2025/07/31 更新

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写真a

ミズノ ユウスケ
水野 祐介
Yusuke Mizuno
所属
附属病院 手術部 准教授
職名
准教授
外部リンク

学位

  • 博士(医学) ( 東京医科歯科大学 )

研究キーワード

  • DDAH1

  • 肺血管平滑筋

  • 低酸素性肺血管収縮

  • MLCK

  • CPI-17

  • Rho-kinase

  • 肺高血圧症

  • PACAP/VIP

  • 脳血管攣縮

  • カルシウム

研究分野

  • ライフサイエンス / 医療薬学

  • ライフサイエンス / 脳神経外科学

  • ライフサイエンス / 麻酔科学

  • ライフサイエンス / 生理学

  • ライフサイエンス / 放射線科学

所属学協会

▼全件表示

論文

  • Role of protein kinase D1 in vasoconstriction and haemodynamics in rats 査読

    Yoh Sugawara, Yusuke Mizuno, Shinya Oku, Yuri Sawada, Takahisa Goto

    Microvascular Research   2023年11月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.mvr.2023.104627

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  • 中心静脈カテーテル挿入時に右内頸静脈内にフラップ様構造物を認めた1症例

    渡邊 南穂, 川名 由貴, 長嶺 祐介, 水野 祐介, 後藤 隆久

    麻酔   71 ( 12 )   1318 - 1321   2022年12月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    右内頸静脈の中心静脈穿刺時に,内頸静脈近位部に限局したフラップ状構造物を認め,静脈解離を疑った。術後経過で所見変化を認めず,既存の内頸静脈弁の可能性が高いと考えられた。十分な範囲のプレスキャンを行うこと,穿刺後にフラップ状構造物を認めた場合は静脈解離を考慮し,慎重な経過観察を行うことが重要である。(著者抄録)

    J-GLOBAL

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    その他リンク: https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01397&link_issn=&doc_id=20221201160006&doc_link_id=%2Fad3msuie%2F2022%2F007112%2F007%2F1318b1321%26dl%3D3&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fad3msuie%2F2022%2F007112%2F007%2F1318b1321%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

  • Asymptomatic Penetration of the Median Nerve by a Peripherally Inserted Central Catheter: A Case Report. 国際誌

    Masaru Kikuchi, Mana Sawada, Takeshi Nomura, Yusuke Mizuno, Takahisa Goto

    A&A practice   16 ( 3 )   e01577   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report a rare case in which a peripherally inserted central catheter (PICC) asymptomatically penetrated the median nerve. The patient was a 71-year-old man who displayed no neurological symptoms until 4 days after PICC placement. An ultrasound scan revealed that the PICC had penetrated the median nerve. He underwent surgery to remove the catheter and had no sequelae. When placing a PICC, selecting the brachial vein as a puncture site is associated with a high risk of nerve injury. Furthermore, circumspect observation is needed until withdrawal as neurological symptoms may be absent even when the catheter has punctured a nerve.

    DOI: 10.1213/XAA.0000000000001577

    PubMed

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  • Right ventricular overloading is attenuated in monocrotaline-induced pulmonary hypertension model rats with a disrupted Gpr143 gene, the gene that encodes the 3,4-l-dihydroxyphenyalanine (l-DOPA) receptor.

    Masayuki Nakano, Motokazu Koga, Tatsuo Hashimoto, Natsuki Matsushita, Daiki Masukawa, Yusuke Mizuno, Hiraku Uchimura, Ryo Niikura, Tomoyuki Miyazaki, Fumio Nakamura, Suo Zou, Takahiro Shimizu, Motoaki Saito, Kouichi Tamura, Takahisa Goto, Yoshio Goshima

    Journal of pharmacological sciences   148 ( 2 )   214 - 220   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pulmonary hypertension (PH) is a severe and progressive disease that causes elevated right ventricular systolic pressure, right ventricular hypertrophy and ultimately right heart failure. However, the underlying pathophysiologic mechanisms are poorly understood. We previously showed that 3,4-l-dihydroxylphenyalanine (DOPA) sensitizes vasomotor response to sympathetic tone via coupling between the adrenergic receptor alpha1 (ADRA1) and a G protein-coupled receptor 143 (GPR143), a DOPA receptor. We investigated whether DOPA similarly enhances ADRA1-mediated contraction in pulmonary arteries isolated from rats, and whether GPR143 is involved in the PH pathogenesis. Pretreating the isolated pulmonary arteries with DOPA 1 μM enhanced vasoconstriction in response to phenylephrine, an ADRA1 agonist, but not to U-46619, a thromboxane A2 agonist or endothelin-1. We generated Gpr143 gene-deficient (Gpr143-/y) rats, and confirmed that DOPA did not augment phenylephrine-induced contractile response in Gpr143-/y rat pulmonary arteries. We utilized a rat model of monocrotaline (MCT)-induced PH. In the MCT model, the right ventricular systolic pressure was attenuated in the Gpr143-/y rats than in WT rats. Phenylephrine-induced cell migration and proliferation were also suppressed in Gpr143-/y pulmonary artery smooth muscle cells than in WT cells. Our result suggests that GPR143 is involved in the PH pathogenesis in the rat models of PH.

    DOI: 10.1016/j.jphs.2021.11.008

    PubMed

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  • 麻酔科術前外来における周麻酔期看護師による麻酔同意書取得補助業務

    井出 悠紀子, 長嶺 祐介, 大山 亜希子, 田中 菜奈子, 水野 祐介, 宮下 徹也, 後藤 隆久

    麻酔   70 ( 12 )   1373 - 1377   2021年12月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    横浜市立大学附属病院の麻酔科術前外来において、新たに周麻酔期看護師による麻酔同意書取得補助業務を開始した。麻酔や手術のリスクが低い患者を対象に、周麻酔期看護師が中心となって診察と麻酔の説明を行い、麻酔科医が最終確認を行って麻酔同意書を取得している。周麻酔期看護師とのタスクシェアリングにより、より効率的な術前外来の運営を行うことが可能となった。(著者抄録)

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  • 術前薬剤師面談と「休薬管理が原因の手術中止」との関連、および病院の経済的損失に及ぼす影響

    勝亦 秀樹, 長嶺 祐介, 川邊 一寛, 田中 美玲, 小池 博文, 水野 祐介, 佐橋 幸子

    日本病院薬剤師会雑誌   57 ( 7 )   735 - 741   2021年7月

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    記述言語:日本語   出版者・発行元:(一社)日本病院薬剤師会  

    周術期医療において、手術中止は切実な問題の1つである。横浜市立大学附属病院では、周術期医療の質の向上を目的に周術期管理センターを設立し、2018年9月より術前薬剤師面談を実施している。本研究は術前薬剤師面談の効果を明らかにする目的で、休薬管理が原因の手術中止とその回避による損失回避額を主要評価項目に設定し調査を行った。術前薬剤師面談の実施により休薬管理が原因の手術中止は減少傾向を認め、年間当たり入院収益11,486,512円、手術利益3,203,456円の損失回避が期待された。術前薬剤師面談は、周術期医療の質の向上と健全な病院経営において重要な役割を担っていると考えられた。(著者抄録)

    J-GLOBAL

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04451&link_issn=&doc_id=20210706250002&doc_link_id=%2Fdg4hppha%2F2021%2F005707%2F003%2F0735-0741%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg4hppha%2F2021%2F005707%2F003%2F0735-0741%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 周麻酔期看護師の新規院内制度導入に伴う整備や倫理的手続き

    井出 悠紀子, 長嶺 祐介, 藤本 寛子, 宮下 徹也, 水野 祐介, 後藤 隆久

    麻酔   70 ( 4 )   431 - 437   2021年4月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    横浜市立大学附属病院では2014年に周麻酔期看護師が業務を開始し、麻酔科医の指示・監督の下、麻酔科の診療の補助を行っている。周麻酔期看護師は院内認定資格であり、業務開始時には各施設でその運用に関する規則を定める必要がある。当院では、それらを業務内規としてまとめ、臨床倫理委員会の承認を得た。管理体制や業務内容、業務を行ううえでの取り決め、責任の所在などについて明らかにし、院内のコンセンサスを得る必要がある。(著者抄録)

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01397&link_issn=&doc_id=20210406130016&doc_link_id=%2Fad3msuie%2F2021%2F007004%2F017%2F0431b0437%26dl%3D3&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fad3msuie%2F2021%2F007004%2F017%2F0431b0437%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

  • 周術期管理センターにおける薬剤師業務の構築および業務拡充の経験

    勝亦 秀樹, 長嶺 祐介, 水野 祐介

    日本手術医学会誌   42 ( 1 )   44 - 48   2021年3月

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    記述言語:日本語   出版者・発行元:日本手術医学会  

    周術期診療は最もチーム医療が必要とされる診療行為と考えられている。特に、観血的医療行為前に休薬する薬剤に関連したインシデントは複数報告され、周術期の服薬管理において薬剤師の関与の必要性が高まっている。しかし、周術期診療における薬剤師の介入状況は非常に限定的である。横浜市立大学附属病院では、周術期医療の質の向上を目的に「周術期管理センター」が組織され、薬剤師は周術期管理センター設立の構想の段階より参画を行った。業務構築・拡大には多くの課題があったが、多職種連携の強みを活かして課題解決を図ることができた。薬剤師が専門性を発揮できる業務体制の構築と、薬剤に関連した周術期医療の質の向上に寄与することができた。(著者抄録)

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01618&link_issn=&doc_id=20210409410012&doc_link_id=%2Fcc4jaort%2F2021%2F004201%2F006%2F0044-0048%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcc4jaort%2F2021%2F004201%2F006%2F0044-0048%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 膵頭十二指腸切除術後に内視鏡下で胃内の破損歯を摘出した1症例

    安西 晃子, 岡村 健太, 水野 祐介, 後藤 隆久

    麻酔   70 ( 3 )   297 - 300   2021年3月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    症例は74歳男性で、膵粘液性嚢胞腫瘍に対し、膵頭十二指腸切除術を施行した。抜管は、患者の強い歯の食いしばりなどはなく、円滑に行われた。抜管後、脱落歯の有無を特に意識した口腔内観察は行わなかった。翌朝、術後回診の際に患者本人より右門歯破損の訴えがあり、診察上も歯牙の破損を認めた。破損歯を誤嚥している可能性があるため、胸部および腹部単純X線検査を施行したところ、胃内部に破損歯と思われる異常陰影を認めた。患者の残存門歯の形状から、破損歯の先端は鋭利と予想された。この破損歯が再建した消化管を通過する際に粘膜を損傷する危険性が懸念されたため、内視鏡的に摘出する方針となった。この時点で1度目のX線検査から時間が経過しており、万が一、破損歯が再建部位よりも尾側にある場合には内視鏡下での摘出が困難になるため、再度胸部単純X線検査を施行し、位置を確認した。異常陰影の位置には変化なく、内視鏡下での摘出は可能であると判断され、緊急内視鏡下摘出術が施行された。内視鏡を挿入すると腎内に破損歯を認め、鉗子で容易に回収できた。その際、胃内の破損歯摘出部分やそのほかの上部消化管粘膜にも明らかな出血や粘膜損傷は認められなかった。

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    その他リンク: https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J01397&link_issn=&doc_id=20210225240009&doc_link_id=%2Fad3msuie%2F2021%2F007003%2F011%2F0297-0300%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fad3msuie%2F2021%2F007003%2F011%2F0297-0300%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 横浜市立大学大学院周麻酔期看護学課程における手術麻酔実習の報告

    大山 亜希子, 井出 悠紀子, 長嶺 祐介, 藤本 寛子, 宮下 徹也, 水野 祐介, 赤瀬 智子, 後藤 隆久

    日本手術医学会誌   41 ( 2 )   175 - 181   2020年6月

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    記述言語:日本語   出版者・発行元:日本手術医学会  

    周麻酔期看護師とは、麻酔にかかわる術前から術後までの医療の流れの中で、患者にとって最善の麻酔が施されるように看護師として麻酔業務を補助する役割を果たす者として、2010年に聖路加国際大学大学院修士課程で養成が開始された。2016年度には横浜市立大学大学院修士課程に同様の教育課程が開講した。筆者は、横浜市立大学大学院周麻酔期看護学分野の1期生として2018年に修士課程を修了し、同年から周麻酔期看護師として活動している。現在までに、本邦では6大学で養成が行われ、各施設で周麻酔期看護師が活動しており、その活動の場はより一層の広がりを見せている。一方、公的には未確立な制度であること、標準化された教育プログラムがないため各養成施設が手探りで実施しているという課題もある。周麻酔期看護学の発展やチーム医療、麻酔医療の安全と質の向上に貢献するためにも、教育の情報を発信・共有していくことは重要である。本稿では筆者が修士課程中に経験した周麻酔期看護学実習について報告する。筆者は、約1年半の実習の中で145症例を経験した。本学では、麻酔科医とマンツーマンで担当麻酔症例の麻酔計画について、綿密なディスカッションを繰り返すことを基本とした実習が行われる。質の担保された周麻酔期看護師の育成にあたり、教育プログラムの確立や実習後の評価方法の確立が今後必要になると考えられた。(著者抄録)

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  • 横浜市立大学附属病院における周麻酔期看護師の業務の実態および患者サービス向上への貢献

    井出 悠紀子, 大山 亜希子, 田中 菜奈子, 長嶺 祐介, 藤本 寛子, 岡村 健太, 宮下 徹也, 水野 祐介, 後藤 隆久

    日本手術医学会誌   41 ( 2 )   182 - 186   2020年6月

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    記述言語:日本語   出版者・発行元:日本手術医学会  

    横浜市立大学では、2014年に周麻酔期看護師が業務を開始し5年が経過した。現在、横浜市立大学附属病院には3名の周麻酔期看護師が在籍し、麻酔科の診療の補助業務を行っている。現在の主な業務内容は手術麻酔であり、術前・術後診察を含め、手術麻酔に関わる一連のケアの提供を麻酔科医の指示・監督下で行っている。当院では2018年度の1年間に麻酔科管理症例が5313件あり、周麻酔期看護師はそのうちの781件(14.6%)に関与した。当院では周麻酔期看護師が導入されたことで、手術室以外の重要な麻酔関連業務に麻酔科医を配置することが可能となった。麻酔科医の業務が拡がり、無痛分娩とRapid Response Teamが開始され、患者サービスの向上につながった。(著者抄録)

    J-GLOBAL

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  • Anterior quadratus lumborum block for postoperative recovery after total hip arthroplasty: a study protocol for a single-center, double-blind, randomized controlled trial. 査読 国際誌

    Masaru Kikuchi, Takahiro Mihara, Yusuke Mizuno, Hiroko Fujimoto, Sachiko Arai, Takeshi Nomura, Takahisa Goto

    Trials   21 ( 1 )   142 - 142   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Appropriate pain management is essential to improve the postoperative recovery after total hip arthroplasty (THA). Various case reports have indicated that anterior quadratus lumborum block (QLB) provides effective postoperative analgesia in lower limb surgeries. However, few randomized controlled trials have confirmed the efficacy of anterior QLB for lower limb surgeries. The aim of this single-center, double-blind, randomized controlled trial is to confirm the efficacy of anterior QLB for postoperative recovery after THA. METHODS: The participants will be randomly assigned to either the anterior QLB or placebo groups, using a set of random numbers for the allocation sequence. Only pharmacists will be aware of the allocations; other investigators will be blinded until study completion. After induction of general anesthesia, anterior QLB will be performed by using 0.25% levobupivacaine or normal saline. Fentanyl will be administered according to blood pressure change during the surgery. The primary outcome will be the quality of recovery 40 score (QoR-40). Secondary outcomes will include the visual analog scale score of pain intensity at rest and movement, intraoperative and postoperative doses of fentanyl, and incidence of postoperative nausea and vomiting. Statistical analysis will be performed by using the Student's t test, Mann-Whitney U test, and Fisher's exact test as appropriate. A P value of less than 0.05 will be considered statistically significant. DISCUSSION: The results of our study will reveal whether anterior QLB is effective for postoperative recovery after THA. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000032255. Registered on 15 April 2018.

