88 results on '"Yoshikazu, Watanabe"'
Search Results
2. Object Detection Acceleration Method by Improving Execution Efficiency of Edge AI Device.
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Yoshikazu Watanabe, Yuki Kobayashi, Noboru Nakajima, Takashi Takenaka, and Hiroyoshi Miyano
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- 2023
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3. Work-in-Progress: Object Detection Acceleration Method by Improving Execution Efficiency of AI Device.
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Yoshikazu Watanabe, Yuki Kobayashi, Noboru Nakajima, Takashi Takenaka, and Hiroyoshi Miyano
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- 2022
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4. A clinical nomogram for the prediction of early mortality in elderly patients initiating dialysis for end-stage renal disease
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Masaki Yoshida, Masanori Otsuka, Yoshikazu Watanabe, Takako Harigai, Noriyuki Sakurai, Keiko Kobatake, Hiroaki Yoshida, Satsuki Kobayashi, Takayuki Matsumoto, Tatsuhiko Sakamoto, and Kazue Ueki
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Nomogram ,Early mortality of dialysis initiation ,End-stage renal disease ,Elderly ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background The number of elderly patients (> 80 years of age) with end-stage renal disease is rapidly increasing. The initiation of dialysis extends the duration of survival; however, the rate of early mortality, that which occurs within the first few months after the initiation of dialysis, is reportedly higher than the rate of late mortality. Methods We retrospectively studied a cohort of 300 patients, aged 80 years or older, in whom dialysis was initiated between January 1, 2010, and December 31, 2017, at TOHO Hospital (Gunma, Japan). The rate of early mortality was assessed using the Kaplan-Meier method, and the equivalence of survival curves was tested using log-rank tests. The univariate and multivariate analyses were performed using the Cox proportional hazards model. To evaluate nomogram performance, we assessed both the discrimination and calibration of these models. Two hundred bootstrap resamples were used for internal validation of the accuracy estimates to reduce overfit bias and to determine 95% confidence intervals. Results The nomogram was built using the following nine predictors: serum albumin grams per deciliter (hazard ratio [HR] 0.63, p
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- 2020
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5. Accelerating NFV application using CPU-FPGA tightly coupled architecture.
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Yoshikazu Watanabe, Yuki Kobayashi, Takashi Takenaka, Takeo Hosomi, and Yuichi Nakamura 0002
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- 2017
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6. STCoS: Software-defined traffic control for smartphones.
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Yoshikazu Watanabe, Shuichi Karino, Yoshinori Saida, Gen Morita, and Takahiro Iihoshi
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- 2014
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7. A Successful Case of Conservative Management for Iatrogenic Aortocoronary Dissection During Percutaneous Coronary Intervention
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Kazuhiro Nitta, Masaki Hamamoto, Takashi Fujiwara, Yoshikazu Watanabe, Tomoki Shokawa, Koji Maeda, Shuji Tsujiyama, and Takashi Fujii
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General Medicine - Published
- 2022
8. Increased left atrial pressure in non-heart failure patients with subclinical hypothyroidism and atrial fibrillation
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Akinori Sairaku, Yukiko Nakano, Yuko Uchimura, Takehito Tokuyama, Hiroshi Kawazoe, Yoshikazu Watanabe, Hiroya Matsumura, and Yasuki Kihara
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atrial fibrillation ,heart failure ,left atrial pressure ,subclinical hypothyroidism ,thyroid-stimulating hormone ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background The impact of subclinical hypothyroidism on the cardiovascular risk is still debated. We aimed to measure the relationship between subclinical hypothyroidism and the left atrial (LA) pressure. Methods The LA pressures and thyroid function were measured in consecutive patients undergoing atrial fibrillation (AF) ablation, who did not have any known heart failure, structural heart disease, or overt thyroid disease. Results Subclinical hypothyroidism (4.5≤ thyroid-stimulating hormone 18 mmHg (odds ratio 3.94, 95% CI 1.28 11.2; P = 0.02). Conclusions Subclinical hypothyroidism may increase the LA pressure in AF patients.
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- 2016
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9. Resource Access Control for Wireless LAN Roaming Systems.
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Yoshikazu Watanabe, Hideaki Goto, and Hideaki Sone
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- 2008
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10. Six recurrences of myocarditis in 3 years: A case report
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Ryo Yamazato, Kenji Masada, Yoshimitsu Hakoda, Naoya Mitsuba, Fumiharu Miura, Nozomu Oda, Hironori Ueda, Yoshikazu Watanabe, Yoji Urabe, Akane Tsuchiya, Shogo Matsui, and Atsuo Mogami
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medicine.medical_specialty ,Percutaneous ,Myocarditis ,medicine.diagnostic_test ,business.industry ,Fulminant ,Case Report ,Autopsy ,Physical examination ,030204 cardiovascular system & hematology ,Chest pain ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Ventricle ,Internal medicine ,Ventricular fibrillation ,medicine ,Cardiology ,030212 general & internal medicine ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
A recent study revealed that recurrence of myocarditis occurs in a significant proportion of patients, but multiple recurrences of myocarditis have rarely been reported. The pathophysiology and best treatments for multiple recurrences of myocarditis remain unclear. A 60-year-old man presented to our emergency department with fever and chest pain. Physical examination, imaging, and laboratory findings were consistent with fulminant myocarditis. Paired titers confirmed adenovirus infection. The patient was treated with intra-aortic balloon pump and percutaneous cardiopulmonary support for 7 days and was discharged with near-normal electrocardiographic and echocardiographic findings on day 26. Over the subsequent 3 years, the patient experienced six episodes of recurrence of myocarditis with a progressive decrease in his ability to perform activities of daily living. At the time of his sixth recurrence, he died of ventricular fibrillation. Autopsy revealed mild enlargement of the left ventricle, extensive inflammatory cell infiltration, and mild interstitial fibrosis, suggesting left ventricle remodeling because of repetitive myocarditis. We have presented a case of multiple recurrences of myocarditis. This is the largest number of recurrences in a single patient reported to date. Further studies are needed to elucidate the underlying pathogenesis and best treatment of this condition.
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- 2021
11. The Role of Antegrade Balloon Aortic Valvuloplasty in a Patient with Low-flow, Low-gradient Aortic Stenosis and ST-elevation Myocardial Infarction
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Ryota Akazawa, Yuki Yoshitomi, Koji Maeda, Takashi Fujii, Tomoki Shokawa, Yoshikazu Watanabe, Shuji Tsujiyama, and Takashi Fujiwara
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,General Medicine ,Balloon ,medicine.disease ,Aortic valvuloplasty ,Stenosis ,St elevation myocardial infarction ,Internal medicine ,medicine ,Cardiology ,Low gradient ,business - Published
- 2021
12. Study on Merge of Overlapped TCP Traffic Using Reliable Multicast Transport.
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Yoshikazu Watanabe, Koji Okamura, and Keijiro Araki
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- 2003
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13. Transport directions’ temporal and spatial changes in lower Pleistocene conglomerates near Nagano-Niigata borders, central Japan
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Iwao, Shimizu, Yoshikazu, Watanabe, and Kotaro, Yamagata
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木崎流紋岩礫 ,小濁層 ,Konigori Formation ,Kizaki rhyolite ,Omine-type welded tuff ,Ogawa Formation ,古流向 ,paleocurrent direction ,Kita-Alps ,河東山地 ,猿橋層 ,古信濃川 ,下部更新統 ,大峰型溶結凝灰岩礫 ,花崗岩礫 ,conglomerates ,北アルプス ,Paleo-Shinano River ,礫層 ,SK火山灰 ,SK-volcanic ash ,大川層 ,Saruhashi Formation ,Lower Pleistocene ,Kato Mountains - Published
- 2019
14. Does atrial fibrillation ablation worsen preexisting anemia? Another anemia paradox in DOAC era
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Akinori Sairaku, Yukiko Nakano, Junji Maeda, Michitaka Amioka, Yoshikazu Watanabe, and Nobuyuki Morishima
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medicine.medical_specialty ,business.industry ,Anemia ,medicine.medical_treatment ,Anticoagulants ,Atrial fibrillation ,medicine.disease ,Ablation ,Treatment Outcome ,Internal medicine ,Atrial Fibrillation ,Oral anticoagulant ,Cardiology ,Catheter Ablation ,Medicine ,Humans ,Female ,Hemoglobin ,Cardiology and Cardiovascular Medicine ,business ,Af ablation - Abstract
There is a concern about worsening anemia after atrial fibrillation (AF) ablation in anemic patients. We aimed to clarify whether or not patients with anemia who are on an oral anticoagulant therapy are more likely to lose blood after AF ablation.We studied AF patients in 3 cardiovascular centers who skipped a single dose of a direct oral anticoagulant prior to the ablation, and compared the drop in the hemoglobin level 24 hours after the procedure and bleeding complications between the patients with and without preexisting anemia.We identified 183 (15.7%) patients with anemia at baseline out of 1163 patients. The reduction in the hemoglobin level (-0.39±0.71 vs. -0.93±0.9 g/dL; p0.001) was smaller in the anemic than non-anemic patients. A fall in the hemoglobin level of ≥2 g/dL, which is a guideline-defined significant hemoglobin drop, was less common in anemic patients (1.6% vs. 11.3%; p0.001). A female gender [odds ratio (OR) 1.62, confidence interval (CI) 1.07-2.45; p=0.02], persistent or long-standing persistent versus paroxysmal AF (OR 1.67, CI 1.13-2.49; p=0.01), ORBIT score ≥3 (OR 3.5, CI 1.34-8.94; p=0.01), and preexisting anemia (OR 0.02, CI 0.004-0.14; p0.001) were independently associated with the fall in the hemoglobin level of ≥2 g/dL. No difference was noted in the rate of major bleeding complications (1.6% vs. 1.2%; p=0.72).Paradoxically, patients with preexisting anemia may be less likely to lose blood following AF ablation.
