研究者総覧

興梠 貴英 (コウロ タカヒデ)

  • 医療情報部 教授
Last Updated :2021/09/22

研究者情報

学位

  • 医学博士(東京大学)

ホームページURL

J-Global ID

研究キーワード

  • 機械学習   医療・福祉   セキュリティ   研究デザイン   統計数学   大規模臨床試験   臨床試験   データベース   生活習慣病   個人情報セキュリティ   TNFα   内皮細胞   知識表現   ヒストン修飾   RNAポリメレース   データベース管理   強化学習   インターネットセキュリティ   循環器・高血圧   指紋認証   

研究分野

  • ライフサイエンス / 医療管理学、医療系社会学
  • ライフサイエンス / 循環器内科学
  • ライフサイエンス / 医療管理学、医療系社会学
  • ライフサイエンス / ゲノム生物学
  • 情報通信 / 統計科学

経歴

  • 2013年04月 - 現在  自治医科大学企画経営部医療情報部准教授
  • 2005年04月 - 2013年04月  東京大学大学院健康医科学創造講座特任助教

学歴

  • 2000年04月 - 2005年03月   東京大学大学院   内科学専攻
  • 1991年04月 - 1995年03月   東京大学   医学部   医学科
  • 1989年04月 - 1991年03月   東京大学   理科III類

研究活動情報

論文

  • Takashi Maejima, Tsuyoshi Inoue, Yasuharu Kanki, Takahide Kohro, Guoliang Li, Yoshihiro Ohta, Hiroshi Kimura, Mika Kobayashi, Akashi Taguchi, Shuichi Tsutsumi, Hiroko Iwanari, Shogo Yamamoto, Hirofumi Aruga, Shoulian Dong, Junko F. Stevens, Huay Mei Poh, Kazuki Yamamoto, Takeshi Kawamura, Imari Mimura, Jun-ichi Suehiro, Akira Sugiyama, Kiyomi Kaneki, Haruki Shibata, Yasunobu Yoshinaka, Takeshi Doi, Akimune Asanuma, Sohei Tanabe, Toshiya Tanaka, Takashi Minami, Takao Hamakubo, Juro Sakai, Naohito Nozaki, Hiroyuki Aburatani, Masaomi Nangaku, Xiaoan Ruan, Hideyuki Tanabe, Yijun Ruan, Sigeo Ihara, Akira Endo, Tatsuhiko Kodama, Youichiro Wada
    PLOS ONE 9 5 e96005  2014年05月 [査読有り][通常論文]
     
    Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells.
  • Seitetsu L. Lee, Masao Daimon, Takayuki Kawata, Takahide Kohro, Koichi Kimura, Tomoko Nakao, Daisuke Koide, Masafumi Watanabe, Tsutomu Yamazaki, Issei Komuro
    CIRCULATION JOURNAL 78 4 962 - 966 2014年04月 [査読有り][通常論文]
     
    Background: Right atrial pressure (RAP) is commonly estimated using inferior vena cava (IVC) diameter and its respirophasic variations. Although a guideline has been provided for estimation of RAP due to variation in IVC dimensions based on studies in Western subjects, echocardiographic values in Asian subjects are unknown. Methods and Results: We studied 369 patients who underwent IVC ultrasound within 24h of right heart catheterization (RHO). The maximum and minimum IVC diameter during a respiratory cycle and the percent collapse after a sniff test were measured. These IVC parameters were compared with mean RAP measured on RHO. Receiver operating characteristic curves were generated for each IVC parameter to determine the optimal cut-off to detect RAP >10 mmHg. The IVC maximum diameter cut-off for detecting RAP >10 mmHg was 19 mm (sensitivity, 75%; specificity, 78%) and the percent collapse cut-off was 30% (sensitivity, 75%; specificity, 83%). Both cut-offs were smaller than those previously reported in patients from Western countries. When the cut-off values from the existing guideline were applied to the present cohort, the sensitivity and specificity for normal RAP (0-5 mmHg) were 38.6% and 74.2%, respectively, and 60.0% and 92.0% for elevated RAP (>10 mmHg). Conclusions: The optimal IVC maximum diameter and percent collapse cut-offs to detect elevated RAP were smaller in Asian subjects than in a previously reported Western cohort.
  • Tsuyoshi Inoue, Takahide Kohro, Toshiya Tanaka, Yasuharu Kanki, Guoliang Li, Huay-Mei Poh, Imari Mimura, Mika Kobayashi, Akashi Taguchi, Takashi Maejima, Jun-ichi Suehiro, Akira Sugiyama, Kiyomi Kaneki, Hirofumi Aruga, Shoulian Dong, Junko F. Stevens, Shogo Yamamoto, Shuichi Tsutsumi, Toshiro Fujita, Xiaoan Ruan, Hiroyuki Aburatani, Masaomi Nangaku, Yijun Ruan, Tatsuhiko Kodama, Youichiro Wada
    GENOME BIOLOGY 15 4 R63  2014年 [査読有り][通常論文]
     
