2025/05/12 更新

写真a

トミタ マコト
冨田 誠
Makoto Tomita
所属
データサイエンス学部 データサイエンス学科 教授
データサイエンス研究科 ヘルスデータサイエンス専攻
職名
教授
プロフィール
2001年に岡山大学大学院自然科学研究科修了 博士(理学)を取得。2004年に南山大学 専任講師、2008年に統計数理研究所 特任准教授、2009年に東京医科歯科大学 准教授を経て2019年より現職。遺伝統計学、多変量統計解析、空間集積性、空間疫学、生物統計学全般が研究領域。
外部リンク

学位

  • 博士(理学) ( 岡山大学大学院 )

研究キーワード

  • ゲノム統計学

  • 生物統計学

  • Association Study for haplotype

  • Linkage Disequilibrium

  • 多変量解析

  • 空間疫学

  • 計算機統計学

研究分野

  • 情報通信 / 生命、健康、医療情報学

  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含まない

  • ライフサイエンス / 衛生学、公衆衛生学分野:実験系を含む

  • 情報通信 / 統計科学

  • ライフサイエンス / ゲノム生物学

  • 環境・農学 / 環境負荷、リスク評価管理

  • ライフサイエンス / 医療管理学、医療系社会学

▼全件表示

学歴

  • 岡山大学大学院   自然科学研究科

    1997年4月 - 2001年3月

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    国名: 日本国

    備考: 博士(理学)

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経歴

  • 横浜市立大学   データサイエンス学部   教授

    2019年4月 - 現在

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  • 東京医科歯科大学   医学部附属病院   准教授

    2009年4月 - 2019年3月

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  • 統計数理研究所   特任准教授

    2008年10月 - 2009年3月

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  • 南山大学   数理情報学部   専任講師

    2004年10月 - 2008年9月

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  • 日本バイオ産業情報化コンソーシアム   特別研究員

    2001年4月 - 2004年9月

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委員歴

  • 統計関連学会連合   理事  

    2025年3月 - 現在   

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    団体区分:学協会

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  • 日本統計学会   代議員  

    2025年 - 現在   

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  • 2025年度統計関連学会連合大会   運営委員長  

    2025年 - 現在   

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  • 日本計算機統計学会   副会長  

    2025年 - 現在   

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  • 統計関連学会連合   幹事  

    2023年4月 - 現在   

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    団体区分:学協会

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  • 日本統計学会   代議員  

    2021年3月 - 2023年6月   

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    団体区分:学協会

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  • 日本計算機統計学会   和文誌 編集委員長  

    2021年1月 - 現在   

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    団体区分:学協会

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  • 2020年度統計関連学会連合大会   プログラム委員長  

    2019年12月 - 2020年12月   

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    団体区分:学協会

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  • 日本分類学会   評議員  

    2019年4月 - 現在   

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    団体区分:学協会

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  • 日本分類学会   幹事長  

    2019年4月 - 2023年4月   

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    団体区分:学協会

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  • 統計関連学会連合   理事  

    2019年4月 - 2023年4月   

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    団体区分:学協会

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  • 日本計算機統計学会   若手奨励理事  

    2019年1月 - 2020年12月   

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    団体区分:学協会

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  • 2019年度統計関連学会連合大会   プログラム副委員長  

    2018年12月 - 2019年12月   

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    団体区分:学協会

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  • Asian Resional Section of IASC (IASC-ARS)   BoD member  

    2017年12月 - 2023年2月   

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    団体区分:学協会

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  • 統計関連学会連合   幹事  

    2017年5月 - 2019年4月   

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    団体区分:学協会

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  • 日本分類学会   庶務幹事  

    2017年4月 - 2019年3月   

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    団体区分:学協会

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  • Japanese Journal of Statistics and Data Science (JJSD)   Associate Editor  

    2017年1月 - 現在   

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    団体区分:学協会

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  • 日本統計学会   代議員  

    2015年3月 - 2017年3月   

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    団体区分:学協会

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  • 日本計算機統計学会   庶務理事  

    2013年1月 - 2018年12月   

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    団体区分:学協会

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  • 日本計算機統計学会   企画理事  

    2011年1月 - 2012年12月   

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    団体区分:学協会

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  • 日本計算機統計学会   評議員  

    2009年1月 - 現在   

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    団体区分:学協会

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  • 日本計算機統計学会   庶務理事  

    2009年1月 - 2010年12月   

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    団体区分:学協会

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  • 日本計算機統計学会   和文誌 編集委員  

    2007年1月 - 現在   

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    団体区分:学協会

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  • 日本計算機統計学会   評議員  

    2005年1月 - 2006年12月   

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    団体区分:学協会

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論文

  • Data validation and statistical issues such as power and other considerations in genome‐wide association study (GWAS) 招待 査読

    Makoto Tomita

    WIREs Computational Statistics   15 ( 3 )   e1601 - e1601   2023年6月

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    担当区分:筆頭著者, 最終著者, 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: 10.1002/wics.1601

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/wics.1601

  • Association between knee cartilage thickness determined by magnetic resonance imaging three-dimensional analysis and the International Cartilage Repair Society (ICRS) arthroscopic grade 査読

    Nobutake Ozeki, Hideyuki Koga, Yusuke Nakagawa, Hiroki Katagiri, Hisako Katano, Makoto Tomita, Jun Masumoto, Ichiro Sekiya

    The Knee   42   90 - 98   2023年6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  

    DOI: 10.1016/j.knee.2023.02.005

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  • Effects of melatonin on postoperative sleep quality: a systematic review, meta-analysis, and trial sequential analysis. 国際誌

    Akito Tsukinaga, Takahiro Mihara, Teppei Takeshima, Makoto Tomita, Takahisa Goto

    Canadian journal of anaesthesia = Journal canadien d'anesthesie   70 ( 5 )   901 - 914   2023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)  

    PURPOSE: Postoperative sleep disturbances are common. Although several studies have examined the effect of melatonin on postoperative sleep disturbances, the results have not reached any definitive conclusion. We sought to conduct a systematic review to compare the effects of melatonin and melatonin agonists on postoperative sleep quality with those of placebo or no treatment in adult patients who underwent surgery under general or regional anesthesia. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Web of Science, ClinicalTrials.gov, and the UMIN Clinical Trials Registry up to 18 April 2022. Randomized clinical trials examining the effects of melatonin or melatonin agonists in patients undergoing general or regional anesthesia with sedation for any surgery were eligible for inclusion. The primary outcome was sleep quality measured using a visual analog scale (VAS). The secondary outcomes were postoperative sleep duration, sleepiness, pain, opioid consumption, quality of recovery, and adverse events. A random-effects model was used to combine the results. We assessed study quality with the Cochrane Risk of Bias Tool version 2. We applied a trial sequential analysis to assess the precision of the combined results. RESULTS: Eight studies (516 participants) were analyzed for sleep quality. Of those, four studies used only a short duration of melatonin, either on the night before and the day of surgery or only on the day of surgery. A random-effects meta-analysis showed that melatonin did not improve sleep quality measured by VAS compared with placebo (mean difference, -0.75 mm; 95% confidence interval, -4.86 to 3.35), with low heterogeneity (I2, 5%). Trial sequential analysis revealed that the accrued information size (n = 516) reached the estimated required information size (n = 295). We downgraded the certainty of the evidence because of the high risk of bias. The effect on postoperative adverse events was comparable between the melatonin and control groups. CONCLUSION: Our results indicate that melatonin supplementation does not improve postoperative sleep quality measured with the VAS compared with placebo in adult patients (GRADE: moderate). STUDY REGISTRATION: PROSPERO (CRD42020180167); registered 27 October 2022.

    DOI: 10.1007/s12630-023-02442-1

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  • Effets de la mélatonine sur la qualité du sommeil postopératoire : une revue systématique, méta-analyse et analyse séquentielle des études 査読

    Akito Tsukinaga, Takahiro Mihara, Teppei Takeshima, Makoto Tomita, Takahisa Goto

    Canadian Journal of Anesthesia/Journal canadien d'anesthésie   2023年3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  

    DOI: 10.1007/s12630-023-02442-1

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    その他リンク: https://link.springer.com/article/10.1007/s12630-023-02442-1/fulltext.html

  • A prospective randomized controlled study to assess the effectiveness of super FIXSORB WAVE® for sternal stabilization after sternotomy 査読

    Kiyotoshi Oishi, Hirokuni Arai, Hidehito Kuroki, Tomoyuki Fujioka, Makoto Tomita, Dai Tasaki, Keiji Oi, Eiki Nagaoka, Tatsuki Fujiwara, Masashi Takeshita, Tomoya Yoshizaki, Takeshi Someya, Tomohiro Mizuno

    General Thoracic and Cardiovascular Surgery   2023年3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  

    DOI: 10.1007/s11748-023-01928-5

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    その他リンク: https://link.springer.com/article/10.1007/s11748-023-01928-5/fulltext.html

  • Effectiveness of acupuncture therapy for the prevention of emergence agitation in children: A systematic review and meta-analysis with trial sequential analysis. 国際誌

    Takahiro Mihara, Daisuke Nakajima, Toshiyuki Hijikata, Makoto Tomita, Takahisa Goto

    PloS one   18 ( 6 )   e0286790   2023年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study aimed to evaluate the effectiveness of acupuncture therapy in preventing emergence agitation (EA) in children. A systematic review and meta-analysis were conducted across multiple locations according to the articles searched. Seven databases, including trial registration sites, were searched. A total of six trials were included involving 489 patients; of them, 244 received acupuncture therapy. Randomized clinical trials (RCTs) evaluating the incidence of EA compared with placebo/sham or standard care in children were included. The primary outcome was the incidence of EA, as evaluated using a specific assessment tool. Data about the incidence rate of EA, heterogeneity, quality of trials and evidence, and adverse events were collected. Additionally, data about patient demographic characteristics, type of anesthesia, duration and onset of acupuncture therapy, EA and pain score, time taken for extubation, and post-anesthesia care unit length of stay were collected. The results indicated that the overall incidence of EA in the acupuncture therapy group and the control group was 23.4% and 39.5%, respectively, with no significant difference (risk ratio, 0.62; 95% confidence interval, 0.26-1.48; I2 = 63%). Subgroup analysis showed a significant difference in the overall incidence of EA in the acupuncture therapy and control groups according to surgery type (high-risk vs. low-risk surgery), suggesting that acupuncture therapy may be effective in reducing EA for patients undergoing high-risk surgery. The quality of evidence was downgraded to "very low" due to the study designs, inconsistency, and possible publication bias. In conclusion, this meta-analysis shows that the currently available RCTs are insufficient to determine the effectiveness of acupuncture therapy in preventing EA in children undergoing general anesthesia.

    DOI: 10.1371/journal.pone.0286790

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  • Add-on effects of oral tocopherol supplementation to surgical varicocelectomy on the outcome of assisted reproductive technology: a single-center pilot study report. 国際誌

    Teppei Takeshima, Takahiro Mihara, Makoto Tomita, Shinnosuke Kuroda, Yasushi Yumura, Hiroe Ueno, Mizuki Yamamoto, Mariko Murase

    Frontiers in reproductive health   5   1325566 - 1325566   2023年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Varicocelectomy is well known to improve the pregnancy outcome of patients with clinical varicoceles in assisted reproductive technologies as well as spontaneous conception. Therefore, this study aimed to evaluate the additional effects of oral antioxidant therapy after varicocelectomy on the pregnancy outcome in the assisted reproductive technology setting. METHODS: This study was a retrospective cohort study. The subjects were couples among whom the male partner had undergone varicocelectomy and was scheduled for subsequent assisted reproductive technology. Pregnancy outcomes were followed retrospectively in 62 couples with male partners who received tocopherol (antioxidant group) and 37 couples who did not (control group). The tocopherol and control groups were assigned dependent on the decision of the physician in charge and the patient's request. The clinical pregnancy rates per couple and embryo transfer, time to pregnancy, and the number of cycles during transfer to pregnancy were evaluated. RESULTS: No significant differences were observed in the pregnancy rate per couple (antioxidant group 70.9% vs. control group 64.9%, P = 0.55) and per embryo transfer (50.4% vs. 39.6%, P = 0.22). Regarding the time to event analyzed by adjusted restricted mean survival time, the mean time to pregnancy was significantly shorter in the antioxidant (tocopherol) group (14.2 vs. 17.4 months, P = 0.025). No significant difference was observed in the embryo transfer cycle to pregnancy (mean embryo transfer cycles: 2.6 vs. 3.0, P = 0.238). CONCLUSIONS: Additional oral tocopherol nicotinate as antioxidant therapy after varicocelectomy was shown to shorten the time to pregnancy. It is recommended that add-on effects be tested in more well-designed randomized controlled trials to examine whether it improves assisted reproductive outcomes.

    DOI: 10.3389/frph.2023.1325566

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  • Effectiveness of acupuncture therapy for preventing emergence agitation in children: A protocol for systematic review and meta-analysis with trial sequential analysis 査読 国際誌

    Daisuke Nakajima, Takahiro Mihara, Toshiyuki Hijikata, Makoto Tomita, Takahisa Goto

    PLOS ONE   17 ( 3 )   e0264197 - e0264197   2022年3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:Public Library of Science (PLoS)  

    Pain, autonomic distress, and emergence agitation occur commonly in children undergoing general anesthesia. While acupuncture therapy has been reported to effectively reduce such pain and autonomic distress in children, its effect in preventing emergence agitation remains unclear. Therefore, we will conduct a systematic review and meta-analysis with trial sequential analysis to evaluate the effect of acupuncture therapy in preventing emergence agitation in children undergoing general anesthesia. Methods and analysis This protocol was prepared according to the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for Protocols guidelines. We will conduct a search for randomized controlled trials that evaluated the effect of acupuncture therapy in preventing emergence agitation. The following databases will be searched for relevant articles: MEDLINE, CENTRAL, Embase, and Web of Science; four pre-registration sites will be accessed from inception to April 1, 2021. No language restrictions will be applied. Two authors will independently scan and select eligible studies, extract the data, and assess the risk of bias. The incidence of emergence agitation will be combined as a risk ratio with a 95% confidence interval using a random-effect model. The I<sup>2</sup> statistics will be used to assess heterogeneity. We will evaluate the quality of the clinical trials using the Cochrane methodology and assess the quality of evidence using the Grading of Recommendation Assessment, Development, and Evaluation approach. If appropriate, a trial sequential analysis will be performed. Expected outcomes This meta-analysis will be the first to evaluate the effect of acupuncture therapy in preventing emergence agitation in children. The findings from this meta-analysis have the potential to reveal pivotal factors that affect the clinical effect of acupuncture therapy, thereby supporting the optimization of acupuncture therapy for emergence agitation.

    Protocol registration University Hospital Medical Information Network Clinical Trials Registry (UMIN000040775).

    DOI: 10.1371/journal.pone.0264197

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  • Three-dimensional MRI shows cartilage defect extension with no separation from the meniscus in women in their 70 s with knee osteoarthritis 査読

    Hisako Katano, Nobutake Ozeki, Hideyuki Koga, Makoto Tomita, Kenji Suzuki, Jun Masumoto, Ichiro Sekiya

    Scientific Reports   12 ( 1 )   2022年3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  

    Abstract

    The positional relationship between cartilage defects and the meniscus is poorly understood for osteoarthritis of the knee. Our purpose was to clarify how cartilage defects extend and their association with the meniscus location during osteoarthritis progression. The subjects were women in their 70 s who were registered in the Kanagawa Knee Study. We obtained 3D MRI images of the tibial surfaces with menisci in subjects with cartilage area ratios &lt; 0.95 and examined the morphological association between cartilage defects and the medial meniscus (MM) by viewing the defects according to the cartilage area ratio at the medial tibial region. Of the 561 Kanagawa Knee Study subjects, 45 were included in the analyses, and 11 had a cartilage area ratio &lt; 0.95 at the medial tibia. Significant differences were observed in the localization of cartilage defects among 9 subregions, with cartilage defects occurring predominantly in the middle external subregion. The inner margin of the MM contacted the cartilage defect in 7 knees and crossed the cartilage defect in 4 knees but was never found separated from the cartilage defect. The cartilage defects occurred from the middle external subregion and extended to the surrounding area without separating from the inner margin of the MM.

    Trial registration UMIN, UMIN000032826; 1 September 2018.

    DOI: 10.1038/s41598-022-08092-5

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    その他リンク: https://www.nature.com/articles/s41598-022-08092-5

  • Comparison of combination therapy of prednisolone and cyclosporine with corticosteroid pulse therapy in Vogt–Koyanagi–Harada disease 査読

    Takashi Ono, Hiroshi Goto, Tsutomu Sakai, Fumihiko Nitta, Nobuhisa Mizuki, Hiroshi Takase, Yutaka Kaneko, Junko Hori, Satoko Nakano, Nobuhisa Nao-I, Nobuyuki Ohguro, Kazunori Miyata, Makoto Tomita, Manabu Mochizuki, Manabu Mochizuki, Takashi Ono, Takashi Komizo, Kazurori Miyata, Hiroshi Goto, Akihiko Umazume, Yoshihiko Usui, Tsutomu Sakai, Hideo Kohno, Ranko Aoyagi, Fumihiko Nitta, Kazuichi Maruyama, Nobuhisa Mizuki, Etsuko Shibuya, Yasutsugu Ida, Hiroshi Takase, Shintaro Horie, Mitsunao Ide, Yuko Iwasaki, Koju Kamoi, Yukiko Terada, Yutaka Kaneko, Junko Hori, Tomoko Yui, Ayaka Takeda, Satoko Nakano, Nobuhisa Nao-I, Nobuyuki Ohguro, Makoto Tomita

    Japanese Journal of Ophthalmology   66 ( 2 )   119 - 129   2022年3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  

    PURPOSE: To compare the efficacy and safety of a combination therapy of prednisolone and cyclosporine and corticosteroid pulse therapy in Vogt-Koyanagi-Harada (VKH) disease. STUDY DESIGN: A prospective, multicenter, randomized, non-inferiority trial. METHODS: Patients of new-onset acute VKH disease at 11 centers in Japan between 2014 and 2018 were randomized to a combination (oral prednisolone 60 mg daily with gradual taper-off to 35 mg/day and cyclosporine 3 mg/kg/day) and corticosteroid (methylprednisolone 1000 mg for 3 days followed by oral prednisolone) groups, and were followed for 1 year. RESULTS: Thirty-four were assigned to the combination and thirty-six patients to the corticosteroid group. Recurrence/worsening risk was 0.15 (95% confidence-interval [CI] 0.03-0.27) in the combination group and 0.25 (95% CI 0.11-0.39) in the corticosteroid group, with a risk difference of - 0.10 (90% CI - 0.27 to 0.06), demonstrating non-inferiority of the combination group with a non-inferiority margin of 0.20 (P = 0.0013). Serious adverse events occurred in three patients (two with hyponatremia and one with severe headaches) in the combination group and none in the corticosteroid group. Sunset glow fundus grades and cataract rates at 1 year were 0.57 (95% CI 0.42-71) and 4.3% in the combination group and 0.91 (95% CI 0.78-1.04) and 34.0% in the corticosteroid group, respectively. CONCLUSIONS: Combination therapy was noninferior to corticosteroid therapy with respect to recurrence/worsening risk. Notably, the recurrence/worsening risk, sunset glow fundus grade, and cataract rate were lower in the combination group than in the corticosteroid group.

    DOI: 10.1007/s10384-021-00878-w

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    その他リンク: https://link.springer.com/article/10.1007/s10384-021-00878-w/fulltext.html

  • Medial Tibial Osteophyte Width Strongly Reflects Medial Meniscus Extrusion Distance and Medial Joint Space Width Moderately Reflects Cartilage Thickness in Knee Radiographs 査読

    Ichiro Sekiya, Sho Sasaki, Yugo Miura, Hayato Aoki, Hisako Katano, Noriya Okanouchi, Makoto Tomita, Jun Masumoto, Hideyuki Koga, Nobutake Ozeki

    Journal of Magnetic Resonance Imaging   2022年1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:Wiley  

    DOI: 10.1002/jmri.28079

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jmri.28079

  • Difference in the joint space of the medial knee compartment between full extension and Rosenberg weight-bearing radiographs. 査読 国際誌

    Yugo Miura, Nobutake Ozeki, Hisako Katano, Hayato Aoki, Noriya Okanouchi, Makoto Tomita, Jun Masumoto, Hideyuki Koga, Ichiro Sekiya

    European radiology   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: Radiographs are the most widespread imaging tool for diagnosing osteoarthritis (OA) of the knee. Our purpose was to determine which of the two factors, medial meniscus extrusion (MME) or cartilage thickness, had a greater effect on the difference in the minimum joint space width (mJSW) at the medial compartment between the extension anteroposterior view (extension view) and the 45° flexion posteroanterior view (Rosenberg view). METHODS: The subjects were 546 participants (more than 50 females and 50 males in their 30 s, 40 s, 50 s, 60 s, and 70 s) in the Kanagawa Knee Study. The mJSW at the medial compartment was measured from both the extension and the Rosenberg views, and the "mJSW difference" was defined as the mJSW in the Rosenberg view subtracted from the mJSW in the extension view. The cartilage region was automatically extracted from MRI data and constructed in three dimensions. The medial region of the femorotibial joint cartilage was divided into 18 subregions, and the cartilage thickness in each subregion was determined. The MME was also measured from MRI data. RESULTS: The mJSW difference and cartilage thickness were significantly correlated at 4 subregions, with 0.248 as the highest absolute value of the correlation coefficient. The mJSW difference and MME were also significantly correlated, with a significantly higher correlation coefficient (0.547) than for the mJSW difference and cartilage thickness. CONCLUSIONS: The MME had a greater effect than cartilage thickness on the difference between the mJSW at the medial compartment in the extension view and in the Rosenberg view. KEY POINTS: • The difference in the width at the medial compartment of the knee between the extension and the flexion radiographic views was more affected by medial meniscus extrusion than by cartilage thickness.

