2021/10/25 更新

写真a

ヤナガワ タカオ
栁川 貴央
YANAGAWA Takao
所属
医歯学総合病院 循環器内科 助教
職名
助教
外部リンク

学位

  • 博士(医学) ( 2009年3月   新潟大学 )

経歴

  • 新潟大学   医歯学総合病院 循環器内科   助教

    2017年4月 - 現在

  • 新潟大学   医歯学総合病院 循環器内科   特任助教

    2015年1月 - 2017年3月

  • 新潟大学   医歯学総合病院 高次救命災害治療センター   助教

    2011年5月 - 2014年12月

 

論文

  • Late-onset Cutaneous Hydrophilic Polymer Embolism: A Case Occurring Two Years after Endovascular Procedures. 国際誌

    Yukino Kase, Ryota Hayashi, Izumi Takei, Osamu Ansai, Takeo Suzuki, Akihiko Yuki, Mitsuhiro Watanabe, Takao Yanagawa, Riichiro Abe

    Acta dermato-venereologica   101 ( 7 )   adv00511   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2340/00015555-3881

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  • Conservative treatment with an intra-aortic balloon pump to treat acute myocardial infarction due to spontaneous coronary artery dissection.

    Yuji Matsuo, Kazuyuki Ozaki, Ryutaro Ikegami, Kota Nishida, Naoki Kubota, Toshiki Takano, Takeshi Okubo, Makoto Hoyano, Takao Yanagawa, Takeshi Kashimura, Tohru Minamino

    Journal of cardiology cases   23 ( 6 )   274 - 280   2021年6月

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    記述言語:英語  

    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. Treatment for SCAD includes conservative approaches, percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery. Although the success rate of PCI is low, conservative treatment often leads to a good clinical course. Three patients with SCAD who were conservatively treated with intra-aortic balloon pumping without coronary intervention are presented. All three patients continue to do well. <Learning objective: The treatment for spontaneous coronary artery dissection (SCAD) has not yet been established. Intra-aortic balloon pumping (IABP) is a potential conservative treatment for SCAD that increases coronary blood flow. However, IABP could worsen the dissection. In this report, IABP was safely used for SCAD and patients had a good clinical course without worsening the dissection.>.

    DOI: 10.1016/j.jccase.2021.01.004

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  • Long-Term Prognosis of Patients Who Underwent Percutaneous Transvenous Mitral Commissurotomy for Mitral Stenosis.

    Naoki Kubota, Kazuyuki Ozaki, Makoto Hoyano, Kota Nishida, Toshiki Takano, Takeshi Okubo, Shinpei Kimura, Takao Yanagawa, Takeshi Kashimura, Tohru Minamino

    International heart journal   61 ( 6 )   1183 - 1187   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The long-term prognosis for up to 20 years of patients who have undergone percutaneous transvenous mitral commissurotomy (PTMC) for mitral stenosis (MS) is unknown.We examined 77 of 93 patients (83%) with MS and who underwent PTMC from 1989 to 2002 at our institute, as well as the occurrence of either one of the following clinical endpoints until September 1, 2018: all-cause death or repeat intervention for the mitral valve.The mean follow-up duration was 20.5 ± 7.3 years. The mean age was 51 ± 11 years. Overall, the 20-year survival rate was 71% ± 5%; without any intervention, the 20-year survival rate was 40% ± 6%. In patients who achieved good immediate results (i.e., mitral valve area (MVA) of ≥ 1.5 cm2 without mitral regurgitation (MR) of > 2/4 after PTMC), the 20-year survival rate was 80% ± 6%; without any intervention, the 20-year survival rate was 54% ± 7%.In our 20-year observational study, patients who have undergone PTMC for MS had favorable prognosis, especially in those who achieved good immediate results. In those who had poor immediate results, careful follow-up is needed because they might have more clinical event and any intervention for the mitral valve.

    DOI: 10.1536/ihj.20-082

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  • Usefulness of Repeat Angiography to Establish Spontaneous Coronary Artery Dissection in Small Vessels.

    Naoki Kubota, Kazuyuki Ozaki, Yasuhiko Tanabe, Yasuhiro Iwasaki, Tsuyoshi Yoshida, Takeshi Okubo, Shinpei Kimura, Makoto Hoyano, Takao Yanagawa, Takeshi Kashimura, Tohru Minamino

    Circulation reports   2 ( 12 )   739 - 743   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background:
    Spontaneous coronary artery dissection (SCAD) is a rare disease that is often misdiagnosed, except in typical cases. Although intracoronary imaging and multislice coronary computed tomography angiography (CCTA) are useful in establishing dissection, they may not be feasible in all instances, especially in small vessels.
    Methods and Results:
    We describe a series of 7 patients with acute coronary syndrome secondary to small vessel SCAD that was detected only upon repeat coronary angiography (CAG). This cohort had a mean (±SD) age of 50±6 years, was predominantly female (n=6; 86%), and had few coronary risk factors. Three patients (43%) had dissection of the distal segment of the right coronary artery, 3 (43%) had distal left circumflex artery dissection, and 1 patient (14%) had a diagonal branch dissection. None of the patients required percutaneous coronary intervention, and received conservative therapy only, because the infarct area was sufficiently small. No definitive diagnosis of SCAD could be established in any of the patients at first admission because CAG alone or CCTA did not reveal the presence of a flap or intraluminal hemorrhage. However, in such patients without a definitive diagnosis, repeat CAG in the chronic stage showed enlargement of vessels, suggesting the healing of an SCAD.
    Conclusions:
    Repeat CAG may be useful for suggesting the occurrence of SCAD.

