Faculty Profiles - OHISHI Mitsuru

Papers - OHISHI Mitsuru

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Yokoyama S, Oguro R, Yamamoto K, Akasaka H, Ito N, Kawai T, Kusunoki H, Takeya Y, Takeya-Onishi M, Yamamoto-Hanasaki H, Sugimoto K, Ikebe K . A klotho gene single nucleotide polymorphism is associated with the onset of stroke and plasma klotho concentration . Aging11 ( 1 ) 104 - 114 2018.12Reviewed

Kawasoe S, Kubozono T, Yoshifuku S, Ojima S, Miyata M, Miyahara H, Maenohara S, Ohishi M. . Uric acid level and new-onset atrial ﬁbrillation in the japanese general population - longitudinal study. . Circ J83 ( 1 ) 156 - 163 2018.12Reviewed

Kawasoe Shin, Kubozono Takuro, Yoshifuku Shiro, Ojima Satoko, Miyata Masaaki, Miyahara Hironori, Maenohara Shigeho, Ohishi Mitsuru . Uric Acid Level and New-Onset Atrial Fibrillation in the Japanese General Population　― Longitudinal Study ― . Circulation Journal83 ( 1 ) 156 - 163 2018.12

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Circulation Society

Background: The independent role of uric acid (UA) as a risk factor for atrial fibrillation (AF) has not been fully elucidated. Methods and Results: We studied 111,566 subjects (53,416 men; 58,150 women) who underwent annual health check-ups. We divided them by sex into tertile of baseline UA. To investigate the predictive power of UA for new-onset AF, we performed Cox proportional hazard analysis including UA tertiles, body mass index, creatinine, smoking and drinking status, and presence of hypertension, diabetes, and dyslipidemia. During 4.1 years, 467 men (0.87%) and 180 women (0.31%) had AF (P<0.001). Cut-off points for tertiles of UA were as follows: women, ≤3.9, 4.0–4.8, and ≥4.9 mg/dL; men, ≤5.4, 5.5–6.4, and ≥6.5 mg/dL. Hazard ratio (HR) for third to first tertile was 1.74 (95% CI: 1.15–2.70; P=0.008), whereas there were no differences between tertiles in men. Rate of new-onset AF was significantly higher in the group with initially increased UA (ΔUA ≥0.3 mg/dL) than that with unchanged UA (ΔUA, −0.2 or +0.2 mg/dL) in the third tertile of baseline UA in both sexes. Conclusions: Higher baseline UA was significantly associated with higher AF incidence in women. Initial increase in UA was significantly associated with AF incidence when baseline UA was ≥6.5 mg/dL in men, and ≥4.9 mg/dL in women.

DOI： 10.1253/circj.cj-18-0508

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Tabata S., Yamamoto M., Goto H., Hirayama A., Ohishi M., Kuramoto T., Mitsuhashi A., Ikeda R., Haraguchi M., Kawahara K., Shinsato Y., Minami K., Saijo A., Toyoda Y., Hanibuchi M., Nishioka Y., Sone S., Esumi H., Tomita M., Soga T., Furukawa T., Akiyama S.I. . Thymidine catabolism promotes NADPH oxidase-derived reactive oxygen species (ROS) signalling in KB and yumoto cells . Scientific Reports8 ( 1 ) 6760 2018.12

Language：Japanese Publisher：Scientific Reports

Thymidine phosphorylase (TP) is a rate-limiting enzyme in the thymidine catabolic pathway. TP is identical to platelet-derived endothelial cell growth factor and contributes to tumour angiogenesis. TP induces the generation of reactive oxygen species (ROS) and enhances the expression of oxidative stress-responsive genes, such as interleukin (IL)-8. However, the mechanism underlying ROS induction by TP remains unclear. In the present study, we demonstrated that TP promotes NADPH oxidase-derived ROS signalling in cancer cells. NADPH oxidase inhibition using apocynin or small interfering RNAs (siRNAs) abrogated the induction of IL-8 and ROS in TP-expressing cancer cells. Meanwhile, thymidine catabolism induced by TP increased the levels of NADPH and intermediates of the pentose phosphate pathway (PPP). Both siRNA knockdown of glucose 6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme in PPP, and a G6PD inhibitor, dihydroepiandrosterone, reduced TP-induced ROS production. siRNA downregulation of 2-deoxy-D-ribose 5-phosphate (DR5P) aldolase, which is needed for DR5P to enter glycolysis, also suppressed the induction of NADPH and IL-8 in TP-expressing cells. These results suggested that TP-mediated thymidine catabolism increases the intracellular NADPH level via the PPP, which enhances the production of ROS by NADPH oxidase and activates its downstream signalling.