    DOI: 10.1007/s00330-021-08253-6

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  • Effect of melatonin and melatonin agonists on postoperative sleep quality in adult patients: a protocol for systematic review and meta-analysis with trial sequential analysis. 査読 国際誌

    Akito Tsukinaga, Takahiro Mihara, Teppei Takeshima, Makoto Tomita, Takahisa Goto, Takeharu Yamanaka

    BMJ open   11 ( 9 )   e047858   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: The circadian rhythm of melatonin secretion is disturbed after general anaesthesia, leading to postoperative sleep disturbance. Small studies investigating the preventive effect of melatonin administration on postoperative sleep disturbance have not reached any conclusions. Therefore, we will conduct a systematic review and meta-analysis to obtain conclusive results. METHODS AND ANALYSIS: We prepared this protocol following the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines. We will conduct a search for randomised controlled trials that evaluated the effect of melatonin and melatonin agonists on postoperative sleep quality in adult patients undergoing general anaesthesia or regional anaesthesia with sedation. We will exclude patients undergoing regional anaesthesia without sedation. Relevant studies will be searched in the following eight databases: MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science and four preregistration sites from inception to 1 January 2021. No language restrictions will be applied. Two authors will independently scan and select eligible studies and perform data extraction and assessment of the risk of bias. The Visual Analogue Scale scores for sleep quality will be combined as the mean difference with a 95% CI using a random-effect model; we will use I2 to assess heterogeneity. We will evaluate the quality of trials using the Cochrane methodology and assess the quality of evidence using the Grading of Recommendation Assessment, Development and Evaluation approach. If appropriate, trial sequential analysis will be performed. ETHICS AND DISSEMINATION: No ethical approval is required for this meta-analysis, as it does not include individual patient data. We will disseminate the results of this meta-analysis in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020180167.

    DOI: 10.1136/bmjopen-2020-047858

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  • Alterations in cartilage quantification before and after injections of mesenchymal stem cells into osteoarthritic knees. 査読 国際誌

    Ichiro Sekiya, Hisako Katano, Mitsuru Mizuno, Hideyuki Koga, Jun Masumoto, Makoto Tomita, Nobutake Ozeki

    Scientific reports   11 ( 1 )   13832 - 13832   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Several studies have reported improvement in knee pain following mesenchymal stem cell (MSC) injections for knee osteoarthritis (OA). We developed a novel 3D magnetic resonance imaging (MRI) analysis software program that provides "projected cartilage area ratios" for automatic detection of changes in cartilage amounts. The primary objective of this prospective interventional study was to compare alterations in the projected cartilage area ratio (thickness ≥ 1.5 mm) at the femoral posteromedial region between 30 weeks before and 30 weeks after synovial MSC injections. Secondary objectives were to assess the clinical scores and safety of MSC injections. Patients with OA who complained of knee pain underwent autologous synovial MSC injections into the knee at time 0 and again 15 weeks later. MRI examinations were performed at - 30, - 15, - 1, and 30 weeks. Patients showing < 3% decreases in the projected cartilage area ratio (thickness ≥ 1.5 mm) at the femoral the posteromedial region from - 30 weeks to - 15 weeks were excluded from the study. The Lysholm Knee Score, Knee Injury and Osteoarthritis Outcome Scale (KOOS), and Numerical Rating Scale (NRS) scores were evaluated at - 30, - 15, - 5, - 2, 0, 5, 10, 15, 20, 25, and 30 weeks. Five patients were excluded because 3D MRI analysis showed no cartilage loss at - 15 weeks. Ultimately, eight OA patients underwent MSC injections. The projected cartilage area ratio significantly decreased by 0.07 in the 30 weeks before MSC injections (p = 0.01), but no further decreases occurred in the 30 weeks after MSC injections. The projected cartilage area ratio at the femoral posteromedial region showed a significant difference between 30 weeks before and 30 weeks after MSC injections. The Lysholm Knee Score, KOOS, and NRS values improved significantly after the injections. MSC injection could not be ruled out as the cause of two adverse events: transient knee pain and itching in both hands. Fully automatic 3D MRI analysis showed that synovial MSC injections suppressed cartilage loss in patients with progressive OA.Trial registration: Intraarticular injections of synovial stem cells for osteoarthritis of the knee (Number UMIN 000026732). Date of registration; June 1, 2017. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000029967 .

    DOI: 10.1038/s41598-021-93462-8

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  • Interscan measurement error of knee cartilage thickness and projected cartilage area ratio at 9 regions and 45 subregions by fully automatic three-dimensional MRI analysis. 査読 国際誌

    Ichiro Sekiya, Yuji Kohno, Akinobu Hyodo, Hisako Katano, Keiichiro Komori, Hideyuki Koga, Makoto Tomita, Kenji Suzuki, Jun Masumoto, Nobutake Ozeki

    European journal of radiology   139   109700 - 109700   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: We have developed a fully automatic three-dimensional MRI analysis software program for automatic segmentation of knee cartilage using a deep neural network. The purpose of this study was to use this software to clarify the interscan measurement error of the knee cartilage thickness and projected cartilage area ratio at 9 regions and 45 subregions in the knee. METHODS: Ten healthy volunteers underwent MRI twice in the same day. The software provided cartilage thickness and projected cartilage area ratio (thickness ≥ 1.5 mm) at 9 regions and 45 subregions of the knee without any manual correction. The interscan measurement error was calculated at each region and subregion from the data of nine donors, except for one donor who had body motion during the MRI examination. RESULTS: The interscan measurement error of cartilage thickness was less than 0.10 mm at all 9 regions and at 39 subregions among 45 subregions. The measurement errors ranged from 0.03 to 0.21 mm. The intraclass correlation coefficients (ICC) of cartilage thickness were higher than 0.75 at all 9 regions and 41 subregions. The interscan measurement error of the projected cartilage area ratio ranged from 0.01 to 0.03 for all 9 regions. CONCLUSIONS: This study clarified the interscan measurement error of the knee cartilage thickness and projected cartilage area ratio.

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  • Clinical Characteristics, Management, and Factors Associated with Poor Visual Prognosis of Acute Retinal Necrosis. 査読 国際誌

    Hiroshi Takase, Hiroshi Goto, Kenichi Namba, Nobuhisa Mizuki, Annabelle A Okada, Nobuyuki Ohguro, Koh-Hei Sonoda, Makoto Tomita, Hiroshi Keino, Takeshi Kezuka, Reo Kubono, Kazuomi Mizuuchi, Etsuko Shibuya, Hiroyuki Takahashi, Ryoji Yanai, Manabu Mochizuki

    Ocular immunology and inflammation   1 - 6   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Purpose: To identify the clinical characteristics of acute retinal necrosis (ARN) and clarify factors associated with poor visual prognosis. Methods: a nationwide multi-center retrospective chart review study was performed in Japan using data from the medical records of 149 consecutive ARN patients. Demographics, ocular signs, virologic testing of intraocular fluids, and treatment were examined. Factors associated with poor visual prognosis were investigated by regression analysis. Results: At initial presentation, anterior chamber cells or mutton-fat keratic precipitates (97%), unilaterality (93%), and yellow-white retinal lesions (86%) were recognized. In the clinical course, rapid circumferential expansion of retinal lesions (39%), development of retinal break or retinal detachment (55%), and optic atrophy (43%) were recorded. Four variables were identified as associated with poor visual prognosis. Conclusions: The present study identified clinical characteristics and factors associated with poor visual prognosis of ARN.

    DOI: 10.1080/09273948.2020.1789179

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  • Changes in serum KL-6 levels during short-term strict antigen avoidance are associated with the prognosis of patients with fibrotic hypersensitivity pneumonitis caused by avian antigens. 査読 国際誌

    Satoshi Hanzawa, Tomoya Tateishi, Masahiro Ishizuka, Yukihisa Inoue, Takayuki Honda, Tatsuo Kawahara, Makoto Tomita, Yasunari Miyazaki

    Respiratory investigation   2020年7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  

    BACKGROUND: Bird-related hypersensitivity pneumonitis (BRHP) is the most common type of fibrotic hypersensitivity pneumonitis (HP). Antigen avoidance (AA) is a key step in the diagnosis and management of HP, but not all fibrotic HP patients improve through AA. Because of the poor prognosis of fibrotic HP, predictive biomarkers to identify patients showing rapid progression during AA are urgently needed. METHODS: From a retrospective review of the medical records of 1941 patients with interstitial lung disease, 75 cases of fibrotic BRHP confirmed by a provocation test or surgical lung biopsy were identified. To identify potential prognostic markers obtained at or around diagnosis, physiological and serological variables at diagnosis and the relative changes in those variables during strict AA were evaluated. Cox proportional hazards models with log-rank testing were used to compare the associations between these variables and survival. RESULTS: Univariate analyses showed that gender, smoking status, and the relative change in the serum levels of Krebs von den Lungen-6 (KL-6) were associated with prognosis (P = 0.02, 0.04, and 0.02, respectively), but the presence of honeycombing and the forced vital capacity were not associated with survival. The relative change in KL-6 levels (greater than vs. less than a 10% decrease) was significantly associated with survival in a stratified analysis (73.9 vs. 34.9 months; P = 0.04). CONCLUSIONS: The relative change in KL-6 levels is associated with the prognosis of patients with fibrotic BRHP independent of previously identified prognostic biomarkers. This finding could help pulmonologists identify fibrotic BRHP patients that are likely to show rapid progression.

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  • Corrugated Sheet of Unsintered Hydroxyapatite Poly-L-Lactide for Sternal Fixation: A Preclinical Study 査読

    Hidehito Kuroki, Hirokuni Arai, Smith Srisont, Keiji Oi, Makoto Tomita, Tomohiro Mizuno

    Annals of Thoracic and Cardiovascular Surgery   26 ( 1 )   40 - 46   2020年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Editorial Committee of Annals of Thoracic and Cardiovascular Surgery  

    DOI: 10.5761/atcs.oa.19-00250

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  • An open-label, randomized controlled trial of sulfamethoxazole-trimethoprim for Pneumocystis prophylaxis: results of 52-week follow-up. 査読 国際誌

    Masako Utsunomiya, Hiroaki Dobashi, Toshio Odani, Kazuyoshi Saito, Naoto Yokogawa, Kenji Nagasaka, Kenchi Takenaka, Makoto Soejima, Takahiko Sugihara, Hiroyuki Hagiyama, Shinya Hirata, Kazuo Matsui, Yoshinori Nonomura, Masahiro Kondo, Fumihito Suzuki, Yasushi Nawata, Makoto Tomita, Mari Kihara, Waka Yokoyama-Kokuryo, Fumio Hirano, Hayato Yamazaki, Ryoko Sakai, Toshihiro Nanki, Ryuji Koike, Nobuyuki Miyasaka, Masayoshi Harigai

    Rheumatology advances in practice   4 ( 2 )   rkaa029   2020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:Oxford University Press (OUP)  

    Objectives: The aim was to investigate the long-term prophylactic efficacy, drug retention and safety of low-dose sulfamethoxazole-trimethoprim (SMX/TMP) prophylaxis against Pneumocystis pneumonia (PCP). Methods: Adult patients with rheumatic diseases receiving prednisolone ≥0.6 mg/kg/day were randomized into the single-strength group (SS; SMX/TMP 400/80 mg daily), the half-strength group (HS; 200/40 mg daily) or the escalation group (ES; starting at 40/8 mg and increasing incrementally to 200/40 mg daily) and treated for 24 weeks, then observed for 52 weeks. The primary endpoint, the PCP non-incidence rate (non-IR) at week 24, has been reported previously. The secondary endpoints were the PCP non-IR at week 52, treatment discontinuation rate and adverse events. Results: Fifty-eight, 59 and 55 patients in the SS, HS and ES, respectively, received SMX/TMP. PCP did not develop in any of the patients by week 52. The estimated PCP non-IR in patients receiving SMX/TMP 200/40 mg daily (HS and ES) was 96.8-100%. Throughout the 52-week observation period, the overall discontinuation rate was significantly lower in HS than in SS (22.7 vs 47.2%, P = 0.004). The discontinuation rates attributable to adverse events were significantly lower in HS (19.1%, P = 0.007) and ES (20.3%, P = 0.007) than in SS (41.8%). The IRs of adverse events requiring SMX/TMP dose reduction before week 52 differed among the three groups, with a significantly higher IR in SS than in HS or ES (P = 0.007). Conclusion: SMX/TMP 200/40 mg had a high PCP prevention rate and was superior to SMX/TMP 400/80 mg in terms of drug retention and safety. Trial registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000007727.

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  • A cognitive bias in diagnostic reasoning and its remediation by the “2-Dimensional Approach” 査読

    Hisashi Shimozono, Nobutoshi Nawa, Makoto Takahashi, Makoto Tomita, Yujiro Tanaka

    MedEdPublish   9 ( 1 )   123 - 123   2020年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Association for Medical Education in Europe (AMEE)  

    <p>This article was migrated. The article was marked as recommended. BackgroundMisdiagnoses are associated with various cognitive biases, which are difficult to reduce even if physicians think about clinical cases deliberately. We propose a new "2-Dimensional Approach" that combines two perspectives in diagnostic reasoning: organs (brain, heart, lung, intestine/liver, kidney) and systems (metabolic, endocrine, blood/tumor, infection, immune, circulatory, nervous systems). Systems involve throughout the whole body and can be pathogenesis of diseases. As a result of diseases, organs show abnormal vital signs and symptoms. We investigated: (1) whether each individual resident has a bias for either organs or systems when they diagnose clinical cases, and (2) whether the 2D Approach can reduce such a bias.MethodsWe randomly assigned PGY1 residents (n=105) to either the 2D Approach group (n=45) or a control group (n=60). After attending either a lecture on the 2D Approach or a non-related lecture, residents were asked to diagnose two clinical cases. We divided each diagnosis into one of the two categories, either "organs" or "systems". We investigated whether each resident would diagnose the two cases into the same category, either organs or systems (i.e., a bias for either organs or systems).ResultsThe participants in the control group tended to diagnose the two cases into the same category, either organs or systems (OR: 5.63, 95% CI: 1.62-21.7, p=0.0030, Fisher's exact test). In the 2D Approach group, the category of diagnoses for the two cases were not related to each other (OR: 2.14, 95% CI: 0.50-9.81, p=0.33).ConclusionThere is a bias for either organs or systems when residents diagnose clinical cases, suggesting that organs and systems are different perspectives in diagnostic reasoning. By combining these 2 different perspectives in a 2-dimensional matrix, the 2D Approach reduces this bias.</p>

    DOI: 10.15694/mep.2020.000123.1

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  • Serum CXCL9 and CCL17 as biomarkers of declining pulmonary function in chronic bird-related hypersensitivity pneumonitis. 査読 国際誌

    Yoshihisa Nukui, Takashi Yamana, Masahiro Masuo, Tomoya Tateishi, Mitsuhiro Kishino, Ukihide Tateishi, Makoto Tomita, Takehiro Hasegawa, Takashi Aritsu, Yasunari Miyazaki

    PLoS One   14 ( 8 )   e0220462   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0220462

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  • ``The 2-Dimensional Approach": a novel tool to help learners organize their knowledge and improve their clinical reasoning skills. 査読

    Hisashi Shimozono, Makoto Takahashi, Makoto Tomita, Kazuki Takada, Yujiro Tanaka

    MedEdPublish   8 ( 3 )   In press - 134   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.15694/mep.2019.000134.1

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  • Comparison of Rigid and Soft-Brace Treatments for Acute Osteoporotic Vertebral Compression Fracture: A Prospective, Randomized, Multicenter Study. 査読 国際誌

    Kato T, Inose H, Ichimura S, Tokuhashi Y, Nakamura H, Hoshino M, Togawa D, Hirano T, Haro H, Ohba T, Tsuji T, Sato K, Sasao Y, Takahata M, Otani K, Momoshima S, Tateishi U, Tomita M, Takemasa R, Yuasa M, Hirai T, Yoshii T, Okawa A

    Journal of clinical medicine   8 ( 2 )   2019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)  

    DOI: 10.3390/jcm8020198

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  • Effects of propofol versus sevoflurane on cerebral circulation time in patients undergoing coiling for cerebral artery aneurysm: a prospective randomized crossover study. 査読

    Ishibashi T, Toyama S, Miki K, Karakama J, Yoshino Y, Ishibashi S, Tomita M, Nemoto S

    Journal of clinical monitoring and computing   2019年1月

  • Projected Cartilage Area Ratio Determined by 3-Dimensional MRI Analysis 査読

    Akinobu Hyodo, Nobutake Ozeki, Yuji Kohno, So Suzuki, Mitsuru Mizuno, Koji Otabe, Hisako Katano, Makoto Tomita, Yusuke Nakagawa, Hideyuki Koga, Shinji Kiuchi, Kenji Suzuki, Yoshinori Itai, Jun Masumoto, Ichiro Sekiya

    JBJS Open Access   4 ( 4 )   e0010 - e0010   2019年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Ovid Technologies (Wolters Kluwer Health)  

    DOI: 10.2106/jbjs.oa.19.00010

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  • Diabetic Retinopathy as a Risk Factor Associated with the Development of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease. 査読 国際誌

    Seishin Azuma, Yasuhiro Asahina, Sei Kakinuma, Keiko Azuma, Masato Miyoshi, Emi Inoue, Tomoyuki Tsunoda, Ayako Sato, Shun Kaneko, Hiroko Nagata, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Makoto Tomita, Mina Nakagawa, Mamoru Watanabe

    Digestive diseases (Basel, Switzerland)   37 ( 3 )   247 - 254   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The risk factors associated with the development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD) are still unclear. The aim of the present study was to identify such risk factors in NAFLD patients who developed HCC. METHODS: Between April 2000 and -December 2016, a total of 182 patients with NAFLD were enrolled in this study; of these, only 22 patients had HCC. To identify risk factors, univariate and multivariate analyses were performed. To identify risk factors other than the degree of fibrosis, propensity matched analysis adjusted by the NAFLD fibrosis score (NFS) was carried out on 44 patients. Multivariate and survival analyses were also performed in HCC patients. RESULTS: In 182 patients, multivariate analysis highlighted the NFS (OR 2.275; p < 0.001) and hypertension (OR 5.868; p = 0.037) as independent factors that were significantly associated with the development of HCC. After adjustment for the NFS, multivariate analysis identified diabetic retinopathy (OR 8.654; p = 0.017) as an independent factor that was significantly associated with the development of HCC. For predicting the development of HCC, the area under the receiver operating characteristic curve of diabetic retinopathy was significantly higher than that of diabetes (0.731 vs. 0.615; p < 0.001). In patients with HCC, multivariate analysis indicated that the NFS were significantly associated with diabetic retinopathy. CONCLUSIONS: Diabetic retinopathy as well as liver fibrosis is a risk factor that associates with the development of HCC in NAFLD patients. Therefore, NAFLD patients with diabetic retinopathy should undergo careful screening for HCC.

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  • Trends in isolated meniscus repair and meniscectomy in Japan, 2011–2016 査読

    Hisako Katano, Hideyuki Koga, Nobutake Ozeki, Koji Otabe, Mitsuru Mizuno, Makoto Tomita, Takeshi Muneta, Ichiro Sekiya

    Journal of Orthopaedic Science   23 ( 4 )   676 - 681   2018年7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  

    Background: Meniscus surgery is the most commonly performed orthopedic surgery, and despite recent emphasis on saving the meniscus, the current status of meniscus surgeries is little known in many countries, including Japan. The National Database of Health Insurance Claims and Specific Health Checkups of Japan and the Statistics of Medical Care Activities in Public Health Insurance track meniscus surgeries through health insurance claims. The National Database provides the numbers for 2014 and 2015, and the Statistics of Medical Care Activities provides the numbers from June 2011 to June 2016. Our aim was to analyze isolated meniscus surgery numbers and meniscus repair ratios by age group based on the National Database and evaluate trends of meniscus repair ratios for the latest six years from the Statistics of Medical Care Activities. Methods: Meniscus surgeries by age group were counted from the National Database for 2014–2015, and meniscus repair ratios (meniscus repairs/meniscus surgeries) were calculated. The numbers were also counted from the Statistics of Medical Care Activities in 2011–2016. For statistical analysis of annual trends of meniscus repair ratios, the Cochran–Armitage trend test was used. Meniscus surgeries with concomitant knee ligament surgeries were excluded. Results: According to the National Database, isolated meniscus surgeries totaled 34,966 in 2015, with peak ages of patients in their late teens and 60s. The meniscus repair ratio was 19% in 2014 and 24% in 2015. According to the Statistics of Medical Care Activities, the meniscus repair ratio was 9% in 2011 and significantly increased to 25% in 2016 (p = 0.0008). The ratio also increased significantly in each age group between the early 20s and late 70s. Conclusions: Approximately 35,000 meniscus surgeries are performed in Japan annually, with peak ages in the late teens and 60s. The number of meniscus repairs has increased over the past six years.

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  • A diagnostic decision tree for adult cerebellar ataxia based on pontine magnetic resonance imaging 査読

    Miwa Higashi, Kokoro Ozaki, Takaaki Hattori, Takashi Ishii, Kazumasa Soga, Nozomu Sato, Makoto Tomita, Hidehiro Mizusawa, Kinya Ishikawa, Takanori Yokota

    Journal of the Neurological Sciences   387   187 - 195   2018年4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 B.V.  

