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  2. 永井 良三

永井 良三

ナガイ リョウゾウ  (Ryozo Nagai)

基本情報

所属
自治医科大学 自治医科大学 学長
学位
博士(医学)
J-GLOBAL ID
200901024033893870
researchmap会員ID
1000190318

研究キーワード

 4

研究分野

 1

委員歴

 5

受賞

 7
もっとみる

論文

 969
  • Yu Yoshiki, Yukio Ozaki, Mitsuru Abe, Tevfik F Ismail, Hiroshi Takahashi, Masaharu Akao, Hideki Kawai, Takashi Muramatsu, Masahide Harada, Masaya Ohta, Yosuke Hashimoto, Yuichiro Shiki, Masayuki Koshikawa, Keiichi Miyajima, Hidemaro Takatsu, Yudai Niwa, Naoyuki Kawashima, Reina Ozaki, Naotake Tsuboi, Satoshi Iimuro, Hiroshi Iwata, Ichiro Sakuma, Yoshihisa Nakagawa, Kiyoshi Hibi, Takafumi Hiro, Yoshihiro Fukumoto, Seiji Hokimoto, Katsumi Miyauchi, Hisao Ogawa, Hiroyuki Daida, Hiroaki Shimokawa, Hideo Izawa, Takeshi Kimura, Ryozo Nagai
    Journal of the American Heart Association 14(2) e034627 2025年1月21日  
    BACKGROUND: The effect of worsening renal function and baseline chronic kidney disease (CKD) on outcomes in patients with chronic coronary syndrome in the setting of optimal medical therapy remains unknown. METHODS AND RESULTS: The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease) study is a prospective, multicenter, randomized trial of high-dose (pitavastatin 4 mg/day) or low-dose (pitavastatin 1 mg/day) statin therapy in 12 118 patients with chronic coronary syndrome. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or unstable angina requiring hospitalization (major adverse cardiac and cerebral events [MACCE]). CKD was defined as an estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m2. WRF was defined as a decrease in eGFR ≥20% in the initial year; borderline renal function was an annual decrease of 0%<eGFR<20%, and stable renal function was no decrease. Of 12 118 patients, 4340 had baseline CKD and 7778 did not. The rate of MACCE at 5 years was significantly lower in those without (5.5%) versus with CKD (9.5%) (P<0.0001). After excluding 1247 patients who had MACCE, were censored, or missing eGFR within 1 year, 10 871 patients were included. Of these, 3885 were baseline CKD and the remaining 6986 did not have baseline CKD. Of the 10 871 patients, 577 patients had WRF, 6014 patients showed borderline renal function, and the remaining 4280 patients maintained stable renal function. In patients with CKD, WRF was an independent predictor for MACCE at 4 years as compared with stable renal function (hazard ratio [HR]: 1.67; [95% CI, 1.03-2.73; P=0.039]). In patients without CKD, borderline renal function was a significant predictor for MACCE at 4 years compared with stable renal function (HR: 1.40 [95% CI, 1.03-1.91; P=0.032]). CONCLUSIONS: Baseline CKD was an independent predictor for MACCE in patients with CCS. WRF was a significant predictor for MACCE in patients with CKD. Because borderline renal function was an independent predictor for MACCE even in patients without CKD, mild-to-moderate annual declines of eGFR should be carefully monitored (NCT01042730). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01042730.
  • Kosuke Nagaoka, Natsuka Kimura, Satoru Inoda, Takuya Takayama, Yusuke Arai, Yasuo Yanagi, Takashi Shimada, Ryozo Nagai, Hidenori Takahashi, Kenichi Aizawa
    International Journal of Molecular Sciences 26(2) 556-556 2025年1月10日  査読有り
  • Yasuhiro Hitomi, Yasushi Imai, Masanari Kuwabara, Yusuke Oba, Tomoyuki Kabutoya, Kazuomi Kario, Hisaki Makimoto, Takahide Kohro, Eiichi Shiraki, Naoyuki Akashi, Hideo Fujita, Tetsuya Matoba, Yoshihiro Miyamoto, Arihiro Kiyosue, Kenichi Tsujita, Masaharu Nakayama, Ryozo Nagai
    IJC Heart &amp; Vasculature 54 101507-101507 2024年10月  
  • Yusuke Oba, Tomoyuki Kabutoya, Takahide Kohro, Yasushi Imai, Kazuomi Kario, Hisahiko Sato, Kotaro Nochioka, Masaharu Nakayama, Naoyuki Akashi, Hideo Fujita, Yoshiko Mizuno, Arihiro Kiyosue, Takamasa Iwai, Yoshihiro Miyamoto, Yasuhiro Nakano, Masanobu Ishii, Taishi Nakamura, Kenichi Tsujita, Tetsuya Matoba, Ryozo Nagai
    Hypertension research : official journal of the Japanese Society of Hypertension 2024年9月19日  
    The Japanese Society of Hypertension have established a blood pressure (BP) target of 130/80 mmHg for patients with coronary artery disease (CAD). We evaluated the data of 8793 CAD patients in the Clinical Deep Data Accumulation System database who underwent cardiac catheterization at six university hospitals and the National Cerebral and Cardiovascular Center (average age 70 ± 11 years, 78% male, 43% with acute coronary syndrome [ACS]). Patients were divided into two groups based on whether or not they achieved the guideline-recommended BP of <130/80 mmHg. We analyzed the relationship between BP classification and major adverse cardiac and cerebral event (MACCE) separately in two groups: those with ACS and those with chronic coronary syndrome (CCS). During an average follow-up period of 33 months, 710 MACCEs occurred. A BP below 130/80 mmHg was associated with fewer MACCEs in both the overall (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-1.00, p = 0.048) and the ACS group (HR 0.67, 95%CI 0.51-0.88, p = 0.003). In particular, stroke events were also lower among those with a BP below 130/80 mmHg in both the overall (HR 0.69, 95%CI 0.53-0.90, p = 0.006) and ACS groups (HR 0.44, 95%CI 0.30-0.67, p < 0.001). In conclusion, the achievement of BP guidelines was associated with improved outcomes in CAD patients, particularly in reducing stroke risk among those with ACS.
  • 西田 翔, 石間 環, 木村 夏花, 岩見 大基, 永井 良三, 今井 靖, 相澤 健一
    移植 59(総会臨時) 292-292 2024年9月  
もっとみる

