研究等業績 - 原著論文 - 渡邊 博之
-
Involvement of the orexin system in adrenal sympathetic regulation.
Takayuki Nemoto, Fumiyo Toyoshima-Aoyama, Yuto Ueda, Takayoshi Ohba, Toshihiko Yanagita, Hiroyuki Watanabe, Tetsuro Shirasaka, Isao Tsuneyoshi, Yasushi Ishida, Kazuyoshi Hirota, Akira Sawaguchi, Manabu Murakami
Pharmacology 91 ( 5-6 ) 250 - 8 2013年04月 [査読有り]
研究論文（学術雑誌）
Orexin (hypocretin) is a neuropeptide secreted from hypothalamic neurons that is known to be activated during motivated behaviors and active waking. Presently, our knowledge of orexin is mainly limited to the central nervous system, and the involvement of the orexin system in peripheral tissues has received little attention. In the present study, we analyzed the existence of the orexin system in the adrenal medulla, which is part of the sympathetic nervous system. Orexin and its receptors are expressed in the bovine adrenal medulla. Orexins stimulated intracellular calcium changes and epinephrine release from cultured bovine adrenal medullary cells. Applied orexin decreased expression of prepro-orexin, orexin receptor-1 and orexin receptor-2, suggesting negative feedback regulation in the adrenal gland. Our results indicate involvement of the orexin system in the sympathetic regulation of the adrenal medulla.
-
Possible involvement of TRP channels in cardiac hypertrophy and arrhythmia.
Hiroyuki Watanabe, Kenji Iino, Takayoshi Ohba, Hiroshi Ito
Current topics in medicinal chemistry 13 ( 3 ) 283 - 94 2013年03月 [査読有り]
研究論文（学術雑誌）
Over the past 20 years, studies of transient receptor potential (TRP) channels have significantly extended our knowledge regarding the molecular basis of Ca2+ signals in cardiac myocytes. The functional significance of cardiac TRP channels is likely connected to the alteration of membrane potential or Ca2+ entry into a noncontractile compartment, where gene expression responsible for various cardiac diseases is induced. This review highlights some aspects of TRP channels with anticipated roles in cardiac disease. Evidence suggests that (a) increased activities of TRPC1, TRPC3, or TRPC6 are involved in the development of cardiac hypertrophy, where these TRPC channels act as unique sensors for a wide range of hypertrophic stimuli, and (b) mutations in TRPM4 are now recognized as causes of human cardiac conduction disorders. Ultimately, TRP channels may become novel pharmacological targets in the treatment of human cardiac disease.
-
Questionnaire survey on the continuity of home oxygen therapy after a disaster with power outages.
Kazuhiro Sato, Ryo Morita, Kazuhito Tsukamoto, Narumi Sato, Yumiko Sasaki, Mariko Asano, Yuji Okuda, Hajime Miura, Masaaki Sano, Toshimitsu Kosaka, Hiroyuki Watanabe, Takanobu Shioya, Hiroshi Ito
Respiratory investigation 51 ( 1 ) 9 - 16 2013年03月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: After the Great East Japan Earthquake, oxygen-dependent patients in areas experiencing power outages could not continue home oxygen therapy (HOT) without oxygen cylinders. The purpose of this study was to examine use of oxygen cylinders in areas experiencing power outages and the effects of HOT interruption on patients' health. METHODS: Questionnaires were mailed to 1106 oxygen-dependent patients and HOT-prescribing physicians in Akita, near the disaster-stricken area. We investigated patients' actions when unable to use an oxygen concentrator and classified the patients based on oxygen cylinder use. Patients who experienced an interruption of or reduction in oxygen flow rate by their own judgment were assigned to the "interruption" and "reduction" groups, respectively; those who maintained their usual flow rate were assigned to the "continuation" group. Differences were tested using analysis of variance and the χ2 tests. RESULTS: In total, 599 patients responded to the questionnaire. Oxygen cylinders were supplied to 574 patients (95.8%) before their oxygen cylinders were depleted. Comparison of the continuation (n=356), reduction (n=64), and interruption (n=154) groups showed significant differences in family structure (p=0.004), underlying disease (p=0.014), oxygen flow rate (p<0.001), situation regarding use (p<0.001), knowledge of HOT (p<0.001), and anxiety about oxygen supply (p<0.001). There were no differences in changes in physical condition. CONCLUSIONS: Most patients could receive oxygen cylinders after the disaster. Some patients discontinued their usual oxygen therapy, but their overall health status was not affected.