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- 2021
15. A nonsynonymous polymorphism in semaphorin 3A as a risk factor for human unexplained cardiac arrest with documented ventricular fibrillation.
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Yukiko Nakano, Kazuaki Chayama, Hidenori Ochi, Masaaki Toshishige, Yasufumi Hayashida, Daiki Miki, C Nelson Hayes, Hidekazu Suzuki, Takehito Tokuyama, Noboru Oda, Kazuyoshi Suenari, Yuko Uchimura-Makita, Kenta Kajihara, Akinori Sairaku, Chikaaki Motoda, Mai Fujiwara, Yoshikazu Watanabe, Yukihiko Yoshida, Kimie Ohkubo, Ichiro Watanabe, Akihiko Nogami, Kanae Hasegawa, Hiroshi Watanabe, Naoto Endo, Takeshi Aiba, Wataru Shimizu, Seiko Ohno, Minoru Horie, Koji Arihiro, Satoshi Tashiro, Naomasa Makita, and Yasuki Kihara
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Genetics ,QH426-470 - Abstract
Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sympathetic innervation. We investigated the relevance of the semaphorin 3A (SEMA3A) gene located at chromosome 5 in the etiology of UCA. Eighty-three Japanese patients diagnosed with UCA and 2,958 healthy controls from two different geographic regions in Japan were enrolled. A nonsynonymous polymorphism (I334V, rs138694505A>G) in exon 10 of the SEMA3A gene identified through resequencing was significantly associated with UCA (combined P = 0.0004, OR 3.08, 95%CI 1.67-5.7). Overall, 15.7% of UCA patients carried the risk genotype G, whereas only 5.6% did in controls. In patients with SEMA3A(I334V), VF predominantly occurred at rest during the night. They showed sinus bradycardia, and their RR intervals on the 12-lead electrocardiography tended to be longer than those in patients without SEMA3A(I334V) (1031±111 ms versus 932±182 ms, P = 0.039). Immunofluorescence staining of cardiac biopsy specimens revealed that sympathetic nerves, which are absent in the subendocardial layer in normal hearts, extended to the subendocardial layer only in patients with SEMA3A(I334V). Functional analyses revealed that the axon-repelling and axon-collapsing activities of mutant SEMA3A(I334V) genes were significantly weaker than those of wild-type SEMA3A genes. A high incidence of SEMA3A(I334V) in UCA patients and inappropriate innervation patterning in their hearts implicate involvement of the SEMA3A gene in the pathogenesis of UCA.
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- 2013
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16. A smaller post-procedural hemoglobin fall in patients with preexisting anemia undergoing atrial fibrillation ablation with a single skipped dose of direct oral anticoagulants: Another anemia paradox
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Yoshikazu Watanabe, Nobuyuki Morishima, Akinori Sairaku, Junji Maeda, Yukiko Nakano, Hiroki Kinoshita, and Michitaka Amioka
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medicine.medical_specialty ,business.industry ,Anemia ,medicine.medical_treatment ,Atrial fibrillation ,Odds ratio ,medicine.disease ,Ablation ,Confidence interval ,Internal medicine ,Cardiology ,Medicine ,In patient ,Hemoglobin ,business ,Major bleeding - Abstract
Background: There is a concern about worsening of anemia after atrial fibrillation (AF) ablation in anemic patients. We aimed to clarify whether or not patients with anemia who are on an oral anticoagulant therapy are more likely to lose blood after AF ablation. Methods: We studied AF patients in 3 cardiovascular centers who skipped a single dose of direct oral anticoagulants prior to the ablation, and compared the drop in the hemoglobin level 24 hours after the procedure and bleeding complications between the patients with and without preexisting anemia. Results: We identified 183 (15.7%) patients with anemia at baseline out of 1163 patients. The reduction in the hemoglobin level (-0.39±0.71 vs. -0.93±0.9 g/dL; P
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- 2020
17. Intraprocedural anticoagulation and postprocedural hemoglobin fall in atrial fibrillation ablation with minimally interrupted direct oral anticoagulants: comparisons across 4 drugs
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Akinori Sairaku, Nobuyuki Morishima, Hiroya Matsumura, Michitaka Amioka, Junji Maeda, Yoshikazu Watanabe, and Yukiko Nakano
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- 2020
18. A clinical nomogram for the prediction of early mortality in elderly patients initiating dialysis for end-stage renal disease
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Noriyuki Sakurai, Hiroaki Yoshida, Takako Harigai, Masanori Otsuka, Keiko Kobatake, Yoshikazu Watanabe, Kazue Ueki, Tatsuhiko Sakamoto, Masaki Yoshida, Takayuki Matsumoto, and Satsuki Kobayashi
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Nephrology ,Transplantation ,medicine.medical_specialty ,Proportional hazards model ,business.industry ,Urology ,medicine.medical_treatment ,Hazard ratio ,Nomogram ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,End stage renal disease ,End-stage renal disease ,Elderly ,Internal medicine ,Early mortality of dialysis initiation ,Cohort ,medicine ,business ,Survival analysis ,Dialysis - Abstract
Background The number of elderly patients (> 80 years of age) with end-stage renal disease is rapidly increasing. The initiation of dialysis extends the duration of survival; however, the rate of early mortality, that which occurs within the first few months after the initiation of dialysis, is reportedly higher than the rate of late mortality. Methods We retrospectively studied a cohort of 300 patients, aged 80 years or older, in whom dialysis was initiated between January 1, 2010, and December 31, 2017, at TOHO Hospital (Gunma, Japan). The rate of early mortality was assessed using the Kaplan-Meier method, and the equivalence of survival curves was tested using log-rank tests. The univariate and multivariate analyses were performed using the Cox proportional hazards model. To evaluate nomogram performance, we assessed both the discrimination and calibration of these models. Two hundred bootstrap resamples were used for internal validation of the accuracy estimates to reduce overfit bias and to determine 95% confidence intervals. Results The nomogram was built using the following nine predictors: serum albumin grams per deciliter (hazard ratio [HR] 0.63, p p = 0.004), chronic obstructive pulmonary disease (HR 2.47, p = 0.014), peripheral vascular disease (HR 2.03, p = 0.019), hemiplegia (HR 2.06, p = 0.001), malignant tumors (no metastasis; HR 2.00, p p = 0.006), cardiovascular disease (HR 1.59, p = 0.002), bone fractures due to falls within 1 year (HR 1.85, p = 0.011), and Karnofsky Performance Status (HR 0.98, p Conclusions We developed and validated a nomogram that predicts early mortality in elderly patients at the initiation of dialysis for end-stage renal disease. The nomogram may help nephrologists make a shared decision with patients and families regarding the initiation of dialysis.
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- 2020
19. A case of long-term dasatinib-induced proteinuria and glomerular injury
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Toru Sakairi, Kana Koinuma, Masao Nakasatomi, Keiju Hiromura, Hiroko Hamatani, Mitsuharu Watanabe, Hidekazu Ikeuchi, Takuma Ishizaki, Yoshikazu Watanabe, Azusa IIzuka, and Yoriaki Kaneko
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Nephrology ,medicine.medical_specialty ,medicine.drug_class ,Biopsy ,Kidney Glomerulus ,030232 urology & nephrology ,Urology ,Dasatinib ,Renal function ,Fluorescent Antibody Technique ,Case Report ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Kidney ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Nitriles ,medicine ,Humans ,Protein Kinase Inhibitors ,Proteinuria ,Aniline Compounds ,medicine.diagnostic_test ,business.industry ,Drug Substitution ,Remission Induction ,General Medicine ,Middle Aged ,medicine.disease ,Microscopy, Electron ,Treatment Outcome ,Withholding Treatment ,Creatinine ,Mesangial Cells ,Quinolines ,Female ,Renal biopsy ,medicine.symptom ,business ,Bosutinib ,medicine.drug ,Chronic myelogenous leukemia - Abstract
A 52-year-old woman was diagnosed with chronic myeloid leukemia. Treatment with dasatinib, a second-generation Bcr–Abl tyrosine kinase inhibitor, was initiated, and complete cytogenetic remission was achieved. Two years later, proteinuria occurred, and the urinary protein level increased gradually in the next 3 years. Moreover, the serum creatinine level increased mildly during this period. The urinary protein level reached 2.18 g/gCr; hence, a renal biopsy was conducted. Light microscopy revealed mild proliferation of mesangial cells, and immunofluorescence analysis revealed IgG and C3 depositions in the mesangial area. Electron microscopy revealed electron-dense deposition in the paramesangial area, partial podocyte foot process effacement, and segmental endothelial cell swelling with a slight expansion of the subendothelial space. Dasatinib was discontinued, and within 3 weeks, the proteinuria disappeared, with improvements in her renal function. After switching to bosutinib, a new second-generation of tyrosine kinase inhibitor, the proteinuria remained negative. The rapid cessation of proteinuria following dasatinib discontinuation indicated that proteinuria was induced by the long-term administration of dasatinib. Proteinuria and renal function should be regularly monitored during dasatinib therapy.