MISC

 1923
  • S Yamada, H Nishigori, H Onda, T Utsugi, T Yanagawa, T Maruyama, K Onigata, K Nagashima, R Nagai, A Morikawa, T Takeuchi, J Takeda
    DIABETES 46(10) 1643-1647 1997年10月  
    One form of maturity-onset diabetes of the young, MODY3, is characterized by a severe insulin secretory defect, compared with MODY2, a glucokinase-deficient diabetes, It has recently been shown that mutations of the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1 alpha cause MODY3. Because of the rapid progress to overt diabetes and the high prevalence of required insulin treatment in patients with MODY3, we screened the HNF-1 alpha gene for mutations in Japanese subjects with IDDM, Ten exons and flanking introns of the HNF-1 alpha gene in these subjects were amplified by polymerase chain reaction and direct sequencing of the products, Mutations were identified in three (5.5%) of the 55 unrelated subjects with IDDM, A missense mutation of R272H (replacement of Arg by His in codon 272) in the DNA binding domain of HNF-1 alpha was found in a subject who developed IDDM 1 year after diagnosis of NIDDM at 8 years of age, A frameshift mutation of P291fsinsC (insertion of a C in a polyC tract around codon 291 for Pro), which would generate a mutant truncated protein of 340 amino acids, was found in a subject who started insulin treatment when hyperglycemia and ketonuria were noticed at 13 years of age, A missense mutation of R583G (replacement of Arg by Gly in codon 583) in the transactivation domain of HNF-1 alpha was found in a subject with sudden-onset IDDM at 20 years of age, None of these mutations were present in 100 nondiabetic subjects (200 normal chromosomes), These results indicate that the HNF-1 alpha gene defects could lead to the development of not only early-onset NIDDM but also IDDM, implicating the importance of subclassification of HNF-1 alpha-deficient IDDM from a classical type of autoimmune-based IDDM in Japanese.
  • T Suzuki, H Katoh, M Kurabayashi, Y Yazaki, R Nagai
    Lancet (London, England) 350(9080) 784-5 1997年9月13日  査読有り
  • T Nakamura, Y Saito, T Kato, H Sumino, J Hoshino, Z Ono, T Sakamaki, R Nagai
    Japanese circulation journal 61(9) 772-80 1997年9月  査読有り
    Arterial conduit vessels dilate in response to increased blood flow stimuli. Our objective was to determine precisely how a change in large arterial diameter results in a change in peripheral tissue blood flow. Using high-resolution ultrasound Doppler echography, we measured the diameter of the right femoral artery at rest, during reactive hyperemia, and after administration of 2.5 mg of sublingual isosorbide dinitrate in 10 healthy young men. Reactive hyperemia was induced by distal circulatory arrest followed by reperfusion of the leg ipsilateral (right) or contralateral (left) to the side of arterial diameter measurements. Femoral arterial blood flow was calculated by simultaneous measurement of femoral arterial diameter and blood velocity. The change in skin blood flow was also analyzed simultaneously by laser Doppler flowmetry. Reactive hyperemia induced a 2-fold increase in femoral arterial blood velocity 30 sec after cuff release. During this flow augmentation, the femoral artery dilated. The peak of skin blood flow was coincident with the peak of femoral arterial vasodilation. The time required for the return of arterial diameter to baseline was longer than that for blood flow in both the conduit artery and the peripheral skin tissue. Equivalent cuff occlusion and release of the contralateral limb had no effect on ipsilateral arterial diameter. Isosorbide dinitrate induced dilation in all subjects, despite the absence of a significant increase in blood velocity. These results indicate that the human femoral artery dilates in response to increased blood velocity, and that the flow-mediated vasodilation of a large conduit artery is involved in the adjustments of blood flow in the downstream peripheral tissue.
  • 遠藤 路子, 金古 善明, 谷口 靖広, 永井 良三
    Japanese circulation journal 61 636-636 1997年8月20日  
  • Y Sawada, M Suda, H Yokoyama, T Kanda, T Sakamaki, S Tanaka, R Nagai, S Abe, T Takeuchi
    The Journal of biological chemistry 272(33) 20545-54 1997年8月15日  査読有り