    DOI: 10.1186/s13063-020-4090-0

    PubMed

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  • 喉頭エコーのピットフォール 披裂部エコーの動きにより正常と誤認したfloppy arytenoidの1症例

    奥 真哉, 小林 綾子, 山口 嘉一, 水野 祐介, 野村 岳志, 後藤 隆久

    麻酔   69 ( 2 )   143 - 146   2020年2月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    喉頭エコーは声帯麻痺の診断に有用とされており、喉頭エコーの正常像において披裂軟骨は、吸気相で外側へ動き、呼気相では内側へ動く「開閉運動」が認められ、声帯麻痺では「開閉運動」が認められないことで診断される。今回、左反回神経麻痺のある患者の喉頭エコーにおいて、披裂部の声門裂への引き込みによる異常運動(floppy arytenoid)を認め、これを「披裂軟骨の開閉運動あり」と誤認してしまった症例を経験したので、喉頭エコーのピットフォールとして報告した。

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  • Pre-anesthetic ultrasonographic assessment of the internal jugular vein for prediction of hypotension during the induction of general anesthesia. 査読

    Kenta Okamura, Takeshi Nomura, Yusuke Mizuno, Tetsuya Miyashita, Takahisa Goto

    Journal of anesthesia   33 ( 5 )   612 - 619   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Severe hypotension caused by anesthetic administration for anesthesia induction, which might cause ischemic stroke, myocardial injury, acute kidney injury and postoperative mortality, should be prevented. Anesthesiologists are familiar with ultrasound examination of the internal jugular vein (IJV). This study aimed to clarify whether ultrasonographic IJV evaluation just before induction could predict the occurrence of such hypotension. METHODS: Adult patients undergoing surgery under general anesthesia were enrolled after excluding patients with cardiovascular disease or ASA-PS ≥ III. Ultrasonographic IJV images were recorded in both the supine and 10° Trendelenburg positions immediately before induction. Using these images, IJV area (IJV-A), diameter and change rate with posture were measured. Hypotension during induction was defined as mean BP < 60 mmHg or > 30% decrease from baseline. RESULTS: Hypotension during induction was observed in 37 of 82 patients. IJV-A in the Trendelenburg position was 2.02 ± 0.86 and 1.72 ± 0.68 in the hypotensive and non-hypotensive groups, respectively (P = 0.08). Logistic regression analysis performed using age, use of calcium antagonists, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, baseline mean BP and IJV-A in the Trendelenburg position as variables showed that IJV-A in the Trendelenburg position was an independent predictor of hypotension, with an adjusted odds ratio of 3.11 (95% CI 1.07-9.03, P = 0.04). Area under the curve was 0.595 (95% CI 0.469-0.722) for IJV-A in the Trendelenburg position. CONCLUSION: IJV-A in the Trendelenburg position was an independent predictor of hypotension during induction. Further study is required to examine the diagnostic accuracy of IJV-A as a predictor for hypotension during induction.

    DOI: 10.1007/s00540-019-02675-9

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  • 横浜市立大学大学院周麻酔期看護学課程における手術麻酔実習の報告

    大山 亜希子, 井出 悠紀子, 長嶺 祐介, 藤本 寛子, 宮下 徹也, 水野 祐介, 赤瀬 智子, 後藤 隆久

    日本手術医学会誌   40 ( Suppl. )   155 - 155   2019年7月

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    記述言語:日本語   出版者・発行元:日本手術医学会  

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  • 横浜市立大学附属病院における周麻酔期看護師の業務の実態および周術期管理への貢献

    井出 悠紀子, 大山 亜希子, 田中 菜奈子, 長嶺 祐介, 藤本 寛子, 宮下 徹也, 水野 祐介, 後藤 隆久

    日本手術医学会誌   40 ( Suppl. )   151 - 151   2019年7月

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    記述言語:日本語   出版者・発行元:日本手術医学会  

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  • Effect of posterior quadratus lumborum blockade on the quality of recovery after major gynaecological laparoscopic surgery: A randomized controlled trial. 査読 国際誌

    Hiroko Fujimoto, Tomoya Irie, Takahiro Mihara, Yusuke Mizuno, Takeshi Nomura, Takahisa Goto

    Anaesthesia and intensive care   47 ( 2 )   146 - 151   2019年3月

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    記述言語:英語  

    Bilateral quadratus lumborum blockade (QLB) using ultrasound guidance has been introduced as an abdominal truncal block to improve postoperative analgesia and quality of recovery (QoR) after abdominal surgery, but efficacy remains controversial. The primary aim of this study was to evaluate the efficacy of posterior QLB on the postoperative QoR, and secondarily to evaluate postoperative pain after gynaecological laparoscopic surgery (LS). This study was a single-centre randomized controlled trial. QLB group patients underwent bilateral posterior quadratus lumborum injections with 25-30 mL of 0.25% levobupivacaine after induction of general anaesthesia; the control group underwent no block. Both groups were administered fentanyl-based intravenous patient-controlled analgesia postoperatively. The postoperative QoR was measured using the Quality of Recovery 40 (QoR-40) questionnaire score; postoperative pain was evaluated using the visual analogue scale (VAS) and the cumulative postoperative fentanyl dose. Thirty-one and 29 patients were randomised to the QLB and control groups, respectively. The intraoperative remifentanil dosage was significantly less in the QLB group. The median (interquartile range) for the QoR-40 score was not different between the groups: 154 (133-168) in the QLB group and 158 (144-172) in the control group. There were no statistically significant differences in secondary outcome variables. Single-shot QLB did not improve the QoR or postoperative pain in patients managed by multimodal analgesia after gynaecological LS.

    DOI: 10.1177/0310057X19838765

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  • Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension. 査読

    Sugawara Y, Mizuno Y, Oku S, Goto T

    British journal of anaesthesia   122 ( 4 )   437 - 447   2019年2月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bja.2019.01.014

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  • Anesthetic management for resection of retroperitoneal massive paraganglioma (extra-adrenal pheochromocytoma): A case report

    Shoko Shkata, Yuriko Kondo, Tomoko Irisawa, Yusuke Nagamine, Yusuke Mizuno, Takahisa Goto

    Japanese Journal of Anesthesiology   67 ( 12 )   1309 - 1312   2018年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Kokuseido Publishing Co. Ltd  

    A 23-year-old woman developed hypertensive crisis three months previously, and was diagnosed as retroperitoneal massive paraganglioma (extra-adrenal pheo-chromocytoma), with a diameter of 77 mm. Preoperative echocardiography revealed normal cardiac function. The open abdominal surgery might include major vascular surgery because the tumor might have infiltrated into the inferior vena cava and abdominal aorta Therefore, in order to discuss the operative procedure, we held a conference with surgeons in gastroenterology and cardiovascular surgery, nurses and clinical engineers. The surgery was performed under general anesthesia. The tumor did not invade surrounding structures, and simple resection was done. During manipulation of the tumor the patient developed hypertension and tachycardia Severe hypotension (75/ 30 mmHg) followed the resection of the tumor. In addi- tion to volume replacement noradrenaline was administered, but the systolic blood pressure rose only to 80 mmHg In order to treat vasodilatory shock, we started arginine vasopressin infusion at 5 units · hr -1 . Her systolic blood pressure rose to 120 mmHg and was stabilized. The patient was transferred to the intensive care unit (ICU) postoperatively. Her general condition was favorable, and was discharged from the ICU on postoperative day 2. In conclusioa multidisciplinary approach was useful for the perioperative management for resection of massive paraganglioma and arginine vasopressin was effective for refractory hypotension after resection of the tumor.

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  • 後腹膜原発の巨大パラガングリオーマ(副腎外褐色細胞腫)摘出術の麻酔管理の1症例 査読

    白田 祥子, 近藤 有理子, 入澤 朋子, 長嶺 祐介, 水野 祐介, 後藤 隆久

    麻酔   67 ( 12 )   1309 - 1312   2018年12月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    23歳女性。後腹膜の巨大パラガングリオーマに対して腫瘍摘出術が予定された。腫瘍が周囲臓器に浸潤している疑いがあったため、術前に関連診療科、手術室看護師、臨床工学技士との合同カンファレンスを行い、対策を検討した。結果的には単純摘出であったが、摘出後に血管拡張性ショックを認めたため、ノルアドレナリンに加えバソプレシンを投与したところ、循環動態は安定した。その後の経過は良好で、術後16日目に退院となった。

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  • A case of awake craniotomy converted to general anesthesia because of insufficient emergence during operation

    Yuko Matsuda, Yumi Saishu, Yusuke Mizuno, Takahisa Goto

    Japanese Journal of Anesthesiology   67 ( 7 )   748 - 751   2018年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Kokuseido Publishing Co. Ltd  

    A 32-year-old man underwent awake craniotomy for oligodendroglioma The patient received general anesthesia and had a laryngeal mask inserted to secure airway, and continuous infusion of propofol and remifentanil was started. After induction of anesthesia the patient developed seizure without obvious causes. To prevent seizure, phenytoin was administered. About seven hours after the induction of anesthesia infusion of propofol and remifentanil was discontinued to awake the patient The patient could not communicate adequately for thirty minutes from discontinuation of anesthetics, and developed complicated laryngospasm. Because of laryngospasm, we could not ventilate, and the patient's end tidal CO2 level increased to 60 mmHg. The patient's brain showed swelling rapidly and bleeding inside the tumor. Then we decided to convert to general anesthesia Although the tumor was excised partially, the patient did not show dysphasia after the operatioa The causes of insufficient emergence were thought to be prolonged infusion of propofol or administration of phenytoin, or effect of seizure. In such a case we should decide to convert to general anesthesia early, and prevent worsening the conditions.

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  • Avoidance of general anesthesia by employing pecs block: A case of breast cancer and interstitial pneumonia

    Natsuhiro Yamamoto, Yusuke Mizuno, Takeshi Nomura, Takahisa Goto

    Japanese Journal of Anesthesiology   67 ( 6 )   611 - 613   2018年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Kokuseido Publishing Co. Ltd  

    PECS block is a regional anesthesia for anterior chest wall. We present herein the case of 64-year-old woman who underwent partial mastectomy and axillary lymph node biopsy for left breast cancer complicated by interstitial pneumonia due to preoperative chemotherapy. We performed PECS-II block avoiding general anesthesia to prevent acute exacerbation of interstitial pneumonia During the operatioa she was lightly sedated using dexmedetomidine. Additional local anesthesia (1% lidocaine 1 ml) was performed during axillary lymph node biopsy. No oxygen was necessary and no evident symptoms of acute exacerbation of the interstitial pneumonia was observed in the perioperative period. Avoidance of general anesthesia by PECS block might be beneficial for the patients with interstitial pneumonia.

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  • pectoral nerve blockのみで乳房部分切除手術を管理しえた1症例

    山本 夏啓, 水野 祐介, 野村 岳志, 後藤 隆久

    麻酔   67 ( 6 )   611 - 613   2018年6月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

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  • Roles and mechanism of protein kinase D in vasoconstriction 査読

    Yusuke Mizuno, Yoh Sugawara, Takahisa Goto

    FASEB JOURNAL   32 ( 1 )   2018年4月

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    記述言語:英語   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

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  • Comparison between High- and Low-Cost Transmission of Tele-Anesthesia in Japan. 査読 国際誌

    Yoh Sugawara, Tetsuya Miyashita, Yusuke Mizuno, Yusuke Nagamine, Tomoyuki Miyazaki, Ayako Kobayashi, Kentaro Tojo, Yasuhiro Iketani, Shunsuke Takaki, Takahisa Goto

    Journal of healthcare engineering   2018   9615264 - 9615264   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: We previously reported a tele-anesthesia system that connected Sado General Hospital (SGH) to Yokohama City University Hospital (YCUH) using a dedicated virtual private network (VPN) that guaranteed the quality of service. The study indicated certain unresolved problems, such as the high cost of constantly using a dedicated VPN for tele-anesthesia. In this study, we assessed whether use of a best-effort system affects the safety and cost of tele-anesthesia in a clinical setting. Methods: One hundred patients were enrolled in this study. We provided tele-anesthesia for 65 patients using a guaranteed transmission system (20 Mbit/s; guaranteed, 372,000 JPY per month: 1 JPY = US$0.01) and for 35 patients using a best-effort system (100 Mbit/s; not guaranteed, 25,000 JPY per month). We measured transmission speed and number of commands completed from YCUH to SGH during tele-anesthesia with both transmission systems. Results: In the guaranteed system, anesthesia duration was 5780 min (88.9 min/case) and surgical duration was 3513 min (54.0 min/case). In the best-effort system, anesthesia duration was 3725 min (106.4 min/case) and surgical duration was 2105 min (60.1 min/case). The average transmission speed in the best-effort system was 17.3 ± 3.8 Mbit/s. The system provided an acceptable delay time and frame rate in clinical use. All commands were completed, and no adverse events occurred with both systems. Discussion: In the field of tele-anesthesia, using a best-effort internet VPN system provided equivalent safety and efficacy at a better price as compared to using a guaranteed internet VPN system.

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  • Roles of protein kinase D in vasoconstriction and hemodynamics 査読

    Yoh Sugawara, Yusuke Mizuno, Hiromasa Kawakami, Takahisa Goto

    FASEB JOURNAL   30   2016年4月

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    記述言語:英語   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

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  • 硬膜外麻酔で安全に管理しえた筋萎縮性側索硬化症患者の麻酔経験

    新井 悠介, 吉田 輔, 水野 祐介, 宮下 徹也, 後藤 隆久

    麻酔   64 ( 10 )   1062 - 1064   2015年10月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    82歳女。74歳時に筋萎縮性側索硬化症(ALS)と診断され、嚥下障害の進行により誤嚥性肺炎を繰り返すようになり、内視鏡的胃瘻造設術が予定された。しかし、局所麻酔下での手術中に胃穿孔を偶発し、緊急開腹術に移行することとなった。重度の呼吸機能障害を呈するALS患者であったことから、硬膜外麻酔を選択しNPPVを併用したところ、安全に麻酔管理を行うことが可能であった。

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  • 症例検討 よくあるトラブルを乗り越えよう 3 脳動脈のクリッピング中に脳動脈瘤が破裂した-術者との意思疎通をしっかりと

    Yusuke Mizuno

    LiSA   22 ( 4 )   398 - 401   2015年4月

  • A pilot study of tele-anaesthesia by virtual private network between an island hospital and a mainland hospital in Japan 国際誌

    Tetsuya Miyashita, Yusuke Mizuno, Yo Sugawara, Yusuka Nagamine, Yukihide Koyama, Tomoyuki Miyazaki, Kazuhiro Uchimoto, Yasuhiro Iketani, Kentaro Tojo, Takahisa Goto

    JOURNAL OF TELEMEDICINE AND TELECARE   21 ( 2 )   73 - 79   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE PUBLICATIONS LTD  

    We studied the use of tele-anaesthesia between Sado General Hospital (SGH) located on Sado Island and Yokohama City University Hospital (YCUH) located in mainland Japan. The two sites were connected via a virtual private network (VPN). We investigated the relationship between the bandwidth of the VPN and both the frame rate and the delay time of the tele-anaesthesia monitoring system. The tool used for communication between the two hospitals was free videoconferencing software (FaceTime), which can be used over Wi-Fi connections. We also investigated the accuracy of the commands given during teleanaesthesia: any commands from the anaesthetist at the YCUH that were not carried out for any reason, were recorded in the anaesthetic records at the SGH. The original frame rate and data rate at the SGH were 5fps and approximately 18 Mbit/s, respectively. The frame rate at the transmission speeds of 1, 5 and 20 Mbit/s was 0.6, 1.6 and 5.0fps, respectively. The corresponding delay time was 12.2, 4.9 and 0.7s. Twenty-five adult patients were enrolled in the study and tele-anaesthesia was performed. The total duration of anaesthesia was 37 hours. All 888 anaesthetic commands were completed. There were 7 FaceTime disconnections, which lasted for 10min altogether. Because no commands needed to be given during the FaceTime disconnection, the telephone was not used. The anaesthesia assistance system might form part of the solution to medical resource shortages.

