研究者総覧

今井 靖 (イマイ ヤスシ)

  • 薬理学講座(臨床薬理学部門) 教授
Last Updated :2021/09/22

研究者情報

学位

  • 医学博士(東京大学)

ホームページURL

J-Global ID

研究キーワード

  • 遺伝子変異   カテーテルアブレーション   植え込み型電子デバイス   臨床薬理学   成人先天性心疾患   マルファン症候群   大動脈解離   

経歴

  • 2017年 - 現在  自治医科大学臨床薬理学部門・循環器内科学部門教授
  • 2013年11月 - 2017年03月  自治医科大学循環器内科学部門准教授
  • 2012年03月 - 2013年10月  東京大学医学部附属病院循環器内科特任講師

学歴

  • 1997年04月 - 2001年03月   東京大学大学院   医学系研究科医学博士課程   循環器内科学専攻
  • 1988年04月 - 1994年03月   東京大学   医学部   医学科

研究活動情報

論文

  • Takashige Tobita, Seitaro Nomura, Takanori Fujita, Hiroyuki Morita, Yoshihiro Asano, Kenji Onoue, Masamichi Ito, Yasushi Imai, Atsushi Suzuki, Toshiyuki Ko, Masahiro Satoh, Kanna Fujita, Atsuhiko T Naito, Yoshiyuki Furutani, Haruhiro Toko, Mutsuo Harada, Eisuke Amiya, Masaru Hatano, Eiki Takimoto, Tsuyoshi Shiga, Toshio Nakanishi, Yasushi Sakata, Minoru Ono, Yoshihiko Saito, Seiji Takashima, Nobuhisa Hagiwara, Hiroyuki Aburatani, Issei Komuro
    Scientific reports 8 1 1998 - 1998 2018年01月 [査読有り][通常論文]
     
    Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are genetically and phenotypically heterogeneous. Cardiac function is improved after treatment in some cardiomyopathy patients, but little is known about genetic predictors of long-term outcomes and myocardial recovery following medical treatment. To elucidate the genetic basis of cardiomyopathy in Japan and the genotypes involved in prognosis and left ventricular reverse remodeling (LVRR), we performed targeted sequencing on 120 DCM (70 sporadic and 50 familial) and 52 HCM (15 sporadic and 37 familial) patients and integrated their genotypes with clinical phenotypes. Among the 120 DCM patients, 20 (16.7%) had TTN truncating variants and 13 (10.8%) had LMNA variants. TTN truncating variants were the major cause of sporadic DCM (21.4% of sporadic cases) as with Caucasians, whereas LMNA variants, which include a novel recurrent LMNA E115M variant, were the most frequent in familial DCM (24.0% of familial cases) unlike Caucasians. Of the 52 HCM patients, MYH7 and MYBPC3 variants were the most common (12 (23.1%) had MYH7 variants and 11 (21.2%) had MYBPC3 variants) as with Caucasians. DCM patients harboring TTN truncating variants had better prognosis than those with LMNA variants. Most patients with TTN truncating variants achieved LVRR, unlike most patients with LMNA variants.
  • Tomoyuki Kabutoya, Yasushi Imai, Satoshi Hoshide, Kazuomi Kario
    JOURNAL OF CLINICAL HYPERTENSION 19 11 1143 - 1147 2017年11月 [査読有り][通常論文]
     
    The authors evaluated a new algorithm for detecting atrial fibrillation (AF) using a home blood pressure monitor. Three serial blood pressure values were measured by the monitor in 16 patients with AF and 20 patients with sinus rhythm. The authors defined monitor AF in irregular pulse peak (IPP) 25 as follows: (1) IPP: |interval of pulse peak-the average of the interval of the pulse peak| the average of the interval of the pulse peak x25%; (2) irregular heart beat: beats of IPP total pulse x20%; and (3) monitor AF: two or more irregular heart beats of the three blood pressure measurements. Cutoff IPP values were set at 20% (IPP20) and 15% (IPP15). The monitor's AF specificity was 1.0 in IPP25, IPP20, and IPP15, and its sensitivity was 0.88 in IPP25, 0.94 in IPP20, and 1.0 in IPP15. The new algorithm had high diagnostic accuracy for detecting AF and a low false-positive rate.
  • Yasushi Imai
    International Heart Journal 58 1 5  2017年 [査読有り][通常論文]
  • Kana Kubota, Taro Shinozaki, Yasushi Imai, Kazuomi Kario
    BMJ Case Reports 2017 2017年 [査読有り][通常論文]
     
    Pulmonary tumour thrombotic microangiopathy (PTTM) is a rare complication of cancer, which can be lethal due to progressive pulmonary hypertension (PH). Several case reports have demonstrated that imatinib, a platelet-derived growth factor receptor-tyrosine kinase inhibitor, can improve severe PH in patients with PTTM. We describe the case of a 56-year-old woman. Her mean pulmonary arterial pressure (mPAP) was 47 mm Hg, and her dyspnoea worsened rapidly over several days. Although pulmonary embolism was not observed on CT, enlargement of the para-aortic lymph nodes was detected. Gastro-oesophageal endoscopy revealed signet-ring cell carcinoma. We diagnosed her as having PTTM based on her clinical course, and started treatment with imatinib. Five days after its administration, her mPAP decreased dramatically. She was discharged and lived without symptoms of PH until her death due to systemic metastasis of carcinoma. In some cases of PTTM, imatinib may be an effective therapeutic option for PH.
  • Yusuke Oba, Satoshi Hoshide, Tadayuki Mitama, Hajime Shinohara, Takahiro Komori, Tomoyuki Kabutoya, Yasushi Imai, Nobuhiko Ogata, Kazuomi Kario
    International Heart Journal 58 6 988 - 992 2017年 [査読有り][通常論文]
     
    A 62-year-old Japanese man presented with chest pain indicating that acute myocardial infarction had occurred. Eleven years earlier, he underwent a splenectomy due to idiopathic portal hypertension. Coronary angiography revealed diffuse stenosis, with calcification in the left anterior descending coronary artery (LAD). We performed a primary percutaneous coronary intervention (PCI). We deployed two drug-eluting stents with sufficient minimal cross-sectional stent area by intravascular ultrasound and thrombolysis in myocardial infarction (TIMI) 3 flow. The initial laboratory examination revealed chronic disseminated intravascular coagulation (DIC). On the 8th hospital day, he developed chest pain indicating early coronary stent thrombosis, although he had been prescribed dual antiplatelet therapy. We performed an emergent second PCI, and the TIMI flow grade improved from 0 to 3. Clopidogrel was replaced with prasugrel. On the 18th hospital day, we detected a repeated coronary stent thrombosis again. We performed a third PCI and the TIMI flow grade improved from 0 to 3. After anticoagulation therapy with warfarin, the DIC was improved and his condition ran a benign course without the recurrence of stent thrombosis for 1 month. Contrast-enhanced CT showed portal vein thrombosis. This patient’s case reveals the possibility that the condition of chronic DIC can lead to recurrent stent thrombosis. Stent thrombosis is infrequent, but remains a serious complication in terms of morbidity and mortality. Although stent thrombosis is multifactorial, the present case suggests that DIC is a factor in stent thrombosis. To prevent stent thrombosis after PCI under DIC, anticoagulation might be a treatment option in addition to antiplatelet therapy.
  • Jun-ichi Suzuki, Yasushi Imai, Mieko Aoki, Daishi Fujita, Norifumi Takeda, Norio Aoyama, Kouji Wakayama, Yuichi Ikeda, Hidetoshi Kumagai, Hiroshi Akazawa, Yuichi Izumi, Mitsuaki Isobe, Issei Komuro, Yasunobu Hirata
    INTERNATIONAL HEART JOURNAL 57 4 456 - 460 2016年07月 [査読有り][通常論文]
     
    Marfan syndrome (MFS) is a systemic connective tissue disorder that is caused by mutations of fibrillin-1. While MFS patients are at a high risk of periodontitis and aortic diseases, little causal information has been provided to date. To clarify the relationship, their oral condition and sinus of Valsalva (SoV) were evaluated. The subjects were patients with MFS (n = 33) who attended the University of Tokyo Hospital. We divided them into two groups; MFS patients with highly dilated (the diameters were equal to or more than 39 mm) SoV (high group, n = 18) and MFS patients with mildly dilated (less than 39 mm) SoV (mild group, n = 15). Blood examinations, echocardiograms, and full-mouth clinical measurements, including number of teeth, probing pocket depth (PPD), bleeding on probing (BOP), and community periodontal index (CPI) were performed. We found that the high group patients had greater rates of BOP compared to that of the mild group. Furthermore, the high group tended to have higher serum levels of C-reactive protein, matrix metalloproteinase-9, and transforming growth factor-beta compared to the mild group. Periodontitis may deteriorate SoV dilatation in MFS patients.
  • Tomoyuki Kabutoya, Yasushi Imai, Hiroaki Watanabe, Tomonori Watanabe, Takahiro Komori, Kazuomi Kario
    International Heart Journal 57 1 118 - 120 2016年01月 [査読有り][通常論文]
     
    48-year-old woman underwent cardiac resynchronization therapy defibrillator implantation. Coronary sinus (CS) venography showed only one adequate anterior branch for a left ventricular lead. We were able to introduce a quadripolar left ventricular lead (Medtronic 4398-88 cm) to the distal portion of the anterior branch. Although phrenic nerve stimulation (PNS) occurred due to distal bipolar pacing (distal 1–mid 2, with 21-mm distance) and proximal pacing (mid 3–proximal 4, distance 21mm), short-spaced bipolar pacing (mid 2-3, distance 1.3 mm) did not induce PNS until 9V pacing. Shared bipolar pacing from each left ventricular electrode (distal 1 to proximal 4) as cathode and a right ventricular (RV) coil as anode resulted in PNS by 3.0V at 0.4 ms. Although quadripolar pacing could avoid PNS by switching the pacing site (ie, from distal bipolar to proximal bipolar), it might not avoid PNS in cases where the phrenic nerve and CS branch are parallel and in close proximity. We found that even though the phrenic nerve and CS branch were parallel and close, short-spaced bipolar pacing could avoid PNS. In conclusion, short-spaced bipolar pacing selected by quadripolar pacing might be beneficial to avoid PNS when the implantable branch is limited.
  • Daishi Fujita, Norifumi Takeda, Hiroyuki Morita, Masayoshi Kato, Hiroshi Nishimura, Ryo Inuzuka, Yuki Taniguchi, Kan Nawata, Hironobu Hyodo, Yasushi Imai, Yasunobu Hirata, Issei Komuro
    INTERNATIONAL JOURNAL OF CARDIOLOGY 201 288 - 290 2015年12月 [査読有り][通常論文]
  • Yusuke Oba, Hiroaki Watanabe, Yoshioki Nishimura, Shuichi Ueno, Takao Nagashima, Yasushi Imai, Masahisa Shimpo, Kazuomi Kario
    INTERNATIONAL HEART JOURNAL 56 6 664 - 667 2015年11月 [査読有り][通常論文]
     
    A 45-year-old hypertensive Japanese woman presented with epigastric pain on inspiration, fever, complete atrioventricular block and polyarthritis. Her antistreptolysin 0 levels were markedly elevated. A diagnosis of rheumatic fever was made according to the modified Jones criteria. She was prescribed loxoprofen sodium, which was partially effective for her extracardiac clinical symptoms. However, she had syncope due to complete atrioventricular block with asystole longer than 10 seconds. Consequently, we implanted a permanent pacemaker. Although we prescribed prednisolone, the efficacy of which was limited for the patient's conduction disturbance, the complete atrioventricular block persisted. In our systematic review of 12 similar cases, the duration of complete heart block was always transient and there was no case requiring a permanent pacemaker. We thus encountered a very rare case of adult-onset acute rheumatic fever with persistent complete atioventricular block necessitating permanent pacemaker implantation.
  • Norifumi Takeda, Hiroyuki Morita, Daishi Fujita, Ryo Inuzuka, Yuki Taniguchi, Yasushi Imai, Yasunobu Hirata, Issei Komuro
    AMERICAN JOURNAL OF MEDICAL GENETICS PART A 167 10 2382 - 2387 2015年10月 [査読有り][通常論文]
     
    Congenital contractural arachnodactyly (CCA) is a connective tissue disease caused by mutations of the FBN2, which encodes fibrillin-2. CCA patients have a marfanoid habitus; however, aortic dilatation and/or dissection as observed in Marfan syndrome have been rarely documented. Here, we report on a Japanese familial case of CCA resulting from a FBN2 splicing mutation (IVS32+5ga), which leads to exon 32 being skipped, and the patients developed aortic dilatation and type A dissection. Although CCA patients have been believed to have favorable prognoses, repetitive aortic imaging studies must be performed in some patients to detect possible aortic disease early, and genetic testing of FBN2 might be useful to identify such high-risk patients. (c) 2015 Wiley Periodicals, Inc.
  • Jun-ichi Suzuki, Yasushi Imai, Mieko Aoki, Daishi Fujita, Norio Aoyama, Yuko Tada, Hiroshi Akazawa, Yuichi Izumi, Mitsuaki Isobe, Issei Komuro, Ryozo Nagai, Yasunobu Hirata
    HEART AND VESSELS 30 5 692 - 695 2015年09月 [査読有り][通常論文]
     
    Marfan syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the extracellular matrix protein fibrillin-1. While it is known that patients with MFS are at high risk of dental disorders and cardiovascular diseases, little information has been provided to date. To clarify the prevalence of periodontitis in patients with MFS, their oral condition and cardiovascular complications were evaluated. The subjects were patients with MFS (n = 40) who attended the University of Tokyo hospital; age- and gender-matched healthy individuals (n = 14) constituted a control group. Cardiovascular complications and full-mouth clinical measurements, including number of teeth, probing of pocket depth (PD), bleeding on probing (BOP), and community periodontal index (CPI) were recorded. MFS patients had more frequent cardiovascular complications (95 %) compared with the controls (0 %). MFS patients had periodontitis (CPI 3 and 4) more frequently (87.5 %) than the age- and gender-matched control subjects (35.7 %). Furthermore, MFS patients had significantly more severe periodontitis (CPI 2.90 +/- 0.12 vs 1.64 +/- 0.32) and fewer remaining teeth (26.7 +/- 0.4 vs 28.4 +/- 0.4) compared with the controls. However, PD and BOP were comparable between MFS patients and the control group. A high incidence of periodontitis and cardiovascular complications was observed in Japanese MFS patients.
  • Yasushi Imai, Hiroyuki Morita, Norifumi Takeda, Fuyuki Miya, Hironobu Hyodo, Daishi Fujita, Tomoyuki Tajima, Tatsuhiko Tsunoda, Ryozo Nagai, Michiaki Kubo, Issei Komuro
    INTERNATIONAL JOURNAL OF CARDIOLOGY 195 290 - 292 2015年09月 [査読有り][通常論文]
  • Megumi Hirokawa, Hiroyuki Morita, Tomoyuki Tajima, Atsushi Takahashi, Kyota Ashikawa, Fuyuki Miya, Daichi Shigemizu, Kouichi Ozaki, Yasuhiko Sakata, Daisaku Nakatani, Shinichiro Suna, Yasushi Imai, Toshihiro Tanaka, Tatsuhiko Tsunoda, Koichi Matsuda, Takashi Kadowaki, Yusuke Nakamura, Ryozo Nagai, Issei Komuro, Michiaki Kubo
    EUROPEAN JOURNAL OF HUMAN GENETICS 23 3 374 - 380 2015年03月 [査読有り][通常論文]
     
    Despite considerable progress in preventive and therapeutic strategies, myocardial infarction (MI) is one of the leading causes of death throughout the world. A total of 55 susceptibility genes have been identified mostly in European genome-wide association studies (GWAS). Nevertheless, large-scale GWAS from other population could possibly find additional susceptibility loci. To identify as many MI susceptibility loci as possible, we performed a large-scale genomic analysis in Japanese population. To identify MI susceptibility loci in Japanese, we conducted a GWAS using 1666 cases and 3198 controls using the Illumina Human610-Quad BeadChip and HumanHap550v3 Genotyping BeadChip. We performed replication studies using a total of 11 412 cases and 28 397 controls in the Japanese population. Our study identified two novel susceptibility loci for MI: PLCL2 on chromosome 3p24.3 (rs4618210: A>G, P = 2.60 x 10(-9), odds ratio (OR) =0.91) and AP3D1-DOT1L-SF3A2 on chromosome 19p13.3 (rs3803915: A>C, P = 3.84 x 10(-9), OR = 0.89). Besides, a total of 14 previously reported MI susceptibility loci were replicated in our study. In particular, we validated a strong association on chromosome 12q24 (rs3782886: A>G: P = 1.14 x 10(-14), OR = 1.46). Following pathway analysis using 265 genes related to MI or coronary artery disease, we found that these loci might be involved in the pathogenesis of MI via the promotion of atherosclerosis. In the present large-scale genomic analysis, we identified PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for MI in the Japanese population. Our findings will add novel findings for MI susceptibility loci.
  • Aiko Sakamoto, Nobukazu Ishizaka, Yasushi Imai, Masae Uehara, Jiro Ando, Ryozo Nagai, Issei Komuro
    JOURNAL OF CARDIOLOGY 65 1-2 150 - 156 2015年01月 [査読有り][通常論文]
     
    Background: Immunoglobulin G4 (IgG4)-related disease has been suggested to be involved in cardiovascular disorders such as chronic periaortitis. However, it remains unclear whether IgG4-related immuno-inflammation affects the subclinical stages of aortic remodeling. Here, we analyzed the relationship between serum IgG4 concentrations and the morphology of the ascending aorta. Methods: Serum concentrations of IgG4 were measured in 322 patients who underwent 320-slice cardiac computed tomography (CT). We assessed the aortic wall area and intravascular area at the portion between the. aortic valve and the bifurcation of the pulmonary artery. Results: In total, 174 patients (54.0%) were diagnosed to have coronary artery disease (CAD) by cardiac CT. The intravascular area was significantly larger in patients with CAD than in those without (893 mm(2) vs. 811 mm(2), p = 0.001). The aortic wall area was slightly, but not significantly, larger in patients with CAD than in those without (183 mm(2) vs. 176 mm(2), p = 0.051). Serum concentrations of IgG4 were significantly higher in patients with an aortic wall area of median or greater size (>= 181 mm(2)) than in those with a smaller area (<181 mm(2)) (32.9 mg/dL vs. 23.1 mg/dL, p = 0.026). In logistic regression analysis using age, gender, and CAD as covariates, the fourth quartile of IgG4 (>= 55.4 mg/dL) was significantly associated with an aortic wall area of median or greater size with an odds ratio of 2.09. Conclusions: Serum concentrations of IgG4 were found to be significantly associated with the aortic wall area. These findings collectively suggest that immuno-inflammatory processes may play a role in the subclinical stages of aortic remodeling. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
  • Aiko Sakamoto, Yasutomi Higashikuni, Makiko Hongo, Yasushi Imai, Kazuhiko Koike, Ryozo Nagai, Issei Komuro, Nobukazu Ishizaka
    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 22 12 1225 - 1234 2015年 [査読有り][通常論文]
     
    Aim: In an insulin-resistant state, excess lipids may accumulate in various non-adipose tissues, leading to histological and functional damage. It has been suggested that peroxisome proliferator-activated receptor-gamma (PPAR gamma) may ameliorate disorganized lipid balance. In the current study, we analyzed whether pioglitazone, an agonist of PPAR gamma, reduces angiotensin II-induced vascular lipid accumulation. Methods: Angiotensin II was infused into rats at doses of 0.7 mg/kg/day via a subcutaneously implanted osmotic minipump for 7 consecutive days. Pioglitazone was orally given at a dose of 2.5 mg/kg/day for 7 days. Results: Pioglitazone significantly reduced angiotensin II-induced enhanced lipid deposition and superoxide production in the adventitia of the aorta, as detected by oil red O and dihydroethidium (DHE) staining, respectively. Increased DHE signals, some observed at the site of lipid deposition, were mainly localized in ED-1-positive monocytes/macrophages. Angiotensin II-induced upregulation of the expression of LDL receptor and Nox1 was inhibited by pioglitazone treatment. In addition, angiotensin II significantly reduced the expression of PCSK9, and this reduction was ameliorated by pioglitazone. On the other hand, pioglitazone did not significantly alter the expression of the phosphorylated forms of AMPK alpha and ACC, which was downregulated by angiotensin II. Conclusions: Pioglitazone treatment suppressed excess lipid accumulation and superoxide production in the aorta in an angiotensin II-induced rat model of hypertension.
  • Daishi Fujita, Norifumi Takeda, Yasushi Imai, Ryo Inuzuka, Issei Komuro, Yasunobu Hirata
    PEDIATRICS INTERNATIONAL 56 4 484 - 491 2014年08月 [査読有り][通常論文]
     