DOI： 10.1038/s41598-018-25189-y

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内門義博, 池田義之, 大石充 . 【心不全(第2版)上-最新の基礎・臨床研究の進歩-】心不全の基礎研究　心不全の分子機序　タンパククオリティーコントロール　ミトコンドリアダイナミクス . 日本臨床76 ( 増刊9 心不全(上) ) 229 - 234 2018.12

神田大輔, 大石充 . 【急性冠症候群-病態・診断・治療の最新知見-】急性冠症候群の二次予防　RAAS抑制薬とβ遮断薬 . 日本臨床76 ( 12 ) 2234 - 2241 2018.12

手塚綾乃, 肥後建樹郎, 榎園圭, 内山洋太, 茶園秀人, 湯浅敏典, 徳本寛人, 武冨榮二, 大石充 . 化膿性脊椎炎を合併した三尖弁感染性心内膜炎の1症例 . 心臓50 ( 12 ) 1316 - 1322 2018.12

Language：Japanese Publisher：(公財)日本心臓財団

症例は74歳、男性。腰痛の精査にて近医より当院整形外科に紹介受診となり精査入院中、低血糖と見当識障害を契機とした全身精査にて、三尖弁に直径20×16mmの疣腫を認め、三尖弁感染性心内膜炎と診断した。直ちにペニシリンG2400万単位を開始した。その後、腰椎においても、初診時にはみられなかった骨破壊像が出現し、化膿性脊椎炎と診断された。三尖弁の疣腫は手術適応とされるサイズであったが、腰椎の感染巣の存在下での開心術は術後感染リスクが高いと判断された。一方、腰椎の骨破壊は進行性で、保存的加療での改善は困難と判断され、腰椎後方固定術を施行された。第79病日にて抗生剤投与終了したが、感染の再燃徴候なく、三尖弁の疣腫にも変化を認めず、開心術は施行せず経過観察の方針となった。(著者抄録)

Kawasoe Shin, Kubozono Takuro, Yoshifuku Shiro, Ojima Satoko, Miyata Masaaki, Miyahara Hironori, Maenohara Shigeho, Ohishi Mitsuru . 日本の一般集団における尿酸値と心房細動の新規発症　縦断研究(Uric Acid Level and New-Onset Atrial Fibrillation in the Japanese General Population: Longitudinal Study) . Circulation Journal83 ( 1 ) 156 - 163 2018.12

Language：English Publisher：(一社)日本循環器学会

定期検診を受診した一般集団被験者111566例(男性53416例、女性58150例、平均53.8±15.6歳)を対象に、尿酸値と心房細動の新規発症の関連を検討した。心不全、冠動脈疾患、甲状腺機能亢進症の患者は除外した。ベースラインの血清尿酸値は男性で5.9±1.3mg/dL、女性で4.4±1.0mg/dLであった。男性および女性被験者を尿酸値の3分位値でそれぞれ3群に分類した。追跡期間中央値は4.1年で、心房細動は女性で180例(0.31%)、男性で467例(0.87%)発生した。血清尿酸値で三分位に分けた心房細動の発症率は、女性では最低値の第1三分位群が0.20%、第2三分位群が0.31%、第3三分位群が0.49%であった。男性では有意な群間差はなかった。Cox比例ハザードモデルを用いた解析で、女性における第1三分位群を基準とした第3三分位群の心房細動発症の調整ハザード比は1.74(95%信頼区間1.15～2.70、P=0.008)であった。男性および女性の第3三分位群ではベースラインに比べて尿酸値が0.3mg/dL以上増加した被験者における心房細動の発症率が有意に高かった。

内門義博, 池田義之, 大石充 . 【心不全(第2版)上-最新の基礎・臨床研究の進歩-】心不全の基礎研究心不全の分子機序タンパククオリティーコントロールミトコンドリアダイナミクス . 日本臨床76 ( 増刊9 心不全(上) ) 229 - 234 2018.12

神田大輔, 大石充 . 【急性冠症候群-病態・診断・治療の最新知見-】急性冠症候群の二次予防 RAAS抑制薬とβ遮断薬 . 日本臨床76 ( 12 ) 2234 - 2241 2018.12

Yamashita Kaoru, Kohjitani Atsushi, Miyata Masaaki, Ohno Sachi, Tohya Akina, Ohishi Mitsuru, Sugimura Mitsutaka . Predictive Factors of Postoperative Blood Pressure Abnormalities Following a Minor-to-Moderate Surgery . International Heart Journal59 ( 6 ) 1359 - 1367 2018.11

Language：English Publishing type：Research paper (scientific journal) Publisher：International Heart Journal Association