    DOI: 10.1253/circrep.CR-20-0100

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  • Angioscopic findings during balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

    Toshiki Takano, Kazuyuki Ozaki, Makoto Hoyano, Takao Yanagawa, Takeshi Kashimura, Tohru Minamino

    Cardiovascular intervention and therapeutics   35 ( 4 )   421 - 422   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12928-019-00635-4

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  • Pulmonary Artery Sarcoma Diagnosed Using an Endovascular Catheter Forceps Biopsy.

    Ryohei Sakai, Kazuyuki Ozaki, Yumi Yamaguchi, Naoki Kubota, Toshiki Takano, Takeshi Okubo, Shinpei Kimura, Makoto Hoyano, Takao Yanagawa, Takeshi Kashimura, Tohru Minamino

    Internal medicine (Tokyo, Japan)   59 ( 17 )   2149 - 2153   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We herein report a case of pulmonary artery sarcoma (PAS) in a 64-year-old woman. She was admitted to our hospital because of massive genital bleeding from endometrial cancer. Contrast-enhanced computed tomography (CT) revealed a left pulmonary artery mass and deep vein thrombosis. She underwent anticoagulant therapy for one year. However, the mass lesion gradually expanded. 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed a positive uptake of FDG by the mass. An endovascular catheter biopsy was performed for the differentiation of endometrial cancer metastasis or primary sarcoma. The biopsy specimen tissue comprised spindle-shaped cells. Thus, the patient was diagnosed with PAS.

    DOI: 10.2169/internalmedicine.4738-20

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  • High-Resolution Angioscopy of Endoluminal Stent Graft at 6 Months After Implantation.

    Makoto Hoyano, Kazuyuki Ozaki, Kota Nishida, Ryohei Sakai, Naoki Kubota, Toshiki Takano, Takeshi Okubo, Shinpei Kimura, Takao Yanagawa, Takuya Ozawa, Takeshi Kashimura, Tohru Minamino

    Circulation journal : official journal of the Japanese Circulation Society   83 ( 9 )   1970 - 1970   2019年8月

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  • Stent malapposition occurred 17 days following percutaneous coronary intervention for a severe calcified lesion in acute myocardial infarction.

    Toshiki Takano, Kazuyuki Ozaki, Makoto Hoyano, Takao Yanagawa, Takuya Ozawa, Tohru Minamino

    Journal of cardiology cases   20 ( 1 )   4 - 7   2019年7月

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    記述言語:英語  

    The occurrence of stent malapposition and coronary artery aneurysm (CAA) during the early phase of drug-eluting stent (DES) implantation is rare. This report presents the case of a 55-year-old man who underwent DES implantation to the left circumflex artery with full-arc severe calcified lesion owing to inferior acute myocardial infarction. Coronary angiography and optical coherence tomography (OCT) at 17 days following percutaneous coronary intervention (PCI) revealed stent malapposition and CAA of diameter 6.5 mm in the distal part of the stented vessel. OCT findings at 5 months following PCI revealed a dilated CAA of diameter 7.5 mm and a luminal structure outside the stent. Based on these findings, it was suggested that the cause of CAA in the early phase following DES implantation to the severe calcified lesion was related to coronary sequelae of Kawasaki disease. <Learning Objective: This was a case of coronary artery aneurysm (CAA) in the stented lesion at early phase post percutaneous coronary intervention (PCI). Despite the patient's young age and low coronary risk, there was full-arc severe calcification lesion. Optical coherence tomography after PCI showed luminal structure outside of the stent. It was similar to recanalized CAA of Kawasaki disease (KD). These findings suggested that CAA in early phase following PCI might be related to the sequelae of coronary arteritis, especially KD.>.

    DOI: 10.1016/j.jccase.2019.02.006

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  • Clinical Predictors of Recurrent Ventricular Arrhythmias in Secondary Prevention Implantable Cardioverter Defibrillator Recipients With Coronary Artery Disease - Lower Left Ventricular Ejection Fraction and Incomplete Revascularization.

