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Limited Effect of Intravenously Administered Indoxyl Sulfate, a Uremic Toxin, on the Hepatic Transport of Pravastatin in Normal Rats

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Pharmacology & Pharmacy 2018年第7期9卷 270-278页

作者： Hideyuki Suga Yuichi Ichimura Satomi Otsuka Kaori Sugaya masako Oda Hiroshi Saitoh Department of Pharmaceutics School of Pharmaceutical Sciences Health Sciences University of Hokkaido Ishikari-Tobetsu Japan

Indoxyl sulfate (IS) is a typical uremic toxin that extensively accumulates in the plasma of patients with seriously impaired renal function. This study seeks to clarify whether IS exerts a potent modulating effect on the hepatic transport of pravastatin, which is a substrate of both organic anion transporting peptides (OATPs) and multidrug resistance-associated protein (Mrp) 2 in rats. When IS is administered intravenously to the normal rats at a dose of 120 μmol/kg;plasma IS levels are approximately 600 μM after 2 min and 100 μM after 120 min. In rats with acute renal failure (ARF) induced by cisplatin, the area under the curve (AUC) was more than 2.5-fold greater compared with that in the normal rats, indicating that IS accumulates in ARF rats. Intravenously administered pravastatin almost disappeared from the plasma by 60 min post-administration and approximately 55% of dose was excreted in the bile within 60 min. This result suggested that pravastatin was efficiently taken up from the sinusoid into hepatocytes via rat OATPs on the sinusoidal membrane and preferentially transported in the bile mediated by Mrp2 on the canalicular membrane. IS administered intravenously at a dose of 120 μmol/kg caused neither an increase in plasma pravastatin levels nor a decrease in its biliary excretion. In conclusion, the present results demonstrate that single intravenous administration of IS does not interfere with the hepatic transport of pravastatin directly in vivo, which is at variance with the results of previous in vitro studies.

关键词： Indoxyl Sulfate Pravastatin Drug Interaction Hepatic Transport Biliary Excretion

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Shift of threshold temperature for the activation of HSF In chicken red blood cells during embryonic development

Shift of threshold temperature for the activation of HSF In ...

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Third Congress of the Asian-Pacific Organization for Cell Biology

作者： Yoshinori Kawazoe masako Tanabe Kazuhiro Nagata Akira Nakai Department of Molecular and Cellular Biology Institute for Frontier Medical ScisncesKyoto UniversitySakyo-kuKyoto 606-8397Japan and CRESTJST

The expression of heat shock genes are regulated mainly at the level of transcription by heat shock transcription factors (HSFs 1-4) in vertebrates. In avian cells, HSF1 is rapidly activated even by mild heat shock, a...

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Effects of a Traditional Japanese Medicine Goshajinkigan, Tokishigyakukagoshuyushokyoto on the Warm and Cold Sense Threshold and Peripheral Blood Flow

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Health 2014年第8期6卷 757-763页

作者： Rika Tsukada Takuji Yamaguchi Liu Hang masako Iseki Hiroyuki Kobayashi Eiichi Inada Center for Advanced Kampo Medicine and Clinical Research Juntendo University School of Medicine Tokyo Japan Department of Anesthesiology and Pain Medicine Juntendo University School of Medicine Tokyo Japan

The purpose of this study was to investigate the effects of a traditional Japanese medicine Goshajinkigan (TJ-107) and Tokishigyakukagoshuyushokyoto (TJ-38) on warm sense threshold, cold sense threshold and the peripheral blood flow. 31 healthy volunteers (control group: 9people, TJ-107 group: 12 people, TJ-38group:10 people) were examined. Drugs administered 2.5 g a dose. Analysis was before and after 1 hour dosage. The warm and cold sense threshold in the thenar of the non-handedness site of these subjects was measured using a thermostimulator (Intercross-200, Intercross Co., Tokyo, Japan). The peripheral blood flow in the finger of the non-handedness site of these subjects was measured using a full-field laser perfusion imager (FLPI, Moor Instruments Ltd., England). Control: The vehicle had no significant effect on the warm sense threshold, cold sense threshold and the peripheral blood flow. TJ-107: The warm sense threshold and cold sense threshold were significantly decreased, and the reaction latency of cold sense was significantly shortening. The peripheral blood flow was significantly increased second and third finger at 115.6%, 119.3%, respectively. TJ-38: The cold sense threshold and the reaction latency of cold sense were significantly increased. The peripheral blood flow was significantly increased second and third finger with 114.3%, 112.8%, respectively. These results suggest that TJ-107 and TJ-38 have effects on the changed warm sense threshold, cold sense threshold and increased peripheral blood flow.

