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Safety, Tolerability, and Pharmacokinetics of E3030, a Novel Peroxisome Proliferator-Activated Receptor <i>α/γ</i>Dual Agonist, in Healthy Japanese Male Subjects

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Pharmacology & Pharmacy 2014年第2期5卷 139-148页

作者： Yutaka takeuchi Yuki Nishioka Yasumi Kitahara Setsuo Hasegawa Akihiro Ohnishi Clinical Development Japan/Asia Clinical Research PCU Eisai Co. Ltd. Tokyo Japan Department of Laboratory Medicine Daisan Hospital Jikei University School of Medicine Tokyo Japan Japan Regulatory Affairs Global Regulatory CFU Eisai Co. Ltd. Tokyo Japan Sekino Clinical Pharmacology Clinic Tokyo Japan Present address: Pharmaspur Inc. Tokyo Japan

Objective: The objectives of the present study were to evaluate the safety of single oral dose E3030 in healthy Japanese male subjects, and to evaluate pharmacokinetics after single oral dose E3030 and food effect on pharmacokinetic profiles. Methods: This study was conducted in a randomized, double-blind, placebo-controlled, ascending single-dose study in 56 healthy Japanese male subjects. Subjects were orally administered E3030 (0.5-40 mg) or placebo. Results: Six of 42 (14%) subjects’ administered E3030 experienced adverse events;however, all adverse events were mild and transient, and there was no dose-dependent increase in any adverse event. Plasma samples were collected over 96 hours after dosing. After administration in the fasted state, Cmax of E3030 was achieved between 1.00 and 1.75 hours, indicating rapid absorption. Both Cmax and AUC were dose-proportional in the range of 0.5 to 40 mg. The average range of elimination half-life was 18.4-23.8 hr. CL/F and Vz/F also remained nearly constant regardless of dose levels. In addition, food effect was exploratorily evaluated in five subjects of administered E3030 (10 mg) in both fasted and fed states. The fed/fasted ratios for the geometric mean of the Cmax and AUC were 0.803 and 0.913, respectively. Conclusion: E3030 was safe and well tolerated at single doses up to 40 mg. The pharmacokinetic profile showed good linearity, and food effect on pharmacokinetics of E3030 was not significant.

关键词： PPAR Agonist Phase 1 Pharmacokinetics Healthy Subjects

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Variations in the mental health and sense of coherence (SOC) of new graduate nurses and the effects of SOC on variations in mental health

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Open Journal of Nursing 2013年第1期3卷 122-129页

作者： Tomoko takeuchi Taisuke Togari Makoto Oe Yukie Takemura Hiromi Sanada Faculty of Liberal Arts The Open University of Japan Chiba Japan Faculty of Nursing Tokyo Healthcare University Tokyo Japan Graduate School of Medicine The University of Tokyo Tokyo Japan Research Hospital The Institute of Medical Science The University of Tokyo Tokyo Japan

The current research conducted a longitudinal study of new graduate nurses at 3 times-prior to their employment as nurses and 3 months and 1 year afterward. This study yielded 3 findings. 1) The mental health of new graduate nurses significantly worsens 3 months after employment as a nurse and mental health 1 year after employment as a nurse was significantly worse than that before employment. 2) A sense of coherence (SOC) is the ability to cope with stressors, and the 3 components of SOC decreased significantly in the year after employment as a nurse. 3) The mental health of new graduate nurses was significantly affected by a low SOC and by previous diminishing of SOC. Findings suggested the importance of support to sustain and improve the mental health of new graduate nurses and the importance of approaches in the workplace to encourage the development of SOC.

关键词： Longitudinal Study Mental Health New Graduate Nurses Sense of Coherence (SOC)

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Hypercalcemia Due to Parathyroid Hormone-Related Protein Induced by Primary Endometrial Clear Cell Adenocarcinoma: Case Report

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Open Journal of Obstetrics and Gynecology 2016年第9期6卷 521-524页

作者： Kyousuke takeuchi Akari Shirakuni Ai Yoshida Akiko Takeda Makoto Sugimoto Department of Obstetrics and Gynecology National Hospital Organization Kobe Medical Center Kobe Japan

Humoral Hypercalcemia of Malignancy (HHM) has been reported in association with a number of malignancies. In gynecologic malignancies, ovarian Clear Cell Carcinoma (CCC) is one of the most commonhistologic subtypes, whereas HHM caused by endometrial CCC is very rare. We report a case of endometrial CCC with HHM, with a low serum intact PTH level, elevated serum PTH-related Peptide (PTH-rP), and immunohistochemically demonstrated PTH-rP in the neoplasm.