    Marfan syndrome is an autosomal dominant heritable disorder of the connective tissue, caused by mutations of the gene FBN1, which encodes fibrillin-1, a major component of the microfibrils of the extracellular matrix. Fibrillin-1 interacts with transforming growth factor- (TGF-), and dysregulated TGF- signaling plays a major role in the development of connective tissue disease and familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an angiotensin II blocker, has the potential to reduce TGF- signaling and is expected to be an additional therapeutic option. Clinical diagnosis is made using the Ghent nosology, which requires comprehensive patient assessment and has been proven to work well, but evaluation of some of the diagnostic criteria by a single physician is difficult and time-consuming. A Marfan clinic was established at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In this review, we discuss the recent progress in diagnosis and treatment of Marfan syndrome, and the characteristics of Japanese patients with Marfan syndrome.
  • Munenori Takata, Eisuke Amiya, Masafumi Watanabe, Kazuko Omori, Yasushi Imai, Daishi Fujita, Hiroshi Nishimura, Masayoshi Kato, Tetsuro Morota, Kan Nawata, Atsuko Ozeki, Aya Watanabe, Shuichi Kawarasaki, Yumiko Hosoya, Tomoko Nakao, Koji Maemura, Ryozo Nagai, Yasunobu Hirata, Issei Komuro
    HEART AND VESSELS 29 4 478 - 485 2014年07月 [査読有り][通常論文]
     
    Marfan syndrome is an inherited disorder characterized by genetic abnormality of microfibrillar connective tissue proteins. Endothelial dysfunction is thought to cause aortic dilation in subjects with a bicuspid aortic valve; however, the role of endothelial dysfunction and endothelial damaging factors has not been elucidated in Marfan syndrome. Flow-mediated dilation, a noninvasive measurement of endothelial function, was evaluated in 39 patients with Marfan syndrome. Aortic diameter was measured at the aortic annulus, aortic root at the sinus of Valsalva, sinotubular junction and ascending aorta by echocardiography, and adjusted for body surface area (BSA). The mean value of flow-mediated dilation was 6.5 +/- A 2.4 %. Flow-mediated dilation had a negative correlation with the diameter of the ascending thoracic aorta (AscAd)/BSA (R = -0.39, p = 0.020) and multivariate analysis revealed that flow-mediated dilation was an independent factor predicting AscAd/BSA, whereas other segments of the aorta had no association. Furthermore, Brinkman index had a somewhat greater influence on flow-mediated dilation (R = -0.42, p = 0.008). Although subjects who smoked tended to have a larger AscAd compared with non-smokers (AscA/BSA: 17.3 +/- A 1.8 versus 15.2 +/- A 3.0 mm/m(2), p = 0.013), there was no significant change in flow-mediated dilation, suggesting that smoking might affect aortic dilation via an independent pathway. Common atherogenic risks, such as impairment of flow-mediated dilation and smoking status, affected aortic dilation in subjects with Marfan syndrome.
  • Koichiro Kinugawa, Ryozo Nagai, Hiroshi Inoue, Hirotsugu Atarashi, Yoshihiko Seino, Takeshi Yamashita, Wataru Shimizu, Takeshi Aiba, Masafumi Kitakaze, Atsuhiro Sakamoto, Takanori Ikeda, Yasushi Imai, Takashi Daimon, Katsuhiro Fujino, Tetsuji Nagano, Tatsuaki Okamura, Masatsugu Hori
    Advances in therapy 31 4 426 - 39 2014年04月 [査読有り][通常論文]
     
    INTRODUCTION: Results from the multicenter trial (J-Land study) of landiolol versus digoxin in atrial fibrillation (AF) and atrial flutter (AFL) patients with left ventricular (LV) dysfunction revealed that landiolol was more effective for controlling rapid HR than digoxin. The subgroup analysis for patient characteristics was conducted to evaluate the impact on the efficacy and safety of landiolol compared with digoxin. METHODS: Two hundred patients with AF/AFL, heart rate (HR) ≥ 120 beats/min, and LV ejection fraction (LVEF) 25-50% were randomized to receive either landiolol (n = 93) or digoxin (n = 107). Successful HR control was defined as ≥20% reduction in HR together with HR < 110 beats/min at 2 h after starting intravenous administration of landiolol or digoxin. The subgroup analysis for patient characteristics was to evaluate the impact on the effectiveness of landiolol in AF/AFL patients complicated with LV dysfunction. RESULTS: The efficacy in patients with NYHA class III/NYHA class IV was 52.3%/35.3% in landiolol, and 13.8%/9.1% in digoxin (p < 0.001 and p = 0.172), lower LVEF (25-35%)/higher LVEF (35-50%) was 45.7%/51.1% in landiolol, and 14.0%/12.7% in digoxin (p < 0.001 and p < 0.001), CKD stage 1 (90 < eGFR)/CKD stage 2 (60 ≤ eGFR < 90)/CKD stage 3 (30 ≤ eGFR < 60)/CKD stage 4 (15 ≤ eGFR < 30) was 66.7%/59.1%/39.6%/66.7% in landiolol, and 0%/13.8%/17.0%/0% in digoxin (p = 0.003, p < 0.001, p = 0.015 and p = 0.040). CONCLUSIONS: This subgroup analysis indicated that landiolol was more useful, regardless of patient characteristics, as compared with digoxin in AF/AFL patients complicated with LV dysfunction. Particularly, in patients with impaired renal function, landiolol should be preferred for the purpose of acute rate control of AF/AFL tachycardia.
  • Jun-ichi Suzuki, Yasushi Imai, Mieko Aoki, Daishi Fujita, Norio Aoyama, Yuko Tada, Kouji Wakayama, Hiroshi Akazawa, Yuichi Izumi, Mitsuaki Isobe, Issei Komuro, Ryozo Nagai, Yasunobu Hirata
    PLOS ONE 9 4 e95521  2014年04月 [査読有り][通常論文]
     
    Background: Although periodontitis is a risk factor for cardiovascular disease (CVD), the influence of periodontitis on Marfan syndrome (MFS) with CVD is unclear. The aim of this study was to assess the relationship between periodontal bacterial burden and MSF with CVD. Methods and Results: The subjects were patients with MFS with CVD (n = 47); age and gender matched non-MFS CVD patients (n = 48) were employed as controls. Full-mouth clinical measurements, including number of teeth, probing of pocket depth (PD), bleeding on probing (BOP) and community periodontal index (CPI) were recorded. We also evaluated the existence of three periodontal pathogens, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia using polymerase chain reaction assays. Serum antibody titers against the pathogens were also measured. We revealed that MFS with CVD patients had periodontitis more frequently than the age and gender matched non-MFS CVD control subjects. MFS with CVD patients had significantly severer periodontitis, fewer remaining teeth and deeper PD compared to the non-MFS CVD controls. Furthermore, the serum antibody titer level against Prevotella intermedia was significantly lower in MFS plus CVD patients compared to the non-MFS CVD patients. Conclusion: Periodontitis may influence the pathophysiology of cardiovascular complications in MFS patients. A specific periodontal pathogen might be a crucial therapeutic target to prevent CVD development.
  • Toshiya Kojima, Yasushi Imai, Kensuke Tsushima, Kansei Uno, Katsuhito Fujiu, Taroh Iiri, Hiroaki Nishimatsu, Takeki Suzuki, Hiroaki Sugiyama, Kazuo Asada, Tomoko Nakao, Hiroshi Yamashita, Yasunobu Hirata, Ryozo Nagai
    JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA 28 1 124 - 127 2014年02月 [査読有り][通常論文]
  • Toshiya Kojima, Yasushi Imai, Issei Komuro
    EUROPACE 16 1 39 - 39 2014年01月 [査読有り][通常論文]
  • Aiko Sakamoto, Nobukazu Ishizaka, Yasushi Imai, Jiro Ando, Ryozo Nagai, Issei Komuro
    CLINICA CHIMICA ACTA 428 63 - 69 2014年01月 [査読有り][通常論文]
     
    Objectives: Immunoglobulin G4 (IgG4)-related immuno-inflammation may play a role in the development of coronary artery disease (CAD). We analyzed the association of serum IgG4 and soluble interleukin-2 receptor (sIL-2R) levels with epicardial fat volume (EFV) and coronary artery calcification (CAC). Methods: Serum IgG4 and sIL-2R levels were measured in 267 patients who underwent 320-slice cardiac computed tomography. Results: The median serum levels of IgG4 and sIL-2R were higher in patients with CAD than in those without. Serum IgG4 levels were significantly greater in patients with EFV within the second and fourth quartile (75 mL) than in those with low EFV (<75 mL) (33.5 mg/dL vs. 22.5 mg/dL). On the other hand, serum sIL-2R levels were significantly higher in patients with CAC than in those without (409 U/mL vs. 345 U/mL). In age- and gender-adjusted logistic regression analysis, the fourth quartile of IgG4 (>= 56.7 mg/dL) was associated with EFV within the second and fourth quartile (>= 75 mL) with an odds ratio of 3.13. Conclusion: Serum IgG4 levels were greater in patients with EFV within the second and fourth quartile, whereas serum sIL-2R levels were increased in patients with CAC. These two biomarkers may reflect different mechanisms underlying development of cardiovascular remodeling. (C) 2013 Elsevier B.V. All rights reserved.
  • Aiko Sakamoto, Nobukazu Ishizaka, Yasushi Imai, Jiro Ando, Ryozo Nagai, Issei Komuro
    CLINICA CHIMICA ACTA 428 63 - 69 2014年01月 [査読有り][通常論文]
     
    Objectives: Immunoglobulin G4 (IgG4)-related immuno-inflammation may play a role in the development of coronary artery disease (CAD). We analyzed the association of serum IgG4 and soluble interleukin-2 receptor (sIL-2R) levels with epicardial fat volume (EFV) and coronary artery calcification (CAC). Methods: Serum IgG4 and sIL-2R levels were measured in 267 patients who underwent 320-slice cardiac computed tomography. Results: The median serum levels of IgG4 and sIL-2R were higher in patients with CAD than in those without. Serum IgG4 levels were significantly greater in patients with EFV within the second and fourth quartile (75 mL) than in those with low EFV (<75 mL) (33.5 mg/dL vs. 22.5 mg/dL). On the other hand, serum sIL-2R levels were significantly higher in patients with CAC than in those without (409 U/mL vs. 345 U/mL). In age- and gender-adjusted logistic regression analysis, the fourth quartile of IgG4 (>= 56.7 mg/dL) was associated with EFV within the second and fourth quartile (>= 75 mL) with an odds ratio of 3.13. Conclusion: Serum IgG4 levels were greater in patients with EFV within the second and fourth quartile, whereas serum sIL-2R levels were increased in patients with CAC. These two biomarkers may reflect different mechanisms underlying development of cardiovascular remodeling. (C) 2013 Elsevier B.V. All rights reserved.
  • Toshiya Kojima, Yasushi Imai, Katsuhito Fujiu, Kazuo Asada, Jiro Ando, Masafumi Watanabe, Hiroshi Yamashita, Issei Komuro
    INTERNATIONAL JOURNAL OF CARDIOLOGY 168 1 E24 - E26 2013年09月 [査読有り][通常論文]
  • Tetsuya Saito, Norihiko Takeda, Eisuke Amiya, Tomoko Nakao, Hajime Abe, Hiroaki Semba, Katsura Soma, Katsuhiro Koyama, Yumiko Hosoya, Yasushi Imai, Takayuki Isagawa, Masafumi Watanabe, Ichiro Manabe, Issei Komuro, Ryozo Nagai, Koji Maemura
    FEBS LETTERS 587 14 2179 - 2185 2013年07月 [査読有り][通常論文]
     
    Vascular endothelial growth factor-A (VEGF-A) is one of the major angiogenic factors, and its actions are primarily mediated through its two membrane receptors, VEGFR-1 and VEGFR-2. A soluble form of VEGFR-1 (sVEGFR-1) sequesters the free form of VEGF-A, and acts as a potent anti-angiogenic factor. While sVEGFR-1 is synthesized as a splice variant of VEGF-R1 gene, the interactions between VEGF-A and sVEGFR-1 remain largely unknown. Here, we show that VEGF-A upregulates sVEGF-R1 expression in human vascular endothelial cells but leaves full-length VEGF-R1 expression unchanged, and that this induction was dependent on the VEGFR-2-protein kinase C-MEK signaling pathway. The VEGF-A-induced sVEGFR-1 upregulation can operate as a negative feedback system, which if modulated can become a novel therapeutic target for regulating pathological angiogenesis. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
  • Eisuke Amiya, Masafumi Watanabe, Norihiko Takeda, Tetsuya Saito, Taro Shiga, Yumiko Hosoya, Tomoko Nakao, Yasushi Imai, Ichiro Manabe, Ryozo Nagai, Issei Komuro, Koji Maemura
    JOURNAL OF BIOLOGICAL CHEMISTRY 288 20 14497 - 14509 2013年05月 [査読有り][通常論文]
     
    Vascular endothelial function is impaired in hypercholesterolemia partly because of injury by modified LDL. In addition to modified LDL, free cholesterol (FC) is thought to play an important role in the development of endothelial dysfunction, although the precise mechanisms remain to be elucidated. The aim of this study was to clarify the mechanisms of endothelial dysfunction induced by an FC-rich environment. Loading cultured human aortic endothelial cells with FC induced the formation of vesicular structures composed of FC-rich membranes. Raft proteins such as phospho-caveolin-1 (Tyr-14) and small GTPase Rac were accumulated toward FC-rich membranes around vesicular structures. In the presence of these vesicles, angiotensin II-induced production of reactive oxygen species (ROS) was considerably enhanced. This ROS shifted endothelial NOS(eNOS) toward vesicle membranes and vesicles with a FC-rich domain trafficked toward perinuclear late endosomes/lysosomes, which resulted in the deterioration of eNOS Ser-1177 phosphorylation and NO production. Angiotensin II-induced ROS decreased the bioavailability of eNOS under the FC-enriched condition.
  • Junko Hiroyoshi, Aya Saito, Nirmal Panthee, Yasushi Imai, Dai Kawashima, Noboru Motomura, Minoru Ono
    Annals of Thoracic Surgery 95 3 1076 - 1079 2013年03月 [査読有り][通常論文]
     
    We report a case of aortic stenosis associated with ochronosis in a 70-year-old man who underwent biologic aortic valve replacement. Intraoperative findings included ochronosis of a severely calcified pigmented aortic valve along with pigmentation of the intima of the aorta. © 2013 The Society of Thoracic Surgeons.
  • Jun-Ichi Okada, Teruyoshi Sasaki, Takumi Washio, Hiroshi Yamashita, Taro Kariya, Yasushi Imai, Machiko Nakagawa, Yoshimasa Kadooka, Ryozo Nagai, Toshiaki Hisada, Seiryo Sugiura
    PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY 36 3 309 - 321 2013年03月 [査読有り][通常論文]
     
    Background Recent studies, supported by advances in computer science, have successfully simulated the excitation and repolarization processes of the heart, based on detailed cell models of electrophysiology and implemented with realistic morphology. Methods In this study, we extend these approaches to simulate the body surface electrocardiogram (ECG) of specific individuals. Patient-specific finite element models of the heart and torso are created for four patients with various heart diseases, based on clinical data including computer tomography, while the parallel multi-grid method is used to solve the dynamic bi-domain problem. Personalization procedures include demarcation of nonexcitable tissue, allocation of the failing myocyte model of electrophysiology, and modification of the excitation sequence. In particular, the adjustment of QRS morphology requires iterative computations, facilitated by the simultaneous visualization of the propagation of excitation in the heart, average QRS vector in the torso, and 12-lead ECG. Results In all four cases we obtained reasonable agreement between the simulated and actual ECGs. Furthermore, we also simulated the ECGs of three of the patients under bi-ventricular pacing, and once again successfully reproduced the actual ECG morphologies. Since no further adjustments were made to the heart models in the pacing simulations, the good agreement provides strong support for the validity of the models. Conclusions These results not only help us understand the cellular basis of the body surface ECG, but also open the possibility of heart simulation for clinical applications. (PACE 2013; 36:309-321)
  • Atsuko Nakayama, Masao Takahashi, Kazuyoshi Hina, Katsuhito Fujiu, Hiroaki Sugiyama, Toshiya Kojima, Jiro Ando, Yasushi Imai, Yasunobu Hirata, Ryozo Nagai
    INTERNATIONAL HEART JOURNAL 54 2 111 - 114 2013年03月 [査読有り][通常論文]
     
    Although hypertrophic cardiomyopathy (HCM) with an accessory pathway is encountered in clinical practice, there is little evidence of a coherent strategy for ablation of the accessory pathway in patients with HCM. We present the case of a 61-year-old man who had type B Wolff-Parkinson-White (WPW) syndrome with hypertrophic obstructive cardiomyopathy (HOCM). Due to paroxysmal atrial fibrillation, he underwent radiofrequency catheter ablation of the accessory pathway located in the right postero-lateral wall to prevent secondary symptomatic events. His LV dyssynchrony improved after the procedure, but the degree of the LV outflow tract (LVOT) pressure gradient was increased. To stabilize the LVOT pressure gradient, he needed additional medications. This case shows that patients with HOCM should be carefully evaluated before making a decision concerning ablation of the accessory pathway.
  • Ogawa N, Imai Y, Nishimura H, Kato M, Takeda N, Nawata K, Taketani T, Morota T, Takamoto S, Nagai R, Hirata Y
    International heart journal 54 1 23 - 26 2013年01月 [査読有り][通常論文]
     
    Marfan syndrome (MFS) is an inherited connective tissue disorder mainly caused by the fibrillin-1 Mutation. Deficient fibrillin-1 is thought to result in the failed sequestration of transforming growth factor beta (TGF beta) and subsequent activation of the TGF beta signaling pathway, suggesting that the circulating TGF beta level may be elevated in MFS, although its accurate measurement is complex due to ex vivo release from platelet stores upon platelet activation. We measured the plasma TGF beta 1 levels of 32 Japanese MFS patients (22 medically untreated, 10 treated, 20 males, 30.1 +/- 9.6 years old) and 30 healthy volunteers (19 males, 29.5 +/- 5.8 years old) by ruthenium-based electrochemiluminescence platform (ECL). PF4 was also measured by enzyme immunoassay (ETA) as a platelet degranulation marker. There was no significant difference in the mean plasma TGF beta 1 level between the MFS group (1.31 +/- 0.40 ng/mL) and controls (1.17 +/- 0.33 ng/mL) (P = 0.16, NS). Also, there was no significant difference between the untreated (1.24 +/- 0.37 ng/mL) and treated (1.46 +/- 0.45 ng/mL) MFS patients (P = 0.15, NS). We also measured PF4, which showed wide deviations but no significant difference between the two groups (P = 0.50). A difference in circulating TGF beta 1 levels between MFS patients and controls was not detected in this Japanese population. Circulating TGF beta 1 is not a diagnostic and therapeutic marker for Japanese MFS patients, although our findings do not eliminate the possible association of TGF beta with the pathogenesis of MFS.
  • Nagai R, Kinugawa K, Inoue H, Atarashi H, Seino Y, Yamashita T, Shimizu W, Aiba T, Kitakaze M, Sakamoto A, Ikeda T, Imai Y, Daimon T, Fujino K, Nagano T, Okamura T, Hori M, J, Investigators
    Circulation journal : official journal of the Japanese Circulation Society 77 4 908 - 16 2013年 [査読有り][通常論文]
     
    BACKGROUND: A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction. METHODS AND RESULTS: The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 25-50% were randomized to receive either landiolol (n=93) or digoxin (n=107). Successful HR control was defined as ≥20% reduction in HR together with HR <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1-10µg·kg(-1)·min(-1) according to the patient's condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively. CONCLUSIONS: Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting.
  • Kazuo Asada, Katsuhito Fujiu, Yasushi Imai, Toshiya Kojima, Hiroaki Sugiyama, Takeki Suzuki, Koichiro Kinugawa, Yasunobu Hirata, Ryozo Nagai
    CIRCULATION JOURNAL 76 11 2592 - 2598 2012年11月 [査読有り][通常論文]
     