关键词： A Traditional Japanese Medicine Goshajinkigan Tokishigyakukagoshuyushokyoto The Warm and Cold Sense Threshold Peripheral Blood Flow

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Effects of scientific explanation on purchasing behavior

Effects of scientific explanation on purchasing behavior

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第十七届国际工效学大会暨中国人类工效学会成立20周年庆祝大会

作者： masako Dohi Masaaki Mochimaru Itsumi Kakefuda Makiko Kouchi Digital Human Research Center AIST Otsuma Women's University

The purpose of this study was to examine the effect of scientific explanation on purchasing behavior in the context of mail-ordered *** function of shock absorption insole for women was tested,and two types of catalogs for the tested insole were created:one included the scientific explanation about the function of the insole and the other did *** 780,000 catalogs were distributed and insoles were sold for 6 *** rate of the insoles between the two types of catalogs were *** a selling period of 6 months,a web survey was conducted targeting the catalog customers who bought the insoles to examine the associations between exposure to scientific information and purchasing *** were as follows:Overall purchase rate did not show a significant difference between the two catalog ***,purchase rate was associated with catalog type when age group was *** subscribers between 40 and 49 ***,purchase rate from the catalog with scientific explanation was higher than those from the catalog without scientific *** decision processes differed according to the type of catalog *** shows the possibility that purchasing behavior will be influenced by scientific *** behavior may change and improve by creating comprehensible scientific explanation pages that increase consumers’interest in functions of products.

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Role of regulatory T cell in the pathogenesis of inflammatorybowel disease

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World Journal of Gastroenterology 2016年第7期22卷 2195-2205页

作者： akiko yamada rieko arakaki masako saito takaaki tsunematsu yasusei kudo naozumi ishimaru Department of Oral Molecular Pathology Tokushima University Graduate SchoolTokushima 770-8504Japan

Regulatory T(Treg) cells play key roles in various immune responses. For example, Treg cells contribute to the complex pathogenesis of inflammatory bowel disease(IBD), which includes Crohn's disease and ulcerative colitis during onset or development of that disease. Many animal models of IBD have been used to investigate factors such as pathogenic cytokines, pathogenic bacteria, and T-cell functions, including those of Treg cells. In addition, analyses of patients with IBD facilitate our understanding of the precise mechanism of IBD. This review article focuses on the role of Treg cells and outlines the pathogenesis and therapeutic strategies of IBD based on previous reports.

关键词： Inflammatory bowel disease Regulatory Tcell Animal model Therapy

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The Impact of Chronic Social Stress on Emotional Behavior in Mice and the Therapeutic Effect of Peripheral Mild-Heat Stimulation

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Health 2015年第10期7卷 1294-1305页

作者： Hang Liu Takuji Yamaguchi Kenji Ryotokuji Satoru Otani Hiroyuki Kobayashi masako Iseki Eichi Inada Department of Anesthesiology and Pain Management School of Medicine Juntendo University Tokyo Japan Center for Advanced Kampo Medicine and Clinical Research Juntendo Graduate School of Medicine Tokyo Japan Institute of Transcultural Studies Ryotokuji University Chiba Japan Center for Medical Education Ryotokuji University Chiba Japan 5Department of Hospital Administration Juntendo University Graduate School of Medicine Tokyo Japan

