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Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines

Joint 48th IEEE Conference on Decision and Control and 28th Chinese Control Conference

作者： Akira kojima Taro Tsuchiya Faculty of System Design Tokyo Metropolitan University

Stability conditions for state-delay systems are derived based on the norm of semigroup, which describes the transition of the internal state. Introducing an exact calculation method of the semigroup norm, the conditions for the internal stability and the marginal stability are characterized by nonsingularity of a transcendental function. The conditions depend on the existence of time interval such that the semigroup turns to a contraction map and enable us to approach the necessary and sufficient condition by extending the interval. The feature of proposed method is discussed with numerical examples.

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World Journal of Gastroenterology 2018年第4期24卷 511-518页

作者： Yuichiro kojima Yosuke Hirotsu Wataru Omata Makoto Sugimori Shinya Takaoka Hiroshi Ashizawa Keiko Nakagomi Dai Yoshimura Kenji Hosoda Yoji Suzuki Hitoshi Mochizuki Masao Omata Department of Gastroenterology Yamanashi Prefectural Central Hospital Genome Analysis Center Yamanashi Prefectural Central Hospital Department of Dermatologic Oncology National Cancer Institute Division of Gastroenterology Department of Medicine Yokohama City University Graduate School of Medicine Department of Gastroenterology Genome Analysis Center Yamanashi Prefectural Central Hospital

AIM The single nucleotide polymorphism(SNP) c.415C>T in exon 3 of NUDT15 affects thiopurine-induced leukopenia in Asian patients with Crohn's disease. Meanwhile, three additional genetic variants of NUDT15 were reported in patients with acute lymphoblastic leukemia. We evaluated the effects of these additional genetic variants of NUDT15 in patients with inflammatory bowel disease(IBD) treated with *** Ninety-six Japanese patients with IBD were enrolled. Genotyping for the NUDT15 and TPMT genes was performed using Custom Taq Man SNP genotyping assays or Sanger sequencing. The changes in white blood cell(WBC) count, mean corpuscular volume(MCV), platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT, and ESR were *** Genetic variants of exon 1 and exon 3 of NUDT15 were identified in 24 of 96 patients(25.0%). C.52G > A and c.36_37 insG GAGTC in exon 1 were found in three patients each. All three patients with c.36_37 insG GAGTC in exon 1 were heterozygotes of ***139 Cys in exon 3. Eighteen patients had ***139 Cys in exon 3 alone. The WBC count gradually decreased after initiation of thiopurine treatment in the mutated cases(n = 24), and was significantly lower at 6, 8, 10, and 16 wk(P = 0.0271, 0.0037, 0.0051, and 0.0185, respectively). The WBC counts were also evaluated in patients with and without prednisolone treatment. In the patients with prednisolone treatment, the WBC count tended to show a greater decrease in the mutated cases, with significant differences at 8 and 10 wk(P = 0.012 and 0.029, respectively). In the patients without prednisolone treatment, the WBC count was significantly lower at 2, 4, 8, and 14 wk in mutated cases(P = 0.0196, 0.0182, 0.0237 and 0.0241, respectively). MCV increased after starting thiopurine treatment in the mutated cases, and was significantly higher at 10 wk(P = 0.0085). Platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT and ESR did not differ significantly between the wildtype and

关键词： Inflammatory bowel disease NUDT15 Leukopenia Mean corpuscular volume Japanese

Inverse Estimation on Trigger Factors of Simultaneous Slope Failures with Purification of Training Data Sets

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Journal of Earth Science and Engineering 2013年第9期3卷 594-602页

作者： Hirohito kojima Ryo Sekine Tomoya Yoshida Ryo Nozaki Department of Civil Engineering Faculty of Science & Technology Tokyo University of Science Chiba 278-8510 Japan Bureau of Waterworks Tokyo Metropolitan Government Tokyo 163-8001 Japan

