  • 血液透析

  • 腹膜透析

研究分野

  • ライフサイエンス / 医療薬学  / レギュラトリーサイエンス

  • ライフサイエンス / 腎臓内科学  / 慢性腎臓病、血液透析、腹膜透析、併用療法

  • ライフサイエンス / 細菌学  / 細菌学

経歴(researchmap)

  • 新潟大学医歯学総合病院   臨床研究推進センター   准教授

    2021年4月 - 現在

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  • 医薬品医療機器総合機構   新薬審査第一部   審査専門員

    2017年4月 - 2021年3月

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    国名:日本国

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  • 東京大学   医学部附属病院 臨床研究支援センター   特任助教

    2015年8月 - 2017年3月

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    国名:日本国

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  • 東京大学   医学部附属病院 腎臓・内分泌内科   特任臨床医

    2015年4月 - 2015年8月

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    国名:日本国

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  • 三井記念病院   内科   シニアレジデント

    2008年10月 - 2011年3月

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    国名:日本国

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  • 東京大学   医学部附属病院 腎臓・内分泌内科   後期臨床研修医

    2008年4月 - 2008年9月

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    国名:日本国

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  • 長崎医療センター   初期臨床研修医

    2006年4月 - 2008年3月

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    国名:日本国

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  • 東京大学   医学部附属病院 腎臓・内分泌内科   届出研究員

    2019年4月 - 2021年3月

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    国名:日本国

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  • 東京大学   医学部附属病院 腎臓・内分泌内科   登録研究員

    2017年4月 - 2019年3月

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    国名:日本国

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▶ 全件表示

経歴

  • 新潟大学   医歯学総合病院 臨床研究推進センター   准教授

    2021年4月 - 現在

学歴

  • 東京大学   大学院医学系研究科

    2011年4月 - 2015年3月

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    国名: 日本国

    備考: 博士課程

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  • 佐賀大学   医学部   医学科

    2000年4月 - 2006年3月

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    国名: 日本国

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所属学協会

  • 日本臨床薬理学会

    2021年3月 - 現在

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  • 日本透析医学会

    2006年6月 - 現在

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  • 日本腎臓学会

    2006年6月 - 現在

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  • 日本内科学会

    2006年4月 - 現在

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委員歴

  • 医薬品医療機器総合機構   専門委員  

    2021年5月 - 現在   

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    団体区分:政府

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取得資格

  • 医師

 

論文

  • A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment 査読 国際誌

    Ryo Kinoshita-Daitoku, Kotaro Kiga, Masatoshi Miyakoshi, Ryota Otsubo, Yoshitoshi Ogura, Takahito Sanada, Zhu Bo, Tuan Vo Phuoc, Tokuju Okano, Tamako Iida, Rui Yokomori, Eisuke Kuroda, Sayaka Hirukawa, Mototsugu Tanaka, Arpana Sood, Phawinee Subsomwong, Hiroshi Ashida, Tran Thanh Binh, Lam Tung Nguyen, Khien Vu Van, Dang Quy Dung Ho, Kenta Nakai, Toshihiko Suzuki, Yoshio Yamaoka, Tetsuya Hayashi, Hitomi Mimuro

    Nature Communications   12 ( 1 )   2021年12月

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    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 Science and Business Media LLC  

    <title>Abstract</title>Long-term infection of the stomach with <italic>Helicobacter pylori</italic> can cause gastric cancer. However, the mechanisms by which the bacteria adapt to the stomach environment are poorly understood. Here, we show that a small non-coding RNA of <italic>H. pylori</italic> (HPnc4160, also known as IsoB or NikS) regulates the pathogen’s adaptation to the host environment as well as bacterial oncoprotein production. In a rodent model of <italic>H. pylori</italic> infection, the genomes of bacteria isolated from the stomach possess an increased number of T-repeats upstream of the HPnc4160-coding region, and this leads to reduced HPnc4160 expression. We use RNA-seq and iTRAQ analyses to identify eight targets of HPnc4160, including genes encoding outer membrane proteins and oncoprotein CagA. Mutant strains with HPnc4160 deficiency display increased colonization ability of the mouse stomach, in comparison with the wild-type strain. Furthermore, HPnc4160 expression is lower in clinical isolates from gastric cancer patients than in isolates derived from non-cancer patients, while the expression of HPnc4160’s targets is higher in the isolates from gastric cancer patients. Therefore, the small RNA HPnc4160 regulates <italic>H. pylori</italic> adaptation to the host environment and, potentially, gastric carcinogenesis.

    添付ファイル: Kinoshita et al_Small RNA regulates H.pylori adaptation_Nat Commun2021.pdf

    DOI: 10.1038/s41467-021-22317-7

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    その他リンク: http://www.nature.com/articles/s41467-021-22317-7

  • The PMDA’s view on the limited pipeline of nephrology drugs in Japan 査読 国際誌

    Mototsugu Tanaka, Mutsuhiro Ikuma

    Kidney International   100 ( 1 )   241 - 242   2021年7月

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    担当区分:筆頭著者, 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:Elsevier BV  

    DOI: 10.1016/j.kint.2021.03.034

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  • The PMDA Perspectives on New Oral Prolyl Hydroxylase Domain Enzyme Inhibitors for Renal Anemia 査読 国際誌

    Mototsugu Tanaka, Mutsuhiro Ikuma, Wataru Asakura, Yasuhiro Fujiwara

    Clinical Pharmacology & Therapeutics   2021年5月

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    担当区分:筆頭著者, 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:Wiley  

    添付ファイル: Tanaka et al_PMDA Perspectives on PHDi for Renal Anemia_CPT2021(online ahead of print).pdf

    DOI: 10.1002/cpt.2275

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cpt.2275

  • Achievements and challenges of the Sakigake designation system in Japan 査読 国際誌

    Mototsugu Tanaka, Mayumi Idei, Hiroshi Sakaguchi, Ryosuke Kato, Daisuke Sato, Kenji Sawanobori, Shuichi Kawarasaki, Toshiyuki Hata, Asako Yoshizaki, Miki Nakamura, Mutsuhiro Ikuma

    British Journal of Clinical Pharmacology   2021年3月

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    担当区分:筆頭著者, 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:Wiley  

    DOI: 10.1111/bcp.14807

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  • Association between age at disease onset of anti-neutrophil cytoplasmic antibody–associated vasculitis and clinical presentation and short-term outcomes 査読 国際誌