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- 2020
20. A case of acute and late coronary events after blunt chest trauma
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Yu Hashimoto, Fumiharu Miura, Hironori Ueda, Shogo Miyamoto, Masashi Takahashi, Hideko Tomimoto, Mitsunori Okamoto, Yoshikazu Watanabe, Naoya Mitsuba, Ryo Yamazato, Yoji Urabe, and Yuichiro Watari
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medicine.medical_specialty ,business.industry ,Flow limitation ,030208 emergency & critical care medicine ,Late onset ,030204 cardiovascular system & hematology ,medicine.disease ,Angina ,03 medical and health sciences ,Stenosis ,0302 clinical medicine ,Blunt ,medicine.anatomical_structure ,Internal medicine ,Right coronary artery ,medicine.artery ,Cardiology ,Medicine ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business ,Artery - Abstract
Mechanisms of acute myocardial infarction caused by traumatic coronary artery injury have been reported. However, late-onset coronary artery stenosis associated with trauma is less well known. We experienced a case in which acute myocardial infarction of the right coronary artery occurred at the time of blunt chest trauma (BCT) caused by a traffic accident and an increase in coronary artery stenosis in the left anterior descending artery (LAD) branch about 1 year later. A comparison of a volume-rendering image created from enhanced-contrast computed tomography at the time of trauma and coronary angiography revealed that the trauma site and the stenotic lesion in the LAD were in very close proximity, suggesting to us that traumatic coronary artery injury without flow limitation may have developed into high-grade stenosis in the LAD 1 year later. In this case we were able to demonstrate a causal relationship between BCT and delayed coronary artery stenosis. After BCT, it is necessary to be aware of the possibility of delayed coronary artery stenosis even if coronary injury is absent in the acute phase.
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- 2018
21. The Origin of Perthite from the Kizaki Rhyolite, Omachi, Nagano Prefecture, Japan
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Yoshikazu, Watanabe, Takanobu, Oba, and Kotaro, Yamagata
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サニディン ,月長石 ,perthite ,木崎流紋岩 ,パーサイト ,sanidine ,Kizaki ,rhyolite moonstone - Published
- 2017
22. Risk stratification of ventricular fibrillation in Brugada syndrome using noninvasive scoring methods
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Shunsuke Tomomori, Yasuki Kihara, Kazuyoshi Suenari, Hidenori Ochi, Takehito Tokuyama, Akinori Awazu, Yusuke Hayashi, Akinori Sairaku, Kyoko Soejima, Yoshikazu Watanabe, Yuko Uchimura, Yukiko Nakano, Hiroshi Kawazoe, Masahiko Takagi, Hiroya Matsumura, Kazuaki Chayama, and Yosuke Miwa
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Adult ,Male ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Logistic regression ,Risk Assessment ,Asymptomatic ,Syncope ,Electrocardiography ,03 medical and health sciences ,QRS complex ,0302 clinical medicine ,Japan ,Risk Factors ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Survival analysis ,Aged ,Brugada Syndrome ,Retrospective Studies ,Brugada syndrome ,Univariate analysis ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Defibrillators, Implantable ,Log-rank test ,Research Design ,Ventricular Fibrillation ,Ventricular fibrillation ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Risk stratification for ventricular fibrillation (VF) in patients with Brugada syndrome (BrS) remains controversial. Objective The purpose of this study was to construct a novel prediction model for VF risk in BrS patients using noninvasive parameters. Methods A total of 143 Japanese BrS patients with VF (n = 35) and without VF (n = 108) were retrospectively enrolled. We built a logistic regression model predicting VF occurrence and evaluated it by cross-validation. Results Frequencies of history of syncope and spontaneous type 1 ECG, r–J interval in V 1 , QRS duration in V 6 , and LAS 40 , Tpeak–Tend dispersion, and max T-wave alternans were significantly associated with VF occurrence in univariate analyses. The history of syncope, r–J interval in V 1 , QRS duration in V 6 , and Tpeak–Tend dispersion were identified as independent predictors by multivariate logistic regression analysis. The predictive model was constructed using all these parameters with good discrimination of VF occurrence (area under the curve 0.869 with 97.1% sensitivity and 65.7% specificity). The area under the curve based on leave-one-out cross-validation was 0.845, with 97.1% sensitivity and 63.0% specificity suggesting good performance of the model. Retrospective survival analysis revealed that the cumulative VF event rate was significantly higher in patients at high risk than in those with low risk using the log rank test ( P = 2.97 × 10 –8 ). Notably, no BrS patient below the cutoff value developed a subsequent VF event. Conclusion This novel prediction method may effectively assesses VF risk in BrS patients, especially when determining implantable cardioverter-defibrillator placement for asymptomatic BrS patients.
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- 2016
23. Novel Baeyer–Villiger-type oxidation of 4,5-epoxymorphinan derivatives
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Naoshi Yamamoto, Tsubasa Hino, Hiroshi Nagase, Yasuyuki Nagumo, Yoshikazu Watanabe, Yuzo Mogi, Noriki Kutsumura, and Tsuyoshi Saitoh
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chemistry.chemical_classification ,Morphinan ,Ketone ,Bicyclic molecule ,010405 organic chemistry ,Stereochemistry ,Carboxylic acid ,Organic Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Oxygen atmosphere ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Cyclopropanecarboxylic acid - Abstract
A novel molecular oxygen-mediated Baeyer–Villiger-type oxidation specific to the morphinan skeleton has been discovered. The reaction of a ketone bearing a bicyclo[2.2.2]octenone skeleton with KOH (pellet) in refluxing tBuOH under an oxygen atmosphere (balloon) afforded unexpected cyclopropanecarboxylic acid and ketolactone derivatives. The reactive sites (carboxylic acid and ester) in those products are oriented over the C-ring in the morphinan skeleton, and thus such morphinan compounds would be useful intermediates to design ideal κ opioid receptor agonists.
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- 2021
24. Increased left atrial pressure in non-heart failure patients with subclinical hypothyroidism and atrial fibrillation
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Yasuki Kihara, Yukiko Nakano, Hiroshi Kawazoe, Takehito Tokuyama, Akinori Sairaku, Hiroya Matsumura, Yuko Uchimura, and Yoshikazu Watanabe
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medicine.medical_specialty ,endocrine system ,Heart disease ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,thyroid-stimulating hormone ,left atrial pressure ,heart failure ,030204 cardiovascular system & hematology ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Thyroid-stimulating hormone ,Internal medicine ,Internal Medicine ,medicine ,atrial fibrillation ,030212 general & internal medicine ,Subclinical infection ,lcsh:RC648-665 ,business.industry ,Thyroid disease ,Research ,Atrial fibrillation ,Odds ratio ,medicine.disease ,subclinical hypothyroidism ,Heart failure ,Cardiology ,Thyroid function ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Background The impact of subclinical hypothyroidism on the cardiovascular risk is still debated. We aimed to measure the relationship between subclinical hypothyroidism and the left atrial (LA) pressure. Methods The LA pressures and thyroid function were measured in consecutive patients undergoing atrial fibrillation (AF) ablation, who did not have any known heart failure, structural heart disease, or overt thyroid disease. Results Subclinical hypothyroidism (4.5≤ thyroid-stimulating hormone P = 0.04). The mean LA pressure (10.9 ± 4.7 vs 9.1 ± 4.3 mmHg; P = 0.002) and LA V-wave pressure (17.4 ± 6.5 vs 14.3 ± 5.9 mmHg; P < 0.001) were, respectively, higher in the patients with subclinical hypothyroidism than in the euthyroid patients. After an adjustment for potential confounders, the LA pressures remained significantly higher in the subclinical hypothyroidism patients. A multiple logistic regression model showed that subclinical hypothyroidism was independently associated with a mean LA pressure of >18 mmHg (odds ratio 3.94, 95% CI 1.28 11.2; P = 0.02). Conclusions Subclinical hypothyroidism may increase the LA pressure in AF patients.
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- 2016
25. A Great Space Weather Event in February 1730
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Hiroaki Isobe, José M. Vaquero, Satoshi Hayakawa, Kentaro Hattori, Yoshikazu Watanabe, Víctor M. S. Carrasco, Kiyomi Iwahashi, Harufumi Tamazawa, Yusuke Ebihara, Hisashi Hayakawa, María Cruz Gallego, and Akito Davis Kawamura
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Physics ,010504 meteorology & atmospheric sciences ,Interdisciplinary education ,Library science ,FOS: Physical sciences ,Astronomy and Astrophysics ,Astrophysics ,01 natural sciences ,Astrophysics - Solar and Stellar Astrophysics ,Space and Planetary Science ,0103 physical sciences ,010303 astronomy & astrophysics ,Solar and Stellar Astrophysics (astro-ph.SR) ,0105 earth and related environmental sciences - Abstract
Aims. Historical records provide evidence of extreme magnetic storms with equatorward auroral extensions before the epoch of systematic magnetic observations. One significant magnetic storm occurred on February 15, 1730. We scale this magnetic storm with auroral extension and contextualise it based on contemporary solar activity. Methods. We examined historical records in East Asia and computed the magnetic latitude (MLAT) of observational sites to scale magnetic storms. We also compared them with auroral records in Southern Europe. We examined contemporary sunspot observations to reconstruct detailed solar activity between 1729 and 1731. Results. We show 29 auroral records in East Asian historical documents and 37 sunspot observations. Conclusions. These records show that the auroral displays were visible at least down to 25.8{\deg} MLAT throughout East Asia. In comparison with contemporary European records, we show that the boundary of the auroral display closest to the equator surpassed 45.1{\deg} MLAT and possibly came down to 31.5{\deg} MLAT in its maximum phase, with considerable brightness. Contemporary sunspot records show an active phase in the first half of 1730 during the declining phase of the solar cycle. This magnetic storm was at least as intense as the magnetic storm in 1989, but less intense than the Carrington event., Comment: 30 pages, 5 figures, and 2 tables, accepted for publication in Astronomy & Astrophysics on 25 April 2018. The figures and transcriptions/translations of historical documents are partially omitted in this manuscript due to the condition of reproduction. They are available in the publisher version
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- 2018
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26. Accelerating NFV application using CPU-FPGA tightly coupled architecture
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Yuki Kobayashi, Takeo Hosomi, Yoshikazu Watanabe, Takashi Takenaka, and Yuichi Nakamura
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010302 applied physics ,business.industry ,Computer science ,020206 networking & telecommunications ,02 engineering and technology ,Internet traffic ,01 natural sciences ,Software ,Server ,Embedded system ,0103 physical sciences ,0202 electrical engineering, electronic engineering, information engineering ,Forwarding plane ,Table (database) ,business ,Field-programmable gate array ,Queue ,Commercial off-the-shelf - Abstract
Network Function Visualization (NFV) is becoming a new networking architecture for telecom carriers. NFV achieves network functions with software and commercial off the shelf (COTS) servers instead of dedicated hardware. While the software-based approach is expected to reduce costs, it could cause performance issues. CPU-FPGA tightly coupled architectures may be available in COTS servers in the near future. This paper proposes accelerating NFV application leveraging such a CPU-FPGA architecture. The proposed method of acceleration uses a data plane development kit (DPDK) ring queue, which is often used in network software, as the communication interface between the FPGA and CPU. We propose two optimizations for ring operation and table lookup operation to efficiently use the bus between FPGA and CPU. We evaluated the proposed method with an actual CPU+FPGA based platform, and an NFV application, i.e., vCPE. The results revealed that the evaluation system could accommodate 2 × 40-GbE Internet traffic, and could increase capacity as a vCPE server by x1.33.