    Toshiki Takano, Komei Tanaka, Kazuyuki Ozaki, Akinori Sato, Kenichi Iijima, Takao Yanagawa, Daisuke Izumi, Takuya Ozawa, Koichi Fuse, Masahito Sato, Naohito Tanabe, Tohru Minamino

    Circulation journal : official journal of the Japanese Circulation Society   82 ( 12 )   3037 - 3043   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The implantable cardioverter defibrillator (ICD) is a standard prevention therapy for patients at high risk for sudden cardiac death (SCD) due to life-threatening ventricular arrhythmia (VA), that is, ventricular fibrillation and ventricular tachycardia. However, clinical predictors of recurrent VA in secondary prevention ICD recipients with coronary artery disease (CAD) remain unknown. Methods and Results: We followed up 96 consecutive patients with CAD undergoing ICD implantation for secondary prevention of SCD. Long-term rates and clinical predictors of appropriate ICD therapy (ICD-Tx) for VA were analyzed. Appropriate ICD-Tx occurred in 41 (42.7%) patients during a median follow-up of 2.4 years (interquartile range, 0.9-6.1). These patients had significantly greater left ventricular end-diastolic diameter (62.3±1.3 vs. 54.6±1.1 mm, P<0.001), lower left ventricular ejection fraction (LVEF; 36.3±2.0% vs. 45.7±1.8%, P<0.001), and more incomplete revascularization (ICR; 70.7% vs. 45.5%, P=0.014) than those without appropriate ICD-Tx. Multivariable analysis showed that LVEF (hazards ratio [HR], 0.950; 95% CI: 0.925-0.975; P<0.001) and ICR (HR, 2.293; 95% CI: 1.133-4.637; P=0.021) were significant predictors of appropriate ICD-Tx for VA. CONCLUSIONS: Lower LVEF and ICR were independent predictors of recurrent VA in secondary prevention ICD recipients with CAD.

    DOI: 10.1253/circj.CJ-18-0646

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  • Efficacy of Corticosteroid Treatment for Refractory Multivessel Vasospastic Coronary Angina with Hypereosinophilia.

    Toshiki Takano, Kazuyuki Ozaki, Komei Tanaka, Takao Yanagawa, Takuya Ozawa, Tohru Minamino

    Internal medicine (Tokyo, Japan)   57 ( 21 )   3111 - 3115   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 43-year-old man was diagnosed with acute myocardial infarction (AMI) due to multivessel coronary vasospasm. Accordingly, two coronary vasodilators were administered, and he was discharged without an angina attack. However, from the following day, he reported frequent chest pain and was re-hospitalized. Despite adding multiple coronary vasodilators, it was difficult to completely suppress the angina attack. He also demonstrated hypereosinophilia from the onset of AMI, and his eosinophil count gradually increased up to 6,238/μL. After corticosteroid administration was started, the vasospasm was completely controlled, and his eosinophil count normalized. He remained free from angina attacks for two years with corticosteroid therapy.

    DOI: 10.2169/internalmedicine.0886-18

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  • Bidirectional Shunt Trajectory in Ventricular Septal Defect With Eisenmenger's Syndrome.

    Hiromi Kayamori, Takeshi Kashimura, Yosuke Horii, Tsutomu Kanazawa, Toshio Fujita, Naoki Kubota, Yasuhiro Ikami, Toshiki Takano, Takeshi Okubo, Makoto Hoyano, Takao Yanagawa, Takuya Ozawa, Kazuyuki Ozaki, Tohru Minamino

    Circulation journal : official journal of the Japanese Circulation Society   82 ( 11 )   2925 - 2926   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1253/circj.CJ-18-0332

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  • Dynamic left ventricular outflow tract obstruction complicated with takotsubo cardiomyopathy: The acute phase of takotsubo cardiomyopathy manifests latent left ventricular outflow tract obstruction.

    Yuta Sakaguchi, Kazuyuki Ozaki, Toshiki Takano, Hitomi Namba, Komei Tanaka, Takao Yanagawa, Takuya Ozawa, Tohru Minamino

    Journal of cardiology cases   18 ( 2 )   60 - 64   2018年8月

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    記述言語:英語  

    Dynamic left ventricular (LV) outflow tract (LVOT) obstruction is sometimes complicated with takotsubo cardiomyopathy (TC). The present case involves a 70-year-old woman with chest discomfort. Seven years earlier, transthoracic echocardiography revealed LVOT obstruction due to a sigmoid-shaped septum. She underwent urgent cardiac catheterization for suspected acute coronary syndrome. She was diagnosed as having TC with LVOT obstruction. After undergoing conservative treatment, her LV function normalized and the LVOT obstruction resolved. After the LV wall motion normalized, administering an intravenous infusion of dobutamine again provoked LVOT obstruction. In this situation, the presence of TC manifested latent LVOT obstruction. <Learning objective: Although dynamic left ventricular outflow tract (LVOT) obstruction is the important compication of takotsubo cardiomyopaty (TC), the mechanism of LVOT obstruction remains unclear. This case had latent LVOT obstruction due to sigmoid-shaped septum, and LVOT obstruction might be manifested in the acute phase of TC. This phenomenon has potential for mechanism of LVOT obstruction complicated with TC.>.

    DOI: 10.1016/j.jccase.2018.04.010

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  • Dual Antiplatelet Therapy Guided by CYP2C19 Polymorphisms after Implantation of Second-Generation Drug-Eluting Stents for Management of Acute Coronary Syndrome.

