研究者詳細 - 廣畑　聡

論文 - 廣畑　聡

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ARB内服中高血圧患者に対するカルシウム拮抗薬もしくは利尿剤の追加がAugmentation indexへ与える影響

三好亨, 土井正行, 小川弘子, 廣畑聡, 草地省蔵, 小出典男, 伊藤浩

臨床病理 59 ( 補冊 ) 219 - 219 2011年10月

急性冠症候群患者における血清ADAMTS1レベルの上昇

廣畑聡, 小比賀真就, 幡中邦彦, 小川弘子, 三好亨, 石井裕子, 坂本かおり, 草地省蔵, 伊藤浩, 二宮善文

臨床病理 59 ( 補冊 ) 116 - 116 2011年10月

Olmesartan reduces arterial stiffness and serum adipocyte fatty acid-binding protein in hypertensive patients

Toru Miyoshi, Masayuki Doi, Satoshi Hirohata, Shigeshi Kamikawa, Shinichi Usui, Hiroko Ogawa, Kosuke Sakane, Reishi Izumi, Yoshifumi Ninomiya, Shozo Kusachi

HEART AND VESSELS 26 ( 4 ) 408 - 413 2011年7月

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

Adipocyte fatty acid binding protein (A-FABP) has been reported to be involved in insulin resistance, lipid metabolism, and atherosclerosis; however, little is known about the effect of medication on the change in circulating A-FABP in human subjects. We evaluated the effects of angiotensin II type 1 receptor blocker (ARB) on arterial stiffness and its association with serum A-FABP in patients with hypertension. Thirty patients newly diagnosed with essential hypertension were treated with olmesartan (20 mg/day), an ARB, for 6 months. Serum levels of A-FABP and high-sensitivity C-reactive protein (hsCRP) were examined and the cardio-ankle vascular index (CAVI), which is a marker of arterial stiffness, was also determined. Serum A-FABP at baseline was significantly correlated with the body mass index (r = 0.45, P = 0.01), homeostasis model assessment as a marker of insulin resistance (r = 0.53, P < 0.01), and systolic blood pressure (r = 0.37, P = 0.047), and tended to be correlated with low-density lipoprotein cholesterol, triglyceride, and CAVI. Olmesartan treatment resulted in a significant decrease in CAVI, serum A-FABP levels, and hsCRP, besides a significant reduction of blood pressure. Multiple regression analysis revealed that the change in CAVI was independently correlated with the change in serum A-FABP. Olmesartan ameliorated arterial stiffness in patients with hypertension, which may be involved in the reduction of serum A-FABP.

DOI： 10.1007/s00380-010-0060-x

アンジオテンシンII受容体拮抗薬(オルメサルタン)によるサイトカイン発現抑制効果と心機能保持効果

大月孝志, 篠畑綾子, 廣畑聡, 草地省蔵, 二宮善文

日本結合組織学会学術大会・マトリックス研究会大会合同学術集会プログラム・抄録集 43回・58回 126 - 126 2011年5月

炎症標的化金コロイド内包リポソームのリウマチ関節炎症部位への集積

古谷満寿美, 松本衣未, 美名口順, 小川弘子, 古松毅之, 廣畑聡, 二宮善文, 西田圭一郎, 大塚愛二, 大橋俊孝

日本結合組織学会学術大会・マトリックス研究会大会合同学術集会プログラム・抄録集 43回・58回 118 - 118 2011年5月

IMPACT OF INCREASED ARTERIAL STIFFNESS AND WAVE REFLECTION ON THE PREVALENCE OF PAROXYSMAL ATRIAL FIBRILLATION

Toru Miyoshi, Msayuki Doi, Satoshi Hirohata, Shozo Kusachi, Kazufumi Nakamura, Satoshi Nagase, Kunihisa Kono, Hiroshi Morita, Kengo Kusano, Hiroshi Ito

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 57 ( 14 ) E563 - E563 2011年4月

ANTI-INFLAMMATORY EFFECT OF OLMESARTAN ON CORONARY PLAQUE PROGRESSION, FINDING FROM THE IMPACT OF OLMESARTAN ON PROGRESSION OF CORONARY ATHEROSCLEROSIS: EVALUATION BY INTRAVASCULAR ULTRASOUND (OLIVUS) TRIAL

Toru Miyoshi, Atsushi Hirohata, Shozo Kusachi, Satoshi Hirohata, Kazufumi Nakamura, Hiroshi Morita, Kengo Kusano, Hiroshi Ito

