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About NCVC About NCVC About NCVC TOP The Center's Mission Organization History of the NCVC Location News Releases Close Hospital Hospital Hospital TOP About the Hospital The Group of Treatment Close Research Institute Research Institute Research Institute TOP About the Research Institute Departments Office for the Promotion of Diversity and Inclusion Research Institute and Open Innovation Center Brochure Close Open Innovation Center Open Innovation Center Open Innovation Center TOP Research Institute and Open Innovation Center Brochure Close Pamphlet National Cerebral and CardiovascularCenter Hospital Res. Inst. OICOpen Innovation Center Access Background White Black Japanese Access Menu National Cerebral and Cardiovascular Center TOP Research Institute Departments Department of Molecular Pathogenesis Research Institute Department of Molecular Pathogenesis  MemberDirectorKoichi KokameLaboratory ChiefMasashi AkiyamaStaff ScientistYuka EuraKeiko MaruyamaResearch AssistantSheng Ye ResearchBlood is required to have opposing functions; continuous fluidity and rapid clotting. Altered balance between fluidity and clotting can lead to bleeding or thrombogenesis. In order to overcome cardiovascular diseases related to hemorrhage and thrombosis, we are conducting research on plasma proteins, platelets, vascular endothelial cells with a wide variety of approaches from the molecular to the physiological level. We are also focusing on putting the results of basic research into clinical medicine, such as the development of new diagnostic methods.Features:･One of the few laboratories in Japan that studies blood coagulation from the perspective of basic biology･Genetic analysis of patients with abnormal blood coagulation and functional analysis of genetic abnormalities･Development of new assay methods that lead to practical use in clinical settings･Analysis of mice lacking proteins involved in endoplasmic reticulum-associated degradationRecent PublicationAlpha-HIT assay: A new assay for heparin-induced thrombocytopenia antibody detection using FcγRIIa-coated beads and Alpha technologyKeiko Maruyama, Shigeki Miyata, Koichi KokameRes. Pract. Thromb. Haemost. 6, e12818 (2022)https://doi.org/10.1002/rth2.12818Siglec-5 and Siglec-14 mediate the endocytosis of ADAMTS13Masashi Akiyama, Yuka Eura, Koichi KokameThromb. Res. 219, 49-59 (2022)https://doi.org/10.1016/j.thromres.2022.09.005Three cases of unprovoked venous thromboembolism with prothrombin p.Arg596Gln variant and literature review of antithrombin resistanceAkihiro Tsuji, Toshiyuki Miyata, Akihiro Sekine, Reiko Neki, Koichi Kokame, Tsutomu Tomita, Yumi Kashima, Ryotaro Asano, Jin Ueda, Tatsuo Aoki, Takeshi OgoIntern. Med. (2022)https://doi.org/10.2169/internalmedicine.9718-22P2Y12 reaction units and clinical outcomes in acute large artery atherosclerotic stroke: a multicenter prospective studyKazuki Fukuma, Hiroshi Yamagami, Masafumi Ihara, Tomotaka Tanaka, Toshiyuki Miyata, Shigeki Miyata, Koichi Kokame, Kunihiro Nishimura, Yuriko Nakaoku, Haruko Yamamoto, Mikito Hayakawa, Kenji Kamiyama, Yukiko Enomoto, Ryo Itabashi, Eisuke Furui, Yasuhiro Manabe, Masayuki Ezura, Kenichi Todo, Kazuo Hashikawa, Shinichiro Uchiyama, Kazunori Toyoda, Kazuyuki NagatsukaJ. Atheroscler. Thromb. 