    Cerebellar ataxias (CAs) are heterogeneous conditions often require differential diagnosis. This study aimed to establish a diagnostic decision tree for differentiating CAs based on pontine MRI findings. Two-hundred and two consecutive ataxia patients were clinically classified into 4 groups: (1) spinocerebellar ataxia (SCA) with brainstem involvement (SCA-BSI), (2) Pure cerebellar SCA, (3) cerebellar dominant multiple system atrophy (MSA-c), and (4) Other CA. Signal intensity in pons was graded into 3 types: hot cross bun sign (HCBS), pontine midline linear T2-hyperintensity (PMH), or normal. The distance ratio of pontine base to tegmentum, named “BT-ratio”, was measured. The presence of HCBS indicated either MSA-c with a specificity of 97.7%, or SCA2. When PMH was observed, a BT-ratio above 3.54 strongly indicated SCA-BSI, namely Machado-Joseph disease, SCA1, or dentatorubral-pallidoluysian atrophy, whereas a BT-ratio below 3.54 indicated MSA-c or SCA2. When the signal intensity was normal, a BT-ratio above 3.52 indicated SCA-BSI, whereas a BT-ratio below 3.52 suggested Pure cerebellar SCA or Other CA with pure cerebellar type. The decision tree was confirmed useful in a different 30 CA patients. We propose that differential diagnosis of CAs can be supported by combining pontine MRI signal intensity changes and BT-ratio.

    DOI: 10.1016/j.jns.2018.02.022

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  • Environmental levels of avian antigen are relevant to the progression of chronic hypersensitivity pneumonitis during antigen avoidance: 査読

    Manabu Sema, Yasunari Miyazaki, Toshiharu Tsutsui, Makoto Tomita, Yoshinobu Eishi, Naohiko Inase

    Immunity Inflammation and Disease   6 ( 1 )   154 - 162   2018年3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:Wiley-Blackwell  

    Background: In chronic hypersensitivity pneumonitis (chronic HP), antigen avoidance is critical for disease management
    however, complete avoidance is difficult because of unrecognized exposure to antigens. Recently, we revealed that the amount of avian antigen (AAA) in household dust at the time of diagnosis predicted the progression of chronic bird-related HP. The purpose of this study is to evaluate the relationship between the prognosis of chronic bird-related HP and the AAA that remained in the environment during antigen avoidance. Methods: First, we measured the AAA in household dust of 28 consecutive patients (22 with chronic bird-related HP and 6 with acute bird-related HP) and 12 healthy volunteers. Second, we measured the AAA and collected questionnaires on the environmental conditions of the homes of 53 patients with various lung diseases, including bird-related HP, to investigate the environmental parameters related to a higher AAA. Finally, we prospectively recruited 14 consecutive patients with chronic bird-related HP, measured the AAA periodically, and collected clinical data. Results: The AAA was higher in patients with chronic bird-related HP at the time of diagnosis compared to healthy volunteers and was highest in patients with acute bird-related HP. Logistic regression analysis showed that birds frequenting a residence was the only significant factor for a higher AAA (odds ratio, 5.686
    95%CI, 1.263-25.59
    P = 0.024). There was a correlation between the mean AAA and decline of vital capacity for 1 year (r = -0.55
    95%CI -0.84 to -0.01
    P = 0.043). Conclusion: Measurements of the AAA after diagnosis predict the progression of chronic bird-related HP. Avian antigen can exist in the indoor environment regardless of antigen avoidance. The presence of avian antigen in the indoor environment can be attributed to wild birds found outdoors.

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  • Overexpression of exchange protein directly activated by cAMP-1 (EPAC1) attenuates bladder cancer cell migration 査読

    Hirona Ichikawa, Momoe Itsumi, Shunichi Kajioka, Tomoko Maki, Ken Lee, Makoto Tomita, Shoji Yamaoka

    Biochemical and Biophysical Research Communications   495 ( 1 )   64 - 70   2018年1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 B.V.  

    Exchange protein directly activated by cAMP (EPAC) is a mediator of a cAMP signaling pathway that is independent of protein kinase A. EPAC has two isoforms (EPAC1 and EPAC2) and is a cAMP-dependent guanine nucleotide exchange factor for the small GTPases, Rap1 and Rap2. Recent studies suggest that EPAC1 has both positive and negative influences on cancer and is involved in cell proliferation, apoptosis, migration and metastasis. We report that EPAC1 and EPAC2 expression levels were significantly lower in bladder cancer tissue than in normal bladder tissue. In addition, bladder cancer cell lines showed reduced EPAC1 mRNA expression. Furthermore, EPAC1 overexpression in bladder cancer cell lines induced morphologic changes and markedly suppressed cell migration without affecting cell viability. The overexpressed EPAC1 preferentially localized at cell-cell interfaces. In conclusion, reduced EPAC1 expression in bladder tumors and poor migration of EPAC1-overexpressing cells implicate EPAC1 as an inhibitor of bladder cancer cell migration.

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  • EDITORIAL: SPECIAL FEATURE ON THE 30TH ANNIVERSARY OF JSCS 査読

    Tomita Makoto

    JOURNAL JAPANESE SOCIETY OF COMPUTATIONAL STATISTICS   30 ( 2 )   35   2018年

  • Characteristics of higher-order aberrations and anterior segment tomography in patients with pathologic myopia 査読

    Kaori Kasahara, Naoyuki Maeda, Takashi Fujikado, Makoto Tomita, Muka Moriyama, Mutsumi Fuchihata, Kyoko Ohno-Matsui

    INTERNATIONAL OPHTHALMOLOGY   37 ( 6 )   1279 - 1288   2017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  

    To investigate prospectively the characteristics in the higher-order aberrations and anterior segment tomography in patients with pathologic myopia.
    One hundred and twelve consecutive highly myopic patients (mean age 43.4 +/- 9.3 years, spherical equivalent of refractive error &gt;= 8 D and an axial length &gt;= 26.5 mm) were studied. Thirty-seven emmetropic individuals (mean age 37.0 +/- 14.5 years, spherical equivalent of refractive error &lt;=+/- 1 D) were analyzed as controls. The ocular and cornea higher-order aberrations were measured using a Hartmann-Shack wavefront sensor (KR-1W; Topcon Corporation, Tokyo, Japan). The crystalline lens rise, the angle-to-angle, and the white-to-white values were measured using anterior segment OCT (SS-1000; Tomey Corporation, Nagoya, Japan). The mean curvature of the anterior corneal surface, the thickness at the thinnest central corneal point, the location of the central corneal point, the corneal volume, the anterior chamber volume, and the anterior chamber depth were measured using the Pentacam HR (Oculus, Inc., Wetzlar, Germany).
    The ocular total higher-order aberration for 4-mm pupil, the ocular spherical aberrations, and internal spherical aberration for 6-mm pupil were significantly higher in highly myopic eyes than in the emmetropic controls. The crystalline lens rise was significantly smaller in highly myopic eyes than in the emmetropic controls. The anterior chamber depth and the anterior chamber volume were significantly larger in highly myopic eyes than in the emmetropic controls.
    Highly myopic eyes had higher-order aberrations than emmetropic eyes because of the increasing internal aberrations.

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  • Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C 査読

    Hiroko Nagata, Ochanomizu Liver Conference Study Group, Mina Nakagawa, Yasuhiro Asahina, Ayako Sato, Yu Asano, Tomoyuki Tsunoda, Masato Miyoshi, Shun Kaneko, Satoshi Otani, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Toshihiko Nouchi, Hideki Sakai, Makoto Tomita, Mamoru Watanabe

    Journal of Hepatology   67 ( 5 )   933 - 939   2017年11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 B.V.  

    Background and Aims Although treatment for hepatitis C virus has been dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment. Methods A restrospective review of a prospective database of 1,897 CHC patients who were treated with IFN-based (1,145) or IFN-free therapies (752) was carried out. Cumulative HCC occurrence and recurrence rates were compared using propensity score-matched analysis. Predictors of HCC development after viral eradication were identified by multivariate analysis. Results Propensity score-matched analysis showed no significant difference in HCC occurrence (p = 0.49) and recurrence rates (p = 0.54) between groups treated with IFN-based or IFN-free therapies. In multivariate analysis, higher levels of post-treatment α-fetoprotein (AFP) or Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+M2BP) were independently associated with HCC occurrence and recurrence after viral eradication. Only post-treatment WFA+M2BP level was significantly associated with HCC occurrence and recurrence among patients without severe fibrosis. The area under the receiver operating characteristic (ROC) curve for WFA+M2BP levels was greater than that for AFP levels in ROC analysis. Conclusion The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy. Patients with high WFA+M2BP levels after antiviral treatment, even without severe fibrosis, must be followed up carefully for HCC development. Lay summary: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy.

    DOI: 10.1016/j.jhep.2017.05.028

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  • Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C 査読

    Hiroko Nagata, Mina Nakagawa, Yasuhiro Asahina, Ayako Sato, Yu Asano, Tomoyuki Tsunoda, Masato Miyoshi, Shun Kaneko, Satoshi Otani, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Toshihiko Nouchi, Hideki Sakai, Makoto Tomita, Mamoru Watanabe

    JOURNAL OF HEPATOLOGY   67 ( 5 )   933 - 939   2017年11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 SCIENCE BV  

    Background and Aims: Although treatment for hepatitis C virus has been dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment.
    Methods: A restrospective review of a prospective database of 1,897 CHC patients who were treated with IFN-based (1,145) or IFN-free therapies (752) was carried out. Cumulative HCC occurrence and recurrence rates were compared using propensity score-matched analysis. Predictors of HCC development after viral eradication were identified by multivariate analysis.
    Results: Propensity score-matched analysis showed no significant difference in HCC occurrence (p = 0.49) and recurrence rates (p = 0.54) between groups treated with IFN-based or IFN-free therapies. In multivariate analysis, higher levels of post-treatment alpha-fetoprotein (AFP) or Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA(+)M2BP) were independently associated with HCC occurrence and recurrence after viral eradication. Only post-treatment WFA(+)M2BP level was significantly associated with HCC occurrence and recurrence among patients without severe fibrosis. The area under the receiver operating characteristic (ROC) curve for WFA(+)M2BP levels was greater than that for AFP levels in ROC analysis.
    Conclusion: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFNfree therapies. Post-treatment levels of WFA(+)M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy. Patients with high WFA(+)M2BP levels after antiviral treatment, even without severe fibrosis, must be followed up carefully for HCC development.
    Lay summary: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFNfree therapies. Post-treatment levels of WFA(+)M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFNfree therapy. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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  • Optimal Regimens of Sulfamethoxazole-Trimethoprim for Chemoprophylaxis of Pneumocystis Pneumonia in Patients with Systemic Rheumatic Diseases: 52-Week Follow-up of a Non-Blinded, Randomized Controlled Trial 査読

    Masako Utsunomiya, Hiroaki Dobashi, Toshio Odani, Kazuyoshi Saito, Naoto Yokogawa, Kenji Nagasaka, Kenchi Takenaka, Makoto Soejima, Takahiko Sugihara, Hiroyuki Hagiyama, Shinya Hirata, Kazuo Matsui, Yoshinori Nonomura, Masahiro Kondo, Fumihito Suzuki, Makoto Tomita, Mari Kihara, Waka Yokoyama, Fumio Hirano, Hayato Yamazaki, Ryoko Sakai, Toshihiro Nanki, Ryuji Koike, Hitoshi Kohsaka, Nobuyuki Miyasaka, Masayoshi Harigai

    ARTHRITIS & RHEUMATOLOGY   69   2017年10月

  • Open-chest versus closed-chest cardiopulmonary resuscitation in blunt trauma: analysis of a nationwide trauma registry 査読

    Akira Endo, Atsushi Shiraishi, Yasuhiro Otomo, Makoto Tomita, Hiroki Matsui, Kiyoshi Murata

    CRITICAL CARE   21   2017年7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:BIOMED CENTRAL LTD  

    Background: Although open-chest cardiopulmonary resuscitation (OCCPR) is often considered as the last salvage maneuver in critically injured patients, evidence on the effectiveness of OCCPR has been based only on the descriptive studies of limited numbers of cases or expert opinions. This study aimed to compare the effectiveness of OCCPR with that of closed-chest cardiopulmonary resuscitation (CCCPR) in an emergency department (ED).
    Methods: A nationwide registry-based, retrospective cohort study was conducted. Patients with blunt trauma, undergoing cardiopulmonary resuscitation (CPR) in an ED between 2004 and 2015 were identified and divided into OCCPR and CCCPR groups. Their outcomes (survival to hospital discharge and survival over 24 hours following ED arrival) were compared with propensity score matching analysis and instrumental variable analysis.
    Results: A total of 6510 patients (OCCPR, 2192; CCCPR, 4318) were analyzed. The in-hospital and 24-hour survival rates in OCCPR patients were 1.8% (40/2192) and 5.6% (123/2192), and those in CCCPR patients were 3.6% (156/4318) and 9.6% (416/4318), respectively. In the propensity score-matched subjects, OCCPR patients (n = 1804) had significantly lower odds of survival to hospital discharge (odds ratio (95% CI)) = 0.41 (0.25-0.68)) and of survival over 24 hours following ED arrival (OR (95% CI) = 0.59 (0.45-0.79)) than CCCPR patients (n = 1804). Subgroup analysis revealed that OCCPR was associated with a poorer outcome compared to CCCPR in patients with severe pelvis and lower extremity injury.
    Conclusions: In this large cohort, OCCPR was associated with reduced in-hospital and 24-hour survival rates in patients with blunt trauma. Further comparisons between OCCPR and CCCPR using additional information, such as time course details in pre-hospital and ED settings, anatomical details regarding region of injury, and neurological outcomes, are necessary.

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  • Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study 査読

    Kazuo Takiguchi, Akihito Uezato, Michio Itasaka, Hidenori Atsuta, Kenji Narushima, Naoki Yamamoto, Akeo Kurumaji, Makoto Tomita, Kazunari Oshima, Kosaku Shoda, Mai Tamaru, Masahito Nakataki, Mitsutoshi Okazaki, Sayuri Ishiwata, Yasuyoshi Ishiwata, Masato Yasuhara, Kunimasa Arima, Tetsuro Ohmori, Toru Nishikawa

    BMC PSYCHIATRY   17 ( 1 )   249   2017年7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:BIOMED CENTRAL LTD  

    Background: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs.
    Methods: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales.
    Results: D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower.
    Conclusion: It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity.

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  • Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery-associated acute kidney injury: A multicenter randomized controlled trial 査読

    Chieko Mitaka, Tetsu Ohnuma, Takanori Murayama, Fumio Kunimoto, Michio Nagashima, Tetsuhiro Takei, Naoya Iguchi, Makoto Tomita

    JOURNAL OF CRITICAL CARE   38   253 - 258   2017年4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:W B SAUNDERS CO-ELSEVIER INC  

    Purpose: To evaluate the effects of atrial natriuretic peptide (ANP) on renal function and medical costs in patients with acute kidney injury (AKI) associated with cardiac surgery.
    Materials and methods: The Japanese trial for AKI in Post-cardiovascular surgery patients by ANP (JAPAN) was a prospective, multicenter, randomized, double-blind, placebo-controlled study conducted in 11 hospitals in Japan. Acute kidney injury was defined as an increase in serum creatinine of at least 0.3 mg/dL within 48 hours. The patients were randomly assigned to receive ANP (0.02 mu g kg(-1) min(-1)) or placebo. The primary end point was a change in renal function. The secondary end points were a need for renal replacement therapy, the lengths of intensive care unit and hospital stays, and medical costs incurred over the 90-day follow-up.
    Results: Of the 77 randomized patients, 37 were in the ANP group and 40 were in the placebo group. Although ANP significantly (P = .018) increased urine output, it did not significantly improve renal function compared with placebo. There were no significant differences between the groups in the renal replacement therapy rate, the lengths of the intensive care unit and hospital stays, or medical costs.
    Conclusion: Atrial natriuretic peptide infusion did not show a renoprotective effect or cost-saving effect in the treatment of cardiac surgery-associated AKI. (C) 2016 The Authors. Published by Elsevier Inc.

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  • Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: Results from a non-blinded, randomized controlled trial 査読 国際誌

    Masako Utsunomiya, Hiroaki Dobashi, Toshio Odani, Kazuyoshi Saito, Naoto Yokogawa, Kenji Nagasaka, Kenchi Takenaka, Makoto Soejima, Takahiko Sugihara, Hiroyuki Hagiyama, Shinya Hirata, Kazuo Matsui, Yoshinori Nonomura, Masahiro Kondo, Fumihito Suzuki, Makoto Tomita, Mari Kihara, Waka Yokoyama, Fumio Hirano, Hayato Yamazaki, Ryoko Sakai, Toshihiro Nanki, Ryuji Koike, Hitoshi Kohsaka, Nobuyuki Miyasaka, Masayoshi Harigai

    Arthritis Research and Therapy   19 ( 1 )   7 - 7   2017年1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:BIOMED CENTRAL LTD  

    © 2017 The Author(s). Background: Sulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PJP) in immunosuppressed patients with systemic rheumatic diseases, but is sometimes discontinued due to adverse events (AEs). The objective of this non-blinded, randomized, 52-week non-inferiority trial was to quest an effective chemoprophylaxis regimen for PJP with a low drug discontinuation rate. Results at week 24 were reported. Methods: Adult patients with systemic rheumatic diseases who started prednisolone ≥0.6 mg/kg/day were randomized into three dosage groups: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, increasing incrementally to 200/40 mg daily). The primary endpoint was non-incidence rates (non-IR) of PJP at week 24. Results: Of 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP. A total of 172 patients were included in the analysis. No cases of PJP were reported up to week 24. Estimated non-IR of PJP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8-100% using the exact confidence interval as a post-hoc analysis. The overall discontinuation rate was significantly lower with HS compared to SS (p = 0.007). The discontinuation rates due to AEs were significantly lower with HS (p = 0.006) and ES (p = 0.004) compared to SS. The IR of AEs requiring reduction in the dose of SMX/TMP (p = 0.009) and AEs of special interest (p = 0.003) were different among the three groups with significantly higher IR in SS compared to HS and ES. Conclusions: Although there were no PJP cases, the combined group of HS and ES had an excellent estimated non-IR of PJP and both were superior in safety to SS. From the perspective of feasibility and drug discontinuation rates, the daily half-strength regimen was suggested to be optimal for prophylaxis of PJP in patients with systemic rheumatic diseases. Trial registration: The University Hospital Medical Information Network Clinical Trials Registry number is UMIN000007727, registered 10 April 2012.

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  • Screening tests for predicting the prognosis of oral intake in elderly patients with acute pneumonia

    Shoko Oba, Haruka Tohara, Ayako Nakane, Makoto Tomita, Shunsuke Minakuchi, Hiroshi Uematsu

    Odontology   105 ( 1 )   96 - 102   2017年1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 Tokyo  

    Many elderly patients with pneumonia have aspiration pneumonia. Therefore they must temporarily abstain from oral intake. However, it is difficult to predict whether or not they will be able to start oral intake. The reason is the standard method to evaluate deglutition about pneumonia patients has not been established. In this study we aimed to develop a simple and convenient method that predicts the prognosis of oral intake as nutrition among elderly patients with acute stage pneumonia. Participants were 77 inpatients fasting due to aspiration risk with acute pneumonia. (86.0 ± 7.7 years
    range 68–105 years
    men: n = 34, women: n = 43) during September 2011 and August 2013. Their consciousness levels were determined by Glasgow coma scale (GCS) and swallowing function and cough reflex were evaluated by repetitive saliva swallowing test (RSST), modified water swallow test, simple swallowing provocation test and cough test. Oral intake status at discharge was considered as the objective variable, and these tests were considered as explanatory variables. Then receiver operating characteristic (ROC) curve and the area under the curve (AUC) for each was done. From the ROC curve analysis, GCS ≥14 had the largest AUC (0.79) with a sensitivity and specificity of 0.71 and 0.80. That was followed by RSST ≥1, AUC (0.77) with a sensitivity and specificity of 0.81 and 0.67. These results suggest that GCS and RSST could be useful screening tests for prognostic prediction of oral intake capability in elderly patients with acute pneumonia.

    DOI: 10.1007/s10266-016-0238-5

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  • Screening tests for predicting the prognosis of oral intake in elderly patients with acute pneumonia 査読

    Shoko Oba, Haruka Tohara, Ayako Nakane, Makoto Tomita, Shunsuke Minakuchi, Hiroshi Uematsu

    ODONTOLOGY   105 ( 1 )   96 - 102   2017年1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  

    Many elderly patients with pneumonia have aspiration pneumonia. Therefore they must temporarily abstain from oral intake. However, it is difficult to predict whether or not they will be able to start oral intake. The reason is the standard method to evaluate deglutition about pneumonia patients has not been established. In this study we aimed to develop a simple and convenient method that predicts the prognosis of oral intake as nutrition among elderly patients with acute stage pneumonia. Participants were 77 inpatients fasting due to aspiration risk with acute pneumonia. (86.0 +/- 7.7 years; range 68-105 years; men: n = 34, women: n = 43) during September 2011 and August 2013. Their consciousness levels were determined by Glasgow coma scale (GCS) and swallowing function and cough reflex were evaluated by repetitive saliva swallowing test (RSST), modified water swallow test, simple swallowing provocation test and cough test. Oral intake status at discharge was considered as the objective variable, and these tests were considered as explanatory variables. Then receiver operating characteristic (ROC) curve and the area under the curve (AUC) for each was done. From the ROC curve analysis, GCS ae&lt;yen&gt;14 had the largest AUC (0.79) with a sensitivity and specificity of 0.71 and 0.80. That was followed by RSST ae&lt;yen&gt;1, AUC (0.77) with a sensitivity and specificity of 0.81 and 0.67. These results suggest that GCS and RSST could be useful screening tests for prognostic prediction of oral intake capability in elderly patients with acute pneumonia.