    Background: Cardiac resynchronization therapy/defibrillators (CRTD) and implantable cardioverter defibrillators (ICD) with continuous intrathoracic impedance monitoring might provide an early warning of thoracic fluid retention. In contrast, volume loss events such as dehydration and bleeding are also common events in heart failure patients treated with diuretics and anticoagulants. The correlation between intrathoracic impedance and a volume loss event is not known. Methods and Results: This study evaluated the association between intrathoracic impedance and volume loss events in 36 patients with chronic heart failure (New York Heart Association [NYHA] II, III and IV) who had received CRTD/ICD implantation. Elevation of thoracic impedance above the reference line was defined as a positive deviation of thoracic impedance (PDI). This study recorded 249 PDIs including 60 spike PDIs defined as over 5 ohms elevation from the reference line and 17 large PDIs as over 5 ohms elevation and continuing for at least 4 days. Clinically, 96 dehydration events and 2 bleeding events were observed over a 1-year period. The sensitivity and positive predictive value (PPV) for spike PDI was 31.6% and 51.7%, respectively, while those for large PDI were 17.3% and 100%, respectively. Conclusions: A large PDI reflected dehydration and bleeding events with a high PPV in severe heart failure patients. The large PDI criteria might therefore be useful for predicting volume loss events in chronic heart failure patients. (Circ J 2012; 76: 2592-2598)
  • Guoqin Wang, Masafumi Watanabe, Yasushi Imai, Kazuo Hara, Ichiro Manabe, Koji Maemura, Momoko Horikoshi, Atsuko Ozeki, Chikako Itoh, Takao Sugiyama, Takashi Kadowaki, Tsutomu Yamazaki, Ryozo Nagai
    JOURNAL OF HUMAN GENETICS 57 11 727 - 733 2012年11月 [査読有り][通常論文]
     
    Modulator recognition factor-2 (Mrf2/AT-rich interaction domain (Arid)5b) has been revealed to be involved in pathogenesis of atherosclerosis and adipogenesis. Single-nucleotide polymorphisms (SNPs) in the MRF2/ARID5B gene are associated with coronary artery disease (CAD) and has been proposed as a candidate gene for type 2 diabetes (T2D). The study was aimed to determine whether any of the four MRF2/ARID5B SNPs (rs2893880, rs10740055, rs7087507 and rs10761600) associated with susceptibility to CAD are also associated with T2D, and to determine whether SNP genotype influences the levels of adiponectin and other clinical factors. Association of MRF2/ARID5B SNPs was investigated in 500 diabetic patients from the Department of Metabolic Diseases at the University of Tokyo and 243 hospital-based nondiabetic individuals from the Institute for Adult Disease Asahi Life Foundation Hospital and 500 community-based nondiabetic individuals from the Hiroshima Atomic Bomb Casualty Council Health Management Center. Associations of haplotypes of these SNP with levels of adiponectin and other clinical factors were evaluated when the data was available. We found rs2893880C, rs10740055A, rs7087507A and rs10761600T were increasingly associated with T2D in terms of allele/genotype frequencies of each SNP and their haplotype combinations. Individuals with haplotype CAAT indicated an 1.86 times higher prevalence of diabetes compared with individuals with GCGA (OR 1.86 (95% confidence interval (CI) 1.43-2.41)). Furthermore, CAAT significantly associated with adiponectin levels and other clinical factors. In conclusion, polymorphisms on the MRF2/ARID5B gene were associated with susceptibility to T2D as well as adiponectin and other clinical factors, which was in a completely concordant way with their associations with CAD. Journal of Human Genetics (2012) 57, 727-733; doi:10.1038/jhg.2012.101; published online 13 September 2012
  • Teruhiko Imamura, Koichiro Kinugawa, Taro Shiga, Miyoko Endo, Toshiro Inaba, Hisataka Maki, Masaru Hatano, Yasushi Imai, Atsushi Yao, Yasunobu Hirata, Takashi Nishimura, Shunei Kyo, Minoru Ono, Ryozo Nagai
    JOURNAL OF ARTIFICIAL ORGANS 15 3 301 - 304 2012年09月 [査読有り][通常論文]
     
    Refractory ventricular tachyarrhythmias are life threatening, especially in patients with stage D heart failure, and left ventricular assist device therapy is virtually the sole option to resolve the fatal conditions in many cases. The Interagency Registry for Mechanically Assisted Circulatory Support defines modifier A as complicating recurrent ventricular tachyarrhythmias. However, the optimal timing to implant a left ventricular assist device remains to be determined in less sick patients with modifier A. We experienced three patients with stage D heart failure with revised modifier A, i.e., at least two appropriate operations of implantable cardiac defibrillators within 2 weeks. Two of them were rescued by extracorporeal left ventricular assist device implantation, but one died because of an electrical storm before left ventricular assist device support was available. We would like to emphasize that we should consider implantable left ventricular assist device therapy as soon as possible for those who are assigned modifier A to prevent sudden arrhythmic death.
  • Naoko Kato, Koichiro Kinugawa, Taro Shiga, Masaru Hatano, Norihiko Takeda, Yasushi Imai, Masafumi Watanabe, Atsushi Yao, Yasunobu Hirata, Keiko Kazuma, Ryozo Nagai
    JOURNAL OF CARDIOLOGY 60 1-2 23 - 30 2012年07月 [査読有り][通常論文]
     
    Background: Little is known about depressive symptoms in heart failure with preserved ejection fraction (HFpEF, EF >= 50%). We aimed to assess the prevalence of depression, to clarify the impact of depressive symptoms upon clinical outcomes. and to identify factors associated with these symptoms in HF with reduced EF (HFrEF, EF <50%) and HFpEF. Methods and results: A total of 106 HF outpatients were enrolled. Of them, 61 (58%) had HFpEF. Most patients were male (HFrEF 80%, HFpEF 70%) and the mean of plasma B-type natriuretic peptide (BNP) level in the HFrEF group was similar to that in the HFpEF group (164.8 +/- 232.8 vs. 98.7 +/- 94.8 pg/mL). HFrEF patients were treated more frequently with beta-blockers compared with HFpEF patients (71% vs. 43%, p = 0.004). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). The prevalence of depression (CES-D score >= 16), and CES-D score did not significantly differ between HFrEF and HFpEF (24% vs. 25%, 14.1 +/- 8.3 vs. 12.1 +/- 8.3, respectively). During the 2-year follow-up, depressed patients had more cardiac death or HF hospitalization in HFrEF (55% vs. 12%, p = 0.002) and HFpEF (35% vs. 11%, p = 0.031). Cox proportional hazard analysis revealed that a higher CES-D score, indicating increased depressive symptoms, predicted cardiac events independent of BNP in HFrEF [hazard ratio (HR) 1.07, 95% confidence interval (CI) 1.01-1.131 and HFpEF (HR 1.09, 95%CI 1.04-1.15). Multiple regression analyses adjusted for BNP showed that independent predictors of depressive symptoms were non-usage of beta-blockers and being widowed or divorced in HFrEF. On the other hand, usage of warfarin was the only independent risk factor for depressive symptoms in HFpEF (all, p < 0.05). Conclusions: Depressive symptoms are common and independently predict adverse events in HFrEF/HFpEF patients. This study suggests that beta-blockers reduce depressive symptoms in HFrEF. In contrast, treatment for depression remains to be elucidated in HFpEF. (c) 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
  • Aiko Sakamoto, Nobukazu Ishizaka, Yasushi Imai, Ryozo Nagai
    ATHEROSCLEROSIS 221 2 602 - 603 2012年04月 [査読有り][通常論文]
  • Nobukazu Ishizaka, Aiko Sakamoto, Yasushi Imai, Fumio Terasaki, Ryozo Nagai
    JOURNAL OF CARDIOLOGY 59 2 132 - 138 2012年03月 [査読有り][通常論文]
     
    The cardiovascular system may be involved as a target organ of multifocal fibrosclerosis, which may manifest as idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm, inflammatory periarteritis, and inflammatory pericarditis. These pathological conditions can sometimes occur concomitantly. Idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm are both characterized by the presence of fibro-inflammatory tissue around the abdominal aorta expanding into the surrounding retroperitoneal structures, and together they may be termed 'chronic periaortitis'. Cardiovascular fibrosclerosis has become non-uncommonly encountered condition since imaging modalities have made its diagnosis more feasible. In addition, recent studies have demonstrated that a certain fraction, but not all, of cardiovascular fibrosclerosis may have a link with immunoglobulin-G4 (IgG4)-related sclerosing disease (IgG4-SD). IgG4-SD is histologically characterized by dense fibrosclerosis and infiltration of lymphocytes and IgG4-positive plasma cells, and these histopathologic findings seem to be essentially similar regardless of the organs involved. In this mini review, we summarize what is known so far about multifocal fibrosclerosis of the cardiovascular system and its association with IgG4-SD, and what remains to be clarified in future investigations. (C) 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
  • Aiko Sakamoto, Nobukazu Ishizaka, Kan Saito, Yasushi Imai, Hiroyuki Morita, Kazuhiko Koike, Takahide Kohro, Ryozo Nagai
    CLINICA CHIMICA ACTA 413 5-6 577 - 581 2012年03月 [査読有り][通常論文]
     
    Background: Immunoglobulin G4 (IgG4)-related immuno-inflammation has been suggested to play a role in the development of remodeling of arterial wall. We investigated the association between serum concentrations of IgG4 or soluble interleukin-2 receptor (sIL-2R) and coronary artery disease (CAD). Methods: Serum concentrations of IgG4 and sIL-2R were measured in 286 patients who underwent coronary angiography. Results: In patients with CAD, the medians of serum concentrations of IgG4 (393 mg/dl) and sIL-2R (388 U/ml) were significantly higher than corresponding values in patients without CAD (IgG4 27.0 mg/dl, sIL-2R 312 U/ml). In receiver-operating characteristic curve analysis, the area under the curve of sIL-2R and IgG4 for the presence of CAD was 0.634 and 0.632, respectively. Age- and gender-adjusted logistic regression analysis showed that both of the fourth quartile of sIL-2R concentrations (>= 509 U/ml) and that of IgG4 concentrations (>= 57.7 mg/dl) were found to be associated with CAD with an odds ratio of 2.82 and 4.08, respectively, compared with the corresponding lowest quartile. Conclusions: Serum concentrations of IgG4 and sIL-2R were increased in patients with angiographically-proven CAD, suggesting that IgG4-related immuno-inflammation may also have a role in the development and/or progression of coronary artery atherosclerosis. (C) 2011 Elsevier B.V. All rights reserved.
  • Aiko Sakamoto, Ryozo Nagai, Kan Saito, Yasushi Imai, Masao Takahashi, Yumiko Hosoya, Norifumi Takeda, Kenji Hirano, Kazuhiko Koike, Yutaka Enomoto, Haruki Kume, Yukio Homma, Daichi Maeda, Hideomi Yamada, Masashi Fukayama, Yasunobu Hirata, Nobukazu Ishizaka
    JOURNAL OF CARDIOLOGY 59 2 139 - 146 2012年03月 [査読有り][通常論文]
     
    Retroperitoneal fibrosis, inflammatory aortic aneurysm, and pericardial and mediastinal fibrosis are characterized by infiltration of immuno-inflammatory cells and deposition of thickened fibrous tissues. Several recent studies suggested that an immunoglobulin-G4 (IgG4)-related immunological mechanism may play a role in these diseases. By searching the clinical database of patients admitted to our department between 2000 and 2010, we summarized the clinical data of 11 patients who were diagnosed to have these disorders. The diagnoses were idiopathic retroperitoneal fibrosis (8 cases), mediastinal and/or pericardial fibrosis (4 cases), inflammatory abdominal aneurysm (2 cases), and inflammatory coronary periarteritis (1 case). Hypertension, diabetes, and dyslipidemia were found in 45%, 36%, and 55%, respectively, in these patients, and they were all either current or former smokers. Two patients with pericardial involvement showed a rushed clinical course, resulting in in-hospital death. Serum levels of IgG were elevated in 67%, and soluble interleukin-2 receptor was elevated in 75%, when measured. Immunohistochemical analysis showed marked infiltration of IgG4-positive plasma cells in the pericardium in patients who died of constrictive pericarditis. Our data support the notion that immune-inflammatory mechanism, which might be IgG4-related sometimes, may play a role in idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm, and mediastinal/pericardial fibrosis, although clinical course may differ substantially. (C) 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
  • Yukako Suzuki, Takeki Suzuki, Yasushi Imai, Ryo Inuzuka, Tsugutoshi Suzuki, Yoshihide Nakamura, Hiroshi Ono
    CARDIOLOGY 123 2 108 - 112 2012年 [査読有り][通常論文]
     
    Wolff-Parkinson-White syndrome is associated with heart failure (HF) mainly via tachycardia. Several case report series have suggested dyssynchrony due to an accessory pathway as a possible cause of HF even in the absence of tachyarrhythmias. The role of cardiac resynchronization in the suppression of anterograde conduction of accessory pathways by catheter ablation or pharmacotherapy in such patients remains unclear, especially in the pediatric population. We describe an infant case with HF due to ventricular dyssynchrony and refractory tachycardia caused by a right anterolateral accessory pathway. Cardiac resynchronization either by catheter ablation or amiodarone appears to be of value in such cases. Copyright (c) 2012 S. Karger AG, Basel
  • Naomi Ogawa, Yasushi Imai, Yuji Takahashi, Kan Nawata, Kazuo Hara, Hiroshi Nishimura, Masayoshi Kato, Norifumi Takeda, Takahide Kohro, Hiroyuki Morita, Tsuyoshi Taketani, Tetsuro Morota, Tsutomu Yamazaki, Jun Goto, Shoji Tsuji, Shinichi Takamoto, Ryozo Nagai, Yasunobu Hirata
    AMERICAN JOURNAL OF CARDIOLOGY 108 12 1801 - 1807 2011年12月 [査読有り][通常論文]
     
    Marfan syndrome (MS) is an inherited connective tissue disorder, and detailed evaluations of multiple organ systems are required for its diagnosis. Genetic testing of the disease-causing fibrillin-1 gene (FBN1) is also important in this diagnostic scheme. The aim of this study was to define the clinical characteristics of Japanese patients with MS and enable the efficient and accurate diagnosis of MS with mutational analysis using a high-throughput microarray-based resequencing system. Fifty-three Japanese probands were recruited, and their clinical characteristics were evaluated using the Ghent criteria. For mutational analysis, an oligonucleotide microarray was designed to interrogate FBN1, and the entire exon and exon-intron boundaries of FBN1 were sequenced. Clinical evaluation revealed more pulmonary phenotypes and fewer skeletal phenotypes in Japanese patients with MS compared to Caucasians. The microarray-based resequencing system detected 35 kinds of mutations, including 23 new mutations The mutation detection rate for patients who fulfilled the Ghent criteria reached 71%. Of note, splicing mutations accounted for 19% of all mutations, which is more than previously reported. In conclusion, this comprehensive approach successfully detected clinical phenotypes of Japanese patients with MS and demonstrated the usefulness and feasibility of this microarray-based high-throughput resequencing system for mutational analysis of MS. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:1801-1807)
  • Eriko Hasumi, Hiroshi Iwata, Kan Saito, Katsuhito Fujiu, Jiro Ando, Yasushi Imai, Hideo Fujita, Yasunobu Hirata, Ryozo Nagai
    INTERNATIONAL HEART JOURNAL 52 4 240 - 242 2011年07月 [査読有り][通常論文]
     
    Procedure-related coronary dissection is associated with an increased risk of major adverse cardiovascular events after percutaneous coronary intervention (PCI). In most patients with such an iatrogenic complication, further PCI or bypass surgery aimed at complete revascularization is performed. Moreover, conventional coronary angiography has been used as a standard modality in the follow-up of such patients. The present report describes a 70 year old female patient who was complicated by catheter-related extensive coronary dissection in the right coronary artery (RCA) when treated for an acute myocardial infarction. Although RCA flow was insufficient, we decided against revascularization and followed her medically without additional revascularization procedures. Her clinical course had been uneventful for 4 years. However, symptoms of effort angina developed and re-examinations were performed at approximately 5 years after the myocardial infarction. Although conventional coronary angiography failed to show the culprit lesion responsible for the angina symptoms, the superior spatial resolution of the coronary CT angiography clearly identified significant progression of the stenotic lesion in the true lumen of the dissected RCA. Thus, coronary CT angiography might be considered as a possible first-line follow-up modality in patients with procedure-related coronary dissection. (Int Heart J 2011; 52: 240-242)
  • Kensuke Tsushima, Tomoko Osawa, Hideyuki Yanai, Akira Nakajima, Akinori Takaoka, Ichiro Manabe, Yusuke Ohba, Yasushi Imai, Tadatsugu Taniguchi, Ryozo Nagai
    FASEB JOURNAL 25 5 1531 - 1543 2011年05月 [査読有り][通常論文]
     
    Hypertension is a typical modern lifestyle-related disease that is closely associated with the development of cardiovascular disorders. Elevation of angiotensin II (ANG II) is one of several critical factors for hypertension and heart failure; however, the mechanisms underlying the ANG II-mediated pathogenesis are still poorly understood. Here, we show that ANG II-mediated cardiac fibrosis, but not hypertrophy, is regulated by interferon regulatory factor 3 (IRF3), which until now has been exclusively studied in the innate immune system. In a ANG II-infusion mouse model (3.0 mg/kg/d), we compared IRF3-deficient mice (Irf3(-/-)/Bcl2l12(-/-)) with matched wild-type (WT) controls. The development of cardiac fibrosis [3.95 +/- 0.62% (WT) vs. 1.41 +/- 0.46% (Irf3(-/-)/Bcl2l12(-/-)); P < 0.01] and accompanied reduction in left ventricle end-diastolic dimension [2.89 +/- 0.10 mm (WT) vs. 3.51 +/- 0.15 mm (Irf3(-/-)/Bcl2l12(-/-)); P=0.012] are strongly suppressed in Irf3(-/-)/Bcl2l12(-/-) mice, whereas hypertrophy still develops. Further, we provide evidence for the activation of IRF3 by ANG II signaling in mouse cardiac fibroblasts. Unlike the activation of IRF3 by innate immune receptors, IRF3 activation by ANG II is unique in that it is activated through the canonical ERK signaling pathway. Thus, our present study reveals a hitherto unrecognized function of IRF3 in cardiac remodeling, providing new insight into the progression of hypertension-induced cardiac pathogenesis.-Tsushima, K., Osawa, T., Yanai, H., Nakajima, A., Takaoka, A., Manabe, I., Ohba, Y., Imai, Y., Taniguchi, T., Nagai, R. IRF3 regulates cardiac fibrosis but not hypertrophy in mice during angiotensin II-induced hypertension. FASEB J. 25, 1531-1543 (2011). www.fasebj.org
  • Satomi Seki, Naoko Kato, Naomi Ito, Koichiro Kinugawa, Minoru Ono, Noboru Motomura, Atsushi Yao, Masafumi Watanabe, Yasushi Imai, Norihiko Takeda, Masashi Inoue, Masaru Hatano, Keiko Kazuma
    EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING 10 1 22 - 30 2011年03月 [査読有り][通常論文]
     
    Background and aims: Assessing the health related quality of life (HRQOL) in patients with a disease specific scale is essential. The purpose of this study was to develop the Japanese version of the coronary revascularisation outcome questionnaire (CROQ), a disease-specific scale to measure HRQOL before and after coronary revascularisation. Methods: The English version of the questionnaire was translated into Japanese; some terms were revised, and some items were eliminated to suit the Japanese medical environment. Eight patients filled out the questionnaire, which was then analyzed for face validity. In the field study, subjects were recruited from a university hospital in Tokyo, and questionnaires were given to fill out. In terms of statistical analysis, factor analysis, internal consistency, known-groups validity, concurrent validity with using Short-Form36 (SF-36) and Seattle Angina Questionnaire-Japanese version (SAQ-J), and test-retest reliability were assessed. Results: Informed consents were obtained from 356 patients, and out of 325 patients responded in the field study (91.3%). The factor structure of CROQ-Japanese version (CROQ-J) was similar to that of the original version. Cronbach's alpha ranged from 0.78 to 0.92. The concurrent validity was mostly supported by the pattern of association between CROQ-J, SAQ-J, and SF-36. Patients without chest symptoms had significantly higher scores of CROQ-J than those with chest symptoms. On the basis of analysis of the test-retest reliability, intra-class correlation coefficients were close to 0.70. Conclusions: The Japanese translation of CROQ is a valid and reliable scale for assessing the patient's HRQOL in CAD. (C) 2010 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
  • Arihiro Kiyosue, Yasunobu Hirata, Jiro Ando, Hideo Fujita, Toshihiro Morita, Masao Takahashi, Daisuke Nagata, Takahide Kohro, Yasushi Imai, Ryozo Nagai
    CIRCULATION JOURNAL 74 11 2441 - 2447 2010年11月 [査読有り][通常論文]
     