30, 39-55 (2023)https://doi.org/10.5551/jat.63369First report of inherited protein S deficiency caused by paternal PROS1 mosaicismSatomi Nagaya*, Keiko Maruyama*, Atsushi Watanabe, Makiko Meguro-Horike, Yuta Imai, Yuki Hiroshima, Shin-Ichi Horike, Koichi Kokame, Eriko MorishitaHaematologica 107, 330-333 (2022)https://doi.org/10.3324/haematol.2021.278527Congenital thrombotic thrombocytopenic purpura: genetics and emerging therapiesKazuya Sakai, Eriko Hamada, Koichi Kokame, Masanori MatsumotoAnn. Blood (2022)https://doi.org/10.21037/aob-22-17V-ATPase V0a1 promotes Weibel-Palade body biogenesis through the regulation of membrane fissionYasuo Yamazaki, Yuka Eura, Koichi KokameeLife 10, e71526 (2021)https://doi.org/10.7554/eLife.71526Commonly used anti-von Willebrand factor antibody for multimer analysis cross-reacts with fibronectin, which is difficult to distinguish from VWFYuka Eura, Koichi KokameRes. Pract. Thromb. Haemost. 5, e12598 (2021)https://doi.org/10.1002/rth2.12598Arf GTPase-Activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factorAsano Watanabe, Hikari Hataida, Naoya Inoue, Kosuke Kamon, Keigo Baba, Kuniaki Sasaki, Rika Kimura, Honoka Sasaki, Yuka Eura, Wei-Fen Ni, Yuji Shibasaki, Satoshi Waguri, Koichi Kokame, Yoko ShibaBiol. Open 10, bio058789 (2021)https://doi.org/10.1242/bio.058789A novel homozygous variant of the thrombomodulin gene causes a hereditary bleeding disorderMakoto Osada*, Keiko Maruyama*, Koichi Kokame, Ryunosuke Denda, Kohei Yamazaki, Hisako Kunieda, Maki Hirao, Seiji Madoiwa, Nobuo Okumura, Mitsuru Murata, Yasuo Ikeda, Kentaro Watanabe, Yuiko Tsukada, Takahide KikuchiBlood Adv. 5, 3830-3838 (2021)https://doi.org/10.1182/bloodadvances.2020003814Current prophylactic plasma infusion protocols do not adequately reduce long-term microvascular events in Japanese patients with congenital TTPKazuya Sakai, Yoshihiro Fujimura, Toshiyuki Miyata, Ayami Isonishi, Koichi Kokame, Masanori MatsumotoBr. J. Haematol. 194, 444-452 (2021)https://doi.org/10.1111/bjh.17560Carrier frequencies of antithrombin, protein C, and protein S deficiency variants estimated using a public database and expression experimentsKeiko Maruyama, Koichi KokameRes. Pract. Thromb. Haemost. 5, 179-186 (2021)https://doi.org/10.1002/rth2.12456Derlin-3 is required for changes in ERAD complex formation under ER stressYuka Eura, Toshiyuki Miyata, Koichi KokameInt. J. Mol. Sci. 21, 6146 (2020)https://doi.org/10.3390/ijms21176146Success and limitations of plasma treatment in pregnant women with congenital thrombotic thrombocytopenic purpuraKazuya Sakai, Yoshihiro Fujimura, Yasuyuki Nagata, Satoshi Higasa, Masato Moriyama, Ayami Isonishi, Mutsuko Konno, Michiko Kajiwara, Yoshiyuki Ogawa, Shigehiko Kaburaki, Tomoko Hara, Koichi Kokame, Toshiyuki Miyata, Kinta Hatakeyama, Masanori MatsumotoThromb. Haemost. 