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- 2017
27. Design and synthesis of novel δ opioid receptor agonists with an azatricyclodecane skeleton for improving blood-brain barrier penetration
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Hiroshi Nagase, Shigeto Hirayama, Toshihiro Takahashi, Kohei Hayashida, Takashi Iwai, Yoshikazu Watanabe, Eriko Nakata, Saito Daisuke, Junichi Sakai, Takashi Kanda, Hideaki Fujii, and Tomio Yamakawa
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Stereochemistry ,medicine.drug_class ,Clinical Biochemistry ,Pharmaceutical Science ,010402 general chemistry ,Administration, Cutaneous ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Mice ,Opioid receptor ,Blood brain barrier penetration ,Receptors, Opioid, delta ,Drug Discovery ,medicine ,Animals ,Humans ,Methylene ,Molecular Biology ,Carbon atom ,010405 organic chemistry ,Organic Chemistry ,In vitro toxicology ,Cyclodecanes ,Skeleton (computer programming) ,0104 chemical sciences ,Analgesics, Opioid ,chemistry ,Permeability (electromagnetism) ,Blood-Brain Barrier ,Drug Design ,Molecular Medicine ,Bbb permeability - Abstract
We designed and synthesized novel δ opioid receptor (DOR) agonists 3a – i with an azatricyclodecane skeleton, which was a novel structural class of DOR agonists. Among them, 3b exhibited high values of binding affinity and potent agonistic activity for the DOR that were approximately equivalent to those of 2 which bore an oxazatricyclodecane skeleton. In vitro assays using the blood-brain barrier (BBB) permeability test kit supported the idea that 3b achieved an excellent BBB permeability by converting an oxygen atom of 2 to a carbon atom (methylene group) in the core skeleton. As a result, 3b showed potent antinociceptive effects.
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- 2017
28. Deterioration of the circadian variation of heart rate variability in Brugada syndrome may contribute to the pathogenesis of ventricular fibrillation
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Chikaaki Motoda, Noboru Oda, Yasuki Kihara, Yuko Uchimura-Makita, Akinori Awazu, Kenta Kajihara, Takehito Tokuyama, Akinori Sairaku, Yoshikazu Watanabe, Mai Fujiwra, and Yukiko Nakano
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Autonomic function ,Adult ,Male ,medicine.medical_specialty ,Autonomic Nervous System ,Sensitivity and Specificity ,Pathogenesis ,Electrocardiography ,Heart Rate ,Internal medicine ,medicine ,Heart rate variability ,Humans ,Circadian rhythm ,Brugada syndrome ,Brugada Syndrome ,medicine.diagnostic_test ,business.industry ,fungi ,Middle Aged ,medicine.disease ,Circadian Rhythm ,Autonomic nervous system ,Ventricular fibrillation ,Ventricular Fibrillation ,Cardiology ,business ,Cardiology and Cardiovascular Medicine - Abstract
Aims Abnormal sympathetic innervation triggers ventricular fibrillation (VF). We examined the circadian variation of autonomic nervous system and its relevance to risk stratification of VF in patients with Brugada syndrome (Brs). Methods We enrolled 12 male Brs patients with documented VF (Brs-S; mean age, 42 ± 4 years), 17 without documented VF (Brs-N; mean age 48 ± 4 years), and 16 age- and gender-matched controls. The clinical data, 12-lead electrocardiography (ECG), signal-averaged ECG, electrophysiological study (EPS), and heart rate variability from 24 h Holter ECG were compared between the groups. Results The low frequency components (LF) in Brs-S and Brs-N and high frequency components (HF) in Brs-S patients were significantly lower than in the controls (409.8 ± 128.6 ms 2 , 329.5 ± 108 ms 2 vs. 945.3 ± 111.3 ms 2 ; 135.1 ± 73.8 ms 2 vs. 391.8 ± 63.9 ms 2 , respectively). The circadian variation of the LF and LF/HF decreased in the Brs patients, the standard deviation (SD) of LF/HF ( 2 ) had sufficiently high sensitivity (96.6%) and specificity (92.9%) for the diagnosis of Brs. Most of the Brs-S patients (83.3%) were located under the line formed by the SD/mean of HF = SD/mean of LF in the scatter plots. Conclusion Lack of the circadian variation of autonomic function occurs in Brs, and this may contribute to the pathogenesis of VF.
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- 2014
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29. Time-Domain T-Wave Alternans is Strongly Associated with a History of Ventricular Fibrillation in Patients with Brugada Syndrome
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Yukiko Nakano, Nozomu Oda, Yuko Uchimura-Makita, Richard L. Verrier, Yasuki Kihara, Hiroya Matsumura, Chikaaki Motoda, Mai Fujiwara, Noboru Oda, Hiroshi Kawazoe, Takehito Tokuyama, Kenta Kajihara, Yoshikazu Watanabe, Akinori Sairaku, and Hiroki Ikanaga
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Incidence (epidemiology) ,T wave alternans ,Implantable cardioverter-defibrillator ,medicine.disease ,Sudden death ,Sudden cardiac death ,Physiology (medical) ,Internal medicine ,Ventricular fibrillation ,medicine ,Cardiology ,cardiovascular diseases ,Family history ,Cardiology and Cardiovascular Medicine ,business ,Brugada syndrome - Abstract
Time-Domain T-Wave Alternans and Brugada Syndrome Aims T-wave alternans (TWA) is an indicator of vulnerability to ventricular arrhythmias and is useful for predicting sudden cardiac death (SCD) in patients with various structural heart diseases. We evaluated whether high levels of time-domain TWA on ambulatory ECG (AECG) are associated with a history of ventricular fibrillation (VF) in Brugada syndrome (BrS) patients. Methods and Results We examined the associations among VF history, family history of SCD, spontaneous type 1 electrocardiogram (ECG), late potentials, VF induction by programmed electrical stimulation, and TWA in 45 BrS patients (44 males; mean age, 45 ± 15 years). TWA analyzed from 24-h AECG recordings using the modified moving average method was positive in 13 of 43 patients (30%). Patients with a history of VF had a significantly higher incidence of a positive TWA test (82% vs. 13%; P < 0.001) and spontaneous type 1 ECG (92% vs. 38%; P = 0.007) than those without VF history. Multivariate analysis indicated that positive TWA (OR 7.217; 95% CI 2.503–35.504; P = 0.002) and spontaneous type 1 ECG (OR 5.530; 95% CI 1.651–34.337; P = 0.020) were closely associated with VF history. Spontaneous type 1 ECG had high sensitivity (92%) but low specificity (63%). Positive TWA was a reliable marker with high sensitivity and specificity (82% and 88%, respectively). Conclusion Elevated time-domain TWA on AECG confirms arrhythmia risk in symptomatic BrS patients without the need for provocative stimuli.
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- 2014
30. Incomplete Cure of Tachycardia-Induced Cardiomyopathy Secondary to Rapid Atrial Fibrillation by Heart Rate Control Without Sinus Conversion
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Yukiko Nakano, Mai Fujiwara, Hiroya Matsumura, Takehito Tokuyama, Hiroshi Kawazoe, Akinori Sairaku, Noboru Oda, Yuko Uchimura, Yasuki Kihara, and Yoshikazu Watanabe
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Cardiomyopathy ,Hemodynamics ,Atrial fibrillation ,medicine.disease ,Tachycardia-induced cardiomyopathy ,Physiology (medical) ,Internal medicine ,Anesthesia ,Heart rate ,medicine ,Cardiology ,Decompensation ,Sinus rhythm ,Cardiology and Cardiovascular Medicine ,business - Abstract
Incomplete Cure of TIC with Rate ControlBackground It is uncertain whether rate or rhythm control is more favorable for patients experiencing tachycardia-induced cardiomyopathy (TIC) secondary to rapid atrial fibrillation (AF). Methods and Results We compared the electrophysiological and hemodynamic properties and outcome after AF ablation in 20 patients with a history of decompensated TIC who maintained sinus rhythm or had paroxysmal AF (group 1), 32 with a history of decompensated TIC who had persistent or longstanding persistent AF (group 2), 377 without TIC who had paroxysmal AF (group 3), and 225 without TIC who had persistent or longstanding persistent AF (group 4). The corrected sinus node recovery time was more prolonged in group 2 than in groups 1, 3, or 4 (1,066 ± 946 vs. 416 ± 188, 450 ± 322 and 590 ± 329 milliseconds; P < 0.001, respectively). The mean left atrial pressure in group 2 was greater than that in groups 1, 3, or 4 (13.9 ± 6.5 vs. 7.5 ± 3.1, 8.2 ± 4.1 and 10.8 ± 4.2 mmHg; P < 0.001, respectively). The left ventricular ejection fraction assessed after the recovery from the decompensation was more decreased in group 2 than in group 1; however, it almost returned to normal if sinus rhythm was maintained after the AF ablation in group 2. The presence of a history of TIC did not predict an AF recurrence after the ablation. Conclusions Heart rate control during AF without sinus conversion may result in an incomplete cure of TIC, suggesting the advantages of rhythm control with ablation in patients with TIC.