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 57 ( 14 ) E604 - E604 2011年4月

Association of serum levels of arachidonic acid and eicosapentaenoic acid with prevalence of major adverse cardiac events after acute myocardial infarction

Masayuki Ueeda, Takenori Doumei, Yoichi Takaya, Nobuhiko Ohnishi, Atsushi Takaishi, Satoshi Hirohata, Toru Miyoshi, Ryoko Shinohata, Shinichi Usui, Shozo Kusachi

HEART AND VESSELS 26 ( 2 ) 145 - 152 2011年3月

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

We studied the association of serum levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA) with the prevalence of major adverse cardiac events (MACE) after acute myocardial infarction (AMI). We measured serum AA and EPA on admission in 146 consecutive AMI patients. The primary clinical endpoint was occurrence of MACE, defined as cardiac death, occurrence of heart failure, reinfarction, recurrent angina pectoris, and requirement of coronary intervention. Common logarithmic transformed serum levels of AA (logAA) and EPA (logEPA) were used in the analyses. The optimum cutoff point of each fatty acid used to distribute patients into two groups for Kaplan-Meier analysis was determined by receiver operating characteristic curves analysis. MACE occurred in 40 patients (27.4%). Kaplan-Meier analysis disclosed that the group with a logAA above the cutoff point [145.3 mu g/mL (logAA 2.162)] showed a higher prevalence of MACE than those with a logAA below the cutoff point (P < 0.01). Conversely, the prevalence of MACE was significantly higher in the group with a logEPA below the cutoff point [52.3 mu g/mL (logEPA 1.719)] compared to the group with a logEPA above it (P < 0.01). Similar to logAA, logAA/logEPA showed significant differences in the MACE-free curve between the two groups (cutoff 1.301, P < 0.001). Cox proportional hazards regression analysis suggested that logAA, logEPA, and logAA/logEPA were independently associated with the prevalence of MACE. Although the present study included a limited number of patients with single-time point measurement, the results suggested an association of logAA, logEPA, and logAA/logEPA with the prevalence of MACE after AMI. The present study warrants further studies involving a large number of patients to confirm that the serum levels of these fatty acids and their ratios are predictors of MACE after AMI.

DOI： 10.1007/s00380-010-0038-8

Distribution Pattern of Urine Albumin Creatinine Ratio and the Prevalence of High-Normal Levels in Untreated Asymptomatic Non-Diabetic Hypertensive Patients

Natsuki Ohmaru, Takaaki Nakatsu, Reishi Izumi, Keiichi Mashima, Misako Toki, Asako Kobayashi, Hiroko Ogawa, Satoshi Hirohata, Satoru Ikeda, Shozo Kusachi

INTERNAL MEDICINE 50 ( 16 ) 1621 - 1629 2011年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN SOC INTERNAL MEDICINE

Background Even high-normal albuminuria is reportedly associated with cardiovascular events.
Objective We determined the urine albumin creatinine ratio (UACR) in spot urine samples and analyzed the UACR distribution and the prevalence of high-normal levels.
Patients and Methods The UACR was determined using immunoturbidimetry in 332 untreated asymptomatic non-diabetic Japanese patients with hypertension and in 69 control subjects. The microalbuminuria and macroalbuminuria levels were defined as a UCAR >= 30 and <300 mu g/mg.creatinine and a UCAR >= 300 mu g/mg.creatinine, respectively.
Results The distribution patterns showed a highly skewed distribution for the lower levels, and a common logarithmic transformation produced a close fit to a Gaussian distribution with median, 25th and 75th percentile values of 22.6, 13.5 and 48.2 mu g/mg.creatinine, respectively. When a high-normal UACR was set at >20 to <30 mu g/mg.creatinine, 19.9% (66/332) of the hypertensive patients exhibited a high-normal UACR. Micro-albuminuria and macroalbuminuria were observed in 36.1% (120/336) and 2.1% (7/332) of the patients, respectively. UACR was significantly correlated with the systolic and diastolic blood pressures and the pulse pressure. A stepwise multivariate analysis revealed that these pressures as well as age were independent factors that increased UACR.
Conclusion The UACR distribution exhibited a highly skewed pattern, with approximately 60% of untreated, non-diabetic hypertensive patients exhibiting a high-normal or larger UACR. Both hypertension and age are independent risk factors that increase the UACR. The present study indicated that a considerable percentage of patients require anti-hypertensive drugs with antiproteinuric effects at the start of treatment.