    When hypertrophic growth is induced in neonatal rat cardiocytes by stretching, the cardiocytes express high levels of brain-type natriuretic peptide (BNP) and the proprotein-processing enzyme furin. A BNP precursor, gammaBNP, possesses a furin-cleavable Arg-X-X-Arg motif, which is cleaved when gammaBNP is processed to form BNP-45. The Arg-X-X-Arg motif is found in many precursors of growth factors and growth-related proteins. To determine if furin converts gammaBNP to BNP-45 as well as other unidentified growth-promoting protein precursors to their active form that may induce hypertrophic growth in cardiocytes, we used two protease inhibitor systems, synthetic peptidyl chloromethyl ketones (CMK) (dec-Arg-Val-Lys-Arg-CMK and dec-Phe-Ala-Lys-Arg-CMK; where dec is decanoyl) and vaccinia vector-integrated native and variant alpha1-antitrypsins. The furin-specific inhibitors, dec-Arg-Val-Lys-Arg-CMK and variant alpha1-antitrypsin with the inhibitory determinant Arg-X-X-Arg, suppressed the stretch-induced hypertrophic growth of cardiocytes as well as the processing of gammaBNP to BNP-45. The other serine protease inhibitors and variant alpha1-antitrypsin against elastase, or thrombin, however, neither suppressed the hypertrophic growth nor prevented the processing of gammaBNP to BNP-45. Thus, we suggest that furin catalyzes the conversion of gammaBNP to BNP-45 as well as growth-promoting proproteins to their active form, which might induce hypertrophic growth in cardiocytes.
  • 星野 洋一, 倉林 正彦, 永井 良三
    モレキュラ-メディシン 34(8) 1030-1041 1997年8月  
  • H Nagaoka, T Iizuka, S Kubota, N Kato, T Suzuki, T Inoue, K Endo, R Nagai
    Nuclear medicine communications 18(8) 761-70 1997年8月  査読有り
    We investigated the presence of subclinical left ventricular dysfunction by determining left ventricular diastolic filling at rest and the left ventricular ejection fraction (LVEF) response to exercise with radionuclide angiography. The subjects were 40 patients with non-insulin-dependent diabetes who showed no evidence of cardiovascular disease based on clinical findings, electrocardiography and 201T1 perfusion scintigraphy. We also used 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy to investigate whether subclinical left ventricular abnormalities were related to adrenergic cardiac dysinnervation. The change on LVEF in response to exercise (delta LVEF) was < 5% in 1 of 20 normal controls and in 22 of 40 diabetic patients (P < 0.01). The peak filling rate was within normal limits in all controls but was abnormal (< 2.3 EDV s-1) in 5 of 40 patients (P = N.S.). Of the clinical and scintigraphic variables that correlated significantly with delta LVEF, the heart-to-mediastinum 123I-MIBG uptake ratio on the late planar images was the most important and independent predictor. Nearly half of the patients with non-insulin-dependent diabetes without apparent cardiovascular disease exhibited a depressed LVEF response to exercise. This subnormal response was significantly associated with diminished myocardial 123I-MIBG uptake, suggesting a causal relationship.
  • A Kimura, H Harada, JE Park, H Nishi, M Satoh, M Takahashi, S Hiroi, T Sasaoka, N Ohbuchi, T Nakamura, T Koyanagi, TH Hwang, TA Choo, KS Chung, A Hasegawa, R Nagai, O Okazaki, H Nakamura, M Matsuzaki, T Sakamoto, H Toshima, Y Koga, T Imaizumi, T Sasazuki
    NATURE GENETICS 16(4) 379-382 1997年8月  
    Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays(1). Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC)(2,3), cardiac troponin T (cTnT)(4,5), alpha-tropomyosin (alpha TM)(5,6), cardiac myosin binding protein C (cMBP-C)(7-9), ventricular myosin essential light chain (vMLC1)(10) and ventricular myosin regulatory light chain (vMLC2)(10) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle(11), we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC)(12) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients(13).
  • K Kaneko, T Kanda, T Yokoyama, Y Nakazato, T Iwasaki, I Kobayashi, R Nagai
    Research communications in molecular pathology and pharmacology 97(1) 3-12 1997年7月  査読有り