This paper presents an procedure for purifying training data sets (i. e., past occurrences of slope failures) for inverse estimation on unobserved trigger factors of "different types of simultaneous slope failures". Due to difficulties in pixel-by-pixel observations of trigger factors, as one of the measures, the authors had proposed an inverse analysis algorithm on trigger factors based on SEM (structural equation modeling). Through a measurement equation, the trigger factor is inversely estimated, and a TFI (trigger factor influence) map can be also produced. As a subsequence subject, a purification procedure of training data set should be constructed to improve the accuracy of TFI map which depends on the representativeness of given training data sets of different types of slope failures. The proposed procedure resamples the matched pixels between original groups of past slope failures (i. e., surface slope failures, deep-seated slope failures, landslides) and classified three groups by K-means clustering for all pixels corresponding to those slope failures. For all cases of three types of slope failures, the improvement of success rates with respect to resampled training data sets was confirmed. As a final outcome, the differences between TFI maps produced by using original and resampled training data sets, respectively, are delineated on a DIF map (difference map) which is useful for analyzing trigger factor influence in terms of "risky- and safe-side assessment" sub-areas with respect to "different types of simultaneous slope failures".

关键词：触发因素数据集逆估计训练故障斜率同步净化

Aerodynamic Behavior of Snowflakes on an Uneven Road Surface during a Snowstorm

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Open Journal of Fluid Dynamics 2017年第4期7卷 696-708页

作者： kojima Tetsuya Yoichi Yamagishi Shigeo Kimura Kengo Sato Meteorological Research Institute for Technology Co. LTD. Tokyo Japan Department of Mechanical Engineering Kanagawa Institute of Technology Kanagawa Japan National Research Institute for Earth Science and Disaster Resilience Yamagata Japan

The removal of snow from a road or railroad results in an uneven surface and thus the formation of snowdrifts. However, the effect of a surface bump on the scale of a snowdrift is not clear. Snowdrift wind tunnel tests have long been performed to predict the snow cover distribution due to a snowstorm. However, such tests require a large-scale experimental device, have high installation and maintenance costs, and are not easy to perform. The present study thus used a small water tunnel that is easier to implement. The snowdrift pattern for the real phenomenon of a cube model was reproduced using the small water tunnel and the performance of the tunnel thus verified. The snowdrift water tunnel was then used to predict the snowdrift distribution for uneven surfaces. The tunnel well reproduced the snow cover distribution when the sedimentation velocity ratio and Stokes number in the water tunnel test were the same as those for the real phenomenon, again verifying the performance of the water tunnel test.

关键词： Snowstorm Water Tank Model Snow Bump Model Snowdrift Distribution Numerical Analysis

Daikenchuto (Da-Jian-Zhong-Tang) ameliorates intestinal fibrosis by activating myofibroblast transient receptor potential ankyrin 1 channel

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World Journal of Gastroenterology 2018年第35期24卷 4036-4053页

作者： Keizo Hiraishi Lin-Hai Kurahara Miho Sumiyoshi Yao-Peng Hu Kaori Koga Miki Onitsuka Daibo kojima Lixia Yue Hidetoshi Takedatsu Yu-Wen Jian Ryuji Inoue Department of Physiology Graduate School of Medical Sciences Fukuoka University Department of Pathology Faculty of Medicine Fukuoka University Department of Gastroenterological Surgery Faculty of Medicine Fukuoka University Department of Cell Biology University of Connecticut Health Center Department of Gastroenterology and Medicine Faculty of Medicine Fukuoka University College of Letters and Science University of CaliforniaDavis