DOI： 10.2169/internalmedicine.50.5075

Significant relationship between changes in brachial-ankle pulse wave velocity relative to blood pressure elevation and coronary artery disease 査読国際誌

Issei Komatsubara, Shinichi Inoue, Rie Koumoto, Shigeru Matano, Tomoki Kitawaki, Satoshi Hirohata, Toru Miyoshi, Hiroko Ogawa, Ryoko Shinohata, Shozo Kusachi

CORONARY ARTERY DISEASE 21 ( 7 ) 407 - 413 2010年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Objectives Based on well-established physiological theories, we studied correlations between changes in brachial-ankle pulse wave velocity (baPWV) relative to blood pressure (BP) elevation (elasticity of large-to-medium-sized arteries), and coronary artery disease (CAD).
Methods The baPWV (in centimeters/second) and BP (in millimeters of mercury) were determined in 101 patients before, during, and/or after a cold pressor test using a volume-plethysmographic system.
Results Significantly higher rates of increase in PWV relative to changes in BP were observed in the CAD(+) group than in the CAD(-) group when mean BP [median (25th-75th percentiles): 14.8 (8.3-24.9) vs. 8.6 (5.7-11.4) cm/s/mmHg, P < 0.0001], and systolic [10.1 (6.0-17.5) vs. 6.4 (4.4-10.6) cm/s/mmHg, P = 0.0023] and diastolic BP [21.0 (14.0-34.4) vs. 10.8 (6.8-16.1) cm/s/mmHg, P < 0.0001] were used as BP indices. Similarly, the rates of increase in baPWV showed a significant correlation with the extent of CAD. The rate of increase in baPWV obtained using the mean, systolic and diastolic BP as indices showed an area under the receiver operating characteristic curve of 0.68-0.76, sensitivity of 65-75%, and specificity of 65-75% for the detection of CAD. The area under the receiver operating characteristic curve, sensitivity, and specificity for the rate of increase were slightly higher than those for baseline baPWV and baseline baPWV/baseline BP ratio, but not to a significant degree.
Conclusion The rate of increase in baPWV relative to BP elevation determined by cold pressor test is significantly and moderately correlated with CAD. To identify patients with CAD, the rate of increase in baPWV relative to changes in BP can provide considerable, but limited, information. Coron Artery Dis 21: 407-413 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

DOI： 10.1097/MCA.0b013e32833e1c19

Serum Adipocyte Fatty Acid-Binding Protein is Associated With Coronary Lesion Complexity in Patients With Coronary Artery Disease

Masayuki Doi, Toru Miyoshi, Mutsumi Iwamoto, Kunio Nogami, Kajiya Masashi, Ko Takeda, Satoshi Hirohata, Shozo Kusachi, Hiroshi Ito

CIRCULATION 122 ( 21 ) 2010年11月

Chronic Kidney Disease is a Strong Predictor Related to the Severity of Coronary Artery Lesion in Patients with Stable Angina Pectoris

Kazuhiro Dan, Masayuki Ueeda, Hiroaki Ohtsuka, Satoko Ugawa, Nobuhiko Ohnishi, Atsushi Takaishi, Satoshi Hirohata, Shozo Kusachi, Kengo Kusano, Hiroshi Ito

CIRCULATION 122 ( 2 ) E363 - E364 2010年7月

Combination Therapy of Calcium Channel Blocker and Angiotensin II Receptor Blocker Reduces Augmentation Index in Hypertensive Patients 査読国際誌

Masayuki Doi, Toru Miyoshi, Satoshi Hirohata, Shigeshi Kamikawa, Shinichi Usui, Youko Kaji, Kosuke Sakane, Hiroko Ogawa, Yoshifumi Ninomiya, Shozo Kusachi