    While an overproduction of interleukin-6 (IL-6) has been observed in patients with acute myocardial infarction (AMI), its clinical significance and localization in the ischemic myocardium have not been elucidated. We examined immunohistochemically the expression of IL-6 in 12 autopsied patients with AMI who had died within seven days of the infarction. Twenty sections of ischemic myocardium and nine of the coronary arteries involved were stained with anti-IL-6 and anti-atrial natriuretic peptide (ANP). The diameter of the myocardium was analyzed. The greatest expression of IL-6 in the infarcted myocardium occurred in patients who had died three to four days after the onset (2.7 +/- 0.4), as judged by a scheme for grading IL-6 expression. Patients who died within one to two days (1.0 +/- 0.3) or five to eight days (0.6 +/- 0.4) less frequently showed an overproduction of IL-6. The IL-6-positive myocardium co-expressed ANP and was significantly (p < 0.05) hypertrophied, when compared with the IL-6-negative myocardium. The diameter of IL-6-positive myocardial myocytes was significantly (p < 0.02) increased in patients who died within one to two days (1.6 +/- 0.2), three to four days (1.8 +/- 0.3), or five to eight days (2.0 +/- 0.2) after the AMI. The involved coronary arteries expressed IL-6 in the intimal and smooth muscle cells, as did atherosclerotic coronary arteries not involved in AMI. An overproduction of IL-6 was confirmed in the injured myocardium with hypertrophy in patients who died of AMI within seven days after onset. The hypertrophied injured myocardium co-expressed IL-6 and ANP. The expression of IL-6 in the myocardium in AMI appears to be associated with the mechanism of cardiac hypertrophy.
  • H Sakamoto, T Sakamaki, T Kanda, Y Hirao, Y Ohyama, K Ogishi, M Negishi, H Masuda, H Sumino, Y Sawada, Z Ono, I Kobayashi, R Nagai
    Research communications in molecular pathology and pharmacology 97(1) 60-6 1997年7月  査読有り
    Cardiac myxoma cells produce large amounts of interleukin (IL)-6 and IL-8. To determine whether immunosuppressive agents could be used to treat cardiac myxoma, we tested the effects of dexamethasone and three of the newer second-generation immunosuppressive drugs, cyclosporin A, tacrolimus, and deoxyspergualin, on the production of IL-6 and IL-8 in these cells. Cultured cardiac myxoma cells were used as in vitro model of cardiac myxoma. Cells were tested for 24 hours with 10(-7) M dexamethasone, 10(-6) M cyclosporin A, 10(-8) M tacrolimus, and 10(-6) M 15-deoxyspergualin, with aliquots of conditioned medium being assayed for cytokine levels at 0, 6, 12, and 24 hours. Cardiac myxoma cells isolated from 4 patients all produced quantities of IL-6 and IL-8. The concentrations of IL-6 in the medium after 7 days in culture ranged from 79,000 to 2,740,000 pg/ml, and the concentrations of IL-8 ranged from 40,000 to 1,000,000 pg/ml. Exposure of cyclosporin A and dexamethasone almost completely inhibited the production of IL-6 and IL-8 after 24 hours of treatment. Tacrolimus inhibited the production of both cytokines by 55%, while 15-deoxyspergualin reduced IL-6 levels by 24% and IL-8 levels by 48% after separate 24 hour treatments. These results suggest that these newer immunosuppressive agents may be useful in reducing the production of IL-6 and IL-8 in patients with cardiac myxoma.
  • M Aikawa, Y Sakomura, M Ueda, K Kimura, I Manabe, S Ishiwata, N Komiyama, H Yamaguchi, Y Yazaki, R Nagai
    Circulation 96(1) 82-90 1997年7月1日  査読有り
    BACKGROUND: The pathophysiology of phenotypic modulation of smooth muscle cells (SMCs) involved in restenosis after angioplasty is not well understood. Smooth muscle myosin heavy chain (SM MHC) isoforms (SM1 and SM2) are specific markers for SMC differentiation. In particular, SM2 is useful as a marker of mature SMCs. SMemb is a nonmuscle myosin heavy chain (NM MHC) whose expression is upregulated in immature or activated SMC. METHODS AND RESULTS: To determine SMC phenotypes in neointimal tissues after percutaneous transluminal coronary angioplasty (PTCA), we performed immunohistochemistry on human coronary arteries with antibodies against alpha-SM actin, SM1, SM2, and SMemb. Tissues were obtained from six autopsied patients and from atherectomy specimens from 16 patients who had undergone PTCA. Medial SMCs were positive for alpha-actin, SM1, and SM2. Expression of SM1 and SM2 in the neointima varied with the time after intervention, whereas alpha-actin was constitutively expressed in all cases studied. Neointimal cells at 16 and 20 days after PTCA contained alpha-actin but little or no SM1 or SM2, indicating that these cells modulated their phenotype to the immature state. Neointimal SMCs recovered SM MHC expression, first SM1 and then SM2, by 6 months after PTCA. Increased expression of SMemb was found in the neointima but without apparent relationship to the time after PTCA. CONCLUSIONS: Neointimal SMCs show features of an undifferentiated state, indicated by altered expression of SM MHC, and undergo redifferentiation in a time-dependent manner. The expression of SM MHC isoforms provides insight into the biology of healing after angioplasty and furnishes useful tools for the understanding of the roles of differentiation and phenotypic modulation of SMCs in human vascular lesions.