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  • Strenuous running exacerbates knee cartilage erosion induced by low amount of mono-iodoacetate in rats 査読

    Ryusuke Saito, Takeshi Muneta, Nobutake Ozeki, Yusuke Nakagawa, Mio Udo, Katsuaki Yanagisawa, Kunikazu Tsuji, Makoto Tomita, Hideyuki Koga, Ichiro Sekiya

    BMC MUSCULOSKELETAL DISORDERS   18   2017年1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:BIOMED CENTRAL LTD  

    Background: It is still debated whether strenuous running in the inflammatory phase produces beneficial or harmful effect in rat knees. We examined (1) the dropout rate of rats during a 30-km running protocol, (2) influences of strenuous running and/or low amounts of mono-iodoacetate injection on cartilage, and (3) the effect of strenuous running on synovitis.
    Methods: Rats were forced to run 30 km over 6 weeks and the dropout rate was examined. One week after 0.1 mg mono-iodoacetate was injected into the right knee, rats were forced to run either 15 km or not run at all over 3 weeks, after which knee cartilage was evaluated. Synovium at the infrapatellar fat pad was also examined histologically.
    Results: Even though all 12 rats run up to 15 km, only 6 rats completed 30 km of running. Macroscopically, 0.1 mg mono-iodoacetate induced erosion at the tibial cartilage irrespective of 15 km of running. Histologically, 0.1 mg mono-iodoacetate induced loss of cartilage matrix in the tibial cartilage, and an additional 15 km of strenuous running significantly exacerbated the loss. Synovitis caused by mono-iodoacetate improved after running.
    Conclusions: Only 50% of rats completed 30 km of running because of foot problems. Strenuous running further exacerbated tibial cartilage erosion but did not influence synovitis induced by mono-iodoacetate.

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  • Effect of two desensitizing agents on dentin permeability in vitro 査読

    Hiroshi Ishihata, Masafumi Kanehira, Werner J. Finger, Hidekazu Takahashi, Makoto Tomita, Keiichi Sasaki

    JOURNAL OF APPLIED ORAL SCIENCE   25 ( 1 )   34 - 41   2017年1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:UNIV SAO PAULO FAC ODONTOLOGIA BAURU  

    Objective: The aim of this in vitro study was to investigate the effect of two desensitizing agents and water on hydraulic conductance in human dentin. Material and Methods: GLUMA Desensitizer PowerGel (GLU) contains glutaraldehyde (GA) and 2-hydroxyethyl methacrylate (HEMA), and Teethmate Desensitizer (TD) is a powder comprising tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) that is mixed with water. Deionized water was used as a negative control (CTR). Thirty discs with a thickness of 1.2 mm were cut from the coronal dentin of the third molars and cleaned with 0.5 M EDTA (pH 7.4). After being mounted in a split-chamber device, the discs were pressurized with water at 1 kPa and 3 kPa in order to measure flow rates with a highly sensitive micro-flow sensor and to calculate hydraulic conductance as a baseline value (BL). Following the application of GLU, TD, and CTR (n=10), hydraulic conductance was remeasured with intermittent storage in water after 15 min, 1 d, 1 w, and 1 m. Reduction in permeability (PR%) was calculated from hydraulic conductance. Data were statistically analyzed using nonparametric methods (alpha&lt;0.05). Representative discs were inspected by SEM. Results: PR% for GLU and TD were 30-50% 15 min and 1 m after their application. Post hoc tests indicated that PR% of CTR was significantly greater than those of GLU and TD at all time points tested. The PR% of GLU and TD were not significantly different. SEM examinations showed noncollapsed collagen meshes at the tubular entrances after GLU, and crystalline precipitates occluding the tubular orifices after TD, whereas CTR specimens showed typical patterns of etched dentin. Conclusions: The present study on hydraulic conductance in dentin discs treated with two chemically different desensitizing agents and water as a control demonstrated that both products may be characterized as effective.

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  • 東京都西多摩地域における扁桃周囲膿瘍症例の検討 査読

    高橋 亮介, 有泉 陽介, 岸根 有美, 冨田 誠, 小田 智三

    日本耳鼻咽喉科学会会   120 ( 6 )   817 - 824   2017年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3950/jibiinkoka.120.817

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  • High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma 査読

    Hiroki Akiyama, Hiroshi Takase, Fumito Kubo, Tohru Miki, Masahide Yamamoto, Makoto Tomita, Manabu Mochizuki, Osamu Miura, Ayako Arai

    Cancer Science   107 ( 10 )   1458 - 1464   2016年10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:Blackwell Publishing Ltd  

    In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m2) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0–82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7–67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).

    DOI: 10.1111/cas.13012

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  • High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma 査読

    Hiroki Akiyama, Hiroshi Takase, Fumito Kubo, Tohru Miki, Masahide Yamamoto, Makoto Tomita, Manabu Mochizuki, Osamu Miura, Ayako Arai

    CANCER SCIENCE   107 ( 10 )   1458 - 1464   2016年10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:WILEY-BLACKWELL  

    In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naive PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m(2)) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).

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  • Dose-reduction gemcitabine and S1 combination therapy in over 70 years old patients with unresectable pancreatic cancer 査読

    Shinya Ooka, Naoaki Dan, Osamu Noguchi, Toshihiko Nouchi, Yoshinori Sakai, Takahiro Kawamura, Hiroyuki Sakashita, Makoto Tomita, Satoshi Miyake, Mamoru Watanabe

    ANNALS OF ONCOLOGY   27   2016年7月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

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  • Hematopoietic stem cell transplantation for adults with EBV-positive T- or NK-cell lymphoproliferative disorders: efficacy and predictive markers 査読

    A. Arai, C. Sakashita, C. Hirose, K-I Imadome, M. Yamamoto, M. Jinta, S. Fujiwara, M. Tomita, N. Shimizu, T. Morio, O. Miura

    BONE MARROW TRANSPLANTATION   51 ( 6 )   879 - 882   2016年6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:NATURE PUBLISHING GROUP  

    DOI: 10.1038/bmt.2016.3

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  • Polymyxin B hemoperfusion prevents acute kidney injury in sepsis model 査読

    Chieko Mitaka, Takahiro Masuda, Koji Kido, Tokujiro Uchida, Shinya Abe, Taku Miyasho, Makoto Tomita, Eiichi Inada

    JOURNAL OF SURGICAL RESEARCH   201 ( 1 )   59 - 68   2016年3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:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Background: Direct hemoperfusion with a polymyxin B-immobilized column (PMX-DHP) adsorbs endotoxin and has been used for the treatment of septic shock. Yet, the mechanisms by which PMX-DHP acts on acute kidney injury are only partially understood.
    Materials and methods: Rats were anesthetized, tracheostomized, and placed on mechanical ventilation. The animals were randomized to three groups: a cecal ligation and puncture (CLP) + dummy-DHP group (n = 10), a CLP + PMX-DHP group (n = 10), and a sham group (n = 4). Four hours after CLP, a dummy-DHP or PMX-DHP was performed for 1 h. The heart rate, mean arterial pressure, arterial blood gases, and plasma concentrations of creatinine, lactate, potassium, interleukin (IL)-6, and IL-10 were measured at 0 h and 8 h. Eight hours after CLP, the kidney was harvested, and histopathologic examination was performed. The expressions of cleaved poly (ADP-ribose) polymerase (PARP) and nuclear factor (NF)-kappa B p65 were examined by immunohistochemistry. A terminal deoxynucleotide transferase dUTP nick-end labeling assay was performed to detect apoptotic nuclei in kidney sections.
    Results: PMX-DHP maintained hemodynamics and the acid-base balance and significantly (P &lt; 0.05) decreased the plasma concentrations of lactate, creatinine, potassium, IL-6, and IL-10 compared with dummy-DHP. PMX-DHP significantly (P &lt; 0.001) attenuated the expressions of cleaved PARP and NF-kappa B p65 in renal tubular cells and renal tubular cell apoptosis compared with dummy-DHP.
    Conclusions: These findings suggest that PMX-DHP may protect against acute kidney injury not only by inhibiting the NF-kappa B signaling pathway but also by preventing renal tubular cell apoptosis. (C) 2016 Elsevier Inc. All rights reserved.

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  • Prognostic Factors for Post-Recurrence Survival in Patients with Thoracic Esophageal Squamous Cell Carcinoma after Curative Resection 査読

    Yasuaki Nakajima, Kenro Kawada, Yutaka Tokairin, Makoto Tomita, Satoshi Miyake, Tatsuyuki Kawano

    DIGESTIVE SURGERY   33 ( 2 )   136 - 145   2016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:KARGER  

    Background/Aims: We investigated factors affecting the post-recurrence prognosis in order to develop adequate therapeutic guidelines for determining the indication for treatment of recurrent esophageal squamous cell carcinoma (ESCC). Methods: Ninety-three thoracic ESCC patients who developed postoperative recurrence after undergoing curative esophagectomy with 3-field lymphadenectomy at our institute and who received treatment for recurrence were enrolled in this study. Results: A univariate analysis showed that distant organ recurrence, the number of recurrent tumors, the longest diameter of the largest recurrent tumor, the sum of all of the longest diameters of the recurrent tumors, invasion into adjacent structures and the speed of growth of the representative recurrent tumors were significantly associated with the post-recurrence prognosis. A multivariate analysis showed that distant organ recurrence, the longest diameter of the largest recurrent tumor, invasion into adjacent structures and the speed of growth of the representative recurrent tumors were significantly associated with the prognosis. The patients whose recurrent tumor(s) did not meet all 4 of these factors showed a better prognosis. In contrast, the prognosis of the patients whose recurrent tumor(s) demonstrated all 4 factors was almost the same as that observed in the patients who did not receive any treatment for recurrence. Conclusions: The evaluation of these 4 factors may potentially be used to determine the indication for treatment for recurrence. (C) 2016 S. Karger AG, Basel

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  • Perioperative elevation in cell-free DNA levels in patients undergoing cardiac surgery: Possible contribution of neutrophil extracellular traps to perioperative renal dysfunction 査読

    Yu Qi, Tokujiro Uchida, Mamoru Yamamoto, Yudai Yamamoto, Koji Kido, Hiroyuki Ito, Nagara Ohno, Miho Asahara, Yoshitsugu Yamada, Osamu Yamaguchi, Chieko Mitaka, Makoto Tomita, Koshi Makita

    Anesthesiology Research and Practice   2016   2016年

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    掲載種別:研究論文(学術雑誌)  

    © 2016 Yu Qi et al. Background. This study aimed to determine the perioperative change in serum double-strand DNA (dsDNA) as a marker potentially reflecting neutrophil extracellular trap concentration in samples from patients undergoing cardiac surgery and to analyze a relationship between serum dsDNA concentrations and perioperative renal dysfunction. Methods. Serum dsDNA concentrations in samples that were collected during a previously conducted, prospective, multicenter, observational study were measured. Eighty patients undergoing elective cardiac surgery were studied. Serum samples were collected at baseline, immediately after surgery, and the day after surgery (POD-1). Results. Serum dsDNA concentration was significantly increased from baseline (median, 398 ng/mL [interquartile range, 372-475 ng/mL]) to immediately after surgery (median, 540 ng/mL [437-682 ng/mL], p < 0.001), and they were reduced by POD-1 (median, 323 ng/mL [256-436 ng/mL]). The difference in serum creatinine concentration between baseline and POD-1 was correlated with dsDNA concentration on POD-1 (r s = 0.61, p < 0.001). Conclusions. In patients undergoing cardiac surgery, serum dsDNA concentration is elevated postoperatively. Prolonged elevation in dsDNA concentration is correlated with perioperative renal dysfunction. Further large-scale studies are needed to determine the relationship between serum concentration of circulating dsDNA and perioperative renal dysfunction.

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  • A Score for Predicting Paroxysmal Atrial Fibrillation in Acute Stroke Patients: iPAB Score 査読

    Kotaro Yoshioka, Kosuke Watanabe, Satoshi Zeniya, Yoko Ito, Masaki Hizume, Toshiro Kanazawa, Makoto Tomita, Satoru Ishibashi, Hirotomo Miake, Hiroaki Tanaka, Takanori Yokota, Hidehiro Mizusawa

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES   24 ( 10 )   2263 - 2269   2015年10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 SCIENCE BV  

    Background: Detection of paroxysmal atrial fibrillation (PAF) after a stroke is challenging. The purpose of this study was to develop a clinical score to predict PAF in a cohort of acute ischemic stroke patients prospectively and to validate it in an independent cohort. Methods: Consecutive acute ischemic stroke patients without permanent atrial fibrillation were enrolled in a derivation sample (n = 294) or a validation sample (n = 155). We developed a score for predicting PAF by independent risk factors derived from a logistic regression analysis of the derivation cohort and validated the score in the external cohort. Results: Multivariate analysis in the derivation cohort identified 3 variables independently associated with PAF. We calculated a score from these variables (history of arrhythmia or antiarrhythmic agent use [yes, 3 points], left atrial dilation [&gt;= 40 mm, 1 point], brain natriuretic peptide [BNP, &gt;50 pg/mL, 1 point; &gt;90 pg/mL, 2 points; &gt;150 pg/ml, 3 points], total score, 0-7). The iPAB score (identified by past history of arrhythmia or antiarrhythmic agent use, atrial dilation, and BNP elevation) predicted PAF in the derivation (c statistic,.90) and validation (. 94) cohorts at levels statistically superior to other biomarkers and clinical scores. For a total score 2 or more, the sensitivity and specificity were 93% and 71%, respectively. For a total score of 4 or more, the corresponding values were 60% and 95%. Conclusions: Our prospective study suggests that this simple risk score superior to other scores help clinicians predict PAF or identify good candidates for further evaluation to detect PAF.

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  • Significance of Development and Reversion of Collaterals on MRI in Early Neurologic Improvement and Long-Term Functional Outcome after Intravenous Thrombolysis for Ischemic Stroke 査読

    M. Ichijo, E. Iwasawa, Y. Numasawa, K. Miki, S. Ishibashi, M. Tomita, H. Tomimitsu, T. Kamata, H. Fujigasaki, S. Shintani, H. Mizusawa

    AMERICAN JOURNAL OF NEURORADIOLOGY   36 ( 10 )   1839 - 1845   2015年10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:AMER SOC NEURORADIOLOGY  

    BACKGROUND AND PURPOSE: Predicting response to rtPA is essential in the era of endovascular therapy for stroke. The purpose of this study was to elucidate prognostic factors of early neurologic improvement and long-term outcome with respect to the development and reversion of leptomeningeal collaterals in recanalization therapy after acute ischemic stroke.
    MATERIALS AND METHODS: We analyzed consecutive patients with proximal MCA occlusion treated with rtPA from 2007 to 2012 at 2 hospital stroke centers. All patients routinely underwent brain MR imaging before rtPA. To assess the reversion of collateral signs, we included patients who underwent follow-up MR imaging. We assessed the development and reversion of collaterals by using a combination of 2 MR imaging collateral markers, the hyperintense vessel sign and the posterior cerebral artery laterality sign. Early neurologic improvement was defined as a decrease in the NIHSS score of &gt;= 10 or a score of &lt;= 2 at 24 hours of treatment.
    RESULTS: Early neurologic improvement was observed in 22 of 48 eligible patients. The development of collaterals at arrival (15/22 versus 9/26, P = .042) was significantly associated with early neurologic improvement. Multivariate analysis adjusting for other variables showed that the development of collaterals at arrival (OR, 4.82; 95% Cl, 1.34-19.98; P = .015) was independently associated with early neurologic improvement. Reversion of collaterals was significantly associated with successful recanalization (P &lt; .001), and multivariate analysis showed that the reversion of collaterals was an independent prognostic factor of long-term functional outcome (OR, 5.07; 95% Cl, 1.38-22.09; P = .013).
    CONCLUSIONS: Our results indicate that the development of leptomeningeal collaterals plays a crucial role in achieving early neurologic improvement, and reversion of collaterals predicts a favorable outcome via arterial recanalization after rtPA treatment for acute stroke.

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  • Spatial Clustering Properties in the Temporal Variation of Suicide Rates/Numbers among Japanese Citizens: A Comprehensive Comparison and Discussion 査読

    Makoto Tomita, Takafumi Kubota, Fumio Ishioka

    PLOS ONE   10 ( 7 )   2015年7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:PUBLIC LIBRARY SCIENCE  

    Objective
    The number of suicides in Japan has remained high for many years. To effectively resolve this problem, firm understanding of the statistical data is required. Using a large quantity of wide-ranging data on Japanese citizens, the purpose of this study was to analyze the geographical clustering properties of suicides and how suicide rates have evolved over time, and to observe detailed patterns and trends in a variety of geographic regions.
    Methods
    Using adjacency data from 2008, the spatial and temporal/spatial clustering structure of geographic statistics on suicides were clarified. Echelon scans were performed to identify regions with the highest-likelihood ratio of suicide as the most likely suicide clusters.
    Results
    In contrast to results obtained using temporal/spatial analysis, the results of a period-by-period breakdown of evolving suicide rates demonstrated that suicides among men increased particularly rapidly during 1988-1992, 1993-1997, and 1998-2002 in certain cluster regions located near major metropolitan areas. For women, results identified cluster regions near major metropolitan areas in 1993-1997, 1998-2002, and 2003-2007.
    Conclusions
    For both men and women, the cluster regions identified are located primarily near major metropolitan areas, such as greater Tokyo and Osaka.

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  • Polymyxin B-immobilized fiber column hemoperfusion mainly helps to constrict peripheral blood vessels in treatment for septic shock 査読

    Makiko Sugiura, Chieko Mitaka, Go Haraguchi, Makoto Tomita, Naohiko Inase

    Journal of Intensive Care   3 ( 1 )   2015年3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:BioMed Central Ltd.  

    Background: Polymyxin B-immobilized fiber column hemoperfusion (PMX) has been reported to be effective for patients with septic shock. It remains unclear, however, how the efficacy of PMX varies according to the characteristics and underlying conditions of the patients treated. The objective of the present study was to clarify the factors that result in clinical efficacy of PMX treatment.Methods: We retrospectively investigated 78 consecutive patients with severe sepsis or septic shock who underwent PMX treatment. We reviewed the demographic data, routine biochemistry, microbiological data, infection focus, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, change in mean arterial pressure (MAP), inotropic score, vasopressor dependency index, plasma levels of endotoxin and lactate, PaO2/FIO2 ratio, and survival time. We also divided the patients into two groups for comparison, namely, those whose inotropic scores improved after PMX treatment (improvement group) and those whose inotropic scores did not improve (non-improvement group).Results: The inotropic score and the vasopressor dependency index significantly decreased from 18.1 to 9.9 (p &lt
    0.05) and from 0.27 to 0.14 (p &lt
    0.05), respectively, after PMX treatment in the overall study population, while no significant change in the PaO2/FIO2 ratio was observed (p = 0.96). The inotropic score at pre-PMX treatment was significantly higher in the improvement group than in the non-improvement group (p &lt
    0.01). The improvement of the PaO2/FIO2 ratio after PMX treatment was significant in the improvement group (p &lt
    0.05).Conclusions: The improvement group's inotropic score was higher, because of peripheral blood vessels dilatation and requirement for more catecholamines. Therefore, our study suggests that PMX treatment is particularly useful for improving hemodynamics in septic shock patients with excessively dilated peripheral blood vessels.

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  • Quantitative Evaluation of Blood Perfusion to Nerves Included in the Anterolateral Thigh Flap using Indocyanine Green Fluorescence Angiography: A Different Contrast Pattern between the Vastus Lateralis Motor Nerve and Femoral Cutaneous Nerve 査読

    Kentaro Tanaka, Mutsumi Okazaki, Tomoyuki Yano, Hiroki Miyashita, Tsutomu Homma, Makoto Tomita

    JOURNAL OF RECONSTRUCTIVE MICROSURGERY   31 ( 3 )   163 - 170   2015年3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:THIEME MEDICAL PUBL INC  

    Background Better postoperative results can be expected in nerve reconstruction when vascularized nerve grafts are used. Previous studies reported reconstruction with flaps including "vascularized" nerves; however, few have evaluated blood supply to these nerves. The aim of this study was to quantitatively assess blood perfusion to nerves included in anterolateral thigh (ALT) flaps by indocyanine green (ICG) fluorescence angiography.
    Patients and Methods Participants comprised eight patients who underwent reconstructive surgery with nerve defects using free ALT flaps, including the vastus lateralis motor nerve and/or femoral cutaneous nerve. Intraoperative ICG fluorescent angiography was performed. Time after the drug injection and the intensity of fluorescence in these nerves were analyzed as time intensity curves. Maximum intensity (Imax), time to Imax (Tmax), and time at the beginning of intensity elevation (Te) were measured at three points: Point C, the central portion of the flap-attached region of the nerve; Point P, 2 cm from the proximal flap-attached edge; and Point D, 2 cm from the distal edge.
    Results Imax and Te at point C and Imax/Tmax-Te at point P were significantly different between these two nerves (p = 0.03125, p = 0.02895, p = 0.03125, respectively). Fluorescence in the vastus lateralis motor nerve was slightly quicker and stronger than that in the femoral cutaneous nerve, and also exhibited an axial pattern of fluorescence.
    Conclusion Intraoperative ICG fluorescent angiography can be used to determine which nerve is better for nerve reconstruction. The indexes of Imax, Te, and Imax/Tmax-Te may be the suitable criteria for decision making regarding donor nerve selection.