-
Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe.
Daisuke Yamazaki, Masaru Ishida, Hiroyuki Watanabe, Kiyoshi Nobori, Yasunori Oguma, Yutaka Terata, Takashi Koyama, Kenji Iino, Toshimitsu Kosaka, Hiroshi Ito
Lipids in health and disease 12 9 - 9 2013年02月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: Statins are frequently administered to reduce low-density lipoprotein cholesterol (LDL-C) and vascular inflammation, because LDL-C and high sensitive C-reactive protein (hs-CRP) are associated with high risk for cardiovascular events. When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease (CAD), ezetimibe can be added or the statin dose can be increased. However, which strategy is more effective for treating patients with CAD has not been established. The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients. METHODS: 46 patients with high-risk CAD and LDL-C and hs-CRP levels of >70 mg/dL and >1.0 mg/L, respectively, that were not improved by 4 weeks of rosuvastatin (2.5 mg/day) were randomly assigned to receive 10 mg (R10, n = 24) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe (R2.5/E10, n = 22) for 12 weeks. The primary endpoint was a change in hs-CRP. RESULTS: Baseline characteristics did not significantly differ between the groups. At 12 weeks, LDL-C and inflammatory markers (hs-CRP, interleukin-6, tumour necrosis factor-alpha and pentraxin 3) also did not significantly differ between the two groups (LDL-C: R10 vs. R2.5/E10: -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL). However, high-density lipoprotein cholesterol (HDL-C) was significantly improved in the R10, compared with R2.5/E10 group (4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL; p < 0.05). CONCLUSION: Both enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin. However, R10 elevated HDL-C more effectively than R2.5/E10. TRIAL REGISTRATION: UMIN000003746.
-
Effect of short-duration adaptive servo-ventilation therapy on cardiac function in patients with heart failure.
Takashi Koyama, Hiroyuki Watanabe, Gen Igarashi, Yoshikazu Tamura, Ken Ikeda, Shigenori Terada, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 76 ( 11 ) 2606 - 13 2012年11月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: The aim of this study was to investigate whether short-duration adaptive servo-ventilation (ASV) therapy improves cardiac function in heart failure (HF) patients. METHODS AND RESULTS: Consecutive HF patients (n=86) were divided into 3 groups: group A, ASV for a mean of ≥4 h; group B, ASV for ≥1 to <4 h per day; and group C, no ASV or ASV <1 h. The frequency of ASV use did not significantly differ between groups A (79.3±19.2%) and B (70.9±17.4%). After 6 months, a significant increase in left ventricular ejection fraction (LVEF), significant decrease in plasma brain natriuretic peptide (BNP) and decrease in LV end-diastolic volume (LVEDV) were observed in groups A (LVEF, 5.0±8.1%; BNP, -24.9±33.7%; LVEDV, -6.2±10.1%) and B (LVEF, 3.5±5.5%; BNP, -16.5±24.6%; LVEDV, -5.1±8.2%) as compared with group C (LVEF, -1.5±6.0%, P=0.004, P=0.017; BNP, 2.8±10.2%, P=0.002, P=0.017; LVEDV, 0.8±9.1%, P=0.031, P=0.043). Significant correlation was seen between the total ASV time and changes of LVEF (r=0.369, P=0.002), BNP (r=-0.445, P<0.001), and LVEDV (r=-0.374, P=0.001). Admission rate was lower in groups A (4.1%) and B (7.1%) than in group C (25%, log-rank test; P=0.042, P=0.045). Multivariate analysis showed that the frequency of ASV use was a strong parameter for the improvement of LVEF (coefficient=0.284, standard error=0.035, P=0.019). CONCLUSIONS: Even a short-duration of ASV therapy may improve cardiac function in HF patients.