    DOI: 10.1177/1357633X14562735

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  • Direct measurement of a patient's entrance skin dose during pediatric cardiac catheterization 査読 国際誌

    Lue Sun, Yusuke Mizuno, Mari Iwamoto, Takahisa Goto, Yasuhiro Koguchi, Yuka Miyamoto, Koji Tsuboi, Koichi Chida, Takashi Moritake

    JOURNAL OF RADIATION RESEARCH   55 ( 6 )   1122 - 1130   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose-area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 +/- 59 (mean +/- standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed.

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  • Role of VPAC2 receptor in monocrotaline-induced pulmonary hypertension in rats 査読 国際誌

    Motokazu Koga, Yusuke Mizuno, Itaru Watanabe, Hiromasa Kawakami, Takahisa Goto

    JOURNAL OF APPLIED PHYSIOLOGY   117 ( 4 )   383 - 391   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Pulmonary hypertension (PH) is associated with significant morbidity and mortality. Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP) have pulmonary vasodilatory and positive inotropic effects via receptors VPAC1 and VPAC2, which possess a similar affinity for both peptides, and PAC1, a PACAP-preferring receptor. VIP is a promising option for PH treatment; however, various physiological effects of VIP have limited its clinical use. We investigated the effects of VPAC1 and VPAC2 selective agonists VIP and PACAP to explore more appropriate means of treatment for PH. We examined hemodynamic changes in right ventricular systolic pressure (RVSP), systemic blood pressure (SBP), total pulmonary resistance index (TPRI), total systemic resistance index, and cardiac index (CI) in response to their agonists with monocrotaline (MCT)-induced PH and explored involvement of VIP/PACAP expression and receptors in PH. Sprague-Dawley rats were divided into the MCT group (administered MCT 60 mg/kg) and control group. In MCT-induced PH, decreased VIP and PACAP were associated with upregulation of VPAC1, VPAC2, and PAC1 in lung tissues. Intravenous injection of VPAC2-selective agonist BAY 55-9837 and VIP, but not [Ala(11,22,28)] VIP, improved the CI. The decrease in SBP with VPAC2 agonist was significantly less than that in the control. Although they decreased SBP, these agonists hardly affected RVSP in the control. Activation of VPAC2 receptor with BAY 55-9837 effectively improved RVSP, TPRI, and CI in MCT-induced PH, suggesting a VPAC2 agonist as a possible promising treatment for PH.

    DOI: 10.1152/japplphysiol.00861.2013

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  • Effect of VPAC2 agonist on improving cardiac output in pulmonary hypertension 査読

    Yusuke Mizuno, Motokazu Koga, Shizuka Kashiwagi, Itaru Watanabe, Takahisa Goto

    FASEB JOURNAL   27   2013年4月

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    記述言語:英語   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

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  • Amount of accidental flush by syringe pump due to inappropriate release of occluded intravenous line 査読 国際誌

    Hiromasa Kawakami, Tetsuya Miyashita, Ryota Yanaizumi, Takahiro Mihara, Hitoshi Sato, Takayuki Kariya, Yusuke Mizuno, Takahisa Goto

    TECHNOLOGY AND HEALTH CARE   21 ( 6 )   581 - 586   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IOS PRESS  

    BACKGROUND: An unintended bolus is delivered by the syringe pump if intravenous line occlusion is released in an inappropriate manner.
    OBJECTIVE: The aim of this study was to measure the amount of flushed fluid when an occlusion is inappropriately released and to assess the effect of different syringe pump settings (flow rate, alarm setting, size of syringe and syringe pump model) on the flushed amount.
    METHODS: After the stopcock was closed, infusions were started with different model syringe pumps (Terufusion (R) TE312 and TE332S), different syringe sizes or at different alarm settings. After the occlusion alarm sounded, the occlusion was released and the amount of fluid emerging from the stopcock was measured.
    RESULTS: The bolus was significantly lower when the alarm was set at a low-pressure setting. The bolus was significantly lower with a 10-ml than a 50-ml syringe. A significant difference was seen only when a 50-ml syringe was used (TE312: 1.99 +/- 0.16 ml vs. TE332S: 0.674 +/- 0.116 ml, alarm High, p &lt; 0.001).
    CONCLUSION: To minimize the amount of accidentally injected medication, a smaller syringe size and a low alarm setting are important. Using a syringe pump capable of reducing the inadvertently administered bolus may be helpful.

    DOI: 10.3233/THC-130754

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  • Erratum: Precise mapping system of entrance skin dose during endovascular embolization for cerebral aneurysm (Radiation Measurements (2011) 46 (2103-2106)) 査読

    Takashi Moritake, Mikito Hayakawa, Yuji Matsumaru, Tomoji Takigawa, Yasuhiro Koguchi, Yuka Miyamoto, Yusuke Mizuno, Koichi Chida, Keiichi Akahane, Koji Tsuboi, Takeji Sakae, Hidehiko Sakurai

    Radiation Measurements   47 ( 6 )   465   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.radmeas.2012.05.009

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  • くも膜下出血を機に大動脈縮窄症が発見された若年者の開頭クリッピング術の麻酔経験

    米川 裕子, 中橋 勇典, 水野 祐介, 紙谷 義孝, 武田 康二, 後藤 隆久

    麻酔   61 ( 3 )   326 - 328   2012年3月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    15歳男性。突然の頭痛と嘔吐により著者らの施設へ救急搬送され、頭部CTにてクモ膜下出血と診断後、入院となった。所見ではほかに聴診上、前胸部に収縮期雑音が聴取され、心電図では左室肥大が認められた。また、両上肢での血圧測定では血圧値の左右差が認められた。そのため脳血管造影とあわせて大動脈造影を行ったところ、脳血管造影では前大脳動脈瘤がみられ、大動脈造影では左鎖骨下動脈分岐部の狭窄が認められた。以上より、本症例は大動脈縮窄とそれに伴う脳動脈瘤破裂と診断され、全身麻酔下に開頭クリッピング術が施行された。術中は左鎖骨下動脈分岐部の大動脈狭窄による上肢血圧の左右差があったことから、右橈骨動脈の観血的動脈圧と左橈骨動脈の観血的動脈圧を測定し、更に左大腿でも非観血的動脈圧を測定した。その結果、左橈骨動脈の平均血圧と左大腿での平均血圧はほぼ等しい値となり、患者は術後経過良好で、入院20日後には独歩退院となった。

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  • Precise mapping system of entrance skin dose during endovascular embolization for cerebral aneurysm

    Takashi Moritake, Mikito Hayakawa, Yuji Matsumaru, Tomoji Takigawa, Yasuhiro Koguchi, Yuka Miyamoto, Yusuke Mizuno, Koichi Chida, Keiichi Akahane, Koji Tsuboi, Takeji Sakae, Hidehiko Sakurai

    RADIATION MEASUREMENTS   46 ( 12 )   2103 - 2106   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Although several cases of radiation-induced skin injury (RSI) have been reported in association with neurointerventional procedures, such as endovascular embolization for cerebral aneurysm, the absorbed doses are not directly measured in most cases. We therefore built a direct measurement system in order to simplify determination of the entrance skin dose (ESD) during neurointerventional procedures. This system was then applied to patients undergoing long and repetitive procedures in order to establish the efficacy of precise mapping of ESDs using a number of radiophotoluminescence glass dosimeters (RPLDs) and to avoid RSI. We also analyzed the correlation between maximum ESDs and angiographic parameters in order to estimate maximum ESD in real-time.
    ESD was measured in 35 procedures in 34 cerebral aneurysm patients with a median age of 65 years (range, 38-79 years). Patients were measured for ESDs while wearing a fitted dosimetry cap equipped with 60 RPLD chips throughout the procedure. Angiographic parameters, including total fluoroscopic time and dose-area product (DAP), were recorded. The Pearson correlation test was used to determine the relationship between maximum ESD and each parameter.
    Five of thirty-five procedures showed temporal epilation (14.3%). The correlations between a patient's maximum ESD and total fluoroscopic time and DAP were r = 0.7372, P &lt; 0.001 and r = 0.6698, P &lt; .001, respectively.
    We concluded that the regional ESD with geometric information could be obtained by applying the RPLDs. Although this passive dosimetry system may not entirely prevent RSI in real-time, precise dose mapping accompanied by monitoring of angiographic parameters during the procedure should contribute to reducing X-ray dose accumulation in repeated prophylactic endovascular embolization for asymptomatic cerebral aneurysm. (C) 2011 Elsevier Ltd. All rights reserved.

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  • Myosin light chain kinase activation and calcium sensitization in smooth muscle in vivo 査読 国際誌

    Yusuke Mizuno, Eiji Isotani, Jian Huang, Hailei Ding, James T. Stull, Kristine E. Kamm

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   295 ( 2 )   C358 - C364   2008年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) in smooth muscle by myosin light chain kinase (MLCK) and dephosphorylation by myosin light chain phosphatase (MLCP) are subject to modulatory cascades that influence the sensitivity of RLC phosphorylation and hence contraction to intracellular Ca2+ concentration ([Ca2+](i)). We designed a CaM-sensor MLCK containing smooth muscle MLCK fused to two fluorescent proteins linked by the MLCK CaM-binding sequence to measure kinase activation in vivo and expressed it specifically in mouse smooth muscle. In phasic bladder muscle, there was greater RLC phosphorylation and force relative to MLCK activation and [Ca2+](i) with carbachol (CCh) compared with KCl treatment, consistent with agonist-dependent inhibition of MLCP. The dependence of force on MLCK activity was nonlinear such that at higher concentrations of CCh, force increased with no change in the net 20% activation of MLCK. A significant but smaller amount of MLCK activation was found during the sustained contractile phase. MLCP inhibition may occur through RhoA/Rho-kinase and/or PKC with phosphorylation of myosin phosphatase targeting subunit-1 (MYPT1) and PKC-potentiated phosphatase inhibitor (CPI-17), respectively. CCh treatment, but not KCl, resulted in MYPT1 and CPI-17 phosphorylation. Both Y27632 (Rho-kinase inhibitor) and calphostin C ( PKC inhibitor) reduced CCh-dependent force, RLC phosphorylation, and phosphorylation of MYPT1 (Thr694) without changing MLCK activation. Calphostin C, but not Y27632, also reduced CCh-induced phosphorylation of CPI-17. CCh concentration responses showed that phosphorylation of CPI-17 was more sensitive than MYPT1. Thus the onset of agonist-induced contraction in phasic smooth muscle results from the rapid and coordinated activation of MLCK with hierarchical inhibition of MLCP by CPI-17 and MYPT1 phosphorylation.

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  • Involvement of accumulated NOS inhibitors and endothelin-1, enhanced arginase, and impaired DDAH activities in pulmonary dysfunction following subarachnoid hemorrhage in the rabbit 査読 国際誌

    Yusuke Mizuno, Eiji Isotani, Kikuo Ohno, Akiko Nagai, Masatoshi Imamura, Hiroshi Azuma

    VASCULAR PHARMACOLOGY   48 ( 1 )   21 - 31   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    We designed the present experiments to investigate the involvement of endogenous nitric oxide synthase (NOS) inhibitors, dimethylarginine dimethylaminohydrolase (DDAB) as a hydrolyzing enzyme of the NOS inhibitors, NOS, arginase which shares L-arginine as a common substrate with NOS, and endothelin-1 (ET-1) in the pulmonary dysfunction after induction of experimental subarachnoid hemorrhage (SAH) in the rabbit. SAH was induced by injecting autologous blood into the cisterna magna, and controls were injected with saline. On day 2, pulmonary arteries were isolated for determinations. A significant impairment of the endothelium-dependent relaxation (EDR) caused by acetylcholine was found in 20 cases (43.5%) out of 46 SAH animals, and the same animals exhibited accompanying the significantly impaired cyclic GMP production, accumulated endogenous NOS inhibitors, attenuated DDAH activity, enhanced arginase activity and accumulated ET-1 within the vessel wall. Meanwhile, there were no differences in endothelial NOS activity per se and sodium nitroprusside-induced relaxation between the animals with an impaired EDR and those without such a change. ET-1 content within aortic wall was increased with concomitant decrease in cyclic GMP production after the intraperitoneal application of authentic monomethylarginine as a NOS inhibitor in the rat. The current results suggest that accumulated endogenous NOS inhibitors and enhanced arginase activity possibly bring about the impaired NO production, thereby attenuating the EDR and contributing to the accumulation of ET-1 within the vessel wall. The accumulated endogenous NOS inhibitors at least partly result from the decreased DDAH activity. These alterations may be relevant to the pulmonary dysfunction after induction of SAH. (C) 2007 Elsevier Inc. All rights reserved.

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  • Alterations of intracellular calcium concentration and nitric oxide generation in pulmonary artery endothelium after subarachnoid hemorrhage of the rabbit 査読 国際誌

    Yoshihiro Kubota, Eiji Isotani, Yusuke Mizuno, Kikuo Ohno, Hiroshi Azuma

    VASCULAR PHARMACOLOGY   47 ( 2-3 )   90 - 98   2007年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    The present study was designed to investigate whether endothelial intracellular calcium concentration ([Ca2+](i)), endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) generation altered in association with impaired endothelium-dependent relaxation (EDR) in pulmonary artery (PA) specimens from experimental subarachnoid hemorrhage (SAH) rabbits. Injecting non-heparinized autologous arterial blood into cisterna magna induced the SAH. Simultaneous measurements of enclotbelial [Ca2+](i) and isometric tension of PA specimens were performed using fura 2. The subjects included normal control rabbits (group N), SAH rabbits with normal EDR (group A) and with impaired EDR (group B). When treated with 10(-7) M acetylcholine (ACh), endothelial [Ca2+](i) was significantly lower in group B (74.1 +/- 8.5 nM) than that in groups A (153.0 +/- 28.0 nM, p &lt; 0.05) and N (184.8 +/- 27.8 nM, p &lt; 0.01). Basal and ACh-stimulated cyclic GMP productions as a marker of NO generation were also significantly (p &lt; 0.005) decreased in group B as compared to those in the other two groups. Meanwhile, there were no differences in eNOS activity per se among the three groups. These results suggest that the attenuated endothelial [Ca2+](i) elevation leads to the impaired NO generation in PA endothelium, which in turn impairs the EDR and possibly increases the vascular resistance of PA following SAH. (C) 2007 Published by Elsevier Inc.