    Takuya Ozawa, Masayoshi Suda, Ryutaro Ikegami, Toshiki Takano, Takayuki Wakasugi, Takao Yanagawa, Komei Tanaka, Kazuyuki Ozaki, Satoru Hirono, Tohru Minamino

    International heart journal   59 ( 1 )   21 - 26   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Prasugrel, a novel P2Y12 receptor inhibitor, is administered to patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI), but it can increase the risk of bleeding. The Japanese exhibit weaker responses to clopidogrel than other races because of CYP2C19 polymorphisms; thus, it is unclear whether these patients should continue dual antiplatelet therapy (DAPT) using prasugrel or switch to clopidogrel in the chronic phase. Here we evaluated the clinical outcomes of DAPT guided by CYP2C19 polymorphisms after implantation of second-generation drug-eluting stents (DESs) for ACS management. Patients with ACS receiving PCI via DES from November 2011 to March 2015 were divided into two groups: conventional DAPT with clopidogrel (n = 41) and gene-guided DAPT (n = 24). In the gene-guided DAPT group, all patients with ACS were given DAPT using prasugrel as soon as possible; extensive and intermediate metabolizers receiving PCI for the first time were switched to clopidogrel at least 2 weeks after discharge, and intermediate metabolizers with repeated ACS and poor metabolizers continued on DAPT using prasugrel. Notably, gene-guided DAPT significantly reduced major adverse cardiovascular/cerebrovascular events (MACCEs; 22.0% versus 4.2%, hazard ratio [HR]: 0.15, 95% confidence interval [CI]: 0.01-0.81; P = 0.0247). Hemorrhagic complications were observed in 3.1% of patients receiving conventional DAPT and absent in the gene-guided group. Moreover, multivariate analysis showed that gene-guided DAPT significantly decreased MACCE incidence (HR: 0.15, 95% CI: 0.01-0.81; P = 0.033). Collectively, these data suggest that CYP2C19 polymorphism analysis may improve treatment decisions in patients with ACS receiving DES-PCI.

    DOI: 10.1536/ihj.17-005

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  • Erythropoietin induces angiogenesis in a manner dependent on the intrinsic auto/paracrine production of interleukin-6 in vitro 国際誌

    Takao Yanagawa, Ken Toba, Tomoyasu Suzuki, Takuya Ozawa, Masato Oda, Tsugumi Takayama, Kiminori Kato, Yoshifusa Aizawa

    INTERNATIONAL JOURNAL OF CARDIOLOGY   168 ( 3 )   2941 - 2943   2013年10月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.ijcard.2013.03.173

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  • Asialoerythropoietin Exerts Stronger Angiogenic Activity than Erythropoietin Via its Binding Affinity to Tissue 国際誌

    Takao Yanagawa, Ken Toba, Kiminori Kato, Tomoyasu Suzuki, Shiro Minagawa, Takashi Saigawa, Takuya Ozawa, Masato Oda, Tsugumi Takayama, Haruo Hanawa, Masato Higuchi, Hideki Saito, Yoshifusa Aizawa

    CARDIOVASCULAR DRUGS AND THERAPY   27 ( 2 )   117 - 124   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Although erythropoietin (EPO) is known to express angiogenic and cardioprotective effects, it also induces hypertension, polycythemia, and platelet activation, which may cause serious adverse effects in patients with cardiovascular diseases. We compared the angiogenic effects of EPO and its nonerythropoietic derivative, asialo-EPO (AEPO).Lower limb ischemia was induced in ICR and C57/BL mice. Mice were injected intramuscularly with 2 mu g/kg of EPO derivatives for 6 or 7 days. To assess biological differences, the tissue affinity of both EPO derivatives was analyzed in vitro using heparin affinity column chromatography. Tissue affinity was also analyzed in vivo using an intramuscular pharmacokinetic study.The survival of ischemic legs was better in the AEPO group than that in the EPO group (5/13 = 38.5 % vs 1/13 = 7.7 %, p < 0.05), and an increase in regenerated vessels was observed in the AEPO group, but not in the EPO group in ICR mice. Vessel/muscle ratios in control, EPO, and AEPO groups were 0.50 +/- 0.34, 0.61 +/- 0.32, and 2.83 +/- 1.13, respectively (p < 0.0001). On the other hand, regenerated vessels were observed in both EPO and AEPO groups (p < 0.001) in C57/BL mice. AEPO, but not EPO, expressed heparin affinity in vitro. Intramuscularly injected EPO gradually decreased in muscle tissue, while AEPO was maintained at 2.5 ng/muscle for 1 day after several hours of a rapid clearance phase in vivo.AEPO exerts stronger angiogenic effects than those of EPO presumably via its tissue affinity. Administration of AEPO is a promising option for the treatment of patients with critical limb ischemia.

    DOI: 10.1007/s10557-013-6438-0

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  • A novel synthetic derivative of human erythropoietin designed to bind to glycosaminoglycans. 国際誌

    Masato Moriyama, Ken Toba, Haruo Hanawa, Kiminori Kato, Takao Yanagawa, Tsugumi Takayama, Takuya Ozawa, Hironori Kobayashi, Masato Higuchi, Hideki Saito, Yoshifusa Aizawa

    Drug delivery   19 ( 4 )   202 - 7   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To synthesize long-acting and antiangiogenic erythropoietin to be clinically applied for treatment of patients with solid tumors, we synthesized a hybrid molecule of human erythropoietin added onto the C-terminus with a heparin-binding motif of human PLGF-2 to develop a novel derivative of long-acting and antiangiogenic erythropoietin: heparin-binding erythropoietin (HEPO), and studied the characteristics of this novel erythropoietin derivative. HEPO cDNA was synthesized, expressed in insect cells, and the protein was purified using a heparin-sepharose affinity column. The erythropoietic and angiogenic effects of the partially purified protein were analyzed in vitro and in vivo. The erythropoietic activity of the protein was equivalent to natural EPO in vitro. In vivo administration of the protein to mice revealed its long-acting erythropoietic activity as expected. Administration of the protein inhibited angiogenesis in a mouse limb ischemia model. In conclusion, the heparin-binding motif of PLGF-2 may act as, so to speak, a superendostatin. This novel long-acting erythropoietin derivative may have an advantage to inhibit tumor growth while preserving hematopoietic and tissue-protective effects.