    Sara Monti, Anthea Craven, Catherine Klersy, Carlomaurizio Montecucco, Roberto Caporali, Richard Watts, Peter A Merkel, Raashid Luqmani, Katerina Achilleos, Matthew Adler, Marco A Alba, Marco A Alba, Daniel A Albert, Fatma Alibaz-Oner, Paul Allcoat, Koichi Amano, Manishka Amarasuriya, Naomi A Amudala, Jacqueline Andrews, Amy M Archer, Yoshihiro Arimura, Inoshi Atukorala, Elsa Azevedo, Shruti Bajad, Corisande Baldwin, Lillian J Barra, Bo Baslund, Neil Basu, Mahire Baykal, Christoph Berger, Ewa Berglin, Emilio Besada, Mamta Bhardwaj, Antje Bischof, Daniel Blockmans, Janet Blood, Juliana Bordignon Draibe, Sarah Brand, Mariana Brandao, Ian N Bruce, Amanda Butler, Leonard H Calabrese, Daniel Camprubi Ferrer, Simon Carette, Diana Carmona, Helga Ceunen, Kuntal Chakravarty, Peter T Chapman, Zdenka Chocova, Sharon A Chung, Weiping Ci, Maria C Cid, Tiffany M Clark, Michael R Clarkson, Felipe de Jesus Contreras-Rodríguez, Richard Conway, Kelly Cooke, Xavier Corbella Virós, Ana Cordeiro, Andreia Costa, Anthea Craven, Karen Culfear, Thomas Daikeler, Debashish Danda, Siddharth K Das, Bhaskar Dasgupta, Alice M De Castro, Natasha Dehghan, Roni Devassy, Navjot Dhindsa, Andreas P Diamantopoulos, Haner Direskeneli, Hiroaki Dobashi, Du Juan, Maumer Durrani, Clive Edelsten, Johanna Eifert, Sallie Elhayek, Sunhoury Elsideeg, Tomomi Endo, Abdulsamet Erden, Burak Erer, Per Eriksson, Zeynep Erturk, Georgina Espígol-Frigolé, Mara Felicetti, Alaistair Ferraro, José M Ferro, Aurore Fifi-Mah, Luis Felipe Flores-Suárez, Oliver Flossmann, Deirdre Flynn, João Eurico Fonseca, Jayne Foot, Michelle Foote, Lindsy Forbess, Shouichi Fujimoto, Kazuhito Fukuoka, Carolina Furtado, Shunsuke Furuta, Angelo L Gaffo, Phil Gallagher, Na Gao, Paul Gatenby, Nagui Gendi, Ruth Geraldes, Anneleen Gerits, Andrea Gioffredi, Luke Gomples, Maria João Gonçalves, Prisca Gondo, Anne Graham, Rebecca Grainger, David T Gray, Peter C Grayson, Laura Griffiths, Yanqiu Guo, Rajiva Gupta, Micael Gylling, Rula A Hajj-Ali, Nevin Hammam, Masayoshi Harigai, Lorraine Hartley, Janine Haslett, Alaa Hassan, Gulen Hatemi, Bernhard Hellmich, Liesbet Henckaerts, Joerg C Henes, Joanna Hepburn, Vera Herd, Christoph Hess, Catherine Hill, Andrea Hinojosa-Azaola, Junichi Hirahashi, Fumio Hirano, Alojzija Hočevar, Julia Holle, Nicole Hollinger, Sakae Homma, Theresa Howard, Rachel K Hoyles, Zdenka Hruskova, Gayle Hutcheon, Maria Ignacak, Annette Igney-Oertel, Kei Ikeda, Noriko Ikegaya, Samyukta Jagadeesh, Jane Jaquith, David R W Jayne, Teresa Jewell, Colin Jones, Abhay Joshi, Umut Kalyoncu, Sevil Kamalı, Sanjeet Kamath, Kan Sow Lai, Shinya Kaname, Suresh Kanchinadham, Ömer Karadağ, Miho Karube, Marek Kaszuba, Ramanjot Kaur, Tamihiro Kawakami, Soko Kawashima, Nader Khalidi, Asad Khan, Masao Kikuchi, Levent Kilic, Makiko Kimura, Maria J King, Sebastian Klapa, Rainer Klocke, Tatsuo Kobayashi, Shigeto Kobayashi, Yoshinori Komagata, Andreas Kronbichler, Pawel Kuczia, Mandal Santosh Kumar, Miho Kurosawa, Peter Lamprecht, Carol A Langford, Peter Lanyon, Catherine Laversuch, Sang Jin Lee, Simona Leoni, Jing Li, Kimberly Liang, Patrick Liang, Hua Liao, Lim Ai Lee, Raashid A Luqmani, Amanda Lyle, Matthew MacDonald, Sarah L Mackie, Leah Madden, Malgorzata Magliano, Hirofumi Makino, Ashima Makol, Ritu Malaiya, Anshuman Malaviya, Ramesh Manthri, Federica Maritati, Ana Martins da Silva, Justin C Mason, Cecilia Matara, Kazuo Matsui, Eric L Matteson, Dawn McBride, Keith McCullough, Lucy McGeoch, John McLaren, Caitlin McMillian, Naval Mendiratta, Ajit Menon, Dimos Merinopoulos, Peter A Merkel, Peter Merkel, Sandra Messier, Robert G Micheletti, Karen Mills, Nataliya Milman, Masahiro Minoda, Ranjana Walker Minz, Claudia Möck, Aladdin J Mohammad, Sergey Moiseev, Marta Moitinho, Eamonn Molloy, Paul A Monach, Marian Montgomery, Frank Moosig, Manoosh Moradizadeh, Matthew Morgan, Ann W Morgan, Ann-Marie Morgan, Alice Muir, Chetan Mukhtyar, Antje Müller, Francesco Muratore, Eri Muso, Ritambhra Nada, Hiroshi Nakajima, Toshiki Nakajima, Hiroto Nakano, Anupapama Nandagudi, Thomas Neumann, Ying Fun Ng, Kooi Heng Ng, Estela L Nogueira, Nilesh Nolkha, Dan Nordström, Pavel Novikov, Asanka Nugaliyadde, John L O’Donnell, Jennifer O’Donoghue, Lorraine O’Neill, Edmond O’Riordan, Margaret Oatley, Koshu Okubo, Elena Oliva, Hideto Oshikawa, Yuichiro Ota, Roberto Padoan, Christian Pagnoux, Lili Pan, Kalliopi Panaritis, Jin Kyun Park, Sanjeev Patel, Pravin Patil, Giulia Pazzola, Adrian Peall, Fiona Pearce, Seval Pehlevan, Liliana Pereira, Tom Pettersson, Christian A Pineau, Laura Pirilä, Bartlomiej Poglodek, Cristina Ponte, Sergio Prieto-González, Sangeetha R Priya, Bally Purewal, Silke Purschke, Jukka Putaala, Stefanie Quickert, Vicki Quincey, Subhra Raghuvanshi, Liza Rajasekhar, Dwarakanathan Ranganathan, Manish Rathi, David Rees, Frances Rees, Ulrike Renken, Giovanna Restuccia, Rennie L Rhee, Brian Rice, Diane Robins, Joanna Robson, Joanna Robson, Miguel Rodrigues, Vasco C Romão, Žiga Rotar, Carlee Ruediger, Abraham Rutgers, Ana C Sá, Maria João Saavedra, Ken-ei Sada, Ilfita Sahbudin, Carlo Salvarani, Namneet Sandhu, Ernestina Santos, Yuji Sato, Valentin S Schäfer, Franco Schiavon, Wolfgang A Schmidt, Mårten Segelmark, Amira Shahin, Aman Sharma, Julie Shotton, Cristiana Silva, Ora Gewurz Singer, Goutham Sivasuthan, Susan Smolen, Xavier Solanich-Moreno, Laura Soldevila Boixader, Yeong Wook Song, Jason Springer, Antoine G Sreih, Antoine G Sreih, Ragini Srivastava, Lisa K Stamp, Robert Stevens, Daniel Strbian, Keishi Sugino, Cord Sunderkötter, Ravi Suppiah, Katsuya Suzuki, Kazuo Suzuki, Zoltán Szekanecz, Jan Sznajd, Kirsi Taimen, Paul P Tak, Tsutomu Takeuchi, Naoho Takizawa, Lilian Tames, Bee Eng Tan, Mototsugu Tanaka, Man Wai Tang, Turgut Tatlisumak, Vladimir Tesar, Alan Thomas, Xinping Tian, Kenichiro Tokunaga, Enrico Tombetti, Matija Tomšič, Bahtiyar Toz, Tatsuo Tsukamoto, Shunya Uchida, Ali Ugur Unal, Maria L Urban, Joichi Usui, Augusto Vaglio, Srinivasan Venkatachalam, Erin Vermaak, Vishad Viswanath, Takashi Wada, Shrikant Wagh, Daniel J Wallace, Giles Walters, Bastian Walz, Jin Wan, Tian Wang, Guochun Wang, Kenneth J Warrington, Richard A Watts, Katarzyna Wawrzycka-Adamczyk, Praveen Weeratunga, Michael H Weisman, Sugeesha Wickramasinghe, Mark Williams, Megan Williams, Krzysztof Wojcik, Laticia Woodruff, Theodoros Xenitidis, Hidehiro Yamada, Kunihiro Yamagata, Chee-Seng Yee, Myeongjae Yoon, Kazuki Yoshida, Hajime Yoshifuji, Steven R Ytterberg, Wako Yumura, Hania Zayed, Xiaofeng Zeng, Ming-Hui Zhao, Anna Zugaj, Joanna Zuk

    Rheumatology   60 ( 2 )   617 - 628   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    <title>Abstract</title>
    <sec>
    <title>Objectives</title>
    ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood.


    </sec>
    <sec>
    <title>Methods</title>
    We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: &amp;lt;65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative).


    </sec>
    <sec>
    <title>Results</title>
    A total of 1338 patients with AAV were included: 66% had disease onset at &amp;lt;65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03].


    </sec>
    <sec>
    <title>Conclusion</title>
    Within 6 months of diagnosis of AAV, patients &amp;gt;65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.


    </sec>

    添付ファイル: Monti et al_DCVAS_Rheumatology2021.pdf

    DOI: 10.1093/rheumatology/keaa215

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  • Ultrafiltration volume by once‐weekly hemodialysis is a predictor of technique survival of combination therapy with peritoneal dialysis and hemodialysis 査読 国際誌

    Mototsugu Tanaka, Yoshitaka Ishibashi, Yoshifumi Hamasaki, Yuka Kamijo, Mayumi Idei, Takahiro Nishi, Michio Takeda, Hiroshi Nonaka, Masaomi Nangaku, Naobumi Mise

    Therapeutic Apheresis and Dialysis   2021年2月

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    担当区分:筆頭著者, 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:Wiley  

    Overhydration is a major cause of technique failure of peritoneal dialysis (PD). Hence, we investigated the impact of ultrafiltration (UF) volume by once-weekly hemodialysis (HD), excess volume beyond their dry weight, on technique survival of PD and HD combination therapy (PD+HD). Forty-six anuric PD+HD patients were divided into three groups according to baseline UF volume by HD: low-UF (<mean - 1SD), middle-UF (≥mean - 1SD and <mean + 1SD), and high-UF (≥mean + 1SD). High-UF group showed larger extracellular water normalized to height (P = .038) and longer HD sessions (P < .001) compared with low-UF group, whereas low-UF group was older than middle-UF group (P = .001). Technique survival rate was significantly lower in high-UF group than in low and middle-UF groups (P < .001), and the rates at 44 months were 80%, 90%, 20% in low, middle, and high-UF groups, respectively. Chronic overhydration was the leading cause of technique failure for all. This study suggests that fluid overload remains a major cause of technique failure of PD even after once-weekly HD is added.