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- 2014
31. Variable Procedural Strategies Adapted to Anatomical Characteristics in Catheter Ablation of the Cavotricuspid Isthmus Using a Preoperative Multidetector Computed Tomography Analysis
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Hiroshi Ogi, Akinori Sairaku, Yukiko Nakano, Noboru Oda, Mai Fujiwara, Yasuki Kihara, Chikaaki Motoda, R T Masao Kiguchi, Takehito Tokuyama, Yukoh Hirai, Kazuyoshi Suenari, Yoshikazu Watanabe, Kenta Kajihara, and Yuko Makita
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Catheter ablation ,medicine.disease ,Ablation ,Preoperative care ,Catheter ,Physiology (medical) ,Predictive value of tests ,Medicine ,Tomography ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Prospective cohort study ,Atrial flutter - Abstract
Variable Strategies for CTI Ablation Objectives This study aimed to investigate the anatomical characteristics complicating cavotricuspid isthmus (CTI) ablation and the effectiveness of various procedural strategies. Methods and Results This study included 446 consecutive patients (362 males; mean age 60.5 ± 10.4 years) in whom CTI ablation was performed. A total of 80 consecutive patients were evaluated in a preliminary study. The anatomy of the CTI was evaluated by multidetector row-computed tomography (MDCT) prior to the procedure. A multivariate logistic regression analysis revealed that the angle and mean wall thickness of the CTI, a concave CTI morphology, and a prominent Eustachian ridge, were associated with a difficult CTI ablation (P < 0.01). In the main study, 366 consecutive patients were divided into 2 groups: a modulation group (catheter inversion technique for a concave aspect, prominent Eustachian ridge, and steep angle of the CTI or increased output for a thicker CTI) and nonmodulation group (conventional strategy). The duration and total amount of radiofrequency energy delivered were significantly shorter and smaller in the modulation group than those in the nonmodulation group (162.2 ± 153.5 vs 222.7 ± 191.9 seconds, P < 0.01, and 16,962.4 ± 11,545.6 vs 24,908.5 ± 22,804.2 J, P < 0.01, respectively). The recurrence rate of type 1 atrial flutter after the CTI ablation in the nonmodulation group was significantly higher than that in the modulation group (6.3 vs 1.7%, P = 0.02). Conclusion Changing the procedural strategies by adaptating them to the anatomical characteristics improved the outcomes of the CTI ablation.
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- 2013
32. Variable Procedural Strategies Adapted to Anatomical Characteristics in Catheter Ablation of the Cavotricuspid Isthmus Using a Preoperative Multidetector Computed Tomography Analysis
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Kenta, Kajihara, Yukiko, Nakano, Yukoh, Hirai, Hiroshi, Ogi, Noboru, Oda, Kazuyoshi, Suenari, Yuko, Makita, Akinori, Sairaku, Takehito, Tokuyama, Chikaaki, Motoda, Mai, Fujiwara, Yoshikazu, Watanabe, Masao, Kiguchi, and Yasuki, Kihara
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Male ,Time Factors ,Original Articles ,Middle Aged ,multidetector row-computed tomography ,eustachian ridge ,Logistic Models ,Treatment Outcome ,Japan ,Atrial Flutter ,Predictive Value of Tests ,Recurrence ,Risk Factors ,cavotricuspid isthmus ,Multivariate Analysis ,Preoperative Care ,catheter ablation ,Multidetector Computed Tomography ,Humans ,Female ,Heart Atria ,Prospective Studies ,Electrophysiologic Techniques, Cardiac ,Aged - Abstract
Variable Strategies for CTI Ablation Objectives This study aimed to investigate the anatomical characteristics complicating cavotricuspid isthmus (CTI) ablation and the effectiveness of various procedural strategies. Methods and Results This study included 446 consecutive patients (362 males; mean age 60.5 ± 10.4 years) in whom CTI ablation was performed. A total of 80 consecutive patients were evaluated in a preliminary study. The anatomy of the CTI was evaluated by multidetector row-computed tomography (MDCT) prior to the procedure. A multivariate logistic regression analysis revealed that the angle and mean wall thickness of the CTI, a concave CTI morphology, and a prominent Eustachian ridge, were associated with a difficult CTI ablation (P < 0.01). In the main study, 366 consecutive patients were divided into 2 groups: a modulation group (catheter inversion technique for a concave aspect, prominent Eustachian ridge, and steep angle of the CTI or increased output for a thicker CTI) and nonmodulation group (conventional strategy). The duration and total amount of radiofrequency energy delivered were significantly shorter and smaller in the modulation group than those in the nonmodulation group (162.2 ± 153.5 vs 222.7 ± 191.9 seconds, P < 0.01, and 16,962.4 ± 11,545.6 vs 24,908.5 ± 22,804.2 J, P < 0.01, respectively). The recurrence rate of type 1 atrial flutter after the CTI ablation in the nonmodulation group was significantly higher than that in the modulation group (6.3 vs 1.7%, P = 0.02). Conclusion Changing the procedural strategies by adaptating them to the anatomical characteristics improved the outcomes of the CTI ablation.
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- 2013
33. Common Variant Near HEY2 Has a Protective Effect on Ventricular Fibrillation Occurrence in Brugada Syndrome by Regulating the Repolarization Current
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Shunsuke Tomomori, Hiroshi Kawazoe, Takehito Tokuyama, Kazuyoshi Suenari, Nozomu Oda, Akinori Sairaku, Noboru Oda, Satoshi Tashiro, Chikaaki Motoda, Yasufumi Hayashida, Shinji Kishimoto, Hiroya Matsumura, Yukihiko Yoshida, Daiki Miki, Masaaki Toshishige, Yoshikazu Watanabe, Hidenori Ochi, Hiroki Ikenaga, Yuko Onohara, Yukiko Nakano, Kazuaki Chayama, and Yasuki Kihara
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Genotype ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Polymorphism, Single Nucleotide ,QT interval ,Disease-Free Survival ,Electrocardiography ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Physiology (medical) ,Internal medicine ,Basic Helix-Loop-Helix Transcription Factors ,Odds Ratio ,medicine ,Humans ,Repolarization ,Survival analysis ,Brugada Syndrome ,Brugada syndrome ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Implantable cardioverter-defibrillator ,Repressor Proteins ,030104 developmental biology ,Ventricular Fibrillation ,Ventricular fibrillation ,Cardiology ,RNA ,Female ,Cardiology and Cardiovascular Medicine ,business ,Genome-Wide Association Study - Abstract
Background— Risk stratification of Brugada syndrome (BrS) remains controversial and the majority of patients with BrS have no genetic explanation. We investigated relationships between genotypes of 3 single-nucleotide polymorphisms reported in a recent genome-wide association study and BrS phenotypes. Methods and Results— SCN10A (rs10428132), SCN5A (rs11708996), and downstream from HEY2 (rs9388451) single-nucleotide polymorphisms were genotyped and compared between 95 Japanese patients with BrS and 1978 controls. Relationships between the single-nucleotide polymorphisms and clinical characteristics, 12-lead ECG findings, signal-averaged ECG findings, and electrophysiological parameters were also examined in patients with BrS. Both rs10428132 and rs9388451 were significantly associated with BrS ( P =2.7×10 −14 ; odds ratio, 3.0; P =9.2×10 −4 ; odds ratio, 1.7, respectively). Interestingly, the HEY2 risk allele C was less frequent in BrS patients with ventricular fibrillation than in those without (59% versus 74%; P =4.1×10 −2 ; odds ratio, 0.5). A significant linear correlation was found between HEY2 genotypes and QTc interval (CC: 422±27 ms; CT: 408±21 ms; and TT: 381±27 ms; P = 4.0×10 −4 ). The HEY2 mRNA expression level in the right ventricular specimens from patients with BrS (n=20) was significantly lower in patients with CC genotype than the other genotypes ( P =0.04). Additionally, during 63±28 months follow-up periods after implantable cardioverter defibrillator implantation (n=90), Kaplan–Meier event-free survival curves revealed that the cumulative rate of ventricular fibrillation events was significantly lower in cases with HEY2 CC genotype ( P =0.04). Conclusions— Our findings suggest that HEY2 CC genotype may be a favorable prognostic marker for BrS, protectively acting to prevent ventricular fibrillation presumably by regulating the repolarization current.
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- 2016
34. Design and synthesis of novel opioid ligands with an azabicyclo[2.2.2]octane skeleton and their pharmacologies
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Hideaki Fujii, Toru Nemoto, Hiroshi Nagase, Shigeto Hirayama, Shota Kitazawa, and Yoshikazu Watanabe
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μ receptor ,Stereochemistry ,Clinical Biochemistry ,Imine ,Receptors, Opioid, mu ,Pharmaceutical Science ,Ligands ,Biochemistry ,Bridged Bicyclo Compounds ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Spiro Compounds ,Molecular Biology ,Octane ,Aza Compounds ,Molecular Structure ,Ligand ,Organic Chemistry ,Octanes ,Skeleton (computer programming) ,Analgesics, Opioid ,Morphinans ,chemistry ,Opioid ,Drug Design ,Receptors, Opioid ,Molecular Medicine ,Protein Binding ,medicine.drug - Abstract
A novel opioid ligand possessing a stable and cyclic imine 16 and its derivatives with an azabicyclo[2.2.2]octane skeleton were synthesized. The imine 16 showed higher affinity for the μ receptor than compound 21 with an oxabicyclo[2.2.2]octane skeleton. Azabicyclo[2.2.2]octane derivative 18d with a cyclopropylmethyl group on the 8-nitrogen showed the highest affinity for the μ receptor among the synthesized derivatives.