    Background: Synergistic transcriptional activation by different stimuli has been reported along with a diverse array of mechanisms, but the full scope of these mechanisms has yet to be elucidated. Results: We present a detailed investigation of hypoxia-inducible factor (HIF) 1 dependent gene expression in endothelial cells which suggests the importance of crosstalk between the peroxisome proliferator-activated receptor (PPAR) beta/delta and HIF signaling axes. A migration assay shows a synergistic interaction between these two stimuli, and we identify angiopoietin-like 4 (ANGPTL4) as a common target gene by using a combination of microarray and ChIP-seq analysis. We profile changes of histone marks at enhancers under hypoxia, PPAR beta/delta agonist and dual stimulations and these suggest that the spatial proximity of two response elements is the principal cause of the synergistic transcription induction. A newly developed quantitative chromosome conformation capture assay shows the quantitative change of the frequency of proximity of the two response elements. Conclusions: To the best of our knowledge, this is the first report that two different transcription factors cooperate in transcriptional regulation in a synergistic fashion through conformational change of their common target genes.
  • Takeshi Inazawa, Kentaro Sakamoto, Takahide Kohro, Raisuke Iijima, Toru Kitazawa, Tsutomu Hirano, Mitsunobu Kawamura, Motoki Tagami, Akira Tanaka, Yasumichi Mori, Tsutomu Yamazaki, Teruo Shiba
    LIPIDS IN HEALTH AND DISEASE 12 142  2013年10月 [査読有り][通常論文]
     
    Aims: Hypercholesterolemia coexisting with diabetes still requires clinical intervention to manage the high risk of cardiovascular disease it poses. No second-step strategy is established, however, for cases where strong statins fail to bring cholesterol down to target levels. In this study we seek to demonstrate the superior effect of ezetimibe in combination with strong statins to reduce LDL-C in Japanese patients suffering from both T2DM and hyper LDL-cholesterolemia. Methods: T2DM outpatients (109 patients from 16 institutes) who failed to achieve the target LDL-C value were recruited and randomly assigned to two groups, a double-dose-statin group and ezetimibe-plus-statin group. Follow-ups were scheduled at 0, 12, 26, and 52 weeks. The primary endpoint was the percentage change in the level of LDL-C from baseline to 12 weeks. Interim results: We could successfully create randomized (gender, age, LDL-C, HbA1c, etc.) two groups except for slight differences in apolipoprotein-B and sd-LDL. Conclusions: RESEARCH is the first prospective, parallel-group, multicenter study comparing a double dose of strong statin with ezetimibe plus strong statin for T2DM patients. The RESEARCH study will provide reliable evidence with which to establish a clinical strategy for diabetics who fail to achieve the target LDL-C value.
  • Eriko Hasumi, Hiroshi Iwata, Takahide Kohro, Ichiro Manabe, Koichiro Kinugawa, Naho Morisaki, Jiro Ando, Daigo Sawaki, Masao Takahashi, Hideo Fujita, Hiroshi Yamashita, Junya Ako, Yasunobu Hirata, Issei Komuro, Ryozo Nagai
    INTERNATIONAL JOURNAL OF CARDIOLOGY 168 2 1429 - 1434 2013年09月 [査読有り][通常論文]
     