    DOI: 10.1111/1744-9987.13509

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1744-9987.13509

  • Rationales of delay and difference in regulatory review by Japan, the USA and Europe among new drugs first approved in Japan 査読 国際誌

    Mototsugu Tanaka, Mayumi Idei, Hiroshi Sakaguchi, Ryosuke Kato, Daisuke Sato, Kenji Sawanobori, Shuichi Kawarasaki, Toshiyuki Hata, Asako Yoshizaki, Miki Nakamura, Mutsuhiro Ikuma

    British Journal of Clinical Pharmacology   2021年1月

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    担当区分:筆頭著者, 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:Wiley  

    DOI: 10.1111/bcp.14749

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  • Need for evidence on long-term prognosis of PD+HD: a commentary 査読 国際誌

    Mototsugu Tanaka, Naobumi Mise

    BMC Nephrology   22 ( 1 )   2021年1月

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    担当区分:筆頭著者, 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:Springer Science and Business Media LLC  

    <title>Abstract</title>Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is an alternative dialysis method for patients with end-stage kidney disease (ESKD). The complementary use of once-weekly HD expedites to achieve adequate dialysis and enables to prolong PD duration. Although PD+HD has been widely employed among Japanese PD patients, it is much less common outside Japan. Clinical evidences are still not enough, especially in long-term prognosis and appropriate treatment duration, suitable patients, and generalizability. A retrospective cohort study by Chung et al. (BMC Nephrol 21:348, 2020) compared the risk of mortality and hospitalization between PD patients who were transferred to PD+HD and those who were transferred to HD in Taiwan. Because the mortality and hospitalization rates did not differ between the groups, the authors concluded that, PD+HD may be a rational and cost-effective treatment option. It should be noted that the effects of PD+HD on long-term prognosis are still unknown due to too-short PD+HD duration. However, the study identified the high-risk patient population and showed the generalizability of PD+HD. PD+HD is a treatment of choice in patients with ESKD who prefer PD lifestyles even after decline in residual kidney function.

    添付ファイル: Tanaka and Mise_ commentary_BMC Nephrol2021.pdf

    DOI: 10.1186/s12882-020-02212-x

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    その他リンク: http://link.springer.com/article/10.1186/s12882-020-02212-x/fulltext.html

  • Evolving Landscape of New Drug Approval in Japan and Lags from International Birth Dates: Retrospective Regulatory Analysis 査読 国際誌

    Mototsugu Tanaka, Mayumi Idei, Hiroshi Sakaguchi, Ryosuke Kato, Daisuke Sato, Kenji Sawanobori, Shuichi Kawarasaki, Toshiyuki Hata, Asako Yoshizaki, Miki Nakamura, Mutsuhiro Ikuma

    Clinical Pharmacology & Therapeutics   2020年11月

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    担当区分:筆頭著者, 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:Wiley  

    The Pharmaceuticals and Medical Devices Agency (PMDA) have approved hundreds of new drugs in recent years. We retrospectively analyzed the new drugs approved in Japan from 2008 to 2019, and identify the first-in-world approvals and clarify the current drug lag. The new drug and the drug lag were defined as a drug with a new active substance and a difference between the approval date in Japan and the international birth date, respectively. Among 400 new drugs approved in Japan during the last 12 years, 80 (20.0%) were first approved in Japan, and 320 were outside Japan (the United States: 202, 50.5%; Europe: 82, 20.5%; other regions: 36, 9.0%). Of these, 45 new drugs have not yet been approved outside Japan, and the remaining 355 have been globally approved in Japan and overseas. The number of new drug approvals were the largest in oncology followed by metabolic/endocrine and infectious diseases. The median drug lags (year) among all 400 new drugs and 355 new drugs with global approvals were 4.3 and 4.7 in the 1st tertile (2008-2011), 1.5 and 2.6 in the 2nd tertile (2012-2015), and reduced to 1.3 and 2.2 in the 3rd tertile (2016-2019), respectively. Substantial drug lag remains in neurology, psychiatry, and therapeutic areas where the number of new drug approvals was relatively small. Collectively, one-fifth of the new drugs approved in Japan are first-in-world approvals. Drug lag has been greatly decreased, although it still exists.

    添付ファイル: Tanaka et al_400NAS_Clin Pharmacol Ther2020.pdf

    DOI: 10.1002/cpt.2080

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cpt.2080

  • International consensus definitions of clinical trial outcomes for kidney failure: 2020 査読 国際誌

    Adeera Levin, Rajiv Agarwal, William G. Herrington, Hiddo L. Heerspink, Johannes F.E. Mann, Shahnaz Shahinfar, Katherine R. Tuttle, Jo-Ann Donner, Vivekanand Jha, Masaomi Nangaku, Dick de Zeeuw, Meg J. Jardine, Kenneth W. Mahaffey, Aliza M. Thompson, Mary Beaucage, Kate Chong, Glenda V. Roberts, Duane Sunwold, Hans Vorster, Madeleine Warren, Sandrine Damster, Charu Malik, Vlado Perkovic, Shuchi Anand, Nicholas Argent, Elena Babak, Debasish Banerjee, Jonathan Barratt, Aminu K. Bello, Angelito A. Bernardo, Jaime Blais, William Canovatchel, Fergus J. Caskey, Josef Coresh, Ian H. de Boer, Kai-Uwe Eckardt, Rhys DR. Evans, Harold I. Feldman, Agnes B. Fogo, Hrefna Gudmundsdottir, Takayuki Hamano, David C.H. Harris, Sibylle J. Hauske, Richard Haynes, Charles A. Herzog, Thomas Hiemstra, Thomas Idorn, Lesley Inker, Julie H. Ishida, David W. Johnson, Charlotte Jones-Burton, Amer Joseph, Audrey Koitka-Weber, Matthias Kretzler, Robert Lawatscheck, Adrian Liew, Louise Moist, Saraladevi Naicker, Reiko Nakashima, Uptal Patel, Roberto Pecoits Filho, Jennifer B. Rose, Noah L. Rosenberg, Marvin Sinsakul, William E. Smoyer, Laura Sola, Amy R. Sood, Benedicte Stengel, Maarten W. Taal, Mototsugu Tanaka, Marcello Tonelli, Allison Tong, Robert Toto, Michele Trask, Ifeoma I. Ulasi, Christoph Wanner, David C. Wheeler, Benjamin O. Wolthers, Harold M. Wright, Yoshihisa Yamada, Elena Zakharova

    Kidney International   98 ( 4 )   849 - 859   2020年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include outcomes based solely on laboratory measurements of glomerular filtration rate: a sustained low glomerular filtration rate and a sustained percent decline in glomerular filtration rate. Discussion included important considerations, such as (i) recognition of existing nomenclature for kidney failure; (ii) applicability across resource settings; (iii) ease of understanding for all stakeholders; and (iv) avoidance of inappropriate complexity so that the definitions can be used across ranges of populations and trial methodologies. The final definitions reflect the consensus for use in clinical trials.

    添付ファイル: Kidney failure clinical trial outcome definitions_A Levin et al_KI2020.pdf

    DOI: 10.1016/j.kint.2020.07.013

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  • Role of Roxadustat for ESA-Resistant Renal Anemia? —Read with Caution 査読 国際誌

    Mototsugu Tanaka, Kayo Shinohara, Akiko Ono, Mutsuhiro Ikuma

    Journal of the American Society of Nephrology   ASN.2020060821 - ASN.2020060821   2020年9月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society of Nephrology (ASN)  

    添付ファイル: Tanaka M, et al_Role of Roxadustat for ESA-Resistant Renal Anemia —Read with Caution_letter_JASN2020.pdf

    DOI: 10.1681/asn.2020060821

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  • Bioimpedance Spectroscopy‐Based Fluid Status in Combined Dialysis Compared With Hemodialysis and Peritoneal Dialysis: A Cross‐Sectional Study 査読 国際誌

    Mototsugu Tanaka, Yoshitaka Ishibashi, Yoshifumi Hamasaki, Yuka Kamijo, Mayumi Idei, Takahiro Nishi, Michio Takeda, Hiroshi Nonaka, Masaomi Nangaku, Naobumi Mise

    Therapeutic Apheresis and Dialysis   24 ( 4 )   373 - 379   2020年8月

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    担当区分:筆頭著者, 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:Wiley  

    Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used in Japan for PD patients with decreased residual renal function. However, fluid status in PD+HD patients has not been well studied. In this cross-sectional study, we compared fluid status in 41 PD+HD patients with that in 103 HD and 92 PD patients using the bioimpedance spectroscopy. Extracellular water normalized to patient height (NECW, kg/m) was the highest in pre-HD (8.3 ± 1.6) followed by PD (7.9 ± 2.7), PD+HD (7.5 ± 2.5), and post-HD patients (6.9 ± 1.5) (P < 0.01). By multiple linear regression analysis, PD+HD was associated with a significantly lower NECW than pre-HD (β = -0.8, P = 0.03) and similar to PD (β = -0.5, P = 0.24) and post-HD (β = 0.6, P = 0.08) after adjustment for age, sex, diabetic nephropathy, ischemic heart disease, dialysis period, and daily urine volume. There was no correlation between NECW and daily urine volume in all dialysis groups. Average daily fluid removal (a sum of urine volume and ultrafiltration volume by dialysis) was positively correlated with NECW in PD+HD and pre-HD, but not in PD and post-HD patients. Our results suggest that fluid status in PD+HD patients with decreased residual renal function is acceptable as compared with that in HD and PD patients.

    DOI: 10.1111/1744-9987.13444

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1744-9987.13444

  • Mutational diversity in mutY deficient Helicobacter pylori and its effect on adaptation to the gastric environment 査読 国際誌

    Ryo Kinoshita-Daitoku, Kotaro Kiga, Takahito Sanada, Yoshitoshi Ogura, Zhu Bo, Tamako Iida, Rui Yokomori, Eisuke Kuroda, Mototsugu Tanaka, Arpana Sood, Toshihiko Suzuki, Kenta Nakai, Tetsuya Hayashi, Hitomi Mimuro

    Biochemical and Biophysical Research Communications   525 ( 3 )   806 - 811   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    Helicobacter pylori, a pathogenic bacterium that colonizes in the human stomach, harbors DNA repair genes to counter the gastric environment during chronic infection. In addition, H. pylori adapts to the host environment by undergoing antigenic phase variation caused by genomic mutations. The emergence of mutations in nucleotide sequences is one of the major factors underlying drug resistance and genetic diversity in bacteria. However, it is not clear how DNA repair genes contribute to driving the genetic change of H. pylori during chronic infection. To elucidate the physiological roles of DNA repair genes, we generated DNA repair-deficient strains of H. pylori (ΔuvrA, ΔuvrB, ΔruvA, Δnth, ΔmutY, ΔmutS, and Δung). We performed susceptibility testing to rifampicin in vitro and found that ΔmutY exhibited the highest mutation frequency among the mutants. The number of bacteria colonizing the stomach was significantly lower with ΔmutY strain compared with wild-type strains in a Mongolian gerbil model of H. pylori infection. Furthermore, we performed a genomic sequence analysis of the strains isolated from the Mongolian gerbil stomachs eight weeks after infection. We found that the isolated ΔmutY strains exhibited a high frequency of spontaneous G:C to T:A mutations. However, the frequency of phase variations in the ΔmutY strain was almost similar to the wild-type strain. These results suggest that MutY may play a role in modes of gastric environmental adaptation distinct from phase variation.