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  • Ca2+ signaling in microdomains - Homer1 mediates the interaction between RyR2 and Cav1.2 to regulate excitation-contraction coupling 査読 国際誌

    Guojin Huang, Joo Young Kim, Marlin Dehoff, Yusuke Mizuno, Kristine E. Kamm, Paul F. Worley, Shmuel Muallem, Weizhong Zeng

    JOURNAL OF BIOLOGICAL CHEMISTRY   282 ( 19 )   14283 - 14290   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Excitation-contraction (E-C) coupling and Ca2+-induced Ca2+ release in smooth and cardiac muscles is mediated by the L-type Ca2+ channel isoform Ca(v)1.2 and the ryanodine receptor isoform RyR2. Although physical coupling between Ca(v)1.1 and RyR1 in skeletal muscle is well established, it is generally assumed that Ca(v)1.2 and RyR2 do not directly communicate either passively or dynamically during E-C coupling. In the present work, we re-examined this assumption by studying E-C coupling in the detrusor muscle of wild type and Homer1(-/-) mice and by demonstrating a Homer1-mediated dynamic interaction between Ca(v)1.2 and RyR2 using the split green fluorescent protein technique. Deletion of Homer1 in mice (but not of Homer2 or Homer3) resulted in impaired urinary bladder function, which was associated with higher sensitivity of the detrusor muscle to muscarinic stimulation and membrane depolarization. This was not due to an altered expression or function of RyR2 and Ca(v)1.2. Most notably, expression of Ca(v)1.2 and RyR2 tagged with the complementary C- and N- terminal halves of green fluorescent protein and in the presence and absence of Homer1 isoforms revealed that H1a and H1b/c reciprocally modulates a dynamic interaction between Ca(v)1.2 and RyR2 to regulate the intensity of Ca2+-induced Ca2+ release and its dependence on membrane depolarization. These findings define the molecular basis of a "two-state" model of E-C coupling by Ca(v)1.2 and RyR2. In one state, Ca(v)1.2 couples to RyR2 by H1b/c, which results in reduced responsiveness to membrane depolarization and in the other state H1a uncouples Ca(v)1.2 and RyR2 to enhance responsiveness to membrane depolarization. These findings reveal an unexpected and novel mode of interaction and communication between Ca(v)1.2 and RyR2 with important implications for the regulation of smooth and possibly cardiac muscle E-C coupling.

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  • ER stress disrupts Ca(2+-)signaling complexes and Ca2+ regulation in secretory and muscle cells from PERK-knockout mice 査読 国際誌

    GJ Huang, J Yao, WZ Zeng, Y Mizuno, KE Kamm, JT Stull, HP Harding, D Ron, S Muallem

    JOURNAL OF CELL SCIENCE   119 ( 1 )   153 - 161   2006年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COMPANY OF BIOLOGISTS LTD  

    Disruption of protein synthesis and folding results in ER stress, which is associated with the pathophysiology of diverse diseases affecting secretory and muscle cells. Cells are protected against ER stress by activation of the unfolded protein response (UPR) that is regulated by the protein kinase PERK, which phosphorylates the translation initiation factor 2 eIF2 alpha to attenuate protein synthesis. PERK-/- cells are unable to modulate ER protein load and experience high levels of ER stress. In addition to its role in protein synthesis, the ER also orchestrates many signaling events essential for cell survival, prominent among which is Ca2+ signaling. It is not known, however, whether there is a relationship between ER stress and the function of the Ca2+ signaling pathway in muscle and nonmuscle cells. To directly address this question we characterized Ca2+ signaling in the secretory pancreatic and parotid acinar cells and in urinary bladder smooth muscle (UBSM) cells obtained from PERK-/- and wild-type mice. Deletion of PERK that results in high levels of ER stress, and distention and fragmentation of the ER slowed the rate of agonist-mediated Ca2+ release from the ER and reduced Ca2+-induced Ca2+ release, although IP3 production, localization of the IP3 receptors, IP3-mediated Ca2+ release, Ca(v)1.2 current and RyRs activity remained unaltered. On the other hand, ER stress disrupted the integrity of the Ca2+-signaling complexes in both secretory and UBSM cells, as revealed by markedly reduced coimmunoprecipitation of plasma membrane- and ER-resident Ca2+-signaling proteins. These findings establish a relationship between the unfolding protein response, ER stress and Ca2+ signaling and highlight the importance of communication within the terminal ER-plasma membrane microdomain for propagation of the Ca2+ signal from the plasma membrane into the cell.

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  • Alterations of intracellular calcium concentration and NO production in rabbit pulmonary artery endothelium after subarachnoid hemorrhage

    Y Kubota, E Isotani, Y Mizuno, K Ohno, H Azuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   100   115P - 115P   2006年

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    記述言語:英語   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Calcium sensitization and myosin light chain kinase activation in smooth muscle contraction

    E Isotani, Y Mizuno, KE Kamm, JT Stull, K Ohno

    JOURNAL OF PHARMACOLOGICAL SCIENCES   100   121P - 121P   2006年

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    記述言語:英語   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Role of nonmuscle myosin II in smooth muscle contraction

    Y Mizuno, Y Dai, KE Kamm, JT Stull

    FASEB JOURNAL   19 ( 4 )   A124 - A124   2005年3月

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    記述言語:英語   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

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  • Endothelial dysfunction of the pulmonary artery changes the neuro-cardio-endocrine axis after subarachnoid hemorrhage

    E Isotani, Y Kubota, Y Mizuno, K Ohno, H Azuma

    JOURNAL OF PHARMACOLOGICAL SCIENCES   97   66P - 66P   2005年

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    記述言語:英語   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • Real-time evaluation of myosin light chain kinase activation in smooth muscle tissues from a transgenic calmodulin-biosensor mouse 査読 国際誌

    E Isotani, G Zhi, KS Lau, J Huang, Y Mizuno, A Persechini, R Geguchadze, KE Kamm, JT Stull

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   101 ( 16 )   6279 - 6284   2004年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATL ACAD SCIENCES  

    Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) by myosin light chain kinase (MLCK) initiates smooth muscle contraction and regulates actomyosin-based cytoskeletal functions in nonmuscle cells. The net extent of RLC phosphorylation is controlled by MLCK activity relative to myosin light chain phosphatase activity. We have constructed a CaM-sensor MLCK where Ca2+-dependent CaM binding increases the catalytic activity of the kinase domain, whereas coincident binding to the biosensor domain decreases fluorescence resonance energy transfer between two fluorescent proteins. We have created transgenic mice expressing this construct specifically in smooth muscle cells to perform real-time evaluations of the relationship between smooth muscle contractility and MLCK activation in intact tissues and organs. Measurements in intact bladder smooth muscle demonstrate that MLCK activation increases rapidly during KCl-incluced contractions but is not maximal, consistent with a limiting amount of cellular CaM. Carbachol treatment produces the same amount of force development and RLC phosphorylation, with much smaller increases in [Ca2+](i) and MLCK activation. A Rho kinase inhibitor suppresses RLC phosphorylation and force but not MLCK activation in carbachol-treated tissues. These observations are consistent with a model in which the magnitude of an agonist-mediated smooth muscle contraction depends on a rapid but limited Ca2+/CaM-dependent activation of MLCK and Rho kinase-mediated inhibition of myosin light chain phosphatase activity. These studies demonstrate the feasibility of producing transgenic biosensor mice for investigations of signaling processes in intact systems.

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  • Ca2+-sensitization of smooth muscle contraction

    Y Mizuno, E Isotani, KS Lau, G Zhi, JT Stull, KE Kamm

    BIOPHYSICAL JOURNAL   84 ( 2 )   107A - 107A   2003年2月

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    記述言語:英語   出版者・発行元:BIOPHYSICAL SOCIETY  

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  • Inhibitory effect of activated protein C on cerebral vasospasm after subarachnoid Hemorrhage in the rabbit 査読 国際誌

    Y Mizuno, H Azuma, Y Ito, E Isotani, K Ohno, K Hirakawa

    JOURNAL OF CARDIOVASCULAR PHARMACOLOGY   39 ( 5 )   729 - 738   2002年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    This study investigated whether activated protein C (APC) improves the cerebral vasospasm in an experimental subarachnoid hemorrhage that was produced by the intracisternal injection of autologous blood. Male rabbits were divided into the following four groups: APC 0.1- and 0.5-mg groups, in which 0.1 and 0.5 mg APC were injected into the cisterna magna, respectively; a placebo group, in which saline was injected instead of APC; and a sham operation group that did not get injections of autologous blood, APC, and saline. On day 2, amount of clot in the basal cistern was significantly (p &lt; 0.01) decreased in the APC 0.5-mg group. Percent diameter of the basilar artery on day 2 to that before injecting the blood was angiographically determined as 97.1 +/- 3.8% in the APC 0.5-mg group, which was significantly (p &lt; 0.001) greater than the corresponding value in the placebo group (74.8 +/- 3.4%). The impaired endothelium-dependent relaxation following subarachnoid hemorrhage was normalized in the APC 0.5-mg group (p &lt; 0.0001). These results suggest that APC would improve cerebral vasospasm following subarachnoid hemorrhage, possibly by decreasing the amount of subarachnoid clot and normalizing the impaired nitric oxide production/release.

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  • Role of endogenous NOS inhibitors in the decreased endothelium-dependent relaxation of the pulmonary artery from experimental SAH rabbit

    Y Mizuno, H Azuma, E Isotani, K Ohno

    JAPANESE JOURNAL OF PHARMACOLOGY   88   247P - 247P   2002年

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  • ウサギクモ膜下出血モデルにおけるactivated protein C(APC)による脳血管攣縮の改善

    水野 祐介, 東 洋, 伊東 芳史, 磯谷 栄二, 大野 喜久郎, 平川 公義

    脳血管攣縮   15   265 - 268   2000年6月

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    記述言語:日本語   出版者・発行元:スパズム・シンポジウム事務局  

    今回APC 0.5mg投与で脳血管攣縮率の改善,クモ膜下残存血腫量の減少,脳底動脈の内皮依存性弛緩反応の改善が得られ,又,APC 0.1mg投与でも内皮依存性弛緩反応の改善が認められた.以上よりAPCによって血腫を溶解・除去することで脳血管攣縮を改善し得ることが示唆された

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  • Effective improvement of the cerebral vasospasm after subarachnoid hemorrhage with low-dose nitroglycerin 査読

    Y Ito, E Isotani, Y Mizuno, H Azuma, K Hirakawa

    JOURNAL OF CARDIOVASCULAR PHARMACOLOGY   35 ( 1 )   45 - 50   2000年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    In the rabbit subarachnoid hemorrhage (SAH) model, the sensitivity of spastic basilar arteries to nitric oxide (NO) was enhanced whereas the endothelial function to release/ produce NO became impaired, as described previously. We assumed from these results that low-dose NO might selectively dilate spastic arteries without influencing normal or systemic blood vessels; therefore, we investigated whether exogenous low-dose NO effectively improves cerebral vasospasm. Low-dose NO was derived from a small size of the tape containing nitroglycerin, which is not invasive and is clinically available. The experimental SAH was induced by injecting autologous blood into the cisterna magna of the rabbit. Experiments were performed on the following three groups: (a) SAH group with nitroglycerin tape (nitroglycerin group), (b) SAH group with placebo tape (placebo group), and (c) saline group injected with saline instead of blood. The tape containing 0.675 mg nitroglycerin was applied once daily for 2 days onto the skin area of the rabbit's ear. Angiograms were performed once before cisternal injection of blood and/or saline and again on day 2. On day 2 the basilar artery was isolated and sliced into 2-mm ring preparations. Relaxations of the basilar artery to acetylcholine, sodium nitroprusside, and calcium ionophore A23187, as well as the contractile responses to serotonin and endothelin-l, were measured. The diameter of the basilar artery on day 2 was reduced to 69.6 +/- 2.2% (n = 7) before the injection of autologous blood. The angiographic vasospasm of the basilar artery was partially but significantly (p &lt; 0.0001) improved to the percentage diameter of 89.4 +/- 1.4% (n = 7) by the application of low-dose nitroglycerin, which did not affect the systemic blood pressure and heart rate. In the basilar artery preparations harvested from SAH rabbits on day 2, the impaired acetylcholine-induced endothelium-dependent relaxation was partially but significantly (p &lt; 0.001) improved in the nitroglycerin group However, this group remained unaffected in the increased sensitivity to nitroglycerin and the contractile responses to serotonin and endothelin-l. Low-dose nitroglycerin tape effectively improved the cerebral vasospasm after SAH without any significant changes in the systemic circulation and would be one of the useful and noninvasive treatments for cerebral vasospasm. The results seem to be partially affected by the effective dilation of the spastic artery and the improvement of the impaired endothelium-dependent relaxation with low-dose NO.

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  • ウサギくも膜下出血モデルに対する低用量ニトログリセリン・塩酸ファスジル併用療法

    磯谷 栄二, 伊東 芳史, 水野 祐介, 大野 喜久郎, 平川 公義, 東 洋

    脳血管攣縮   14   313 - 317   1999年6月

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    記述言語:日本語   出版者・発行元:スパズム・シンポジウム事務局  

    低用量NTG・塩酸ファスジル併用療法によってウサギくも膜下出血モデルにおける脳血管攣縮は完全に予防し得た.予防的薬物療法には内因性NOと同様のパラクリン作用を有するNO donorが望ましい

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MISC

  • 手術時のタイムアウトの形骸化を防ぐ 手術同意書との照合による部位誤認の確実な防止と麻酔科医進行による手術チームの行動変容

    菊地 龍明, 植田 瑛子, 水野 祐介, 我妻 恵, 斉藤 佳代子, 若杉 正, 島田 朋子

    医療の質・安全学会誌   18 ( Suppl. )   372 - 372   2023年11月

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    記述言語:日本語   出版者・発行元:(一社)医療の質・安全学会  

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  • リンパ管静脈吻合術を受ける患者に対するSF-12による術前QOLの調査

    荒屋 和江, 長嶺 祐介, 水野 祐介, 後藤 隆久

    日本手術医学会誌   43 ( Suppl. )   159 - 159   2022年10月

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    記述言語:日本語   出版者・発行元:日本手術医学会  

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  • 手術を受ける患者の病棟出棟から麻酔導入までの自律神経活動の変化 ウェアラブルデバイスを用いた検証

    岩佐 葵, 福田 真佑, 立石 由紀子, 三浦 友也, 水野 祐介, 赤瀬 智子, 後藤 隆久

    臨床モニター   33 ( Suppl. )   107 - 107   2022年6月

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    記述言語:日本語   出版者・発行元:医学図書出版(株)  

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  • 当施設におけるCOVID-19流行期の手術件数の推移と手術室運営

    永田桃子, 鈴木芽衣, 藤本寛子, 入江友哉, 水野祐介, 後藤隆久

    日本麻酔科学会学術集会(Web)   69th   2022年

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  • 周術期管理センターにおける情報の一元化とデータベース

    水野祐介

    日本麻酔科学会学術集会(Web)   69th   2022年

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  • L-DOPA受容体(GPR143)による血管平滑筋細胞の遊走と増殖はラットにおけるモノクロタリン誘発性肺高血圧に関与する

    中野 雅友樹, 橋本 達夫, 古賀 資和, 増川 太輝, 奥 真哉, 水野 祐介, 後藤 隆久, 田村 功一, 五嶋 良郎

    日本薬理学会年会要旨集   95   1-YIA-06   2022年

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    記述言語:日本語   出版者・発行元:公益社団法人 日本薬理学会  

    We previously demonstrated that L-DOPA modulated the vascular α1-adrenergic receptor through GPR143, a G-protein coupled receptor, and sensitized vasomotor tone. In this study, we examined a possible role of GPR143 in the pathogeneisis of pulmonary hypertension (PH). In isolated pulmonary arteries, L-DOPA (1 μM) augmented contractile response to phenylephrine, an α1 adrenergic receptor agonist. We generated GPR143 gene-deficient (<i>Gpr143</i><sup><i>-/y</i></sup>) rats and comparatively studied the effect of L-DOPA. L-DOPA did not modify phenylephrine-induced response in the pulmonary arteries of <i>Gpr143</i><sup><i>-/y</i></sup> rats, thereby indicating that the action of L-DOPA was mediated by GPR143. We next established monocrotaline (MCT, 60 mg/kg) -induced PH model in wild type (WT) and <i>Gpr143</i><sup><i>-/y</i></sup> rats. One month after injection subcutaneously with MCT , the right ventricular systolic pressure (RVSP) was attenuated in <i>Gpr143</i><sup><i>-/y</i></sup> rats as compared to the WT rats (49.7 +/- 1.1 mmHg and 41.4 +/- 1.4 mmHg in WT and <i>Gpr143</i><sup><i>-/y</i></sup>, p&lt;0.05, N=5). Coordinately, the right ventricle to body weight (RV/BW) (5.4 +/- 0.2 × 10<sup>-4</sup> and 4.7 +/- 0.1 × 10<sup>-4</sup> in WT and <i>Gpr143</i><sup><i>-/y</i></sup>, p&lt;0.01, N=12) was also reduced in <i>Gpr143</i><sup><i>-/y</i></sup> rats compared to the WT rats. Furthermore, in primary cultures of pulmonary artery smooth muscle cells (PASMCs), the proliferative and migratory capacity of <i>Gpr143</i><sup><i>-/y</i></sup> PASMCs after phenylephrine treatment was reduced compared to <i>Gpr143</i>-WT PASMCs. We here provide evidence that GPR143 may be involved in MCT-induced PH in rats by affecting the proliferative and migratory capacity of PASMCs.

