Yoko Tomikura

Publications (8)29.35 Total impact

• Article: Status of endothelial dependent vasodilation in patients with hyperuricemia.

  Masahiko Kato, Ichiro Hisatome, Yoko Tomikura, Kazuhiko Kotani, Toru Kinugawa, Kazuhide Ogino, Katsunori Ishida, Osamu Igawa, Chiaki Shigemasa, Virend K Somers
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  ABSTRACT: Hyperuricemia has been associated with an increased risk for cardiovascular disease and increased mortality. However, the biologic mechanisms that link elevated serum uric acid to cardiovascular disease are uncertain. This study tested the hypothesis that elevated serum uric acid is associated with impaired endothelial function in hyperuricemic patients without any overt cardiovascular disease. Seventeen male patients with hyperuricemia (mean age 42+/-4 years) and 9 control subjects (mean age 45+/-5 years) were studied. All subjects were nonsmokers. All patients had never been treated for hyperuricemia, were on no medications, and were free of any other known diseases. Endothelial function was evaluated by flow-mediated dilation measured by ultrasound. Flow-mediated dilation was significantly impaired in patients with hyperuricemia (4.0+/-0.7%) compared with control subjects (6.4+/-0.8%) (p=0.044). Flow-mediated dilation correlated inversely with uric acid levels (r=-0.4, p=0.05). Nitrate-induced dilation was 12.3+/-1.0% in patients with hyperuricemia and 11.8+/-2.3% in control subjects (p=0.82). Impaired endothelial-dependent vasodilation is present in hyperuricemic patients even in the absence of any overt cardiovascular disease. The elevated serum uric acid, per se, may constitute a novel risk factor for endothelial dysfunction.
  The American Journal of Cardiology 01/2006; 96(11):1576-8. · 3.37 Impact Factor
• Article: Neurohumoral profiles in patients with hypertrophic cardiomyopathy: differences to hypertensive left ventricular hypertrophy.

  Kazuhide Ogino, Kazuyoshi Ogura, Toru Kinugawa, Shuichi Osaki, Masahiko Kato, Yoshiyuki Furuse, Yoshiharu Kinugasa, Yoko Tomikura, Osamu Igawa, Ichiro Hisatome, Chiaki Shigemasa
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  ABSTRACT: Patients with hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) have increased concentrations of various neurohumoral factors. Thus, the aim of the present study was to evaluate the differences in the neurohumoral profiles of HCM and HHD. Plasma concentrations of epinephrine, norepinephrine, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), angiotensin II and endothelin-1 were measured in 40 patients with HCM, 35 with HHD, and 15 controls. Additionally, the concentrations of these neurohumoral factors in the coronary sinus and aortic root were measured in 12 HCM patients and 10 controls. Plasma concentrations of norepinephrine, ANP and BNP were significantly higher in HCM than HHD and controls. In HCM, there was no significant correlation between the left ventricular mass index and any neurohumoral factor. The plasma BNP concentration significantly correlated with left intraventricular pressure gradient in HCM. There were significant differences in the plasma concentrations of ANP and BNP between HCM with and without left ventricular diastolic dysfunction. Transcardiac production of BNP was significantly higher in patients with obstructive HCM than in those with non-obstructive HCM. The significant neurohumoral differences between HCM and HHD were the plasma concentrations of norepinephrine, ANP and BNP. In HCM patients, the plasma BNP concentration may reflect the intraventricular pressure gradient and left ventricular diastolic dysfunction whereas the plasma ANP concentration reflects only the left ventricular diastolic dysfunction.
  Circulation Journal 06/2004; 68(5):444-50. · 3.77 Impact Factor
• Article: Excessive purine degradation during semi-ischemic forearm test in patients with diabetes mellitus.

  Yasushi Tanaka, Ichiro Hisatome, Toru Kinugawa, Hiroaki Tanaka, Yoko Tomikura, Fumihiro Ando, Takashi Matsuura, Gou Igawa, Koichi Matsubara, Yasutaka Yamamoto, Masahiro Yamawaki, Rei Yamamoto, Kazuhide Ogino, Osamu Igawa, Tadasu Ikeda, Chiaki Shigemasa, Akira Takeda
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  ABSTRACT: The aim of this study was to investigate whether or not the purine degradation in the skeletal muscle during forearm exercise is augmented in patients with diabetes mellitus (DM). We used the semi-ischemic forearm test to examine the release of lactate (deltaLAC), ammonia (deltaAmm) and hypoxanthine (deltaHX) before exercise, 0, 4, 10, and 60 minutes after exercise in eleven diabetic patients and seven normal controls. The sum of the increased HX (DM vs Controls: 26.1 +/- 21.2 vs 7.8 +/- 5.9 micromol/L, p < 0.05) was greater in diabetic patients. When patients were divided into the excessive response group (n = 7) and normal response group (n = 4), the maximum increments in deltaHX and deltaAmm in the excessive response group (16.8 +/- 3.2 micromol/l and 122 +/- 60 micromol/l) were greater (p < 0.05) than those in the control group (3.6 +/- 3.0 micromol/l and 32 +/- 34 micromol/l and the normal response group (2.9 +/- 2.9 micromol/l and 27.4 +/- 12.7 micromol/l). DeltaLAC both in the excessive response group (5.4 +/- 1.5 mmol/l) and the normal response group (3.6 +/- 1.0 mmol/l) were higher (p < 0.05) than that of the control group (1.7 +/- 0.5 mmol/l). The prevalence of diabetic retinopathy was higher in the excessive response group than in the normal response group (75% vs. 25%). These data suggest that patients with DM, especially with microangiopathy have augmented purine degradation during the semi-ischemic forearm test. Factors responsible for the augmented purine degradation in these patients remain to be determined.
  Internal Medicine 09/2003; 42(9):788-92. · 0.94 Impact Factor
• Article: Coordinate induction of AMP deaminase in human atrium with mitochondrial DNA deletion.