Myocardial ischemic events after non-cardiac surgery is still a serious problem, especially in older, high-risk patients. However, the prevalence and risk factors of blood pressure (BP) abnormalities, which may possibly lead to myocardial ischemic attack, have not been reported. Our aim is to elucidate predictive factors of postoperative BP abnormalities following a minor-to-moderate surgery, employing preoperative left ventricular diastolic function. Patients who underwent cardiac echocardiogram examination and received oral and maxillofacial surgery under general anesthesia were enrolled. The echocardiographic parameters of diastolic function were compared between patients who had postoperative BP abnormalities (hypertension-systolic blood pressure [SBP] ≥ 170 mmHg-or hypotension-SBP < 80 mmHg-episode) that required therapeutic interventions until 7 days after surgery and those who had no BP abnormalities. Of the 173 patients analyzed, 25 (14.4%) had BP abnormalities. BP abnormalities patients were older, having a larger proportion of diabetes mellitus, lower E/A ratio and e', and larger E/e' and left atrial dimension than those without BP abnormalities. Subanalyses revealed that the independent risk factors responsible for hypertension episodes (14 patients) were the mean e' (odd ratio [OR]: 0.434; 95% confidence interval [CI]: 0.229-0.824), diabetes mellitus (OR: 5.018; 95% CI: 1.030-24.436), SBP at hospitalization (OR: 1.099; 95% CI: 1.036-1.165), and operation time (hour; OR: 1.326; 95%CI: 1.109-1.586), while hypotension episodes (11 patients) were associated solely with operation time (OR: 1.206; 95% CI: 1.046-1.391). In conclusion, left ventricular diastolic dysfunction, increased insulin resistance, boosted SBP at hospitalization, and prolonged operation should be taken into consideration as risk factors of postoperative BP abnormalities, especially hypertension, following minor-to-moderate surgery.

DOI： 10.1536/ihj.17-612

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Yamashita K, Kohjitani A, Miyata M, Ohno S, Tohya A, Ohishi M, Sugimura M. . Predictive Factors of Postoperative Blood Pressure Abnormalities Following a Minor-to-Moderate Surgery. . Int Heart J.59 ( 6 ) 1359 - 1367 2018.11Reviewed

Kawasoe S, Ide K, Usui T, Kubozono T, Yoshifuku S, Miyahara H, Maenohara S, Ohishi M, Kawakami K. . Association of serum triglycerides with arterial stiffness in subjects with low levels of low-density lipoprotein cholesterol. . Cir J82 ( 12 ) 3052 - 3057 2018.11Reviewed

Kawasoe Shin, Ide Kazuki, Usui Tomoko, Kubozono Takuro, Yoshifuku Shiro, Miyahara Hironori, Maenohara Shigeho, Ohishi Mitsuru, Kawakami Koji . Association of Serum Triglycerides With Arterial Stiffness in Subjects With Low Levels of Low-Density Lipoprotein Cholesterol . Circulation Journal82 ( 12 ) 3052 - 3057 2018.11

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Circulation Society

Background: The independent role of serum triglyceride (TG) levels as a cardiovascular risk factor is still not elucidated. We aimed to investigate if the effect of TG on arterial stiffness is influenced by the serum level of low-density lipoprotein cholesterol (LDL-C). Methods and Results: We studied 11,640 subjects who underwent health checkups. They were stratified into 4 groups according to LDL-C level (≤79, 80–119, 120–159, and ≥160 mg/dL). Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). In each group, univariate and multivariete logistic regression analyses were performed to investigate the association between high TG (≥150 mg/dL) and high baPWV (>1,400 cm/s). In the univarite analysis, high TG was significantly associated with high baPWV in LDL-C <79 mg/dL (OR, 3.611, 95% CI, 2.475–5.337; P<0.0001) and 80–119 mg/dL (OR, 1.881; 95% CI, 1.602–2.210; P<0.0001), but not in LDL-C 120–159 mg/dL and ≥160 mg/dL. In the multivariate analysis, high TG was significantly associated with high baPWV in LDL-C ≤79 mg/dL (OR, 2.558; 95% CI, 1.348–4.914; P=0.0040) and LDL-C 80–119 mg/dL (OR, 1.677; 95% CI, 1.315–2.140; P<0.0001), but not in LDL-C 120–159 mg/dL and ≥160 mg/dL. Conclusions: High TG and increased arterial stiffness showed an independent relationship in a Japanese general population with LDL-C ≤119 mg/dL. TG-lowering therapy might be an additional therapeutic consideration in these subjects.