    DOI: 10.1254/jpssuppl.95.0_1-yia-06

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  • モノクロタリン誘発肺高血圧症ラットの肺動脈におけるprotein kinase Dの役割の解明

    奥 真哉, 長嶺 祐介, 菅原 陽, 水野 祐介, 後藤 隆久

    Cardiovascular Anesthesia   25 ( Suppl. )   89 - 89   2021年10月

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    記述言語:日本語   出版者・発行元:(一社)日本心臓血管麻酔学会  

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  • 「麻酔科医と働き方改革」 手術室・麻酔科医のタスクシフティング 周術期業務の効率化

    水野 祐介

    神奈川医学会雑誌   48 ( 1 )   54 - 54   2021年1月

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    記述言語:日本語   出版者・発行元:(公社)神奈川県医師会  

    J-GLOBAL

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  • 麻酔科医の業務効率化,業務委託のための全麻酔科医タイムスタディ

    水野祐介, 山内朋子, 後藤隆久

    日本麻酔科学会学術集会(Web)   68th   2021年

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  • 低酸素誘発性肺高血圧クライシス動物モデルにおけるドブタミン単剤投与の有効性の検討

    奥真哉, 澤田侑理, 水野祐介, 菅原陽, 後藤隆久

    日本麻酔科学会学術集会(Web)   68th   2021年

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  • 低酸素誘発性肺高血圧クライシス動物モデルにおけるドブタミン単剤投与の有効性の検討

    武田悠, 奥真哉, 古賀資和, 菅原陽, 水野祐介, 後藤隆久

    日本麻酔科学会学術集会(Web)   67th   2020年

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  • 十分な覚醒が得られず、覚醒下開頭腫瘍摘出術を断念した1症例

    松田 優子, 西周 祐美, 水野 祐介, 後藤 隆久

    麻酔   67 ( 7 )   748 - 751   2018年7月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

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  • pectoral nerve blockのみで乳房部分切除手術を管理しえた1症例

    山本 夏啓, 水野 祐介, 野村 岳志, 後藤 隆久

    麻酔   67 ( 6 )   611 - 613   2018年6月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    症例は64歳女性で、左外上部乳がんの診断で約半年前から術前化学療法を受け、乳房部分切除術および腋窩リンパ節生検を予定された。間質性肺炎再燃のリスクを考慮し、全身麻酔を避けpectoral nerve blockブロックのみで麻酔管理する方針とした。ブロックは仰臥位で、リニアプローブと22G Tuohy針を用いて超音波ガイド下に第4肋骨上、大胸筋と前鋸筋の間に0.25%レボブピバカインを40ml投与し、さらに傍胸骨で大胸筋全面に0.25%レボブピバカインを15ml投与した。術中は腋窩の最も背側の部分で疼痛を認め、1%リドカイン1mlの局所浸潤麻酔を要したが、その他は問題なく手術は予定どおり終了した。予術終了後の経過観察で、間質性肺炎の増悪を疑う症状および検査所見は認めなかった。

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    その他リンク: https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01397&link_issn=&doc_id=20180608080010&doc_link_id=%2Fad3msuie%2F2018%2F006706%2F011%2F0611-0613%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fad3msuie%2F2018%2F006706%2F011%2F0611-0613%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 筋委縮性側索硬化症合併患者に対する喉頭気管分離術3症例における全身麻酔管理

    奥山志織, 入江友哉, 水野祐介, 後藤隆久

    日本麻酔科学会学術集会(Web)   65th   2018年

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  • L-DOPAの肺高血圧モデル肺血管におけるフェニレフリン応答の修飾作用

    古賀資和, 古賀資和, 増川太輝, 中村史雄, 中村史雄, 菅原陽, 水野祐介, 後藤隆久, 五嶋良郎

    日本薬理学雑誌   150 ( Supplement )   2017年

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  • 心臓術後の重度左心低機能患者に対する鎖骨下動脈送血によるECMO

    春原 啓人, 寺端 昭博, 岡村 健太, 入江 友哉, 水野 祐介, 後藤 隆久

    日本臨床麻酔学会誌   36 ( 6 )   S288 - S288   2016年10月

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    記述言語:日本語   出版者・発行元:日本臨床麻酔学会  

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  • 硬膜外麻酔で安全に管理しえた筋萎縮性側索硬化症患者の麻酔経験

    新井 悠介, 吉田 輔, 水野 祐介, 宮下 徹也, 後藤 隆久

    麻酔   64 ( 10 )   1062 - 1064   2015年10月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    82歳女。74歳時に筋萎縮性側索硬化症(ALS)と診断され、嚥下障害の進行により誤嚥性肺炎を繰り返すようになり、内視鏡的胃瘻造設術が予定された。しかし、局所麻酔下での手術中に胃穿孔を偶発し、緊急開腹術に移行することとなった。重度の呼吸機能障害を呈するALS患者であったことから、硬膜外麻酔を選択しNPPVを併用したところ、安全に麻酔管理を行うことが可能であった。

    PubMed

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J01397&link_issn=&doc_id=20151013060012&doc_link_id=40020609764&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40020609764&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • Involvement of increased protein arginine methyltransferases 2 and decreased dimethylarginine dimethylaminohydrolases in impaired NOS activity in pulmonary hypertension in rats 査読

    水野 祐介

    European Journal of Anaesthesiology   31   2014年

  • 小児心カテーテル術中の患者の入射皮膚線量の直接測定法(Direct measurement of patient's entrance skin dose during pediatric cardiac catheterization)

    孫 略, 水野 祐介, 岩本 眞理, 後藤 隆久, 小口 靖弘, 坪井 康次, 千田 浩一, 盛武 敬

    日本放射線技術学会雑誌   69 ( 9 )   1070 - 1070   2013年9月

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    記述言語:日本語   出版者・発行元:(公社)日本放射線技術学会  

    J-GLOBAL

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  • くも膜下出血を機に大動脈縮窄症が発見された若年者の開頭クリッピング術の麻酔経験

    米川 裕子, 中橋 勇典, 水野 祐介, 紙谷 義孝, 武田 康二, 後藤 隆久

    麻酔   61 ( 3 )   326 - 328   2012年3月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

    15歳男性。突然の頭痛と嘔吐により著者らの施設へ救急搬送され、頭部CTにてクモ膜下出血と診断後、入院となった。所見ではほかに聴診上、前胸部に収縮期雑音が聴取され、心電図では左室肥大が認められた。また、両上肢での血圧測定では血圧値の左右差が認められた。そのため脳血管造影とあわせて大動脈造影を行ったところ、脳血管造影では前大脳動脈瘤がみられ、大動脈造影では左鎖骨下動脈分岐部の狭窄が認められた。以上より、本症例は大動脈縮窄とそれに伴う脳動脈瘤破裂と診断され、全身麻酔下に開頭クリッピング術が施行された。術中は左鎖骨下動脈分岐部の大動脈狭窄による上肢血圧の左右差があったことから、右橈骨動脈の観血的動脈圧と左橈骨動脈の観血的動脈圧を測定し、更に左大腿でも非観血的動脈圧を測定した。その結果、左橈骨動脈の平均血圧と左大腿での平均血圧はほぼ等しい値となり、患者は術後経過良好で、入院20日後には独歩退院となった。

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  • 脊髄小脳変性症患者におけるロクロニウム筋弛緩の遷延がスガマデクスにより著明に回復した1例

    鈴木ちえ子, 水野祐介, 佐藤逸郎, 三浦倫一, 後藤隆久

    日本臨床麻酔学会誌   31 ( 6 )   S420 - S420   2011年10月

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    記述言語:日本語   出版者・発行元:日本臨床麻酔学会  

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  • 静脈血栓塞栓症予防策施行後に発生した術後腓骨神経麻痺の2症例

    水野 祐介, 丸田 秀郎, 中山 啓子, 金子 和裕

    麻酔   57 ( 1 )   111 - 111   2008年1月

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    記述言語:日本語   出版者・発行元:克誠堂出版(株)  

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  • くも膜下出血後の肺動脈内皮機能障害

    久保田叔宏, 磯谷栄二, 水野祐介, 大野喜久郎, 東洋

    脳卒中   28 ( 1 )   126 - 126   2006年3月

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    記述言語:日本語   出版者・発行元:(一社)日本脳卒中学会  

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  • くも膜下出血における肺動脈内皮細胞機能障害

    久保田叔宏, 水野裕介, 磯谷栄二, 大野喜久郎, 東洋

    日本脳神経外科学会総会抄録集(CD-ROM)   64th   2005年

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  • くも膜下出血後の脳血管れん縮期における肺動脈内皮細胞機能障害

    磯谷栄二, 水野祐介, 久保田叔宏, 大野喜久郎

    日本脳神経外科学会総会抄録集   63rd ( CD-ROM Abstracts )   P626   2004年10月

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    記述言語:日本語  

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  • ウサギクモ膜下出血モデル肺動脈における内皮依存性弛緩反応減弱に対する内因性NOS inhibitorsの関与

    水野 祐介, 東 洋, 鈴木 弘幸, 後藤 守兄, 磯谷 栄二, 大野 喜久郎

    日本脳神経外科学会総会抄録集   59回 ( Abstract )   180 - 180   2000年10月

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    記述言語:日本語   出版者・発行元:(一社)日本脳神経外科学会  

    J-GLOBAL

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  • ウサギクモ膜下出血モデルにおけるactivated protein C(APC)による脳血管攣縮の改善

    水野 祐介, 伊東 芳史, 磯谷 栄二, 大野 喜久郎, 東 洋, 平川 公義

    日本脳神経外科学会総会抄録集   58回 ( Abstract )   370 - 370   1999年10月

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    記述言語:日本語   出版者・発行元:(一社)日本脳神経外科学会  

    J-GLOBAL

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  • MRIで確定診断したクモ膜下出血の1例

    水野 祐介

    茨城県臨床医学雑誌   ( 33 )   188 - 188   1997年8月

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    記述言語:日本語   出版者・発行元:(一社)茨城県医師会  

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  • 頸部頸動脈瘤の1症例

    水野 祐介

    茨城県臨床医学雑誌   ( 32 )   178 - 178   1996年8月

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    記述言語:日本語   出版者・発行元:(一社)茨城県医師会  

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▼全件表示

講演・口頭発表等

  • Role of protein kinase D1 in vasoconstriction and haemodynamics in rats

    Yoh Sugawara, Yusuke Mizuno, Shinya Oku, Yuri Sawada, Takahisa Goto

    Microvascular Research  2023年11月 

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    開催年月日: 2023年11月

    記述言語:英語  

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  • Right ventricular overloading is attenuated in monocrotaline-induced pulmonary hypertension model rats with a disrupted Gpr143 gene, the gene that encodes the 3,4-l-dihydroxyphenyalanine (l-DOPA) receptor.

    Masayuki Nakano, Motokazu Koga, Tatsuo Hashimoto, Natsuki Matsushita, Daiki Masukawa, Yusuke Mizuno, Hiraku Uchimura, Ryo Niikura, Tomoyuki Miyazaki, Fumio Nakamura, Suo Zou, Takahiro Shimizu, Motoaki Saito, Kouichi Tamura, Takahisa Goto, Yoshio Goshima

    Journal of pharmacological sciences  2022年2月 

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    開催年月日: 2022年2月

    記述言語:英語  

    Pulmonary hypertension (PH) is a severe and progressive disease that causes elevated right ventricular systolic pressure, right ventricular hypertrophy and ultimately right heart failure. However, the underlying pathophysiologic mechanisms are poorly understood. We previously showed that 3,4-l-dihydroxylphenyalanine (DOPA) sensitizes vasomotor response to sympathetic tone via coupling between the adrenergic receptor alpha1 (ADRA1) and a G protein-coupled receptor 143 (GPR143), a DOPA receptor. We investigated whether DOPA similarly enhances ADRA1-mediated contraction in pulmonary arteries isolated from rats, and whether GPR143 is involved in the PH pathogenesis. Pretreating the isolated pulmonary arteries with DOPA 1 μM enhanced vasoconstriction in response to phenylephrine, an ADRA1 agonist, but not to U-46619, a thromboxane A2 agonist or endothelin-1. We generated Gpr143 gene-deficient (Gpr143-/y) rats, and confirmed that DOPA did not augment phenylephrine-induced contractile response in Gpr143-/y rat pulmonary arteries. We utilized a rat model of monocrotaline (MCT)-induced PH. In the MCT model, the right ventricular systolic pressure was attenuated in the Gpr143-/y rats than in WT rats. Phenylephrine-induced cell migration and proliferation were also suppressed in Gpr143-/y pulmonary artery smooth muscle cells than in WT cells. Our result suggests that GPR143 is involved in the PH pathogenesis in the rat models of PH.

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  • Anterior quadratus lumborum block for postoperative recovery after total hip arthroplasty: a study protocol for a single-center, double-blind, randomized controlled trial.

    Masaru Kikuchi, Takahiro Mihara, Yusuke Mizuno, Hiroko Fujimoto, Sachiko Arai, Takeshi Nomura, Takahisa Goto

    Trials  2020年2月 

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    開催年月日: 2020年2月

    記述言語:英語  

    BACKGROUND: Appropriate pain management is essential to improve the postoperative recovery after total hip arthroplasty (THA). Various case reports have indicated that anterior quadratus lumborum block (QLB) provides effective postoperative analgesia in lower limb surgeries. However, few randomized controlled trials have confirmed the efficacy of anterior QLB for lower limb surgeries. The aim of this single-center, double-blind, randomized controlled trial is to confirm the efficacy of anterior QLB for postoperative recovery after THA. METHODS: The participants will be randomly assigned to either the anterior QLB or placebo groups, using a set of random numbers for the allocation sequence. Only pharmacists will be aware of the allocations; other investigators will be blinded until study completion. After induction of general anesthesia, anterior QLB will be performed by using 0.25% levobupivacaine or normal saline. Fentanyl will be administered according to blood pressure change during the surgery. The primary outcome will be the quality of recovery 40 score (QoR-40). Secondary outcomes will include the visual analog scale score of pain intensity at rest and movement, intraoperative and postoperative doses of fentanyl, and incidence of postoperative nausea and vomiting. Statistical analysis will be performed by using the Student's t test, Mann-Whitney U test, and Fisher's exact test as appropriate. A P value of less than 0.05 will be considered statistically significant. DISCUSSION: The results of our study will reveal whether anterior QLB is effective for postoperative recovery after THA. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000032255. Registered on 15 April 2018.