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  • Mouse Synovial Mesenchymal Stem Cells Increase in Yield with Knee Inflammation 査読

    Yu Matsukura, Takeshi Muneta, Kunikazu Tsuji, Kazumasa Miyatake, Jun Yamada, Kahaer Abula, Hideyuki Koga, Makoto Tomita, Ichiro Sekiya

    JOURNAL OF ORTHOPAEDIC RESEARCH   33 ( 2 )   246 - 253   2015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:WILEY-BLACKWELL  

    Even though mouse studies have various advantages, harvesting an adequate number of synovial mesenchymal stem cells (MSCs) is difficult in mice. We investigated whether the total yield of MSCs increased in synovium with inflammation in mice. Infrapatellar fat pads (IFPs) were harvested from 10 knees of 5 mice 3, 7, and 14 days after intraarticular injection of carrageenan. Ten IFPs were also harvested from untreated knees as a control. Seven days after initial plating, the total yield of cells was compared among the 4 groups (n = 4-6). The harvested cells were analyzed for multipotentiality and surface epitopes. Furthermore, knee synovitis was compared among the 4 groups in histology. The number of cells in the 3 and 7 days treated group was significantly higher than the other groups. The harvested cells had characteristics of MSCs. Synovitis in the 3 and 7 days treated groups was significantly severer than the other groups. There seemed to be a relationship between the synovitis score and the total yield of cells derived from IFPs. In mice, it became possible to increase the yield 50-fold by inducing inflammation. This method makes it possible to analyze the molecular mechanisms of cartilage regeneration of synovial MSCs in mice models. (C) 2014 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society.

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  • Development and validation of new diagnostic criteria for acute retinal necrosis 査読

    Hiroshi Takase, Annabelle A. Okada, Hiroshi Goto, Nobuhisa Mizuki, Kenichi Namba, Nobuyuki Ohguro, Koh-Hei Sonoda, Makoto Tomita, Hiroshi Keino, Takeshi Kezuka, Reo Kubono, Kazuomi Mizuuchi, Etsuko Shibuya, Hiroyuki Takahashi, Ryoji Yanai, Manabu Mochizuki

    JAPANESE JOURNAL OF OPHTHALMOLOGY   59 ( 1 )   14 - 20   2015年1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 JAPAN KK  

    The purposes of this study are to develop and validate new diagnostic criteria for acute retinal necrosis (ARN) based on the ocular findings, clinical course, and virologic testing of intraocular fluids.
    The Japanese ARN Study Group, comprising 8 uveitis specialists and 1 statistician, was formed to develop new diagnostic criteria for ARN. The criteria used a combination of clinical features consistent with ARN including 6 early-stage ocular findings ([1a] anterior chamber cells or mutton-fat keratic precipitates; [1b] yellow-white lesion(s) in the peripheral retina [granular or patchy in the early stage, then gradually merging]; [1c] retinal arteritis; [1d] hyperemia of the optic disc; [1e] inflammatory vitreous opacities; and [1f] elevated intraocular pressure), 5 clinical courses ([2a] rapid expansion of the retinal lesion(s) circumferentially, [2b] development of retinal breaks or retinal detachment, [2c] retinal vascular occlusion, [2d] optic atrophy, and [2e] response to antiviral agents), and the results of virologic testing of intraocular fluids by means of either polymerase chain reaction or the Goldmann-Witmer coefficient for herpes simplex virus or varicella zoster virus. Various combinations of findings were analyzed to maximize the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The criteria were then used to retrospectively analyze patients who had been diagnosed as having ARN or control uveitis. Patients were followed at 1 of 7 tertiary uveitis clinics between 2009 and 2011.
    Analysis of the data allowed delineation of 2 levels of diagnosis: "virus-confirmed ARN" (defined as the presence of both early-stage ocular findings 1a and 1b, the presence of any 1 of the 5 clinical courses, and a positive virologic test result) and "virus-unconfirmed ARN" (defined as the presence of 4 of 6 early-stage ocular findings including 1a and 1b, presence of any 2 of the 5 clinical courses, and a negative virologic test result, or when virologic testing had not been performed). The new diagnostic criteria were applied to 45 patients with ARN and 409 patients with control uveitis, resulting in a sensitivity of 0.89, a specificity of 1.00, a PPV of 1.00, and an NPV of 0.99.
    New diagnostic criteria for ARN were developed and found to achieve high statistical values.

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  • Clinical characteristics of Japanese oropharyngeal squamous cell carcinoma positive for human papillomavirus infection 査読

    Fuminori Nomura, Taro Sugimoto, Keisuke Kitagaki, Takashi Ito, Hiroshi Kawachi, Yoshinobu Eishi, Ken Watanabe, Miki Igaue, Norio Shimizu, Makoto Tomita, Ken Kitamura, Seiji Kishimoto

    ACTA OTO-LARYNGOLOGICA   134 ( 12 )   1265 - 1274   2014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:INFORMA HEALTHCARE  

    Conclusion: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is considered to be a distinct entity in Japan. The combination of both HPV-DNA sequencing analysis and immunohistochemistry (IHC) for p16(INK4A) is useful to discriminate the OPSCC patients with a better prognosis from other cases, especially in the advanced stage. Surgical treatment is recommended for HPV-negative advanced cancer. Objective: The number of HPV-related OPSCCs has been increasing worldwide. However, the incidence and prognostic significance of this cancer in Japan have not yet been fully elucidated. Methods: Seventy-seven Japanese patients with OPSCC were enrolled in this study. The prevalence of HPV-DNA was assessed by PCR and sequencing. The expression of p16(INK4A) and p53 was examined by IHC. The clinicopathological parameters and disease-specific survival were analyzed for HPV-positive and -negative patients. Results: HPV-DNA was detected in 32 patients. Thirty-four patients were p16(INK4A)-positive by IHC. The patients who were positive for HPV infection were significantly younger. Furthermore, in the stage III or IV cases, the 3-year disease-specific survival of the HPV infection-positive group was significantly better than that of the HPV-negative group. Surgical treatment was demonstrated to lead to a good prognosis for the patients with HPV-negative advanced cancer.

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  • Clinical characteristics of Japanese oropharyngeal squamous cell carcinoma positive for human papillomavirus infection. 査読 国際誌

    Fuminori Nomura, Taro Sugimoto, Keisuke Kitagaki, Takashi Ito, Hiroshi Kawachi, Yoshinobu Eishi, Ken Watanabe, Miki Igaue, Norio Shimizu, Makoto Tomita, Ken Kitamura, Seiji Kishimoto

    Acta Otolaryngol.   134 ( 12 )   1265 - 1274   2014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)  

    Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is considered to be a distinct entity in Japan. The combination of both HPV-DNA sequencing analysis and immunohistochemistry (IHC) for p16(INK4A) is useful to discriminate the OPSCC patients with a better prognosis from other cases, especially in the advanced stage. Surgical treatment is recommended for HPV-negative advanced cancer.<br />
    The number of HPV-related OPSCCs has been increasing worldwide. However, the incidence and prognostic significance of this cancer in Japan have not yet been fully elucidated.<br />
    Seventy-seven Japanese patients with OPSCC were enrolled in this study. The prevalence of HPV-DNA was assessed by PCR and sequencing. The expression of p16(INK4A) and p53 was examined by IHC. The clinicopathological parameters and disease-specific survival were analyzed for HPV-positive and -negative patients.<br />
    HPV-DNA was detected in 32 patients. Thirty-four patients were p16(INK4A)-positive by IHC. The patients who were positive for HPV infection were significantly younger. Furthermore, in the stage III or IV cases, the 3-year disease-specific survival of the HPV infection-positive group was significa

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  • Systemic Following Intravitreal MTX Administration Prevents CNS Infiltration of Primary Intraocular Lymphoma 査読

    Hiroki Akiyama, Hiroshi Takase, Fumito Kubo, Tohru Miki, Masahide Yamamoto, Makoto Tomita, Manabu Mochizuki, Osamu Miura, Ayako Arai

    BLOOD   124 ( 21 )   2014年12月

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    記述言語:英語   出版者・発行元:AMER SOC HEMATOLOGY  

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  • Oral Dysesthesia Rating Scale: a tool for assessing psychosomatic symptoms in oral regions 査読

    Akihito Uezato, Akira Toyofuku, Yojiro Umezaki, Motoko Watanabe, Akira Toriihara, Makoto Tomita, Naoki Yamamoto, Akeo Kurumaji, Toru Nishikawa

    BMC PSYCHIATRY   14   2014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:BIOMED CENTRAL LTD  

    Background: The concept of cenesthopathy was first introduced by Dupre and Camus in 1907 to describe clinically unexplainable bodily sensations mainly attributed to psychiatric pathology. If it occurs in oral regions, it is termed oral cenesthopathy and it has been of special interest to psychiatrists and dentists. While there is no independently defined criteria for this condition, which is classified as either a delusional or a somatoform disorder, clinical practice and research require a standard scale to measure and rate its symptoms. In this study, we included any types of psychosomatic symptoms in oral regions as oral dysesthesia, and developed an Oral Dysesthesia Rating Scale (Oral DRS) and evaluated its validity and reliability as an assessment tool.
    Methods: The scale was developed based on literature review and extensive clinical experience. Twelve reviewers assessed relevancy of each item to oral dysesthesia symptoms by 1-4 scoring scale and item content validity index was computed. To evaluate the inter-rater reliability of Oral DRS, pairs of raters administered the scale to 40 randomly selected patients with complaints of oral dysesthesia symptoms and Cohen's weighted kappa coefficient was determined for each item.
    Results: The scale assesses the severity of feelings of foreign body [A1], exudation [A2], squeezing-pulling [A3], movement [A4], misalignment [A5], pain [A6], and spontaneous thermal sensation or tastes [A7], and the degree of impairment in eating [B1], articulation [B2], work [B3], and social activities [B4] on a scale of 0-5. Items A1, A2, A3, A4, B3, and B4 demonstrated acceptable content validity. Inter-rater reliabilities were good or excellent for all items evaluated.
    Conclusion: The Oral DRS can help define the nosography of clinically unexplainable oral dysesthesia through further case evaluation and clinical research and facilitate devising of treatment modalities.

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  • Comparison of the ocular characteristics of anterior uveitis caused by herpes simplex virus, varicella-zoster virus, and cytomegalovirus 査読

    Hiroshi Takase, Reo Kubono, Yukiko Terada, Ayano Imai, Shoko Fukuda, Makoto Tomita, Masaru Miyanaga, Koju Kamoi, Sunao Sugita, Kazunori Miyata, Manabu Mochizuki

    JAPANESE JOURNAL OF OPHTHALMOLOGY   58 ( 6 )   473 - 482   2014年11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 JAPAN KK  

    To compare the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), or cytomegalovirus (CMV).
    The medical records were reviewed of 46 patients whose diagnoses were based on their clinical characteristics [e.g., unilateral involvement, presence of keratic precipitates (KPs), and elevation of intraocular pressure (IOP)] and on PCR detection of herpes virus DNA in the aqueous humor. The demographics, chief complaints, and clinical characteristics of the three types of herpetic AU were compared.
    Of the 46 patients with AU, eight had HSV-AU, 20 had VZV-AU, and 18 had CMV-AU. HSV-AU and VZV-AU shared common features, i.e., a relatively acute disease process and the presence of large KPs. Among the three groups of patients, the characteristic features of those with VZV-AU were severe intraocular inflammation, as shown by severe aqueous flare, highest viral load in the aqueous humor, and presence of segmental iris atrophy. In comparison, patients with CMV-AU had the mildest intraocular inflammation, lowest corneal endothelial cell density, and highest IOP.
    Although the AU caused by each of the three types of herpes viruses has a number of common features, each disease also has distinct features that should facilitate an accurate diagnosis.

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  • Elevated levels of angiopoietin-2 as a biomarker for respiratory failure after cardiac surgery 査読

    Tokujiro Uchida, Hiroyuki Ito, Hiroto Yamamoto, Nagara Ohno, Miho Asahara, Yoshitsugu Yamada, Osamu Yamaguchi, Makoto Tomita, Koshi Makita

    Journal of Cardiothoracic and Vascular Anesthesia   28 ( 5 )   1293 - 1301   2014年10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:W.B. Saunders  

    Objectives Angiopoietin-1 and angiopoietin-2 are important factors in regulating endothelial vascular permeability. This study evaluated perioperative changes in serum levels of angiopoietin-1 and -2 in patients undergoing cardiac surgery.
    Design Measurement of serum levels of angiopoietin-1 and angiopoietin-2 in samples collected during a previously conducted prospective, multicenter, observational study.
    Setting Three university hospitals.
    Participants Eighty-four adult patients undergoing cardiac surgery. Intervention Serum levels of angiopoietins were measured at baseline, immediately after surgery, and the day after surgery (POD-1).
    Measurements and Main Results Serum levels of angiopoietin-2 were elevated by POD-1 (median 3.3 ng/mL, interquartile range [IQR] 2.5-4.6 ng/mL) compared with baseline (median 1.6 ng/mL, IQR 1.3-2.1 ng/mL, p &lt
    0.0001), and angiopoietin-1 levels were decreased immediately after surgery (baseline median 23.2 ng/mL, IQR 10.2-32.8 ng/mL
    postoperative median 8.0 ng/mL, IQR 1.5-13.2 ng/mL, p&lt
    0.0001). Angiopoietin-2 levels on POD-1 in patients undergoing off-pump coronary artery bypass grafting were significantly lower than those in patients undergoing aortic surgery (p = 0.0009) and valve surgery (p = 0.008). Angiopoietin-2 levels on POD-1 had a predictive performance of the area under the curve (AUC) of the receiver operating characteristic curve 0.74 for mechanical ventilation&gt
    3 days. Angiopoietin-1 levels and the angiopoietin-2/angiopoietin-1 ratio showed lower predictive performance (AUC values 0.58 and 0.68, respectively).
    Conclusions Angiopoietin-2 serum levels were elevated after cardiac surgery. Elevated angiopoietin-2 had a good predictive performance for respiratory failure after cardiac surgery, perhaps reflecting the severity of lung dysfunction related to postoperative increases in vascular permeability.

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  • Polymyxin B-immobilized fiber column hemoperfusion removes endotoxin throughout a 24-hour treatment period 査読

    Chieko Mitaka, Naoto Fujiwara, Mamoru Yamamoto, Takahiro Toyofuku, Go Haraguchi, Makoto Tomita

    JOURNAL OF CRITICAL CARE   29 ( 5 )   728 - 732   2014年10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:W B SAUNDERS CO-ELSEVIER INC  

    Purpose: The purpose of this study was to evaluate the extent of endotoxin adsorption by polymyxin B-immobilized fiber column hemoperfusion (PMX) performed for a 24-hour treatment period in patients with septic shock.
    Materials and methods: Nineteen patients with septic shock were retrospectively studied. The plasma endotoxin concentrations of blood drawn from the radial artery and from the outlet circuit of the PMX column were measured by kinetic turbidimetric limulus assay using an MT-358 Toxinometer (Wako Pure Chemical Industries, Ltd, Osaka, Japan) after 24 hours of PMX treatment. The endotoxin removal rate was defined by the following equation: ([radial artery endotoxin concentration - outlet circuit of PMX column endotoxin concentration]/radial artery endotoxin concentration) x 100%.
    Results: The patients had a median Acute Physiology and Chronic Health Evaluation II score of 29 at intensive care unit admission and a 28-day mortality of 47%. Before the start of the PMX treatment, the median radial arterial plasma endotoxin concentration was 16.48 pg/mL. After 24 hours of PMX treatment, the median radial plasma endotoxin concentration had decreased to 1.857 pg/mL, and the concentration at the outlet circuit of the PMX column was further decreased to 0.779 pg/mL. The median endotoxin removal rate was 74.4%.
    Conclusion: These findings suggest that 24-hour PMX treatment was effective in removing endotoxin continuously throughout the entire treatment period. (C) 2014 Elsevier Inc. All rights reserved.

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  • Elevated Levels of Angiopoietin-2 as a Biomarker for Respiratory Failure After Cardiac Surgery 査読

    Tokujiro Uchida, Hiroyuki Ito, Hiroto Yamamoto, Nagara Ohno, Miho Asahara, Yoshitsugu Yamada, Osamu Yamaguchi, Makoto Tomita, Koshi Makita

    JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA   28 ( 5 )   1293 - 1301   2014年10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:W B SAUNDERS CO-ELSEVIER INC  

    Objectives: Angiopoietin-1 and angiopoietin-2 are important factors in regulating endothelial vascular permeability. This study evaluated perioperative changes in serum levels of angiopoietin-1 and -2 in patients undergoing cardiac surgery.
    Design: Measurement of serum levels of angiopoietin-1 and angiopoietin-2 in samples collected during a previously conducted prospective, multicenter, observational study.
    Setting: Three university hospitals.
    Participants: Eighty-four adult patients undergoing cardiac surgery.
    Intervention: Serum levels of angiopoietins were measured at baseline, immediately after surgery, and the day after surgery (POD-1).
    Measurements and Main Results: Serum levels of angiopoietin-2 were elevated by POD-1 (median 3.3 ng/mL, interquartile range [IOR] 2.5-4.6 ng/mL) compared with baseline (median 1.6 ng/mL, IQR 1.3-2.1 ng/mL, p &lt; 0.0001), and angiopoietin-1 levels were decreased immediately after surgery (baseline median 23.2 ng/mL, IQR 10.2-32.8 ng/mL; postoperative median 8.0 ng/mL, IQR 1.5-13.2 ng/mL, p &lt; 0.0001). Angiopoietin-2 levels on POD-1 in patients undergoing off-pump coronary artery bypass grafting were significantly lower than those in patients undergoing aortic surgery (p = 0.0009) and valve surgery (p = 0.008). Angiopoietin-2 levels on POD-1 had a predictive performance of the area under the curve (AUC) of the receiver operating characteristic curve 0.74 for mechanical ventilation &gt;3 days. Angiopoietin-1 levels and the angiopoietin-2/angiopoietin-1 ratio showed lower predictive performance (AUC values 0.58 and 0.68, respectively).
    Conclusions: Angiopoietin-2 serum levels were elevated after cardiac surgery. Elevated angiopoietin-2 had a good predictive performance for respiratory failure after cardiac surgery, perhaps reflecting the severity of lung dysfunction related to postoperative increases in vascular permeability. (C) 2014 Elsevier Inc. All rights reserved.

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  • Long- Term Follow- Up After Catheter Ablation of Paroxysmal Atrial Fibrillation The Incidence of Recurrence and Progression of Atrial Fibrillation 査読

    Masateru Takigawa, Atsushi Takahashi, Taishi Kuwahara, Kenji Okubo, Yoshihide Takahashi, Yuji Watari, Katsumasa Takagi, Tadashi Fujino, Shigeki Kimura, Hiroyuki Hikita, Makoto Tomita, Kenzo Hirao, Mitsuaki Isobe

    CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY   7 ( 2 )   267 - 273   2014年4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:LIPPINCOTT WILLIAMS & WILKINS  

    Background Although catheter ablation (CA) is a standard treatment for atrial fibrillation (AF), its long-term efficacy remains unclear. This study aimed to elucidate the incidences of AF recurrence and of progression from paroxysmal to persistent AF, after CA, in patients with paroxysmal AF.
    Methods and Results We examined the incidence of AF recurrence and AF progression in 1220 consecutive patients (mean age, 61 years), with symptomatic paroxysmal AF, undergoing CA, based on extensive pulmonary vein isolation and focal ablation for nonpulmonary vein foci. AF recurrence-free survival probabilities at 5 years were 59.4% after the initial CA and 81.1% after the final CA (average, 1.3 procedures). During a median follow-up period of 47.9 (range, 5.3-123.3) months after the initial CA, AF progressed from paroxysmal to persistent in 15 (1.2%) patients (0.3%/y). The duration of AF history (hazard ratio [HR], 1.03; P&lt;0.0001), number of ineffective antiarrhythmics (HR, 1.09; P=0.005), and left atrial diameter indexed by the body surface area (HR, 1.05; P=0.001) were significant predictors of AF recurrence. Patient age (HR, 1.12; P=0.0001) and left atrial diameter indexed by the body surface area (HR, 1.26; P=0.0006) were significantly associated with AF progression. Patients aged 65 years and with a left atrial diameter indexed by the body surface area of 24.0 mm/m(2) did not develop AF progression for 10 years after the initial CA.
    Conclusions Although the long-term follow-up revealed the effect of CA on preventing AF recurrence, repeated CA sessions might be required. The rate of progression from paroxysmal to persistent AF was 0.3%/y.

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  • Predictive factors for comorbid psychiatric disorders and their impact on vision-related quality of life in patients with high myopia 査読

    Tae Yokoi, Muka Moriyama, Kengo Hayashi, Noriaki Shimada, Makoto Tomita, Naoki Yamamoto, Toru Nishikawa, Kyoko Ohno-Matsui

    INTERNATIONAL OPHTHALMOLOGY   34 ( 2 )   171 - 183   2014年4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  

    To determine the incidence of depression and anxiety disorders in patients with high myopia as well as the factors that would predict the development of psychiatric complications and their impact on vision-related quality of life (VR-QoL). Two hundred and five patients with pathologic myopia (axial length a parts per thousand yen26.50 mm) were studied. Incidence of depression and anxiety disorders was determined using the Hospital Anxiety and Depression Scale (HADS). VR-QoL was determined by the 25-item National Eye Institute Visual Function Questionnaire. Incidence of depression was 22.0 % and incidence of anxiety disorder was 25.9 %. Absence of children was the only factor significantly associated with the presence of depression, and a past history of cataract surgery was the only factor significantly associated with the presence of anxiety disorder. Factors which decreased the VR-QoL were in order of importance-anxiety disorder, decreased visual acuity in the best eye, depression, and being female. Responses of the subjects to two HADS statements 'I can laugh and see the funny side of things' and 'I can enjoy a good book or radio or television program' identified 82.2 % of depressed patients, and 'I get sudden feelings of panic' and 'I can sit at ease and feel relaxed' identified 71.7 % of patients with anxiety disorder. Twenty-two to 26 % of highly myopic patients had psychiatric disorders which had a strong negative impact on their VR-QoL. Two statements from the HADS questionnaire can be used to screen highly myopic patients for depression or anxiety disorders.

