Faculty Profiles - NAKAMURA Kazufumi

MISC - NAKAMURA Kazufumi

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Prednisolone inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension.

Ogawa A, Nakamura K, Matsubara H, Fujio H, Ikeda T, Kobayashi K, Miyazaki I, Asanuma M, Miyaji K, Miura D, Kusano FK, Date H, Ohe T

Circulation 2005

頻回の心室細動発作に対してキニジンが著効したBrugada症候群の1例

渡辺敦之, 森田宏, 草野研吾, 角田和歌子, 伴場主一, 西井伸洋, 永瀬聡, 中村一文, 斎藤博則, 大江透

心臓 37,SUPPL.3,68-72 2005

臨床心臓の病気・病態での突然死 QT延長症候群

渡辺敦之, 中村一文, 森田宏, 草野研吾, 大江透

日本臨床 63,7,1171-1177 2005

Para-hisian accessory pathwayに対しアブレーションを施行した肥大型心筋症の2例

永瀬聡, 草野研吾, 西井伸洋, 渡辺敦之, 伴場主一, 平松茂樹, 中村一文, 斉藤博則, 大江透

不整脈 21 ( 2 ) 2005

右室心尖部以外に留置された植込み型除細動器の心室リードの安全性について

西井伸洋, 草野研吾, 平松茂樹, 村上正人, 渡辺敦之, 伴場主一, 永瀬聡, 中村一文, 斉藤博則

不整脈 21 ( 2 ) 2005

94) 原発性肺高血圧症患者におけるMCP-1(第84回日本循環器学会中国地方会)

橋本克史, 中村一文, 藤尾栄起, 永瀬聡, 宮地克維, 森田宏, 齋藤博則, 草野研吾, 江森哲郎, 大江透, 松原広己

Circulation journal : official journal of the Japanese Circulation Society 68 948 - 948 2004.10

65) 院内AEDによる除細動にて救命された2症例(第84回日本循環器学会中国地方会)

斉藤博則, 江森哲郎, 森田宏, 中村一文, 大江透, 林峰栄, 氏家良人

Circulation journal : official journal of the Japanese Circulation Society 68 945 - 945 2004.10

8) マラソン中に心肺停止をきたした右冠動脈起始異常の一症例(第84回日本循環器学会中国地方会)

伴場主一, 宮地晃平, 清藤哲司, 永瀬聡, 中村一文, 森田宏, 齋藤博則, 村上充, 江森哲郎, 大江透, 谷本耕司郎

Circulation journal : official journal of the Japanese Circulation Society 68 939 - 939 2004.10

72) 高齢にて発症したQT延長症候群の一例(第84回日本循環器学会中国地方会)

三浦大志, 中村一文, 久松研一, 永瀬聡, 森田宏, 竹中志保, 斉藤博則, 江森哲郎, 大江透, 西内崇将, 幡芳樹, 水尾浩三

Circulation journal : official journal of the Japanese Circulation Society 68 946 - 946 2004.10

Characterization of the bone morphogenetic protein (BMP) system in human pulmonary arterial smooth muscle cells isolated from a sporadic case of primary pulmonary hypertension: Roles of BMP type IB receptor (activin receptor-like kinase-6) in the mitotic action

M Takeda, F Otsuka, K Nakamura, K Inagaki, J Suzuki, D Miura, H Fujio, H Matsubara, H Date, T Ohe, H Makino