  • Tomono Shoichi, Kawazu Shoji, Hasegawa Akira, Nagai Ryozo, Murata Kazuhiko
    Japanese circulation journal 61(7) 612-612 1997年6月20日  
  • Ohyama Yoshio, Masuda Hiroaki, Okamoto Ei-ichi, Sakamoto Hironosuke, Nagai Ryozo, Simomura Yukio, Kuro-o Makoto, Kurabayashi Masahiko, Manabe Ichiro
    Japanese circulation journal 61(7) 574-575 1997年6月20日  
  • Saito Yuichiro, Nakamura Tetsuya, Sumino Hiroyuki, Mochida Manabu, Ohyama Yoshio, Hoshino Jin, Kato Tatsuya, Sato Kunio, Ono Zenpei, Sakamaki Tetsuo, Nagai Ryozo
    Japanese circulation journal 61(7) 582-583 1997年6月20日  
  • Saito Yuichiro, Nakamura Tetsuya, Sumino Hiroyuki, Mochida Manabu, Ohyama Yoshio, Hoshino Jin, Kato Tatsuya, Sato Kunio, Ono Zenpei, Sakamaki Tetsuo, Nagai Ryozo
    Japanese circulation journal 61(7) 556-557 1997年6月20日  
  • 中島 忠, 永井 良三
    医学のあゆみ 181(10) 906-910 1997年6月7日  
  • S Tomono, S Kawazu, T Ohno, T Utsugi, N Kato, Y Itoh, Y Ohyama, T Uchiyama, R Nagai
    DIABETOLOGIA 40 1765-1765 1997年6月  
  • Y von Kodolitsch, C A Nienaber, T Suzuki, R Nagai, Y Yazaki, T Meinertz
    Zeitschrift fur Kardiologie 86(6) 469-73 1997年6月  査読有り
    Despite the availability of diagnostic modalities such as transesophageal echocardiography, computed tomography or magnetic resonance imaging up to 30% of patients with acute aortic dissection remain undiagnosed before death. A novel immunoassay of serum smooth muscle myosin heavy chain was recently developed as a potential diagnostic tool for the detection of aortic dissection. The immunoassay was applied in two patients with an acute chest pain syndrome but no initial clinical suspicion of aortic disease. In both patients myocardial ischemia was ruled out by laboratory, electrocardiographic and echocardiographic examinations. In the first patient both dilation of the aorta and long-standing arterial hypertension were known; however, it was not before 48 h until dissection was suspected and a spiral-CT was performed demonstrating a localized ascending aortic dissection. At this time (48 h after onset of symptoms) the smooth muscle myosin heavy chain concentration in the serum was close to normal. In the other patient there was neither a suggestive history nor any clinical sign of aortic dissection. Widening of the abdominal aortic wall on an ultrasound examination was the key to the incidental diagnosis of a clinically unsuspected type B dissection. The serum test 12 h after onset of pain revealed elevated (diagnostic) serum levels of smooth muscle myosin heavy chains. Both cases exemplify important gaps in the diagnostic strategy for the detection of acute aortic dissection. A novel immunoassay for smooth muscle myosin heavy chains provides rapid and reliable diagnostic information especially in patients without clinically suspected aortic dissection and may avoid limitations in the diagnostic work-up of patients with acute aortic disease, if used early in the evaluation of patients with chest pain syndromes.
  • N Suzuki, K Kimura, R Nagai, S Ohba, N Mise, J Hiroi, A Tojo, Y Hirata, A Nagaoka, A Goto, M Omata
    NEPHROLOGY 3(3) 251-259 1997年6月  
    The aim of this study was to determine the phenotypic modulation in preglomerular vascular smooth muscles and glomerular cells in hypertension. Eight-week-old stroke-prone spontaneously hypertensive rats (SHRSP) fed high sodium pellets (3%) were untreated or treated with a calcium antagonist, manidipine HCl (2 mg/kg per day), for 8 weeks. The expression of myosin heavy chain isoforms (MHC), SM2 (muscle-type) and SMemb (non-muscle-type) or alpha-actin was examined by the immunohistochemical technique. In normotensive Wistar-Kyoto rats, both SM2 and alpha-actin were expressed equally in the smooth muscles of preglomerular vessels, and SMemb was expressed slightly in the glomerular epithelial cells. In the SHRSP, however, the expression of SM2 and alpha-actin was significantly decreased or disappeared in the afferent arterioles, depending on the degree of vascular damage. In damaged glomeruli, SMemb and alpha-actin were newly expressed in mesangial cells. Manidipine HCl attenuated the renal damage and restored the expression of alpha-actin in the afferent arterioles. There was a significant correlation between the glomerular damage and the attenuation of SM2 expression (r=0.87). In conclusion, phenotypic modulation of vascular smooth muscles occurred in hypertensive renal damage and was correlated with the glomerular damage, where the phenotypic modulation also took place in the mesangial cells. These results indicate that the phenotypic modulations revealed by the expression of myosin isoforms might play an important role in the development of hypertensive renal damage.