18, 2929-2941 (2020)https://doi.org/10.1111/jth.15064Low-dose activated protein C suppresses the development of cerebral infarction and neurological deficits in miceKeiko Yamato, Yukako Nakajo, Hitomi Yamamoto-Imoto, Koichi Kokame, Toshiyuki Miyata, Jun C Takahashi, Hiroharu Kataoka, Hiroji YanamotoNeurosurg. Open 1, okaa014 (2020)https://doi.org/10.1093/neuopn/okaa014Knock-in mice bearing constitutively active αIIb(R990W) mutation develop macrothrombocytopenia with severe platelet dysfunctionKeigo Akuta, Kazunobu Kiyomizu, Hirokazu Kashiwagi, Shinji Kunishima, Nobuko Nishiura, Fumiaki Banno, Koichi Kokame, Hisashi Kato, Yuzuru Kanakura, Toshiyuki Miyata, Yoshiaki TomiyamaThromb. Haemost. 18, 497-509 (2020)https://doi.org/10.1111/jth.14678Predictive value of protein S-specific activity and ELISA testing in patients with the protein S K196E mutationTakekazu Miyoshi, Keiko Maruyama, Hisato Oku, Saiko Asahara, Hironori Hanada, Reiko Neki, Jun Yoshimatsu, Koichi Kokame, Toshiyuki MiyataThromb. Res. 185, 1-4 (2020)https://doi.org/10.1016/j.thromres.2019.10.026Cerebral venous sinus thrombosis associated with protein S deficiency during pregnancy: a case reportMiyu Usui, Tadashi Ozawa, Younhee Kim, Takafumi Mashiko, Kosuke Matsuzono, Keiko Maruyama, Koichi Kokame, Rie Usui, Reiji Koide, Shigeru FujimotoObstet. Gynaecol. 40, 135-136 (2020)https://doi.org/10.1080/01443615.2019.1606789Patent ductus arteriosus generates neonatal hemolytic jaundice with thrombocytopenia in Upshaw-Schulman syndromeYoshihiro Fujimura, Bernhard Lämmle, Saori Tanabe, Kazuya Sakai, Toshiyuki Kimura, Koichi Kokame, Toshiyuki Miyata, Yukihiro Takahashi, Shigeki Taniguchi, Masanori MatsumotoBlood Adv. 3, 3191-3195 (2019)https://doi.org/10.1182/bloodadvances.2019000601Novel CFHR2-CFHR1 hybrid in C3 glomerulopathy identified by genomic structural variation analysisYuka Sugawara, Hideki Kato, Yoko Yoshida, Madoka Fujisawa, Koichi Kokame, Toshiyuki Miyata, Yuko Akioka, Kenichiro Miura, Motoshi Hattori, Masaomi NangakuKidney Int. Rep. 4, 1759-1762 (2019)https://doi.org/10.1016/j.ekir.2019.09.008Experience of the use of octreotide for refractory gastrointestinal bleeding in a patient with Jarvik2000 left ventricular assist deviceSeiko Nakajima-Doi, Osamu Seguchi, Yasuhiro Shintani, Tomoyuki Fujita, Satsuki Fukushima, Yorihiko Matsumoto, Yuka Eura, Koichi Kokame, Shigeki Miyata, Sachi Matsuda, Hiroki Mochizuki, Keiichiro Iwasaki, Yuki Kimura, Koichi Toda, Yuto Kumai, Kensuke Kuroda, Takuya Watanabe, Masanobu Yanase, Junjiro Kobayashi, Norihide FukushimaArtif. Organs 22, 334-337 (2019)https://doi.org/10.1007/s10047-019-01121-7Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational studyTakekazu Miyoshi, Hisato Oku, Saiko Asahara, Akira Okamoto, Koichi Kokame, Michikazu Nakai, Kunihiro Nishimura, Fumiyuki Otsuka, Aya Higashiyama, Jun Yoshimatsu, Toshiyuki MiyataInt. J. Hematol. 