AIM To investigate the anti-fibrotic effects of the traditional oriental herbal medicine Daikenchuto(DKT) associated with transient receptor potential ankyrin 1(TRPA1) channels in intestinal myofibroblasts. METHODS Inflammatory and fibrotic changes were detected in a2,4,6-trinitrobenzenesulfonic acid(TNBS) chronic colitis model of wild-type and TRPA1-knockout(TRPA1-KO) mice via pathological staining and immunoblotting ***^(2+) imaging experiments examined the effects of DKT and its components/ingredients on intestinal myofibroblast(In Myo Fib) cell TRPA1 channel *** factors and transforming growth factor (TGF) -β1-associated signaling were tested in an In Myo Fib cell line by q PCR and immunoblotting *** from non-stenotic and stenotic regions of the intestines of patients with Crohn’s disease (CD) were used for pathological analysis. RESULTS Chronic treatment with TNBS caused more severe inflammation and fibrotic changes in TRPA1-KO than in wild-type mice.A one-week enema administration of DKT reduced fibrotic lesions in wild-type but not in TRPA1-KO *** active ingredients of DKT,i.e.,hydroxyα-sanshool and 6-shogaol,induced Ca^(2+) influxes in In Myo Fib,and this was antagonized by co-treatment with a selective TRPA1 channel blocker,*** counteracted TGF-β1-induced expression of TypeⅠcollagen andα-smooth muscle actin (α-SMA) ,which were accompanied by a reduction in the phosphorylation of Smad-2 and p38-mitogen-activated protein kinase (p38-MAPK) and the expression of ***,24-h incubation with a DKT active component Japanese Pepper increased the m RNA and protein expression levels of TRPA1 in In Myo Fibs,which in turn negatively regulated collagen *** the stenotic regions of the intestines of CD patients,TRPA1 expression was significantly *** The effects of DKT on the expression and activation of the TRPA1 channel could be advantageous for suppressing intestinal fibrosis

关键词： Intestinal fibrosis Myofibroblast Transient receptor potential ankyrin 1 Crohn’s disease Collagen α-smooth muscle actin

Induction heating for desorption of surface contamination for high-repetition laser-driven carbon-ion acceleration

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Matter and Radiation at Extremes 2023年第5期8卷 19-25页

作者： Sadaoki kojima Tatsuhiko Miyatake Hironao Sakaki Hiroyoshi Kuroki Yusuke Shimizu Hisanori Harada Norihiro Inoue Thanh Hung Dinh Masayasu Hata Noboru Hasegawa Michiaki Mori Masahiko Ishino Mamiko Nishiuchi Kotaro Kondo Masaharu Nishikino Masaki Kando Toshiyuki Shirai Kiminori Kondo Kansai Institute for Photon Science National Institutes for Quantum Science and Technology(QST)8-1-7 UmemidaiKizugawaKyoto 619-0215Japan Interdisciplinary Graduate School of Engineering Sciences Kyushu University6-1Kasuga-KoenKasugaFukuoka 816-8580Japan Hitachi Zosen Corporation 7-89 Nanko-Kita 1-chomeSuminoe-kuOsaka 559-8559Japan Department of Accelerator and Medical Physics Institute for Radiological ScienceNational Institutes for Quantum Science and Technology(QST)4-9-1 AnagawaInage-kuChiba 263-8555Japan

This study reports the first experimental demonstration of surface contamination cleaning from a high-repetition supply of thin-tape targets for laser-driven carbon-ion *** adsorption of contaminants containing protons,mainly water vapor and hydrocarbons,on the surface of materials exposed to low vacuum(>10^(−3)Pa)suppresses carbon-ion *** newly developed contamination cleaner heats a 5-μm-thick nickel tape to over 400℃in 100 ms by induction *** the future,this heating method could be scaled to laserdriven carbon-ion acceleration at rates beyond 10 *** contaminant hydrogen is eliminated from the heated nickel surface,and a carbon source layer—derived from the contaminant carbon—is spontaneously formed by the catalytic effect of *** species of ions accelerated from the nickel film heated to various temperatures have been observed *** the nickel film is heated beyond∼150℃,the proton signal considerably decreases,with a remarkable increase in the number and energy of carbon *** Langmuir adsorption model adequately explains the temperature dependence of desorption and re-adsorption of the adsorbed molecules on a heated target surface,and the temperature required for proton-free carbon-ion acceleration can be estimated.

关键词： acceleration heated nickel

Local regulator adrenomedullin contributes to the circulatory disturbance in cirrhotic rats

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World Journal of Gastroenterology 2006年第13期12卷 2095-2102页

作者： Shinya Sakurai Hideyuki kojima Masahito Uemura Hiroyasu Satoh Hiroshi Fukui Third Department of Internal Medicine Nara Medical University 840 Shijo-cho Kashihara-shiNara 634-8522Japan Department of Pharmacology Nara Medical University 840 Shijo-cho Kashihara-shiNara 634-8522Japan

瞄准：调查是否 adrenomedullin，有势力血管扩张药肽，在肝硬化在循环骚乱起一个作用。方法：肝硬化被四氯化碳的每周的管饲法在老鼠导致。血液动力学的研究用孤立的大动脉的戒指是用放射性的微范围和在试管内的执行在活体内。adrenome... 详细信息