  • T Suzuki, T Kanda, H Nagaoka, S Kubota, T Iizuka, R Nagai, I Kobayashi
    Angiology 48(6) 497-502 1997年6月  査読有り
    The objective of this study was to determine noninvasively the likelihood of recovery of the left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy (DCM) verified by radionuclide ventriculography. Twenty patients with DCM were classified into two groups according to the LVEF by M-mode echocardiographic findings two years after ventriculographic examination. The LVEF recovered to > or = 50% in 10 patients (Group A), while it was sustained at < 50% in 10 patients (Group B). The clinical features of each group were compared, based on results of physical examination, radionuclide ventriculography, and other diagnostic tests performed on their referral to hospital. Only the systolic blood pressure differed significantly between the two groups, being slightly, but significantly, increased in Group A over that in Group B (P < 0.05). LVEF at rest by radionuclide did not differ (Group A: 31.5 +/- 10.3% vs Group B: 26.5 +/- 9.4%). Peak exercise EF-EF at rest (peak delta EF) in Group A was apparently increased (3.4 +/- 4.0%), while that in Group B was decreased (-4.4 +/- 5.2%). The positive peak delta EF had a highly predictive value of 90% for patients with DCM whose LVEF will recover to more than 50%. The recovery EF-EF at rest did not differ significantly between groups (Group A: 8.4 +/- 4.7 vs Group B: 3.9 +/- 2.3, P < 0.05). Other clinical parameters such as functional class, cardiothoracic ratio, LVEF by echocardiography, cardiac index by Swan-Ganz catheter examination, and histologic examination of biopsied endocardium were indistinguishable in the two groups. The authors conclude that peak delta EF of radionuclide ventriculography on exercise indicates a preservation of LVEF and predicts a good clinical recovery in patients with DCM.
  • 奥村 渉, 宇都木 敏浩, 石井 主税, 須賀 達夫, 佐藤 秀樹, 関口 賢一, 中村 哲也, 伴野 祥一, 河津 捷二, 永井 良三, 児島 高寛, 長町 幸雄, 桜井 信司, 福里 利夫
    糖尿病 40(5) 285-291 1997年5月30日  
  • Y Ohyama, T Utsugi, T Ohno, T Suga, T Uchiyama, M KuroO, Y Nabeshima, R Nagai
    DIABETES 46 1161-1161 1997年5月  
  • T Utsugi, T Kanda, Kobayashi, I, N Katoh, A Tanaka, S Tomono, S Kawazu, R Nagai
    DIABETES 46 151-151 1997年5月  
  • N Akuzawa, T Nakamura, A Tanaka, S Ikeda, T Fukuda, T Sakamaki, R Nagai
    INTERNAL MEDICINE 36(4) 289-292 1997年4月  
    A 29-year-old man with von Recklinghausen's disease suddenly developed severe epigastric pain and was admitted to hospital, Physical examination revealed elevated blood pressure (200/130 mmHg) and tachycardia (162 bpm),Initially, he was suspected to have appendicitis, and appendectomy was performed immediately; however, appendicitis was not demonstrable pathologically, Retroperitoneal hematoma was found incidentally during the operation, Further clinical and laboratory examination demonstrated a marked increase in the urinary excretion of catecholamines, There was no evidence of pheochromocytoma on computed tomography or magnetic resonance imaging; however, these imaging studies simply showed a hematoma at the right adrenal gland, Transient hypertension and tachycardia, resembling pheochromocytoma, was caused by adrenal hemorrhage.
  • T Nakamura, Y Ohyama, H Masuda, T Kurashina, Y Saito, T Kato, H Sumino, K Sato, T Sakamaki, A Sasaki, R Nagai
    JOURNAL OF HYPERTENSION 15(4) 373-381 1997年4月  