-
Right atrial giant myxoma occupying the right ventricular cavity.
Teruki Sato, Hiroyuki Watanabe, Megumi Okawa, Takako Iino, Kenji Iino, Kazuyuki Ishibashi, Hiroshi Yamamoto, Fumio Yamamoto, Hiroshi Ito
The Annals of thoracic surgery 94 ( 2 ) 643 - 6 2012年08月 [査読有り]
研究論文（学術雑誌）
We report a case of a giant right atrial myxoma mimicking the right ventricular tumor. The 75-year-old patient underwent cardiac surgery, and the tumor was excised along with the stalk. Tricuspid valve annuloplasty was performed before closure of the right atriotomy. The tumor may have caused intraventricular stenosis, hepatic dysfunction, and progressive fatigue as a result of low cardiac output. This case is of special interest because the myxoma was very large compared with those ever reported, and a right atrial myxoma occupying the right ventricular cavity is rare.
-
A free-floating left atrial thrombus develops intermittent entrapment in the mid-ventricle during diastole.
Mikiko Fujiwara, Hiroyuki Watanabe, Yasunori Oguma, Genbu Yamaura, Kazuyuki Ishibashi, Hiroshi Yamamoto, Kiyoshi Nobori, Kenji Iino, Fumio Yamamoto, Hiroshi Ito
Heart and vessels 27 ( 4 ) 428 - 31 2012年07月 [査読有り]
研究論文（学術雑誌）
Free-floating left atrial thrombi are rare. Here we report a case of a 75-year-old woman with atrial fibrillation who was admitted for treatment of acute myocardial infarction. A free-floating left atrial thrombus was found incidentally on echocardiography. Ten days after percutaneous coronary intervention, the patient had mild faintness with transient hypotension, and it was found that the left atrial thrombus had developed intermittent entrapment in the mid-ventricle during diastole, with abrupt rebound back to the left atrial cavity during systole. Urgent removal of the thrombus was performed successfully. Although the free-floating thrombus had appeared to be spherical, like a ball thrombus, on echocardiography, the excised thrombus was pedunculated. A cut section revealed a laminated thrombus with an onion-skin-like appearance.
-
Candesartan improves impaired endothelial function in the human coronary artery.
Kenji Iino, Hiroyuki Watanabe, Takako Iino, Mitsuaki Katsuta, Takashi Koyama, Toshimitsu Kosaka, Gen Terui, Hiroshi Ito
Coronary artery disease 23 ( 4 ) 278 - 83 2012年06月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: Endothelial dysfunction is closely related to cardiovascular events. Several studies have documented that angiotensin II type 1 receptor blockers (ARB) improve peripheral endothelial dysfunction. However, the effect of ARB on coronary endothelial function remains elusive. The purpose of this study was to ascertain the beneficial effects of ARB on human coronary artery endothelial function. METHODS AND RESULTS: Twenty-seven patients were randomly assigned to either the candesartan group (n=14) or the control group (n=13) and followed for 12 months. Coronary blood flow velocity was measured in the left anterior descending artery without stenosis using an intracoronary Doppler-tipped guide-wire. We evaluated coronary endothelial function as the coronary blood flow velocity reserve (CFR), which was defined as the percent change in the coronary blood flow velocity after an intracoronary acetylcholine infusion. At baseline, the CFR in both groups was below 300%, implying that these patients had endothelial dysfunction. After treatment with candesartan for 6 months, the CFR increased significantly from 199 ± 20 to 337 ± 27% (P<0.001), whereas the CFR did not change in the control group (194 ± 32 vs. 185 ± 41%, P=0.52). During 12 months of observation, the cardiovascular event-free survival rate of the patients with an increased CFR was significantly greater than the rate in patients with a decreased CFR (P=0.02). Moreover, the cardiovascular event-free survival rate was greater in the candesartan group than in the control group (P=0.04). CONCLUSION: Our results suggest that candesartan improves coronary endothelial dysfunction of human coronary arteries and may prevent cardiac events.