    Background: This study examines whether the serum concentration of cystatin C (Cys C) correlates with the severity of coronary artery disease (CAD) and whether it provides additional information on the risk for CAD in patients without chronic kidney disease (CKD) estimated by the creatinine-based glomerular filtration rate (GFR). Methods and Results: The relationship between serum Cys C and the severity of CAD in 526 patients was investigated. Based on GFR, patients were divided into those with and without CKD. The relationship of serum Cys C with the severity of CAD was examined. Serum Cys C was closely correlated with GFR in all cases and in CKD patients, but not in non-CKD patients. The average number of stenotic coronary arteries was significantly higher in the quartiles of higher concentration of Cys C as well as in those of GFR. In 348 patients (66%) the GFR was >= 60ml.min(-1).1.73 m(-2). Those patients with increased Cys C (>0.90 mg/L, 143 patients) had a significantly larger number of stenotic coronary arteries than those patients with normal Cys C. Conclusions: Among patients considered to be at low risk based on the estimated GFR using serum creatinine, those with high concentrations of Cys C could have severe CAD. Besides CKD, Cys C might serve as a marker of CAD severity. (Circ J 2010; 74: 2441-2447)
  • Satomi Seki, Naoko Kato, Naomi Ito, Koichiro Kinugawa, Minoru Ono, Noboru Motomura, Atsushi Yao, Masafumi Watanabe, Yasushi Imai, Norihiko Takeda, Masashi Inoue, Masaru Hatano, Keiko Kazuma
    Asian Nursing Research 4 2 57 - 63 2010年07月 [査読有り][通常論文]
     
    Purpose The aim of this study was to evaluate the validity and reliability of the Seattle Angina Questionnaire, Japanese version (SAQ-J) as a disease-specific health outcome scale in patients with coronary artery disease. Methods Patients with coronary artery disease were recruited from a university hospital in Tokyo. The patients completed self-administered questionnaires, and medical information was obtained from the subjects medical records. Face validity, concurrent validity evaluated using Short Form 36 (SF-36), known group differences, internal consistency, and test-retest reliability were statistically analyzed. Results A total of 354 patients gave informed consent, and 331 of them responded (93.5%). The concurrent validity was mostly supported by the pattern of association between SAQ-J and SF-36. The patients without chest symptoms showed significantly higher SAQ-J scores than did the patients with chest symptoms in 4 domains. Cronbachs alpha ranged from .51 to .96, meaning that internal consistency was confirmed to a certain extent. The intraclass correlation coefficient of most domains was higher than the recommended value of 0.70. The weighted kappa ranged from .24 to .57, and it was greater than .4 for 14 of the 19 items. Conclusions The SAQ-J could be a valid and reliable disease-specific scale in some part for measuring health outcomes in patients with coronary artery disease, and requires cautious use.
  • Yumiko Oishi, Ichiro Manabe, Yasushi Imai, Kazuo Hara, Momoko Horikoshi, Katsuhito Fujiu, Toshihiro Tanaka, Tadanori Aizawa, Takashi Kadowaki, Ryozo Nagai
    FASEB JOURNAL 24 6 1780 - 1788 2010年06月 [査読有り][通常論文]
     
    Kruppel-like factor 5 (KLF5) is a zinc-finger-type transcription factor that mediates the tissue remodeling in cardiovascular diseases, such as atherosclerosis, restenosis, and cardiac hypertrophy. Our previous studies have shown that KLF5 is induced by angiotensin II (AII), although the precise molecular mechanism is not yet known. Here we analyzed regulatory single nucleotide polymorphisms (SNPs) within the KLF5 locus to identify clinically relevant signaling pathways linking AII and KLF5. One SNP was located at -1282 bp and was associated with an increased risk of hypertension: subjects with the A/A and A/G genotypes at -1282 were at significantly higher risk for hypertension than those with the G/G genotype. Interestingly, a reporter construct corresponding to the -1282G genotype showed much weaker responses to AII than a construct corresponding to -1282A. Electrophoretic mobility shift, chromatin immunoprecipitation, and reporter assays collectively showed that the -1282 SNP is located within a functional myocyte enhancer factor 2 (MEF2) binding site, and that the -1282G genotype disrupts the site and reduces the AII responsiveness of the promoter. Moreover, MEF2 activation via reactive oxygen species and p38 mitogen-activated protein kinase induced KLF5 expression in response to AII, and KLF5 and MEF2 were coexpressed in coronary atherosclerotic plaques. These results suggest that a novel signaling and transcription network involving MEF2A and KLF5 plays an important role in the pathogenesis of cardiovascular diseases such as hypertension.-Oishi, Y., Manabe, I., Imai, Y., Hara, K., Horikoshi, M., Fujiu, K., Tanaka, T., Aizawa, T., Kadowaki, T., Nagai, R. Regulatory polymorphism in transcription factor KLF5 at the MEF2 element alters the response to angiotensin II and is associated with human hypertension. FASEB J. 24, 1780-1788 (2010). www.fasebj.org
  • Arihiro Kiyosue, Yasunobu Hirata, Jiro Ando, Hideo Fujita, Toshihiro Morita, Masao Takahashi, Daisuke Nagata, Takahide Kohro, Yasushi Imai, Ryozo Nagai
    CIRCULATION JOURNAL 74 4 786 - 791 2010年04月 [査読有り][通常論文]
     
    Background: The relationship between renal dysfunction and the severity of coronary artery disease (CAD) was examined. Methods and Results: The severity of CAD in 572 patients was graded according to the number of stenotic coronary arteries, and the estimated glomerular filtration rate (eGFR) was monitored for 3 years. Patients were stratified into 3 eGFR groups: normal (>75 ml.min(-1).1.73 m(-2)), mild reduction (60-75) and chronic kidney disease (CKD: <60). There were 161 patients in the CKD group. The average number of stenotic coronary arteries was larger in the CKD group than in the other groups (normal vs mild reduction vs CKD =1.35 +/- 0.07 (SE) vs 1.22 +/- 0.08 vs 1.69 +/- 0.08 vessel disease (VD), P<0.001). During the 3-year follow-up, the renal function of 13.8% of the patients worsened. Those who showed more deterioration of eGFR had more severe CAD than those who did not (1.20 +/- 0.06 vs 1.61 +/- 0.06 VD, P<0.001). Multivariate analysis revealed that the severity of CAD was independently and significantly associated with the deterioration of eGFR. Conclusions: Patients with CKD had more severe CAD, which may explain the high rate of cardiovascular events in these patients. Moreover, the prognosis of renal function was poor in patients with severe CAD, and CAD was found to be an independent risk factor for worsening of renal dysfunction. (Circ J 2010; 74: 786-791)
  • Kenta Tsutsui, Kohsuke Ajiki, Katsuhito Fujiu, Yasushi Imai, Noriyuki Hayami, Yuji Murakawa
    INTERNATIONAL HEART JOURNAL 51 1 72 - 74 2010年01月 [査読有り][通常論文]
     
    Atrial tachycardia (AT) and atrial fibrillation (AF) were observed in a 21-year old male who had a history of patch closure for an atrial septal defect (ASD) at the age of 5 and a persistent left superior vena cava (LSVC). During electrophysiologic study, atrial extrastimuli reproducibly induced AT which spontaneously terminated or changed into AF. Electroanatomical mapping revealed focal AT arising from the floor of the proximal LSVC. Radiofrequency applications within LSVC targeted to the earliest activation site of AT as well as the complex fractionated potential eliminated both AT and AF without trans-septal puncture. (Int Heart J 2010; 51: 72-74)
  • Naomi Ogawa, Yasushi Imai, Hiroyuki Morita, Ryozo Nagai
    International Journal of Hypertension 2010 790539  2010年 [査読有り][通常論文]
     
    Coronary artery disease (CAD) is a multifactorial disease with environmental and genetic determinants. The genetic determinants of CAD have previously been explored by the candidate gene approach. Recently, the data from the International HapMap Project and the development of dense genotyping chips have enabled us to perform genome-wide association studies (GWAS) on a large number of subjects without bias towards any particular candidate genes. In 2007, three chip-based GWAS simultaneously revealed the significant association between common variants on chromosome 9p21 and CAD. This association was replicated among other ethnic groups and also in a meta-analysis. Further investigations have detected several other candidate loci associated with CAD. The chip-based GWAS approach has identified novel and unbiased genetic determinants of CAD and these insights provide the important direction to better understand the pathogenesis of CAD and to develop new and improved preventive measures and treatments for CAD. © 2010 Naomi Ogawa et al.
  • Kariya T, Imai Y, Murakami A
    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 36 3 603; author reply 604  2009年09月 [査読有り][通常論文]
  • Naoko Kato, Koichiro Kinugawa, Naomi Ito, Atsushi Yao, Masafumi Watanabe, Yasushi Imai, Norihiko Takeda, Masaru Hatano, Keiko Kazuma
    HEART & LUNG 38 5 398 - 409 2009年09月 [査読有り][通常論文]
     
    BACKGROUND: Adherence to self-care behavior is important for patients with heart failure (HF) to prevent exacerbation of HF. The aim of this study was to evaluate adherence, identify associated factors, and clarify the impact of previous HF hospitalizations on adherence in outpatients with HF. METHODS: A total of 116 outpatients completed a questionnaire, including the Japanese version of the European Heart Failure Self-Care Behavior Scale, to assess adherence. RESULTS: Regardless of previous hospitalizations, adherence to seek help if HF worsened was poor. Multivariate analysis adjusted for age and brain natriuretic peptide showed that diabetes mellitus and being employed were independent predictors of poorer adherence to self-care behavior (P = .03, P = .02, respectively), but the experience of previous HF hospitalizations was not a predictor. CONCLUSIONS: Self-care strategies for HF should target patients with diabetes mellitus and employed patients. Further study is necessary to develop effective programs for such patients. (Heart Lung (R) 2009; 38:398-409.)
  • Hiroaki Sugiyama, Makoto Sahara, Yasushi Imai, Minoru Ono, Koh Okamoto, Ken Kikuchi, Ryozo Nagai
    CARDIOLOGY 114 3 208 - 211 2009年 [査読有り][通常論文]
     
    The Bartonella species have been recently recognized as important causative agents of culture-negative bacterial endocarditis. Antineutrophil cytoplasmic antibodies (ANCAs) have been associated with the spectrum of idiopathic small vessel vasculitis. However, a variety of infections can result in a false-positive ANCA test, and especially subacute bacterial endocarditis (SBE) with the presence of ANCAs occasionally mimics the clinical manifestations of an ANCA-associated vasculitis such as skin purpura and glomerulonephritis. In contrast, noninfectious endocardial involvement is known to be part of the spectrum of the manifestations of the ANCA-associated vasculitis. Therefore, it is crucial to distinguish an ANCA-positive SBE from an ANCA-associated vasculitis with endocardial compromise, because the misdiagnosis of an SBE as an ANCA-associated vasculitis can lead to an inappropriate immunosuppressive therapy with catastrophic consequences. The differential diagnosis is sometimes difficult, especially in the case of culture-negative infective endocarditis with a positive ANCA test. We describe here a case of a culture-negative SBE caused by Bartonella quintana, accompanied with a positive cytoplasmic ANCA test and clinical findings masquerading as ANCA-associated vasculitis. Both a serological test for Bartonella and polymerase chain reaction restriction fragment length polymorphism analysis were helpful for a correct diagnosis and appropriate treatment. Copyright (C) 2009 S. Karger AG, Basel
  • Kariya T, Imai Y, Murakami A, Minegishi S, Katori T, Kato H, Ajiki K, Hirata Y, Nagai R
    Circulation 118 9 e133 - 5 2008年08月 [査読有り][通常論文]
  • Hajime Fujimoto, Jun-Ichi Taguchi, Yasushi Imai, Seiji Ayabe, Hideki Hashimoto, Hisae Kobayashi, Ken Ogasawara, Tadanori Aizawa, Minoru Yamakado, Ryozo Nagai, Minoru Ohno
    EUROPEAN HEART JOURNAL 29 10 1267 - 1274 2008年05月 [査読有り][通常論文]
     
    Aims Oxidative damage promotes atherosclerosis. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme localized in mitochondria. We investigated the associations of the MnSOD polymorphism (valine-to-alanine in the mitochondrial-targeting domain) with its activity in leukocytes, with macrophage apoptosis by oxidized low-density lipoprotein (oxLDL), and with coronary artery disease (CAD). Methods and results Blood samples were taken from 50 healthy subjects. The mitochondrial MnSOD activities in leukocytes were 542.4 +/- 71.6 U/mg protein (alanine/alanine, n = 2), 302.0 +/- 94.9 U/mg protein (alanine/valine, n = 12), and 134.0 +/- 67.1 U/mg protein (valine/valine, n = 36; P < 0.0001 for non-valine/valine vs. valine/valine). Macrophages were treated with oxLDL. After incubation, the percentages of apoptotic macrophages were 48.6 +/- 3.6% (alanine/alanine), 78.6 +/- 9.8% (alanine/valine), and 87.5 +/- 7.0% (valine/valine) (P < 0.0001, non-valine/valine vs. valine/valine). The association of the MnSOD polymorphism with CAD was investigated using blood samples collected from 498 CAD patients and 627 healthy subjects; the alanine allele was found to reduce the risk of CAD and acute myocardial infarction (AMI). Conclusion Our data indicate that the alanine variant of signal peptide increases the mitochondrial MnSOD activity, protects macrophages against the oxLDL-induced apoptosis, and reduces the risk of CAD and AMI.
  • Guoqin Wang, Masafumi Watanabe, Yasushi Imai, Kazuo Hara, Ichiro Manabe, Koji Maemura, Momoko Horikoshi, Takahide Kohro, Eisuke Amiya, Takao Sugiyama, Takeshi Fujita, Takashi Kadowaki, Tsutomu Yamazaki, Ryozo Nagai
    INTERNATIONAL HEART JOURNAL 49 3 313 - 327 2008年05月 [査読有り][通常論文]
     
    A phenotypic change of smooth muscle cells (SMCs) is considered to be critical in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD). Mrf-2/ARID5B, a member of the AT-rich interaction domain family of transcription factors, is highly expressed in the cardiovascular system and is believed to play essential roles in the phenotypic change of SMCs through its regulation of SMC differentiation. In addition, recent studies on gene-engineered mice suggested that this transcriptional factor is involved in obesity and adipogenesis, which are critical aspects for the pathogenesis of atherosclerosis. Thus, we hypothesized that genetic variations of the Mrf-2 gene might be associated with susceptibility to CAD. We investigated 11 common genetic variations of Mrf-2 to determine whether they were associated with susceptibility to CAD in 475 CAD subjects and 3 10 control Subjects. The prevalence of homozygotes for the minor allele G of SNP4 (rs2893890) and minor allele G of SNP6 (rs7087507) were significantly more frequent in the control Subjects than in patients with CAD (P = 0.0002, rs2893880, P = 0.0058, rs7087507). Four nearby SNPs (SNP4 to SNP7) (rs2893880, rs10740055, rs7087507 and rs10761600) showed almost complete linkage disequilibrium, and haplotype analysis revealed that the haplotype G (rs2893880)-C (rs10740055)-G (rs7087507)-A (rs10761600) was also significantly negatively associated with susceptibility to CAD (P = 0.049). Moreover, these negative disease associations still existed after logistic regression analysis was taken into account to eliminate confounding conventional coronary risk factors. The results implicate possible disease relevance of the polymorphisms in the Mrf-2 gene with Susceptibility to CAD. However, a larger scale prospective study is needed to clarify these findings.
  • Yoshiko Munemasa, Toru Suzuki, Kenichi Aizawa, Saku Miyamoto, Yasushi Imai, Takayoshi Matsumura, Masami Horikoshi, Ryozo Nagai
    MOLECULAR AND CELLULAR BIOLOGY 28 3 1171 - 1181 2008年02月 [査読有り][通常論文]
     
    Regulation of chromatin in eukaryotic transcription requires histone-modifying enzymes, nucleosome remodeling complexes, and histone chaperones. Specific regulation of histone incorporation/eviction by histone chaperones on the promoter (e.g., region specific) is still poorly understood. In the present study, we show that direct and functional interaction of histone chaperone and DNA-binding transcription factor leads to promoter region-specific histone incorporation and inhibition of histone acetylation. We report here that the DNA-binding transcription factor Kruppel-like factor 5 (KLF5) interacts with the novel histone chaperone acidic nuclear phosphoprotein 32B (ANP32B), leading to transcriptional repression of a KLF5-downstream gene. We further show that recruitment of ANP32B onto the promoter region requires KLF5 and results in promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B. Extracellular stimulus (e.g., phorbol ester) regulates this mechanism in the cell. Collectively, we have identified a novel histone chaperone, ANP32B, and through analysis of the actions of this factor show a new mechanism of promoter region-specific transcriptional regulation at the chromatin level as mediated by the functional interaction between histone chaperone and DNA-binding transcription factor.
  • Norihiko Takeda, Koji Maemura, Shuichi Horie, Katsutaka Oishi, Yasushi Imai, Tomohiro Harada, Tetsuya Saito, Taro Shiga, Eisuke Amiya, Ichiro Manabe, Norio Ishida, Ryozo Nagai
    JOURNAL OF BIOLOGICAL CHEMISTRY 282 45 32561 - 32567 2007年11月 [査読有り][通常論文]
     
    Cardiovascular diseases are closely related to circadian rhythm, which is under the control of an internal biological clock mechanism. Although a biological clock exists not only in the hypothalamus but also in each peripheral tissue, the biological relevance of the peripheral clock remains to be elucidated. In this study we searched for clock- controlled genes in vascular endothelial cells using microarray technology. The expression of a total of 229 genes was up- regulated by CLOCK/ BMAL2. Among the genes that we identified, we examined the thrombomodulin ( TM) gene further, because TM is an integral membrane glycoprotein that is expressed primarily in vascular endothelial cells and plays a major role in the regulation of intravascular coagulation. TM mRNA and protein expression showed a clear circadian oscillation in the mouse lung and heart. Reporter analyses, gel shift assays, and chromatin immunoprecipitation analyses using the TM promoter revealed that a heterodimer of CLOCK and BMAL2 binds directly to the E- box of the TM promoter, resulting in TM promoter transactivation. Indeed, the oscillation of TM gene expression was abolished in clock mutant mice, suggesting that TM expression is regulated by the clock gene in vivo. Finally, the phase of circadian oscillation of TM mRNA expression was altered by temporal feeding restriction, suggesting TM gene expression is regulated by the peripheral clock system. In conclusion, these data suggest that the peripheral clock in vascular endothelial cells regulates TM gene expression and that the oscillation of TM expression may contribute to the circadian variation of cardiovascular events.
  • Yoshinori Seko, Akihiro Matsumoto, Taira Fukuda, Yasushi Imai, Tsutonm Fujimura, Hikari Taka, Reiko Mineki, Kimie Murayama, Yasunobu Hirata, Ryozo Nagai
    INTERNATIONAL HEART JOURNAL 48 3 407 - 415 2007年05月 [査読有り][通常論文]
     
    Patients with neonatal lupus erythematosus (NLE) often have congenital heart block with or without heart failure and are born to mothers who have anti-SS-A and/or anti-SSB antibodies. NLE has been considered to result from the placental transmission of maternal autoantibodies into the fetal circulation causing myocardial damage. We report a case of NLE with congenital heart block who had undergone pacemaker implantation at the age of 17, and then developed dilated cardiomyopathy (DCM) at the age of 19, which is much later than in most other cases. The patient's mother was positive for anti-SS-A and anti-SS-B antibodies, whereas the patient was negative for both anti-SS-A and anti-SS-B antibodies. There were some autoantibodies against cell surface antigens of cardiac myocytes in the serum from the patient, and annexin A6 was identified as one of the autoantigens. This is the first report demonstrating that annexin A6 is involved in the myocardial injury in patients with NLE. The results indicate that inhibition of annexin A6 function may prevent autoantibody-mediated myocardial injury in at least some cases of DCM.
  • Kazuo Hara, Toshimasa Yamauchi, Yasushi Imai, Ichiro Manabe, Ryozo Nagai, Takashi Kadowaki
    INTERNATIONAL HEART JOURNAL 48 2 149 - 153 2007年03月 [査読有り][通常論文]
     