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  • Pre-anesthetic ultrasonographic assessment of the internal jugular vein for prediction of hypotension during the induction of general anesthesia.

    Kenta Okamura, Takeshi Nomura, Yusuke Mizuno, Tetsuya Miyashita, Takahisa Goto

    Journal of anesthesia  2019年10月 

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    開催年月日: 2019年10月

    記述言語:英語  

    PURPOSE: Severe hypotension caused by anesthetic administration for anesthesia induction, which might cause ischemic stroke, myocardial injury, acute kidney injury and postoperative mortality, should be prevented. Anesthesiologists are familiar with ultrasound examination of the internal jugular vein (IJV). This study aimed to clarify whether ultrasonographic IJV evaluation just before induction could predict the occurrence of such hypotension. METHODS: Adult patients undergoing surgery under general anesthesia were enrolled after excluding patients with cardiovascular disease or ASA-PS ≥ III. Ultrasonographic IJV images were recorded in both the supine and 10° Trendelenburg positions immediately before induction. Using these images, IJV area (IJV-A), diameter and change rate with posture were measured. Hypotension during induction was defined as mean BP < 60 mmHg or > 30% decrease from baseline. RESULTS: Hypotension during induction was observed in 37 of 82 patients. IJV-A in the Trendelenburg position was 2.02 ± 0.86 and 1.72 ± 0.68 in the hypotensive and non-hypotensive groups, respectively (P = 0.08). Logistic regression analysis performed using age, use of calcium antagonists, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, baseline mean BP and IJV-A in the Trendelenburg position as variables showed that IJV-A in the Trendelenburg position was an independent predictor of hypotension, with an adjusted odds ratio of 3.11 (95% CI 1.07-9.03, P = 0.04). Area under the curve was 0.595 (95% CI 0.469-0.722) for IJV-A in the Trendelenburg position. CONCLUSION: IJV-A in the Trendelenburg position was an independent predictor of hypotension during induction. Further study is required to examine the diagnostic accuracy of IJV-A as a predictor for hypotension during induction.

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  • Effect of posterior quadratus lumborum blockade on the quality of recovery after major gynaecological laparoscopic surgery: A randomized controlled trial.

    Hiroko Fujimoto, Tomoya Irie, Takahiro Mihara, Yusuke Mizuno, Takeshi Nomura, Takahisa Goto

    Anaesthesia and intensive care  2019年3月 

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    開催年月日: 2019年3月

    記述言語:英語  

    Bilateral quadratus lumborum blockade (QLB) using ultrasound guidance has been introduced as an abdominal truncal block to improve postoperative analgesia and quality of recovery (QoR) after abdominal surgery, but efficacy remains controversial. The primary aim of this study was to evaluate the efficacy of posterior QLB on the postoperative QoR, and secondarily to evaluate postoperative pain after gynaecological laparoscopic surgery (LS). This study was a single-centre randomized controlled trial. QLB group patients underwent bilateral posterior quadratus lumborum injections with 25-30 mL of 0.25% levobupivacaine after induction of general anaesthesia; the control group underwent no block. Both groups were administered fentanyl-based intravenous patient-controlled analgesia postoperatively. The postoperative QoR was measured using the Quality of Recovery 40 (QoR-40) questionnaire score; postoperative pain was evaluated using the visual analogue scale (VAS) and the cumulative postoperative fentanyl dose. Thirty-one and 29 patients were randomised to the QLB and control groups, respectively. The intraoperative remifentanil dosage was significantly less in the QLB group. The median (interquartile range) for the QoR-40 score was not different between the groups: 154 (133-168) in the QLB group and 158 (144-172) in the control group. There were no statistically significant differences in secondary outcome variables. Single-shot QLB did not improve the QoR or postoperative pain in patients managed by multimodal analgesia after gynaecological LS.

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  • Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension.

    Sugawara Y, Mizuno Y, Oku S, Goto T

    British journal of anaesthesia  2019年2月 

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    開催年月日: 2019年2月

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  • Roles and mechanism of protein kinase D in vasoconstriction

    Yusuke Mizuno, Yoh Sugawara, Takahisa Goto

    FASEB JOURNAL  2018年4月  FEDERATION AMER SOC EXP BIOL

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    開催年月日: 2018年4月

    記述言語:英語  

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  • Comparison between High- and Low-Cost Transmission of Tele-Anesthesia in Japan.

    Yoh Sugawara, Tetsuya Miyashita, Yusuke Mizuno, Yusuke Nagamine, Tomoyuki Miyazaki, Ayako Kobayashi, Kentaro Tojo, Yasuhiro Iketani, Shunsuke Takaki, Takahisa Goto

    Journal of healthcare engineering  2018年 

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    開催年月日: 2018年

    記述言語:英語  

    Background: We previously reported a tele-anesthesia system that connected Sado General Hospital (SGH) to Yokohama City University Hospital (YCUH) using a dedicated virtual private network (VPN) that guaranteed the quality of service. The study indicated certain unresolved problems, such as the high cost of constantly using a dedicated VPN for tele-anesthesia. In this study, we assessed whether use of a best-effort system affects the safety and cost of tele-anesthesia in a clinical setting. Methods: One hundred patients were enrolled in this study. We provided tele-anesthesia for 65 patients using a guaranteed transmission system (20 Mbit/s; guaranteed, 372,000 JPY per month: 1 JPY = US$0.01) and for 35 patients using a best-effort system (100 Mbit/s; not guaranteed, 25,000 JPY per month). We measured transmission speed and number of commands completed from YCUH to SGH during tele-anesthesia with both transmission systems. Results: In the guaranteed system, anesthesia duration was 5780 min (88.9 min/case) and surgical duration was 3513 min (54.0 min/case). In the best-effort system, anesthesia duration was 3725 min (106.4 min/case) and surgical duration was 2105 min (60.1 min/case). The average transmission speed in the best-effort system was 17.3 ± 3.8 Mbit/s. The system provided an acceptable delay time and frame rate in clinical use. All commands were completed, and no adverse events occurred with both systems. Discussion: In the field of tele-anesthesia, using a best-effort internet VPN system provided equivalent safety and efficacy at a better price as compared to using a guaranteed internet VPN system.

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  • Roles of protein kinase D in vasoconstriction and hemodynamics

    Yoh Sugawara, Yusuke Mizuno, Hiromasa Kawakami, Takahisa Goto

    FASEB JOURNAL  2016年4月  FEDERATION AMER SOC EXP BIOL

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    開催年月日: 2016年4月

    記述言語:英語  

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  • A pilot study of tele-anaesthesia by virtual private network between an island hospital and a mainland hospital in Japan

    Tetsuya Miyashita, Yusuke Mizuno, Yo Sugawara, Yusuka Nagamine, Yukihide Koyama, Tomoyuki Miyazaki, Kazuhiro Uchimoto, Yasuhiro Iketani, Kentaro Tojo, Takahisa Goto

    JOURNAL OF TELEMEDICINE AND TELECARE  2015年3月  SAGE PUBLICATIONS LTD

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    開催年月日: 2015年3月

    記述言語:英語  

    We studied the use of tele-anaesthesia between Sado General Hospital (SGH) located on Sado Island and Yokohama City University Hospital (YCUH) located in mainland Japan. The two sites were connected via a virtual private network (VPN). We investigated the relationship between the bandwidth of the VPN and both the frame rate and the delay time of the tele-anaesthesia monitoring system. The tool used for communication between the two hospitals was free videoconferencing software (FaceTime), which can be used over Wi-Fi connections. We also investigated the accuracy of the commands given during teleanaesthesia: any commands from the anaesthetist at the YCUH that were not carried out for any reason, were recorded in the anaesthetic records at the SGH. The original frame rate and data rate at the SGH were 5fps and approximately 18 Mbit/s, respectively. The frame rate at the transmission speeds of 1, 5 and 20 Mbit/s was 0.6, 1.6 and 5.0fps, respectively. The corresponding delay time was 12.2, 4.9 and 0.7s. Twenty-five adult patients were enrolled in the study and tele-anaesthesia was performed. The total duration of anaesthesia was 37 hours. All 888 anaesthetic commands were completed. There were 7 FaceTime disconnections, which lasted for 10min altogether. Because no commands needed to be given during the FaceTime disconnection, the telephone was not used. The anaesthesia assistance system might form part of the solution to medical resource shortages.

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  • Direct measurement of a patient's entrance skin dose during pediatric cardiac catheterization

    Lue Sun, Yusuke Mizuno, Mari Iwamoto, Takahisa Goto, Yasuhiro Koguchi, Yuka Miyamoto, Koji Tsuboi, Koichi Chida, Takashi Moritake

    JOURNAL OF RADIATION RESEARCH  2014年11月  OXFORD UNIV PRESS

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    開催年月日: 2014年11月

    記述言語:英語  

    Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose-area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 +/- 59 (mean +/- standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed.

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  • Role of VPAC2 receptor in monocrotaline-induced pulmonary hypertension in rats

    Motokazu Koga, Yusuke Mizuno, Itaru Watanabe, Hiromasa Kawakami, Takahisa Goto

    JOURNAL OF APPLIED PHYSIOLOGY  2014年8月  AMER PHYSIOLOGICAL SOC

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    開催年月日: 2014年8月

    記述言語:英語  

    Pulmonary hypertension (PH) is associated with significant morbidity and mortality. Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP) have pulmonary vasodilatory and positive inotropic effects via receptors VPAC1 and VPAC2, which possess a similar affinity for both peptides, and PAC1, a PACAP-preferring receptor. VIP is a promising option for PH treatment; however, various physiological effects of VIP have limited its clinical use. We investigated the effects of VPAC1 and VPAC2 selective agonists VIP and PACAP to explore more appropriate means of treatment for PH. We examined hemodynamic changes in right ventricular systolic pressure (RVSP), systemic blood pressure (SBP), total pulmonary resistance index (TPRI), total systemic resistance index, and cardiac index (CI) in response to their agonists with monocrotaline (MCT)-induced PH and explored involvement of VIP/PACAP expression and receptors in PH. Sprague-Dawley rats were divided into the MCT group (administered MCT 60 mg/kg) and control group. In MCT-induced PH, decreased VIP and PACAP were associated with upregulation of VPAC1, VPAC2, and PAC1 in lung tissues. Intravenous injection of VPAC2-selective agonist BAY 55-9837 and VIP, but not [Ala(11,22,28)] VIP, improved the CI. The decrease in SBP with VPAC2 agonist was significantly less than that in the control. Although they decreased SBP, these agonists hardly affected RVSP in the control. Activation of VPAC2 receptor with BAY 55-9837 effectively improved RVSP, TPRI, and CI in MCT-induced PH, suggesting a VPAC2 agonist as a possible promising treatment for PH.

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  • Effect of VPAC2 agonist on improving cardiac output in pulmonary hypertension

    Yusuke Mizuno, Motokazu Koga, Shizuka Kashiwagi, Itaru Watanabe, Takahisa Goto

    FASEB JOURNAL  2013年4月  FEDERATION AMER SOC EXP BIOL

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    開催年月日: 2013年4月

    記述言語:英語  

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  • Amount of accidental flush by syringe pump due to inappropriate release of occluded intravenous line

    Hiromasa Kawakami, Tetsuya Miyashita, Ryota Yanaizumi, Takahiro Mihara, Hitoshi Sato, Takayuki Kariya, Yusuke Mizuno, Takahisa Goto

    TECHNOLOGY AND HEALTH CARE  2013年  IOS PRESS

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    開催年月日: 2013年

    記述言語:英語  

    BACKGROUND: An unintended bolus is delivered by the syringe pump if intravenous line occlusion is released in an inappropriate manner. OBJECTIVE: The aim of this study was to measure the amount of flushed fluid when an occlusion is inappropriately released and to assess the effect of different syringe pump settings (flow rate, alarm setting, size of syringe and syringe pump model) on the flushed amount. METHODS: After the stopcock was closed, infusions were started with different model syringe pumps (Terufusion (R) TE312 and TE332S), different syringe sizes or at different alarm settings. After the occlusion alarm sounded, the occlusion was released and the amount of fluid emerging from the stopcock was measured. RESULTS: The bolus was significantly lower when the alarm was set at a low-pressure setting. The bolus was significantly lower with a 10-ml than a 50-ml syringe. A significant difference was seen only when a 50-ml syringe was used (TE312: 1.99 +/- 0.16 ml vs. TE332S: 0.674 +/- 0.116 ml, alarm High, p &lt; 0.001). CONCLUSION: To minimize the amount of accidentally injected medication, a smaller syringe size and a low alarm setting are important. Using a syringe pump capable of reducing the inadvertently administered bolus may be helpful.

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  • Precise mapping system of entrance skin dose during endovascular embolization for cerebral aneurysm

    Takashi Moritake, Mikito Hayakawa, Yuji Matsumaru, Tomoji Takigawa, Yasuhiro Koguchi, Yuka Miyamoto, Yusuke Mizuno, Koichi Chida, Keiichi Akahane, Koji Tsuboi, Takeji Sakae, Hidehiko Sakurai

    RADIATION MEASUREMENTS  2011年12月  PERGAMON-ELSEVIER SCIENCE LTD

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    開催年月日: 2011年12月

    記述言語:英語  

    Although several cases of radiation-induced skin injury (RSI) have been reported in association with neurointerventional procedures, such as endovascular embolization for cerebral aneurysm, the absorbed doses are not directly measured in most cases. We therefore built a direct measurement system in order to simplify determination of the entrance skin dose (ESD) during neurointerventional procedures. This system was then applied to patients undergoing long and repetitive procedures in order to establish the efficacy of precise mapping of ESDs using a number of radiophotoluminescence glass dosimeters (RPLDs) and to avoid RSI. We also analyzed the correlation between maximum ESDs and angiographic parameters in order to estimate maximum ESD in real-time. ESD was measured in 35 procedures in 34 cerebral aneurysm patients with a median age of 65 years (range, 38-79 years). Patients were measured for ESDs while wearing a fitted dosimetry cap equipped with 60 RPLD chips throughout the procedure. Angiographic parameters, including total fluoroscopic time and dose-area product (DAP), were recorded. The Pearson correlation test was used to determine the relationship between maximum ESD and each parameter. Five of thirty-five procedures showed temporal epilation (14.3%). The correlations between a patient's maximum ESD and total fluoroscopic time and DAP were r = 0.7372, P &lt; 0.001 and r = 0.6698, P &lt; .001, respectively. We concluded that the regional ESD with geometric information could be obtained by applying the RPLDs. Although this passive dosimetry system may not entirely prevent RSI in real-time, precise dose mapping accompanied by monitoring of angiographic parameters during the procedure should contribute to reducing X-ray dose accumulation in repeated prophylactic endovascular embolization for asymptomatic cerebral aneurysm. (C) 2011 Elsevier Ltd. All rights reserved.