-
Impact of obesity on plasma B-type natriuretic peptide levels in Japanese community-based subjects.
Megumi Koizumi, Hiroyuki Watanabe, Yoshihiro Kaneko, Kenji Iino, Masaru Ishida, Toshimitsu Kosaka, Yutaka Motohashi, Hiroshi Ito
Heart and vessels 27 ( 3 ) 287 - 94 2012年05月 [査読有り]
研究論文（学術雑誌）
The plasma B-type natriuretic peptide (BNP) concentration was recently shown to be inversely correlated with body mass index (BMI). However, very few attempts have been made to associate abdominal obesity and BNP in the Japanese general population. Here, we conducted a cross-sectional study, and examined 339 male and 429 female residents without heart disease in a rural Japanese community who received an annual health checkup in 2006. BNP was inversely associated with both BMI and abdominal circumference (AC) in the age-adjusted regression analysis (p < 0.05). Following adjustment for traditional risk factors, multiple regression analysis revealed that BNP was negatively correlated with AC (p < 0.05), but not BMI. Although metabolic syndrome was not associated with BNP levels, AC had an influence on low BNP levels in the multiple regression analysis using both AC and BMI concurrently (p < 0.05 for AC and p > 0.60 for BMI). These effects were more prominent in men than in women. Collectively, plasma BNP levels are inversely related with obesity, as measured by AC, in Japanese community-based subjects.
-
Adaptive servo-ventilation improves renal function in patients with heart failure.
Takashi Koyama, Hiroyuki Watanabe, Shigenori Terada, Shin Makabe, Gen Igarashi, Kiyoshi Nobori, Hiroshi Ito
Respiratory medicine 105 ( 12 ) 1946 - 53 2011年12月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: Impaired cardiac function and sleep-disordered breathing (SDB) are associated with progression of chronic kidney disease (CKD) in heart failure (HF) patients. Adaptive servo-ventilation (ASV) therapy improves cardiac function in HF patients regardless of the SDB severity through hemodynamic support and prevention of repetitive hypoxic stress. This study was designed to test the hypothesis that ASV therapy improves renal function in HF patients with SDB. METHODS AND RESULTS: Of 59 consecutively enrolled HF patients, 43 with moderate-to-severe SDB underwent ASV therapy. HF patients were divided into the ASV-treated group (n = 27) and the non-ASV-treated group (n = 16). Estimated glomerular filtration rate (eGFR), echocardiographic parameters, and inflammatory biomarkers were measured before and 12 months after ASV initiation. Improvement in the eGFR was found in the ASV-treated group, but not in the non-ASV-treated group. There was a positive correlation between the increases in eGFR and left ventricular ejection fraction (r = 0.488, p = 0.001). The changes in high-sensitivity C-reactive protein were negatively correlated with change in the eGFR (r = -0.416, p = 0.006). CONCLUSIONS: ASV therapy could improve renal dysfunction in HF patients through hemodynamic support. Additionally, prevention of SDB with the use of ASV therapy could exert anti-inflammatory effects, which could contribute to the improvement of renal function in HF patients.
-
Endothelial progenitor cells are associated with response to chemotherapy in human non-small-cell lung cancer.