AMERICAN JOURNAL OF THE MEDICAL SCIENCES 339 ( 5 ) 433 - 439 2010年5月

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

Introduction: The optimal combination treatment for hypertension has not been established. We investigated the effect of a calcium channel blocker or a diuretic added to angiotensin II receptor blockers (ARBs) on the augmentation index (AI), as a marker of arterial stiffness and wave reflection, in hypertensive patients. Methods: Thirty-seven patients treated with ARBs were randomly allocated to either of the 2 groups receiving an ARB plus azelnidipine (AZ group) or trichlormethiazide (TCM group). Changes in brachial blood pressure (BP), AI, high-sensitive C-reactive protein (hsCRP), and serum asymmetric dimethylarginine, as an endogenous nitric oxide synthase inhibitor, were determined. Results: Systolic and diastolic blood pressure after 6 months were significantly reduced in both the groups similarly; however, after adjustment for baseline covariates, the extent of the reduction in AI (%) in the AZ group was significantly greater than in the TCM group (between-group difference was 3.2; 95% CI: 0.2-6.3; P = 0.03). The reduction of high-sensitive C-reactive protein (mg/L) and serum asymmetric dimethylarginine (mu mol/L) was significantly greater in the AZ group than in the TCM group (between-group difference was 0.18 and 0.05; 95% CI: -0.01 to 0.36 and -0.01 to 0.11; P = 0.04 and 0.02, respectively). Further, when patients were analyzed according to age younger than 60 years or older than 60 years, the reduction in AI in the AZ group aged older than 60 years was significantly greater than in the TCM group. Conclusion: The results suggest that azelnidipine has a more beneficial effect on vascular properties in combination therapy with ARB than trichlormethiazide.

DOI： 10.1097/MAJ.0b013e3181d658c4

AHR (Acute hypoxia responsive element) As a New Tool Detecting Acute Hypoxia

Mehmet Zeynel Cilek, Satoshi Hirohata, Omer Faruk Hatipoglu, Yoshifumi Ninomiya

FASEB JOURNAL 24 2010年4月

Effect of Cilnidipine on Normal to Marginally Elevated Urine Albumin-Creatinine Ratio in Asymptomatic Non-Diabetic Hypertensive Patients An Exponential Decay Curve Analysis 査読国際誌

Takaaki Nakatsu, Shinji Toyonaga, Keiichi Mashima, Yoko Yuki, Aya Nishitani, Hiroko Ogawa, Toru Miyoshi, Satoshi Hirohata, Reishi Izumi, Shozo Kusachi

CLINICAL DRUG INVESTIGATION 30 ( 10 ) 699 - 706 2010年

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

Background: High-normal urinary albumin excretion has been reported to have clinical significance with respect to progression of proteinuria and hypertension.
Objective: We analysed the effect of cilnidipine (10 mg/day) on morning systolic blood pressure (SBP) and urine albumin-creatinine ratio (UACR) in 16 non-diabetic hypertensive patients with a normal to marginally elevated UACR (mean +/- SD 29.4 +/- 21.7; range 7.5-72.9 mg/g creatinine).
Methods: Sequential home BP and UACR data were fitted to a simple exponential function as follows: y = alpha.e(-t/beta) + gamma, where y is SBP (mmHg) or UACR (mg/g creatinine); alpha is the extent of the SBP (mmHg)- or UACR (mg/g creatinine)-lowering effect; 13 (days) is the time-constant for SBP or UACR decrease; t is the number of days after the start of cilnidipine administration; and gamma is the finally stabilized SBP (mmHg) or UACR (mg/g creatinine).
Results: Mean +/- SD morning SBP and UACR decreased by 20.4 +/- 11.4 mmHg and 15.2 +/- 13.1 mg/g creatinine, respectively, as determined by coefficient alpha. The mean SD time-constant for UACR decrease was significantly longer than that for BP decrease (43.5 +/- 22.9 vs 15.4 +/- 7.1 days). UACR reduction correlated with pre-treatment UACR values (correlation coefficient [R] = 0.88, p < 0.01) but not with BP decrease.
Conclusions: The present study demonstrated that cilnidipine reduced UACR in hypertensive patients with normal to marginally elevated UACR independent of its BP-lowering effect.

DOI： 10.2165/11538510-000000000-00000

Cardio-Ankle Vascular Index is Independently Associated with the Severity of Coronary Atherosclerosis and Left Ventricular Function in Patients with Ischemic Heart Disease 査読

Toru Miyoshi, Masayuki Doi, Satoshi Hirohata, Kosuke Sakane, Shigeshi Kamikawa, Tomoki Kitawaki, Youko Kaji, Kengo Fukushima Kusano, Yoshifumi Ninomiya, Shozo Kusachi