    Adipocyte-derived adiponectin has an antiatherosclerotic effect that acts independently of its antidiabetic effect. Plasma adiponectin levels are generally low in subjects with coronary artery disease. In this study, the relationship between the plasma adiponectin level and the severity of coronary artery disease, as assessed using the Gensini score, an index for the severity of coronary artery stenosis, was investigated. The subjects of the study were 104 patients (72 men and 32 women; BMI, 23.5 +/- 3.3 kg/m(2); age, 63.6 +/- 10.1 years) admitted to Tokyo University Hospital for coronary angiography. Plasma adiponectin levels were inversely correlated with the insulin resistance index HOMA-IR (P =0.0127). The plasma adiponectin level was significantly associated with the Gensini score (P = 0.0332). After adjustment for conventional risk factors for cardiovascular diseases, the plasma adiponectin level tended to be inversely correlated with the Gensini score (P = 0.087). The measurement of plasma adiponectin levels may be useful for predicting the severity of coronary artery stenosis.
  • Kohsuke Ajiki, Noriyuki Hayami, Yuji Kasaoka, Yasushi Imai, Katsuhito Fujiu, Yuji Murakawa
    INTERNATIONAL HEART JOURNAL 48 2 253 - 259 2007年03月 [査読有り][通常論文]
     
    Supraventricular tachycardia (SVT) was observed in a 13-year-old male patient with complex clinical features that included univentricular heart with single atrium, pulmonary atresia, and polysplenia syndrome. During electrophysiologic study, atrial burst stimuli reproducibly induced and terminated the SVT, while the occurrence of ventriculoatrial block did not interrupt the SVT. His bundle electrograms (HBEs) were recognized both in the anterior and posterior regions on the common atrioventricular (AV) valve annulus. The posterior His bundle activation was progressively delayed along with the shortening of atrial pacing cycle length until it finally lagged behind local ventricular activation. Thus, antegrade AV conduction was solely via the anterior AV node. In contrast, during the SVT, the earliest activation was observed in the posterior HBE. These observations suggested that the posterior AV node serves as an origin of the SVT and that two AV nodes were linked together possibly through a sling at the infra-Hisian level. Radiofrequency catheter ablation applied to the posterior HBE eliminated the SVT.
  • Makoto Sahara, Toshiyuki Takahashi, Yasushi Imai, Toshiaki Nakajima, Atsushi Yao, Toshihiro Morita, Yasunobu Hirata, Ryozo Nagai
    CARDIOVASCULAR DRUGS AND THERAPY 20 5 377 - 386 2006年10月 [査読有り][通常論文]
     
    Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease. In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil. We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.
  • Go Nishimura, Ichiro Manabe, Kensuke Tsushima, Katsuhito Fujiu, Yumiko Oishi, Yasushi Imai, Koji Maemura, Makoto Miyagishi, Yujiro Higashi, Hisato Kondoh, Ryozo Nagai
    DEVELOPMENTAL CELL 11 1 93 - 104 2006年07月 [査読有り][通常論文]
     
    Alteration in the differentiated state of smooth muscle cells (SMCs) is known to be integral to vascular development and the pathogenesis of vascular disease. However, it is still largely unknown how environmental cues translate into transcriptional control of SMC genes. We found that delta EF1 is upregulated during SMC differentiation and selectively transactivates the promoters of SMC differentiation marker genes, SM alpha-actin and SM myosin heavy chain (SM-MHC). delta EF1 physically interacts with SRF and Smad3, resulting in a synergistic activation of SM a-actin promoter. Chromatin immunoprecipitation assays and knockdown experiments showed that delta EF1 is involved in the control of the SMC differentiation programs induced by TGF-beta signaling. Overexpression of delta EF1 inhibited neointima formation and promoted SMC differentiation, whereas heterozygous dEF1 knockout mice exhibited exaggerated neointima formation. It thus appears delta EF1 mediates SMC differentiation via interaction with SRF and Smad3 during development and in vascular disease.
  • Kazuo Hara, Momoko Horikoshi, Toshimasa Yamauchi, Hirokazu Yago, Osamu Miyazaki, Hiroyuki Ebinuma, Yasushi Imai, Ryozo Nagai, Takashi Kadowaki
    DIABETES CARE 29 6 1357 - 1362 2006年06月 [査読有り][通常論文]
     
    OBJECTIVE - The high-molecular weight (HMW) form of adiponectin, an adipocyte-derived insulin-sensitizing hormone, has been reported to be the most active form Of this hormone. We investigated whether measurement of plasma HMW adiponectin levels, using our newly developed enzyme-linked immunosorbent assay system for selective measurement of human HMW adiponectin level, may be useful for the prediction of insulin resistance and metabolic syndrome. RESEARCH DESIGN AND METHODS - A total of 298 patients admitted for diabetes treatment or coronary angiography served as study subjects. Receiver operator characteristic (ROC) curves for the HMW ratio (HMWR; ratio of plasma level of HMW adiponectin to that of total adiponectin) and plasma total adiponectin levels were plotted to predict the presence of insulin resistance and metabolic syndrome. RESULTS - The area under the ROC curve (AUC) of the HMWR Values to predict the presence of insulin resistance was significantly larger than that of plasma total adiponectin level in total subjects (0.713 [95% CI 0.620-0.805] vs. 0.615 [0.522-0.708], P = 0.0160). The AUC for the HMWR values to predict the presence of metabolic syndrome was significantly larger than that for plasma total adiponectin levels in men (0.806 [0.747-0.865] vs. 0.730 [0.660-0.800], P = 0.0025) and in women (0.743 [0.659-0.828] vs. 0.637 [0.532-0.742], P = 0.0458). CONCLUSIONS - The HMWR value has better predictive power for the prediction of insulin resistance and metabolic syndrome than plasma total adiponectin level.
  • D Kawanami, K Maemura, N Takeda, T Harada, T Nojiri, T Saito, Manabe, I, Y Imai, R Nagai
    ATHEROSCLEROSIS 185 1 39 - 46 2006年03月 [査読有り][通常論文]
     
    Recent studies have shown that C-reactive protein (CRP) is not just a predictor of cardiovascular events but also acts directly as a proinflammatory stimulus in vascular cells. In this report, we studied the molecular mechanisms underlying vascular cellular adhesion molecule-1 (VCAM-1) induction by CRP. CRP-induced VCAM-1 mRNA expression and this induction was inhibited by protein kinase C (PKC) inhibitors, p38 mitogen-activated protein kinase (MAPK) inhibitor, and tyrosine kinase inhibitors. In addition, parthenolide, a nuclear factor kappa B (NF-kappa B) inhibitor, abolished VCAM-1 induction. Moreover, CRP increased VCAM-1 promoter activity, indicating that CRP induces VCAM-1 mRNA expression at the transcriptional level. Mutation of NF-kappa B-binding sites resulted in a loss of induction. Finally, an electrophoretic mobility shift assay confirmed binding of the p65 subunit of NF-kappa B to kappa B-binding sites. Taken together, our findings suggest that VCAM-1 induction by CRP is mediated by PKC, p38MAPK, tyrosine kinase and the NF-kappa B-dependent signaling pathways in vascular endothelial cells. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
  • Tsutomu Shimizu, Norifumi Takeda, Masao Takahashi, Yasushi Imai, Nobukazu Ishizaka, Yasunobu Hirata, Ryozo Nagai
    INTERNAL MEDICINE 45 20 1189 - 1190 2006年 [査読有り][通常論文]
  • K Monzen, T Hosoda, D Hayashi, Y Imai, Y Okawa, T Kohro, H Uozaki, T Nishiyama, M Fukayama, R Nagai
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 337 2 534 - 539 2005年11月 [査読有り][通常論文]
     
    Current medical transplantation confronts major problems such as the shortage of donors and geographical restrictions that inhibit efficient utilization of finite donor organs within their storage lives. To overcome these issues, expanding organ preservation time has become a major concern. We investigated whether a strategy which best preserves organ grafts can be achieved by the use of a newly developed refrigerating chamber, which is capable of establishing a supercooled and unfrozen state stably by generating an electrostatic field in its inside. When adult rat organs such as heart, liver, and kidneys were stored in the supercooled conditions, the levels of major biochemical markers leaked from the preserved organs were significantly lower than in the ordinary hypothermic storage. No apparent tissue damages were observed histologically after the supercooled preservation. Our results suggest that the use of this supercooling refrigerator improves organ preservation and may provide an innovative technique for human organ transplantation. (c) 2005 Elsevier Inc. All rights reserved.
  • Imai Y, Taketani T, Maemura K, Takeda N, Harada T, Nojiri T, Kawanami D, Monzen K, Hayashi D, Murakawa Y, Ohno M, Hirata Y, Yamazaki T, Takamoto S, Nagai R
    Circulation journal : official journal of the Japanese Circulation Society 69 8 994 - 995 2005年08月 [査読有り][通常論文]
  • T Taketani, Y Imai, T Morota, K Maemura, H Morita, D Hayashi, T Yamazaki, R Nagai, S Takamoto
    INTERNATIONAL HEART JOURNAL 46 2 265 - 277 2005年03月 [査読有り][通常論文]
     
    Changes in the expression levels of several genes have been described in aortic aneurysm specimens, however, the spectrum of diverse molecular alterations remains to be elucidated. We attempted to identify key molecules that modulate the pathogenesis of aortic aneurysm, using a complimentary DNA inicroarray carrying approximately 13,000 human genes. Segments of thoracic aortic aneurysms (TAA) and adjacent normal thoracic aortic tissues without aneurysmal changes (NTA) were obtained from 20 patients undergoing Graft Surgery. RNA obtained from five pairs of TAA and NTA samples was compared to determine aneurysm-specific alterations using microarray. Further, the expression levels of several genes of interest were verified in the remaining specimens by real-time reverse transcription-polymerase chain reaction (RT-PCR). In microarray assays, several types of the matrix rnetalloproteinases were upregulated as reported previously. Also, 220 genes suggested to be involved in protein degradation, inflammation, apoptosis, stress response, intracellular signaling, and other processes were significantly upregulated. Many of these genes have not been previously implicated in cardiovascular disease. The real time RT-PCR independently confirmed that the expression levels of MMP-2, NIMP-9, ADAMTS-1, and caspase 4 were consistently increased in TAA. The results indicate that many genes are involved in a complicated manner in the pathogenesis of TAA. Investigation of these genes will help clarify the pathogenesis of this disease, and may lead to the discovery of novel therapeutic targets.
  • D Hayashi, S Kudoh, Shiojima, I, YZ Zou, K Harada, M Shimoyama, Y Imai, K Monzen, T Yamazaki, Y Yazaki, R Nagai, Komuro, I
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 322 1 310 - 319 2004年09月 [査読有り][通常論文]
     
    Cardiac hypertrophy is formed in response to hemodynamic overload. Although a variety of factors such as catecholamines, angiotensin II (AngII), and endothelin-1 (ET-1) have been reported to induce cardiac hypertrophy, little is known regarding the factors that inhibit the development of cardiac hypertrophy. Production of atrial natriuretic peptide (ANP) is increased in the hypertrophied heart and ANP has recently been reported to inhibit the growth of various cell types. We therefore examined whether ANP inhibits the development of cardiac hypertrophy. Pretreatment of cultured cardiomyocytes with ANP inhibited the AngII- or ET-1-induced increase in the cell size and the protein synthesis. ANP also inhibited the AngII- or ET-1-induced hypertrophic responses such as activation of mitogen-activated protein kinase (MAPK) and induction of immediate early response genes and fetal type genes. To determine how ANP inhibits cardiomyocyte hypertrophy, we examined the mechanism of ANP-induced suppression of the MAPK activation. ANP strongly induced expression of MAPK phosphatase-1 (MKP-1) and overexpression of MKP-1 inhibited AngII- or ET-1-induced hypertrophic responses. These growth-inhibitory actions of ANP were mimicked by a cyclic GMP analog 8-bromo-cyclic GMP. Taken together, ANP directly inhibits the growth factor-induced cardiomyocyte hypertrophy at least partly via induction of MKP-1. Our present study suggests that the formation of cardiac hypertrophy is regulated not only by positive but by negative factors in response to hemodynamic load. (C) 2004 Elsevier Inc. All rights reserved.
  • Y Nakashima, K Okano, K Kojima, H Shirakura, S Ishida, M Watanabe, K Maeda, H Tsunoda, Y Imai, K Nagai
    CLINICAL CHEMISTRY 50 8 1417 - 1420 2004年08月 [査読有り][通常論文]
  • N Takeda, K Maemura, Y Imai, T Harada, D Kawanami, T Nojiri, Manabe, I, R Nagai
    CIRCULATION RESEARCH 95 2 146 - 153 2004年07月 [査読有り][通常論文]
     
    Endothelial PAS domain protein 1 (EPAS1) is a basic-helix-loop-helix/PAS domain transcription factor that is expressed preferentially in vascular endothelial cells. EPAS1 shares high homology with hypoxia-inducible factor-1alpha (HIF-1alpha) and is reported to transactivate vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1), and Tie2 promoters. In this study, we analyzed the role of EPAS1 in the process of angiogenesis. Using microarray technology, we looked for target genes regulated by EPAS1 in vascular endothelial cells. A total of 130 genes were upregulated by EPAS1, including fms-like tyrosine kinase-1 (Flt-1). Reporter analysis using human Flt-1 promoter and gel mobility shift assays showed that the heterodimer of EPAS1 and aryl hydrocarbon receptor nuclear translocator binds directly to HIF-1-binding site upstream of Flt-1 promoter and transactivates it. Small interfering RNA targeted to EPAS1 but not HIF-1alpha attenuated desferrioxamine-induced Flt-1 mRNA expression, thus EPAS1 is thought to play an essential role in hypoxic induction of Flt-1 gene. Furthermore, using mouse wound healing models, we demonstrated that adenovirus-mediated delivery of EPAS1 gene significantly induced the expression of VEGF, Flt-1, Flk-1, and Tie2 mRNA at the wound site and promoted mature angiogenesis. The proportion of the number of mural cells in newly formed vessels was significantly higher in EPAS1-treated wound area than VEGF-treated area. In conclusion, EPAS1 promotes Flt-1 gene expression and induces mRNA expression of VEGF, Flk-1, and Tie2, leading to enhancement of mature angiogenesis in vivo. Thus, EPAS1 may contribute to the construction of mature vessels by modulating the coordinated expressions of VEGF, Flt-1, Flk-1, and Tie2.
  • Y Ikeda, Y Imai, H Kumagai, T Nosaka, Y Morikawa, T Hisaoka, Manabe, I, K Maemura, T Nakaoka, T Imamura, K Miyazono, Komuro, I, R Nagai, T Kitamura
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 101 29 10732 - 10737 2004年07月 [査読有り][通常論文]
     
    Growth factors, cell-surface receptors, adhesion molecules, and extracellular matrix proteins play critical roles in vascular pathophysiology by affecting growth, migration, differentiation, and survival of vascular cells. In a search for secreted and cell-surface molecules expressed in the cardiovascular system, by using a retrovirus-mediated signal sequence trap method, we isolated a cell-surface protein named vasorin. Vasorin is a typical type I membrane protein, containing tandem arrays of a characteristic leucine-rich repeat motif, an epidermal growth factor-like motif, and a fibronectin type III-like motif at the extracellular domain. Expression analyses demonstrated that vasorin is predominantly expressed in vascular smooth muscle cells, and that its expression is developmentally regulated. To clarify biological functions of vasorin, we searched for its binding partners and found that vasorin directly binds to transforming growth factor (TGF)-beta and attenuates TGF-beta signaling in vitro. Vasorin expression was down-regulated during vessel repair after arterial injury, and reversal of vasorin down-regulation, by using adenovirus-mediated in vivo gene transfer, significantly diminished injury-induced vascular lesion formation, at least in part, by inhibiting TGF-beta signaling in vivo. These results suggest that down-regulation of vasorin expression contributes to neointimal formation after vascular injury and that vasorin modulates cellular responses to pathological stimuli in the vessel wall. Thus, vasorin is a potential therapeutic target for vascular fibroproliferative disorders.
  • Hayashi D, Imai Y, Morita H, Fujita H, Monzen K, Harada T, Nojiri T, Yamazaki T, Yamazaki T, Nagai R
    Japanese heart journal 45 2 315 - 324 2004年03月 [査読有り][通常論文]
  • D Kawanami, K Maemura, N Takeda, T Harada, T Nojiri, Y Imai, Manabe, I, K Utsunomiya, R Nagai
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 314 2 415 - 419 2004年02月 [査読有り][通常論文]
     
    Resistin is an adipocytokine which plays a role in the development of insulin resistance. In this study, we investigated the direct effect of resistin on vascular endothelial cells. Resistin induced the expression of adhesion molecules such as VCAM-1 and ICAM-1, and long pentraxin 3, a marker of inflammation. The induction of VCAM-1 by resistin was inhibited partially by pitavastatin. Moreover, the induction of VCAM-1 and ICAM-1 by resistin was inhibited by adiponectin, an adipocytokine that improves insulin resistance. Taken together, these results suggest that the balance in the concentrations of adipocytokines such as resistin and adiponectin determines the inflammation status of vasculature, and in turn the progress of atherosclerosis. (C) 2003 Elsevier Inc. All rights reserved.
  • Y Hiroi, K Fujiu, S Komatsu, M Sonoda, Y Sakomura, YS Imai, Y Oishi, F Nakamura, K Ajiki, N Hayami, Y Murakawa, M Ohno, Y Hirata, K Ohtomo, R Nagai
    JAPANESE HEART JOURNAL 45 1 169 - 177 2004年01月 [査読有り][通常論文]
     
    An asymptomatic 35 year-old man was referred to our hospital because of abnormal ECG findings. The ECG showed complete right bundle branch block and left anterior hemiblock. Echocardiography revealed a moderately enlarged right ventricle (RV) and all apical aneurysm. RV wall motion showed diffusely moderate impairment, while the systolic function of the left ventricle (LV) was slightly decreased. The ejection fractions (EF) of the RV and LV were calculated as 28.1% and 41.9% by Simpson's method using multiple cardiac computed tomography (CT) scans. A 24 hour ambulatory ECG showed only 372 single premature ventricular contractions (PVC). Cardiac catheterizaion revealed that the RV was enlarged with prominent trabeculation and decreased motion. In an electrophysiologic study, neither electrical stimulation of the RV nor electrical Stimulation plus isoproterenol infusion Could induce ventricular tachycardia. Pathological examination of a biopsy from the interventricular septum of the RV revealed fibrofatty change in the myocardium. Based on these results, we made a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) and administered 5 mg of carvedilol. Sixty days after the initiation of carvedilol therapy, we performed repeat cardiac CT, The EF of the LV was markedly improved from 41.9% to 62.0%, although the EF of the RV was not changed. The number of PVCs showed no change. This case suggests that carvedilol is not only Useful for controlling arrhythmia but also for improving left ventricular function in some patients with ARVC. Sympathetic overactivity is reported to cause sudden death, so carvedilol may be a first-line drug for some patients with ARVC.
  • S Miyamoto, T Suzuki, S Muto, K Aizawa, A Kimura, Y Mizuno, T Nagino, Y Imai, N Adachi, M Horikoshi, R Nagai
    MOLECULAR AND CELLULAR BIOLOGY 23 23 8528 - 8541 2003年12月 [査読有り][通常論文]
     
    Here we show a novel pathway of transcriptional regulation of a DNA-binding transcription factor by coupled interaction and modification (e.g., acetylation) through the DNA-binding domain (DBD). The oncogenic regulator SET was isolated by affinity purification of factors interacting with the DBD of the cardiovascular transcription factor KLF5. SET negatively regulated KLF5 DNA binding, transactivation, and cell-proliferative activities. Down-regulation of the negative regulator SET was seen in response to KLF5-mediated gene activation. The coactivator/acetylase p300, on the other hand, interacted with and acetylated KLF5 DBD, and activated its transcription. Interestingly, SET inhibited KLF5 acetylation, and a nonacetylated mutant of KLF5 showed reduced transcriptional activation and cell growth complementary to the actions of SET. These findings suggest a new pathway for regulation of a DNA-binding transcription factor on the DBD through interaction and coupled acetylation by two opposing regulatory factors of a coactivator/acetylase and a negative cofactor harboring activity to inhibit acetylation.
  • T Nojiri, H Morita, Y Imai, K Maemura, M Ohno, K Ogasawara, T Aizawa, S Saito, D Hayashi, Y Hirata, T Sugiyama, T Yamazaki, R Nagai
    INTERNATIONAL JOURNAL OF CARDIOLOGY 92 2-3 181 - 186 2003年12月 [査読有り][通常論文]
     