    DOI: 10.1016/j.bbrc.2020.02.087

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  • Hospitalization for Patients on Combination Therapy With Peritoneal Dialysis and Hemodialysis Compared With Hemodialysis 査読 国際誌

    Mototsugu Tanaka, Yoshitaka Ishibashi, Yoshifumi Hamasaki, Yuka Kamijo, Mayumi Idei, Takuya Kawahara, Takahiro Nishi, Michio Takeda, Hiroshi Nonaka, Masaomi Nangaku, Naobumi Mise

    Kidney International Reports   5 ( 4 )   468 - 474   2020年4月

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    担当区分:筆頭著者, 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:Elsevier BV  

    Introduction: Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used for PD patients with decreased residual kidney function in Japan; however, hospitalization for this combined dialysis has not been investigated so far. We compared the risk of hospitalization for PD+HD with that for HD.
    Methods: A multicenter, prospective observational study was conducted on 42 PD+HD and 42 HD patients matched for age and diabetic nephropathy. The main outcome measure was the cumulative incidence of hospitalization for any cause assessed with the Kaplan-Meier method. Hospitalization rates (the number of admissions per 100 patient-years) associated with dialysis modality were also calculated. The impact of dialysis modality on time to hospitalization was analyzed using the Cox proportional hazard model.
    Results: There was no significant difference between groups in terms of age, sex, dialysis vintage, diabetic nephropathy, and comorbidities. The cumulative incidence of hospitalization did not significantly differ between the groups (log-rank test, P = 0.36). Although total hospitalization rates were 66.0 in PD+HD and 59.2 in HD, hospitalization rates for the sum of PD-related infections (a composite of catheter-related infection and peritonitis) and vascular access troubles were 21.7 in PD+HD and 7.2 in HD. On univariate Cox proportional hazard analysis, dialysis modality had no significant impact on time to hospitalization.
    Conclusion: The risk of hospitalization was not significantly different between PD+HD and HD, although PD+HD patients had a higher risk of dialysis access-related complications than HD patients.

    添付ファイル: Tanaka M, et al. Hospitalization for PD+HD Versus HD_KI rep2020.pdf

    DOI: 10.1016/j.ekir.2020.01.004

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  • Group A Streptococcus establishes pharynx infection by degrading the deoxyribonucleic acid of neutrophil extracellular traps 査読 国際誌

    Mototsugu Tanaka, Ryo Kinoshita-Daitoku, Kotaro Kiga, Takahito Sanada, Bo Zhu, Tokuju Okano, Chihiro Aikawa, Tamako Iida, Yoshitoshi Ogura, Tetsuya Hayashi, Koshu Okubo, Miho Kurosawa, Junichi Hirahashi, Toshihiko Suzuki, Ichiro Nakagawa, Masaomi Nangaku, Hitomi Mimuro

    Scientific Reports   10 ( 1 )   3251 - 3251   2020年2月

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    担当区分:筆頭著者, 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:Springer Science and Business Media LLC  

    Group A Streptococcus (GAS) secretes deoxyribonucleases and evades neutrophil extracellular killing by degrading neutrophil extracellular traps (NETs). However, limited information is currently available on the interaction between GAS and NETs in the pathogenicity of GAS pharyngitis. In this study, we modified a mouse model of GAS pharyngitis and revealed an essential role for DNase in this model. After intranasal infection, the nasal mucosa was markedly damaged near the nasal cavity, at which GAS was surrounded by neutrophils. When neutrophils were depleted from mice, GAS colonization and damage to the nasal mucosa were significantly decreased. Furthermore, mice infected with deoxyribonuclease knockout GAS mutants (∆spd, ∆endA, and ∆sdaD2) survived significantly better than those infected with wild-type GAS. In addition, the supernatants of digested NETs enhanced GAS-induced cell death in vitro. Collectively, these results indicate that NET degradation products may contribute to the establishment of pharyngeal infection caused by GAS.

    添付ファイル: Tanaka M, et al. GAS_SciRep2020.pdf

    DOI: 10.1038/s41598-020-60306-w

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    その他リンク: http://www.nature.com/articles/s41598-020-60306-w

  • Health-related quality of life on combination therapy with peritoneal dialysis and hemodialysis in comparison with hemodialysis and peritoneal dialysis: A cross-sectional study 査読 国際誌

    Mototsugu Tanaka, Yoshitaka Ishibashi, Yoshifumi Hamasaki, Yuka Kamijo, Mayumi Idei, Takuya Kawahara, Takahiro Nishi, Michio Takeda, Hiroshi Nonaka, Masaomi Nangaku, Naobumi Mise

    Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis   40 ( 5 )   462 - 469   2020年1月

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    担当区分:筆頭著者, 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:SAGE Publications  

    Background: The health-related quality of life (HRQOL) of dialysis patients has not been well examined, especially in combination therapy with peritoneal dialysis and hemodialysis (PD+HD) patients. We compared the HRQOL of PD+HD patients with that of HD and PD patients.
    Methods: A multicenter, cross-sectional study was conducted on 36 PD+HD, 103 HD, and 90 PD patients in Japan who completed the Kidney Disease Quality of Life Short Form 36, version 1.3. HRQOL scores were summarized into physical- (PCS), mental- (MCS), role/social- (RCS), and kidney disease component summaries (KDCS).
    Results: Of the PD+HD patients, 31 (86%) transferred from PD and 5 (14%) transferred from HD. They had the longest dialysis vintage and the smallest urine volume. PCS, MCS, and KDCS HRQOL scores of PD+HD patients were comparable with those of HD and PD patients. However, the RCS score for PD+HD was significantly higher than that for HD (p = 0.020) and comparable with that for PD. PD+HD and PD were associated with significantly higher RCS scores than HD after adjusting for age, gender, diabetic nephropathy, dialysis vintage, ischemic heart disease, and peripheral arterial disease.
    Conclusions: For RCS, HRQOL in PD+HD patients was better than that in HD and comparable with that in PD patients, whereas the PCS, MCS, and KDCS HRQOL scores of PD+HD patients were comparable with those of HD and PD patients.

    DOI: 10.1177/0896860819894066

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    その他リンク: http://journals.sagepub.com/doi/full-xml/10.1177/0896860819894066

  • ESA Resistance May Be a Potential Confounder for Mortality among Different ESA Types 査読 国際誌

    Mototsugu Tanaka, Kayo Shinohara, Akiko Ono, Mutsuhiro Ikuma

    Journal of the American Society of Nephrology   30 ( 9 )   1772.1 - 1772   2019年9月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society of Nephrology (ASN)  

    添付ファイル: Tanaka M, et al_ESA resistance may be a potential confounder for mortality among different ESA types_JASN2020.pdf

    DOI: 10.1681/asn.2019060556

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  • A multicenter, randomized controlled trial comparing the identification rate of stigmata of recent hemorrhage and rebleeding rate between early and elective colonoscopy in outpatient-onset acute lower gastrointestinal bleeding: study protocol for a randomized controlled trial 査読 国際誌

    Ryota Niikura, Naoyoshi Nagata, Atsuo Yamada, Hisashi Doyama, Yasutoshi Shiratori, Tsutomu Nishida, Shu Kiyotoki, Tomoyuki Yada, Tomoki Fujita, Tetsuya Sumiyoshi, Kenkei Hasatani, Tatsuya Mikami, Tetsuro Honda, Katsuhiro Mabe, Kazuo Hara, Katsumi Yamamoto, Mariko Takeda, Munenori Takata, Mototsugu Tanaka, Tomohiro Shinozaki, Mitsuhiro Fujishiro, Kazuhiko Koike

    Trials   19 ( 1 )   2018年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Background: The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes.
    Methods: This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%.
    Discussion: This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients.

    添付ファイル: Niikura R, Tanaka M, et al. Trials2018.pdf

    DOI: 10.1186/s13063-018-2558-y

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    その他リンク: http://link.springer.com/article/10.1186/s13063-018-2558-y/fulltext.html

  • A prospective randomized controlled study on the Suppression of Prostate Cancer by Naftopidil (SNAP) 査読 国際誌

    Daisuke Yamada, Haruki Kume, Hideyo Miyazaki, Mototsugu Tanaka, Munenori Takata, Yukari Uemura, Teppei Morikawa, Yutaka Enomoto, Motofumi Suzuki, Hiroaki Nishimatsu, Tohru Nakagawa, Tetsuya Fujimura, Hiroshi Fukuhara, Yasuhiko Igawa, Yukio Homma

    Preventive Medicine and Community Health   1 ( 1 )   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Open Access Text Pvt, Ltd.  