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  • Atrial natriuretic peptide attenuates kidney-lung crosstalk in kidney injury 査読

    Miniwan Tulafu, Chieko Mitaka, May Khin Hnin Si, Shinya Abe, Masanobu Kitagawa, Satoshi Ikeda, Yoshinobu Eishi, Shunichi Kurata, Makoto Tomita

    JOURNAL OF SURGICAL RESEARCH   186 ( 1 )   217 - 225   2014年1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:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Background: Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury after cardiovascular surgery, which in turn deteriorates oxygenation. Atrial natriuretic peptide (ANP) has natriuretic, diuretic, and anti-inflammatory effects. To elucidate whether renal IRI induces inflammation in the kidney and lung and ANP attenuates kidney-lung crosstalk.
    Materials and methods: The rats were anesthetized, tracheostomized, mechanically ventilated, and randomized to four groups: saline + IRI (n = 12), ANP + IRI (n = 12), ANP + sham (n = 6), and saline + sham (n = 6). Saline (6 mL/kg/h) or ANP (0.2 mu g/kg/min) at the rate of 6 mL/kg/h was started 5 min before clamping, respectively. Renal IRI was induced by clamping the left renal pedicle for 30 min. The hemodynamics, arterial blood gases, and plasma concentrations of creatinine and lactate were measured at baseline and 1, 2, and 3 h after declamping. Lung wet-to-dry ratio was measured. The mRNA expression of tumor necrosis factor (TNF)-alpha, interleukin (IL) 1 beta, and IL-6 and histologic localization of TNF-alpha in the kidney and lung were measured.
    Results: Renal IRI induced metabolic acidosis, pulmonary edema, increases in plasma concentrations of creatinine and lactate, and augmentation of the cytokine mRNA expression and histologic localization of TNF-alpha in the kidney and Renal IRI induced lung. ANP prevented IRI-induced metabolic acidosis, pulmonary edema, increases in creatinine, lactate, and the cytokine mRNA expression, attenuated histologic localization of TNF-alpha in the kidney and lung, and increased oxygenation.
    Conclusions: ANP has renoprotective and anti-inflammatory effects on the kidney and lung in a rat model of renal IRI, suggesting that ANP attenuates kidney-lung crosstalk. (C) 2014 Elsevier Inc. All rights reserved.

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  • Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene 査読

    Temu Qina, Nobuo Sanjo, Masaki Hizume, Maya Higuma, Makoto Tomita, Ryuichiro Atarashi, Katsuya Satoh, Ichiro Nozaki, Tsuyoshi Hamaguchi, Yosikazu Nakamura, Atsushi Kobayashi, Tetsuyuki Kitamoto, Shigeo Murayama, Hiroyuki Murai, Masahito Yamada, Hidehiro Mizusawa

    BMJ OPEN   4 ( 5 )   2014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:BMJ PUBLISHING GROUP  

    Objectives: Genetic Creutzfeldt-Jakob disease (CJD) due to V180I mutation in the prion protein gene (PRNP) is of great interest because of the differences from sporadic CJD and other genetic prion diseases in terms of clinical features, as well as pathological and biochemical findings. However, few systematic observations about the clinical features in patients with this unique mutation have been published. Therefore, the goal of this study was to relate this mutation to other forms of CJD from a clinical perspective.
    Design: We analysed clinical symptoms, prion protein genetics, biomarkers in cerebrospinal fluid (CSF) and MRI of patients.
    Participants: 186 Japanese patients with the V180I mutation in PRNP.
    Results: Our results indicate that the V180I mutation caused CJD at an older age, with a slower progression and a lower possibility of developing myoclonus, cerebellar, pyramidal signs and visual disturbance compared with classical sporadic CJD with methionine homozygosity at codon 129 of PRNP. Cognitive impairment was the major symptom. Diffuse hyperintensity of the cerebral cortex in diffusion-weighted MRI might be helpful for diagnosis. Owing to the low positivity of PrPSc in the CSF, genetic analysis was often required for a differential diagnosis from slowly progressive dementia.
    Conclusions: We conclude that the V180I mutation in PRNP produces a late-developing and slow-developing, less severe form of CJD, whose lesions are uniquely distributed compared with sporadic and other genetic forms of CJD.

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  • HIGHER SERUM CCL17 MAY BE A PROMISING PREDICTOR OF ACUTE EXACERBATIONS IN CHRONIC HYPERSENSITIVITY PNEUMONITIS 査読

    Miyazaki Yasunari, Unomura Koji, Tateishi Tomoya, Akashi Takumi, Takemura Tamiko, Tomita Makoto, Inase Naohiko, Yoshizawa Yasuyuki

    RESPIROLOGY   18   58   2013年11月

  • Human immunodeficiency virus-related retinal microangiopathy and systemic cytomegalovirus disease association (vol 57, pg 372, 2013) 査読

    Yuko Iwasaki, Narumichi Yamamoto, Tatsushi Kawaguchi, Noriko Ozaki, Makoto Tomita, Atsushi Ajisawa, Manabu Mochizuki, Kimio Murakami

    JAPANESE JOURNAL OF OPHTHALMOLOGY   57 ( 6 )   580 - 580   2013年11月

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    記述言語:英語   出版者・発行元:SPRINGER JAPAN KK  

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  • Inhibition of poly (adenosine diphosphate-ribose) polymerase attenuates lung-kidney crosstalk induced by intratracheal lipopolysaccharide instillation in rats 査読

    May Khin Hnin Si, Chieko Mitaka, Miniwan Tulafu, Shinya Abe, Masanobu Kitagawa, Satoshi Ikeda, Yoshinobu Eishi, Shunichi Kurata, Makoto Tomita

    RESPIRATORY RESEARCH   14   2013年11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:BIOMED CENTRAL LTD  

    Background: Acute respiratory distress syndrome (ARDS) is a severe form of lung injury that frequently occurs during pneumonia and sepsis. Lung inflammation in ARDS patients may have deleterious effects on remote organs such as the kidney. The nuclear enzyme poly(adenosine diphosphate-ribose) polymerase (PARP) enhances the nuclear factor (NF)-kappa B-dependent transcription of inflammatory cytokines. This study was conducted to elucidate two questions: first, whether the activation of PARP and NF-kappa B mediates the renal inflammation secondary to the lipopolysaccharide (LPS)-induced acute lung inflammation; second, whether a PARP inhibitor, 3-aminobenzamide (3-AB), attenuates lung and kidney inflammation by inhibiting NF-kappa B-dependent proinflammatory cytokines.
    Methods: Male Sprague-Dawley rats were anesthetized, ventilated, and divided into three groups; a control group (n = 8); an LPS group (n = 12) intratracheally instilled with LPS (16 mg/kg), and an LPS + 3-AB group (n = 12) given the same dose of LPS by the same method followed by an intravenous injection of 3-AB (20 mg/kg). Hemodynamics, arterial blood gas, and the plasma levels of lactate, creatinine and potassium were measured at 0,1,2,3, and 4 h after treatment. The lung wet/dry ratio was measured at 4 h. The mRNA expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 in the lung and kidney were measured by TaqMan real-time PCR. PARP and NF-kappa B in the lung and kidney were histologically examined by immunostaining and assigned expression scores.
    Results: LPS induced metabolic acidosis, hypotension, hypoxemia, increased the lung wet/dry ratio, increased the plasma levels of creatinine and potassium, and increased the cytokine mRNA expressions in the lung and kidney. All of these effects were associated with strong expression of PARP and NF-kappa B. Treatment with 3-AB prevented the LPS-induced metabolic acidosis and hypotension, reduced the plasma levels of lactate, creatinine and potassium, reduced the cytokine mRNA expressions, reduced the expression of PARP and NF-kappa B, improved pulmonary edema and oxygenation and preserved renal function.
    Conclusions: The PARP inhibition attenuated lung-kidney crosstalk induced by intratracheal LPS instillation, partly via an inhibition of NF-kappa B dependent proinflammatory cytokines.

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  • Erratum: Human immunodeficiency virus-related retinal microangiopathy and systemic cytomegalovirus disease association (Japanese Journal of Ophthalmology (2013) 57 (372-378) DOI: 10.1007/s10384-013-0247-7) 査読

    Yuko Iwasaki, Narumichi Yamamoto, Tatsushi Kawaguchi, Noriko Ozaki, Makoto Tomita, Atsushi Ajisawa, Manabu Mochizuki, Kimio Murakami

    Japanese Journal of Ophthalmology   57 ( 6 )   580   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Polymyxin B-immobilized fiber column hemoperfusion therapy for septic shock. Reply 査読

    Mitaka Chieko, Tomita Makoto

    SHOCK   40 ( 3 )   233 - 234   2013年9月

  • 空間データベースを用いた隣接情報の作成と自殺データの集積性 査読

    久保田 貴文, 藤野 友和, 冨田 誠, 石岡 文生, 藤田 利治

    統計数理   61 ( 1 )   167 - 176   2013年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Soluble Isoform of the Receptor for Advanced Glycation End Products as a Biomarker for Postoperative Respiratory Failure after Cardiac Surgery 査読

    Tokujiro Uchida, Nagara Ohno, Miho Asahara, Yoshitsugu Yamada, Osamu Yamaguchi, Makoto Tomita, Koshi Makita

    PLoS ONE   8 ( 7 )   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Purpose:Postoperative respiratory failure is a major problem which can prolong the stay in the intensive care unit in patients undergoing cardiac surgery. We measured the serum levels of the soluble isoform of the receptor for advanced glycation end products (sRAGE), and we studied its association with postoperative respiratory failure.Methods:Eighty-seven patients undergoing elective cardiac surgery were enrolled in this multicenter observational study in three university hospitals. Serum biomarker levels were measured perioperatively, and clinical data were collected for 7 days postoperatively. The duration of mechanical ventilation was studied for 28 days.Results:Serum levels of sRAGE elevated immediately after surgery (median, 1751 pg/mL
    interquartile range (IQR) 1080-3034 pg/mL) compared with the level after anesthetic induction (median, 884 pg/mL
    IQR, 568-1462 pg/mL). Postoperative sRAGE levels in patients undergoing off-pump coronary artery bypass grafting (median, 1193 pg/mL
    IQR 737-1869 pg/mL) were significantly lower than in patients undergoing aortic surgery (median, 1883 pg/mL
    IQR, 1406-4456 pg/mL
    p = 0.0024) and valve surgery (median, 2302 pg/mL
    IQR, 1447-3585 pg/mL
    p = 0.0005), and postoperative sRAGE correlated moderately with duration of cardiopulmonary bypass (rs = 0.44, p&lt
    0.0001). Receiver operating characteristic curve analysis demonstrated that postoperative sRAGE had a predictive performance with area under the curve of 0.81 (95% confidence interval 0.71-0.88) for postoperative respiratory failure, defined as prolonged mechanical ventilation &gt
    3 days. The optimum cutoff value for prediction of respiratory failure was 3656 pg/mL, with sensitivity and specificity of 62% and 91%, respectively.Conclusions:Serum sRAGE levels elevated immediately after cardiac surgery, and the range of elevation was associated with the morbidity of postoperative respiratory failure. Early postoperative sRAGE levels appear to be linked to cardiopulmonary bypass, and may have predictive performance for postoperative respiratory failure
    however, large-scale validation studies are needed. © 2013 Uchida et al.

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  • Human immunodeficiency virus-related retinal microangiopathy and systemic cytomegalovirus disease association 査読

    Yuko Iwasaki, Narumichi Yamamoto, Tatsushi Kawaguchi, Noriko Ozaki, Makoto Tomita, Atsushi Ajisawa, Manabu Mochizuki, Kimio Murakami

    JAPANESE JOURNAL OF OPHTHALMOLOGY   57 ( 4 )   372 - 378   2013年7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 JAPAN KK  

    To determine whether there is a significant association between human immunodeficiency virus (HIV)-related retinal microangiopathy and systemic cytomegalovirus (CMV) disease in HIV-infected patients.
    Participants in this single-center, cross-sectional, retrospective study were 383 HIV-infected patients assessed for ocular manifestations before the beginning of antiretroviral therapy. The presence of HIV-related retinal microangiopathy, the presence of systemic CMV disease, laboratory data, and demographic information were determined by referring to medical records. The significance of any association between HIV-related retinal microangiopathy and systemic CMV disease was determined by use of the Chi-squared test and by multivariate analysis.
    HIV-related retinal microangiopathy was present in 85 patients, and was significantly associated with systemic CMV disease both by use of the Chi-squared test (P = 0.006) and by multivariate analysis (P = 0.045, odds ratio 2.03, 95 % confidence interval 1.02-4.06 adjusted for CD4+ cell count and plasma HIV-RNA level).
    These findings indicate that microangiopathy may be involved in the development of CMV disease in HIV-infected patients. Thus, detection of the presence of HIV-related retinal microangiopathy is important in the management of HIV-infected patients.

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  • 日本人自殺者数とその増減による空間集積性の評価 査読

    冨田 誠, 石岡 文生, 久保田 貴文

    厚生の指標   60 ( 6 )   1 - 8   2013年6月

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    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:厚生労働統計協会  

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  • Higher serum CCL17 may be a promising predictor of acute exacerbations in chronic hypersensitivity pneumonitis 査読

    Yasunari Miyazaki, Koji Unoura, Tomoya Tateishi, Takumi Akashi, Tamiko Takemura, Makoto Tomita, Naohiko Inase, Yasuyuki Yoshizawa

    RESPIRATORY RESEARCH   14   2013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:BIOMED CENTRAL LTD  

    Background: Recent research has suggested that the Th1 and Th2 chemokine/cytokine axis contributes to the development of chronic hypersensitivity pneumonitis (HP). Acute exacerbations (AE) are significant factors in the prognosis of chronic HP. Little is known, however, about these biomarkers in association with AE in chronic HP patients.
    Methods: Fifty-six patients with chronic HP were evaluated, including 14 patients during episodes of AE. Th1 mediators (C-X-C chemokine ligand [CXCL] 10 and interferon [IFN]-gamma), Th2 mediators (C-C chemokine ligand [CCL] 17, interleukin-4, and interleukin-13), and pro-fibrotic mediator (transforming growth factor [TGF]-beta) were measured to evaluate the mediators as predictors of AE. C-C chemokine receptor (CCR) 4 (receptor for CCL17)-positive lymphocytes were quantified in lung specimens.
    Results: Serum CCL17 levels at baseline independently predicted the first episode of AE (HR, 72.0; 95% CI, 5.03-1030.23; p = 0.002). AE was significantly more frequent in the higher-CCL17 group (&gt;= 285 pg/ml) than in the lower-CCL17 group (&lt;285 pg/ml) (log-rank test, p = 0.0006; 1-year incidence: higher CCL17 vs. lower CCL17, 14.3% vs. 0.0%). Serum CCL17 levels and CCR4-positive cells during episodes of AE were increased from the baseline (p = 0.01 and 0.031).
    Conclusions: Higher serum concentrations of CCL17 at baseline may be predictive of AE in patients with chronic HP, and CCL17 may contribute to the pathology of AE by inducing the accumulation of CCR4-positive lymphocytes in the lungs.

    DOI: 10.1186/1465-9921-14-57

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  • Long-term changes of aortic F-18-FDG uptake and calcification in health-screening subjects 査読

    Yoshiharu Ryu, Katsuya Yoshida, Yoshifumi Suzuki, Masashi Nakadate, Isao Umehara, Makoto Tomita, Hitoshi Shibuya

    ANNALS OF NUCLEAR MEDICINE   27 ( 3 )   239 - 246   2013年4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  

    We investigated long-term changes in aortic F-18-fluorodeoxyglucose (F-18-FDG) uptake and calcification in health-screening subjects and their relation with atherogenic risk factors.
    A total of 94 consecutive subjects (72 men, 22 women; age 47-85 years, mean 57.9 years) participating in a health-screening protocol were evaluated retrospectively. All subjects had follow-up PET/CT scans 3.0-5.8 years (mean 4.1 years) later. We measured F-18-FDG uptake (maximum SUV) and calcium score (Agatston score) of the ascending, descending thoracic and infrarenal abdominal aorta on PET/CT images. F-18-FDG uptake and calcium score of the whole aorta (FUWA and CSWA) increased significantly in the follow-up study compared with the initial study (p = 0.02 and p &lt; 0.0001, respectively). Multiple regression analysis showed that the change in FUWA per year was significantly associated with visceral fat area, while the change of CSWA per year was significantly associated with age and smoking habit. The degrees of F-18-FDG uptake and calcium score increases were significantly greater in the abdominal aorta than in the thoracic aorta (p = 0.05 and p &lt; 0.0001, respectively).
    Our data demonstrated the longitudinal progressions of vascular inflammation and calcification of health-screening subjects. Inflammation and calcification were observed to progress significantly faster in the abdominal aorta than in the thoracic aorta. The progressions of vascular inflammation and calcification may be associated with different atherogenic risk factors.

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  • ぶどう膜炎の白内障手術における術後前眼部炎症の予測因子 査読

    岩崎 優子, 高瀬 博, 諸星 計, 宮永 将, 川口 龍史, 冨田 誠, 望月 學

    あたらしい眼科   30 ( 1 )   123 - 126   2013年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Posterior cerebral artery laterality on magnetic resonance angiography predicts long-term functional outcome in middle cerebral artery occlusion 査読

    Masahiko Ichijo, Kazunori Miki, Satoru Ishibashi, Makoto Tomita, Tomoyuki Kamata, Hiroto Fujigasaki, Hidehiro Mizusawa

    Stroke   44 ( 2 )   512 - 515   2013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:LIPPINCOTT WILLIAMS & WILKINS  

    BACKGROUND AND PURPOSE - : Prominent posterior cerebral artery (PCA) laterality upon 3-dimensional time-of-flight magnetic resonance angiography is often encountered in patients with middle cerebral artery occlusion. We hypothesized that this sign is correlated with improved functional outcome in patients with middle cerebral artery occlusion treated with intravenous recombinant tissue plasminogen activator. METHODS - : Fifty acute ischemic stroke patients with middle cerebral artery occlusion were treated with intravenous recombinant tissue plasminogen activator from April 2007 to October 2009. All patients routinely underwent initial (first 3 hours) magnetic resonance scans on admission, and additional follow-up (14-21 days after stroke onset) computed tomography scans. Two film readers blinded to all clinical information assessed the presence or absence of PCA laterality on magnetic resonance angiography. We retrospectively analyzed the clinical and radiologic data on all patients. RESULTS - : Out of 50 patients, 20 showed PCA laterality on magnetic resonance angiography. National Institute of Health Stroke Scale score 7 days after stroke onset was significantly lower (P=0.007), and infarct volume on follow-up computed tomography was significantly smaller (P=0.009) in patients with PCA laterality than in patients without this sign. Multivariate logistic regression analyses showed an adjusted odds ratio of 8.49 for a favorable outcome (modified Rankin Scale score 0-1 at 6 months) in patients with PCA laterality (95% CI: 1.82 to 55.8, P=0.005). CONCLUSIONS - : The presence of PCA laterality on magnetic resonance angiography before intravenous recombinant tissue plasminogen activator can be used as a predictor of favorable functional outcome in patients with middle cerebral artery occlusion, probably due to improvement of recanalization rate. © 2012 American Heart Association, Inc.

    DOI: 10.1161/STROKEAHA.112.674101

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  • Long-term Results of Brachytherapy in Early Mobile Tongue Cancer with 10-Year Minimal Follow-up 査読

    Mais M. Abdalmear, Makoto Tomita, Hitoshi Shibuya

    ANTICANCER RESEARCH   33 ( 1 )   317 - 324   2013年1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:INT INST ANTICANCER RESEARCH  

    Aim: To retrospectively analyze the long-term toxicities of low-dose-rate interstitial brachytherapy (LDR-BT) with related prognostic factors for patients with early mobile tongue cancer (T1/2N0M0) at a minimum of 10 years' follow-up. Patients and Methods: The records of 187 patients treated with LDR-BT between 1980 and 2000, out of whom 25 were treated with additional prior external beam irradiation, were reviewed. Results: Overall survival at 15 and 20 years was 88.4% and 76.2%, respectively. Complications included tongue ulcer (26%), tongue erosion (3%), tongue atrophy (2%), bone exposure (15%), and osteoradionecrosis (4%). No patient presented xerostomia or taste disorders. Multivariate analysis revealed that tongue ulcer and the use of spacer were significantly associated with bone exposure and osteoradionecrosis. Local recurrence was demonstrated in 15 (8%) cases, 93% of which were salvaged by operation. Fifty patients (27%) experienced neck metastasis. Conclusion: LDR-BT is an acceptable treatment option, with low rates of long-term toxicity.

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  • Focusing Approach Using LD Block and Association Study with Haplotype Combination on DNA data 査読

    Makoto Tomita

    2013 ELEVENTH INTERNATIONAL CONFERENCE ON ICT AND KNOWLEDGE ENGINEERING (ICT&KE)   2013年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:IEEE  

    In statistical genetics, SNPs, haplotype and diplotype are the major polymorphic markers in DNA data. Therefore, over approximately the last 10 years, the relative frequencies of different haplotypes have been estimated, their structures have been examined, and haplotypes have been used for association studies. We focus haplotype analyses, e.g., identification of haplotype blocks and haplotype association studies.