瞄准：调查是否 adrenomedullin，有势力血管扩张药肽，在肝硬化在循环骚乱起一个作用。方法：肝硬化被四氯化碳的每周的管饲法在老鼠导致。血液动力学的研究用孤立的大动脉的戒指是用放射性的微范围和在试管内的执行在活体内。adrenomedullin 集中被放射性免疫测定测量。结果：到控制老鼠的 adrenomedullin 的尖锐管理与氮的氧化物(NOx ) 的稳定的代谢物的浆液层次的增加一起减少了全身的动脉压，以一种剂量依赖者方式。adrenomedullin 的长期的注入减少了脉管的抵抗并且在全身、内脏的发行量增加了血流。而这抗体改善了， anti-adrenomedullin 抗体的静脉内的管理没在肝脏硬化症的老鼠影响任何血液动力学的参数对脱羟肾上腺素的弄钝的可收缩的反应， alpha 肾上腺素能的受体收缩筋，在肝脏硬化症的老鼠的大动脉的戒指。在主动脉的 adrenomedullin 集中比在控制在肝脏硬化症的老鼠是更高的，并且在肝脏硬化症的老鼠与吝啬的动脉压相关。而且， adrenomedullin 弄钝可收缩的反应到脱羟肾上腺素在控制主动脉和肝脏硬化症的主动脉，然而并非面对 NG-nitro-L-arginine 甲基酉旨，一没有 synthase 禁止者。结论：Adrenomedullin 在脉管的墙中生产过多可以作为脉管的音调而非传播荷尔蒙的一个本地管理者在肝硬化贡献循环骚乱。

关键词：肝硬化循环治疗血管舒张病理机制

高温快速加热条件下压力对煤气化反应特性的影响

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燃烧科学与技术 2012年第1期18卷 15-19页

作者：刘皓黄永俊杨落恢祝贺任瑞琪严丽叶 kojima Toshinori 苏州大学能源学院苏州215006 成蹊大学物质与生命科学系

建立了一套能同时实现高温高压和快速加热的实验设备和研究方法,使煤气化反应动力学基础研究能在与实际气流床煤气化炉相近的条件下进行.研究表明,当CO2体积分数相同时,最大CO生成速度随压力的升高而升高;煤焦的气化反应速度随全压的升... 详细信息

建立了一套能同时实现高温高压和快速加热的实验设备和研究方法,使煤气化反应动力学基础研究能在与实际气流床煤气化炉相近的条件下进行.研究表明,当CO2体积分数相同时,最大CO生成速度随压力的升高而升高;煤焦的气化反应速度随全压的升高而升高.即使全压和CO2体积分数不同,只要CO2的分压、温度等其他条件相同,煤焦的气化反应速度就基本上一致.说明全压和CO2体积分数对煤焦气化反应速度的影响可以归纳为CO2分压的影响.高温快速加热条件下,除了温度以外,CO2分压是影响煤气化特性的重要因素.

关键词：煤气化流化床

Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice

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World Journal of Gastroenterology 2008年第41期14卷 6303-6305页

作者： Simona Perboni Cyril Bowers Shinya kojima Akihiro Asakawa Akio Inui Unità Operativa Day Hospital Area Medica Azienda Ospedaliera di Desenzano sul Garda Ospedale di Manerbio Tulane University Health Science Center New Orleans Department of Psychosomatic Internal Medicine Kagoshima University Graduate School of Medical and Dental Sciences

The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemo- therapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin agonist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumourbearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU + GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was signifi cantly increased in mice treated with the combination of 5-FU + GHRP-2 versus the 5-FU alone (P = 0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2,5-FU and 5-FU + GHRP-2 signifi cantly increased com- pared with naive and vehicle groups (P = 0.0007, P = 0.0038 and P = 0.0166, respectively). The median survival time was longer in 5-FU + GHRP-2 treated mice than in those with 5-FU, although it was not signifi cant (18 d versus 15.5 d, P = 0.7). For the fi rst time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the effi cacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.

关键词： GHS 癌症食欲缺乏食物摄取癌细胞