  Yoko Tomikura, Ichiro Hisatome, Mariko Tsuboi, Masahiro Yamawaki, Masaki Shimoyama, Yasutaka Yamamoto, Norihito Sasaki, Kazuhide Ogino, Osamu Igawa, Chiaki Shigemasa, Shingo Ishiguro, Shigetsugu Ohgi, Eiji Nanba, Goshi Shiota, Hiroko Morisaki, Takayuki Morisaki, Masafumi Kitakaze
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  ABSTRACT: Despite the heteroplasmic lower population of mitochondrial (mt) DNA deletion, mtDNA deletion is significantly related to the loss of atrial adenine nucleotides. To elucidate its mechanism, we examined the frequency of a 7.4-kb mtDNA deletion, the concentration of adenine nucleotides, and the activity of AMP catabolic enzymes in 10 human right atria obtained from cardiac surgery, using quantitative PCR, HPLC, and immunoprecipitations. The atrial concentrations of ATP, ADP, AMP, and the total adenine nucleotides were significantly lower in patients with deletion than those in patients without deletion, despite the lower frequency of their deletion. The activities of total AMP deaminase (AMPD), liver-type (AMPD 2), and heart-type isoform (AMPD 3) were significantly higher in patients with deletion than in patients without deletion, although there was no significant difference in the cytosolic 5(')-nucleotidase among them. In conclusion, mtDNA deletion coordinately induces AMP deaminase to contribute to the loss of atrial adenine nucleotides through degrading AMP excessively.
  Biochemical and Biophysical Research Communications 04/2003; 302(2):372-6. · 2.48 Impact Factor
• Article: Interleukin-6 and tumor necrosis factor-alpha levels increase in response to maximal exercise in patients with chronic heart failure.

  Toru Kinugawa, Masahiko Kato, Kazuhide Ogino, Shuichi Osaki, Yoko Tomikura, Osamu Igawa, Ichiro Hisatome, Chiaki Shigemasa
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  ABSTRACT: Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. Strenuous exercise causes activation of both systems but the effect of acute bouts of exercise on cytokines is not known in patients with CHF. This study determined whether maximal exercise induces activation of cytokines in CHF. Plasma interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, epinephrine, norepinephrine, and atrial and brain natriuretic peptides (ANP and BNP) were determined before and after symptom-limited cardiopulmonary exercise testing in 80 patients with CHF (LVEF=38+/-1%, peak VO(2)=18.8+/-0.5 ml/min/kg) and age-matched 33 controls. Resting IL-6 (Controls vs. CHF: 1.3+/-0.2 vs. 2.5+/-0.3 pg/ml, P<0.001) and TNF-alpha (2.7+/-0.2 vs. 3.8+/-0.2 pg/ml, P<0.01) were elevated in CHF. LogIL-6 and logTNF-alpha were positively correlated (r=0.34 and r=0.35, respectively) with logplasma norepinephrine, and were negatively correlated (r=-0.39 and r=-0.32, respectively) with peak VO(2). Maximal exercise increased IL-6 and TNF-alpha both in controls and CHF (all P<0.01). Changes in IL-6 (DeltaIL-6) correlated with Deltaepinephrine (r=0.63, P<0.0001) and Deltanorepinephrine (r=0.57, P=0.0006) in controls, but not in CHF. DeltaTNF-alpha correlated with DeltaANP (r=0.28, P=0.01) only in CHF. In summary, cytokine activation at rest was associated with high plasma norepinephrine and exercise intolerance. Maximal exercise caused increases in IL-6 and TNF-alpha concentrations. Sympathetic activation seems to be important for the IL-6 increase during exercise in controls. In CHF, changes in ANP during exercise were associated with the exercise-induced increase in TNF-alpha, but still unknown mechanisms are involved for the cytokine activation during exercise.
  International Journal of Cardiology 02/2003; 87(1):83-90. · 7.08 Impact Factor
• Article: Effects of the angiotensin-converting enzyme inhibitor alacepril on exercise capacity and neurohormonal factors in patients with mild-to-moderate heart failure.