    DOI: 10.3109/10717544.2012.690004

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  • Hypocellularity and insufficient expression of angiogenic factors in implanted autologous bone marrow in patients with chronic critical limb ischemia.

    Masato Oda, Ken Toba, Kiminori Kato, Takuya Ozawa, Takao Yanagawa, Noboru Ikarashi, Tsugumi Takayama, Tomoyasu Suzuki, Haruo Hanawa, Masayoshi Masuko, Hironori Kobayashi, Yoshifusa Aizawa

    Heart and vessels   27 ( 1 )   38 - 45   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The aim of this study was to identify the clinical parameters of absolutely poor-prognosis patients with chronic critical limb ischemia (AP-CLI). Sixteen no-option CLI patients with arteriosclerosis obliterans: ASO (nine) and non-ASO patients (seven) treated with bone marrow-mononuclear cell implantation (BMI) were analyzed. There were three AP-CLI patients (all ASO). The mRNA expression of several angiogenic factors in the implanted cells was analyzed in comparison with normal donor bone marrow. To observe the response of bone marrow components to hypoxia, normal bone marrow cells were cultured for 24 h in 2.5% O(2), and mRNA expression of angiogenic factors were measured. AP-CLI patients exhibited extraordinary low bone marrow cellularity as well as the percentage of CD34-positive cells. Among angiogenic factors, only VEGF expression was maintained in response to HIF-1, while other factors such as HGF, Ang-1, PLGF, and SDF-1 decreased in the implanted bone marrow cells of the patients with CLI compared to normal bone marrow cells. HIF-1 and all of the five angiogenic factors increased in vitro in response to hypoxia. Thus it is highly likely that angiogenic factors except VEGF do not respond to chronic ischemia in bone marrow in vivo. An organ-protection system against tissue ischemia may be applied for acute hypoxia, but it may be insufficient for chronic ischemia.

    DOI: 10.1007/s00380-011-0125-5

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  • Erythropoietin, but not asialoerythropoietin or carbamyl-erythropoietin, attenuates monocrotaline-induced pulmonary hypertension in rats. 国際誌

    Noboru Ikarashi, Ken Toba, Kiminori Kato, Takuya Ozawa, Masato Oda, Tsugumi Takayama, Hironori Kobayashi, Takao Yanagawa, Haruo Hanawa, Tomoyasu Suzuki, Mikio Nakazawa, Minoru Nomoto, Fuyuki Asami, Masato Higuchi, Hideki Saito, Yoshifusa Aizawa

    Clinical and experimental hypertension (New York, N.Y. : 1993)   34 ( 8 )   575 - 81   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Erythropoietin (EPO) has long been utilized for the treatment of renal anemia. The erythropoietin receptor (EPOR) is also expressed in the cardiovascular and central nervous systems in addition to an erythroid lineage, to provide an organoprotective role against several types of cellular stress. Pulmonary hypertension (PH) is a poor prognostic disease caused by primary and secondary pulmonary vascular injury. We observed the effects of EPO derivatives on monocrotaline-induced PH in rats on the supposition that EPO may protect small arteries from injury. Asialoerythropoietin (AEPO) lacks sialic acids in the termini of carbohydrate chains that results in rapid clearance from blood. Carbamyl-erythropoietin (CEPO) interacts with EPOR/βc heterodimers, but not with EPOR homodimers expressed in erythroid cells. Monocrotaline-injected rats were treated with continuous intravenous injection of 2500 ng/kg/day of EPO, AEPO, or CEPO for 21 days, and lung histology, cardiac function, and mRNA expression in the lungs were examined. Wall thickening of small arteries in the lungs and PH were improved by administration of EPO, but not by its non-hematopoietic derivatives, AEPO, or CEPO. Erythropoietin administration increased mRNA expression of the anti-apoptotic molecule, Bcl-xL, and maintained expression of the CD31 antigen. We conclude that lungs may express EPOR homoreceptors, but not heteroreceptors. Adequate serum erythropoietin levels may be essential for pulmonary protective effects.