    添付ファイル: Yamada D, Tanaka M, et al. Naftpidil protocol_Prev Med Commun Health2018.pdf

    DOI: 10.15761/pmch.1000106

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  • ベポタスチンベシル酸塩OD錠10 mg「日医工」の健康成人における生物学的同等性試験 査読

    坂中千恵, 石井伸弥, 上田恵子, 亀山祐美, 岸暁子, 切原賢治, 鈴木一詩, 高田宗典, 田中基嗣, 和田千賀子, 伊藤誠, 西村優理子

    診療と新薬   55   91 - 99   2018年

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  • Age-Related Differences of Organism-Specific Peritonitis Rates: A Single-Center Experience 査読 国際誌

    Nagaaki Kotera, Mototsugu Tanaka, Mari Aoe, Masatomo Chikamori, Tomoko Honda, Ayako Ikenouchi, Rika Miura, Mai Sugahara, Satoshi Furuse, Katsunori Saito, Naobumi Mise

    Therapeutic Apheresis and Dialysis   20 ( 6 )   655 - 660   2016年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Peritonitis remains an important cause of morbidity and mortality in peritoneal dialysis (PD) patients, but its incidence and the distribution of causative organisms vary widely between institutions and age groups. This study was performed to investigate the recent status and risk factors of PD-related peritonitis and to clarify differences between age groups. We retrospectively reviewed the medical records of 119 PD patients treated at our department between January 2002 and January 2013. We calculated both overall and organism-specific peritonitis rates and also analyzed risk factors. Sixty-three episodes of peritonitis occurred during 261.5 patient-years for an incident rate of 0.24 episodes/patient-year. Multivariate analysis showed that older age (≥65 years) and hypoalbuminemia (<3.0 g/dL) were associated with an increased risk of peritonitis (P = 0.035 and P = 0.029, respectively). In elderly patients (≥65 years old), the rate of peritonitis due to Gram-positive and Gram-negative bacteria was 0.17 and 0.08 episodes/patient-year, respectively, and Gram-positive peritonitis was markedly more frequent than in younger patients (<65 years old). In particular, there was a high frequency of Staphylococcus aureus peritonitis in elderly patients (0.09 episodes/patient-year) and it had a poor outcome. At our department, the risk of peritonitis was increased in older patients and patients with hypoalbuminemia. The distribution of causative organisms was markedly different between age groups and analysis of organism-specific peritonitis rates helped to identify current problems with our PD program.

    DOI: 10.1111/1744-9987.12449

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  • Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation

    Koshu Okubo, Mako Kamiya, Yasuteru Urano, Hiroshi Nishi, Jan M. Herter, Tanya Mayadas, Daigoro Hirohama, Kazuo Suzuki, Hiroshi Kawakami, Mototsugu Tanaka, Miho Kurosawa, Shinji Kagaya, Keiichi Hishikawa, Masaomi Nangaku, Toshiro Fujita, Matsuhiko Hayashi, Junichi Hirahashi

    EBioMedicine   10   204 - 215   2016年8月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.ebiom.2016.07.012

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  • Immunomodulation with eicosapentaenoic acid supports the treatment of autoimmune small-vessel vasculitis 査読 国際誌

    Junichi Hirahashi, Kimito Kawahata, Makoto Arita, Ryo Iwamoto, Keiichi Hishikawa, Mie Honda, Yoshifumi Hamasaki, Mototsugu Tanaka, Koshu Okubo, Miho Kurosawa, Osamu Takase, Masanori Nakakuki, Kan Saiga, Kazuo Suzuki, Shoji Kawachi, Akihiro Tojo, George Seki, Takeshi Marumo, Matsuhiko Hayashi, Toshiro Fujita

    Scientific Reports   4 ( 1 )   2015年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Small-vessel vasculitis is a life-threatening autoimmune disease that is frequently associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Conventional immunotherapy including steroids and cyclophosphamide can cause serious adverse events, limiting the efficacy and safety of treatment. Eicosapentaenoic acid (EPA), a key component of fish oil, is an omega-3 polyunsaturated fatty acid widely known to be cardioprotective and beneficial for vascular function. We report two elderly patients with systemic ANCA-associated vasculitis (AAV) in whom the administration of EPA in concert with steroids safely induced and maintained remission, without the use of additioal immunosuppressants. To explore the mechanisms by which EPA enhances the treatment of AAV, we employed SCG/Kj mice as a spontaneous murine model of AAV. Dietary enrichment with EPA significantly delayed the onset of crescentic glomerulonephritis and prolonged the overall survival. EPA-derived anti-inflammatory lipid mediators and their precursors were present in the kidney, plasma, spleen, and lungs in the EPA-treated mice. Furthermore, a decrease in ANCA production and CD4/CD8-double negative T cells, and an increase in Foxp3(+) regulatory T cells in the lymph nodes of the kidney were observed in the EPA-treated mice. These clinical and experimental observations suggest that EPA can safely support and augment conventional therapy for treating autoimmune small-vessel vasculitis.

    添付ファイル: Hirahashi J, Tanaka M, et al. EPA for small-vessel vasculitis. Sci Rep2014.pdf

    DOI: 10.1038/srep06406

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  • Dialysis Amyloid Deposition in the Aortic Valve and Its Association with Aortic Stenosis 査読 国際誌

    Noriaki Kurita, Akiko Fujii, Nagaaki Kotera, Mototsugu Tanaka, Shinji Tanaka, Takeshi Miyairi, Tokuichiro Sugimoto, Masaya Mori, Shunichi Fukuhara, Naobumi Mise

    Blood Purification   40 ( 2 )   146 - 154   2015年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:S. Karger AG  

    Background: The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown.
    Methods: This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-β2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS.
    Results: DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with ‘Amyloid (1+) and Calcification >1 mm' and ‘Amyloid (2+) and Calcification >1 mm' (vs. ‘Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with ‘Amyloid (2+) and Calcification >1 mm' (OR: 24.3).
    Conclusions: DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.

    DOI: 10.1159/000381938

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  • Increased peritoneal permeability at peritoneal dialysis initiation is a potential cardiovascular risk in patients using biocompatible peritoneal dialysis solution 査読 国際誌

    Yoshifumi Hamasaki, Kent Doi, Mototsugu Tanaka, Haruki Kume, Yoshitaka Ishibashi, Yutaka Enomoto, Toshiro Fujita, Yukio Homma, Masaomi Nangaku, Eisei Noiri

    BMC Nephrology   15 ( 1 )   2014年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Background: Cardiovascular disease is a frequent cause of death in peritoneal dialysis patients. Biocompatible peritoneal dialysis solutions with neutral pH have been anticipated to reduce cardiovascular disease more than conventional peritoneal dialysis solutions with low pH, but it remains unclear which factors at peritoneal dialysis initiation increase cardiovascular risk in patients using biocompatible peritoneal dialysis solutions. This study was undertaken to investigate which clinical factors at peritoneal dialysis initiation, including peritoneal transport status, are associated with cardiovascular event in patients using biocompatible peritoneal dialysis solution.
    Methods: This retrospective cohort study of peritoneal dialysis patients using biocompatible solutions with neutral pH assessed relations of clinical parameters at peritoneal dialysis initiation to cardiovascular event during the subsequent five years.
    Results: Of 102 patients who started peritoneal dialysis, cardiovascular event occurred in 18. Age, history of cardiovascular disease before peritoneal dialysis initiation, hemoglobin, serum albumin, C-reactive protein, peritoneal permeability defined by the ratio of dialysate to plasma creatinine concentration at 4 hr (D/Pcre) in peritoneal equilibration test (PET), number of patients in each PET category defined by D/Pcre, and peritoneal protein clearance significantly differed between patients with and without cardiovascular event. For patients divided according to PET category using Kaplan-Meier method, the group of high average to high peritoneal transporters exhibited significantly high incidence of cardiovascular event and mortality compared with the groups of low and low-average peritoneal transporters (Log rank; p=0.0003 and 0.005, respectively). A Cox proportional hazards model showed independent association of PET category classification with cardiovascular event.
    Conclusions: Peritoneal permeability expressed as PET category at peritoneal dialysis initiation is an independent cardiovascular risk factor in peritoneal dialysis patients using biocompatible peritoneal dialysis solution with neutral pH. Greater peritoneal permeability at peritoneal dialysis initiation might reflect subclinical vascular disorders.

    添付ファイル: Hamasaki Y, Tanaka M, et al. CV risk and peritoneal permeability BMC Nephrol2014.pdf

    DOI: 10.1186/1471-2369-15-173

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  • Successful Treatment of Acute Kidney Injury in Patients with Idiopathic Nephrotic Syndrome Using Human Atrial Natriuretic Peptide 査読 国際誌

    Kohei Ueda, Junichi Hirahashi, George Seki, Mototsugu Tanaka, Natsuki Kushida, Yusuke Takeshima, Yoshitaka Nishikawa, Toshiro Fujita, Masaomi Nangaku

    Internal Medicine   53 ( 8 )   865 - 869   2014年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Internal Medicine  

    The acute onset of idiopathic nephrotic syndrome (NS) is often accompanied by acute kidney injury, which can lead to congestive heart failure and lung edema. In this report, we present two cases of NS-induced acute kidney injury successfully treated with a low dose of carperitide, a human atrial natriuretic peptide. In combination with standard diuretic therapy and immunotherapy, carperitide retained the renal function and spared the need for renal replacement therapy, including hemodialysis. Although further investigation in clinical trials is required to validate these findings, carperitide may be useful for maintaining the renal function in cases of NS-induced acute kidney injury.