关键词： Humoral Hypercalcemia of Malignancy Endometrial Cancer Clear Cell Adenocarcinoma Parathyroid Hormone-Related Protein

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JNK-Mediated FOXO Expression Plays a Critical Role in EGFR Tyrosine Kinase Inhibitor-Induced BIM Expression and Apoptosis

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Journal of Cancer Therapy 2012年第4期3卷 424-434页

作者： Kenji takeuchi Anh Ho Viet Katsumi Kawasaki Kazuto Nishio Fumiaki Ito Department of Biochemistry Faculty of Pharmaceutical Sciences Setsunan University Osaka Japan Department of Genome Biology Kinki University School of Medicine Osaka Japan

BIM, a key proapoptotic member of the BCL-2 family of proteins, is essential for apoptosis triggered by tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR). However, the precise molecular mechanism by which EGFR-TKIs induce BIM expression has remained unclear. A previous study of ours showed that the activetion of c-Jun NH2-terminal kinase (JNK) is critical for the TKI-induced apoptosis in PC-9 cells, a gefitinib-sensitive human NSCLC cell line. In this study, we therefore examined the effect of JNK activation on BIM expression and further investigated the mechanism responsible for TKI-induced apoptosis in PC-9 cells. Northern blotting analysis revealed that the TKI AG1478 induced a substantial increase in the level of BIM mRNA. However, this TKI-induced increase was not observed in dominant-negative JNK overexpressing cell line J12A5 or in the TKI-resistant cell line HP-5R, in which JNK is not activated in response to AG1478. Therefore, JNK activation was correlated with the up-regulation of BIM expression. BIM is known to be a downstream target of forkhead box protein O (FOXO) transcription factors. Immunoblot analysis indicated that the levels of FOXO1, FOXO3a, and FOXO4 transcription factors increased after AG1478 treatment of PC-9 cells but that they were not increased in either J12A5 or HP-5R cells, indicating that FOXO was increased in PC-9 cells through JNK activation. FOXO1 knockdown in PC-9 cells decreased EGFR-TKI-induced BIM expression and apoptosis. These findings provide evidence that JNK activation and subsequent increased FOXO expression play a critical role in EGFR-TKI-induced BIM expression and apoptosis.

关键词： EGFR-TKI FOXO BIM JNK NSCLC

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Separation of Inorganic Anions on A Chemically-Bonded 18-Crown-6 Ether Stationary Phase in Capillary Ion Chromatography

Separation of Inorganic Anions on A Chemically-Bonded 18-Cro...

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第六届上海国际分析化学研讨会

作者： Toyohide takeuchi Kimi Tokunaga Lee Wah Lim Department of Chemistry Faculty of EngineeringGifu University1-1 YanagidoGifu 501-1193Japan

＜正＞Introduction and Results Crown ethers,typically 18-crown-6 ether （18C6E）,have been used to improve the resolution of cations in ion chromatography [1-4]. For example,the addition of 18C6E in the eluent apparently increases the retention of potassium ion to improve the resolution. This is because the association constant of complexation between

关键词： Ion chromatography 18-crown-6 ether inorganic anions retention behavior

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松材线虫的表被层蛋白(英文)

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南京林业大学学报（自然科学版） 2010年第2期34卷 150-151页

作者： Ryoji Shinya Yuko takeuchi Hironobu Morisaka Mitsuyoshi Ueda Kazuyoshi Futai 日本京都大学研究生院环境菌物研究室日本国科学促进会日本京都大学生物大分子研究室

线虫表被层在寄主-寄生者互作中起着多种关键作用。几种凝集素在不同虫龄的表被层中的结合能力测定证明,麦胚凝集素(WGA)仅结合到3龄繁殖幼虫及卵壳表面,但这种结合经常发生在毒性松材线虫分离物中,而不是低毒松材线虫分离物的表被层。... 详细信息

