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The New Molecular Entity Evolocumab, One Kind of PCSK9 Inhibitor, Reduce Plasma Small Size LDL-Cholesterol Levels by Using a New Standardized Method of Measuring LDL Size

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Open Journal of Molecular and Integrative Physiology 2017年第1期7卷 1-23页

作者： Ikuo Inoue Ryo Kubota Shohan Yanagi Masumi Akita takanari nakano Shigehiro Katayama Akira Shimada Mistuhiko Noda Department of Endocrinology and Diabetology Saitama Medical University Saitama Japan Department of Health Sciences Saitama Prefectural University Saitama Japan Research and Development Department Advanced Materials Development Sector Tokyo Metropolitan Industrial Technology Research Institute Tokyo Japan Division of Morphological Science Biomedical Research Center Saitama Medical University Saitama Japan Department of Biochemistry Saitama Medical University Saitama Japan

Aims: There has been no evidence on the effects of evolocumab, protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on small size LDL. We observationally investigated the efficacy and side effects of evolocumab on the LDL subfraction particle diameter using PAGE system for lipoprotein analysis. Methods: We defined 30 patients with high-risk hyperlipidemia. As for analysis of LDL subfraction profile, we used polyacrylamide gel electrophoresis three methods: 1) 3% nondenatured poly-acrylamide gel electrophoresis method (3%PAGE), 2) 2% - 16% nondenatured poly-acrylamide gradient gel electro-phoresis method (2% - 16% GGE) and 3) 2.7% - 5% GGE. Evolocumab 140 mg/day administered together with statin significantly improved serum total cholesterol (TC), triglyceride (TG), high-dense lipoprotein-cholesterol (HDL-C), and LDL-C after four-week treatment. Results: TC, TG, HDL-C and LDL-C levels were improved by, respectively, 33%, 20%, 10%, and 54%. The mean LDL size significantly increased from 25.6 ± 0.4 nm to 26.4 ± 0.8 nm. The small dense LDL-cholesterol (sdLDL-C), large buoyant LDL-cholesterol (lbLDL-C), and mid-band lipoprotein-cholesterol were reduced, respectively. Therefore, the preliminary study on this paper can be the first step into a new insight on the world of lipid metabolism. Conclusion: Short-term administration of evolocumab addedons to statin therapy, significantly reduced small size LDL levels.

关键词： PCSK9 Inhibitor Evolocumab LDL Heterogeneicity Small Size LDL 3% PAGE 2% - 16% GGE

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The Cytomegalovirus Enhancer Induces an Immediate Response to the Myosin Light Chain 2v Promoter during P19CL6 Cell Differentiation

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American Journal of Molecular Biology 2017年第4期7卷 190-203页

作者： takanari Wakayama Kazuaki Ohashi Yasuyuki Fujimoto Masatomo Maeda Laboratory of Biochemistry and Molecular Biology Graduate School of Pharmaceutical Sciences Osaka University Osaka Japan Department of Medical Biochemistry School of Pharmacy Iwate Medical University Shiwa-Gun Japan Department of Molecular Biology School of Pharmacy Iwate Medical University Shiwa-Gun Japan Laboratory of Gene Therapy Faculty of Pharmaceutical Sciences Niigata University of Pharmacy and Applied Life Sciences Niigata Japan

The P19CL6 mouse embryonic carcinoma cells efficiently differentiate into cardiac muscle cells in the presence of DMSO. A reporter plasmid for cardiac muscle differentiation was constructed by connecting the CMV enhancer and a 250 bp MLC-2v promoter in front of the GFP gene to further evaluate the role of the CMV enhancer. This plasmid (pCBVenh/MLC-2vpro/EGFP) was stably introduced into P19CL6 cells, and the transfectant differentiated into cardiomyocytes with DMSO. Upon DMSO addition, GFP was immediately transcribed (within 2 days) and the amount of the transcript increased with cultivation. Concomitantly, GFP fluorescence was detected in the cells under a microscope. However, native MLC-2v was transcribed later on day 4. This expression time course is different from that of GFP. Clearly the CMV enhancer responded immediately to DMSO. Since GATA DNA-binding proteins play crucial roles in the initiation of cardiomyocyte differentiation, such a response could be ascribed to the presence of multiple GATA motifs in the enhancer sequence but not in the native MLC-2v promoter. Thus the CMV enhancer may be not only useful for gene therapy and monitoring cell differentiation but also the study of the role of GATA transcription factors expressed in P19CL6 cells.