    DOI: 10.3109/10641963.2012.681728

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  • Establishment of culturing system for ex-vivo expansion of angiogenic immature erythroid cells, and its application for treatment of patients with chronic severe lower limb ischemia. 国際誌

    Masato Oda, Ken Toba, Takuya Ozawa, Kiminori Kato, Takao Yanagawa, Noboru Ikarashi, Tsugumi Takayama, Tomoyasu Suzuki, Haruo Hanawa, Ichiro Fuse, Kou Nakata, Miwako Narita, Masuhiro Takahashi, Yoshifusa Aizawa

    Journal of molecular and cellular cardiology   49 ( 3 )   347 - 53   2010年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Angiogenesis therapy by bone marrow-mononuclear cell implantation (BMI) has been utilized. We found that erythroid cells played an essential role in angiogenesis by BMI. We then tried to establish a novel cell therapy by implantation of ex vivo expanded immature erythroblasts cultured from hematopoietic stem/precursor cells. Immature to mature erythroblasts were purified from human bone marrow, and mRNA expression were analyzed. Strongly expressed VEGF and PLGF in immature erythroid cells decreased according to erythroid maturation. To expand very immature erythroid cells, we established a two-step culturing system, i.e., bone marrow cells were cultured in the presence of Flt-3L, SCF and TPO for 7 days, and the cells were further cultured in the presence of SCF, IGF-I and EPO for an additional 7 days. The in vivo angiogenic effects of implantation of the ex vivo expanded cells were stronger than that of BMI in mouse limb ischemia model. Three patients with severe chronic lower limb ischemia accompanied by Burger's disease or collagen arteritis were enrolled in a pilot clinical trial of the novel cell therapy by transplantation of ex-vivo expanded immature erythroid cells. In the clinical trial, most clinical symptoms such as rest pain and skin ulcers improved in 4 weeks, and did not recur in the one-year follow-up. No adverse events were observed in any of the patients. Moreover this novel cell therapy required only a small amount of bone marrow collection. Further enrollment of patients with chronic severe lower limb ischemia is necessary to confirm the efficacy and safety of this novel cell therapy, and to estimate the necessary amount of bone marrow aspirate.

    DOI: 10.1016/j.yjmcc.2010.04.001

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  • Coronary vasospasm triggered ventricular fibrillation delayed after radiofrequency ablation of the right accessory pathway. 国際誌

    Yukio Hosaka, Masaomi Chinushi, Kazuyoshi Takahashi, Kazuyuki Ozaki, Takao Yanagawa, Tsutomu Miida, Hirotaka Oda, Yoshifusa Aizawa

    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology   11 ( 11 )   1554 - 6   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Ventricular fibrillation associated with coronary vasospasm developed 8 h after successful radiofrequency (RF) ablation of the right accessory pathway in an 81-year-old male. A segment of the coronary vasospasm was located close to the accessory pathway, where seven RF ablations had been applied. Although rare, physicians should carefully consider the risk of such events when an RF current is applied near a coronary artery.

    DOI: 10.1093/europace/eup219

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  • Serum erythropoietin level as a marker of limb ischemia. 国際誌

    Takuya Ozawa, Kiminori Kato, Ken Toba, Masato Oda, Manabu Isoda, Fuyuki Asami, Noboru Ikarashi, Takao Yanagawa, Masato Moriyama, Masutaka Higashimura, Toshiki Kitajima, Keita Otaki, Tsugumi Takayama, Satoru Hirono, Yuji Okura, Haruo Hanawa, Makoto Kodama, Yoshifusa Aizawa

    International journal of cardiology   130 ( 1 )   106 - 8   2008年10月

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    記述言語:英語  

    Bone marrow implantation (BMI) has been utilized for the treatment of limb ischemia, however, serum markers have not yet been reported to express the degree of limb ischemia. We analyzed the serum levels of several cytokines including erythropoietin (EPO) in the treated legs and the contralateral ones in 11 patients with limb ischemia treated with BMI. The EPO level in the pre-treated legs in the 5 patients with arteriosclerosis obliterans revealed a good correlation with ankle-brachial pressure index. The EPO level, but not the levels of TNF-alpha, VEGF, and bFGF in the pre-treated legs was significantly higher than that in the contralateral legs in the 11 patients, and the EPO level decreased in 4 weeks after BMI. The serum EPO level may express the degree of limb ischemia presumably through the reactive production of EPO in ischemic tissue.

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  • 重症下肢虚血に対する骨髄単核球移植治療後の予後因子 国際誌

    小田 雅人, 加藤 公則, 鳥羽 健, 大瀧 啓太, 北嶋 俊樹, 五十嵐 登, 柳川 貴央, 東村 益孝, 浅見 冬樹, 礒田 学, 小澤 拓也, 森山 雅人, 廣野 暁, 大倉 裕二, 塙 晴雄, 小玉 誠, 相澤 義房

    Journal of Cardiology   50 ( 4 )   235 - 242   2007年10月

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    記述言語:日本語   出版者・発行元:(一社)日本心臓病学会  

    2001年12月〜2005年3月に骨髄細胞移植治療を施行した重症下肢虚血患者21例(平均60.0±13.6歳)を対象に、骨髄細胞移植治療後の長期予後因子を解析した。対象疾患は閉塞性動脈硬化症(ASO)12例、Buerger病5例、血栓塞栓症3例、好酸球増多症候群1例であった。ASO例は非ASOの9例に比べて高脂血症や糖尿病が多く、移植されたCD34陽性細胞数が少なく、組織酸素分圧(TcO2)及び上肢下肢血圧比が低かった。下肢切断に有意な影響を示した因子は、ASOの診断及び術前TcO2が30mmHg以下の低値で、実際に下肢切断に至った6例は、全て術前TcO2が30mmHg以下のASO例であった。一方、骨髄細胞移植治療後の短期効果からは下肢切断の予測はできなかった。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J02134&link_issn=&doc_id=20071023270003&doc_link_id=10019775044&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10019775044&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • Serial electrocardiographic findings in women with Takotsubo cardiomyopathy. 国際誌