线虫表被层在寄主-寄生者互作中起着多种关键作用。几种凝集素在不同虫龄的表被层中的结合能力测定证明,麦胚凝集素(WGA)仅结合到3龄繁殖幼虫及卵壳表面,但这种结合经常发生在毒性松材线虫分离物中,而不是低毒松材线虫分离物的表被层。卵壳表面WGA的结合最强。WGA经常结合到线虫表被层上。表被层蛋白提取物的分析显示其碳氢化合物及蛋白质谱随线虫发育和对松树寄主的入侵而变化。研究结果表明,松材线虫的表被层蛋白在松树寄主和线虫间的互作中起着重要作用。

关键词：松材线虫麦胚凝集素表被层蛋白

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Measurement of shear wave velocities coupled with an evaluation of elasticity using ARFI elastography in diagnosis of papillary thyroid carcinoma

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Open Journal of Clinical Diagnostics 2013年第4期3卷 178-182页

作者： Ryuhei Okada Masami Suzuki Koji takeuchi Hiroyuki Horikoshi Atsunobu Tsunoda Department of Head and Neck Surgery Gunma Prefectural Cancer Center Gunma Japan Department of Otolaryngology Tokyo Medical and Dental University Tokyo Japan Department of Radiological Diagnosis Gunma Prefectural Cancer Center Gunma Japan

This study aimed to evaluate the diagnostic value of measuring the shear wave velocities (Vs) of thyroid nodules in diagnosis of the thyroid carcinoma. Using Virtual Touch Tissue Quantification (VTTQ) of acoustic radiation force impulse (ARFI) elastography (ACUSON S2000®, Siemens Medical Solutions, Mountain View, CA, USA), we measured the Vs of thyroid nodules in 39 nodules from 34 patients (four males and 30 females) before surgery. Elasticity itself was also estimated by VTTI (Virtual Touch Tissue Imaging) using ARFI. The average Vs of normal thyroid tissue was 2.24 ± 0.68 m/s. Twenty-three out of 39 nodules showed an average 2.52 ± 1.33 m/s. However, 16 other nodules showed “*** m/s”. These 16 nodules showed either “black” or “honeycomb” patterns of elasticity in VTTI. This value suggested that the Vs of these nodules were too fast or heterogenous to measure by this device. After the surgery, the pathologies of these nodules were revealed to be papillary carcinoma (21 cases), adenomatous goiter (11), follicular carcinoma (4), follicular adenoma (2) and follicular lymphoma (1). Five papillary carcinomas were found within adenomatous goiters. Nodules from four follicular carcinomas showed average Vs of 1.92 ± 0.48 m/s, while two follicular adenomas and follicular lymphoma showed 2.19 ± 0.06 and 2.34 m/s respectively. Nodules of adenomatous goiter showed 2.14 ± 0.60 m/s. On the other hand, nodules from five out of 21 papillary carcinomas showed average Vs of 4.00 ± 2.37 m/s. In the nodules of 16 papillary carcinomas, Vs were measured as “*** m/s” and this value was only observed in nodules of papillary carcinoma. These data reflected high and/or heterogenous elasticity of papillary carcinoma, in other words, the tissue of papillary carcinoma was hard and/or heterogenous. It was notable that the Vs value of “*** m/s” strongly suggested papillary carcinoma.

关键词： ARFI Elastography Thyroid Thyroid Nodule

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Successful balloon-occluded retrograde transvenous obliteration for bleeding duodenal varices using cyanoacrylate

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World Journal of Gastroenterology 2013年第6期19卷 951-954页

作者： Rintaro Hashimoto Keitaro Sofue Yoshito takeuchi Kentaro Shibamoto Yasuaki Arai Department of Diagnostic Radiology National Cancer Center Central Hospital

A 76-year-old woman with hepatitis C cirrhosis presented with tarry stools and *** endoscopy demonstrated bleeding duodenal varices in the second portion of the ***-enhanced computed tomography revealed markedly tortuous varices around the wall in the *** afferent veins appeared to have developed,and the right ovarian vein draining into the inferior vena cava was detected as an efferent ***-occluded retrograde transvenous obliteration (BRTO) of the varices using cyanoacrylate was successfully performed in combination with the temporary occlusion of the portal *** no previous publications have used cyanoacrylate as an embolic agent for BRTO to control bleeding duodenal varices,this strategy can be considered as an alternative procedure to conventional BRTO using ethanolamine oleate when numerous afferent vessels that cannot be embolized are present.