    DOI: 10.2169/internalmedicine.53.1724

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  • Peritoneal Dialysis Combined with Extracorporeal Ultrafiltration in Refractory Heart Failure: A Case Report 査読 国際誌

    Yu Ishimoto, Naobumi Mise, Mototsugu Tanaka, Mai Sugahara, Takafumi Kanemitsu, Masafumi Kobayashi, Lisa Uchida, Nagaaki Kotera, Shinji Tanaka, Tokuichiro Sugimoto

    Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis   33 ( 5 )   582 - 583   2013年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE Publications  

    DOI: 10.3747/pdi.2012.00212

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  • AA amyloid nephropathy with predominant vascular deposition in Crohn's disease 査読 国際誌

    Noriaki Kurita, Nagaaki Kotera, Yu Ishimoto, Mototsugu Tanaka, Shinji Tanaka, Nobuo Toda, Akiko Fujii, Kiyonori Kobayashi, Tokuichiro Sugimoto, Naobumi Mise

    Clinical Nephrology   79 ( 03 )   229 - 232   2013年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Dustri-Verlgag Dr. Karl Feistle  

    A 44-year-old man with a 17-year history of Crohn's disease (CD) was referred to our nephrology department on suspicion of drug-induced nephrotoxicity. Over the preceding 18 months, he had slowly progressive renal insufficiency with slight urinary abnormalities. His disease activity had been well controlled up to that point with 5-aminosalicylic acid and azathiopurine. Laboratory examination revealed slight proteinuria without hematuria and an elevated serum creatinine level of 1.4 mg/dl. Pathological examination revealed amyloid A (AA) deposition in the kidney, predominantly in the arterial and arteriolar walls with little to none in the glomerular capillaries. AA amyloidosis is typically accompanied by glomerular amyloid deposition and massive proteinuria. In the present case, however, vascular amyloid deposition was predominant, and the renal function was deteriorated with slight urinary abnormalities. The present case confirmed the importance of conducting a definitive pathological diagnosis of renal insufficiency in CD patients.

    DOI: 10.5414/cn107151

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  • Acute Kidney Injury after a Pelvic Surgery 査読 国際誌

    Mototsugu Tanaka, Junichi Hirahashi, Takamoto Ohse, Toshiro Fujita

    Nephrology   18 ( 1 )   73 - 74   2013年1月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/j.1440-1797.2012.01609.x

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  • Successful Long-Term Peritoneal Dialysis in Combination with Once-Weekly Hemodialysis: A Case Report 査読 国際誌

    Naobumi Mise, Shinji Tanaka, Lisa Uchida, Yu Ishimoto, Nagaaki Kotera, Mototsugu Tanaka, Tokuichiro Sugimoto

    Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis   32 ( 5 )   572 - 573   2012年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE Publications  

    DOI: 10.3747/pdi.2011.00301

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  • Peritoneal Dialysis With Takayasu Arteritis: A Report of Three Cases 査読 国際誌

    Mototsugu Tanaka, Yoshitaka Ishibashi, Junichi Hirahashi, Toshiro Fujita

    Therapeutic Apheresis and Dialysis   16 ( 2 )   198 - 199   2012年4月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/j.1744-9987.2011.01041.x

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  • Glomerular capillary light chain thrombi in multiple myeloma 査読 国際誌

    Noriaki Kurita, Mototsugu Tanaka, Shinji Tanaka, Akiko Fujii, Tokuichiro Sugimoto, Yutaka Yamaguchi, Naobumi Mise

    Kidney International   80 ( 12 )   1378 - 1378   2011年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    添付ファイル: Kurita N, Tanaka M, et al. Glomerular light chain in Myeloma case. KI2011.pdf

    DOI: 10.1038/ki.2011.342

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  • Acute systemic hypotension after arteriovenous fistula construction in a patient with severe aortic stenosis 査読 国際誌

    Naobumi Mise, Lisa Uchida, Mototsugu Tanaka, Shinji Tanaka, Hiroyoshi Nakajima, Tokuichiro Sugimoto

    Clinical and Experimental Nephrology   15 ( 5 )   788 - 790   2011年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    We report the case of a 53-year-old hemodialysis patient with severe aortic stenosis, who developed acute systemic hypoperfusion after arteriovenous fistula (AVF) construction. He presented with hypotension and repeated syncope soon after distal radiocephalic AVF construction, and finally developed a respiratory arrest. His blood pressure and hemodynamics recovered promptly by sub-emergent aortic valve replacement surgery. In the present case, the heart with severe aortic stenosis could not increase cardiac output in response to the reduction in peripheral vascular resistance caused by the AVF. High-output heart failure, a relatively rare AVF-associated disorder, occurs with an excessive AVF flow, usually more than 3 L/min or 30% of cardiac output. However, heart failure may develop soon after construction of an AVF with a moderate blood flow if a patient's cardiac function is severely impaired. In addition, heart failure may improve with AVF preservation if the underlying heart disease is treatable.

    DOI: 10.1007/s10157-011-0484-3

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  • Effects of Combination Therapy with Peritoneal Dialysis and Hemodialysis on Left Ventricular Hypertrophy 査読 国際誌

    Mototsugu Tanaka, Naobumi Mise, Hiroyoshi Nakajima, Lisa Uchida, Yu Ishimoto, Nagaaki Kotera, Shinji Tanaka, Noriaki Kurita, Tokuichiro Sugimoto

    Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis   31 ( 5 )   598 - 600   2011年9月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE Publications  

    DOI: 10.3747/pdi.2010.00273

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  • IgG4関連硬化性疾患による下垂体炎から中枢性副腎不全,中枢性尿崩症を発症した1型糖尿病の1例 査読

    小寺永章, 五十川陽洋, 内田梨沙, 石本遊, 田中基嗣, 田中真司, 岸智, 三瀬直文, 杉本徳一郎, 柴輝男

    日内会誌   100 ( 4 )   1044 - 1047   2011年4月

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    掲載種別:研究論文(学術雑誌)  

    1 型糖尿病の 60 歳男性.IgG4 関連硬化性疾患による後腹膜線維症,同リンパ節腫脹,硬化性唾液腺炎のため経過観察していたが,血清総蛋白の上昇,腎機能障害と共に全身倦怠感,口渇が出現・増悪した.中枢性副腎不全,中枢性尿崩症を呈しており頭部MRIで下垂体炎を認めた.IgG4 関連硬化性疾患による一連の病変でありステロイドが著効した.IgG4 関連硬化性疾患による下垂体炎の貴重な症例を経験したので報告する.

    DOI: 10.2169/naika.100.1044

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  • Arteriovenous Access Closure in Hemodialysis Patients With Refractory Heart Failure: A Single Center Experience 査読 国際誌

    Noriaki Kurita, Naobumi Mise, Shinji Tanaka, Mototsugu Tanaka, Keiko Sai, Takahiro Nishi, Sumio Miura, Ikutaro Kigawa, Takeshi Miyairi, Tokuichiro Sugimoto

    Therapeutic Apheresis and Dialysis   15 ( 2 )   195 - 202   2011年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Arteriovenous dialysis access may impose a burden on the cardiac system. The objective of this study is to examine the usefulness of access closure in hemodialysis patients with refractory heart failure and to identify possible factors associated with symptomatic improvements. The study population comprised 33 hemodialysis patients with symptomatic heart failure (New York Heart Association [NYHA] class ≥ II), who underwent arteriovenous access closure (30 fistulas and three grafts) between 1991 and 2008. In all patients, heart failure was refractory to all possible medical and surgical treatments, and persisted after optimal dry weight control. First, short-term changes in hemodynamics, clinical symptoms and echocardiographic morphology were examined. Second, clinical and echocardiographic parameters were compared between responders (N=23), who demonstrated NYHA class improvement after access closure, and non-responders (N=10). After access closure, systolic blood pressure rose and the heart rate decreased significantly. Body weight and echocardiographic parameters did not change significantly. Twenty-three patients (70%) demonstrated NYHA class improvement and were designated as responders. In responders, the duration from access creation to closure was significantly shorter and fewer had ischemic heart disease, compared with non-responders. Access flow, cardiac output and ejection fraction were comparable between the two groups. Although the five-year survival was 20.2% in all patients, responders showed better early survival than non-responders. Arteriovenous access closure improved clinical symptoms in 70% of patients with refractory heart failure. This improvement was especially likely to be achieved in patients without ischemic heart disease and those who developed heart failure within a relatively short time after access creation.