ENDOCRINOLOGY 145 ( 9 ) 4344 - 4354 2004.9

Language：English Publisher：ENDOCRINE SOC

The functional involvement of bone morphogenetic protein (BMP) system in primary pulmonary hypertension (PPH) remains unclear. Here we demonstrate a crucial role of the BMP type 113 receptor, activin receptor-like kinase (ALK)-6 for pulmonary arterial smooth muscle cell (pphPASMC) mitosis isolated from a sporadic PPH patient bearing no mutations in BMPR2 gene. A striking increase in the levels of ALK-6 mRNA was revealed in pphPASMC compared with control PASMCs, in which ALK-6 transcripts were hardly detectable. BMP-2 and -7 stimulated the mitosis of pphPASMCs, which was opposite to their suppressive effects on the mitosis of the control PASMCs. BMP-4 and -6 and activin inhibited pphPASMC mitosis, whereas these did not affect control PASMCs. The presence of BMP signaling machinery in pphPASMCs was elucidated based on the analysis on Id-1 transcription and Smad-reporter genes. Overexpression of a dominant-negative ALK-6 construct revealed that ALK-6 plays a key role in the mitosis as well as intracellular BMP signaling of pphPASMCs. Gene silencing of ALK-6 using small interfering RNA also reduced DNA synthesis as well as Id-1 transcription in pphPASMCs regardless of BMP-2 stimulation. Although Id-1 response was not stimulated by BMP-2 in control PASMCs, the gene delivery of wild-type ALK-6 caused significant increase in the Id-1 transcripts in response to BMP-2. Additionally, inhibitors of ERK and p38 MAPK pathways suppressed pphPASMC mitosis induced by BMP-2, implying that the mitotic action is in part MAPK dependent. Thus, the BMP system is strongly involved in pphPASMC mitosis through ALK-6, which possibly leads to activation of Smad and MAPK, resulting in the progression of vascular remodeling of pulmonary arteries in PPH.

DOI： 10.1210/en.2004-0234

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Diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome

W Shimizu, T Noda, H Takaki, N Nagaya, K Satomi, T Kurita, K Suyama, N Aihara, K Sunagawa, S Echigo, Y Miyamoto, Y Yoshimasa, K Nakamura, T Ohe, JA Towbin, SG Priori, S Kamakura

HEART RHYTHM 1 ( 3 ) 276 - 283 2004.9

Language：English Publisher：ELSEVIER SCIENCE INC

OBJECTIVES The aim of this study was to test the hypothesis that epinephrine test may have diagnostic value for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome (LQTS).
BACKGROUND A differential response of dynamic QT interval to epinephrine infusion between LQT1, LQT2, and LQT3 syndromes has been reported, indicating the potential diagnostic value of the epinephrine test for genotyping the three forms.
METHODS The responses of 12-lead ECG parameters to epinephrine were retrospectively examined in 15 LQT1, 10 LQT2, 8 LQT3, and 10 healthy volunteers to select the best ECG criteria for separating the four groups. The epinephrine test then was prospectively conducted in 42 probands clinically affected with LQTS, their 67 family members, and 10 new volunteers. The best criteria were applied in a blinded fashion to prospectively separate a different group of 31 LQT1, 23 LQT2, 6 LQT3, and 30 Control patients (10 genotype-negative LQT1, 10 genotype-negative LQT2 family members, and 10 volunteers).
RESULTS The sensitivity (penetrance) by ECG diagnostic criteria was lower in LQT1 (68%) than in LQT2 (83%) or LQT3 (83%) before epinephrine and was improved with steady-state epinephrine in LQT1 (87%) and LQT2 (91%) but not in LQT3 (83%), without the expense of specificity (100%). The sensitivity and specificity to differentiate LQT1 from LQT2 were 97% and 96%, those from LQT3 were 97% and 100%, and those from Control were 97% and 100%, respectively, when Delta mean corrected Q-Tend greater than or equal to35ms at steady state was used. The sensitivity and specificity to differentiate LQT2 from LQT3 or Control were 100% and 100%, respectively, when Delta mean corrected Q-Tend greater than or equal to80ms at peak was used.
CONCLUSIONS Epinephrine infusion is a powerful test to predict the genotype of LQT1, LQT2, and LQT3 syndromes as well as to improve the clinical diagnosis of genotype-positive patients, especially those with LQT1 syndrome.