关键词： Cytomegalovirus Enhancer Differentiation GATA Transcription Factor Gene Expression Heart Muscle MLC-2v P19CL6 Cells Promoter

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Structural Change in Dimyristoyl Phosphatidyl Choline (DMPC) Molecule Alkyl Chains on the Addition of Cholesterol to DMPC Monolayer: Specific Addition Effect of Cholesterol

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Journal of Biophysical Chemistry 2019年第2期10卷 15-29页

作者： Daiki Ito takanari Ikeda Keijiro Taga Yasushi Yamamoto Zameer Shervani Masato Yamamoto Department of Life Science and Applied Chemistry Graduate School of Engineering Nagoya Institute of Technology Nagoya Aichi Japan Nanomaterials Production Division Food and Energy Security Research and Product Center Sendai Japan Department of Chemistry School of Arts and Sciences Showa University Kamiyoshida Fujiyoshida Yamanashi Japan

We have investigated the morphology of dimyristoyl phosphatidyl choline (DMPC)—cholesterol mixed monolayer formed on the water surface by dropping method using surface tension measurement (STm), Brewster angle microscopy (BAM), and infrared external reflection spectroscopy (IERS). STm results showed negative deviation of the limiting molecular area (A0) of cholesterol occurred when cholesterol was added to the DMPC monolayer. BAM images showed the expandable DMPC monolayer changed to the condensed rigid monolayer at more than cholesterol mole fraction (xChol) 0.4. IERS recordings showed that the addition of cholesterol at xChol = 0.4 occurred structural change from gauche- to trans- conformation of two DMPC molecule alkyl chains. From these results, it is found that cholesterol molecule has specific properties that cause structural transition of DMPC molecule alkyl chains.

关键词： Dimyristoyl Phosphatidyl Choline (DMPC) Cholesterol Surface Tension Measurement (STm) Brewster Angle Microscopy (BAM) Infrared External Reflection Microscopy (IERS) Structural Transition

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Suppression of <i>N</i>-Methyl-<i>N</i>-Nitrosourea-Induced Retinal Damage in Mice by Oligonol, an Oligomerized Polyphenol Formulation

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Advances in Biological Chemistry 2014年第2期4卷 138-147页

作者： Jun Kisugi Miwako Nasui Koji Wakame Jun takanari Masatoshi Yamazaki Satoru Yui Amino Up Chemical Co. Ltd. Sapporo Japan Laboratory of Basic Biology Department of Pharma-Sciences Teikyo University Tokyo Japan Laboratory of Host Defense Department of Pharma-Sciences Teikyo University Tokyo Japan

Oligonol is a lychee fruit-derived functional food that contains oligomerized polyphenol compounds. Oligonol exhibits a number of beneficial biological effects, primarily due to its antioxidant activity. Retinitis pigmentosa (RP) is an inherited chronic degenerative disease affecting retinal photoreceptor cells. There is currently no effective therapy capable of stopping or reversing the progression of the disease. In RP, apoptosis of photoreceptor cells resulting from oxidative damage is considered to be the final common pathway. In this report, we present an evaluation of the suppressive activity of Oligonol against N-methyl-N-nitrosourea (MNU)-induced retinal damage in mice, which is a commonly used animal model of RP. Both intraperitoneal and oral administration of Oligonol reduced the loss of photoreceptor cells 7 days after MNU injection, as evaluated by histological staining. Photoreceptor cells derived from MNU-treated mice exhibited increased TUNEL-positive staining, suggesting increased DNA fragmentation, a hallmark of apoptosis. Oligonol treatment reduced the number of TUNEL-positive cells. Additionally, Oligonol suppressed MNU-induced retinal production of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress. Moreover, Oligonol attenuated the MNU-induced decrease in the visual activity of mice, as evaluated by the visual cliff test. Oligonol, therefore, effectively suppresses NMU-induced retinal degeneration.