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- 2012
35. Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR5)
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Eyup Akgün, Mary M. Lunzer, Yoshikazu Watanabe, Michael D. Powers, Yuk Y. Sham, Philip S. Portoghese, and Muhammad I. Javed
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Agonist ,Male ,Models, Molecular ,Chemokine ,Receptors, CCR5 ,medicine.drug_class ,Heteromer ,Receptors, Opioid, mu ,CCR5 receptor antagonist ,Pharmacology ,Article ,Chemokine receptor ,Mice ,Drug Discovery ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Inflammation ,Analgesics ,biology ,Chemistry ,HEK293 Cells ,Opioid ,CCR5 Receptor Antagonists ,Chronic Disease ,Morphine ,biology.protein ,Molecular Medicine ,Neuralgia ,μ-opioid receptor ,medicine.drug - Abstract
Chemokine release promotes cross-talk between opioid and chemokine receptors that in part leads to reduced efficacy of morphine in the treatment of chronic pain. On the basis of the possibility that a MOR-CCR5 heteromer is involved in such cross-talk, we have synthesized bivalent ligands (MCC series) that contain mu opioid agonist and CCR5 antagonist pharmacophores linked through homologous spacers (14–24 atoms). When tested on lipopolysaccharide-inflamed mice, a member of the series (MCC22; 3e) with a 22-atom spacer exhibited profound antinociception (i.t. ED50 = 0.0146 pmol/mouse) that was 2000× greater than morphine. Moreover, MCC22 was ∼3500× more potent than a mixture of mu agonist and CCR5 antagonist monovalent ligands. These data strongly suggest that MCC22 acts by bridging the protomers of a MOR-CCR5 heteromer having a TM5,6 interface. Molecular simulation studies are consistent with such bridging. This study supports the MOR-CCR5 heteromer as a novel target for the treatment of chronic pain.
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- 2015
36. Novel rearrangement reaction of a 6,14-endoethanomorphinan derivative to a benzomorphan derivative
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Yoshikazu Watanabe, Yumiko Osa, Hideaki Fujii, Toru Nemoto, Noriko Sato, and Hiroshi Nagase
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chemistry.chemical_classification ,Reaction mechanism ,Stereochemistry ,Trifluoromethanesulfonic anhydride ,Organic Chemistry ,Reaction intermediate ,Biochemistry ,Chemical synthesis ,Benzomorphan ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Rearrangement reaction ,Derivative (chemistry) ,Lactone - Abstract
Treatment of 7α-hydroxymethylendoethenomorphinan derivative with trifluoromethanesulfonic anhydride at rt and subsequent toluene reflux afforded a novel lactone by rearrangement reaction. The skeleton of the lactone is analogous to that of the benzomorphan like pentazocine, which is a useful analgesic. The rearrangement reaction opens the door to a facile synthesis from the 4,5-epoxymorphinans to the benzomorphan derivatives. On the basis of careful examination of the reaction intermediates, a reaction mechanism was proposed.
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- 2009
37. Impact of Metabolic Syndrome on Coronary Plaque Vulnerability in Japanese Women With Acute Coronary Syndrome
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Kentaro Ueda, Yoshinori Nakano, Keigo Dote, Shota Sasaki, Toru Naganuma, Yoshikazu Watanabe, Haruko Yokoyama, and Masaya Kato
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Carotid Artery Diseases ,medicine.medical_specialty ,Acute coronary syndrome ,Coronary Angiography ,Severity of Illness Index ,Coronary artery disease ,Lesion ,Asian People ,Japan ,Predictive Value of Tests ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,Prevalence ,medicine ,Humans ,Acute Coronary Syndrome ,Aged ,Ultrasonography ,Aged, 80 and over ,Metabolic Syndrome ,business.industry ,Carotid ultrasonography ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Pathophysiology ,Cardiology ,Female ,Metabolic syndrome ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Previous study has demonstrated that metabolic syndrome (MetS) can predict cardiovascular mortality in men, but the prediction was weak for women. In the present study predictors for multiple complex coronary lesions were investigated to clarify the impact of MetS in Japanese women with acute coronary syndrome (ACS). Methods and Results Subjects were Japanese women with ACS (n=81) who underwent emergency coronary angiography and B-mode carotid ultrasonography. They were divided into 2 groups based on the number of complex plaques. Although the MetS prevalence identified using the Japanese criteria was similar between the 2 groups, using the modified ATP III criteria it was more in patients with multiple coronary lesions than in those with a single coronary lesion (p
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- 2008
38. SmI2-mediated reduction of gamma, gamma-difluoro-alpha,beta-enoates with application to the synthesis of functionalized (Z)-fluoroalkene-type dipeptide isosteres
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Otaka, Akira, Watanabe, Junko, Yukimasa, Akira, Sasaki, Yoshikazu ; Watanabe, Hideaki ; Kinoshita, Takayoshi, and Oishi, Shinya ; Tamamura, Hirokazu ; Fujii, Nobutaka
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Organic compounds -- Research ,Oxidation-reduction reaction -- Research ,Peptides -- Research ,Amino acids -- Research ,Biological sciences ,Chemistry - Abstract
The study conducted to examine the feasibility of the (SmI2)-mediated reduction of gamma, gamma-difluoro-alpha,beta-enoates and its application to the synthesis of fluoroalkene dipeptide isosteres, is presented. The synthesis of chiral alpha-functionalized (Z)-fluoroalkene dipeptide isosteres is demonstrated.
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- 2004
39. Abstract 13486: Risk Stratification of Ventricular Fibrillation in Brugada Syndrome Using Non-invasive Scoring Methods
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Hiroshi Kawazoe, Yukiko Nakano, Takehito Tokuyama, Yuko Uchimura, Yoshikazu Watanabe, Akinori Sairaku, Hiroya Matsumura, Shinji Kishimoto, Shunsuke Tomomori, and Yasuki Kihara
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congenital, hereditary, and neonatal diseases and abnormalities ,Physiology (medical) ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine - Abstract
Aim: Risk stratification of ventricular fibrillation (VF) in Brugada syndrome remains controversial and it is difficult to describe using one parameter. We investigated whether we are able to assess VF risk using our non-invasive scoring method of each Brugada syndrome patients. Methods: We enrolled 46 patients with Brugada syndrome (45 men, average age 42 ± 3 years). Thirteen of the subjects had VF history or subsequent VF events (VF+) after implantable cardioverter defibrillator implantation. The frequency of Type1 Brugada ECG and positive TWA were significantly higher in VF+ patients than those without (Type 1 ECG 50% vs 4.8%, P=0.0003 and positive TWA 73.3% vs 6.7%, P Conclusions: The new scoring method using previous reported non-invasive risk factors of VF in Brugada syndrome is useful for assessing risk stratification in daily medical practice.
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- 2014
40. Abstract 13618: Negative Association of H558r Polymorphism and Ventricular Fibrillation in Patients With Brugada Syndrome
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Shunsuke Tomomori, Yoshikazu Watanabe, Takehito Tokuyama, Masaaki Toshishige, Hidenori Ochi, Hiroya Matsumura, Yasuki Kihara, Kazuaki Chayama, Yukiko Nakano, Sinji Kishimoto, and Hiroshi Kawazoe
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Sodium channel activity ,medicine.medical_specialty ,business.industry ,medicine.disease ,QT interval ,Minor allele frequency ,QRS complex ,Polymorphism (computer science) ,Physiology (medical) ,Internal medicine ,Ventricular fibrillation ,Cardiology ,Medicine ,Population study ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business ,Brugada syndrome - Abstract
BACKGROUND: The common SCN5A polymorphism H558R has been reported as a genetic modulator that improves sodium channel activity in mutated channels by repairing abnormal channel gating kinetics and membrane trafficking. We investigated the possible effects of H558R on the clinical manifestations of Brugada syndrome. METHODS: The study population comprised 95 Brugada syndrome patients (mean age 42 ± 14 years, 91 males and 4 females) and 1,875 normal controls. H558R was genotyped by TaqMan assay in all subjects. The SCN5A gene mutation was screened by resequencing. We evaluated the PR, QRS, and QTc intervals from lead II and the J-point amplitude from leads V1 and V2 of a 12-lead electrocardiogram (ECG). We also evaluated signal-averaged ECG and electrophysiological parameters. RESULTS: H558R was less frequent in patients with Brugada syndrome than normal controls (4.7% vs. 10.3%, P = 0.01). Surprisingly, H558R (minor allele A) was not observed in patients with Brugada syndrome without ventricular fibrillation (VF; n = 60), whereas 7.5% of patients with VF had H558R (n = 35). Nonsynonymous mutation of SCN5A was not detected in patients with H558R. The H558R carriers showed lower J-point elevation in lead V1 than noncarriers (1.8 ± 0.4 vs. 3.3 ± 0.3 mV, P = 0.04). Other parameters in the 12-lead and signal-averaged ECG were similar in patients with and without H558R. CONCLUSION: We demonstrated that the H558R polymorphism was a strong protective genetic modulator even in Brugada syndrome patients without SCN5A mutation.