    DOI: 10.1109/ICTKE.2013.6756266

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  • A Familial History of Pulmonary Fibrosis in Patients with Chronic Hypersensitivity Pneumonitis 査読

    Tsukasa Okamoto, Yasunari Miyazaki, Makoto Tomita, Meiyo Tamaoka, Naohiko Inase

    RESPIRATION   85 ( 5 )   384 - 390   2013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:KARGER  

    Background: Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by the inhalation of a variety of antigens. Patients with chronic HP often have a family history of pulmonary fibrosis. This strongly suggests that both genetic and environmental factors play an important role in the pathogenesis of chronic HP. Objectives: We aimed to investigate the epidemiology and clinical features of chronic HP patients with a family history of pulmonary fibrosis. Methods: We retrospectively reviewed the clinical information of 114 cases diagnosed with chronic HP with insidious onset between 1992 and 2009. Results: Twenty cases (17.5%) were identified as having a family history of pulmonary fibrosis. All of these patients had lived apart from their afflicted relatives for at least several decades. The familial cases were younger than the nonfamilial cases at onset (57.5 +/- 9.6 vs. 64.0 +/- 7.0 years old, p = 0.008). The predicted vital capacity percentage and partial pressure of oxygen in arterial blood gas were significantly higher in the familial cases. There were no differences between the 2 groups in gender, smoking history, bronchoalveolar lavage fluid profile, radiologic findings or other clinical features. Conclusions: We found a familial clustering in patients with chronic HP. Various factors including genetic susceptibility to pulmonary fibrosis and environmental factors may contribute to the development of familial chronic HP. Copyright (C) 2012 S. Karger AG, Basel

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  • Proposal of a novel index for selection of optimal annuloplasty ring size for tricuspid annuloplication 査読

    Shuhei Fujita, Hirokuni Arai, Makoto Tomita, Tomohiro Mizuno, Satoru Kawaguchi, Susumu Manabe, Tsuyoshi Hachimaru, Naoto Miyagi

    Circulation Journal   77 ( 10 )   2505 - 2513   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Optimal ring size in tricuspid annuloplasty (TAP) surgery to treat functional tricuspid regurgitation (TR) was investigated because optimal ring size remains undefined. Methods and Results: Sixty seven patients who underwent TAP at our institution were retrospectively studied. Tricuspid Annuloplasty Ring size Index (TARI) was defined as implanted tricuspid annuloplasty ring size divided by body surface area (BSA). Different TARI cut-off values were tested to determine which value produced the greatest difference in TR improvement (TRI=preoperative minus postoperative TR grade) between patients with TARI smaller (group S) and larger (group L) than the cut-off. Group S was also subdivided by ring type: Cosgrove rings (SC) and MC3 rings (SM). TARI and TRI were negatively correlated (r=-0.307). A TARI threshold of 18.9 mm/m2 produced the greatest and most significant difference (P&lt
    0.0005) in TRI. Defining groups S and L using this threshold, TRI was significantly greater for group S (1.77±0.80) than for group L (0.97±0.83)
    P &lt
    0.0005. There was no difference in TRI between groups SC and SM. Conclusions: A novel index TARI that normalizes tricuspid annuloplasty ring size by BSA was developed. Choosing ring size to make TARI &lt
    18.9 mm/m2 is likely to be better than setting an upper limit of absolute ring size in the surgical treatment of TR.

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  • Visual Reproduction on the Wechsler Memory Scale-Revised as a Predictor of Alzheimer's Disease in Japanese Patients with Mild Cognitive Impairments 査読

    Takumi Hori, Nobuo Sanjo, Makoto Tomita, Hidehiro Mizusawa

    Dementia and Geriatric Cognitive Disorders   35 ( 3-4 )   165 - 176   2013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:S. Karger AG  

    Background: The Visual Reproduction (VR) test is used to assess mild cognitive impairment (MCI), but the characteristics of visual memory in Japanese MCI patients remain unclear. Methods: VR scores of 27 MCI patients were evaluated using the Wechsler Memory Scale-Revised. Scores of MCI, no-dementia, and Alzheimer's disease (AD) groups were then compared. Results: The annual conversion rate of MCI to AD was 18.8%. Mean VR-I and VR-II baseline scores for MCI patients were 33.3 ± 5.6 and 20.5 ± 14.0, respectively. Mean VR-II scores for converted and nonconverted MCI patients were 7.2 ± 8.7 and 29.8 ± 9.3, respectively. Conclusions: It is likely that VR-II and VR-II/I scores are more sensitive for predicting conversion to AD in Japanese than in American MCI patients. Our results indicate that VR is a sensitive and useful measure for predicting the conversion of Japanese MCI patients to AD within 2 years.

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  • ハプロタイプ解析における推定・ブロック同定および関連解析 査読

    冨田 誠

    計算機統計学   25 ( 1 )   53 - 68   2012年12月

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    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:日本計算機統計学会  

    DNAデータにおける多型マーカー,特にSNPデータについて染色体上のアレルの並び「ハプロタイプ」を推定し,その構造を考察し,疾患などの関連解析に用いられるといった遺伝統計解析の流れは2000年以前から10年間ほど取り組まれてきた.ハプロタイプの推定やそのブロック構造の同定,ハプロタイプを用いた関連解析についての近年の状況を紹介し,これをまとめた.

    DOI: 10.20551/jscswabun.25.1_53

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  • Association between Shape of Sclera and Myopic Retinochoroidal Lesions in Patients with Pathologic Myopia 査読

    Kyoko Ohno-Matsui, Masahiro Akiba, Toshio Modegi, Makoto Tomita, Tatsuro Ishibashi, Takashi Tokoro, Muka Moriyama

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   53 ( 10 )   6046 - 6061   2012年9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:ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

    PURPOSE. The purpose of the study was to analyze the shape of the sclera determined by swept-source optical coherence tomography (OCT) and to determine the relationship between the shape and the myopic retinochoroidal lesions.
    METHODS. We studied 488 eyes of 272 patients with high myopia (refractive error &gt;=-8.00 diopters [D] or axial length &gt;26.5 mm) and 43 emmetropic eyes of 43 controls (refractive error &lt;=+/- 3 D). An image of the sclera was obtained by a swept-source OCT prototype instrument that uses a wavelength sweeping laser centered on 1 mu m wavelength with an A-scan repetition rate of 100,000 Hz. The scans were 12 mm radial scans centered on the fovea. Seventy eyes were also examined by three-dimensional magnetic resonance imaging (3D MRI) to obtain the contour of the outer surface of the eyes. The main outcome measures, visibility of the entire sclera layer, scleral thickness, scleral contour, and location of the most protruded point of the globe, were obtained by swept-source OCT and 3D MRI.
    RESULTS. The entire thickness of the sclera was observed in 278 of 488 (57.0%) highly myopic eyes, but the outer border was not observed in any of the emmetropic eyes. The mean subfoveal scleral thickness was 227.9 +/- 82.0 mu m in the highly myopic eyes. The sclera was thickest at 3000 mu m nasal to the fovea. The curvatures of the inner scleral surface of highly myopic eyes could be divided into curvatures that sloped toward the optic nerve, those that were symmetrical and centered on the fovea, those that were asymmetrical, and those that were irregular. Patients with irregular curvature were significantly older and had significantly longer axial lengths than those with other curvatures. Myopic fundus lesions were present significantly more frequently in the eyes with irregular curvature. All of the eyes whose scleral curvature sloped toward the optic nerve had nasally distorted shape in the 3D MRI images, and all eyes with temporally dislocated shape had irregular curvature.
    CONCLUSIONS. In vivo evaluations of the sclera in highly myopic eyes by swept-source OCT can provide important information on deformations of the sclera and how such deformities are related to myopic fundus lesions. (Invest Ophthalmol Vis Sci. 2012; 53: 6046-6061) DOI: 10.1167/iovs.12-10161

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  • Quantitative Analyses of High-Resolution 3D MR Images of Highly Myopic Eyes to Determine Their Shapes 査読

    Muka Moriyama, Kyoko Ohno-Matsui, Toshio Modegi, Junichi Kondo, Yoichi Takahashi, Makoto Tomita, Takashi Tokoro, Ikuo Morita

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   53 ( 8 )   4510 - 4518   2012年7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:ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

    PURPOSE. We analyzed the symmetry and pointedness of the posterior segment of highly myopic eyes.
    METHODS. We studied 234 eyes of 117 patients with bilateral high myopia (refractive error &lt;=-8.00 diopters [D]) and 40 eyes of 20 patients with emmetropia (refractive error between -1.0 and +1.0 D). Volume renderings of high-resolution magnetic resonance (MR) images were performed to obtain 3D images of the eye. To analyze the symmetry and pointedness of the posterior surface, a software was developed to measure the area and angle of a fan-shaped segment formed by selected points on the MR images.
    RESULTS. All of the emmetropic eyes were symmetrical in the horizontal and sagittal planes with no deformity. In highly myopic eyes, the shape was symmetrical in the horizontal plane in 146 eyes (62.4%) and in the sagittal plane in 162 (69.2%). The shape of the posterior pole was pointed (angle of fan-shaped segment &lt;150 degrees) in 45.7% and blunted (angle &gt;= 150 degrees) in 54.3% of highly myopic eyes. The most common shape was symmetrical in the horizontal and sagittal planes, and the posterior surface was blunt. The shape of the two eyes of the same individual was the same in 61 of 117 patients (52.1%). In 56 patients whose two eyes had different shapes, the most frequent pattern was a difference in the pointedness (51.8%).
    CONCLUSIONS. Quantitative assessments of the shape of eyes were useful in determining the pattern of eye shape deformity specific to pathologic myopia. (Invest Ophthalmol Vis Sci. 2012;53:4510-4518) DOI:10.1167/iovs.12-9426

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  • POLYMYXIN B-IMMOBILIZED FIBER COLUMN HEMOPERFUSION THERAPY FOR SEPTIC SHOCK 査読

    Chieko Mitaka, Makoto Tomita

    SHOCK   36 ( 4 )   332 - 338   2011年10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:LIPPINCOTT WILLIAMS & WILKINS  

    Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column hemoperfusion (PMX) has been used for the treatment of septic shock patients in Japan since 1994. The covalent binding of polymyxin B onto the surface of the polystyrene-based carrier fiber in PMX inactivates the endotoxin in the blood without exerting toxicity. This study was performed as a systematic review to evaluate the efficacy and mechanism of PMX treatment in patients with septic shock. The PubMed database and references from identified articles were used to search and review the literature relating to the efficacy and mechanism of PMX treatment in patients with septic shock. Polymyxin B-immobilized fiber column hemoperfusion adsorbed monocytes, activated neutrophils, and anandamide, as well as endotoxin through direct covalent bond, hydrophobic and ionic interactions, and hydrodynamics, and reduced the blood concentrations of inflammatory cytokines, plasminogen activator inhibitor 1 and adhesion molecules. Polymyxin B-immobilized fiber column hemoperfusion increased blood pressure and reduced the dosage requirements for vasopressive/inotropic agents. The meta-analysis showed that PMX treatment had beneficial effects on the hemodynamics, pulmonary oxygenation, and mortality. These beneficial effects may be attributable to the direct adsorption of endotoxin, monocytes, activated neutrophils, and anandamide, as well as indirect decrease in inflammatory cytokines and other mediators. Polymyxin B-immobilized fiber column hemoperfusion treatment has additional effects on reducing endothelial damage, proapoptotic activity, and immunosuppression. Further studies will be needed to confirm the efficacy and mechanism of PMX treatment in septic shock.

    DOI: 10.1097/SHK.0b013e318225f839

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  • Association study for the relationship between a haplotype or haplotype set and multiple quantitative responses 査読

    Makoto Tomita, Noboru Hashimoto, Yutaka Tanaka

    COMPUTATIONAL STATISTICS & DATA ANALYSIS   55 ( 6 )   2104 - 2113   2011年6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 SCIENCE BV  

    Though there have been several works on the analysis of the association between genotype and phenotype, little can be found for the association analysis between a haplotype or haplotype sets and multivariate quantitative responses. For example, QTLmarc is available for the analysis of multivariate responses, but it cannot be applied to the case of stochastic diplotype configurations and complex genetic models. The present paper proposes a method of association analysis between diplotype configuration and multivariate quantitative responses assuming the dominant, recessive and additive models. A comparative study is performed between the proposed method and QTLmarc by applying the two methods to numerical examples and small size simulated data sets with actual genotype information taken from the data set of the Hapmap project and artificial quantitative phenotype data which follow multivariate normal distributions. The results show that the proposed method is superior to QTLmarc in finding the assumed association. (C) 2011 Elsevier B.V. All rights reserved.

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  • Cardiovascular and renal effects of carperitide and nesiritide in cardiovascular surgery patients: a systematic review and meta-analysis 査読

    Chieko Mitaka, Toshifumi Kudo, Go Haraguchi, Makoto Tomita

    CRITICAL CARE   15 ( 5 )   2011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:BIOMED CENTRAL LTD  

    Introduction: Acute kidney injury (AKI) following cardiovascular surgery is a common disease process and is associated with both morbidity and mortality. The aim of our study was to evaluate the cardiovascular and renal effects of an atrial natriuretic peptide (ANP, carperitide) and a B-type (or brain) natriuretic peptide (BNP, nesiritide) for preventing and treating AKI in cardiovascular surgery patients.
    Methods: Electronic databases, including PubMed, EMBASE and references from identified articles were used for a literature search.
    Results: Data on the infusion of ANP or BNP in cardiovascular surgery patients was collected from fifteen randomized controlled trials and combined. The infusion of ANP or BNP increased the urine output and creatinine clearance or glomerular filtration rate, and reduced the use of diuretics and the serum creatinine levels. A meta-analysis showed that ANP infusion significantly decreased peak serum creatinine levels, incidence of arrhythmia and renal replacement therapy. The meta-analysis also showed that ANP or BNP infusion significantly decreased the length of ICU stay and hospital stay compared with controls. However, the combined data were insufficient to determine how ANP or BNP infusion during the perioperative period influences long-term outcome in cardiovascular surgery patients.
    Conclusions: The infusion of ANP or BNP may preserve postoperative renal function in cardiovascular surgery patients. A large, multicenter, prospective, randomized controlled trial will have to be performed to assess the therapeutic potential of ANP or BNP in preventing and treating AKI in the cardiovascular surgical setting.

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  • 日本の自殺データにおける時空間解析 査読

    冨田 誠, 石岡文生, 藤田 利治

    計算機統計学   23 ( 1 )   25 - 43   2010年12月

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    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:日本計算機統計学会  

    昨今,急激に増加している日本の自殺者数について,各省庁でも様々な対策を講じているが,統計的な把握が重要であることは明白である.1973年から2007年までに収集された各市区町村の自殺者数を,5年間ごとの6期間(最初は10年間)と二次医療圏の348領域にまとめ,その推移・傾向をEchelon解析を用いて,空間分析を行った.また空間の集積性だけでなく,6期間の時間的な流れを考慮した時空間解析も行い,統合的な推移・傾向を考察した.

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  • Association of resistin polymorphism, its serum levels and prevalence of stroke in Japanese type 2 diabetic patients 査読

    Eitaro Nakashima, Atsuko Watarai, Takayoshi Tsukahara, Yoji Hamada, Keiko Naruse, Hideki Kamiya, Jiro Kato, Norihiro Kato, Makoto Tomita, Yutaka Oiso, Jiro Nakamura

    JOURNAL OF DIABETES INVESTIGATION   1 ( 4 )   154 - 158   2010年8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:WILEY-BLACKWELL  

    Aims/Introduction: Resistin, an inflammatory cytokine, might be involved in the development of atherosclerosis. In a recent paper, we showed that resistin polymorphism might be a risk marker for stroke susceptibility in Japanese type 2 diabetic patients. We tested whether the serum resistin levels might be also a risk marker of stroke independently from RETN polymorphism.
    Materials and Methods: Type 2 diabetic outpatients from our hospitals were enrolled. Patients (n = 89) with a history of coronary heart disease and stroke, and randomly selected controls (n = 178) matched for sex and age, but without a history of coronary heart disease and stroke, were examined for polymorphism -420 (C &gt; G) and cytokines levels.
    Results: Serum resistin levels were significantly higher in patients with cardiovascular diseases (CVD) than in those without CVD (P = 0.024), and were highest in patients with stroke among the CVD. In multiple logistic regression analysis, serum resistin levels was an independent risk marker of stroke even after adjusted by RETN polymorphism, age, sex, body mass index, HbA(1c), systolic and diastolic blood pressure, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, creatinine, history of coronary heart disease, treatment of insulin, sulfonylurea and aspirin (odds ratio 1.33, 95% confidence interval [CI] 1.02-1.73, P = 0.039). The enrolled patients were divided by their serum resistin levels (high or low group) and their genotypes (CC, CG, GG at -420) into six groups. Patients with the GG genotype and high resistin levels showed the highest odds ratio, 5.69 (95% CI 1.24-26.1), compared with the group with CC and low levels.
    Conclusions: The results suggest that serum resistin levels might be a good marker of susceptibility to stroke as well as RETN polymorphism. (J Diabetes Invest, doi: 10.1111/j.2040-1124.00040.x, 2010)

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  • Lung-lung interaction in isolated perfused unilateral hyperventilated rat lungs 査読

    Aishan Bilali, Shunichi Kurata, Satoshi Ikeda, Gabriela S. Georgieva, Chenting Zhu, Makoto Tomita, Iyoko Katoh, Chieko Mitaka, Yoshinobu Eishi, Takasuke Imai

    TRANSLATIONAL RESEARCH   155 ( 5 )   228 - 237   2010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 SCIENCE INC  

    The technique of conducting high tidal volume (TV) ventilation-induced lung inflammation including remote organs is still open to discussion, and our aim is to investigate this issue in isolated ventilated rat lungs perfused with salt solution. Selective right lung (RI) hyperventilation (TV of 15 mL/kg with air containing 5% CO(2) on zero or 2.5 cm H(2)O end expiratory pressure (ZEEP or PEEP) in addition to left lung (LL) on 2.5 cm H(2)O continuous positive airway pressure (CPAP) for 60 min, was realized after 30 min both lungs ventilation by occluding the left main bronchus, and it was allocated to the following 5 groups: groups 1 and 2 underwent hyperventilation under ZEEP, groups 3 and 4 underwent hyper ventilation under PEEP with recirculation or nonrecirculation (R-ZEEP or NR-ZEEP and R-PEEP or NR-PEEP), and group 5 served as the control group. Recirculation means the same perfusate recirculates the system throughout the procedure. The wet/dry ratio and protein content of bronchoalveolar lavage fluid (Prot-BALF), cytokine messenger RNAs (mRNAs), localization of tumor necrosis factor-alpha (TNF-alpha) by immunofluorescence double staining, and TNF-alpha concentration in the perfusate and BALF in each lung were measured and compared between groups by Kruskal-Wallis test. Lung injury (increased wet/dry ratio, Prot-BALF, and TNF-alpha on endothelial and epithelial cells) was shown in the hyperventilated RLs with ZEEP compared with their corresponding CPAP Lis. PEEP prevented these injuries. Lung injury was also demonstrated in the recirculated LL compared with the nonrecirculated LL (Prot-BALF, TNF-alpha and interleukin-1 beta (IL-1 beta) mRNAs: the LL of the R-ZEEP is greater than the LL of NR-ZEEP by P &lt; 0.01). Unilateral hyperventilated lungs with ZEEP induced TNF-alpha, increased permeability, and injured the control lung via perfusion. (Translational Research 2010;155:228-237)

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  • 大規模なゲノムデータにおける関連解析の手法とソフトウェア 査読

    冨田 誠, 藤田 利治, 神出 計, 花田 裕典, 宮田 敏行, 河野 雄平

    計算機統計学   22 ( 2 )   131 - 142   2010年5月

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    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:日本計算機統計学会  

    ゲノムデータを扱う解析は,特に2000年前後から急激に活発なものとなり,近年はその提案されたさまざまな手法をまとめあげる解説書も増えてきている.単なるDNAの配列の解読だけでなく,その機能的な意味を求め,特に医療の分野で,ある疾患とDNA配列のどの範囲が関連があるかを探索するポストゲノム研究の時代へ本格的に突入している.これらの解析を行うため,基本的にLinux上で実行するよう,C言語やスクリプト言語を用いたソフトウェアが公開されており,遺伝統計解析を行う研究者はLinux上に解析環境を構築して実践することが常であった.しかし,この2,3年では統計解析者にも馴染みの深いR環境で実行できる遺伝統計解析パッケージが多く提供され,一般の統計関係者に取り組みやすくなってきた.これらの手法・ソフトウェアを紹介するとともに,大規模なゲノムワイドなデータ解析の実例も交えて解説する.