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  • Myosin light chain kinase activation and calcium sensitization in smooth muscle in vivo

    Yusuke Mizuno, Eiji Isotani, Jian Huang, Hailei Ding, James T. Stull, Kristine E. Kamm

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY  2008年8月  AMER PHYSIOLOGICAL SOC

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    開催年月日: 2008年8月

    記述言語:英語  

    Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) in smooth muscle by myosin light chain kinase (MLCK) and dephosphorylation by myosin light chain phosphatase (MLCP) are subject to modulatory cascades that influence the sensitivity of RLC phosphorylation and hence contraction to intracellular Ca2+ concentration ([Ca2+](i)). We designed a CaM-sensor MLCK containing smooth muscle MLCK fused to two fluorescent proteins linked by the MLCK CaM-binding sequence to measure kinase activation in vivo and expressed it specifically in mouse smooth muscle. In phasic bladder muscle, there was greater RLC phosphorylation and force relative to MLCK activation and [Ca2+](i) with carbachol (CCh) compared with KCl treatment, consistent with agonist-dependent inhibition of MLCP. The dependence of force on MLCK activity was nonlinear such that at higher concentrations of CCh, force increased with no change in the net 20% activation of MLCK. A significant but smaller amount of MLCK activation was found during the sustained contractile phase. MLCP inhibition may occur through RhoA/Rho-kinase and/or PKC with phosphorylation of myosin phosphatase targeting subunit-1 (MYPT1) and PKC-potentiated phosphatase inhibitor (CPI-17), respectively. CCh treatment, but not KCl, resulted in MYPT1 and CPI-17 phosphorylation. Both Y27632 (Rho-kinase inhibitor) and calphostin C ( PKC inhibitor) reduced CCh-dependent force, RLC phosphorylation, and phosphorylation of MYPT1 (Thr694) without changing MLCK activation. Calphostin C, but not Y27632, also reduced CCh-induced phosphorylation of CPI-17. CCh concentration responses showed that phosphorylation of CPI-17 was more sensitive than MYPT1. Thus the onset of agonist-induced contraction in phasic smooth muscle results from the rapid and coordinated activation of MLCK with hierarchical inhibition of MLCP by CPI-17 and MYPT1 phosphorylation.

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  • Involvement of accumulated NOS inhibitors and endothelin-1, enhanced arginase, and impaired DDAH activities in pulmonary dysfunction following subarachnoid hemorrhage in the rabbit

    Yusuke Mizuno, Eiji Isotani, Kikuo Ohno, Akiko Nagai, Masatoshi Imamura, Hiroshi Azuma

    VASCULAR PHARMACOLOGY  2008年1月  ELSEVIER SCIENCE INC

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    開催年月日: 2008年1月

    記述言語:英語  

    We designed the present experiments to investigate the involvement of endogenous nitric oxide synthase (NOS) inhibitors, dimethylarginine dimethylaminohydrolase (DDAB) as a hydrolyzing enzyme of the NOS inhibitors, NOS, arginase which shares L-arginine as a common substrate with NOS, and endothelin-1 (ET-1) in the pulmonary dysfunction after induction of experimental subarachnoid hemorrhage (SAH) in the rabbit. SAH was induced by injecting autologous blood into the cisterna magna, and controls were injected with saline. On day 2, pulmonary arteries were isolated for determinations. A significant impairment of the endothelium-dependent relaxation (EDR) caused by acetylcholine was found in 20 cases (43.5%) out of 46 SAH animals, and the same animals exhibited accompanying the significantly impaired cyclic GMP production, accumulated endogenous NOS inhibitors, attenuated DDAH activity, enhanced arginase activity and accumulated ET-1 within the vessel wall. Meanwhile, there were no differences in endothelial NOS activity per se and sodium nitroprusside-induced relaxation between the animals with an impaired EDR and those without such a change. ET-1 content within aortic wall was increased with concomitant decrease in cyclic GMP production after the intraperitoneal application of authentic monomethylarginine as a NOS inhibitor in the rat. The current results suggest that accumulated endogenous NOS inhibitors and enhanced arginase activity possibly bring about the impaired NO production, thereby attenuating the EDR and contributing to the accumulation of ET-1 within the vessel wall. The accumulated endogenous NOS inhibitors at least partly result from the decreased DDAH activity. These alterations may be relevant to the pulmonary dysfunction after induction of SAH. (C) 2007 Elsevier Inc. All rights reserved.

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  • Alterations of intracellular calcium concentration and nitric oxide generation in pulmonary artery endothelium after subarachnoid hemorrhage of the rabbit

    Yoshihiro Kubota, Eiji Isotani, Yusuke Mizuno, Kikuo Ohno, Hiroshi Azuma

    VASCULAR PHARMACOLOGY  2007年8月  ELSEVIER SCIENCE INC

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    開催年月日: 2007年8月

    記述言語:英語  

    The present study was designed to investigate whether endothelial intracellular calcium concentration ([Ca2+](i)), endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) generation altered in association with impaired endothelium-dependent relaxation (EDR) in pulmonary artery (PA) specimens from experimental subarachnoid hemorrhage (SAH) rabbits. Injecting non-heparinized autologous arterial blood into cisterna magna induced the SAH. Simultaneous measurements of enclotbelial [Ca2+](i) and isometric tension of PA specimens were performed using fura 2. The subjects included normal control rabbits (group N), SAH rabbits with normal EDR (group A) and with impaired EDR (group B). When treated with 10(-7) M acetylcholine (ACh), endothelial [Ca2+](i) was significantly lower in group B (74.1 +/- 8.5 nM) than that in groups A (153.0 +/- 28.0 nM, p &lt; 0.05) and N (184.8 +/- 27.8 nM, p &lt; 0.01). Basal and ACh-stimulated cyclic GMP productions as a marker of NO generation were also significantly (p &lt; 0.005) decreased in group B as compared to those in the other two groups. Meanwhile, there were no differences in eNOS activity per se among the three groups. These results suggest that the attenuated endothelial [Ca2+](i) elevation leads to the impaired NO generation in PA endothelium, which in turn impairs the EDR and possibly increases the vascular resistance of PA following SAH. (C) 2007 Published by Elsevier Inc.

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  • Ca2+ signaling in microdomains - Homer1 mediates the interaction between RyR2 and Cav1.2 to regulate excitation-contraction coupling

    Guojin Huang, Joo Young Kim, Marlin Dehoff, Yusuke Mizuno, Kristine E. Kamm, Paul F. Worley, Shmuel Muallem, Weizhong Zeng

    JOURNAL OF BIOLOGICAL CHEMISTRY  2007年5月  AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

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    開催年月日: 2007年5月

    記述言語:英語  

    Excitation-contraction (E-C) coupling and Ca2+-induced Ca2+ release in smooth and cardiac muscles is mediated by the L-type Ca2+ channel isoform Ca(v)1.2 and the ryanodine receptor isoform RyR2. Although physical coupling between Ca(v)1.1 and RyR1 in skeletal muscle is well established, it is generally assumed that Ca(v)1.2 and RyR2 do not directly communicate either passively or dynamically during E-C coupling. In the present work, we re-examined this assumption by studying E-C coupling in the detrusor muscle of wild type and Homer1(-/-) mice and by demonstrating a Homer1-mediated dynamic interaction between Ca(v)1.2 and RyR2 using the split green fluorescent protein technique. Deletion of Homer1 in mice (but not of Homer2 or Homer3) resulted in impaired urinary bladder function, which was associated with higher sensitivity of the detrusor muscle to muscarinic stimulation and membrane depolarization. This was not due to an altered expression or function of RyR2 and Ca(v)1.2. Most notably, expression of Ca(v)1.2 and RyR2 tagged with the complementary C- and N- terminal halves of green fluorescent protein and in the presence and absence of Homer1 isoforms revealed that H1a and H1b/c reciprocally modulates a dynamic interaction between Ca(v)1.2 and RyR2 to regulate the intensity of Ca2+-induced Ca2+ release and its dependence on membrane depolarization. These findings define the molecular basis of a "two-state" model of E-C coupling by Ca(v)1.2 and RyR2. In one state, Ca(v)1.2 couples to RyR2 by H1b/c, which results in reduced responsiveness to membrane depolarization and in the other state H1a uncouples Ca(v)1.2 and RyR2 to enhance responsiveness to membrane depolarization. These findings reveal an unexpected and novel mode of interaction and communication between Ca(v)1.2 and RyR2 with important implications for the regulation of smooth and possibly cardiac muscle E-C coupling.

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  • ER stress disrupts Ca(2+-)signaling complexes and Ca2+ regulation in secretory and muscle cells from PERK-knockout mice

    GJ Huang, J Yao, WZ Zeng, Y Mizuno, KE Kamm, JT Stull, HP Harding, D Ron, S Muallem

    JOURNAL OF CELL SCIENCE  2006年1月  COMPANY OF BIOLOGISTS LTD

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    開催年月日: 2006年1月

    記述言語:英語  

    Disruption of protein synthesis and folding results in ER stress, which is associated with the pathophysiology of diverse diseases affecting secretory and muscle cells. Cells are protected against ER stress by activation of the unfolded protein response (UPR) that is regulated by the protein kinase PERK, which phosphorylates the translation initiation factor 2 eIF2 alpha to attenuate protein synthesis. PERK-/- cells are unable to modulate ER protein load and experience high levels of ER stress. In addition to its role in protein synthesis, the ER also orchestrates many signaling events essential for cell survival, prominent among which is Ca2+ signaling. It is not known, however, whether there is a relationship between ER stress and the function of the Ca2+ signaling pathway in muscle and nonmuscle cells. To directly address this question we characterized Ca2+ signaling in the secretory pancreatic and parotid acinar cells and in urinary bladder smooth muscle (UBSM) cells obtained from PERK-/- and wild-type mice. Deletion of PERK that results in high levels of ER stress, and distention and fragmentation of the ER slowed the rate of agonist-mediated Ca2+ release from the ER and reduced Ca2+-induced Ca2+ release, although IP3 production, localization of the IP3 receptors, IP3-mediated Ca2+ release, Ca(v)1.2 current and RyRs activity remained unaltered. On the other hand, ER stress disrupted the integrity of the Ca2+-signaling complexes in both secretory and UBSM cells, as revealed by markedly reduced coimmunoprecipitation of plasma membrane- and ER-resident Ca2+-signaling proteins. These findings establish a relationship between the unfolding protein response, ER stress and Ca2+ signaling and highlight the importance of communication within the terminal ER-plasma membrane microdomain for propagation of the Ca2+ signal from the plasma membrane into the cell.

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  • Role of nonmuscle myosin II in smooth muscle contraction

    Y Mizuno, Y Dai, KE Kamm, JT Stull

    FASEB JOURNAL  2005年3月  FEDERATION AMER SOC EXP BIOL

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    開催年月日: 2005年3月

    記述言語:英語  

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  • Real-time evaluation of myosin light chain kinase activation in smooth muscle tissues from a transgenic calmodulin-biosensor mouse

    E Isotani, G Zhi, KS Lau, J Huang, Y Mizuno, A Persechini, R Geguchadze, KE Kamm, JT Stull

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA  2004年4月  NATL ACAD SCIENCES

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    開催年月日: 2004年4月

    記述言語:英語  

    Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) by myosin light chain kinase (MLCK) initiates smooth muscle contraction and regulates actomyosin-based cytoskeletal functions in nonmuscle cells. The net extent of RLC phosphorylation is controlled by MLCK activity relative to myosin light chain phosphatase activity. We have constructed a CaM-sensor MLCK where Ca2+-dependent CaM binding increases the catalytic activity of the kinase domain, whereas coincident binding to the biosensor domain decreases fluorescence resonance energy transfer between two fluorescent proteins. We have created transgenic mice expressing this construct specifically in smooth muscle cells to perform real-time evaluations of the relationship between smooth muscle contractility and MLCK activation in intact tissues and organs. Measurements in intact bladder smooth muscle demonstrate that MLCK activation increases rapidly during KCl-incluced contractions but is not maximal, consistent with a limiting amount of cellular CaM. Carbachol treatment produces the same amount of force development and RLC phosphorylation, with much smaller increases in [Ca2+](i) and MLCK activation. A Rho kinase inhibitor suppresses RLC phosphorylation and force but not MLCK activation in carbachol-treated tissues. These observations are consistent with a model in which the magnitude of an agonist-mediated smooth muscle contraction depends on a rapid but limited Ca2+/CaM-dependent activation of MLCK and Rho kinase-mediated inhibition of myosin light chain phosphatase activity. These studies demonstrate the feasibility of producing transgenic biosensor mice for investigations of signaling processes in intact systems.

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  • Inhibitory effect of activated protein C on cerebral vasospasm after subarachnoid Hemorrhage in the rabbit

    Y Mizuno, H Azuma, Y Ito, E Isotani, K Ohno, K Hirakawa

    JOURNAL OF CARDIOVASCULAR PHARMACOLOGY  2002年5月  LIPPINCOTT WILLIAMS & WILKINS

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    開催年月日: 2002年5月

    記述言語:英語  

    This study investigated whether activated protein C (APC) improves the cerebral vasospasm in an experimental subarachnoid hemorrhage that was produced by the intracisternal injection of autologous blood. Male rabbits were divided into the following four groups: APC 0.1- and 0.5-mg groups, in which 0.1 and 0.5 mg APC were injected into the cisterna magna, respectively; a placebo group, in which saline was injected instead of APC; and a sham operation group that did not get injections of autologous blood, APC, and saline. On day 2, amount of clot in the basal cistern was significantly (p &lt; 0.01) decreased in the APC 0.5-mg group. Percent diameter of the basilar artery on day 2 to that before injecting the blood was angiographically determined as 97.1 +/- 3.8% in the APC 0.5-mg group, which was significantly (p &lt; 0.001) greater than the corresponding value in the placebo group (74.8 +/- 3.4%). The impaired endothelium-dependent relaxation following subarachnoid hemorrhage was normalized in the APC 0.5-mg group (p &lt; 0.0001). These results suggest that APC would improve cerebral vasospasm following subarachnoid hemorrhage, possibly by decreasing the amount of subarachnoid clot and normalizing the impaired nitric oxide production/release.

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  • Effective improvement of the cerebral vasospasm after subarachnoid hemorrhage with low-dose nitroglycerin

    Y Ito, E Isotani, Y Mizuno, H Azuma, K Hirakawa

    JOURNAL OF CARDIOVASCULAR PHARMACOLOGY  2000年1月  LIPPINCOTT WILLIAMS & WILKINS

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    開催年月日: 2000年1月

    記述言語:英語  

    In the rabbit subarachnoid hemorrhage (SAH) model, the sensitivity of spastic basilar arteries to nitric oxide (NO) was enhanced whereas the endothelial function to release/ produce NO became impaired, as described previously. We assumed from these results that low-dose NO might selectively dilate spastic arteries without influencing normal or systemic blood vessels; therefore, we investigated whether exogenous low-dose NO effectively improves cerebral vasospasm. Low-dose NO was derived from a small size of the tape containing nitroglycerin, which is not invasive and is clinically available. The experimental SAH was induced by injecting autologous blood into the cisterna magna of the rabbit. Experiments were performed on the following three groups: (a) SAH group with nitroglycerin tape (nitroglycerin group), (b) SAH group with placebo tape (placebo group), and (c) saline group injected with saline instead of blood. The tape containing 0.675 mg nitroglycerin was applied once daily for 2 days onto the skin area of the rabbit's ear. Angiograms were performed once before cisternal injection of blood and/or saline and again on day 2. On day 2 the basilar artery was isolated and sliced into 2-mm ring preparations. Relaxations of the basilar artery to acetylcholine, sodium nitroprusside, and calcium ionophore A23187, as well as the contractile responses to serotonin and endothelin-l, were measured. The diameter of the basilar artery on day 2 was reduced to 69.6 +/- 2.2% (n = 7) before the injection of autologous blood. The angiographic vasospasm of the basilar artery was partially but significantly (p &lt; 0.0001) improved to the percentage diameter of 89.4 +/- 1.4% (n = 7) by the application of low-dose nitroglycerin, which did not affect the systemic blood pressure and heart rate. In the basilar artery preparations harvested from SAH rabbits on day 2, the impaired acetylcholine-induced endothelium-dependent relaxation was partially but significantly (p &lt; 0.001) improved in the nitroglycerin group However, this group remained unaffected in the increased sensitivity to nitroglycerin and the contractile responses to serotonin and endothelin-l. Low-dose nitroglycerin tape effectively improved the cerebral vasospasm after SAH without any significant changes in the systemic circulation and would be one of the useful and noninvasive treatments for cerebral vasospasm. The results seem to be partially affected by the effective dilation of the spastic artery and the improvement of the impaired endothelium-dependent relaxation with low-dose NO.