关键词： Bleeding duodenal varices Balloon-occluded retrograde transvenous obliteration Cyanoacrylate Combination therapy Temporary portal vein occlusion

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3D晶体取向测试技术在铝合金晶粒变形分析中的应用(英文)

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Transactions of Nonferrous Metals Society of China 2014年第7期24卷 2094-2101页

作者： M.KOBAYASHI H.TODA D.J.LECLERE T.KAMIKO K.UESUGI A.takeuchi Y.SUZUKI Department of Mechanical Engineering Toyohashi University of Technology Department of Mechanical Engineering Kyushu University Japan Synchrotron Radiation Research Institute

非均匀变形在材料工程领域是一个有趣的问题。同步辐射成像技术通过跟踪多晶体铝合金的显微组织的特性,提供了局部应变的3D分布图。为了更加深入地分析非均匀的过程,开发了三维X射线衍射分析技术。它利用跟踪晶界获得的信息(GBT),描述... 详细信息

非均匀变形在材料工程领域是一个有趣的问题。同步辐射成像技术通过跟踪多晶体铝合金的显微组织的特性,提供了局部应变的3D分布图。为了更加深入地分析非均匀的过程,开发了三维X射线衍射分析技术。它利用跟踪晶界获得的信息(GBT),描述了三维空间中新的晶体取向测试技术。

关键词：同步加速器辐射 X射线断层扫描 X射线衍射塑性变形晶体学取向

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天山哈密榆树沟冰川冰尘特征及其成因

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干旱区地理 2014年第3期37卷 429-438页

作者：许慧李忠勤 Nozomu takeuchi 张晓宇洛书飞中国科学院寒区旱区环境与工程研究所冰冻圈科学国家重点实验室/天山冰川站甘肃兰州730000 西北师范大学地理与环境科学学院甘肃兰州730070 日本千叶大学千叶263-8522

利用2011年8月在哈密榆树沟冰川采集的5个冰样,通过石蜡切片技术、16SrRNA系统发育分析及无机颗粒粒度分析方法,结合野外考察,对榆树沟冰川冰尘(cryoconite)的结构特征及形成过程进行了分析研究。结果表明:榆树沟冰川冰尘粒径为0.22～2.... 详细信息

利用2011年8月在哈密榆树沟冰川采集的5个冰样,通过石蜡切片技术、16SrRNA系统发育分析及无机颗粒粒度分析方法,结合野外考察,对榆树沟冰川冰尘(cryoconite)的结构特征及形成过程进行了分析研究。结果表明:榆树沟冰川冰尘粒径为0.22～2.9mm,由有机部分(蓝藻、有机质)与无机部分(无机矿物颗粒)结合形成球状聚合体,它的生长具有季节性并且具有生长、裂解交替循环的生命周期;通过核糖体DNA扩增片段限制性内切酶分析(Amplifed Ribosomal DNA Restriction Analysis,ARDRA),将蓝藻16SrRNA基因文库中的214个阳性克隆分为9个不同的操作分类单元(Operational Taxonomic Unites,OTUs)。经过基因测序、BLAST比对及系统发育分析将9个OTUs归为:颤藻目,色球藻目和未定类群,其中颤藻目为冰尘中蓝藻的绝对优势类群;冰尘中无机矿物颗粒(d<3.5μm)在数量上占绝对优势,体积分布的粒径众数值为14μm,较其它冰川而言,粒径众数较大。经估算,冰尘中有机部分所占比例明显大于无机颗粒,故影响冰川消融区表面反照率的主要因素为冰尘中的有机部分。

关键词：榆树沟冰川冰尘有机物质蓝藻无机矿物颗粒冰川反照率

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