    Objectives Our objective was to determine the effect of nitric oxide (NO) inhibition on renal synthesis of endothelin-l (ET-1) in vivo. Design and methods Rats were administered 500 mg/l N-G-nitro-L-arginine methyl ester (L-NAME) in their drinking water or its vehicle for 2 weeks (PW-L-NAME, n=10; SW-CONT, n=10) or for 6 weeks (6W-L-NAME, n=13; 6W-CONT, n=11). We measured the levels of albumin, NO metabolites and ET-1 both in their blood and in 24 h urine samples, and determined the expression of preproET-1 messenger RNA in the renal cortex and the inner medulla. We also examined renal histology, Results L-NAME administration for 6 weeks reduced NO metabolites both in serum (21.5 versus 3.66 nmol/ml in 6W-CONT) and in urine (5.72 Versus 22.53 nmol/24 h in 6W-CONT), raised the systolic blood pressure (228 versus 162 mmHg in 6W-CONT), and the increased urinary excretion of albumin (24.29 +/- 11.66 versus 0.60 +/- 0.08 mg/day in 6W-CONT) and of ET-1 (112.0 +/- 38.3 versus 35.8 +/- 4.4 pg/day in 6W-CONT), There were no significant differences between the plasma levels of ET-1 in the control and L-NAME groups. Expression of preproET-1 messenger RNA increased in the renal cortex but not in the inner medulla in the 6W-L-NAME group, Bleeding and marked arteriolar narrowing were observed in the renal cortex of the 6W-L-NAME group. Conclusions Prolonged inhibition of NO synthesis increases urinary excretion of ET-1 and albumin without having any effect on plasma ET-1 levels. These results do not support the hypothesis that NO plays an inhibitory role in the regulation of ET-1 in the systemic circulation, although it is possible that such a role could exist in renal tissue. However, in view of the albuminuria, a more likely explanation is that increased urinary ET-l is secondary to L-NAME-induced renal hyperfiltration injury.
  • 斎藤 勇一郎, 中村 哲也, 角野 博之, 持田 学, 星野 仁, 加藤 達也, 佐藤 邦雄, 小野 善平, 酒巻 哲夫, 永井 良三
    Japanese circulation journal 61 332-332 1997年3月5日  
  • 鈴木 淳一, 磯部 光章, 山崎 論, 関口 守衛, 川内 基裕, 古瀬 彰, 永井 良三
    Japanese circulation journal 61 508-508 1997年3月5日  
  • 角野 博之, 佐藤 邦雄, 増田 浩明, 斎藤 勇一郎, 星野 仁, 坂本 浩之助, 大山 良雄, 加藤 達也, 中村 哲也, 小野 善平, 酒巻 哲夫, 永井 良三, 神田 享勉
    Japanese circulation journal 61 377-377 1997年3月5日  
  • 渡辺 徳, 倉林 正彦, 相原 康, 海老原 文, 渡辺 昌文, 鈴木 享, 矢崎 義雄, 永井 良三, 磯部 光章
    Japanese circulation journal 61 219-219 1997年3月5日  
  • 坂本 浩之助, 酒巻 哲夫, 神田 享勉, 大山 良雄, 原沢 充子, 永井 良三, 清籐 勉
    Japanese circulation journal 61 224-224 1997年3月5日  
  • 星野 仁, 中村 哲也, 斎藤 勇一郎, 角野 博之, 酒巻 哲夫, 永井 良三
    Japanese circulation journal 61 285-285 1997年3月5日  
  • 大山 良雄, 増田 浩明, 岡本 栄一, 坂本 浩之助, 永井 良三, 下村 行生, 黒尾 誠, 倉林 正彦, 真鍋 一郎
    Japanese circulation journal 61 293-293 1997年3月5日  
  • 山岸 高宏, 中村 哲也, 大山 良雄, 須賀 達夫, 岡本 栄一, 斉藤 勇一郎, 星野 仁, 宇都木 敏浩, 酒巻 哲夫, 永井 良三, 松村 穣, 相澤 宏樹, 黒尾 誠, 鍋島 陽一
    Japanese circulation journal 61 295-295 1997年3月5日  
  • 伴野 祥一, 河津 捷二, 長谷川 昭, 永井 良三, 村田 和彦
    Japanese circulation journal 61 476-476 1997年3月5日  
  • 馬場 俊曉, 神田 享勉, 中野 正幸, 永井 良三
    Japanese circulation journal 61 473-473 1997年3月5日  
  • 神田 享勉, 瀬田 享博, 関口 賢一, 金子 克己, 井上 雅浩, 横山 知行, 岩崎 勉, 永井 良三, 鈴木 忠
    Japanese circulation journal 61 461-461 1997年3月5日  
  • 渡辺 昌文, 倉林 正彦, 海老原 文, 相原 康, 鈴木 亨, 矢崎 義雄, 迫村 泰成, 永井 良三
    Japanese circulation journal 61 370-370 1997年3月5日  
  • 金古 善明, 谷口 靖広, 中島 忠, 間仁田 守, 伊藤 敏夫, 永井 良三
    Japanese circulation journal 61 187-187 1997年3月5日  
  • 斎藤 勇一郎, 中村 哲也, 角野 博之, 持田 学, 星野 仁, 加藤 達也, 佐藤 邦雄, 小野 善平, 酒巻 哲夫, 永井 良三
    Japanese circulation journal 61 196-196 1997年3月5日  
  • 鈴木 亨, 倉林 正彦, 矢崎 義雄, 永井 良三
    Japanese circulation journal 61 231-231 1997年3月5日  
  • 栗原 由紀子, 栗原 裕基, 鈴木 亨, 矢崎 義雄, 永井 良三
    Japanese circulation journal 61 231-231 1997年3月5日  
  • 渡辺 昌文, 倉林 正彦, 相原 康, 海老原 文, 鈴木 亨, 矢崎 義雄, 真鍋 一郎, 永井 良三
    Japanese circulation journal 61 229-229 1997年3月5日  
  • 佐藤 秀樹, 外山 卓二, 金古 善明, 太田 直樹, 金沢 紀雄, 鈴木 忠, 永井 良三, 井上 登美夫, 遠藤 啓吾
    Japanese circulation journal 61 234-234 1997年3月5日  
  • 木村 彰方, 原田 晴仁, 広井 知歳, 佐藤 真夏, 笹岡 大史, 高橋 めぐみ, 大渕 信二, 中村 剛之, 西 宏文, 小柳 毅, 中田 真詩, 今泉 勉, 古賀 義則, 戸嶋 裕徳, 永井 良三, 廣江 道昭, 和泉 徹, 沼野 藤夫, 河村 慧四郎, 横田 慶之, 横山 光宏, 矢崎 義雄, 坂本 二哉
    Japanese circulation journal 61 83-83 1997年3月5日  
  • 田中 敏博, 永井 良三, 矢崎 義雄, 中村 祐輔
    Japanese circulation journal 61(SupplementI) 1997年3月5日  
  • 鈴木 亨, 林 同文, 山崎 力, 水野 健彦, 小室 一成, 倉林 正彦, 山沖 和秀, 矢崎 義雄, 永井 良三
    Japanese circulation journal 61 1997年3月5日  
  • H Nagaoka, N Isobe, S Kubota, T Iizuka, S Imai, T Suzuki, R Nagai
    CARDIOLOGY 88(2) 180-188 1997年3月  