DOI： 10.1253/circj.cj-18-0607

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Kawasoe Shin, Ide Kazuki, Usui Tomoko, Kubozono Takuro, Yoshifuku Shiro, Miyahara Hironori, Maenohara Shigeho, Ohishi Mitsuru, Kawakami Koji . LDLコレステロール低値の被験者における血清中性脂肪と動脈壁硬化の関連性(Association of Serum Triglycerides With Arterial Stiffness in Subjects With Low Levels of Low-Density Lipoprotein Cholesterol) . Circulation Journal82 ( 12 ) 3052 - 3057 2018.11

Language：English Publisher：(一社)日本循環器学会

定期検診を受けた被験者11640例(男性56.1%、平均54.6±11.7歳)をLDLコレステロール濃度により層別化して、中性脂肪(TG)と動脈硬化の関連性における影響について検討した。脂質異常症、高血圧症、糖尿病患者は除外した。被験者をLDLコレステロール濃度に応じて79mg/dL以下の第1群、80～119mg/dLの第2群、120～159mg/dLの第3群、160mg/dL以上の第4群の4群に分類した。動脈壁硬化は上腕-足首脈波伝播速度(baPWV)により評価し、1400cm/秒以上を高値(動脈硬化)とした。各群におけるTG高値(150mg/dL以上)とbaPWV高値の関連性を単変量および多重ロジスティック回帰分析を用いて解析した。単変量解析でTG高値とbaPWV高値は第1群と第2群で有意に関連した。多変量解析でも同様の関連が第1群(OR 2.558,95%CI 1.348～4.914,P=0.0040)と第2群(OR1.677,95%CI 1.315～2.140,P<0.0001)で見られた。以上より、LDLコレステロール低値の被験者でTG高値と動脈硬化は有意に関連することが示唆された。

Yamashita Kaoru, Kohjitani Atsushi, Miyata Masaaki, Ohno Sachi, Tohya Akina, Ohishi Mitsuru, Sugimura Mitsutaka . 小手術～中等度手術後の術後血圧異常の予測因子(Predictive Factors of Postoperative Blood Pressure Abnormalities Following a Minor-to-Moderate Surgery) . International Heart Journal59 ( 6 ) 1359 - 1367 2018.11

Language：English Publisher：(一社)インターナショナルハートジャーナル刊行会

心エコー検査と全身麻酔で口腔・顎顔面手術を施行された患者173例を対象とする後ろ向き単施設観察症例対照研究を行い、術後血圧異常の予測因子を調べた。術後に血圧異常を認め術後7日目までに治療的介入を行った患者と、血圧異常のなかった患者で拡張機能の心エコーパラメータを比較した。173例のうち25例(14.4%)に血圧異常を認めた。血圧異常群は非血圧異常群と比較して高齢であり、糖尿病である割合が高く、E/A比およびe'が低く、E/e'および左房径が大きかった。サブ解析では、高血圧エピソード(14例)に対する独立リスク因子は平均e'、糖尿病、入院、手術時間であった。一方、低血圧エピソード(11例)は手術時間のみに関連した。以上から、小手術～中等度手術後の左室拡張機能障害、インスリン抵抗性の亢進、入院時の上昇収縮期血圧、長時間の手術は、術後高血圧異常、特に高血圧のリスク因子であることが示唆された。

沖野秀人, 田端宏之, 福元大地, 安崎和博, 大石充 . 急性下壁心筋梗塞に対するPCI後にTIMI flow grade 0で終了するも、慢性期に再灌流が得られた1例 . 日本冠疾患学会雑誌 ( Suppl. ) 166 - 166 2018.11

Shimono H, Kajiya T, Atsuchi Y, Atsuchi N, Ohishi M. . Giant left ventricular pseudo-aneurysm after posterior myocardial infarction. . Eur Heart J39 ( 37 ) 3479 - 3479 2018.10Reviewed

赤崎雄一, 大石充 . 【血圧変動と臓器合併症】血圧変動と臓器合併症のUpDate . 血圧25 ( 10 ) 682 - 685 2018.10

Language：Japanese Publisher：(株)先端医学社

コホート研究、ランダム化比較試験のサブ解析、システマティックレビューおよびメタ解析の結果から、受診間血圧変動(VVV)は、心血管疾患イベントのリスクとなり、死亡率に相関する。またVVVは、血管硬化度および血管抵抗に相関し、また脳萎縮や認知機能低下に関係する。VVV以外でも、日間血圧変動は心血管疾患のみならず、認知機能低下にも関連し、24時間血圧変動は、心血管病のリスクであり、認知機能低下や呼吸機能とも関係していた。動物実験でも、血圧変動と臓器障害について、その機序が報告されている。今後も、様々な血圧変動と臓器障害の機序が解明されることによって、臓器障害の進展抑制につながる研究が期待される。(著者抄録)

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Papers - OHISHI Mitsuru