关键词： Oligonol Oligomerized Polyphenols Retinitis Pigmentosa N-Methyl-N-Nitrosourea Retinal Degeneration Antioxidant

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Novel Approaches for Inhibitor Screening and Target Identification using Arabidopsis Full-Length cDNA Overexpression （FOX） Lines

Novel Approaches for Inhibitor Screening and Target Identifi...

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The 1st International Conference on Plant Secondary Metabolism

作者： Hiroyuki Kasahara takanari Ichikawa Minami Matsui Yuji Kamiya RIKEN Plant Science CenterYokohama Japan RIKEN Plant Science Center Yokohama Japan

＜正＞Organisms have two possible routes for the biosynthesis of isoprenoids;the mevalonate （MVA） and methylerythritol phosphate （MEP） *** MEP pathway has been recently recognized as important target of drug and agrochemical developments and chemical genetics studies,*** shows antima- larial activity by inhibition of 1-deoxyxylulose-5-phosphate reductoisomerase （DXR）,and clomazone has been used for herbicide,which metabolite ketoclomazone inhibits 1-deoxyxylulose-5-phosphate *** have

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Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations

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World Journal of Gastroenterology 2019年第14期25卷 1753-1763页

作者： Yuichi Matsuno Junji Umeno Motohiro Esaki Yoichiro Hirakawa Yuta Fuyuno Yasuharu Okamoto Atsushi Hirano Shigeyoshi Yasukawa Fumihito Hirai Toshiyuki Matsui Shuhei Hosomi Kenji Watanabe Naoki Hosoe Haruhiko Ogata Tadakazu Hisamatsu Shunichi Yanai Shuji Kochi Koichi Kurahara Tsuneyoshi Yao Takehiro Torisu takanari Kitazono Takayuki Matsumoto Department of Medicine and Clinical Science Graduate School of Medical Sciences Kyushu University Department of Endoscopic Diagnostics and Therapeutic Saga University Hospital Department of Epidemiology and Public Health Graduate School of Medical Sciences Kyushu University Department of Gastroenterology Fukuoka University Chikushi Hospital Department of Gastroenterology Osaka City University Graduate School of Medicine Department of Intestinal Inflammation Research Hyogo College of Medicine Center for Diagnostic and Therapeutic Endoscopy School of Medicine Keio University the Third Department of Internal Medicine Kyorin University School of Medicine Division of Gastroenterology Department of Internal Medicine Iwate Medical University Division of Gastroenterology Matsuyama Red Cross Hospital Department of Gastroenterology Sada Hospital

BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS). Crohn's disease(CD) is a major differential diagnosis of CEAS, because these diseases share some clinical features. Therefore, there is a need to develop a convenient screening test to distinguish CEAS from *** To examine whether prostaglandin E major urinary metabolites(PGE-MUM) can serve as a biomarker to distinguish CEAS from *** This was a transactional study of 20 patients with CEAS and 98 patients with *** was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1. We measured the concentration of PGEMUM in spot urine by radioimmunoassay, and the concentration was compared between the two groups of patients. We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC) curve *** Twenty Japanese patients with CEAS and 98 patients with CD were ***-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9 μg/g × Cre, P < 0.0001). One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS [95% confidence interval(CI) 3.2-16.7]. A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6, 95%CI 4.7-185.7). ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9 μg/g × Cre with 95.0% sensitivity and 79.6% *** PGE-MUM measurement is a convenient, non-invasive and useful test for the distinction of CEAS from CD.