    Background: Restenosis after percutaneous coronary intervention (PCI) is still a great concern even in the recent drug-eluting stent (DES) era. As less invasive and sensitive parameter to detect restenosis is needed, this study was aimed to assess whether the clinical implication of temporal change in plasma BNP levels might be a useful indicator of restenosis after DES implantation. Methods and results: 847 consecutive patients who underwent elective PCI using silorimus-eluting sent (SES) between 2005 and 2009 were analyzed. Primary endpoint was subsequent target-lesion revascularization (TLR) after PCI. There was no significant difference in either baseline (TLR + vs. TLR-: 107.2 +/- 172.2 vs. 96.2 +/- 175.5 pg/mL, P=0.53) or follow-up plasma B-type natriuretic peptide (BNP) levels (TLR + vs. TLR-: 88.6 +/- 111.6 vs. 68.5 +/- 226.0 pg/mL, P=0.35) between patients with and without subsequent TLR. Conversely, ratio of follow-up to baseline BNP was significantly higher in patients with TLR (TLR + vs. TLR-: 1.55 +/- 1.58 vs. 1.07 +/- 1.04, P<0.001). Multivariate analysis using logistic regression showed log transformed BNP-ratio was an independent predictor of TLR (adjusted odds ratio (aOR): 1.94, 95%CI: 1.42-2.66, P<0.001). A closer relationship between BNP elevation greater than 2-fold and subsequent TLR was found (aOR: 2.69, 95%CI: 1.27-5.69, P<0.009). Furthermore, propensity score matching analysis showed that the incidence of subsequent TLR was significantly higher in patients with BNP elevation (P<0.001). Conclusion: Serial measurement of plasma BNP levels and its change might be a useful approach to predict restenosis in patients without typical chest symptoms receiving SES. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
  • Takahide Kohro, Tsutomu Yamazaki, Hiroki Sato, Kazuhiko Ohe, Ryozo Nagai
    HYPERTENSION RESEARCH 36 6 559 - 563 2013年06月 [査読有り][通常論文]
     
    The Japanese Society of Hypertension (JSH) updated its hypertension management guidelines in 2009. One of the most significant changes with respect to the 2004 version was the stance towards the use of diuretics: in 2004, their use was cautioned against, but in 2009, it was actively promoted. The purpose of this study was to measure the impact of this change in guidelines on prescription patterns for antihypertensive medications, and to investigate the overall trend in the use of antihypertensives. We used monthly claims data obtained from a database company. Data of patients who were 20 or more years old and prescribed antihypertensives were extracted and analyzed. There were 66 223 patients who were prescribed antihypertensives (mean age 53.6 +/- 11.0). Of these, 38 130 were men and 28 093 were women. The two most prescribed classes of antihypertensives were angiotensin receptor blockers, whose usage steadily increased over a 7-year period, and calcium channel blockers. Prescriptions for antihypertensives in these two classes were also more likely to be continued than those for other antihypertensive classes. The prescription rate for diuretics increased from December 2006 (P<0.0001), but the rate of increase was the same before and after 2009 (P=0.09). The clinical guidelines published in 2009 had no apparent impact on the trend of diuretic prescriptions, despite the radical change in stance concerning the use of antihypertensives. Further effort to disseminate the content of these guidelines, so that it is reflected in actual clinical practice, may be warranted.
  • Shota Fukuda, Kenei Shimada, Masatoshi Fujita, Minoru Yoshiyama, Junichi Yoshikawa, Takahide Kohro, Doubun Hayashi, Tsutomu Yamazaki, Ryozo Nagai
    Journal of Cardiology 61 6 387 - 392 2013年06月 [査読有り][通常論文]
     