In today’s stressful society, mental diseases such as adjustment disorder, affective disorders including anxiety and depression, and chronic fatigue syndrome could be attributed to social stress and are considered as serious social problems. It has been long known in the acupuncture and moxibustion therapies in Japan and China that stimulation at Zhongwan and Taichong points have effects on stress-related anxiety and depression. In the present study, we therefore tested the effect of peripheral mild-heat stimulation at Zhongwan and Taichong on anxiety and brain biochemistry using a mouse model of chronic social stress. Male ddY mice (4 weeks old) were stressed by isolated rearing for 6 weeks. They received mild-heat stimulation (43℃?for 5 min) at Zhongwan and Taichong under isoflurane anesthesia after 4 weeks of the social isolation 3 times a week for 2 weeks, using the “Stress Free Apparatus” (Ryoken Co., Ltd). Control mice received only isoflurane anesthesia. Group-reared mice also underwent the same stimulus/anesthesia sessions. Two days after the last peripheral heat stimulation, anxiety was determined by the light/dark box test as the time spent in the light compartment and the number of transfer between the light and dark compartments. Before and after the last stimulation, blood was collected from an artery at the back of the eye, and serum corticosterone, immunoglobulin E (IgE) which was an index of the inflammatory immune system, and interleukin 6 (IL-6) were measured using ELISA Kit. The frontal cortex was collected after the behavioral test, and the dopamine and serotonin contents were measured also by ELISA Kit. A significant decrease of the time spent in the light compartment was observed after the isolated rearing (p < 0.01). Mild-heat stimulation significantly increased the time spent in the light compartment, indicating an anti-anxiety effect. Serum corticosterone, IgE and IL-6 were increased after stress, and the amount of serotonin in the frontal c

关键词： Chronic Stress Anxiety Acupuncture Frontal Cortex Corticosterone

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Developing Thick Cardiac Tissue with a Multilayer Fiber Sheet for Treating Myocardial Infarction

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Advanced Fiber Materials 2023年第6期5卷 1905-1918页

作者： Junjun Li Xiang Qu Li Liu Lingjun Li Ying Hua Jingbo Zhang masako Ishida Noriko Yoshida Akiko Tabata Nagako Sougawa Emiko Ito Noriko Mochizuki‑Oda Akima Harada Takuji Kawamura Ryohei Matsuura Yingzhe Wang Keisuke Morishima Shigeru Miyagawa Yoshiki Sawa Department of Cardiovascular Surgery Osaka University Graduate School of Medicine2‑2 YamadaokaSuita 565‑0871Japan Frontier of regenerative medicine Osaka University Graduate School of Medicine2‑2 YamadaokaSuita 565‑0871Japan Department of Physiology Osaka Dental University8‑1 Kuzuha Hanazono‑choHirakata 573‑1121Japan Department of Mechanical Engineering Graduate School of EngineeringOsaka UniversitySuita 565‑0871Japan Global Center for Medical Engineering and Informatics Osaka UniversityOsaka 565‑0071Japan Division of Health Sciences Osaka University Graduate School of MedicineSuita 565‑0871Japan

Human-induced pluripotent stem cell (hiPSC)-derived cardiac patches have been extensively used for treating myocardialinfarction and have shown potential for clinical application. However, the limited patch thickness can hamper its therapeuticeffect. We previously developed a fibrous scaffold that allowed the formation of well-organized cardiac tissue constructs. Inthe present study, based on the above technology, we developed a three-dimensional multilayer fibrous scaffold with dynamicperfusion, on which approximately 20 million hiPSC-derived cardiomyocytes (CMs) could be seeded in a single step andorganized into 1 mm thick and viable tissue. The multilayer cardiac tissue demonstrated enhanced contractile properties andupregulated cytokine secretion compared with the control group. Notably, when used on the myocardial infarction model,the multilayer group showed improved functional recovery and less fibrosis. These results indicated that the appropriatehiPSC-CM dose requires careful evaluation in developing clinical therapy. The multilayer cardiac tissue group demonstratedsignificant improvement than the control group, indicating that higher doses of transplanted cells may have improvedtherapeutic effects in treating myocardial infarction.

关键词： Fiber Tissue engineering Pluripotent stem cell Cardiomyocyte Myocardial infarction Regenerative therapy

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Crucial roles of macrophages in the pathogenesis of autoimmune disease

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World Journal of Immunology 2017年第1期7卷 1-8页

作者： Aya Ushio Rieko Arakaki Akiko Yamada masako Saito Takaaki Tsunematsu Yasusei Kudo Naozumi Ishimaru Department of Oral Mole-cular Pathology Tokushima University Graduate School of Biomedical Sciences Department of Human Genetics Tokushima University Graduate School of Biomedical Sciences Department of Pathology and Laboratory Medicine Tokushima University Graduate School of Biomedical Sciences