    Wataru Mitsuma, Makoto Kodama, Masahiro Ito, Komei Tanaka, Takao Yanagawa, Noboru Ikarashi, Kanako Sugiura, Shinpei Kimura, Nobue Yagihara, Takeshi Kashimura, Koichi Fuse, Satoru Hirono, Yuji Okura, Yoshifusa Aizawa

    The American journal of cardiology   100 ( 1 )   106 - 9   2007年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study aimed to clarify detailed and serial electrocardiographic findings in patients with Takotsubo cardiomyopathy from onset to recovery. Nine consecutive women aged 65 to 84 years (mean 74) with Takotsubo cardiomyopathy were investigated. Standard 12-lead electrocardiograms were recorded during hospitalization and ST-segment elevation and T-wave inversion were manually measured daily in each patient. All 9 patients had 4 phases found electrocardiographically. Phase 1 was characterized by ST-segment elevation immediately after onset. Subsequently, T-wave inversion was observed from days 1 to 3 (phase 2), then inverted T waves improved transiently from days 2 to 6 (phase 3). After this phase, giant inverted T waves with QT prolongation appeared and persisted > or =2 months until recovery (phase 4). Serum creatine kinase levels were increased only at onset. Left ventricular wall motion abnormalities evaluated using echocardiography improved gradually after phase 3 in all patients. Second T-wave inversions (phase 4) were significantly deeper than those of the first one (phase 2; p <0.05). In conclusion, 4 electrocardiographic phases in patients with Takotsubo cardiomyopathy were shown. This observation may be helpful to understand the pathophysiologic process of Takotsubo cardiomyopathy.

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  • Dynamic intraventricular obstruction in acute myocardial infarction with administration of cilostazol.

    Kazuyuki Ozaki, Chiyo Maeda, Tsugumi Takayama, Makoto Hoyano, Takao Yanagawa, Keiichi Tsuchida, Kazuyoshi Takahashi, Tsutomu Miida, Hirotaka Oda

    Circulation journal : official journal of the Japanese Circulation Society   71 ( 4 )   608 - 12   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Dynamic intraventricular obstruction is a less well-known mechanical complication of acute myocardial infarction (AMI). Its hallmark is the development of a new systolic murmur, and echocardiography is necessary for diagnosis. We describe a case of a 74-year-old woman with dynamic intraventricular obstruction complicating AMI. Serial echocardiography suggested that the intraventricular gradient was a consequence of basal hyperkinesis, which was a reciprocal response to akinesis of the apical wall. Cilostazol, which was administered to prevent subacute stent thrombosis after percutaneous coronary intervention, might have contributed to the transient intraventricular obstruction.

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  • Serum endostatin in the coronary circulation of patients with coronary heart disease and its relation to coronary collateral formation. 国際誌

    Wataru Mitsuma, Makoto Kodama, Haruo Hanawa, Masahiro Ito, Mahmoud M Ramadan, Satoru Hirono, Hiroaki Obata, Shinsuke Okada, Fumihiro Sanada, Takao Yanagawa, Takeshi Kashimura, Koichi Fuse, Naohito Tanabe, Yoshifusa Aizawa

    The American journal of cardiology   99 ( 4 )   494 - 8   2007年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The role of endostatin in coronary heart disease (CHD) is not well known. This study aimed to investigate the dynamics of endostatin, an antiangiogenic growth factor, within the coronary circulation and to elucidate its relation to coronary collateral formation in patients with CHD. We recruited 72 subjects with suspected or previously diagnosed CHD. Blood samples from the left ventricular (LV) cavity and coronary sinus (CS) were obtained during coronary angiography, and the serum concentration of endostatin was measured by enzyme-linked immunosorbent assay kits. Patients were then divided into 2 groups: the normal group (n = 15) defined as patients with atypical chest pain and no evidence of organic cardiac diseases and the CHD group (n = 57) defined as patients with >or=75% coronary stenosis at coronary angiography and chest pain on exertion. Endostatin in CS sera was significantly elevated in patients with CHD compared with normal subjects (median 79.7 [interquartile range 46.2 to 130.3] vs median 49.6 [interquartile range 29.1 to 84.5] ng/ml, p = 0.02). Spillover of endostatin (CS - LV value) from the coronary circulation in patients with CHD with severe stenosis was higher than in those with moderate stenosis (28.2 [4.8 to 48.6] vs 7.3 [-37.0 to 25.6] ng/ml, p = 0.01). In addition, endostatin production within the coronary circulation was higher in patients with poorly developed collaterals than in those with well-developed collaterals. In conclusion, endostatin is suggested to be produced from the coronary circulation in patients with CHD and may play an important role in the regulation of the growth of coronary collateral vessels.