    The diagnostic values of adenosine, dobutamine, and exercise radionuclide ventriculography (RNVG) in the detection of coronary artery disease (CAD), and the characteristics of those patients who showed myocardial ischemia during the infusion of adenosine or dobutamine were assessed in 41 patients with suspected CAD. Sensitivity, specificity, and accuracy, respectively, for detecting patients with CAD were 35 (p &lt; 0.01 vs. exercise RNVG), 100 and 46% (p &lt; 0.01 vs. exercise RNVG) with adenosine RNVG, 74, 100 and 78% with dobutamine RNVG and 88, 71 and 85% with exercise RNVG. There was a significant difference in physiologic parameters during the provocation of ischemia by adenosine versus exercise RNVG, although these parameters were similar by dobutamine and exercise RNVG. Stepwise discriminant analysis revealed that the number of stenotic vessels was an important and independent predictor for the myocardial ischemia induced by each stress; the peak filling rate was the only predictor for adenosine-induced ischemia. Dobutamine induced myocardial ischemia in a way similar to that of exercise, and was more useful than adenosine for pharmacologic stress RNVG, The mechanism of the adenosine-induced ischemia seemed to differ from that of the ischemia induced by dobutamine or exercise, and to be closely associated with left ventricular diastolic function.
  • T Okazaki, H S Sharma, M Aikawa, A Yamataka, R Nagai, T Miyano, D Tibboel
    Journal of pediatric surgery 32(3) 391-4 1997年3月  査読有り
    Abnormalities of the pulmonary vasculature are well documented in cases of congenital diaphragmatic hernia (CDH). Vascular endothelial growth factor (VEGF), an angiogenic factor, is a recently described endothelial cell-specific growth factor. Myosin heavy chain (MHC) isoforms such as SMemb, SM1 and SM2 are important molecular markers used to study vascular smooth muscle cell differentiation. SMemb is predominantly expressed in immature smooth muscle cells (SMC), and SM2 is expressed in mature SMCs. The authors investigated the expression of VEGF and SMC differentiation in pulmonary vessels in CDH rat lungs and in controls. The lungs of nitrofen-induced CDH rat fetuses (n = 16, gestational age 16, 18, 20, and 22 days) were stained immunohistochemically using antibodies against VEGF, SMemb and SM2, while alpha-actin was used as a general marker of vascular smooth muscle cells. In the CDH group VEGF expression was negative in pulmonary vessels before birth, and in the control group VEGF was positive in smooth muscle cells in vessel walls from 20 days both in vessels at the hilum and in pulmonary parenchyma. In both control and CDH groups, SMemb expression was positive from 16 days' gestation. SM2 expression was negative in vessel walls during the prenatal period in both groups. Alpha-actin was localized in both lungs obtained from control and CDH groups in the lung hilum from 16 days and around peripheral vessels from 18 days. Differences in vascular smooth muscle cell differentiation were not observed between control and CDH lung. These findings suggest that differences in pulmonary vascular development exist between control and CDH rats for VEGF expression, and maturational differences in smooth muscle cell differentiation are not present. This role of altered endothelial cell growth might be related to the different pulmonary vascular reactivity present in CDH lungs.
  • T Nakajima, Y Kaneko, Y Taniguchi, K Hayashi, T Takizawa, T Suzuki, R Nagai
    European heart journal 18(3) 530-1 1997年3月  査読有り
  • T Tanaka, R Nagai, H Tomoike, S Takata, K Yano, K Yabuta, N Haneda, O Nakano, A Shibata, T Sawayama, H Kasai, Y Yazaki, Y Nakamura
    Circulation 95(3) 565-7 1997年2月4日  査読有り
    BACKGROUND: Familial long-QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur due to ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far. We investigated mutations of these genes in LQTS families. METHODS AND RESULTS: Thirty-two Japanese families with LQTS were brought together for screening for mutations. Genomic DNA from each proband was examined by the polymerase chain reaction-single-strand conformation polymorphism technique followed by direct DNA sequencing. In four of the families, comprising 16 patients, mutations were identified in KVLQT1; five other families (9 patients) segregated mutant alleles of HERG. All 25 of these patients carried the specific mutations present in their respective families, and none of 80 normal individuals carried these alleles. Mutations were confirmed by endonuclease digestion or hybridization of mutant allele-specific oligonucleotides. No mutation in SCN5A was found in any family. CONCLUSIONS: We identified nine different mutations among 32 families with LQTS. Eight of these were novel and account for 25% of all types of mutations reported to date. Such a variety of mutations makes it difficult to screen high-risk groups using simple methods such as endonuclease digestion or mutant allele-specific amplification.

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