Macrophages are key players in various immune responses. In addition to functions in innate immunity such as antigen phagocytosis and cytokine production, antigen presentation by macrophage represents a link between innate and acquired immunity. During inflammatory processes, naive monocytes differentiate into pro-inflammatory M1 and anti-inflammatory M2 macrophages. Resident monocytes/macrophages contribute to immune response that maintains tissue-specific homeostasis. In the target organs of autoimmune diseases, macrophages have dual functions in both the induction and suppression of autoimmune responses, which are mediated by production of various cytokines and chemokines, or by interaction with other immune cells. This review focuses on selected autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and Sjogren’s syndrome, to illustrate the key roles of macrophages in the cellular or molecular patho-genesis of autoimmunity. In addition, the contribution of macrophages to each autoimmune disease is compared.

关键词： Macrophage Autoimmunity Differentiation Cytokines Chemokines

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Detection of the <i>PIK3CA</i>Mutation in Circulating Tumor DNA as a Possible Predictive Indicator for Poor Prognosis of Early-Stage Breast Cancer

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Journal of Cancer Therapy 2018年第1期9卷 42-54页

作者： Ayaka Sato Masahiko Tanabe Yumi Tsuboi masako Ikemura Keiichiro Tada Yasuyuki Seto Yoshinori Murakami Division of Molecular Pathology Institute of Medical Science The University of Tokyo Tokyo Japan Department of Breast and Endocrine Surgery Graduate School of Medicine The University of Tokyo Tokyo Japan Department of Pathology Graduate School of Medicine The University of Tokyo Tokyo Japan

Objectives: Circulating tumor DNA (ctDNA) is shown to provide the real-time genomic information of metastatic breast cancer. This study elucidates the clinico-pathological significance of ctDNA in early-stage breast cancer using the PIK3CA mutation as an indicator. Materials and Methods: Twenty-seven primary breast cancers without metastasis were surgically resected and pathologically diagnosed at the University of Tokyo Hospital, Japan. Genomic DNA of primary tumor was extracted from formalin-fixed and paraffin-embedded specimens. ctDNA was extracted from fresh-frozen plasma from patients. The PIK3CA mutations at E542K, E545K and H1047R were examined by Sanger sequencing or droplet digital PCR in 27 tumors and pre- and post-surgery plasma. Results: The PIK3CA mutations were detected in 13 (48%) of 27 primary tumors. These mutations did not significantly correlate with specific clinico-pathological characteristics of tumors. When ctDNA was examined, 4 (33%) of 12 cases carrying the mutated PIK3CA showed the identical mutation in pre-surgery plasma and 2 (50%) of them showed the identical mutations in post-surgery plasma. Interestingly, in these 2 cases in pathological stages IIIA and IA, fractional abundance of the mutated PIK3CA alleles to the total alleles in pre-surgery ctDNA was around 1% or more and was higher than that of the other two cases without PIK3CA mutations in post-surgery ctDNA. Conclusions: The PIK3CA mutation in ctDNA is detectable even in a subset of early-stage breast cancer. Furthermore, fractional abundance of the mutated PIK3CA in pre-surgery ctDNA could provide a possible predictive indicator for tumor burden and for choosing the appropriate adjuvant treatment of breast cancer.

关键词： Early-Stage Breast Cancer PIK3CA Circulating Tumor DNA Plasma Droplet Digital PCR

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日本财阀和帝国主义--以三井物产株式会社为例

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抗日战争研究 2009年第2期 106-112页

作者：坂本雅子[日] 名古屋经济大学经济学部教授

日本的财阀企业和侵略战争之间究竟是一种什么样的关系?日本侵华战争背后的资本主义要求是什么?这一要求是以什么样的方式表现出来的?资本主义和企业的经济利害关系如何转化为侵略战争?为解决这些问题,本文以不同于列宁的帝国主义论的... 详细信息

日本的财阀企业和侵略战争之间究竟是一种什么样的关系?日本侵华战争背后的资本主义要求是什么?这一要求是以什么样的方式表现出来的?资本主义和企业的经济利害关系如何转化为侵略战争?为解决这些问题,本文以不同于列宁的帝国主义论的新视角,选取日本资本主义的代表性企业三井物产株式会社为研究对象,具体分析日本财阀和侵略战争之间的内在联系,努力探求侵略和战争的真正原因和规律性。

关键词：日本财阀帝国主义三井物产侵略战争

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