    Background: Although increased attention is given to assess absolute values of serum cholesterol profiles as optimal markers for preventing future cardiovascular (CV) events, changes in cholesterol profiles also have the potential to be associated with CV disease outcome in Japanese patients with acute coronary syndrome (ACS). Methods: From the database of the Japanese Coronary Artery Disease (JCAD) study, 2664 patients with ACS who had serial measurements of serum cholesterol profile parameters were enrolled. These patients were followed-up for a mean period of 2.7 years. The endpoint was all CV events. Baseline clinical characteristics of patients with and without CV events were adjusted by the propensity score matching analysis. Results: None of the serum absolute cholesterol profiles at baseline and 6 months later was associated with CV events, except for baseline serum total cholesterol level. However, large improvements in cholesterol profiles correlated with better CV disease outcome. Conclusions: This subanalysis of JCAD demonstrated the importance of serial assessment of serum cholesterol profiles for secondary prevention of CV events in Japanese patients with ACS. Changes in serum cholesterol profiles, rather than their absolute values, correlated with future CV events. © 2013.
  • Takahide Kohro, Tsutomu Yamazaki
    CIRCULATION JOURNAL 77 1 43 - 44 2013年01月 [査読有り][通常論文]
  • Takahide Kohro, Tsutomu Yamazaki, Hiroki Sato, Kenji Harada, Kazuhiko Ohe, Issei Komuro, Ryozo Nagai
    International Heart Journal 54 2 93 - 97 2013年 [査読有り][通常論文]
     
    There have been few reports concerning the trends in antidiabetic drug use in Japan. In 2009, a dipeptidyl peptidase- 4 inhibitor (DPP4I), an antidiabetic with a new mechanism of action, was made available. This study was conducted to analyze the antidiabetic prescription trends in Japan in recent years and the influence of DPP4Is on those trends. We used monthly claims data obtained from a database company. Data from patients 20 years of age or older and who were prescribed antidiabetics were extracted and analyzed. A total of 18,457 patients were prescribed antidiabetics (mean age, 53.6 ± 11.0). The sulfonylurea prescription rate decreased while that of biguanides increased. After the introduction of DPP4Is, use of these agents rapidly increased and the rate further increased one year after DPP4I introduction. DPP4Is also became the most prescribed antidiabetics for those prescribed antidiabetics for the first time. The decrease in the use of sulfonylureas and the increase in the use of biguanides are in accordance with trends observed in the United States and Europe, and probably reflect Japanese physicians' awareness of cumulating evidence gained from studies such as the UK Prospective Diabetes Study (UKPDS). The rapid increase in the DPP4I prescription rate might be the result of several factors including their safety profiles, which were highlighted in clinical studies published just prior to the drugs becoming available. However, there is little data regarding the efficacy of DPP4Is in reducing diabetes related complications, which should be determined in future studies.
  • Papantonis A, Kohro T, Baboo S, Larkin JD, Deng B, Short P, Tsutsumi S, Taylor S, Kanki Y, Kobayashi M, Li G, Poh HM, Ruan X, Aburatani H, Ruan Y, Kodama T, Wada Y, Cook PR
    The EMBO journal 31 23 4404 - 4414 23 2012年11月 [査読有り][通常論文]
     
    Tumour necrosis factor alpha (TNF alpha) is a potent cytokine that signals through nuclear factor kappa B (NF kappa B) to activate a subset of human genes. It is usually assumed that this involves RNA polymerases transcribing responsive genes wherever they might be in the nucleus. Using primary human endothelial cells, variants of chromosome conformation capture (including 4C and chromatin interaction analysis with paired-end tag sequencing), and fluorescence in situ hybridization to detect single nascent transcripts, we show that TNF alpha induces responsive genes to congregate in discrete 'N F kappa B factories'. Some factories further specialize in transcribing responsive genes encoding micro-RNAs that target downregulated mRNAs. We expect all signalling pathways to contain this extra leg, where responding genes are transcribed in analogous specialized factories. The EMBO Journal (2012) 31, 4404-4414. doi:10.1038/emboj.2012.288; Published online 26 October 2012

MISC

  • 麻生 英樹, 城 真範, 神蔦 敏弘, 赤穂 昭太郎, 興梠 貴英 電子情報通信学会技術研究報告. NLP, 非線形問題 112 (389) 13 -17 2013年01月 [査読無し][通常論文]
     
