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写真a

オガワ フミヒロ
小川 史洋
Fumihiro Ogawa
所属
医学研究科 医科学専攻 救急医学 講師
医学部 医学科
職名
講師
プロフィール

臨床研究では、原発性肺癌術後症例における肺年齢と術後合併症・再入院についての研究を行った。

2010年大学院入学後、呼吸器外科医という特性を生かし、肺癌研究に没頭。基礎研究ではマウスを用いた肺癌転移モデルおよびノックアウトマウスを用いたpremetastatic nicheの解明、ヒト気道上皮基底細胞に対する喫煙が及ぼす細胞分化に対する影響につき遺伝子レベルで解析し、癌再発・転移、および喫煙関連疾患に対する治療アプローチを研究していた。
2014年よりアメリカ・ニューヨーク Weill Cornell Medical College, Department of Genetics (Ronald G. Crystal Lab)においてKRASのヒト正常気道上皮細胞に対する機能解析を遺伝子レベルで解析し、特殊培養系(Air liquid Interface)を用いて報告した。
現職では、救急現場における前向き試験を準備しており、また基礎研究において急性呼吸窮迫症候群(ARDS)における分子レベルからの革命的根本治療の開発とARDS発症と喫煙との関連性についての研究を行なっている。

外部リンク

学位

  • 博士(医学) ( 北里大学 )

研究キーワード

  • 分化

  • 喫煙

  • 喘息

  • Glycocalyx

  • Cigarette Smoking

  • 急性呼吸窮迫症候群

  • COVID-19

  • Prostaglandin

  • 肺年齢

  • 外科手術

  • 肺がん

  • がん転移

  • 気道上皮基底細胞

研究分野

  • ライフサイエンス / 救急医学

  • ライフサイエンス / 薬理学

  • ライフサイエンス / 呼吸器外科学

学歴

  • 北里大学   医療系研究科

    2010年4月 - 2014年3月

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  • 北里大学   医学部

    1996年4月 - 2002年3月

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経歴

  • 横浜市立大学   医学部医学科 救急医学   講師

    2024年4月 - 現在

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    国名:日本国

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  • 横浜市立大学   附属病院 救急科   診療講師   診療講師

    2022年4月 - 2024年3月

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    国名:日本国

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  • 横浜市立大学   医学部 救急医学教室   助教

    2019年4月 - 2022年3月

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  • 横浜市立大学市民総合医療センター   高度救命救急センター   助教

    2018年4月 - 2019年3月

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  • コーネル大学   遺伝医学   博士研究員

    2014年9月 - 2018年3月

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  • 北里大学医学部   臨床研究センター   助教

    2014年4月 - 2014年8月

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  • 北里大学医療系研究科   分子薬理学   大学院生

    2010年4月 - 2014年3月

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  • 北里大学医学部   呼吸器外科学   助教

    2008年4月 - 2010年3月

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  • 癌研究会有明病院   呼吸器外科   レジデント

    2006年4月 - 2008年3月

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  • 独立行政法人国立病院機構相模原病院   外科   レジデント

    2005年4月 - 2006年3月

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  • 北里大学病院   胸部外科   研修医

    2002年4月 - 2005年5月

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▼全件表示

所属学協会

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委員歴

  • 日本救急医学会   ICLS委員会 運営企画委員 関東地方統括業務担当  

    2025年1月 - 2027年12月   

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    団体区分:学協会

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  • 日本集中治療学会関東甲信越支部   関東甲信越支部連絡協議会委員  

    2024年2月 - 2024年12月   

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    団体区分:学協会

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  • 日本救急医学会   第52回日本救急医学会総会基礎研究部門プログラム委員  

    2023年11月 - 2024年11月   

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    団体区分:学協会

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  • 日本救急医学会   研究支援ワーキンググループ  

    2019年4月 - 2022年3月   

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    団体区分:学協会

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論文

  • Temporal change in Syndecan-1 as a therapeutic target and a biomarker for the severity classification of COVID-19 国際誌

    Fumihiro Ogawa, Yasufumi Oi, Kento Nakajima, Reo Matsumura, Tomoki Nakagawa, Takao Miyagawa, Kazuya Sakai, Ryo Saji, Hayato Taniguchi, Kohei Takahashi, Takeru Abe, Masayuki Iwashita, Mototsugu Nishii, Ichiro Takeuchi

    Thrombosis Journal   19 ( 1 )   55 - 55   2021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)  

    BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microembolism or microvascular endothelial injuries. Here, we report that syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury. METHODS AND ANALYSIS: We analyzed the data of COVID-19 patients for 1 year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with SDC-1 by ELISA. RESULTS: We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P = 0.032, P < 0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, d-dimer, ISTH score; P = 0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p < 0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P = 0.009 and P < 0.0001, respectively). CONCLUSIONS: Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

    DOI: 10.1186/s12959-021-00308-4

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  • Combining IL-6 and SARS-CoV-2 RNAaemia-based risk stratification for fatal outcomes of COVID-19. 国際誌