    Matrix metalloproteinases (MMPs) are involved in plaque rupture, which is the main pathological cause of myocardial infarction (MI). Recently, several genetic studies have demonstrated that MMP-1 1G/2G polymorphism and MMP-3 5A/6A polymorphism modify each transcriptional activity in allele specific manners. Within this context, we conducted case-control studies to examine whether these genetic polymorphisms are associated with susceptibility to MI. Two groups comprising patients with MI (group-1 164 patients, group-2 302 patients) were compared with control group comprising 335 patients without cardiovascular diseases. The MMP-3 5A allele was more frequent in patients with MI than in the control subjects (P = 0.018 MI group-1, P = 0.0059 MI group-2), whereas there was no disease association for MMP-1 genotypes. Logistic regression analyses revealed that MMP-3 5A/6A polymorphism was associated with susceptibility to MI [odds ratio(OR) (95% confidential interval) 1.67 (1.02-2.74); P = 0.042, MI group-1; 1.61 (1.12-2.23); P = 0.0095, MI group-2]. Other important findings were that there was strong linkage disequilibrium between these polymorphisms, which are located closely on chromosome 11q.22, and that the 5A-1G haplotype was a genetic risk factor for MI (OR 1.97 P = 0.0082, MI group-1 OR 1.51 P = 0.017, MI group-2). Taken together, the present findings suggest that genetic variations in these MMP genes and especially their haplotype may be useful genetic markers for determining susceptibility to MI in Japanese. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
  • Yamano HO, Imai Y, Maeda S, Nakazato M, Matsushita HO, Yamanaka Y, Sato K
    Nihon rinsho. Japanese journal of clinical medicine 61 Suppl 7 156 - 163 2003年09月 [査読有り][通常論文]
  • T Harada, Y Imai, T Nojiri, H Morita, D Hayashi, K Maemura, K Fukino, D Kawanami, G Nishimura, K Tsushima, K Monzen, T Yamazaki, S Mitsuyama, T Shintani, N Watanabe, K Seto, T Sugiyama, F Nakamura, M Ohno, Y Hirata, T Yamazaki, R Nagai
    ATHEROSCLEROSIS 169 1 105 - 112 2003年07月 [査読有り][通常論文]
     
    Recently, variants in ATP-binding cassette transporter Al (ABCA1) were demonstrated to be associated with increased level of high density lipoprotein cholesterol (HDL-C) and decreased risk of coronary artery disease (CAD) in Caucasians. However, this is not universally applicable due to the ethnic or environmental differences. In this context, to clarify the effect of ABCAI in Japanese, we evaluated the phenotypic effects of I/M 823 and R/K 219 variants on the plasma level of HDL-C in 410 patients recruited in our hospital. Subjects with M 823 allele had significantly higher level of HDL-C than those without M823 allele (49.0 +/- 15.1 vs. 44.9 +/- 11.5 mg/dl, respectively, P < 0.05). This statistical significance did not change even after multiple regression analysis. In contrast, there was no difference in HDL-C level among the genotypes in R/K 219 polymorphism. Further, in our study population an inverse relationship was shown to exist between HDL-C level and incidence of CAD. However, no positive association was observed between those variants and susceptibility to CAD. In this study, we provide evidence that I/M 823 variant, not R/K 219 variant, in ABCA1 is one of the determinants of HDL-C level, suggesting the importance of this gene on lipid metabolism in Japanese. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
  • T Harada, H Morita, Y Imai, D Hayashi, N Takeda, K Maemura, Y Yazaki, R Nagai
    ANGIOLOGY 54 3 377 - 381 2003年05月 [査読有り][通常論文]
     
    Deficiency of protein S causes potential problems of thrombosis. Cases of familial venous thrombosis due to deficiency of protein S were presented. First, an 85-year-old woman had pulmonary thromboembolism due to left deep femoral venous thrombosis, which might be triggered by leg fracture and the long-term treatment with a plaster cast. Next, her 29-year-old granddaughter had episodes of recurrent venous thrombosis in her legs and arms, which might be triggered by the treatment with a plaster cast and abortion. In the latter part, the aspects of risks for thromboembolism, potential problems in gestational period, and an advisability of thromboprophylaxis in patients with deficiency of protein S are described.
  • T Yamauchi, J Kamon, H Waki, Y Imai, N Shimozawa, K Hioki, S Uchida, Y Ito, K Takakuwa, J Matsui, M Takata, K Eto, Y Terauchi, K Komeda, M Tsunoda, K Murakami, Y Ohnishi, T Naitoh, K Yamamura, Y Ueyama, P Froguel, S Kimura, R Nagai, T Kadowaki
    JOURNAL OF BIOLOGICAL CHEMISTRY 278 4 2461 - 2468 2003年01月 [査読有り][通常論文]
     
    The adipocyte-derived hormone adiponectin has been shown to play important roles in the regulation of energy homeostasis and insulin sensitivity. In this study, we analyzed globular domain adiponectin (gAd) transgenic (Tg) mice crossed with leptin-deficient ob/ob or apoE-deficient mice. Interestingly, despite an unexpected similar body weight, gAd Tg ob/ob mice showed amelioration of insulin resistance and beta-cell degranulation as well as diabetes, indicating that globular adiponectin and leptin appeared to have both distinct and overlapping functions. Amelioration of diabetes and insulin resistance was associated with increased expression of molecules involved. in fatty acid oxidation such as acyl-CoA oxidase, and molecules involved in energy dissipation such as uncoupling proteins 2 and 3 and increased fatty acid oxidation in skeletal muscle of gAd Tg ob/ob mice. Moreover, despite similar plasma glucose and lipid levels on an apoE-deficient background, gAd Tg apoE-deficient mice showed amelioration of atherosclerosis, which was associated with decreased expression of class A scavenger receptor and tumor necrosis factor alpha. This is the first demonstration that globular adiponectin can protect against atherosclerosis in vivo. In conclusion, replenishment of globular adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis.
  • K Hara, K Ohe, T Kadowaki, N Kato, Y Imai, K Tokunaga, R Nagai, M Omata
    JOURNAL OF HUMAN GENETICS 48 6 327 - 330 2003年 [査読有り][通常論文]
     
    As the number of the genetic studies has rapidly increased in recent years, there has been growing concern that the privacy of the participants in such studies can be invaded unless effective measures are adopted to protect confidentiality. It is crucial for the scientific community to establish a method to anonymize DNA samples so that the public will trust genetic researchers. Here, we present a reliable and practical method of making DNA samples used in the genetic research anonymous. It assures complete anonymity by coding samples and personal information twice. Since it does not require equipment, such as bar-code readers or a software package, its cost is nominal compared with the laboratory costs. All institutions engaged in genetic research may wish to take measures such as the one described here to ensure the privacy and confidentiality of the participants in their genetic studies.
  • Shindo T, Manabe I, Fukushima Y, Tobe K, Aizawa K, Miyamoto S, Kawai-Kowase K, Moriyama N, Imai Y, Kawakami H, Nishimatsu H, Ishikawa T, Suzuki T, Morita H, Maemura K, Sata M, Hirata Y, Komukai M, Kagechika H, Kadowaki T, Kurabayashi M, Nagai R
    Nature medicine 8 8 856 - 863 2002年08月 [査読有り][通常論文]
     
    We recently isolated a Kruppel-like zinc-finger transcription factor 5 (KLF5; also known as BTEB2 and IKLF), which is markedly induced in activated vascular smooth-muscle cells and fibroblasts. Here we describe our analysis of the in vivo function of KLF5 using heterozygous KLF5-knockout mice ( Klf5(+/-)). In response to external stress, Klf5(+/-) mice showed diminished levels of arterial- wall thickening, angiogenesis, cardiac hypertrophy and interstitial fibrosis. Also, angiotensin II induced expression of KLF5, which in turn activated platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta (TGF-beta) expression. In addition, we determined that KLF5 interacted with the retinoic-acid receptor (RAR), that synthetic RAR ligands modulated KLF5 transcriptional activity, and that in vivo administration of RAR ligands affected stress responses in the cardiovascular system in a KLF5-dependent manner. KLF5 thus seems to be a key element linking external stress and cardiovascular remodeling.
  • Y Imai, T Shindo, K Maemura, M Sata, Y Saito, Y Kurihara, M Akishita, J Osuga, S Ishibashi, K Tobe, H Morita, Y Oh-hashi, T Suzuki, H Maekawa, K Kangawa, N Minamino, Y Yazaki, R Nagai, H Kurihara
    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 22 8 1310 - 1315 2002年08月 [査読有り][通常論文]
     
    Objective-Several in vitro studies have implicated that adrenomedullin (AM) plays an important role in the pathogenesis of vascular injury and fatty streak formation. To test this possibility in vivo, we evaluated 2 experimental models using transgenic mice overexpressing AM in a vessel-selective manner (AMTg mice). Methods and Results-Placement of a periarterial cuff on femoral arteries resulted in neointimal formation at 2 to 4 weeks to a lesser extent in AMTg mice than in their wild-type littermates (at 28 days, intima/media area ratio 0.45+/-0.14 versus 1.31+/-0.41, respectively, P<0.001). This vasculoprotective effect observed in AMTg mice was inhibited by N-w-nitro-L-arginine methyl ester. We further examined the effect of AM on hypercholesterolemia-induced fatty streak formation by crossing AMTg mice with apolipoprotein E knockout mice (ApoEKO mice). The extent of the formation of fatty streak lesions was significantly less in ApoEKO/AMTg mice than in ApoEKO mice (percent lesion area 12.0+/-3.9% versus 15.8+/-2.8%. respectively; P<0.05). Moreover, endothelium-dependent vasodilatation as indicative of NO production was superior in AMTg/ApoEKO mice compared with ApoEKO mice. Conclusions-Taken together, our data demonstrated that AM possesses a vasculoprotective effect in vivo, which is at least partially mediated by NO.
  • Tomohiro Harada, Eiji Ohtaki, Ryuta Asano, Yasushi Imai, Tetsuya Sumiyoshi
    Journal of Cardiology 40 1 37 - 40 2002年07月 [査読有り][通常論文]
  • Y Imai, H Morita, H Kurihara, T Sugiyama, N Kato, A Ebihara, C Hamada, Y Kurihara, T Shindo, Y Oh-hashi, Y Yazaki
    ATHEROSCLEROSIS 149 2 435 - 442 2000年04月 [査読有り][通常論文]
     
    Paraoxonase 1 (PON1) is proposed to have an anti-atherogenic action. Two polymorphisms at the PON1 (M/L55 and Q/R192) have been shown to be associated with coronary artery disease (CAD). This conclusion is not drawn universally, however, and specific ethnic characteristics may be important determinants in this association. Recently two homologues of PON1 - PON2 and PON3 - were identified and Sanghera et al. demonstrated C/S311 polymorphism at PON2 was associated with the risk of CAD. Within that context, we investigated the association between the aforementioned three polymorphisms and CAD and ischemic stroke in a Japanese population. The study population included 431 control subjects, 210 CAD patients, and 235 ischemic stroke patients. Genotype distributions and allele frequencies of M/L55 and C/S311 were similar among the control and patient groups, whereas the R192 allele frequency was significantly higher (P < 0.001) in CAD (75%) and ischemic stroke (76%) patients than in control subjects (65%). When confounding influences of other risk factors were controlled for by multivariate analysis, R192 remained an independent risk determinant (additive model: OR (95% CI), P value CAD: 2.01 (1.45-2.79), 0.0001; ischemic stroke: 1.84 (1.34-2.52), 0.0002 (three genotypes into calculation)). Taken together, our data indicate that the Q/R192 is principally associated with both CAD and ischemic stroke in Japanese. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
  • Y. Imai, K. Hara, M. Yamasaki, K. Kozuma, H. Nakajima, H. Hara, F. Saeki, T. Tamura
    Journal of Cardiology 33 4 201 - 208 1999年 [査読有り][通常論文]
     
    Coronary artery aneurysm (CAA) occurs in 6-12% of lesions after directional coronary atherectomy (DCA). The prognosis and the optimal treatment for DCA-related CAAs have not been well known. Therefore, we reviewed the clinical course of 214 consecutive patients with DCA-related CAAs who underwent DCA in our hospital. Follow-up coronary angiography 6 months after DCA was completed in 193 patients (212 lesions)and 14 lesions with CAAs (14 patients) were detected. We evaluated these 14 lesions by repeat coronary angiography at an average of 32 months after DCA in comparison with the adjacent reference vessel. Twelve of the 14 patients have been uneventful but 2 suffered from de novo angina due to new stenotic lesion unrelated to the DCA procedures. We compared the preprocedual angiographic characteristics and periprocedural parameters between the 14 lesions with CAAs [CAA (+) group] and the 198 without CAAs [CAA (-) group], but found no significant differences. Histological examination of specimens retrieved during atherectomy demonstrated that subintimal resection was more frequent in the CAA(+)group(57%) than the CAA (-)group (31%). The diameter of the aneurysm divided by the reference diameter was significantly larger at 6 months immediately after DCA (1.71 ± 0.21 vs 1.31 ± 0.18, p < 0.05) but did not change subsequently (1.68 ± 0.23). Our retrospective analysis revealed a good mid-term (an average of 32 months) prognosis for CAAs found by routine follow-up coronary angiography and also demonstrated that the depth of resection was significantly associated with aneurysm formation.
  • Seko Y, Imai Y, Suzuki S, Kamijukkoku S, Hayasaki K, Sakomura Y, Tobe K, Kadowaki T, Maekawa H, Takahashi N, Yazaki Y
    Clinical science (London, England : 1979) 92 5 453 - 454 1997年05月 [査読有り][通常論文]

MISC

  • 高齢者心不全のトータルマネージメント
    原田 和昌, 安斉 俊久, 今井 靖, 絹川 弘一郎 Therapeutic Research 39 (1) 9 -16 2018年01月 [査読無し][通常論文]
  • 糖尿病患者の心房細動診療update CHADS2スコア、直接経口抗凝固薬(DOAC;Direct Oral AntiCoagulant)からablationまで
    横山 靖浩, 今井 靖 内分泌・糖尿病・代謝内科 45 (4) 300 -305 2017年10月 [査読無し][通常論文]
  • ペースメーカーからCRTへのアップグレード症例のQRS幅の変化の検討
    奥山 貴文, 甲谷 友幸, 横田 彩子, 小森 孝洋, 今井 靖, 苅尾 七臣 日本心臓病学会学術集会抄録 65回 P -267 2017年09月 [査読無し][通常論文]
  • 【循環器疾患薬物療法Trends & Topics 2017】 不整脈
    今井 靖 Mebio 34 (8) 12 -17 2017年08月 [査読無し][通常論文]
     
    <Point>不整脈の治療では非薬物療法として頻脈性不整脈に対するカテーテルアブレーションが普及し、わが国では年間5万例以上実施されている。また植込み型電子デバイスとしてのペースメーカー、植込み型除細動器、心臓再同期療法も同数程度実施され、その進歩が目覚ましい。代表的不整脈は心房細動であるが、直接経口抗凝固薬DOACの普及により抗凝固療法が様変わりし、非弁膜症性心房細動でかつ腎機能が高度に障害されていなければDOACが多用される時代となった。心房細動では器質的心疾患・心不全の有無に注意し、レートコントロール・リズムコントロールがなされる。期外収縮は多くは放置可能である。上室頻拍はベラパミル、アデノシン三リン酸で対処することが多い。心室頻拍は血行動態が破綻するものは速やかに除細動し、維持されるものではリドカイン・アミオダロン・ニフェカラントで対処する。器質的心疾患があるものは特に集学的対応を要する。(著者抄録)
  • トリメチルアミンNオキシドは心疾患患者の心臓リモデリングを反映し、予後予測マーカーとして有用である
    相澤 健一, 根岸 経太, 今井 靖, 苅尾 七臣, 永井 良三, 鈴木 亨 JSBMS Letters 42 (Suppl.) 75 -75 2017年08月 [査読無し][通常論文]
  • 【脳血管障害 診療のエッセンス】 脳血管障害の画像検査・血液学的検査 心電図
    今井 靖 日本医師会雑誌 146 (特別1) S144 -S147 2017年06月 [査読無し][通常論文]
  • 【動脈・静脈の疾患(上)-最新の診断・治療動向-】 動脈・静脈疾患(四肢体幹) Marfan症候群 Marfan症候群の診断
    神崎 綱, 今井 靖 日本臨床 75 (増刊4 動脈・静脈の疾患(上)) 397 -401 2017年05月 [査読無し][通常論文]
  • 【総合内科医の必修臨床問題182問】 循環器 (Question 64)40歳の女性 主訴「労作時呼吸困難と心雑音」
    今井 靖, 神崎 綱 Medicina 54 (4) 147 -149 2017年04月 [査読無し][通常論文]
  • 渡部 智紀, 甲谷 友幸, 渡辺 裕昭, 佐藤 彰洋, 小森 孝洋, 今井 靖, 三橋 武司, 苅尾 七臣 心臓 49 (2) 103 -109 2017年02月 [査読無し][通常論文]
     
    背景:Brugada症候群における心室性不整脈イベントにおいて就寝中や食後などの副交感神経活性との関連性が示唆されている。しかしながら不整脈発生時の状況およびtriggerとなる生活要因に関して、いまだ不明な点も多い。われわれはBrugada症候群における不整脈イベントの発生状況を検討した。方法:当院で植込み型除細動器(ICD)植込み術を施行したBrugada症候群連続32例を対象にICD適切作動を認めた患者背景を検討した。心室性不整脈に対しての適切動作を起こした9例と作動のなかった23例を比較検討した。ICD植込み前を含め心室性不整脈のみられた11例においてイベント発生時の血清カリウム値の関連について検討した。結果:適切作動と習慣性飲酒の関連性について検討した結果、適切作動群において有意に習慣性飲酒を多く認めた(適切作動群89%vs非作動群35%、p=0.002)。適切作動イベントに関するKaplan-Meyer生存曲線では、習慣性飲酒のある群において有意に適切作動を認めていた(Log rank 8.06、p=0.0045)。またICD植込み時と比して心室性不整脈発生時には有意に血清カリウム値が低かった(血清K濃度4.4±0.2vs3.4±0.4mmol/L、p<0.0001)。結論:Brugada症候群における不整脈イベントと飲酒との関連性を認めた。低カリウム血症が不整脈イベントの一因であるかどうかは不明であるが、就寝前の高炭水化物食の摂取やアルコールの摂取が不整脈イベントに関係している可能性が示唆された。(著者抄録)
  • 【Beyond the textbook 心電図 実践診療で役立つコツ】 12誘導心電図を読み解くコツ 注意すべき心電図変化のエトセトラ 心臓周囲・非心臓疾患も想定を
    今井 靖 診断と治療 105 (2) 219 -222 2017年02月 [査読無し][通常論文]
  • TOF修復術後3回目のTVR 人工弁の選択と併用手技
    河田 政明, 吉積 功, 片岡 功一, 久保田 香菜, 今井 靖 日本成人先天性心疾患学会雑誌 6 (1) 110 -110 2017年01月 [査読無し][通常論文]
  • 心房間での右左短絡を有する成人Ebstein奇形に対する治療戦略
    岡 健介, 片岡 功一, 鈴木 峻, 松原 大輔, 佐藤 智幸, 南 孝臣, 吉積 功, 河田 政明, 久保田 香菜, 今井 靖之, 山形 崇倫 日本成人先天性心疾患学会雑誌 6 (1) 134 -134 2017年01月 [査読無し][通常論文]
  • 【大動脈解離の診断と治療の最近の動向】 大動脈解離の遺伝子解析 Marfan症候群と類縁疾患
    根岸 経太, 今井 靖 カレントテラピー 34 (9) 860 -866 2016年09月 [査読無し][通常論文]
  • 高血圧治療を臓器管理に生かす 高血圧を合併した心房細動のトータルマネージメント
    今井 靖, 苅尾 七臣 日本心臓病学会学術集会抄録 64回 S5 -5 2016年09月 [査読無し][通常論文]
  • 初診時に巨大陰性T波を認めた若年の特発性心室頻拍の1例
    有馬 生悟, 甲谷 友幸, 小森 孝洋, 今井 靖, 苅尾 七臣 日本心臓病学会学術集会抄録 64回 P -529 2016年09月 [査読無し][通常論文]
  • 久保田 香菜, 矢野 裕一朗, 村田 光延, 今井 靖, 新保 昌久, 苅尾 七臣 心臓 48 (8) 966 -972 2016年08月 [査読無し][通常論文]
     