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- 2014
41. Mechanical and substrate abnormalities of the left atrium assessed by 3-dimensional speckle-tracking echocardiography and electroanatomic mapping system in patients with paroxysmal atrial fibrillation
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Hiroshi Kawazoe, Takehito Tokuyama, Chikaaki Motoda, Akinori Sairaku, Yuko Uchimura, Kenta Kajihara, Hiroya Matsumura, Takayuki Hidaka, Yasuki Kihara, Noboru Oda, Yoshikazu Watanabe, Yukiko Nakano, and Mai Fujiwara
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Male ,Electroanatomic mapping ,medicine.medical_specialty ,Paroxysmal atrial fibrillation ,Echocardiography, Three-Dimensional ,Speckle tracking echocardiography ,Pulmonary vein ,Electrocardiography ,Heart Conduction System ,Physiology (medical) ,Internal medicine ,Atrial Fibrillation ,Medicine ,Humans ,In patient ,Sinus rhythm ,Heart Atria ,Aged ,business.industry ,Atrial fibrillation ,Middle Aged ,medicine.disease ,Confidence interval ,Pulmonary Veins ,Cardiology ,Catheter Ablation ,Atrial Function, Left ,Female ,Cardiology and Cardiovascular Medicine ,business ,Electrophysiologic Techniques, Cardiac - Abstract
Left atrial (LA) remodeling progresses to electrical remodeling, contractile remodeling, and subsequently structural remodeling. Little is known about the relationship between LA electrical and anatomical remodeling and LA mechanical function.We aimed to clarify the relationship between LA mechanical function using 3-dimensional speckle-tracking echocardiography (3D-STE) and LA electrical remodeling using an electroanatomic mapping system (CARTO 3) and to estimate atrial fibrillation (AF) substrate in patients with paroxysmal AF (PAF).A total of 52 patients with PAF (41 (79%) men; mean age 61 ± 11 years) undergoing their initial pulmonary vein isolation (PVI) were examined. The standard deviation of the time to peak strain in each LA segment (%SD-TPS) was analyzed as an index of LA dyssynchrony using 3D-STE before PVI. Contact LA bipolar voltage and activation maps were constructed during sinus rhythm before PVI using CARTO 3. The LA total activation time was measured and low-voltage zones (LVZs) were determined with a local bipolar electrogram amplitude of0.5 mV. The patients were divided into those with an LVZ (LVZ group; n = 23) and those without an LVZ (non-LVZ group; n = 29).The %SD-TPS was significantly higher (14.1 ± 5.7 vs 8.0 ± 5.1; P=.0002) in the LVZ group than in the non-LVZ group and was an independent determinant of the LVZ (odds ratio 1.21; 95% confidence interval 1.04-1.49; P=.01). In addition, the LA total activation time was weakly correlated with the %SD-TPS.LA dyssynchrony and conduction delay exist in patients with PAF. The 3D-STE enabled noninvasive estimation of LA electrical remodeling and AF substrate.
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- 2014
42. Design, synthesis, and structure-activity relationship of novel opioid κ receptor selective agonists: α-iminoamide derivatives with an azabicyclo[2.2.2]octene skeleton
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Yoshikazu Watanabe, Hideaki Fujii, Shuichi Hirono, Hiroaki Gouda, Shota Kitazawa, Shigeto Hirayama, Toru Nemoto, Hiroshi Nagasea, and Takashi Iwai
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Agonist ,medicine.drug_class ,Stereochemistry ,Clinical Biochemistry ,Molecular Conformation ,Pharmaceutical Science ,Biochemistry ,chemistry.chemical_compound ,Bridged Bicyclo Compounds ,Structure-Activity Relationship ,Amide ,Drug Discovery ,medicine ,Structure–activity relationship ,Humans ,Octene ,Molecular Biology ,Octane ,Aza Compounds ,Molecular Structure ,Receptors, Opioid, kappa ,Organic Chemistry ,Chemical modification ,Amides ,chemistry ,Opioid ,Drug Design ,Molecular Medicine ,Selectivity ,medicine.drug ,Protein Binding - Abstract
The α-iminoamide derivative, 4b was designed and synthesized as a novel agonist selective for the opioid κ receptor. The amide was constrained to an orientation horizontal to the F-ring of the azabicyclo[2.2.2]octane skeleton, which remarkably improved its affinity, selectivity, and agonistic activity for the κ receptor. This finding was newly established by chemical modification of the nitrogen atom at the 8-position in the azabicyclo[2.2.2]octane skeleton. This modification would never have been found with KNT-63, a derivation of oxabicyclo[2.2.2]octane. These results may provide valuable information for the future development of novel κ selective agonists.
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- 2014
43. Incomplete cure of tachycardia-induced cardiomyopathy secondary to rapid atrial fibrillation by heart rate control without sinus conversion
- Author
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Akinori, Sairaku, Yukiko, Nakano, Noboru, Oda, Yuko, Uchimura, Takehito, Tokuyama, Hiroshi, Kawazoe, Mai, Fujiwara, Yoshikazu, Watanabe, Hiroya, Matsumura, and Yasuki, Kihara
- Subjects
Male ,Comorbidity ,Middle Aged ,Disease-Free Survival ,Causality ,Treatment Outcome ,Japan ,Risk Factors ,Atrial Fibrillation ,Catheter Ablation ,Prevalence ,Tachycardia, Ventricular ,Humans ,Female ,Treatment Failure ,Cardiomyopathies - Abstract
It is uncertain whether rate or rhythm control is more favorable for patients experiencing tachycardia-induced cardiomyopathy (TIC) secondary to rapid atrial fibrillation (AF).We compared the electrophysiological and hemodynamic properties and outcome after AF ablation in 20 patients with a history of decompensated TIC who maintained sinus rhythm or had paroxysmal AF (group 1), 32 with a history of decompensated TIC who had persistent or longstanding persistent AF (group 2), 377 without TIC who had paroxysmal AF (group 3), and 225 without TIC who had persistent or longstanding persistent AF (group 4). The corrected sinus node recovery time was more prolonged in group 2 than in groups 1, 3, or 4 (1,066 ± 946 vs. 416 ± 188, 450 ± 322 and 590 ± 329 milliseconds; P0.001, respectively). The mean left atrial pressure in group 2 was greater than that in groups 1, 3, or 4 (13.9 ± 6.5 vs. 7.5 ± 3.1, 8.2 ± 4.1 and 10.8 ± 4.2 mmHg; P0.001, respectively). The left ventricular ejection fraction assessed after the recovery from the decompensation was more decreased in group 2 than in group 1; however, it almost returned to normal if sinus rhythm was maintained after the AF ablation in group 2. The presence of a history of TIC did not predict an AF recurrence after the ablation.Heart rate control during AF without sinus conversion may result in an incomplete cure of TIC, suggesting the advantages of rhythm control with ablation in patients with TIC.
- Published
- 2014
44. Time-domain T-wave alternans is strongly associated with a history of ventricular fibrillation in patients with Brugada syndrome
- Author
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Yuko, Uchimura-Makita, Yukiko, Nakano, Takehito, Tokuyama, Mai, Fujiwara, Yoshikazu, Watanabe, Akinori, Sairaku, Hiroshi, Kawazoe, Hiroya, Matsumura, Nozomu, Oda, Hiroki, Ikanaga, Chikaaki, Motoda, Kenta, Kajihara, Noboru, Oda, Richard L, Verrier, and Yasuki, Kihara
- Subjects
Male ,Ventricular Fibrillation ,Electrocardiography, Ambulatory ,Humans ,Female ,Middle Aged ,Brugada Syndrome ,Retrospective Studies - Abstract
T-wave alternans (TWA) is an indicator of vulnerability to ventricular arrhythmias and is useful for predicting sudden cardiac death (SCD) in patients with various structural heart diseases. We evaluated whether high levels of time-domain TWA on ambulatory ECG (AECG) are associated with a history of ventricular fibrillation (VF) in Brugada syndrome (BrS) patients.We examined the associations among VF history, family history of SCD, spontaneous type 1 electrocardiogram (ECG), late potentials, VF induction by programmed electrical stimulation, and TWA in 45 BrS patients (44 males; mean age, 45 ± 15 years). TWA analyzed from 24-h AECG recordings using the modified moving average method was positive in 13 of 43 patients (30%). Patients with a history of VF had a significantly higher incidence of a positive TWA test (82% vs. 13%; P0.001) and spontaneous type 1 ECG (92% vs. 38%; P = 0.007) than those without VF history. Multivariate analysis indicated that positive TWA (OR 7.217; 95% CI 2.503-35.504; P = 0.002) and spontaneous type 1 ECG (OR 5.530; 95% CI 1.651-34.337; P = 0.020) were closely associated with VF history. Spontaneous type 1 ECG had high sensitivity (92%) but low specificity (63%). Positive TWA was a reliable marker with high sensitivity and specificity (82% and 88%, respectively).Elevated time-domain TWA on AECG confirms arrhythmia risk in symptomatic BrS patients without the need for provocative stimuli.
- Published
- 2014
45. Prediction of atrial fibrillation after off-pump coronary artery bypass grafting using preoperative total atrial conduction time determined on tissue Doppler imaging
- Author
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Sueda T, Katsuhiko Imai, Noboru Oda, Yoshikazu Watanabe, Kenta Kajihara, Yuko Uchimura, Hiroki Ikenaga, Takehito Tokuyama, Akinori Sairaku, Chikaaki Motoda, Takayuki Hidaka, Yasuki Kihara, Yukiko Nakano, and Mai Fujiwara
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Coronary Artery Bypass, Off-Pump ,Doppler echocardiography ,Doppler imaging ,Electrocardiography ,Postoperative Complications ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,Off-pump coronary artery bypass ,Aged ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Atrial fibrillation ,General Medicine ,Middle Aged ,medicine.disease ,Confidence interval ,Echocardiography, Doppler ,Cardiac surgery ,Predictive value of tests ,Anesthesia ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery and results in increased health-care utilization. This study identified new transthoracic echocardiographic predictors of POAF using an index of the total atrial conduction time derived on tissue Doppler imaging (PA-TDI duration) in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Methods and results A total of 88 patients undergoing isolated OPCAB were enrolled. They were examined preoperatively on transthoracic echocardiography with tissue Doppler evaluations and monitored postoperatively with continuous electrocardiographic telemetry for 7 days. POAF occurred in 35 patients (39.8%). Patients with POAF had a significantly longer duration of hospital stay than those without (44.9±6.2 vs. 37.3±3.3 days, P=0.04). Multivariate analysis showed that PA-TDI duration (odds ratio [OR], 1.11; 95% confidence interval [CI]: 1.06-1.16; P=0.0001) and left atrial volume index (LAVI; OR, 1.11; 95% CI: 1.02-1.20; P=0.01) were independent predictors of POAF. Moreover, PA-TDI duration was more reliable, given an area under the receiver operating characteristic curve of 0.85 (sensitivity, 74.3%; specificity, 86.8%). Conclusions PA-TDI duration was an independent predictor of POAF following OPCAB. Awareness of risk of POAF may lead to the prevention of POAF, a rapid response to POAF, shortened hospital stay, and improved prognosis.