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産業財産権

  • 脳血管攣縮治療剤および血腫除去剤

    磯谷 栄二, 大野 喜久郎, 水野 祐介, 小林 恒文, 東 洋

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    出願人:財団法人化学及血清療法研究所, 帝人株式会社

    出願番号:特願平11-048321  出願日:1999年2月

    公開番号:特開2000-247904  公開日:2000年9月

    J-GLOBAL

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  • 脳血管攣縮治療剤および血腫除去剤

    磯谷 栄二, 大野 喜久郎, 水野 祐介, 小林 恒文, 東 洋

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    出願人:財団法人化学及血清療法研究所, 帝人株式会社

    出願番号:特願平11-048321  出願日:1999年2月

    公開番号:特開2000-247904  公開日:2000年9月

    特許番号/登録番号:特許第3836267号  発行日:2006年8月

    J-GLOBAL

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共同研究・競争的資金等の研究課題

  • 肺高血圧クライシスに対する薬物療法の多面的な検討

    研究課題/領域番号:22K09025  2022年4月 - 2025年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    渡辺 至, 菅原 陽, 新井 悠介, 水野 祐介

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • Protein kinase Dの肺高血圧症への関与解明と核酸医薬による制御

    研究課題/領域番号:20K09225  2020年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    水野 祐介, 菅原 陽, 古賀 資和

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    Protein kinase Dは細胞骨格、運動、増殖、DNA合成等で細胞内で主要な役割を担い、生理的、病理的にも多数の機能を担う。心血管障害への関与が報告されており、心肥大、心不全の新たな治療標的の一つとされている。一方、PKDの血管障害における役割は不明な部分が多い。我々はPKD活性が、PKCやROCK依存性経路とは独立したbranchを形成して血管収縮に関与していることを見出した。更に、肺高血圧患者の肺組織においてPKD活性の上昇が報告され、実験的高血圧動物の血管からもPKD活性上昇が報告されている。
    我々は更に、肺高血圧を血管障害にPKDが関与していると考え、モノクロタリン誘発肺高血圧ラット、培養肺血管平滑筋細胞等を用いて検討している。PKDが肺高血圧ラット肺血管において、発現と活性が亢進していることを見出した。またPKD阻害剤投与により肺血管弛緩と右室圧低下をきたすことが分かった。肺高血圧ラット肺血管においてPKDの活性経路とeffectorを検索しており、今後の新たな肺高血圧治療へ可能性を探索する。

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  • 重症肺高血圧モデルラットを用いた肺動脈コンプライアンスの検討および治療戦略の確立

    研究課題/領域番号:19K09332  2019年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    菅原 陽, 古賀 資和, 水野 祐介

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    拍動流である肺循環の生理学的、病理学的解明のため、これまでの肺血管抵抗に代わり、拍動流としてより生理的状態を示すと考えられる肺動脈コンプライアンス、特定インピーダンスの計測をwindkessel 3要素model から行う。肺高血圧クライシスは治療法は確立しておらず、また周術期に生じる肺高血圧の鑑別は容易でない状況もある。
    インピーダンスは異なる病態から生じる肺高血圧を鑑別できる可能性があり、また軽症でも変化を表すと報告されている。従って、肺高血圧の病態解明や周術期に増悪した肺高血圧の鑑別の一助になる可能性がある。
    本研究ではインピーダンス等の測定により、異なる病態の肺高血圧やその増悪における循環動態の解析を行う事を目的としている。Windkesselを用いた肺動脈コンプライアンス、インピーダンスの計測のための肺動脈圧と肺血流量を同時測定は行っており、血管作動薬投与の効果に対するデータ収集、解析を行っていく予定である。肺高血圧クライシスモデルと上記計測系を用い、バソプレッシン、ドブダミン、ノルエピネフリン、フェニレフリン等に対する循環動態、肺動脈コンプライアンス測定、インピーダンス等への影響から治療効果を解析する。

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  • protein kinase Dによる血管収縮制御の解明と血管障害への応用

    研究課題/領域番号:17K11058  2017年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    水野 祐介, 古賀 資和, 渡辺 至, 川上 裕理

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    プロテインキナーゼD(PKD)は細胞運動、心筋収縮、血管新生、平滑筋収縮など、様々な細胞プロセスや生理機能に関与することが知られてるが、血管機能におけるPKDの役割は不明であった。我々は、ラットにおける全身循環と大動脈の収縮におけるPKDの役割について、また、ヒト大動脈平滑筋細胞(HASMCs)を用いPKDアイソフォームの正確な役割を検討した。その結果、PKD1 は大動脈および全身循環の収縮に関与している可能性があり、PKD1による血管運動活性の制御は、MYPT1のリン酸化と関連している可能性があった。PKDの血管収縮における役割の解明は、新たな循環動態の制御につながる可能性がある。

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  • 間質系幹細胞のexosomeを利用したmicroRNAによる肺高血圧症治療の検討

    研究課題/領域番号:17K11059  2017年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    渡辺 至, 古賀 資和, 水野 祐介, 川上 裕理

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    間葉系幹細胞は血管障害に有用との報告がある。当研究でモノクロタリン誘発肺高血圧ラットに骨髄由来および臍帯血由来幹細胞を静注し、肺高血圧が完成期に肺高血圧の程度を観察した。ラットモデルにおいて、両由来の間葉系幹細胞の静脈投与による有意な肺高血圧軽減効果は認められなかった。先行研究においては、モノクロタリン誘発を含む実験的肺高血圧モデルにおいて改善の報告例もあるが、有効性についてより詳細な検討が必要と考えられた。miRNAに加えlong non-coding RNAを含む他のRNAが心血管障害における役割が重要視されている。デリバリーのターゲットを再検討を含む計画の検討が必要と考えられた。

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  • Arginase阻害による肺高血圧治療の検討

    研究課題/領域番号:16K10968  2016年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    新堀 博展, 古賀 資和, 水野 祐介

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    肺血管内皮機能の低下が肺高血圧発症の原因の一つとされている。我々は肺動脈内皮機能依存性弛緩反応及び、eNOS活性がモノクロタリン誘発肺高血圧ラットにおいて減弱していることを観察した。一方でNOS発現は変化なく基質を競合するarginaseは亢進してした。以上からarginaseの発現亢進が内皮機能低下に関与していると可能性が示唆された。肺高血圧ラットにおいてarginase阻害剤NOHA単独では内皮依存性弛緩反応を変化なかったが、基質であるarginineを加えると改善が見られた。以上からarginase発現亢進とarginineの利用障害の可能性が示唆された。

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  • VPAC2 アゴニスト発現ベクター構築と肺高血圧治療

    研究課題/領域番号:26462342  2014年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    水野 祐介, 渡辺 至, 新堀 博展, 川上 裕理

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    VIP は血管拡張作用と心収縮力亢進作用と持ち、肺高血圧症 (PH) 治療薬の一つとされてきた。我々は、VIPの受容体VPAC1,VPAC2に対する各アゴニスト、および関連ペプチドPACAPの肺高血圧ラットの循環への影響を検討した。VPAC2アゴニストはMCT肺高血圧ラットの右室圧および全肺血管抵抗を低下させ、心拍出量を増加させたが、VPAC1アゴニスト,PACAPは改善させなかった。次に、間葉系幹細胞をベクターとし、肺局所でVPAC2アゴニストを発現をさせる方法の検討を開始した。静脈内投与した間葉系幹細胞は肺高血圧ラットの循環動態に影響を与えなかった。

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  • 内因性NOS阻害物質代謝酵素の導入による肺血圧低下効果

    研究課題/領域番号:25462447  2013年4月 - 2017年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    新堀 博展, 渡辺 至, 水野 祐介, 川上 裕理

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    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    一酸化窒素(NO)は血管拡張などの様々な生理機能を担い、肺高血圧症では内皮機能の障害からNOの産生が減弱している。我々はモノクロタリン誘発肺高血圧ラットを用い、肺血管内皮機能の減弱とな内皮型一酸化窒素合成酵素eNOSの活性低下の機序を検討した。内因性eNOS阻害物質であるADMAの増加とその合成酵素であるPRMT2の発現亢進、および代謝酵素DDAH1,2の発現減少が認めれた。更に、eNOSと基質l-arginineを競合するarginaseの発現亢進もみられ、肺血管内皮期の低下に複数の経路、物質が関与している可能性が示唆された.

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  • VIP受容体VPAC2 選択的アゴニストを用いた肺高血圧症治療

    研究課題/領域番号:25462446  2013年4月 - 2016年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    川上 裕理, 水野 祐介, 三浦 倫一, 渡邊 至

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    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    VIPはVPAC1, VPAC2受容体を持ちPACAPをこれら受容体を共有する。これら受容体選択的アゴニスト等によるモノクロタリンMCT肺高血圧モデルへの影響を検討した。MCTにおいてVPAC2選択的アゴニストBAY55-9837はVIPに比較し右室圧低下作用が強く、また心拍出量も増加させることが示された。VPAC1選択的アゴニストは右室圧低下作用を認めなかった。本研究はVPAC2受容体の肺高血圧における新たな役割を示し、選択的アゴニストの治療薬としての可能性が示唆された。MCTモデル以外の肺高血圧症における役割の解明や、適切な投与方法の検討が今後の課題である。

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  • レンチウイルスベクターを用いた肺高血圧症治療

    研究課題/領域番号:24592309  2012年4月 - 2016年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    渡辺 至, 水野 祐介, 川上 裕理, 馬場 靖子

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    配分額:5330000円 ( 直接経費:4100000円 、 間接経費:1230000円 )

    心臓の神経支配は交感、副交感神経以外に多種の神経ペプチドが関与していることが知られている。心肥大、心不全を来した場合、交感神経系は代償性に亢進し順応するが、他の神経ペプチドの心肥大、心不全における役割、順応の影響等の詳細は不明である。本研究では、神経伝達物質PACAPシグナル系が右心負荷、右肥大に対して順応し、PACAP静脈内投与によりcontrol群と同様の心拍出量が得られた。右心肥大から来る心不全の機序解明につながる可能性があり、今後は、MCTモデル以外の右心負荷におけるPACAPの関与を検討する必要がある。

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  • 肺高血圧症におけるリアルタイムなカルシウム感受性測定による血管収縮機構の解明

    研究課題/領域番号:23592304  2011年 - 2013年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    水野 祐介, 川上 裕理, 渡邊 至, 馬場 康子

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    配分額:5200000円 ( 直接経費:4000000円 、 間接経費:1200000円 )

    本研究においてMLCK sensorを用いたカルシウム感受性の亢進機序の検討する過程で、ラット肺高血圧モデルにおいてカルシウム感受性を亢進させるRHO-kinase経路のみならず、感受性を減弱させるMLCK自身のリン酸化状態も変化していることを見出した。このMLCKのリン酸化機序解明は新たな肺血管抵抗制御に関する手段をもたらす可能性がある。カルシウムに対する感受性を亢進させる機構ののみならず、減弱させる機構を解明することで新たな肺高血圧治療法の開発につながる可能性がある。

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  • IVR患者被ばく測定法の標準化に関する基礎的研究

    研究課題/領域番号:21611012  2009年 - 2011年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    盛武 敬, 榮 武二, 千田 浩一, 松丸 祐司, 水野 祐介, 早川 幹人

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    患者の身体に低侵襲であるインターベンショナル・ラジオロジーでは、被ばく線量が1回の手技あたり数Gy(グレイ)に達することがある。そこで、精密な患者被ばく線量情報を得るために、蛍光ガラス線量計を配した専用装具と、線量分布を医療情報として活用し、これを患者単位で管理するためのシステムを構築した。この線量分布は直ぐに表示することはできないが、リアルタイムに把握可能なX線透視時間や面積線量計の情報と組み合わせることで、被ばく線量を効果的に低減できることが示された。

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  • 心室肥大におけるVIP受容体の機能解明と遺伝子治療の検討

    研究課題/領域番号:21591981  2009年 - 2011年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    渡辺 至, 水野 祐介, 川上 裕理

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    VIPとPACAPは70%アミノ酸相同性を持つ神経伝達物質であり多様な生理活性を持つ。しかし心肺にも多く分布しているにもかかわらず機能は不明な点が多い。モノクロタリン誘発右心肥において、PACAPが減少する一方PACAP選択的受容体PAC1とVIP/PACAPの共通受容体VPAC2は発現充進していた。 VIPではなくPACAPが心肥大発症によりドミナントな関与が疑われた。

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  • プラスミドベクターの肺高血圧症に対する遺伝子治療への応用

    研究課題/領域番号:20591810  2008年 - 2010年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    水野 祐介, 馬場 靖子, 川上 裕理

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    肺高血圧ラットの肺組織中において神経伝達物質VIP, PACAPの発現低下とその受容体の亢進を発見した。VIP, PACAPは血管拡張、臓器保護作用が報告されており、肺高血圧ではこれらの低下に対し、受容体が代償的に増加していると推定された。PACAP発現誘導により肺高血圧症の改善を図れると仮説を立てた。肺組織に持続的に発現させるため、PACAP発現プラスミドベクター及びレンチウイルスベクターを作成し、導入条件を検討した。

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  • 神経保護因子としてのエリスロポイエチンの新しい作用メカニズムの解明

    研究課題/領域番号:19591813  2007年 - 2009年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    安藤 富男, 水野 祐介, 越後 憲之, 紙谷 義孝

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    ラット大脳皮質一次培養ニューロンにおいて、エリスロポイエチン(Epo)は正常状態では細胞内カルシウム濃度を増加させ、グルタミン酸受容体刺激状態では低下させた。Epoによるカルシウム濃度上昇は電位依存性Caチャネルを介するCa流入に依存しており、カルシウム濃度の低下はCa依存性Kチャネルの活性化に由来すると考えられる。細胞内カルシウム濃度の中等度の増加はsurvival signal活性化に、その低下はグルタミン酸の神経細胞毒性の軽減に寄与することが考えられるが、これらの意義はさらに検討を要する。

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  • 低酸素性肺血管収縮におけるカルシウム依存性、非依存性収縮の機序解明

    研究課題/領域番号:18890155  2006年 - 2007年

    日本学術振興会  科学研究費助成事業  若手研究(スタートアップ)

    水野 祐介

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    配分額:2400000円 ( 直接経費:2400000円 )

    平成18年度に引き続き
    ラット肺動脈リング標本を低酸素に暴露させ低酸素性肺血管収縮(HPV)における張力及び平滑筋細胞内カルシウム濃度測定を行った。HPVは初期に比較的急峻な収縮を示し、一端弛緩した後緩徐に収縮する2相性の収縮を示した。一方、カルシウム濃度は初期の収縮において張力とほぼ一致した上昇を呈するが、その後の変化は少なかった。現在、再現性を確認している。今後、フリーラジカルも同様の実験手法で測定予定である。
    HPVにおける張力とカルシウム濃度の推移の差異より、緩徐な収縮相はカルシウム非依存性の収縮機序が関与していると推測される。HPV惹起中のMYPT1,CPI-17リン酸化状態を経時的に測定し、MYPT1のリン酸化は緩徐な収縮相において増加傾向を認めたが、十分な実験数を得るため引き続き行っている。
    MYPT1,CPI-17,MLCKのHPVにおける役割を検討するためin vivoでRNAiを検討していたが、十分なKnockdownが得られず、現在は薬理学的検討を行っている。In vivoにおけるRNAiは様々な方法が考案されているが、近年エレクトロポレーションによってplasmidをin vivoで発現させる効率が高まった。そこでshRNA発現またはdominant negative変異体タンパクを発現させるplasmidを用いる方法を検討している。大腿筋内でplasmidによるタンパクを発現させる方法は当教室で確立されており、肺における条件を検討している。

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