    症例は52歳の男性。拡張型心筋症の経過中にうっ血性心不全をきたし、夜間就寝中に心室細動(ventricular fibrillation;VF)の頻発を認めた。VFをきたした際に著しい低CO2血症、および呼吸性アルカローシスを呈しており、その原因としては重症の中枢性睡眠時無呼吸による無呼吸の後に引き続く一過性過呼吸が原因と考えられた。突然死回避のため植込み型除細動器(implantable cardioverter defibrillator;ICD)を挿入した上で、無呼吸に対してadaptive servo ventilation(ASV)導入を行ったところ心室性不整脈の頻度は著減した。今回われわれは、著しい低CO2血症または呼吸性アルカローシスがVFのトリガーになったと思われる症例を経験したので文献的考察を加え報告する。(著者抄録)
  • 【そこが識りたい補助循環-現場で活かすbest strategy-】 識る CRT-Dの至適病態とその限界
    今井 靖 Heart View 20 (4) 342 -348 2016年04月 [査読無し][通常論文]
  • 【内科診断の道しるべ-その症候、どう診る どう考える】 胸部 動悸・脈拍異常
    今井 靖 Medicina 53 (4) 236 -239 2016年04月 [査読無し][通常論文]
  • 久保田 香菜, 今井 靖 内科 117 (4) 797 -803 2016年04月 [査読無し][通常論文]
  • 滝 瑞里, 小森 孝洋, 今井 靖, 苅尾 七臣, 河田 政明 循環器専門医 24 (1) 116 -122 2016年02月 [査読無し][通常論文]
     
    症例は68歳女性で、小学6年時に健診で雑音を指摘されたが経済的理由で精査をしなかった。問題なく運動は可能で、同年代と比べ息切れしやすい自覚もなかった。60歳頃から下腿浮腫、口唇チアノーゼを認め、入院半年前から、徐々に労作性息切れ、下腿浮腫増悪を自覚して受診し、心不全の診断で入院した。意識レベルJCS0、血圧164/77mmHg、心拍数76拍/分・整、呼吸数16回/分、体温37.1℃、経皮的酸素飽和度(自発呼吸、酸素鼻カヌラ4L/分)82%であった。眼瞼結膜に貧血なく、眼球結膜に黄疸なく、顔面浮腫あり、頸静脈怒張ありであった。心音不整、IIp音亢進、頸部への放散を伴わない胸骨左縁第3肋間を最強点とするLevine III/IVの収縮期駆出性雑音を聴取し、呼吸音は両側で減弱していた。入院時検査から重症肺動脈弁狭窄症および三尖弁狭窄兼閉鎖不全症による慢性心不全の急性増悪、および心拡大に伴う肺容積減少によるII型呼吸不全と診断し、フロセミド、ドパミン静注を開始し、NIPPV装着を行った。NIPPVはBiPAPモードで、IPAP/EPAP 8/4mmHg、FiO2 1.0の設定で経皮的酸素濃度90%前半をどうにか維持できた。治療開始後、利尿反応は良好で、約1週間で体重は3kg減少し、下腿浮腫は消失した。酸素化の改善は乏しかったためスピロノラクトン25mg/日内服を追加しさらに利尿を図ったが、低拍出量症候群となり腎機能障害の悪化、肝機能障害の出現を認めた。内科的治療は限界と判断し、外科手術しかないと考え、患者も希望したため、第58病日に手術を行った。術後1日目には抜管でき、その後内服調整、リハビリを行い全身状態が徐々に改善した。第82病日、酸素投与なしで経皮的酸素濃度95%前後を保てるようになり、独歩で退院し、外来通院中である。
  • 血管型ミオシン(MYH11)欠失変異による日本人大動脈解離・動脈管開存症家系の経験 家族性大動脈解離における遺伝子診断の意義
    今井 靖, 森田 啓行, 武田 憲文, 藤田 大司, 兵藤 博信, 河田 政明, 苅尾 七臣, 平田 恭信, 永井 良三, 小室 一成 日本成人先天性心疾患学会雑誌 5 (1) 72 -72 2016年01月 [査読無し][通常論文]
  • 成人先天性心疾患のチーム医療における小児集中治療部(PICU)の役割
    片岡 功一, 河田 政明, 佐藤 智幸, 松原 大輔, 横溝 亜希子, 岡 健介, 古井 貞浩, 安済 達也, 南 孝臣, 大塚 洋司, 永野 達也, 中村 文人, 岩井 英隆, 原 鉄人, 多賀 直行, 今井 靖, 前川 慶之, 吉積 功, 竹内 護 日本成人先天性心疾患学会雑誌 5 (1) 78 -78 2016年01月 [査読無し][通常論文]
  • 成人期に施行したAVSDに対する再手術
    河田 政明, 前川 慶之, 吉積 功, 片岡 功一, 佐藤 智幸, 大塚 洋司, 多賀 直行, 竹内 護, 久保田 香菜, 今井 靖 日本成人先天性心疾患学会雑誌 5 (1) 110 -110 2016年01月 [査読無し][通常論文]
  • アイゼンメンジャー症候群患者の在宅療養への取り組み
    久保田 香菜, 今井 靖, 苅尾 七臣 日本成人先天性心疾患学会雑誌 5 (1) 127 -127 2016年01月 [査読無し][通常論文]
  • 【新しい循環器病のバイオマーカー-臨床的意義を理解する-】 オーバービュー 大規模臨床試験に際してのバイオマーカー測定の意義について
    横山 靖浩, 今井 靖 Heart View 19 (12) 16 -21 2015年11月 [査読無し][通常論文]
  • 今井 靖, 藤田 大司, 武田 憲文, 西村 敬史, 加藤 昌義, 鈴木 淳一, 小室 一成, 平田 恭信 脈管学 55 (Suppl.) S105 -S105 2015年10月 [査読無し][通常論文]
  • 【心臓弁膜症-初期診断・治療・管理のすべて】 心臓弁膜症診療の温故知新
    今井 靖, 大門 雅夫, 林 同文, 竹谷 剛 内科 116 (3) 479 -491 2015年09月 [査読無し][通常論文]
  • 高齢になって自覚症状が出現し手術に至った先天性肺動脈二尖弁の一例
    滝 瑞里, 小森 孝洋, 今井 靖, 新保 昌久, 苅尾 七臣, 河田 政明 日本心臓病学会学術集会抄録 63回 85 -85 2015年09月 [査読無し][通常論文]
  • 【循環器疾患のtrends & topics 2015】 循環器遺伝子診療の新展開
    今井 靖, 藤田 大司 Mebio 32 (7) 82 -90 2015年07月 [査読無し][通常論文]
  • 森 絵美, 細谷 弓子, 今井 靖, 大橋 俊則, 田澤 英克, 馬渡 和真, 森田 啓行, 北森 武彦 分析化学 64 (6) 461 -468 2015年06月 [査読無し][通常論文]
     
    マイクロフルイディクス(微小流体工学)と熱レンズ顕微鏡を応用して酵素結合免疫測定(enzyme-linked immunosorbent assay:ELISA)をシステム化した新しい機能デバイス(μELISA)を開発した。μELISAは、これまでの研究成果で、ヒト血清でも優れた性能を発揮してきた。しかしながら、様々な患者検体でマイクロリットルオーダーの微量分析を行う場合には、患者ごとに異なる検体の成分組成や粘度の違いによる影響などが課題となる可能性がある。本研究では、測定対象とするマーカーをC反対性タンパク(CRP)として、実際の患者血清に対して考慮すべき測定条件を検討した。その結果、マイクロ流体系では検体に由来する影響があることが分かり、信頼性のある測定値を得るためには、緩衝液にて希釈をする必要があることが分かった。(著者抄録)
  • 【疾患バイオマーカー】 循環器分野におけるバイオマーカー
    横山 靖浩, 今井 靖 細胞 47 (3) 115 -119 2015年03月 [査読無し][通常論文]
     
    近年、循環器診療における各種バイオマーカーは多岐にわたっており臨床の現場で広く活用されており、循環器救急の診療の場において各種疾患の診断や予後予測、治療効果判定など客観的な評価が可能である。本稿においてはその中でも虚血性心疾患、心不全、肺塞栓、大動脈解離におけるバイオマーカーを中心に概説をする。(著者抄録)
  • 【心不全のすべて】 心不全に関連する不整脈 心不全に合併する不整脈
    今井 靖, 甲谷 友幸, 苅尾 七臣 診断と治療 103 (Suppl.) 302 -304 2015年03月 [査読無し][通常論文]
     
    心不全においては心房細動、心室期外収縮、心室頻拍など、多くの不整脈が認められ、その不整脈が多いほど予後不良である。一方で、不整脈を減少させることの努力は必ずしも予後を改善するものではなく、心不全自体の管理が重要である。β遮断薬、レニン-アンジオテンシン系抑制薬、必要に応じて利尿薬投与といった標準的心不全治療を行い、不整脈管理のために必要な場合にはアミオダロンに代表されるIII群抗不整脈薬の使用、心房細動、心室頻拍などに対するカテーテルアブレーション、致死的転帰を回避するためのICD、心臓再同期を改善させるCRTなどの非薬物治療を含めた集学的な管理が求められる。(著者抄録)
  • 【循環器系の人工臓器】 ペースメーカーの最近の進歩
    渡邉 裕昭, 今井 靖, 小森 孝洋, 甲谷 友幸, 苅尾 七臣 医学と薬学 72 (3) 405 -416 2015年02月 [査読無し][通常論文]
  • マルファン症候群 フィブリリン変異と臨床表現型
    藤田 大司, 武田 憲文, 加藤 昌義, 西村 敬史, 犬塚 亮, 今井 靖, 平田 恭信, 小室 一成 日本成人先天性心疾患学会雑誌 4 (1) 67 -67 2015年01月 [査読無し][通常論文]
  • 【それって本当?最近、気になる循環器の七つの疑問】 β遮断薬は呼吸器疾患に必ずしも禁忌でなくなったか?
    今井 靖 メディカル朝日 43 (12) 16 -17 2014年12月 [査読無し][通常論文]
  • 横田 彩子, 今井 靖 人工臓器 43 (3) 161 -166 2014年12月 [査読無し][通常論文]
  • 【ここが知りたい循環器診療-パールとピットフォール】 救急でよくみる循環器疾患 発作性心房細動への対応
    渡部 智紀, 今井 靖 Medicina 51 (9) 1662 -1668 2014年09月 [査読無し][通常論文]
     
    <パールとピットフォール>◎発作性心房細動をみたら,バイタルが安定しているか,心不全がないか,緊急性を判断する.◎心房細動治療において,まず抗凝固療法の適応の有無について評価する.◎心機能や左房拡大の有無,持続時間などに応じて洞調律維持か心拍数調整かを選択する.◎wide QRSの頻脈性心房細動に要注意.◎困ったら,迷わず循環器内科専門医へ相談を(そのままにしない).(著者抄録)
  • 脳卒中予防におけるアピキサバンの実力を検証する
    山下 武志, 今井 靖, 藤生 克仁, 三谷 治夫 Pharma Medica 32 (8) 101 -107 2014年08月 [査読無し][通常論文]
  • 藤田 大司, 武田 憲文, 今井 靖, 平田 恭信 日本臨床 72 (6) 1163 -1171 2014年06月 [査読無し][通常論文]
     
    マルファン症候群(MFS)はこれまで症候群としてとらえられてきたが、類縁疾患を含めた遺伝子解析の幾つかが可能となり、疾患概念の再構築が進められている。今後は、フィブリリン-1という結合組織を構成する蛋白の異常に伴う物理的構造・強度の障害という側面と、トランスフォーミング増殖因子βシグナル伝達経路の異常に伴う細胞分化の障害、標的蛋白の機能破綻などの側面などから、この疾患を理解してゆく必要がある。MFSに関する研究の歴史、現時点で判明している病態生理、診断基準や治療法について概説した。
  • 【虚血性心疾患up to date-内科医によるトータルマネジメント】 虚血性心疾患診療の最近の動向
    今井 靖, 丹沢 俊弘, 安東 治郎, 杉下 靖之 Medicina 51 (4) 574 -584 2014年04月 [査読無し][通常論文]
  • 遺伝性大動脈疾患における妊娠中の大動脈解離のリスクについての鑑別診断を含めた考察
    兵藤 博信, 矢部 慎一郎, 今井 靖, 井上 恵莉, 山下 隆博, 山中 美智子, 百枝 幹雄, 藤井 知行, 森本 康子, 丹羽 公一郎 日本成人先天性心疾患学会雑誌 3 (1) 81 -81 2014年01月 [査読無し][通常論文]
  • 【不整脈の診断と治療-ポイントをおさえよう】 不整脈の治療 患者を前に ICDの適応と植込みの実際
    嵯峨 亜希子, 今井 靖 Medicina 50 (13) 2222 -2226 2013年12月 [査読無し][通常論文]
     
    <ポイント>植込み型除細動器の適応は,致死性心室性不整脈の再発予防(二次予防)とハイリスク症例に対する予防的適応(一次予防)に分けられる.植込み型除細動器の適応が考えられる症例は速やかに専門医へ紹介する.日本循環器学会が示すガイドラインを参照し,患者の臨床的,社会的背景も考慮し最終的な判断を行う.(著者抄録)
  • 人工臓器 最近の進歩 ペースメーカに関する最近の話題
    今井 靖 人工臓器 42 (3) 181 -183 2013年12月 [査読無し][通常論文]
  • 標準12誘導心電図から導出した起電力心電図の臨床的有用性に関する検討
    假屋 太郎, 今井 靖, 藤生 克仁 福田記念医療技術振興財団情報 (25) 49 -62 2012年12月 [査読無し][通常論文]
  • 【循環器病のバイオマーカー】 オーバービュー 大規模臨床試験にみるバイオマーカー
    今井 靖, 山崎 力 Heart View 16 (12) 16 -20 2012年11月 [査読無し][通常論文]
     
    循環器疾患は生活習慣病に根ざすものが多く、予後についてはイベント発生が相対的に低いことが予想される。そのため、心血管イベント発生での差異を評価するまでの時間・コストといった観点からすればバイオマーカーが臨床試験の評価項目として活用されることも少なくない。即ち、バイオマーカー自体をエンドポイントとする臨床試験も多い。心不全に関する大規模臨床試験とそこで活用されるバイオマーカー、動脈硬化に関する大規模試験とバイオマーカーについて述べた。
  • カフレス・ウェアラブル血圧センシングを用いた自由行動下での高齢者高血圧管理の試み
    飯島 勝矢, Lopez Guillaume, 酒造 正樹, 山田 一郎, 柳元 伸太郎, 今井 靖, 稲島 司, 矢作 直樹, 秋下 雅弘, 大内 尉義 日本高血圧学会総会プログラム・抄録集 35回 450 -450 2012年09月 [査読無し][通常論文]
  • バイオマーカーを使って日本の臨床試験を活性化する 心疾患におけるバイオマーカーと臨床試験における活用
    今井 靖, 山崎 力 日本内分泌学会雑誌 88 (2) 801 -801 2012年09月 [査読無し][通常論文]
  • ARID5Bヘテロ欠損マウスは高脂肪食下で肥満が抑制されインスリン抵抗性は改善した
    大関 敦子, 渡辺 昌文, 眞鍋 一郎, 王 国琴, 今井 靖, 山内 敏正, 原 一雄, 渡邉 綾, 河原崎 秀一, 前村 浩二, 門脇 孝, 山崎 力, 永井 良三 肥満研究 18 (Suppl.) 144 -144 2012年09月 [査読無し][通常論文]
  • 心血管疾患発症進展における遺伝・環境的要因 歯周病と心血管疾患の関連 マルファン症候群患者における観察とマウス大動脈瘤モデルでの検討
    鈴木 淳一, 今井 靖, 磯部 光章, 永井 良三, 平田 恭信 日本心臓病学会誌 7 (Suppl.I) 186 -186 2012年08月 [査読無し][通常論文]
  • 脈波伝播速度法による持続的収縮期血圧推定デバイスの臨床的有用性
    稲島 司, 今井 靖, 酒造 正樹, Lopez Guillaume, 柳元 伸太郎, 飯島 勝矢, 森田 啓行, 永井 良三, 矢作 直樹, 山田 一郎 日本心臓病学会誌 7 (Suppl.I) 324 -324 2012年08月 [査読無し][通常論文]
  • 【知っておきたい内科症候群】 循環器《先天性疾患》 マルファン症候群
    藤田 大司, 今井 靖, 平田 恭信 内科 109 (6) 1059 -1061 2012年06月 [査読無し][通常論文]
  • 【内科医が知っておくべき最新医療機器(1)】 循環器 ペースメーカ、植込み型除細動器、心臓再同期療法
    今井 靖, 永井 良三 診断と治療 100 (1) 91 -99 2012年01月 [査読無し][通常論文]
  • 高度大動脈弁狭窄症を呈し人工弁置換術を施行したアルカプトン尿症の1例
    沼田 玄理, 今井 靖, 田中 悌史, 稲島 司, 山下 尋史, 絹川 弘一郎, 平田 恭信, 永井 良三, 齋藤 綾, 小野 稔 日本内科学会関東地方会 583回 31 -31 2011年11月 [査読無し][通常論文]
  • 青木 美穂子, 今井 靖, 藤田 大司, 小川 直美, 加藤 昌義, 西村 敬史, 鈴木 淳一, 平田 恭信, 永井 良三 呼吸と循環 59 (9) 939 -942 2011年09月 [査読無し][通常論文]
     
    マルファン症候群は,骨格異常,眼異常,心血管異常など多くの器官に病変を引き起こす常染色体優性遺伝の全身性結合組織疾患である.以前より口腔内所見として,高口蓋,歯列不正などが知られている.近年,諸外国においてマルファン症候群と歯周病との関係が注目されてきており,日本人におけるマルファン症候群の実態調査としてGhent基準陽性20名のマルファン症候群症例につき歯周病罹患状態を評価した.現在歯数は27歯とほぼ保たれていたが,歯周ポケットの深さ(PD)は2.815±0.624mm,PD測定部位での出血の有無(BOP)は11.567±8.394%,地域歯周疾患指数(CPI)は中等度・重度に該当するコード3,4の症例が15名(75%)も認められた.以上よりマルファン症候群では,中等度から重度の歯周病が高頻度に認められマルファン症候群における歯周組織の脆弱性が示唆された.(著者抄録)
  • 【大動脈疾患の最新知見】 非動脈硬化性遺伝性疾患 Marfan症候群と関連疾患
    藤田 大司, 今井 靖, 平田 恭信 最新医学 66 (7) 1655 -1663 2011年07月 [査読無し][通常論文]
     
    Marfan症候群は,大動脈病変,眼症状,骨格異常を主徴とする常染色体優性遺伝疾患である.原因として結合組織を構成するfibrillin 1の遺伝子異常が同定されており,またTGFβの活性化の関与も判明してきている.従来の身体的特徴をもととした診断基準から,原因遺伝子や分子メカニズムを考慮した新基準に移行しつつあり,類縁疾患の概念の確立や診断・治療方法の進歩が期待される.(著者抄録)
  • Bedside Teaching IgG4と循環器疾患
    今井 靖, 永井 良三 呼吸と循環 59 (5) 499 -505 2011年05月 [査読無し][通常論文]
  • 嵯峨 亜希子, 今井 靖, 杉山 裕章, 小島 敏弥, 藤生 克仁, 海老原 文, 安喰 恒輔, 絹川 弘一郎, 山下 尋史, 平田 恭信, 永井 良三 心臓 43 (5) 670 -677 2011年05月 [査読無し][通常論文]
     
    41歳、男性。生後、修正大血管転位(congenitally corrected transposition of the great arteries;cc-TGA)、心室中隔欠損(ventricular septal defect;VSD)を指摘され、VSD閉鎖術を施行。その後、三尖弁閉鎖不全が悪化し33歳時に三尖弁置換術を施行された。2008年10月突然心肺停止となり、蘇生に成功したが解剖学的右室の著明な収縮低下による心不全管理に難渋した。高度心不全治療を目的に2009年2月当院へ転院となったが、極度の悪液質、開放創(胃瘻)やMRSA保菌もあり、心移植や補助人工心臓は適応外とされた。著明な心室内伝導障害とともに、組織ドプラ法で収縮非同期を認めたため、心臓再同期療法(cardiac resynchronization therapy;CRT)を導入した。植え込みは冠静脈リードの留置も容易で内科的に施行可能であった。CRT治療後、自覚症状およびBNP値が著明に改善し、カテコラミンからも離脱し得た。成人期に達したcc-TGAでは体心室の適応破綻による心不全管理にしばしば難渋するが、同病態に対し、CRTが極めて有効な治療となり得ることを示唆する貴重な症例と考えられたため、報告する。(著者抄録)
  • 【薫風吹く膠原病診療-臨床を駆ける進歩の風】 特殊病態診療の進歩 膠原病に伴う心病変とその治療
    今井 靖, 永井 良三 内科 107 (4) 623 -629 2011年04月 [査読無し][通常論文]
     