- Published
- 2013
46. [Untitled]
- Author
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Akihiro Abe, Yoshikazu Watanabe, and Kenichi Minamino
- Subjects
Political science ,Regional science ,Information society - Published
- 2000
47. Influence of Firing Times and Temperature on Color Stability of Low-fusing Porcelains for High-functional Gold Alloys
- Author
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Mari Yamada, Yoshikazu Watanabe, Hiroaki Komatsu, Takayuki Nakai, Akiyoshi Shinya, and Yoshimi Ooe
- Subjects
Standard conditions for temperature and pressure ,Materials science ,Technology, Dental ,Metal Ceramic Alloys ,Temperature ,Analytical chemistry ,Color ,Gold Alloys ,Mineralogy ,General Medicine ,Gold alloys - Abstract
The purpose of this study was to investigate the effect of firing conditions on color stability. Three commercially available porcelains for high functional gold alloys, Carrara (CA), Deguceram Gold (DE) and Duceragold (DU) were used. In this study color stability was investigated under fire treatment of 1st, 3rd, 5th times and firing temperatures of 0, 20, and 40 degrees C higher than the manufactures standard temperature (CA: 845 degrees C, DE: 780 degrees C, DU: 780 degrees C). L* was degreased in CA 5 times, DE 3 times, DU by repeated firing. No difference was observed among L* of firing temperatures DE and DU, but L* was degreased in CA with firing temperatures of 40 degrees C higher. a* was degreased in CA, DU, DE with repeated firing, a* was degreased 5 times at firing temperatures of higher. b* was degreased in DU, but b* was increased in CA and DE with 5 firings. b* was increased with 5 findings at firing temperatures of 40 degrees C higher.
- Published
- 1999
48. A Nonsynonymous Polymorphism in Semaphorin 3A as a Risk Factor for Human Unexplained Cardiac Arrest with Documented Ventricular Fibrillation
- Author
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Seiko Ohno, Hidenori Ochi, Hidekazu Suzuki, Akihiko Nogami, Kazuyoshi Suenari, Noboru Oda, Takehito Tokuyama, Satoshi Tashiro, C. Nelson Hayes, Akinori Sairaku, Naoto Endo, Daiki Miki, Koji Arihiro, Kimie Ohkubo, Takeshi Aiba, Chikaaki Motoda, Masaaki Toshishige, Yoshikazu Watanabe, Wataru Shimizu, Mai Fujiwara, Kazuaki Chayama, Yasuki Kihara, Kenta Kajihara, Yuko Uchimura-Makita, Yasufumi Hayashida, Yukiko Nakano, Kanae Hasegawa, Hiroshi Watanabe, Yukihiko Yoshida, Naomasa Makita, Minoru Horie, and Ichiro Watanabe
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Sympathetic Nervous System ,lcsh:QH426-470 ,Sinus bradycardia ,Biology ,Arrhythmias ,Cardiovascular ,Autonomic Nervous System ,Sudden cardiac death ,Pathogenesis ,Polymorphism (computer science) ,Risk Factors ,Internal medicine ,medicine ,Genetics ,Humans ,Risk factor ,Molecular Biology ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,Aged ,medicine.diagnostic_test ,Myocardium ,Human Genetics ,Heart ,Semaphorin-3A ,Middle Aged ,medicine.disease ,Heart Arrest ,lcsh:Genetics ,Endocrinology ,Neurology ,Ventricular fibrillation ,Genetics of Disease ,Ventricular Fibrillation ,Cardiology ,Etiology ,Medicine ,Female ,medicine.symptom ,Electrocardiography ,Research Article - Abstract
Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sympathetic innervation. We investigated the relevance of the semaphorin 3A (SEMA3A) gene located at chromosome 5 in the etiology of UCA. Eighty-three Japanese patients diagnosed with UCA and 2,958 healthy controls from two different geographic regions in Japan were enrolled. A nonsynonymous polymorphism (I334V, rs138694505A>G) in exon 10 of the SEMA3A gene identified through resequencing was significantly associated with UCA (combined P = 0.0004, OR 3.08, 95%CI 1.67–5.7). Overall, 15.7% of UCA patients carried the risk genotype G, whereas only 5.6% did in controls. In patients with SEMA3A I334V, VF predominantly occurred at rest during the night. They showed sinus bradycardia, and their RR intervals on the 12-lead electrocardiography tended to be longer than those in patients without SEMA3A I334V (1031±111 ms versus 932±182 ms, P = 0.039). Immunofluorescence staining of cardiac biopsy specimens revealed that sympathetic nerves, which are absent in the subendocardial layer in normal hearts, extended to the subendocardial layer only in patients with SEMA3A I334V. Functional analyses revealed that the axon-repelling and axon-collapsing activities of mutant SEMA3A I334V genes were significantly weaker than those of wild-type SEMA3A genes. A high incidence of SEMA3A I334V in UCA patients and inappropriate innervation patterning in their hearts implicate involvement of the SEMA3A gene in the pathogenesis of UCA., Author Summary Unexplained cardiac arrest with documented ventricular fibrillation (UCA) is defined as spontaneous ventricular fibrillation (VF) that is not associated with known structural or electrical heart diseases and is one of the major causes of sudden cardiac death. Identification of the genes responsible for UCA may further increase our understanding of mechanisms of UCA and facilitate more accurate diagnosis and preventive treatment, especially in asymptomatic disease-carrying relatives of the patient. However, molecular mechanisms of UCA have not been fully clarified due to the high mortality rate and difficulty of diagnosis. In this study, UCA patients are shown to have a high incidence of a polymorphism in the Semaphorin 3A gene (rs138694505, SEMA3A I334V). The result confirms previous reports that the abnormal sympathetic innervation is a trigger of UCA because SEMA3A is crucial for the establishment of normal innervation patterns in the heart. Furthermore, experimental data presented here indicate that SEMA3A I334V disrupts the SEMA3A function and impairs appropriate innervation patterning. Finally, the study suggests that SEMA3A I334V is a risk factor for human UCA and contributes to the etiology of UCA.
- Published
- 2013
49. Design and synthesis of novel opioid ligands with an azabicyclo[2.2.2]octane skeleton having a 7-amide side chain and their pharmacologies
- Author
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Yoshikazu Watanabe, Toru Nemoto, Hideaki Fujii, Shigeto Hirayama, Takashi Iwai, Shota Kitazawa, and Hiroshi Nagase
- Subjects
medicine.drug_class ,Stereochemistry ,Clinical Biochemistry ,Substituent ,Receptors, Opioid, mu ,Pharmaceutical Science ,Ligands ,Biochemistry ,Sensitivity and Specificity ,chemistry.chemical_compound ,Structure-Activity Relationship ,Opioid receptor ,Amide ,Receptors, Opioid, delta ,Drug Discovery ,Side chain ,medicine ,Humans ,Molecular Biology ,Octane ,Receptors, Opioid, kappa ,Organic Chemistry ,Affinities ,Amides ,Analgesics, Opioid ,chemistry ,Drug Design ,Molecular Medicine ,Biological Assay ,Selectivity ,Azabicyclo Compounds ,Nalfurafine ,medicine.drug - Abstract
Several derivatives with an azabicyclo[2.2.2]octane skeleton having a 7-amide side chain were synthesized. Compounds that had an electron-donating group exhibited high affinity for the μ opioid receptor while those with a bulky substituent at the 8-nitrogen atom had low affinities for all receptor types. High affinities and selectivities for the κ receptor resulted from the introduction of the longer amide side chain at the 7α-position. Our studies indicate that the orientation of the amide side chain at the 7-position within the azabicyclo[2.2.2]octane skeleton is related to selectivity for the κ receptor.
- Published
- 2013
50. Fabrication of Optically Transparent Lead Lanthanum Zirconate Titanate ((Pb,La)(Zr,Ti)O3) Ceramics by a Three-Stage-Atmosphere-Sintering Technique
- Author
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Yoshikazu Watanabe, Hiroshi Ushijima, Yoshinori Sasaki, Kazuyuki Kakegawa, and Yoshiyuki Abe
- Subjects
Controlled atmosphere ,Materials science ,Transparent ceramics ,Mineralogy ,Sintering ,chemistry.chemical_element ,Lead zirconate titanate ,Oxygen ,Titanate ,Atmosphere ,chemistry.chemical_compound ,chemistry ,visual_art ,Materials Chemistry ,Ceramics and Composites ,visual_art.visual_art_medium ,Ceramic ,Composite material - Abstract
An easy technique has been developed to fabricate optically transparent lanthanum-modified lead zirconate titanate (PLZT) ceramics. This technique consists of three stages: (1) sintering in an oxygen atmosphere, (2) elimination of pores in a carbon dioxide atmosphere, and (3) elimination of oxygen vacancies in an oxygen atmosphere. The carbon dioxide atmosphere enhances the diffusion of oxygen from the pores to outside the sintered body. The experimental results reveal that use of a carbon dioxide atmosphere effectively decreases residual pores and improves optical transmittance. From commercially available raw powders, an optical transmittance of 51% (wavelength of 550 nm) can be achieved for 0.7 mm thick polished PLZT9/65/35 ceramics using a carbon dioxide atmosphere, whereas the value is only 34% without a carbon dioxide atmosphere. The advantage of this technique is that PLZT ceramics having high optical quality can be obtained using conventional sintering tools.
- Published
- 2004
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