Ryo Morita, Kazuhiro Sato, Mariko Nakano, Hajime Miura, Hidesato Odaka, Kiyoshi Nobori, Toshimitsu Kosaka, Masaaki Sano, Hiroyuki Watanabe, Takanobu Shioya, Hiroshi Ito
Journal of cancer research and clinical oncology 137 ( 12 ) 1849 - 57 2011年12月 [査読有り]
研究論文（学術雑誌）
PURPOSE: Bone marrow-derived endothelial progenitor cells (EPCs) play an important role in angiogenesis and tumor growth. However, the clinical relevance of EPCs in non-small-cell lung cancer (NSCLC) remains unclear. Recently, some reports suggested that EPCs correlate with clinical behavior of cancer patients. We assessed the hypothesis that EPCs correlate with efficient of therapy, prognosis, and clinicopathological factors, and EPCs may offer a possible biomarker for treatment outcome in NSCLC. METHODS: EPCs labeled with CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR-2) antibodies were counted by flow cytometry in the peripheral blood of 31 NSCLC patients. We categorized two groups of NSCLC patients according to circulating EPC numbers. We examined age, pathological stage, histological type, Fluoro-D: -glucose Positron emission tomography (FDG-PET), response to therapy, progression-free survival, and tumor size of NSCLC patients and investigated whether these factors correlate with EPC counts. RESULTS: Circulating EPC numbers before antitumor therapy were increased in NSCLC patients compared with healthy controls (P < 0.05). In NSCLC patients, therapy was significantly effective in low circulating EPC group compared with that of high (P < 0.05). Furthermore, the low EPC group showed significantly longer progression-free survival times than that of high (P < 0.05). However, no significant associations with age, gender, histological type, pathological stage, or FDG-PET were detected. CONCLUSION: Peripheral blood levels of bone marrow-derived EPCs are significantly increased in patients with NSCLC and correlate with response to chemotherapy. EPCs may offer a possible biomarker for efficient of treatment and prognosis.
-
Low mean corpuscular hemoglobin level is a predictor of discontinuation of antiplatelet therapy in patients with acute coronary syndrome.
Masaru Ishida, Hiroyuki Watanabe, Kenji Iino, Megumi Okawa, Toshimitsu Kosaka, Hiroshi Ito
Internal medicine (Tokyo, Japan) 50 ( 24 ) 2933 - 9 2011年12月 [査読有り]
研究論文（学術雑誌）
OBJECTIVE: Premature discontinuation of antiplatelet therapy (APT) increases the risk of thrombosis in patients who have undergone placement of a drug-eluting stent for acute coronary syndrome (ACS). The goal of the present study was to identify predictors of patients who would prematurely discontinue APT following stent implantation. METHODS: One-hundred and sixty-one ACS patients who underwent percutaneous coronary intervention in our institution between November 2004 and September 2008 were enrolled in this study. RESULTS: Over the 12-month follow-up period, 18 patients (11.2%) discontinued APT. Among baseline demographic and laboratory variables, multivariate analysis revealed that mean corpuscular hemoglobin (MCH) level was an independent risk factor for APT discontinuation (OR: 0.738, p=0.017). Kaplan-Meier survival analysis showed that the incidence of APT discontinuation was significantly higher in patients with low MCH (<30.0 pg) than in patients with high MCH (≥30.0 pg) (p=0.0006). CONCLUSION: Low baseline MCH level was a predictor of APT discontinuation in ACS patients. Thus, careful consideration should be made before employing a drug-eluting stent in patients with low MCH levels.
-
Expression of the transient receptor potential channel c3 correlates with a favorable prognosis in patients with adenocarcinoma of the lung.