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共同研究・競争的資金等の研究

  • デノスマブによる心血管イベント抑制効果評価のための多施設共同研究

    研究課題/領域番号:18K08030  2018年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    小澤 拓也, 柳川 貴央, 高山 亜美, 池上 龍太郎, 須田 将吉, 久保田 直樹

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    デノスマブは破骨細胞を活性化させるRANKLに対する抗体で骨粗鬆症の治療薬であるが,RANKLは血管にも発現しており,血管石灰化に関与していることがin vitroで示されている.実際我々は平成26年~28年の科学研究費助成事業にて施行したPilot studyにおいて,デノスマブ投与により冠動脈石灰化スコアの進行を抑制することを明らかにした.Pilot studyの更なる検証として、我々は新たに「冠動脈疾患合併骨粗鬆症症例に対するデノスマブ群とアレンドロン酸群の冠動脈石灰化に与える影響を評価するための非盲検化群間比較試験」を立案した.本試験は2019年3月7日に新潟大学中央臨床研究審査委員会にて承認を得た.jRCTに2019年5月17日登録し(計画番号jRCT1031190025)、症例の登録作業を進めている.今までに1例症例を登録した.

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  • 重症下肢虚血におけるメタボローム解析を用いた病態および治療マーカーの解明

    研究課題/領域番号:17K09550  2017年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    柳川 貴央, 南野 徹, 小澤 拓也

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    血管内治療を予定している末梢動脈疾患患者において、同意書の得られた計11例に対して、治療前の下肢動静脈から血液サンプリングが得られ、現在解析中であ る。 跛行患者においては臨床的パラメータはいずれも改善しているが、重症下肢虚血患者においては皮膚灌流圧などのデータは十分な改善が得られていない。 しかし、皮膚潰瘍など創部の状態においては軽快しているケースもある。 血管内治療以外の集学的な治療において、一般的な皮膚灌流圧などで評価不能な組織代謝の変化が生じている可能性があり、さらなる症例の集積と解析が必要と考えている。

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  • メタボロミクスを用いた心肺血管疾患における代謝リモデリングの解析

    研究課題/領域番号:16K09422  2016年4月 - 2019年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    尾崎 和幸, 南野 徹, 小澤 拓也, 柳川 貴央, 保屋野 真, 田中 孔明, 清水 逸平, 高野 俊樹, 久保田 直樹, 崎村 建司, 奥田 修二郎, 曽我 朋義

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    これまで、我々は138名の心肺血管疾患患者において探索的にメタボローム解析を行った。その結果、特に虚血性心筋症における低心機能患者において、ピルビン酸、乳酸の心臓への取り込みの減少等、いくつかの代謝産物に変化があることを確認した。さらに、非虚血性心筋症に伴う低心機能患者では、一部の代謝産物において虚血性心筋症とは異なる動態を示すことも判明しつつある。詳細な臨床データとの解析も現在進行中である。また、重要と思われる代謝産物では心不全モデルマウスでの検討も開始した。今後、さらなる症例の蓄積、フォローアップデータの解析を行う予定である。

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  • 体外増幅自己赤芽球移植と自己骨髄単核細胞移植による血管新生治療の比較試験

    研究課題/領域番号:15K09117  2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    小澤 拓也, 柳川 貴央, 森山 雅人, 増子 正義, 須田 将吉

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    重症虚血肢への自己骨髄細胞移植(BMI)による血管新生治療はある一定の効果はあるが、問題点が多い。我々は次世代血管新生治療として「重症下肢虚血に対する体外増幅自己赤芽球移植による血管新生治療の第I/II相臨床試験(EVEETA)」を開発し良好な結果を得た。本研究では従来法であるBMI療法と体外培養法によるEVEETA療法、この2つの血管新生療法の治療効果および安全性を検討した。いずれの治療法も急性期効果は得られたが、長期効果を検討するとBMI療法では1年以内に約半数の症例で何らかの切断術が施行された。EVEETA療法では下肢切断術を要する症例はなく、治療効果が長期間持続していると考えられた。

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  • 体外増幅赤芽球移植を用いた血管新生治療の長期予後と治療効果の予測因子の検討

    研究課題/領域番号:24591037  2012年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    小澤 拓也, 鳥羽 健, 塙 晴雄, 小田 雅人, 栁川 貴央, 森山 雅人, 増子 正義, 須田 将吉

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    配分額:5460000円 ( 直接経費:4200000円 、 間接経費:1260000円 )

    重症虚血肢に対する体外増幅自己赤芽球移植(EVEETA)による血管新生治療の第I/II相臨床試験を開始しその急性期効果および中長期予後について検討した。局所麻酔下に採取した少量の骨髄細胞を2段階培養法にて未熟赤芽球を体外増幅・培養し虚血下肢に筋肉内投与した。全13症例に対し施行し、すみやかな下肢痛の軽減、難治性皮膚潰瘍の縮小、局所組織酸素分圧や皮膚灌流圧の上昇といった非常に良好な結果を得ることができた。本法は局所麻酔下で採取骨髄も平均71.2 ± 20.1 mLと少量ですみ、赤芽球細胞の増幅効率も平均64.5 ± 41.3倍と安定していた。いずれの症例においても明らかな有害事象は認めなかった。

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