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 17 ( 3 ) 249 - 258 2010年

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

Aim: The cardio-ankle vascular index (CAVI) has been proposed as a new noninvasive marker of arterial stiffness independent of blood pressure. We investigated the association of the CAVI with coronary atherosclerosis and left ventricular (LV) systolic and diastolic function in patients with ischemic heart disease (IHD).
Methods: A total of 206 consecutive subjects undergoing coronary angiography were enrolled. CAVI measurement and echocardiography were performed simultaneously. Patients having significant coronary stenosis were classified into the IHD group.
Results: CAVI in the IHD group (n = 133) was significantly higher than in the non-IHD group (n = 73) (9.1 +/- 1.3 vs. 8.7 +/- 1.2, p = 0.02). In all IHD patients, CAVI was negatively correlated with LV ejection fraction (LVEF) (r = -0.31, p < 0.01), LV mass index (r = 0.24, p < 0.01) and angiographic scores of coronary atherosclerosis. Stepwise regression analysis revealed that CAVI was independently associated with LVEF, along with a history of myocardial infarction, LV mass index, and left atrial diameter in all IHD patients (p < 0.01). In the sub-analysis of IHD patients with preserved LVEF, CAVI was correlated with echocardiographic parameters regarding LV diastolic function. Multivariate analysis demonstrated that the increased CAVI was significantly associated with LV diastolic dysfunction in patients with preserved LVEF.
Conclusion: CAVI, a new parameter of aortic stiffness, was independently associated with LV systolic and diastolic function as well as coronary artery disease in IHD patients.

DOI： 10.5551/jat.1636

A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression by chondrocytes during endochondral ossification

Kanae Kumagishi, Keiichiro Nishida, Tomoichiro Yamaai, Ryusuke Momota, Shigeru Miyaki, Satoshi Hirohata, Ichiro Naito, Hiroshi Asahara, Yoshifumi Ninomiya, Aiji Ohtsuka

ARCHIVES OF HISTOLOGY AND CYTOLOGY 72 ( 3 ) 175 - 185 2009年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：INT SOC HISTOLOGY & CYTOLOGY

A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) is known to influence aggrecan degradation in endochondral ossification, but its role has not been well understood. In the present study, in vitro gene expression of ADAMTS9 was investigated by RT-PCR in ATDC5 cells in which experimentally chondrogenic differentiation had been induced. We also investigated the protein localization and gene expression pattern of ADAMTS9 in the tibia growth plate cartilage of male mice in a day 1 neonate, 7-week-old young adult, and a 12-week-old adult by immunohistochemistry and in situ hybridization and compared the results with the expression of proliferating cell nuclear antigen (PCNA) and type X collagen for the identification of proliferative and hypertrophic chondrocyte phenotypes, respectively. We found the gene expression of ADAMTS9 by ATDC5 cells as a dual mode, both before the expression of type X collagen and after hypertrophic differentiation. The immunoreactivity of ADAMTS9 was observed in chondrocytes of proliferative and hypertrophic zones in the growth plate. The population of ADAMTS9 positive cells decreased with age. The results of the present study suggest that ADAMTS9 might have a role in aggrecan cleavage around the chondrocytes to allow chondrocyte proliferation and hypertrophy.

DOI： 10.1679/aohc.72.175

Association of Increased Plasma Adipocyte Fatty Acid-binding Protein With Coronary Artery Disease in Men

Shunichi Higashiya, Masayuki Doi, Kunio Nogami, Mutsumi Iwamoto, Akihisa Yumoto, Kou Takeda, Masayuki Ueeda, Toru Miyoshi, Satoshi Hirohata, Shozo Kusachi, Yoshifumi Ninomiya, Hiroshi Ito

CIRCULATION 120 ( 18 ) S397 - S398 2009年11月

A Novel Cationic Protein Reduced Infracted Size and Protected Myocytes From Oxidative Stress Through Modification of Akt Signaling

Shigeshi Kamikawa, Satoshi Hirohata, Syougo Watanabe, Takashi Ohtsuki, Toru Miyoshi, Hiroko Ogawa, Shozo Kusachi, Masaharu Senoo, Yoshifumi Ninomiya, Hiroshi Itoh

CIRCULATION 120 ( 18 ) S888 - S889 2009年11月

ADAMTS-1 is an Endothelial Cell-specific Hypoxia-inducible Gene

Satoshi Hirohata, Faruk O. Hatipoglu, Toru Miyoshi, Hiroko Ogawa, Masanari Obika, Shigeshi Kamikawa, Shozo Kusachi, Hiroshi Itoh, Yoshifumi Ninomiya

CIRCULATION 120 ( 18 ) S1172 - S1172 2009年11月

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