DOI： 10.1016/j.hrthm.2004.04.021

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Differences between flow profiles of pulmonary vein anastomoses affected by peripheral atelectasis in cadaveric and bilateral living-donor lobar lung transplantations

K Miyaji, H Matsubara, K Nakamura, T Maruo, H Morita, H Saito, KF Kusano, T Emori, K Goto, H Date, T Ohe

JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY 17 ( 9 ) 1003 - 1004 2004.9

Language：English Publisher：MOSBY, INC

We report two cases of peripheral atelectasis during cadaveric and living-donor lobar lung transplantation, which had different effects on the flow profile of pulmonary vein (PV) anastomoses. In the patient who underwent living-donor lobar lung transplantation, we detected the increase in the velocity of blood flow through the left PV anastomosis by intraoperative transesophageal echocardiography. Then peripheral atelectasis occurred in the transplanted left lung lobe. On the other hand, in the patient who underwent cadaveric bilateral lung transplantation, peripheral atelectasis occurred, but no changes in velocities of blood flow through PV anastomoses were detected by intraoperative transesophageal echocardiography. This difference may have been caused by the difference in sizes of pulmonary beds of transplanted grafts. These findings indicate the necessity of careful monitoring of PV anastomoses, especially in cases of living-donor lobar lung transplantation.

DOI： 10.1016/j.echo.2004.04.034

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Effect of a kink in unilateral pulmonary artery anastomosis on velocities of blood flow through bilateral pulmonary vein anastomose's in living-donor lobar lung transplantation

K Miyaji, K Nakamura, T Maruo, H Morita, H Saito, T Emori, K Goto, H Date, T Ohe

JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY 17 ( 9 ) 998 - 999 2004.9

Language：English Publisher：MOSBY, INC

Intraoperative transesophageal echocardiography is generally performed to detect vascular complications during lung transplantation. We report a case with a kink in pulmonary artery (PA) anastomosis suggested by an abnormal flow profile of pulmonary vein (PV) anastomoses during living-donor lobar lung transplantation. During the transplantation, velocity of blood flow through the right PV anastomosis showed abnormal elevation. Then, the patient's PA pressure elevated abnormally and a kink in the left PA anastomosis was found. Careful monitoring of PV anastomoses; may enable detection of not only an abnormality of PV anastomoses but also that of PA anastomoses, especially in living-donor lobar lung transplantation.

DOI： 10.1016/j.echo.2004.04.014

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Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome - Multicenter study in Japan

W Shimizu, M Horie, S Ohno, K Takenaka, M Yamaguchi, M Shimizu, T Washizuka, Y Aizawa, K Nakamura, T Ohe, T Aiba, Y Miyamoto, Y Yoshimasa, JA Towbin, SG Priori, S Kamakura

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 44 ( 1 ) 117 - 125 2004.7

Language：English Publisher：ELSEVIER SCIENCE INC

OBJECTIVES We sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome (LQTS).
BACKGROUND The LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms.
METHODS Sixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes.
RESULTS Patients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p < 0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p < 0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patients with transmembrane mutations (p < 0.005).
CONCLUSIONS In this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations. (C) 2004 by the American College of Cardiology Foundation.

DOI： 10.1016/j.jacc.2004.03.043

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Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia

K Ueda, K Nakamura, T Hayashi, N Inagaki, M Takahashi, T Arimura, H Morita, Y Higashiuesato, Y Hirano, M Yasunami, S Takishita, A Yamashina, T Ohe, M Sunamori, M Hiraoka, A Kimura

JOURNAL OF BIOLOGICAL CHEMISTRY 279 ( 26 ) 27194 - 27198 2004.6

Language：English Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Hyperpolarization-activated cyclic nucleotide-gated channel 4 gene HCN4 is a pacemaker channel that plays a key role in automaticity of sinus node in the heart, and an HCN4 mutation was reported in a patient with sinus node dysfunction. Expression of HCN4 in the heart is, however, not confined to the sinus node cells but is found in other tissues, including cells of the conduction system. On the other hand, mutations in another cardiac ion channel gene, SCN5A, also cause sinus node dysfunction as well as other cardiac arrhythmias, including long QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, and progressive cardiac conduction disturbance. These observations imply that HCN4 abnormalities may be involved in the pathogenesis of various arrhythmias, similar to the SCN5A mutations. In this study, we analyzed patients suffering from sinus node dysfunction, progressive cardiac conduction disease, and idiopathic ventricular fibrillation for mutations in HCN4. A missense mutation, D553N, was found in a patient with sinus node dysfunction who showed recurrent syncope, QT prolongation in electrocardiogram, and polymorphic ventricular tachycardia, torsade de pointes. In vitro functional study of the D553N mutation showed a reduced membranous expression associated with decreased If currents because of a trafficking defect of the HCN4 channel in a dominant-negative manner. These data suggest that the loss of function of HCN4 is associated with sinus nodal dysfunction and that a consequence of pacemaker channel abnormality might underlie clinical features of QT prolongation and polymorphic ventricular tachycardia developed under certain conditions.