    DOI: 10.1111/j.1744-9987.2010.00907.x

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  • 多中心性Castleman病に合併したメサンギウム増殖性腎炎の1例 査読

    藤原弘明, 三瀬直文, 石本遊, 小寺永章, 田中基嗣, 田中真司, 栗田宜明, 藤井晶子, 山口裕, 杉本徳一郎

    日本腎臓学会誌   53 ( 2 )   189 - 194   2011年1月

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    掲載種別:研究論文(学術雑誌)  

    多中心性 Castleman 病の経過中に進行性腎障害,メサンギウム増殖性腎炎を認め,IgA 腎症と診断した症例を経験した。症例は 47 歳,男性,36 歳時に健康診断で高蛋白血症を指摘された後,全身リンパ節腫脹,血尿・蛋白尿,腎機能障害が出現した。41 歳時,リンパ節生検を施行したところ,濾胞間に血管増生が優位でない形質細胞の増殖を認め,多中心性 Castleman 病(形質細胞型)と診断した。ステロイドパルス療法にてリンパ節腫脹の縮小と腎機能改善を認めたが,ステロイド減量中に再度腎機能が増悪したため,47 歳時に腎臓内科に紹介され腎生検を施行。半月体を伴う活動性の高い IgA 腎症に,形質細胞浸潤主体の軽度尿細管間質性腎炎を合併していた。ステロイドパルス療法にて,腎機能の軽度改善と血尿・蛋白尿の減少を認めた。Castleman 病と IgA 腎症の合併が稀であること,また尿所見・腎機能障害の程度が Castleman 病の活動性と比例しており,Castleman 病で過剰産生された IL-6 が IgA 腎症の病勢に関与している可能性があることから,示唆に富む症例と考え報告する。

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  • Aberrantly Glycosylated IgA1 as a Factor in the Pathogenesis of IgA Nephropathy 招待 査読 国際誌

    Mototsugu Tanaka, George Seki, Tomonosuke Someya, Michio Nagata, Toshiro Fujita

    Clinical and Developmental Immunology   2011   1 - 7   2011年

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hindawi Limited  

    Predominant or codominant immunoglobulin (Ig) A deposition in the glomerular mesangium characterizes IgA nephropathy (IgAN). Accumulated glomerular IgA is limited to the IgA1 subclass and usually galactose-deficient. This underglycosylated IgA may play an important role in the pathogenesis of IgAN. Recently, antibodies against galactose-deficient IgA1 were found to be well associated with the development of IgAN. Several therapeutic strategies based on corticosteroids or other immunosuppressive agents have been shown to at least partially suppress the progression of IgAN. On the other hand, several case reports of kidney transplantation or acquired IgA deficiency uncovered a remarkable ability of human kidney to remove mesangial IgA deposition, resulting in the long-term stabilization of kidney function. Continuous exposure to circulating immune complexes containing aberrantly glycosylated IgA1 and sequential immune response seems to be essential in the disease progression of IgAN. Removal of mesangial IgA deposition may be a challenging, but fundamental approach in the treatment of IgAN.

    添付ファイル: Tanaka M, Seki G, et al. IgAN Review. ClinDevImmunol2011.pdf

    DOI: 10.1155/2011/470803

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    その他リンク: http://downloads.hindawi.com/journals/jir/2011/470803.xml

  • Neisseria subflava腹膜炎を発症した1型糖尿病の腹膜透析患者の1例 査読

    小寺永章, 三瀬直文, 内田梨沙, 石本遊, 田中基嗣, 田中真司, 栗田宜明, 杉本徳一郎

    透析会誌   44 ( 4 )   319 - 322   2011年

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    34歳,男性.1型糖尿病による腎不全のため,2008年4月腹膜透析(peritoneal dialysis:PD)導入し,マニュアル接続によるダブルバッグシステムにて夜間間欠的腹膜透析(nocturnal intermittent peritoneal dialysis:NIPD)を施行していた.2009年1月22日腹痛・下痢・嘔吐・PD排液混濁を認め受診.来院時体温37.4℃,腹膜刺激症状あり,WBC 12,800/μL,CRP 1.1mg/dL,PD排液WBC 2,500/μLと上昇しており,腹膜炎と診断した.セファゾリン(CEZ),セフタジジム(CAZ)の腹腔内あるいは静脈内投与8日間に加え,セフォチアム(CTM)経口投与を6日間施行したところ,腹膜炎は治癒し,現在まで再発は認められていない.PD液からはNeisseria subflavaが検出され,起因菌と考えられた.分離菌はCEZ,CAZ,CTMに感受性であった. Neisseria subflavaは口腔内常在菌で,まれに心内膜炎,髄膜炎などの起因菌となる.PD患者のNeisseria腹膜炎も少数ながら報告されており,腎不全以外に合併症のない症例でも発症している.本症例は糖尿病患者の感染脆弱性,およびバッグ交換時のマスク非着用がリスクと考えられ,感染経路は飛沫による経カテーテルと推察された.マスク着用による,バッグ交換時の飛沫感染予防の重要性が再確認された.

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  • Resolution of Henoch-Schönlein purpura nephritis after acquired IgA deficiency 査読 国際誌

    Mototsugu Tanaka, George Seki, Kenichi Ishizawa, Junichi Hirahashi, Kenichiro Miura, Takashi Sekine, Tomonosuke Someya, Hiroshi Hataya, Michio Nagata, Toshiro Fujita

    Pediatric Nephrology   25 ( 11 )   2355 - 2358   2010年11月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    We report a case of Henoch-Schönlein purpura nephritis (HSPN) with acquired IgA deficiency due to parvovirus B19 infection. The patient was diagnosed as having Henoch-Schönlein purpura (HSP) at 6 years old, and subsequently developed macrohematuria and massive proteinuria of 7.4 g/day with decreased creatinine clearance of 70.2 ml/min/1.73 m(2) and significantly elevated serum IgA level of 449 mg/dl. The first kidney biopsy yielded the diagnosis of severe HSPN. After the initiation of the immunosuppressive therapy, the patient was infected with parvovirus B19 and developed virus-associated hemophagocytic syndrome (VAHS). Thereafter, the serum level of IgA selectively decreased and remained undetectable until the present time. Repeated kidney biopsies performed over a period of 14 years revealed a remarkable histological improvement in association with stabilization of the patient's kidney function. Considering the severity of initial kidney injury, persistent acquired IgA deficiency was likely to add favorable effects to the immunosuppressive therapy in this patient with HSPN.

    DOI: 10.1007/s00467-010-1568-0

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  • A Case of Churg-Strauss Syndrome With Necrotizing Crescentic Glomerulonephritis Accompanied by Acute Coronary Syndrome Due to Vasospasm 査読 国際誌

    Mototsugu Tanaka, Naobumi Mise, Noriaki Kurita, Takeshi Suzuki, Kazuhiro Hara, Akiko Fujii, Noriko Uesugi, Tokuichiro Sugimoto

    American Journal of Kidney Diseases   56 ( 2 )   e5 - e9   2010年8月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    We report a case of Churg-Strauss syndrome coexistent with coronary vasospasm and pauci-immune necrotizing crescentic glomerulonephritis. A 54-year-old man with bronchial asthma and allergic rhinitis was admitted to our hospital because of acute coronary syndrome. Angiography showed diffuse coronary artery spasm without anatomic stenosis. Acute coronary syndrome due to vasospasm was diagnosed. However, subsequent administration of vasodilators did not suppress angina symptoms. In addition, marked eosinophilia, eosinophilic pneumonitis, chronic sinusitis, pericardial effusion, and slight hematuria with red blood cell casts were detected. Although kidney function was normal, a kidney biopsy showed necrotizing crescentic glomerulonephritis with eosinophilic infiltration in both glomeruli and interstitium. With the diagnosis of Churg-Strauss syndrome, oral prednisolone at a dose of 60 mg/d was administered. Cardiac symptoms, pulmonary and sinonasal lesions, pericardial effusion, and urine sediment resolved rapidly. Six months later, a repeated kidney biopsy showed remarkable improvement and no eosinophilic infiltration. Coronary vasospasm with eosinophilia might be refractory to vasodilators and sensitive to corticosteroid therapy and often has been related to Churg-Strauss syndrome. Slight abnormalities in urine sediment can be the clue to the diagnosis of severe kidney involvement of Churg-Strauss syndrome.

    DOI: 10.1053/j.ajkd.2010.03.011

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  • MEFV mutations in Japanese rheumatoid arthritis patients. 査読 国際誌

    Kiyoshi Migita, Tadashi Nakamura, Yumi Maeda, Taichiro Miyashita, Tomohiro Koga, Mototsugu Tanaka, Minoru Nakamura, Atsumasa Komori, Hiromi Ishibashi, Tomoki Origuchi, Hiroaki Ida, Eiji Kawasaki, Michio Yasunami, Katsumi Eguchi

    Clinical and experimental rheumatology   26 ( 6 )   1091 - 1094   2008年11月

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    掲載種別:研究論文(学術雑誌)  

    Objective: Familiar Mediterranean Fever (FMF) is common among Mediterranean populations, while other populations are rarely affected. The aim of this study was to assess the involvement of MEFV gene mutations among Japanese rheumatoid arthritis patients with or without amyloid A (AA) amyloidosis.

    Methods: The frequency of the MEFV mutations, which were identified in Japanese FMF patients, was determined in 126 Japanese RA patients and 76 Japanese healthy subjects.

    Results: The M694I mutation was not observed among RA patients and healthy subjects. Allele frequency of R408Q, P369S, E148Q, L110P mutations account respectively for 3.3%, 3.9%, 23.7%, 9.2% in healthy subjects and 5.6%, 6.7%, 24.2%, 9.5% in RA patients. The overall mutation rate was comparable between the RA patients and healthy subjects, as well as between the RA patients with and without amyloidosis.

    Conclusion: This study shows the high prevalence of mutations of the MEFV genes in Japanese RA patients. However, our data suggest that the MEFV gene mutations may not be a genetic factor affecting the susceptibility of RA or the development of amyloidosis in a Japanese population.

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  • Acute hepatitis in a patient with familial Mediterranean fever 査読 国際誌

    Kiyoshi Migita, Seigo Abiru, Mototsugu Tanaka, Masahiro Ito, Taichiro Miyashita, Yumi Maeda, Tomohiro Koga, Minoru Nakamura, Atsumasa Komori, Hiroshi Yatsuhashi, Hiroaki Ida, Katsumi Eguchi, Kenji Hirayama, Michio Yasunami, Hiromi Ishibashi

    Liver International   28 ( 1 )   140 - 142   2007年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Familial Mediterranean fever (FMF) is a hereditary syndrome characterized by recurrent episodes of fever and serositis. In this report, we describe a Japanese patient with FMF and Sjögren's syndrome, in whom acute elevations of transaminase occurred. The histological findings from the liver biopsy specimens demonstrated a nonspecific hepatitis, with liver cell necrosis and interlobular inflammatory cell invasion, without the presence of interface hepatitis or bile duct injury. This case underscores the possibility that MEFV mutations contribute to hepatic inflammation, as seen in this case, by way of an alteration of the pyrin function.