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  • BDNF is not associated with schizophrenia: Data from a Japanese population study and meta-analysis 査読

    Kunihiro Kawashima, Masashi Ikeda, Taro Kishi, Tsuyoshi Kitajima, Yoshio Yamanouchi, Yoko Kinoshita, Tomo Okochi, Branko Aleksic, Makoto Tomita, Takeya Okada, Hiroshi Kunugi, Toshiya Inada, Norio Ozaki, Nakao Iwata

    SCHIZOPHRENIA RESEARCH   112 ( 1-3 )   72 - 79   2009年7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 SCIENCE BV  

    A variety of evidence suggests brain-derived neurotrophic factor (BDNF) as a candidate gene for schizophrenia, and several genetic studies have shown a significant association between the disease and certain SNPs within BDNF (specifically, Val66Met and C270T). According to a recent study, the functional microsatellite marker BDNF-LCPR (BDNF-linked complex polymorphic region), which affects the expression level of BDNF, is associated with bipolar disorder. The goals of our current study were to 1) evaluate the quality of HapMap-based linkage disequilibrium (LD) tagging of BDNF-LCPR, 2) examine whether these tagging SNPs are associated with schizophrenia in a Japanese population, and 3) conduct a meta-analysis of the two most extensively studied polymorphisms: Val66Met and C270T. We genotyped eight tagging SNPs, including Val66Met and C270T. Our LID evaluation showed that BDNF-LCPR could be represented by these tagging SNPs in controls (with 73.5% allelic coverage). However, the functional A1 allele was not captured due to its low minor allele frequency (2.2%). In a case-control study (1117 schizophrenics and 1102 controls), no association was found in single-marker or multimarker analysis. Moreover, in a meta-analysis, the Val66Met polymorphism was not associated with schizophrenia, whereas C270T showed a trend for association in a fixed model (p = 0.036), but not in a random model (p = 0.053). From these findings, we conclude that if BDNF is indeed associated with schizophrenia, the A1 allele in BDNF-LCPR would be the most promising candidate. Further LD evaluation, as well as an association study in which BDNF-LCPR is genotyped directly, would be required for a more conclusive result. (C) 2009 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.schres.2009.03.040

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  • Meta-analysis of association between genetic variants in COMT and schizophrenia: An update 査読

    Tomo Okochi, Masashi Ikeda, Taro Kishi, Kunihiro Kawashima, Yoko Kinoshita, Tsuyoshi Kitajima, Yoshio Yamanouchi, Makoto Tomita, Toshiya Inada, Norio Ozaki, Nakao Iwata

    SCHIZOPHRENIA RESEARCH   110 ( 1-3 )   140 - 148   2009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 SCIENCE BV  

    A common functional polymorphism, Val108/1581Met (rs4680), and haplotypes rs737865-rs4680-rs165599 in the Catechol-O-methyltransferase gene (COMT) have been extensively examined for association to schizophrenia; however, results of replication studies have been inconsistent. The aim of this study was to comprehensively evaluate the genetic risk of COMT for schizophrenia.
    First, we performed a mutation scan to detect the existence of potent functional variants in the 5&apos;-flanking and exon regions. Second, we conducted a gene-based case-control study between tagging single nucleotide polymorphisms (SNPs) in COMT [19 SNPs including six possible functional SNPs (rs2075507, rs737865, rs4680, rs165599, rs165849)] and schizophrenia in large Japanese samples (schizophrenics 1118, controls 1100). Lastly, we carried out a meta-analysis of 5 functional SNPs and haplotypes (rs737865-rs4680-rs165599).
    No novel functional variant was detected in the mutation scan. There is no association between these tagging SNPs in COMT and Japanese schizophrenia. In this updated meta-analysis, no evidence was found for an association between Val108/158Met polymorphisms, rs6267, rs165599, and haplotypes (rs7378655-rs4680-rs165599) and schizophrenia, although rs2075507 and rs737865 showed trends for significance in allele-wise analyses (P=0.039 in a multiplicative model, P=0.025 in a recessive model for rs2075507, P=0.018 in a dominant model for rs737865, uncorrected). This significance did not remain, however, after correcting the P-values using a false discovery rate controlling procedure.
    Our results suggest that the COMT is unlikely to contribute to susceptibility to schizophrenia. (c) 2009 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.schres.2009.02.019

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  • Polymorphism in resistin promoter region at-420 determines the serum resistin levels and may be a risk marker of stroke in Japanese type 2 diabetic patients 査読

    Takayoshi Tsukahara, Eitaro Nakashima, Atsuko Watarai, Yoji Hamada, Keiko Naruse, Hideki Kamiya, Nobuhisa Nakamura, Norihiro Kato, Nobuyuki Hamajima, Yoshitaka Sekido, Toshimitsu Niwa, Makoto Tomita, Yutaka Oiso, Jiro Nakamura

    DIABETES RESEARCH AND CLINICAL PRACTICE   84 ( 2 )   179 - 186   2009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 IRELAND LTD  

    Resistin, which appears to be related to insulin resistance, is secreted mainly from macrophages in human and some of its polymorphisms have been reported. Based on recent in vitro studies, resistin may be associated with atherosclerosis by mediating endothelial hyperactivity. We investigated whether resistin polymorphism at -420C&gt;G is associated with serum resistin levels and diabetic macroangiopathy (coronary heart disease, arteriosclerosis obliterans, and stroke) in 349 Japanese type 2 diabetic patients (DM) and 286 nondiabetic controls (non-DM). Serum resistin levels in DM with a history of stroke were significantly higher than those without, 19.6 +/- 2.1 and 12.4 +/- 0.5 ng/ml (P &lt; 0.001), respectively. Furthermore, the levels were significantly increased in a genotype-dependent manner (CC, CG, GG) based on the polymorphism at -420C&gt;G (P &lt; 0.001) in both DM and non-DM. The prevalence of stroke in DM significantly increased according to the presence of mutations (P &lt; 0.035). In multivariate logistic-regression analysis, individuals with the CG or GG genotypes were significantly more likely to have had a stroke than individuals with the CC genotype (vs. CG; OR 2.99, P = 0.024, vs. GG; OR 4.49, P = 0.010). These data suggested that the genotyping of resistin polymorphism. at -420(C&gt;G) can be a risk marker for stroke susceptibility in Japanese type 2 diabetic patients. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.diabres.2008.10.021

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  • Genetic correlation between autistic traits and IQ in a population-based sample of twins with autism spectrum disorders (ASDs) (vol 54, pg 56, 2009) 査読

    Takeshi Nishiyama, Hiroko Taniai, Taishi Miyachi, Koken Ozaki, Makoto Tomita, Satoshi Sumi

    JOURNAL OF HUMAN GENETICS   54 ( 3 )   191 - 191   2009年3月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    DOI: 10.1038/jhg.2009.19

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  • Genetic correlation between autistic traits and IQ in a population-based sample of twins with autism spectrum disorders (ASDs) 査読

    Takeshi Nishiyama, Hitomi Taniai, Taishi Miyachi, Koken Ozaki, Makoto Tomita, Satoshi Sumi

    JOURNAL OF HUMAN GENETICS   54 ( 1 )   56 - 61   2009年1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:NATURE PUBLISHING GROUP  

    Although there is accumulating evidence that intelligence quotient (IQ) indexes some aspects of the autistic spectrum disorders (ASDs), the causal relationship between autistic traits and IQ remains controversial. We examined the sources of covariation between autistic traits and IQ. As males have a four times greater risk of ASDs than females, gender-specific effects were also explored. Autistic traits and IQ were assessed in 45 twin male-male, female-female and opposite-sex pairs ascertained by the regional screening system in Nagoya, Japan. Sex-limited Cholesky structural equation models were used to decompose the correlations between autistic traits and IQ into genetic and environmental components, including sex-specific factors. Genetic correlations between autistic traits and IQ were high and not significantly different between boys and girls (-0.94 and -0.95, respectively), but genetic factors underlying the autistic traits were not entirely shared with the IQ. The individual-specific environmental correlation between autistic traits and IQ was estimated at -0.29 for boys and -0.59 for girls. There is a substantial overlap between the genetic factors that influence individual variation in autistic traits and IQ, irrespective of gender. The individual life experiences that increase autistic traits, however, have a moderate overlap with those that contribute to individual IQs.

    DOI: 10.1038/jhg.2008.3

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  • Identify LD blocks based on hierarchical spatial data 査読

    Makoto Tomita, Masahiro Hatsumichi, Koji Kurihara

    COMPUTATIONAL STATISTICS & DATA ANALYSIS   52 ( 4 )   1806 - 1820   2008年1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 SCIENCE BV  

    A domain where recombination does not occur often, yet maintained linkage disequilibrium exists on DNA sequence is known as a "haplotype blocks' or "LD block". Many methods are available to identify LD blocks using disequilibrium parameters, such as the well-known Gabriel's method, Zhu's method and so on. We considered that Echelon analysis can be applied to identify LD block, and report herein that LD blocks can be identified according to our new method applying Echelon analysis. The results of numerical examples are also provided. (C) 2007 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.csda.2007.05.035

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  • 主成分分析における軸の回転について 査読

    林 邦好, 冨田 誠, 田中 豊

    計算機統計学   19 ( 2 )   89 - 101   2007年12月

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    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:日本計算機統計学会  

    主成分分析(PCA)は,変量の次元を縮約する多変量統計解析の代表的な手法である.主成分の意味付けをするために,固有ベクトルを解釈することになるが,特に主成分数を多くとる場合など,しばしば主成分の解釈が困難な状況に遭遇する.解釈を容易にするために,因子分析の場合のように軸を回転させることができれば便利である.先行研究では,主成分係数を回転対象とする方法と主成分負荷量を目転対象とする2つの立場がある.本論文ではPCAを次元縮約の方法と捉え,縮約された低次元空間の中で解釈し易いように座標軸を導入するという立場で,Jolliffe(1995)の提唱した3つの基準化の方法及び回転対象として主成分係数・主成分負荷量のどちらを選ぶかという問題を整理し,2組の実データ及び因子分析モデルに従って生成した人工データに適用して数値的検討を行った.その結果,基準化3(分散が1に等しくなるように基準化した場合)では,主成分負荷量を直交回転する方が対比が形成されにくく,く1つの軸に1つの意味が付与できることが明らかになった.

    DOI: 10.20551/jscswabun.19.2_89

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  • ISI2005に参加して

    冨田 誠

    計算機統計学   18 ( 1 )   51 - 53   2006年

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    記述言語:日本語   出版者・発行元:日本計算機統計学会  

    DOI: 10.20551/jscswabun.18.1_51

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  • Estimation of haplotype frequencies, linkage-disequilibrium measures, and combination of haplotype copies in each pool by use of pooled DNA data 査読

    T Ito, S Chiku, E Inoue, M Tomita, T Morisaki, H Morisaki, N Kamatani

    AMERICAN JOURNAL OF HUMAN GENETICS   72 ( 2 )   384 - 398   2003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:UNIV CHICAGO PRESS  

    Inference of haplotypes is important for many genetic approaches, including the process of assigning a phenotype to a genetic region. Usually, the population frequencies of haplotypes, as well as the diplotype configuration of each subject, are estimated from a set of genotypes of the subjects in a sample from the population. We have developed an algorithm to infer haplotype frequencies and the combination of haplotype copies in each pool by using pooled DNA data. The input data are the genotypes in pooled DNA samples, each of which contains the quantitative genotype data from one to six subjects. The algorithm infers by the maximum-likelihood method both frequencies of the haplotypes in the population and the combination of haplotype copies in each pool by an expectation-maximization algorithm. The algorithm was implemented in the computer program LDPooled. We also used the bootstrap method to calculate the standard errors of the estimated haplotype frequencies. Using this program, we analyzed the published genotype data for the SAA (n = 156), MTHFR (n = 80), and NAT2 (n = 116) genes, as well as the smoothelin gene (n = 102). Our study has shown that the frequencies of major (frequency &gt;0.1 in a population) haplotypes can be inferred rather accurately from the pooled DNA data by the maximum-likelihood method, although with some limitations. The estimated D and D' values had large variations except when \D\ values were &gt;0.1. The estimated linkage-disequilibrium measure rho(2)for 36 linked loci of the smoothelin gene when one- and two- subject pool protocols were used suggested that the gross pattern of the distribution of the measure can be reproduced using the two-subject pool data.

    DOI: 10.1086/346116

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▼全件表示

書籍等出版物

  • ゲノムデータ解析 -統計学One Point 1巻-

    冨田 誠( 担当: 共著)

    共立出版  2016年9月 

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  • 一般化線形モデル入門 原著 第2版

    冨田 誠( 担当: 共訳)

    共立出版  2008年9月 

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  • Statistical Methods for Biostatistics and Related Fields

    冨田 誠( 担当: 共著)

    2006年11月 

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  • 実感と納得の統計学

    冨田 誠( 担当: 共著)

    羊土社  2006年4月 

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  • ポストゲノム時代の遺伝統計学

    冨田 誠( 担当: 共著 範囲: 2章5節 Mapmaker/sibsの使い方)

    羊土社  2001年10月 

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MISC

  • 橋MRIを用いた脊髄小脳変性症の診断方法の樹立

    東 美和, 尾崎 心, 服部 高明, 佐藤 望, 冨田 誠, 水澤 英洋, 石川 欽也, 横田 隆徳

    臨床神経学   59 ( Suppl. )   S359 - S359   2019年11月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • Optimal Regimens of Sulfamethoxazole-Trimethoprim for Chemoprophylaxis of Pneumocystis Pneumonia in Patients with Systemic Rheumatic Diseases: 52-Week Follow-up of a Non-Blinded, Randomized Controlled Trial

    Masayoshi Harigai, Masako Utsunomiya, Hiroaki Dobashi, Toshio Odani, Kazuyoshi Saito, Naoto Yokogawa, Kenji Nagasaka, Kenchi Takenaka, Makoto Soejima, Takahiko Sugihara, Hiroyuki Hagiyama, Shinya Hirata, Kazuo Matsui, Yoshinori Nonomura, Masahiro Kondo, Fumihito Suzuki, Makoto Tomita, Mari Kihara, Waka Yokoyama, Fumio Hirano, Hayato Yamazaki, Ryoko Sakai, Toshihiro Nanki, Ryuji Koike, Hitoshi Kohsaka, Nobuyuki Miyasaka

    ARTHRITIS & RHEUMATOLOGY   69   2017年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY  

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  • 脊髄小脳失調症患者における橋底部MRI信号変化と臨床所見の関連性についての研究

    東 美和, 尾崎 心, 曽我 一將, 石井 俊, 佐藤 望, 冨田 誠, 石川 欽也, 横田 隆徳

    臨床神経学   56 ( Suppl. )   S487 - S487   2016年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • 急性網膜壊死のあたらしい診断基準の作成

    高瀬 博, 大黒 伸行, 岡田 アナベルあやめ, 後藤 浩, 園田 康平, 冨田 誠, 南場 研一, 水木 信久, 望月 學

    日本眼科学会雑誌   117 ( 11 )   935 - 935   2013年11月

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    記述言語:日本語   出版者・発行元:(公財)日本眼科学会  

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  • SC4-5 年齢階級別日本自殺死亡データの時空間集積性の検出について(特別セッション 人間の心と体のリスク解析-方法と実証-)

    石岡 文生, 冨田 誠, 久保田 貴文, 椿 広計

    日本行動計量学会大会発表論文抄録集   41   254 - 257   2013年9月

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    記述言語:日本語   出版者・発行元:日本行動計量学会  

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  • Reply

    Chieko Mitaka, Makoto Tomita

    Shock   40 ( 3 )   233 - 234   2013年9月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)  

    DOI: 10.1097/SHK.0b013e31829f21a8

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  • 自殺死亡の地域統計の可視化について(Session 6A)

    久保田 貴文, 冨田 誠, 石岡 文生, 椿 広計

    日本計算機統計学会シンポジウム論文集   26 ( 0 )   91 - 94   2012年

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    記述言語:日本語   出版者・発行元:日本計算機統計学会  

    DOI: 10.20551/jscssymo.26.0_91

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  • 自殺死亡データの空間相関モデルへの応用(セッション3B)

    久保田 貴文, 石岡 文生, 冨田 誠, 藤田 利治

    日本計算機統計学会大会論文集   25 ( 0 )   127 - 130   2011年

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    記述言語:日本語   出版者・発行元:日本計算機統計学会  

    DOI: 10.20551/jscstaikai.25.0_127

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  • 欧州における患者への臨床試験の情報提供および各国民の認知度などについて

    冨田 誠, 大柳菜歩

    医薬ジャーナル   46 ( 3 )   951 - 953   2010年3月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

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  • データベースをうまく利用するためには-遺伝子関連を中心に-

    池田匡志, 冨田 誠, 岩田 仲生

    臨床精神医学   38   133 - 138   2009年11月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

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  • 臨床疫学における生存時間解析

    冨田 誠

    リウマチ科   42 ( 4 )   455 - 460   2009年10月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

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  • Estimation of haplotype frequencies and diplotype configuration for each subject using pooled DNA data.

    T Ito, S Chiku, E Inoue, M Tomita, N Kamatani

    AMERICAN JOURNAL OF HUMAN GENETICS   71 ( 4 )   449 - 449   2002年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:UNIV CHICAGO PRESS  

    Web of Science

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講演・口頭発表等

  • Genetic Approach and Statistical Approach for Association Study on DNA Data 招待 国際会議

    TOMITA Makoto

    Joint Meeting of 10th Asian Regional Section (ARS) of the International Association for Statistical Computing (IASC) and the NZ Statistical Association (NZSA)  2017年12月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

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  • Real situations on clinical research support and the role of biostatisticians in Japan 国際会議

    TOMITA Makoto

    61st ISI World Statictics Congress  2017年7月 

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    記述言語:英語   会議種別:ポスター発表  

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  • Summary of bio-statistical consultation for clinical research support in Japan 招待 国際会議

    TOMITA Makoto

    62nd ISI World Statistics Congress 2019  2019年8月 

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    記述言語:英語   会議種別:ポスター発表  

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  • Genetic and Statistical Problems for Genome Association Study 招待 国際会議

    TOMITA Makoto

    7th German-Japanese Symposium at TU Dortmund University  2018年7月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

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  • Current situations on clinical research support and the role of biostatisticians in Japan 招待 国際会議

    TOMITA Makoto

    2016 International Conference for JSCS 30th Anniversary in Seattle  2016年10月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

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  • Evaluation an association study and spatial clustering methods applied to DNA data 国際会議

    TOMITA Makoto

    60th World Statistics Congress (ISI2015)  2015年7月 

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    記述言語:英語   会議種別:ポスター発表  

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受賞

  • 貢献賞

    2020年5月   日本計算機統計学会  

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  • 第4回 藤田利治賞(薬剤疫学部門)

    2017年2月  

    冨田 誠

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  • 第15回 堀情報科学振興財団 研究助成(一般)受賞

    2005年4月   堀情報科学振興財団  

    冨田 誠

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共同研究・競争的資金等の研究課題

  • 造血細胞移植後難治性感染症に対する複数ウイルス特異的T細胞療法の臨床研究(研究分担者)

    2019年4月 - 2020年3月

    AMED  日本医療研究開発機構研究費 

    森尾 友宏

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    資金種別:競争的資金

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  • 遺伝・疫学・臨床データへの統計解析アプローチと対象集団へのフィードバック

    2018年4月 - 2023年3月

    日本学術振興会  科学研究費補助金 基盤研究(C) 

    冨田 誠

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    担当区分:研究代表者  資金種別:競争的資金

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  • 自家滑膜幹細胞の半月板損傷を対象とする医師主導治験(研究分担者)

    2018年4月 - 2020年3月

    AMED  日本医療研究開発機構研究費 

    関矢 一郎

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    資金種別:競争的資金

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  • 変形性膝関節症に対する滑膜幹細胞の関節内注射(研究分担者)

    2017年4月 - 2020年3月

    AMED  日本医療研究開発機構研究費 

    関矢 一郎

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    資金種別:競争的資金

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  • 滑膜幹細胞による変形性膝関節症(軟骨・半月板)の再生医療の実用化(研究分担者)

    2015年4月 - 2018年3月

    AMED  日本医療研究開発機構研究費 

    関矢 一郎

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    資金種別:競争的資金

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  • 多発性筋炎・皮膚筋炎へのTK-98薬事承認に向けた研究(研究分担者)

    2014年4月 - 2016年3月

    厚生労働省  厚生労働省科学研究費補助金 

    大山 喬史

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    資金種別:競争的資金

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  • 骨粗鬆症性椎体骨折に対する保存的初期治療の指針策定(研究分担者)

    2014年4月 - 2015年3月

    厚生労働省  厚生労働省科学研究委託業務 

    大川 淳

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    資金種別:競争的資金

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  • 遺伝子多様性データを解明する統合的分析とその発展

    2012年4月 - 2015年3月

    日本学術振興会  科学研究費補助金 基盤研究(C) 

    冨田 誠

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    担当区分:研究代表者  資金種別:競争的資金

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  • DNAデータにおける配列集積性の研究

    2011年12月

    財団法人遺伝学普及会  23年度研究助成(海外渡航費) 

    冨田 誠

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    担当区分:研究代表者  資金種別:競争的資金

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  • 科学的政策決定のための統計数理基盤整備とその有効性実証

    研究課題/領域番号:22240030  2010年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業  基盤研究(A)

    北川 源四郎, 椿 広計, 藤田 利治, 津田 博史, 西山 慶彦, 川﨑 能典, 佐藤 整尚, 土屋 隆裕, 久保田 貴文, 藤田 晴啓, 奥原 浩之, 村上 政勝, 片桐 英樹, 宮本 道子, 曽根原 登, 冨田 誠, 笛田 薫, 蓮池 隆, 宮原 孝夫, 安藤 雅和, 奥原 浩之

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    配分額:49010000円 ( 直接経費:37700000円 、 間接経費:11310000円 )

    本研究では,科学的情報収集に基づく社会価値選択,価値を決定する構造モデル導出,価値のモデル上での最適化,最適化された価値の社会への還元からなる情報循環設計を科学的政策決定の統計数理科学的枠組みと位置づけ,政策の科学的決定に資する統計数理体系構築を目的とした.
    本研究を通じて,公的ミクロ情報分析統計基盤の確立,情報循環加速ツールの開発,時空間可視化ツールの開発を達成し,同成果を自殺予防対策研究,観光政策研究,産業環境政策研究に応用し,それぞれの政策立案に資する新たな知見を得るとともに,データに基づく政策を提言した.

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  • 遺伝子多様性データを解明する統合的分析について

    2009年4月 - 2012年3月

    日本学術振興会  科学研究費補助金若手研究(B) 

    冨田 誠

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    担当区分:研究代表者  資金種別:競争的資金

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  • 抗好中球細胞質抗体関連血管炎患者のgenomic DNA収集に関する研究(研究分担者)

    2009年4月 - 2010年3月

    厚生労働省  厚生労働省科学研究費補助金 

    針谷 正祥

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    資金種別:競争的資金

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  • ポストゲノムにおける遺伝子多様性と疾患情報の関連解析

    2006年4月 - 2007年3月

    堀情報科学振興財団  第15回 堀情報科学振興財団 研究助成(一般) 

    冨田 誠

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    担当区分:研究代表者  資金種別:競争的資金

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  • Identifing Haplotype Block for SNPs data

    2005年 - 2008年

    Gene Science Research 

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    資金種別:競争的資金

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