Hajime Saito, Yoshihiro Minamiya, Hiroyuki Watanabe, Naoko Takahashi, Manabu Ito, Hiroshi Toda, Hayato Konno, Masafumi Mitsui, Satoru Motoyama, Jun-ichi Ogawa
Annals of surgical oncology 18 ( 12 ) 3377 - 83 2011年11月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: The cation channels of the transient receptor potential (TRP) superfamily are implicated in cancer formation; in particular, TRPC3 has been shown to contribute to the progression of human ovarian cancer. However, the relationship between TRP expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood. Therefore, we investigated the relationship between TRP expression and the prognosis of patients with adenocarcinoma of the lung. METHODS: We used semiquantitative real-time reverse transcription polymerase chain reaction to assess the expression of TRP mRNA in tumor samples from 95 patients with adenocarcinoma of the lung. We then correlated the TRP mRNA levels with clinicopathological factors. We also used immunohistochemical staining to determine the localization of expressed TRP. RESULTS: The 5-year overall and disease-free survival rates among patients expressing higher levels of TRPC3 mRNA were significantly better than the corresponding rates among patients expressing lower levels (P=0.004, P=0.002, respectively, by log-rank test). Multivariate Cox proportional hazard analyses revealed that tumor size (hazard ratio, 2.46; 95% confidence interval [CI], 1.06 to 5.79; P=0.036), n2 (hazard ratio, 3.81; 95% CI, 1.29 to 11.77; P=0.015) and TRPC3 (hazard ratio, 2.71; 95% CI, 1.33 to 5.59; P=0.006) were independent factors affecting the 5-year overall survival rate. Immunohistochemistry showed that the cytoplasm of tumor cells were stained positively for TRPC3. CONCLUSIONS: Higher levels of TRPC3 expression in tumor cells are an independent predictor of a better prognosis in patients with adenocarcinoma of the lung.
-
The prevalence of apical wall motion abnormalities in patients with long-term right ventricular apical pacing.
Takako Sato-Iino, Hiroyuki Watanabe, Takashi Koyama, Kenji Iino, Toshimitsu Kosaka, Hiroshi Ito
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 24 ( 5 ) 556 - 564 2011年05月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: Long-term right ventricular apical pacing (RVAP) can lead to adverse clinical outcomes. Although left ventricular (LV) dyssynchrony is the major causative factor, other potential mechanisms are not fully understood. We sought to clarify whether RVAP elicits apical wall motion abnormalities that contribute to LV contractile dysfunction. METHODS: We studied annual echocardiographic data over a 5-year period after pacemaker implantation (PMI) for 74 patients who underwent RVAP. The patients were divided into two groups according to the percentage of ventricular pacing: right ventricular (RV) pacing < 50% and RV pacing ≥ 50%. We assessed LV ejection fraction, LV end-diastolic volume, and left atrial dimension. To assess regional wall motion abnormalities, the wall motion score index was calculated. RESULTS: LV wall motion abnormality was observed in 64% of the subjects and was more pronounced in apical segments than in other segments. At 2 years after PMI, brain natriuretic peptide levels were significantly higher in the group with RV pacing ≥ 50% than in the group with RV pacing < 50%. The subjects with RV pacing ≥ 50% had higher LV end-diastolic dimension and lower ejection fraction at 3 years after PMI. CONCLUSION: Long-term RVAP elicits apical wall motion abnormalities that could in part contribute to LV contractile dysfunction.
-
Short-term prognosis of adaptive servo-ventilation therapy in patients with heart failure.
Takashi Koyama, Hiroyuki Watanabe, Gen Igarashi, Shigenori Terada, Shin Makabe, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 75 ( 3 ) 710 - 2 2011年03月 [査読有り]
研究論文（学術雑誌）
BACKGROUND: This study tested the hypothesis that adaptive servo-ventilation (ASV) therapy improves the prognosis of heart failure (HF) patients, regardless of the severity of sleep-disordered breathing (SDB). METHODS AND RESULTS: 88 consecutive patients were divided into 4 groups based on ASV therapy and SDB severity. The incidence of HF, brain natriuretic peptide (BNP) levels, and left ventricular ejection fraction (LVEF) were followed for 12 months. Fewer HF events, together with an increase in LVEF and a decrease in BNP, occurred in ASV-treated patients with both non-to-mild and moderate-to-severe SDB. CONCLUSIONS: ASV therapy improves the short-term prognosis in HF-patients, regardless SDB severity.