    DOI: 10.1111/j.1478-3231.2007.01598.x

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  • ステロイド治療中にEBVの再活性化を認めたChurg-Strauss Syndromeの一例 査読

    田中 基嗣, 本間 雄一, 堀江 一郎, 小野 咲弥子, 宮下 賜一郎, 大角 光彦, 木村 博典, 枡田 智子, 岩永 洋, 一瀬 克浩, 新野 大介, 伊東 正博, 本村 政勝, 江口 勝美, 右田 清志

    九州リウマチ   27   56 - 62   2007年9月

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    担当区分:筆頭著者   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:九州リウマチ学会  

    症例は57歳、女性。2年前より気管支喘息で加療をうけていたが、2006年4月上旬、両下腿の腫脹が出現し、その後、比較的急速に歩行障害と両下肢痛が出現して進行を認めたため、当科緊急入院となった。入院後、気管支喘息の既往、好酸球増多、多発性単神経炎の所見、およびMPO-ANCA強陽性からChurg-Strauss Syndrome(CSS)と診断した。ステロイドパルス療法を施行したところ、好酸球増多、MPO-ANCA高値などの所見は速やかに改善したが、神経症状の改善には2ヵ月を要した。治療経過中に認めたリンパ球増加の原因検索で施行した、ヒト全血Epstein-Barr virus(EBV)-DNA定量リアルタイムPCRにてEBVの増加を認めたため、更なる免疫抑制は行わず経過を観察したところ、EBVウイルス量の低下および神経症状の改善が認められた。CSSなどの血管炎の免疫抑制療法中には、日和見感染を起こすことがあり、しばしば致命的となりうるため、各種免疫抑制療法の適応を慎重に検討し治療を行う必要があると考えられた。(著者抄録)

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  • Coexistence of familial Mediterranean fever and Sjögren's syndrome in a Japanese patient. 査読 国際誌

    Mototsugu Tanaka, Kiyoshi Migita, Taichiro Miyashita, Yumi Maeda, Minoru Nakamura, Atsumasa Komori, Hiromi Ishibashi, Katsumi Eguchi, Mihoko Kikuchi, Kenji Hirayama, Michio Yasunami

    Clinical and experimental rheumatology   25 ( 5 )   792   2007年9月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)  

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書籍等出版物

  • 腹膜透析ハンドブック

    石橋, 由孝, 衣笠, 哲史, 田中, 基嗣, 塚本, 真貴

    中外医学社  2012年9月  ( ISBN:9784498124905

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    総ページ数:8, 255p   記述言語:日本語

    CiNii Books

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  • 保存期慢性腎臓病治療薬の薬事承認について

    田中基嗣( 担当: 分担執筆)

    週刊日本医事新報 5065号  2021年5月 

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  • 腹膜透析・腎移植ハンドブック

    石橋, 由孝, 衣笠, 哲史( 担当: 分担執筆 ,  範囲: PD+HD併用療法)

    中外医学社  2018年10月  ( ISBN:9784498224421

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    総ページ数:xi, 339p   記述言語:日本語

    CiNii Books

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  • 現場で役立つ腎臓内科ポケットブック

    三瀬, 直文, 石橋, 由孝( 担当: 分担執筆 ,  範囲: 浮腫・体液過剰のみかた)

    文光堂  2018年3月  ( ISBN:9784830620461

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    総ページ数:xiv, 252p   記述言語:日本語

    CiNii Books

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  • 臨牀と研究

    ( 担当: 分担執筆 ,  範囲: 生化学検査―腎機能の評価)

    大道学館出版部  2013年7月 

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  • 血管炎 : 基礎と臨床のクロストーク

    ( 担当: 分担執筆 ,  範囲: ANCA関連血管炎における好中球と血管内皮障害)

    日本臨牀社  2013年2月 

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  • 内科レジデント実践マニュアル : 経時的流れに応じた適切な治療

    田川, 一海, 杉本, 徳一郎, 三井記念病院( 担当: 分担執筆)

    文光堂  2012年3月  ( ISBN:9784830620263

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    総ページ数:x, 468p   記述言語:日本語

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  • スタンダード透析療法

    腎と透析, 編集委員会( 担当: 分担執筆 ,  範囲: 高齢者への透析治療)

    東京医学社  2011年6月 

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  • 透析患者の合併症50 : 患者さんにもわかりやすいシートでらくらく説明できる! : 基礎知識からナースのケアまでまるわかり!

    大平, 整爾( 担当: 分担執筆 ,  範囲: 高血圧;不整脈)

    メディカ出版  2010年12月  ( ISBN:9784840431231

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    総ページ数:249p   記述言語:日本語

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  • 透析療法事典

    中本, 雅彦, 佐中, 孜, 秋沢, 忠男( 担当: 分担執筆 ,  範囲: 糖尿病透析患者の脳血管障害)

    医学書院  2009年6月  ( ISBN:9784260008457

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    総ページ数:31, 560p   記述言語:日本語

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共同研究・競争的資金等の研究

  • わが国におけるドラッグラグの現状と課題

    研究課題/領域番号:21K18094  2021年4月 - 2026年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    田中 基嗣

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    担当区分:研究代表者 

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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  • 新規化膿レンサ球菌性扁桃炎モデルによる好中球細胞外トラップ分解産物の病原性解析

    研究課題/領域番号:17K14974  2017年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    田中 基嗣

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    担当区分:研究代表者 

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    化膿レンサ球菌菌株を経鼻感染させた致死的マウスモデルを構築した。本モデルでは、感染24時間後から体重減少がみられ、感染72時間後に菌血症となり、感染6日後までに全数が死亡した。感染マウスでは、経時的に鼻粘膜破壊が生じ、著しい鼻粘膜上皮細胞のアポトーシスが観察された。感染局所では、好中球とマクロファージの浸潤がみられたが、菌塊の中心部には好中球のみが観察された。薬剤を用いて好中球除去マウス及びマクロファージ除去マウスを作製し、化膿レンサ球菌を感染させたところ、好中球除去マウスでは感染局所菌数が減少し、マクロファージ除去マウスでは菌数の増加が見られた。このことから、好中球が化膿レンサ球菌の感染拡大に寄与したと考えられた。化膿レンサ球菌は、分泌型DNaseにより好中球細胞外トラップを分解するため、同分解産物によるマクロファージ細胞死が起きている可能性を検討した。ヒト単球系細胞を用いたin vitroの実験において、化膿レンサ球菌培養液上清には強い細胞毒性が観察された。好中球を刺激して、好中球細胞外トラップを発生させた後、化膿レンサ球菌培養上清を添加して得られた好中球細胞外トラップ分解産物は、ヒト単球系細胞に対して化膿レンサ球菌培養上清に相加的な細胞毒性を示した。当該化膿レンサ球菌の有する分泌型DNase構成遺伝子のノックアウト菌株をマウスへ感染させたところ、著しい生存期間の延長及び感染局所菌数の減少が見られた。これらは、化膿レンサ球菌に関する研究報告及び化膿レンサ球菌によって生じた好中球細胞外トラップ分解産物が生体へ不利に作用するという本研究の仮説に矛盾しない結果と考えられた。

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  • 化膿レンサ球菌感染症における好中球細胞外トラップ分解産物の同定と機能解析

    研究課題/領域番号:15H06158  2015年8月 - 2017年3月

    日本学術振興会  科学研究費助成事業 研究活動スタート支援  研究活動スタート支援

    田中 基嗣

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    担当区分:研究代表者 

    配分額:2990000円 ( 直接経費:2300000円 、 間接経費:690000円 )

    先行研究で用いた化膿レンサ球菌菌株の全ゲノム解析を実施し、好中球細胞外トラップ分解産物(NETDP)産生に関与している可能性があるDNase遺伝子を3つ、また新規に5’-nucleotidase遺伝子(領域)を2つ選定した。このうち4種類の欠損変異株の作製に成功したが、いずれもDNase作用が残存した。またNETDPの細胞毒性評価系において、細菌培養液上清と比較して高い細胞毒性が示唆されたものの、NETDPを含む細菌培養液上清に菌体が混入して測定値が高値となることが判明した。今後、上記5つの遺伝子(領域)の重複欠損菌株を作製し、混入菌体の影響の少ない実験系でNETDP産生関与因子を精査する。

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メディア報道

  • Asia-Pacific Roundup: PMDA puts patients at heart of push for Japan-first approvals 新聞・雑誌

    Regulatory Affairs Professionals Society  Regulatory Focus  https://www.raps.org/news-and-articles/news-articles/2020/12/asia-pacific-roundup-pmda-puts-patients-at-heart-o  2020年12月

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    執筆者:本人以外 

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  • PMDA Eyes More Japan-First Approvals In Access Push 新聞・雑誌

    Informa PLC  Pink Sheet Informa Pharma Intelligence  https://pink.pharmaintelligence.informa.com/PS143361/PMDA-Eyes-More-Japan-First-Approvals-In-Access-Push  2020年11月

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    執筆者:本人以外 

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  • To Boost Japan-first Medical Product Approvals ~ PMDA Now Looks at Next Steps ~ 会誌・広報誌

    Pharmaceuticals and Medical Devices Agency  Chief Executive’s Statement  https://www.pmda.go.jp/english/about-pmda/0001.pdf  2020年11月

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    執筆者:本人以外 

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