109, 641-649 (2019)https://doi.org/10.1007/s12185-019-02633-xThe international hereditary thrombotic thrombocytopenic purpura (TTP) registry: Key findings at enrolment until 2017Anette van Dorland, Magnus Mansouri Taleghani, Kazuya Sakai, Kenneth D. Friedman, James N. George, Ingrid Hrachovinova, Paul N. Knöbl, Anne Sophie von Krogh, Reinhard Schneppenheim, Isabella Aebi-Huber, Lukas Bütikofer, Carlo R. Largiadèr, Zuzana Cermakova, Koichi Kokame, Toshiyuki Miyata, Hideo Yagi, Deirdra R. Terrell, Sara K. Veseley, Masanori Matsumoto, Bernhard Lämmle, Yoshihiro Fujimura, Johanna A. Kremer Hovinga; Hereditary TTP RegistryHaematologica 104, 2107-2115 (2019)https://doi.org/10.3324/haematol.2019.216796Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in miceShiro Ono, Hideto Matsui, Masashi Noda, Shogo Kasuda, Noritaka Yada, Kiyomi Yoshimoto, Masashi Akiyama, Toshiyuki Miyata, Mitsuhiko Sugimoto, Kenji NishioSci. Rep. 9, 14453 (2019)https://doi.org/10.1038/s41598-019-51013-2Acquired von Willebrand syndrome associated with cardiovascular diseasesHisanori Horiuchi, Tsuyoshi Doman, Koichi Kokame, Yoshikatsu Saiki, Masanori MatsumotoAtheroscler. Thromb. 26, 303-314 (2019)https://doi.org/10.5551/jat.RV17031Upshaw-Schulman syndrome diagnosed during pregnancy complicated by reversible cerebral vasoconstriction syndromeMariko Tsuda, Motoaki Shiratsuchi, Motohiko Ikeda, Masanori Matsumoto, Yoshihiro Fujimura, Koichi Kokame, Takamitsu Matsushima, Yasuhiro Nakashima, Yoshihiro OgawaTransfus. Apher. Sci. 57, 790-792 (2018)https://doi.org/10.1016/j.transci.2018.10.023Protein S K196E mutation reduces its cofactor activity for APC but not for TFPIKeiko Maruyama, Masashi Akiyama, Toshiyuki Miyata, Koichi KokameRes. Pract. Thromb. Haemost. 2, 751-756 (2018)https://doi.org/10.1002/rth2.12152Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndromeMadoka Fujisawa, Hideki Kato, Yoko Yoshida, Tomoko Usui, Munenori Takata, Mika Fujimoto, Hideo Wada, Yumiko Uchida, Koichi Kokame, Masanori Matsumoto, Yoshihiro Fujimura, Toshiyuki Miyata, Masaomi NangakuClin. Exp. Nephrol. 22, 1088-1099 (2018)https://doi.org/10.1007/s10157-018-1549-3Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axisMario Navarro-Marquez, Natalia Torrealba, Rodrigo Troncoso, Cesar Vasquez-Trincado, Marcelo Rodriguez, Pablo E Morales, Elisa Villalobos, Yuka Eura, Lorena Garcia, Mario Chiong, Amira Klip, Enrique Jaimovich, Koichi Kokame, Sergio LavanderoBiochim. Biophys. Acta Mol. Basis Dis. 1864, 1653-1662 (2018)https://doi.org/10.1016/j.bbadis.2018.02.018Congenital coagulation factor X deficiency: Genetic analysis of five patients and functional characterization of mutant factor X proteinsSatomi Nagaya, Masashi Akiyama, Morika Murakami, Akiko Sekiya, Hidesaku Asakura, Eriko MorishitaHemophilia 24, 774-785 (2018)https://doi.org/10.1111/hae.13606von Willebrand factor aggravates hepatic ischemia-reperfusion injury by promoting neutrophil recruitment in miceYasuyuki Urisono, Asuka Sakata, Hideto Matsui, Shogo Kasuda, Shiro Ono, Kiyomi Yoshimoto, Kenji Nishio, Masayuki Sho, Masashi Akiyama, Toshiyuki Miyata, Kazuo Okuchi, Satoshi Nishimura, Mitsuhiko SugimotoThromb Haemost 118, 700-708 (2018)https://doi.org/10.1055/s-0038-1636529       last updated : 2024/04/09 (Corporate number:3120905003033) 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan TEL：81-6-6170-1070 Access Copyright © National Cerebral and Cardiovascular Center All rights reserved. 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