    ・膠原病では心血管関連合併症の頻度は高く、膠原病の予後に大きく関与する。・SLEでは心臓弁膜症、心外膜炎、心筋炎、冠動脈疾患の合併に注意する。・多発性筋炎・皮膚筋炎では心筋炎の合併があり、心不全・不整脈などをきたす。・強皮症では心筋線維化・心筋障害、心嚢液貯留、肺高血圧に注意する。・血管炎や血栓症を伴う膠原病では、多彩な心血管系疾患を伴う。・RAやSLEなどの膠原病では、動脈硬化性冠動脈疾患が高頻度である。(著者抄録)
  • 嚥下性失神に対するペーシング治療
    杉山 裕章, 今井 靖, 藤生 克仁, 小島 敏弥, 鈴木 健樹, 永井 良三, 横田 順, 長谷川 菜美, 宮崎 進, 村澤 孝秀 Therapeutic Research 32 (4) 479 -482 2011年04月 [査読無し][通常論文]
     
    嚥下性失神はまれな状況失神の一つであり、ペーシング治療がときに有効である。今回、われわれが経験した2症例を提示し、嚥下性失神の診断、ペースメーカー適応や問題点などにつき文献的知見と併せて報告する。症例1:32歳、男性。既往症なし。友人と飲酒時に痙攣を伴う失神発作を生じ近医受診。その後の精査で頭蓋内疾患や器質的心疾患は認めなかったが、ホルター心電図にて夕食時に最大2.5秒の洞停止を指摘された。その後、約3ヵ月間に計3回の失神発作を生じ、精査目的にて当院紹介。心臓電気生理学的検査(EPS)では洞機能および房室伝導能は正常であったが、水分摂取時に一致して洞停止および房室ブロックを認め、最大2.8秒のR-R間隔の延長、血圧低下を生じた。硫酸アトロピン静注により同現象は消失した。嚥下性失神を疑い、この時点でペースメーカー植込みが考慮された。しかし、最大R-R間隔延長が著明ではなく、失神との関係も明確ではないため、植込み型ループ心電計(ILR)にて失神時のR-R間隔の同定、薬物療法の効果判定を行う方針とした。症例2:70歳、男性。陳旧性心筋梗塞、高血圧で加療中。夕食時およびコーヒー摂取中に意識消失を認め、精査目的にて当院紹介。ホルター心電図にて最大2.6秒の洞停止、心エコーにて下後壁の壁運動低下を認めた。Head-up tilt試験は異常なく、冠動脈造影検査では右冠動脈ステント留置部に50%狭窄を認めるのみであった。EPSでは洞機能・房室伝導障害ともに認めず、心室性不整脈も誘発不能であった。嚥下時には最大2.1秒の洞停止および左脚ブロックを生じたが、めまいや失神、血圧低下は認めなかった。症例1と同様、徐脈と失神との関係も不明確なためILR植え込み予定としていたが、その後の経過中に早朝ベッド上で飲水した際、前失神症状に一致して約7.5秒の洞停止が記録された。嚥下性失神と診断し、rate-drop response(RDR)機能付きペースメーカー植込みを行った。術後は失神の再発なく経過している。(著者抄録)
  • 嵯峨 亜希子, 今井 靖, 杉山 裕章, 小島 敏弥, 藤生 克仁, 海老原 文, 安喰 恒輔, 絹川 弘一郎, 山下 尋史, 平田 恭信, 永井 良三 Shinzo 43 (5) 670 -677 2011年 [査読無し][通常論文]
  • 杉山 裕章, 今井 靖, 藤生 克仁, 鈴木 健樹, 縄田 寛, 小野 稔, 絹川 弘一郎, 平田 恭信, 永井 良三 心電図 30 (5) 402 -409 2010年12月 [査読無し][通常論文]
     
    症例は31歳,男性.24歳時より心筋炎後の心機能低下による難治性心不全をくり返し,左心補助装置などを経て29歳時に心臓移植が施行された.2010年4月,移植2年後の各種検査施行目的にて入院.心臓カテーテル検査では左室壁運動異常なく,有意な冠動脈狭窄病変も認めなかった.一方,入院時より徐脈が遷延しており,一過性に「完全房室ブロック」と思われる心電図波形を示した.電気生理学的検査(EPS)では,移植されたドナー心および残存するレシピエント心由来と思われる2種類の心房電位を認め,後者はドナー心から電気的に隔離されていた.ドナー心の房室伝導能は正常ながら,著明な洞結節機能不全が示唆された.心房高頻度刺激後には洞停止のため房室接合部補充調律を示し,レシピエント心由来のP波が存在するため,体表心電図上は「完全房室ブロック」様の所見を呈したものと考えられた.<BR>本症例は心移植後に合併する徐脈性不整脈にEPSを行い,その主病態が房室ブロックではなく洞結節機能不全と診断でき,貴重と考えられたため報告する.
  • 【虚血性心疾患 プライマリケアは内科医が担う】 虚血性心疾患の救急診療 救急外来での初期診療
    今井 靖 Medicina 47 (9) 1566 -1571 2010年09月 [査読無し][通常論文]
     
    <ポイント>★患者の来院前からすでに情報収集は始まっている.症状,検査所見から速やかに急性循環器疾患の鑑別を行う.★心電図,X線,エコー,血液検査など,一連の検査を迅速に行う.検査所見が陰性でも疑わしいときには経過観察を.★急性心筋梗塞の初期治療としてMONA[モルヒネ(M),酸素(O),硝酸薬(N),アスピリン(A)]を忘れないようにする.(著者抄録)
  • 【事例に学ぶ。実践、臨床応用研究の進め方】 臨床応用の取り組みにかかる事例 アカデミアにおけるTR支援体制の必要性
    小池 恒, 今井 靖, 永井 良三 遺伝子医学MOOK (17) 78 -83 2010年05月 [査読無し][通常論文]
     
    新たな疾患の予防や治療,診断技術の開発をテーマとして研究を行っている医学研究者に対して,医学研究におけるトランスレーショナルリサーチの実践に必要な情報や考え方を紹介し,トランスレーショナルリサーチ推進のための支援組織のあり方を提案する。特に,アカデミアで多く行われる先端生命科学領域(遺伝子治療や再生医療など)について,臨床研究を倫理的・科学的に質の高い臨床研究として行うための考え方についても述べてみたい。(著者抄録)
  • ウェアラブルな血圧モニタリングシステムの医療現場での応用
    柳元 伸太郎, 今井 靖, 酒造 正樹, ロペズ・ギヨーム, 亀山 祐美, 飯島 勝矢, 秋下 雅弘, 大内 尉義, 矢作 直樹, 山田 一郎 ITヘルスケア 5 (1) 65 -68 2010年05月 [査読無し][通常論文]
     
    メタボリック症候群(MetS)に代表される生活習慣病は動脈硬化を介して脳血管障害、心血管障害発症のリスクを高めることが知られている。特にMetSの構成因子の中でも高血圧は有病者が多く、脳・心血管病の最大の危険因子である。現在、高血圧症のスクリーニングは健康診断や一般外来などにおける単回の血圧測定が中心だが、仮面高血圧や白衣高血圧などの存在や血圧変動の有無を把握することができず、十分な診断や管理が出来ていないのが現状である。また、血圧の日内変動の把握に従来からいくつかの方法が用いられているが、問題点も指摘されている。我々は脈波伝播速度を用いて連続的に血圧をモニタできるシステムを開発し、臨床への応用を進めているところである。現在開発中のモニタリングシステムの既存のシステムに対する優位性、非劣性について検証を進めており、これについて報告する。また、本システムを活用した医療サービスや臨床研究について実情や今後の展望を紹介する。(著者抄録)
  • 杉山 裕章, 今井 靖, 海老原 文, 藤生 克仁, 平田 恭信, 永井 良三, 田中 信大, 山科 章 心電図 = Electrocardiology 30 (1) 63 -72 2010年03月 [査読無し][通常論文]
     
    症例は41歳,男性.生後,修正大血管転位(C-TGA),心室中隔欠損(VSD),右胸心の指摘を受け,2歳時にVSD閉鎖術,33歳時に三尖弁置換術(TVR)が施行された.以後,心機能低下はあるものの心不全の顕在化なく経過していたが,2008年10月,突然心肺停止となった.搬送先で蘇生されたが,体心室(解剖学的右室)の収縮能低下を伴う心不全管理に難渋し,カテコラミン依存状態となった.当院転院後,非薬物療法の検討が行われたが,悪液質,MRSA保菌や胃瘻の存在もあり,補助人工心臓・心臓移植が躊躇された.他方,心室内伝導障害と体心室の収縮非同期を認めたため心室再同期療法(CRT)を先行導入したところ,著効を示しカテコラミンからも離脱しえた.成人期に達したC-TGAにおける体心室の適応破綻はしばしば問題となるが,本症例は補助循環も考慮されるほどの最重症心不全に対してもCRTが著効する場合があることを示唆した貴重な症例と考える.
  • 今井 靖, 永井 良三 日本内科学会雑誌 99 (2) 219 -221 2010年02月 [査読無し][通常論文]
  • 今井 靖, 小川 直美, 西村 敬史, 加藤 昌義, 武田 憲文, 平田 恭信, 縄田 寛, 竹谷 剛, 師田 哲郎, 高本 眞一 呼吸と循環 57 (11) 1099 -1103 2009年11月 [査読無し][通常論文]
  • 杉山 裕章, 今井 靖, 藤生 克仁, 岩田 洋, 平田 恭信, 永井 良三 心電図 = Electrocardiology 29 (4) 298 -305 2009年10月 [査読無し][通常論文]
     
    症例は 22歳,男性.心疾患既往,突然死家族歴ともになし.大学構内でアメリカン・フットボール練習中に心肺停止となり救急要請後,自動体外除細動器(AED)にて蘇生された.心電図,心エコー,心臓 MRIはほぼ正常であり,冠動脈 CTでも特記すべき病変なし.電気生理学的検査では致死性不整脈は誘発されず,ピルジカイニド負荷試験も陰性であったが,electroanatomical(CARTO™)mappingで右室流出路に低電位領域を認め,心室遅延電位も陽性を示した.スポーツ種などからは心臓震とうが考慮されたが,不整脈原性右室心筋症をはじめとする心疾患も完全には否定できず,本人・家族の希望もあり植込み型除細動器(ICD)移植の方針とした.その後1年半の経過観察で,計 4回の ICD適正作動を認めている.本症例は運動中の突然死予防,AED設置拡充および競技関係者への心肺蘇生法普及を考えるうえで種々の示唆に富むと思われる.
  • 杉山 裕章, 佐原 真, 今井 靖, 松岡 理恵, 廣井 透雄, 平田 恭信, 永井 良三, 小野 稔, 高本 眞一, 岡本 耕, 小池 和彦, 菊池 賢 心臓 41 (10) 1102 -1108 2009年10月 [査読無し][通常論文]
     
    症例は64歳、土木作業員の男性。3ヵ月前からの労作時息切れ、倦怠感を主訴に来院した際、大動脈弁への疣腫付着と重症大動脈弁閉鎖不全を指摘され入院となった。直前の歯科処置歴なし、感染性心内膜炎(IE)が最も疑われたが、発熱に乏しく炎症所見も軽度で血液培養はすべて陰性であった。一方、血管炎を示唆する下腿紫斑や糸球体腎炎による腎機能増悪とともに細胞質型抗好中球細胞質抗体(c-ANCA)陽性を示した。血液培養陰性心内膜炎を想定しceftriaxoneおよびgentamicinによる抗菌薬治療を開始した後、Bartonella抗体陽性と判明したためdoxycyclineを追加し待機的に大動脈弁置換術を施行した。摘出弁検体による培養および組織診でもBartonella属は証明されなかったが、PCR(polymerase chain reaction)法を用いた制限酵素断片長多型(RFLP)解析により起炎菌はB.quintanaと判明した。近年、Bartonella属は血液培養陰性IEの起因菌として認識されつつあるが、診断法の困難性などから本邦での報告は稀少である。さらには高力価c-ANCAとともに細小血管炎の徴候が見られたのに加えて、血液培養陰性でもあり、心内膜病変を合併したANCA関連血管炎との鑑別を要した点でも臨床的示唆に富んでおり、文献的考察を交えて報告する。(著者抄録)
  • 【抗血栓療法 最近の動向】 虚血性心疾患に対する抗血栓療法
    今井 靖, 永井 良三 日本医師会雑誌 138 (3) 505 -510 2009年06月 [査読無し][通常論文]
  • 開心術時に留置した心筋リードを利用した薬物抵抗性重症心不全に対する心室三点ペーシングの有用性
    今井 靖, 藤生 克仁, 小島 敏弥, 杉山 裕章, 安喰 恒輔, 永井 良三, 小野 稔, 速水 紀幸, 村川 裕二 心電図 29 (Suppl.3) S -3 2009年06月 [査読無し][通常論文]
  • マイクロアレイを用いたマルファン症候群原因遺伝子FBN1の遺伝子診断の有用性
    小川 直美, 今井 靖, 西村 敬史, 加藤 昌義, 武田 憲文, 縄田 寛, 竹谷 剛, 師田 哲郎, 原 一雄, 興梠 貴英, 高橋 祐二, 後藤 順, 高本 眞一, 平田 恭信, 永井 良三 日本臨床分子医学会学術総会プログラム・抄録集 46回 58 -58 2009年04月 [査読無し][通常論文]
  • 【心筋症 診断の進歩と治療のブレークスルー2009】 心筋症診療の進歩と今後の展望
    森田 啓行, 今井 靖, 高野 博之, 谷本 耕司郎 内科 103 (3) 543 -553 2009年03月 [査読無し][通常論文]
  • 【血栓症治療の最新動向】 ワルファリン pharmacogeneticsによる投与量の予測
    稲島 司, 今井 靖 Pharma Medica 27 (1) 45 -48 2009年01月 [査読無し][通常論文]
  • 古屋 仁美, 桜井 亮太, 今井 靖, 石坂 信和, 山下 尋史, 平田 恭信, 永井 良三 Circulation journal : official journal of the Japanese Circulation Society 72 (0) 2008年10月 [査読無し][通常論文]
  • 腎機能障害と心血管病 現状と対策 腎機能障害と冠動脈疾患重症度の相互関係
    清末 有宏, 平田 恭信, 今井 靖, 興梠 貴英, 高橋 政夫, 藤田 英雄, 森田 敏宏, 安東 治郎, 永井 良三 日本心臓病学会誌 2 (Suppl.I) 150 -150 2008年08月 [査読無し][通常論文]
  • Long pentraxin3(PTX3)は不安定狭心症で高値を示し、心血管イベント発症の予測因子となる
    志賀 太郎, 前村 浩二, 今井 靖, 齊藤 哲也, 網谷 英介, 中尾 倫子, 安東 治郎, 森田 敏宏, 真鍋 一郎, 相良 三奈, 宮本 恭子, 伊藤 行夫, 平田 恭信, 児玉 龍彦, 永井 良三 日本心臓病学会誌 2 (Suppl.I) 245 -245 2008年08月 [査読無し][通常論文]
  • 假屋 太郎, 今井 靖, 木村 公一, 原田 智浩, 内野 悠一, 安喰 恒輔, 絹川 弘一郎, 山下 尋史, 平田 恭信, 永井 良三, 賀藤 均, 村上 新 Circulation journal : official journal of the Japanese Circulation Society 71 (0) 2007年10月 [査読無し][通常論文]
  • 室野 浩司, 松崎 弦, 江口 航生, 正路 由紀, 高橋 通, 斉藤 哲也, 山本 雄士, 今井 靖, 松本 晃裕, 安喰 恒輔, 前村 浩二, 本江 純子, 大野 実, 世古 義規, 平田 恭信, 永井 良三 心臓 38 (3) 292 -297 2006年03月 [査読無し][通常論文]
     
    先天性QT延長症候群は,原因遺伝子により1〜8型までの8つのサブタイプに分けられるが,日本人では1〜3型が9割以上を占める.このようなQT延長症候群は無治療で経過した場合,13%の患者において40歳となる前に心停止または突然死を生じるといわれており,抗不整脈薬などによる治療が必要となる.LQT1はβ遮断薬が有効であるのに対し,一方,LQT2,LQT3では効果が乏しいかあるいは無効である.一方,LQT3においてはメキシレチンなどのナトリウムチャネル拮抗性の抗不整脈薬またペースメーカー療法が有効とされる.このようにQT延長症候群は均一な疾患でないために臨床症状により,さらには可能ならば遺伝子診断を追加することで病型を推定・診断し,最適な治療を選択する必要がある.今回われわれは11歳頃に発症した先天性QT延長症候群の27歳女性で,入院中にtorsade de pointes(TdP)による失神を繰り返した1例を経験した.臨床症状からはLQT1は否定的であり,LQT2またはLQT3が疑われた.薬物治療にて発作は抑えられたがQTcの短縮効果は乏しくペースメーカー植え込み術を施行,以降発作は認めていない.植え込み型除細動器に関しては適応症例と考えられたが,同意が得られなかった.若年女性であり今後は妊娠・出産の予定があるため,薬物療法,非薬物療法を含めて治療方針について本人から十分な理解を得るとともに,詳細な検討を要する(著者抄録)
  • 瀬戸 久美子, 新谷 隆彦, 斎藤 聡, 藤尾 正和, 光山 訓, 今井 靖, 林 同文, 永井 良三 医療情報学 = Japan journal of medical informatics 25 (2) 99 -105 2005年11月 [査読無し][通常論文]
  • PlGF遺伝子の発現調節の解析
    齊藤 哲也, 前村 浩二, 武田 憲彦, 川浪 大治, 原田 智浩, 野尻 剛史, 今井 靖, 永井 良三 日本動脈硬化学会総会プログラム・抄録集 37回 240 -240 2005年07月 [査読無し][通常論文]
  • 心臓血管外科の際に得られる切除標本を活用した動脈硬化性疾患の病態解析
    今井 靖, 竹谷 剛, 前村 浩二, 原田 智浩, 武田 憲彦, 川浪 大治, 山崎 力, 高本 眞一, 永井 良三 血栓と循環 11 (4) 375 -376 2003年12月 [査読無し][通常論文]
  • 今井 靖, 前村 浩二, 和泉 梢, 小川 陽子, 村川 祐二, 世古 義規, 大野 実, 平田 恭信, 永井 良三, 竹谷 剛, 高本 眞一, 高野 幸路, 三橋 知明, 藤田 敏郎 Circulation journal : official journal of the Japanese Circulation Society 67 (0) 2003年04月 [査読無し][通常論文]
  • 【アドレノメデュリンと循環器疾患】 アドレノメデュリンと遺伝子改変マウス
    今井 靖, 新藤 隆行, 前村 浩二, 永井 良三, 栗原 裕基 循環器科 49 (6) 537 -541 2001年06月 [査読無し][通常論文]
  • 今井 靖, 栗原 裕基, 新藤 隆行, 前村 浩二, 佐田 政隆, 斉藤 勇一郎, 秋下 雅弘, 大須賀 淳一, 矢崎 義雄, 永井 良三 動脈硬化 29 (Suppl.) 211 -211 2001年05月 [査読無し][通常論文]
  • EDHF(Endothelium-Derived Hyperpolazing Factor)内皮由来血管過分極因子
    今井 靖, 栗原 裕基, 永井 良三 BIO Clinica 15 (14) 1156 -1161 2000年12月 [査読無し][通常論文]
  • 【高血圧治療のストラテジー】 合併症をもつ患者への降圧療法 心臓疾患を伴った高血圧
    今井 靖, 永井 良三 治療 82 (4) 1309 -1314 2000年04月 [査読無し][通常論文]
  • 今井 靖, 秋山 暢, 花園 豊, 稲盛 健, 三谷 絹子, 平井 久丸, 永井 良三, 矢崎 義雄 臨床血液 36 (10) 1233 -1236 1995年10月 [査読無し][通常論文]


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