关键词： Chronic enteropathy associated with SLCO2A1 gene Prostaglandin E major urinary metabolites Chronic nonspecific multiple ulcers of the small intestine Crohn's disease Small intestine

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千叶6号高炉快速大修技术

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浙江冶金 2000年第3期 24-29页

作者： Masao Fujita Hirotaka Kojima Hironari Marushima takanari Kawai 吕杏春杭州钢铁集团公司技术处杭州310022

千叶6号高炉(内容积4500m^3)于1977年6月17日投产到1998年3月24日停产,创造了两项世界纪录:铁水总产量达到6023万吨,累计运行7586天(20年零9个月)。在投入第二代炉役(内容积扩大到5153m^3)前,为了缩短大修时间,研究和采用了旧炉体大块... 详细信息

千叶6号高炉(内容积4500m^3)于1977年6月17日投产到1998年3月24日停产,创造了两项世界纪录:铁水总产量达到6023万吨,累计运行7586天(20年零9个月)。在投入第二代炉役(内容积扩大到5153m^3)前,为了缩短大修时间,研究和采用了旧炉体大块拆卸和新炉体提前装配的大块环形构件法。其结果,大修仅用了62天(3月25日到5月25日),比传统的大修缩短近一半时间。

关键词：高炉快速大修技术大块环形构件法耐火材料

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Metabolomic Screening Applied to Rice FOX Arabidopsis Lines Leads to the Identification of a Gene-Changing Nitrogen Metabolism

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Molecular Plant 2010年第1期3卷 125-142页

作者： Doris Albinsky Miyako Kusano Mieko Higuchi Naomi Hayashi Makoto Kobayashi Atsushi Fukushima Masaki Mori takanari Ichikawa Keiko Matsui Hirofumi Kuroda Yoko Horii Yuko Tsumoto Hitoshi Sakakibara Hirohiko Hirochika Minami Matsui Kazuki Saito RIKEN Plant Science Center Tsurumi-ku Yokohama 230-0045 Japan National Institute of Agrobiological Sciences Tsukuba 305-8602 Japan Graduate School of Pharmaceutical Sciences Chiba University Inage-ku Chiba 263-8522 Japan

Plant metabolomics developed as a powerful tool to examine gene functions and to gain deeper insight into the physiology of the plant cell. In this study, we screened Arabidopsis lines overexpressing rice full-length （FL） cDNAs （rice FOX Arabidopsis lines） using a gas chromatography-time-of-flight mass spectrometry （GC-TOF/MS）-based technique to identify rice genes that caused metabolic changes. This screening system allows fast and reliable identification of candi- date lines showing altered metabolite profiles. We performed metabolomic and transcriptomic analysis of a rice FOX Ara- bidopsis line that harbored the FL cDNA of the rice ortholog of the Lateral Organ Boundaries （LOB） Domain （LBD）/ Asymmetric Leaves2-1ike （ASL） gene of Arabidopsis, At-LBD37/ASL39. The investigated rice FOX Arabidopsis line showed prominent changes in the levels of metabolites related to nitrogen metabolism. The transcriptomic data as well as the results from the metabolite analysis of the Arabidopsis At-LBD37/ASL39-overexpressor plants were consistent with these findings. Furthermore, the metabolomic and transcriptomic analysis of the Os-LBD37/ASL39-overexpressing rice plants indicated that Os-LBD37/ASL39 is associated with processes related to nitrogen metabolism in rice. Thus, the combination of a metabolomics-based screening method and a gain-of-function approach is useful for rapid characterization of novel genes in both Arabidopsis and rice.

关键词： Metabolite profiling GC-TOF/MS rice FOX Arabidopsis lines transcript profiling LBD37/ASL39 nitrogenmetabolism.

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CONCEPTUAL DESIGN STUDY ON SULFURIC-ACID DECOMPOSER FOR THERMO-CHEMICAL IODINE-SULFUR PROCESS

CONCEPTUAL DESIGN STUDY ON SULFURIC-ACID DECOMPOSER FOR THER...

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第十三届国际核工程大会

作者： Hiroyuki Ota Seiji Kasahara Atsuhiko Terada Masatoshi Hodotsuka Shinji Kubo Ryutaro Hino takanari Inatomi Kenji Ogura Masahiko Kobayashi Shigeki Maruyama Department of Advanced Nuclear Heat Technology Japan Atomic Energy Research Institute Japan Atomic Energy Research Institute Toshiba Corporation Toshiba Corporation IPS CompanyAdvanced Systems Design & Engineering Dept

The Japan Atomic Energy Research Institute(JAERI) has been conducting R&D on HTGR and also on thermo-chemical hydrogen production by using a thermo-chemical iodine-sulfur cycle(IS process).In the I

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