    近年電子的に蓄積されるようになっている大量の医療臨床情報を活用し,治療過程の質の向上につなげることは重要な課題である.我々は,診療過程を医師と患者の間のインタラクションと見なす立場から,循環器内科における診療記録データをマルコフ決定過程でモデル化し,患者の予後のシミュレーションや医師の措置の価値評価を行うことを試みている.医師の措置の価値を評価するためには,なんらかの報酬情報が必要であるが,診療記録データにはその情報は含まれていない.こうした問題に対処するため,エキスパートの観測・行動系列から,エキスパートが想定している報酬情報を推定する逆強化学習の枠組みが提案され,様々なアルゴリズムが提案されている.本発表では,その中からベイズ的逆強化学習のアルゴリズムを紹介し,医療臨床データに適用した結果について述べる
  • 麻生 英樹, 城 真範, 神蔦 敏弘, 赤穂 昭太郎, 興梠 貴英 電子情報通信学会技術研究報告. NC, ニューロコンピューティング 112 (390) 13 -17 2013年01月 [査読無し][通常論文]
     
    近年電子的に蓄積されるようになっている大量の医療臨床情報を活用し,治療過程の質の向上につなげることは重要な課題である.我々は,診療過程を医師と患者の間のインタラクションと見なす立場から,循環器内科における診療記録データをマルコフ決定過程でモデル化し,患者の予後のシミュレーションや医師の措置の価値評価を行うことを試みている.医師の措置の価値を評価するためには,なんらかの報酬情報が必要であるが,診療記録データにはその情報は含まれていない.こうした問題に対処するため,エキスパートの観測・行動系列から,エキスパートが想定している報酬情報を推定する逆強化学習の枠組みが提案され,様々なアルゴリズムが提案されている.本発表では,その中からベイズ的逆強化学習のアルゴリズムを紹介し,医療臨床データに適用した結果について述べる
  • 岩崎 圭悟, 村澤 孝秀, 玉井 久義, 安東 治郎, 脇 嘉代, 内村 祐之, 藤田 英雄, 興梠 貴英, 大江 和彦, 大前 浩司 医療機器学 = The Japanese journal of medical instrumentation 82 (4) 322 -329 2012年08月 [査読無し][通常論文]
  • 麻生 英樹, 城 真範, 神嶌 敏弘, 赤穂 昭太郎, 興梠 貴英 電子情報通信学会技術研究報告. NC, ニューロコンピューティング 111 (419) 107 -112 2012年01月 [査読無し][通常論文]
     
    強化学習は環境中で動作するエージェントのオンライン行動最適化学習のモデルとして用いられることが多いが,マルコフ決定過程や部分観測マルコフ決定過程の上の状態・行動価値評価アルゴリズムや方策最適化アルゴリズムを用いて,あらかじめ収集された報酬つき時系列データをオフラインで分析し,行動や状態の価値評価,方策の改善,将来予測などを行う研究も行われてきている.本稿では,これまでの研究を紹介するとともに,循環器内科における診療記録データへの適用可能性を検討した結果について述べる.
  • 興梠 貴英, 山崎 力 日本循環器病予防学会誌 = Japanese journal of cardiovascular disease prevention 45 (1) 49 -53 2010年02月 [査読無し][通常論文]
  • 橋口 猛志, 林 同文, 興梠 貴英, 真鍋 一郎, 永井 良三 社会技術研究論文集 3 196 -204 2005年 [査読無し][通常論文]
     
    Our group of medical safety, mission program 1 in Shakai-Gijutsu, has been making inter-disciplinary researches for improvement of medical safety. We has developed "Clinical Navigation System", which will be taken advantage of as tools for communication of clinical knowledge, between patients & medical doctors, between medical doctors & medical doctors, and between clinics & hospitals.
  • 高桑 啓輔, 興梠 貴英, 半下石 美佐子, 村田 一郎, 園田 誠, 竹中 克, 大野 実, 小室 一成, 平田 恭信, 永井 良三, 高本 眞一 Japanese circulation journal 64 (0) 2000年04月 [査読無し][通常論文]


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