  Toru Kinugawa, Shuichi Osaki, Masahiko Kato, Kazuhide Ogino, Masaki Shimoyama, Yoko Tomikura, Osamu Igawa, Ichiro Hisatome, Chiaki Shigemasa
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  ABSTRACT: 1. Alacepril is a long-acting, sulphydryl-containing angiotensin-converting enzyme inhibitor. Data are limited regarding the effects of alacepril on exercise tolerance in patients with chronic heart failure (CHF). The aim of the present study was to determine the effects of chronic alacepril treatment on exercise capacity and neurohormones in patients with CHF. 2. The effects of 12 weeks treatment with alacepril on clinical, echocardiographic and cardiopulmonary exercise variables were studied in 18 CHF patients (mean age: 63 +/- 2 years; New York Heart Association (NYHA) class I n = 6, class II n = 10, class III n = 2) in a cross-over fashion. Resting levels of plasma noradrenaline, renin-angiotensin system activity and natriuretic peptides were evaluated. 3. Treatment with alacepril significantly improved NYHA functional class and decreased cardiothoracic ratio (60.1 +/- 2.0 vs 58.1 +/- 1.9% for baseline vs alacepril, respectively; P < 0.01). Cardiac dimensions by echocardiogram were decreased after alacepril therapy. Peak Vo2 (17.7 +/- 1.2 vs 19.5 +/- 1.3 mL/min per kg; P < 0.01) and anaerobic threshold (11.7 +/- 0.6 vs 13.2 +/- 0.9 mL/min per kg; P < 0.01) increased with alacepril treatment. Plasma noradrenaline and plasma angiotensin II levels were not altered, but plasma aldosterone (77.7 +/- 13.5 vs 51.7 +/- 9.7 pg/mL; P < 0.01), atrial natriuretic peptide (ANP; 86.5 +/- 20.3 vs 43.6 +/- 7.6 pg/mL; P < 0.05) and brain natriuretic peptide (BNP; 222.7 +/- 59.3 vs 117.7 +/- 34.3 pg/mL; P < 0.05) levels decreased after alacepril treatment. 4. These results suggest that treatment with alacepril improves functional status and exercise capacity in patients with mild-to-moderate CHF. Neurohormones were favourably influenced by alacepril therapy, with significant decreases in plasma aldosterone, ANP and BNP levels.
  Clinical and Experimental Pharmacology and Physiology 12/2002; 29(12):1060-5. · 1.85 Impact Factor
• Article: Parathyroid hormone-related protein is produced in the myocardium and increased in patients with congestive heart failure.

  Kazuhide Ogino, Kazuyoshi Ogura, Yoshiharu Kinugasa, Yoshiyuki Furuse, Kazuhiko Uchida, Masaki Shimoyama, Toru Kinugawa, Shuichi Osaki, Masahiko Kato, Yoko Tomikura, Osamu Igawa, Ichiro Hisatome, John P Bilezikian, Chiaki Shigemasa
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  ABSTRACT: PTHrP is produced in a wide variety of different cells, including cardiomyocytes. Its production is augmented by mechanical and neurohumoral stimulation, and PTHrP has positive chronotropic and vasodilatory effects. Thus, in the heart, PTHrP has the potential to serve as a mechano-sensitive regulatory molecule. We evaluated peripheral and central levels of PTHrP in patients with congestive heart failure (CHF) and tested the hypothesis that PTHrP is released from the heart in patients with CHF. Intact full-length PTHrP (i-PTHrP) and C-terminal PTHrP (c-PTHrP) levels were measured in the plasma of 64 patients with CHF and 12 controls. Plasma PTHrP concentrations in the coronary sinus and aortic root were also measured in 18 CHF patients and 10 controls. Both plasma i-PTHrP and c-PTHrP levels in CHF patients were significantly higher than control levels and increased as a function of New York Heart Association classification. There were significant correlations between c-PTHrP levels and plasma norepinephrine, brain natriuretic peptide, angiotensin II, and endothelin-1 levels. Plasma i-PTHrP was significantly correlated with left ventricular ejection fraction and end-diastolic and end-systolic dimensions. Plasma i-PTHrP levels were significantly higher in the coronary sinus than in the aortic root in CHF patients, but among controls concentrations of i-PTHrP were indistinguishable at these two sites. This is the first report demonstrating that PTHrP is produced in the myocardium and is increased in CHF; these findings suggest that PTHrPs levels might be modulated by cardiac performance in patients with CHF.
  Journal of Clinical Endocrinology &amp Metabolism 11/2002; 87(10):4722-7. · 6.50 Impact Factor
• Article: Relation between neurohormonal activation and enhanced ventilatory response to exercise in patients with chronic congestive heart failure.

  Toru Kinugawa, Yoko Tomikura, Kazuhide Ogino, Shuichi Osaki, Masahiko Kato, Osamu Igawa, Ichiro Hisatome, Chiaki Shigemasa
  The American Journal of Cardiology 04/2002; 89(5):604-7. · 3.37 Impact Factor