DOI： 10.1074/jbc.M311953200

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Sarcomere-length dependence of lattice volume and radial mass transfer of myosin cross-bridges in rat papillary muscle

N Yagi, H Okuyama, H Toyota, J Araki, J Shimizu, G Iribe, K Nakamura, S Mohri, K Tsujioka, H Suga, F Kajiya

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY 448 ( 2 ) 153 - 160 2004.5

Language：English Publisher：SPRINGER-VERLAG

We examined the sarcomere length-dependence of the spacing of the hexagonal lattice of the myofilaments and the mass transfer of myosin cross-bridges during contraction of right ventricular papillary muscle of the rat. The lattice spacing and mass transfer were measured by using X-ray diffraction, and the sarcomere length was monitored by laser diffraction at the same time. Although the lattice spacing and the sarcomere length were inversely related, their relationship was not exactly isovolumic. The cell volume decreased by about 15% when the sarcomere length was shortened from 2.3 mum to 1.8 mum. Twitch tension increased with sarcomere length (the Frank-Starling law). At the peak tension, the ratio of the intensity of the (1,0) equatorial reflection to that of the (1,1) reflection was smaller when the tension was greater, showing that the larger tension at a longer sarcomere length accompanies a larger amount of mass transfer of cross-bridges from the thick to the thin filament. The result suggests that the Frank-Starling law is due to an increase in the number of myosin heads attached to actin, not in the average force produced by each head.

DOI： 10.1007/s00424-004-1243-z

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121) プロスプロスタグランディンI2による薬剤性間質性肺炎を来した原発性肺高血圧症の一例(第83回日本循環器学会中国・四国合同地方会)

木村英夫, 宮地晃平, 河野康之, 伴場圭一, 藤尾栄起, 宮地克維, 中村一文, 森田宏, 齋藤博則, 江森哲郎, 大江透, 松原広己

Circulation journal : official journal of the Japanese Circulation Society 68 836 - 836 2004.4

129) 冠動脈炎による急性心筋梗塞を発症した若年女性の一症例(第83回日本循環器学会中国・四国合同地方会)

伴場圭一, 木村英夫, 永瀬聡, 中村一文, 森田宏, 齋藤博則, 江森哲郎, 大江透

Circulation journal : official journal of the Japanese Circulation Society 68 837 - 837 2004.4

130) 心室細動にて発症し救命しえた冠動脈瘤病変を有した一症例(第83回日本循環器学会中国・四国合同地方会)

伴場主一, 木村英夫, 永瀬聡, 中村一文, 森田宏, 齋藤博則, 江森哲郎, 大江透

Circulation journal : official journal of the Japanese Circulation Society 68 837 - 837 2004.4

OE-297 Elevated Levels of 8-Hydroxy-2-Deoxyguanosine in Serum and Myocardium of Patients with Dilated Cardiomyopathy(Cardiomyopathy, Clinical 6 (M) : OE37)(Oral Presentation (English))

Nakamura Kazufumi, Kusano Kengo, Miura Aya, Nishii Nobuhiro, Miyaji Katsumasa, Nagase Satoshi, Morita Hiroshi, Saitoh Hironori, Emori Tetsuro, Nakamura Yoichi, Murakami Takashi, Matsubara Hiromi

Circulation journal : official journal of the Japanese Circulation Society 68 212 - 213 2004.3

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MISC - NAKAMURA Kazufumi