    Ryo Saji, Mototsugu Nishii, Kazuya Sakai, Kei Miyakawa, Yutaro Yamaoka, Tatsuma Ban, Takeru Abe, Yutaro Ohyama, Kento Nakajima, Taro Hiromi, Reo Matsumura, Naoya Suzuki, Hayato Taniguchi, Tsuyoshi Otsuka, Yasufumi Oi, Fumihiro Ogawa, Munehito Uchiyama, Kohei Takahashi, Masayuki Iwashita, Yayoi Kimura, Satoshi Fujii, Ryosuke Furuya, Tomohiko Tamura, Akihide Ryo, Ichiro Takeuchi

    PloS one   16 ( 8 )   e0256022   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic rapidly increases the use of mechanical ventilation (MV). Such cases further require extracorporeal membrane oxygenation (ECMO) and have a high mortality. OBJECTIVE: We aimed to identify prognostic biomarkers pathophysiologically reflecting future deterioration of COVID-19. METHODS: Clinical, laboratory, and outcome data were collected from 102 patients with moderate to severe COVID-19. Interleukin (IL)-6 level and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copy number in plasma were assessed with ELISA kit and quantitative PCR. RESULTS: Twelve patients died or required ECMO owing to acute respiratory distress syndrome despite the use of MV. Among various variables, a ratio of oxygen saturation to fraction of inspired oxygen (SpO2/FiO2), IL-6, and SARS-CoV-2 RNA on admission before intubation were strongly predictive of fatal outcomes after the MV use. Moreover, among these variables, combining SpO2/FiO2, IL-6, and SARS-CoV-2 RNA showed the highest accuracy (area under the curve: 0.934). In patients with low SpO2/FiO2 (< 261), fatal event-rate after the MV use at the 30-day was significantly higher in patients with high IL-6 (> 49 pg/mL) and SARS-CoV-2 RNAaemia (> 1.5 copies/μL) compared to those with high IL-6 or RNAaemia or without high IL-6 and RNAaemia (88% vs. 22% or 8%, log-rank test P = 0.0097 or P < 0.0001, respectively). CONCLUSIONS: Combining SpO2/FiO2 with high IL-6 and SARS-CoV-2 RNAaemia which reflect hyperinflammation and viral overload allows accurately and before intubation identifying COVID-19 patients at high risk for ECMO use or in-hospital death despite the use of MV.

    DOI: 10.1371/journal.pone.0256022

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  • Environmental Maintenance with Effective and Useful Zoning for Severe COVID‐19 due to Protect to and from Patients and Medical Staffs 査読

    Fumihiro Ogawa, Hideaki Kato, Kazuya Sakai, Kana Nakamura, Mizuki Ogawa, Munehito Uchiyama, Kento Nakajima, Yutaro Ohyama, Takeru Abe, Ichiro Takeuchi

    Acute Medicine & Surgery   7 ( 1 )   2020年6月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Aim: The coronavirus disease 2019 (COVID-19) pandemic has accelerated all over the world, and global health-care systems have become overwhelmed with potentially infectious patients seeking testing and care. It is essential to set up effective and useful zoning to prevent the spread of infection to and from medical staff or other patients with effective use of standard precautions with personal protective equipment (PPE).Methods: We repurposed a general ward into an acute care unit for severe COVID-19 patients taking into consideration airflow, the direction of movement of medical staff, and prevention of the spread of infection to medical staff and other patients. We checked the daily condition and body temperature of all medical staff for 60 days.Results: There was no evidence of COVID-19 infection in any medical staff or other patients during the period thanks to effective and useful zoning with PPE.Conclusion: Special wards and rooms should be set up for future protection of medical staff and other patients, and prevent the explosion of COVID-19 infection with effective and useful zoning with PPE.

    DOI: 10.1002/ams2.536

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  • Prostanoid induces premetastatic niche in regional lymph nodes 査読

    Fumihiro Ogawa, Hideki Amano, Koji Eshima, Yoshiya Ito, Yoshio Matsui, Kanako Hosono, Hidero Kitasato, Akira Iyoda, Kazuya Iwabuchi, Yuji Kumagai, Yukitoshi Satoh, Shuh Narumiya, Masataka Majima

    JOURNAL OF CLINICAL INVESTIGATION   124 ( 11 )   4882 - 4894   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:AMER SOC CLINICAL INVESTIGATION INC  

    The lymphatic system is an important route for cancer dissemination, and lymph node metastasis (LNM) serves as a critical prognostic determinant in cancer patients. We investigated the contribution of COX-2-derived prostaglandin E-2 (PGE(2)) in the formation of a premetastatic niche and LNM. A murine model of Lewis lung carcinoma (LLC) cell metastasis revealed that COX-2 is expressed in DCs from the early stage in the lymph node subcapsular regions, and COX-2 inhibition markedly suppressed mediastinal LNM. Stromal cell-derived factor-1 (SDF-1) was elevated in DCs before LLC cell infiltration to the lymph nodes, and a COX-2 inhibitor, an SDF-1 antagonist, and a CXCR4 neutralizing antibody all reduced LNM. Moreover, LNM was reduced in mice lacking the PGE(2) receptor EP3, and stimulation of cultured DCs with an EP3 agonist increased SDF-1 production. Compared with WT CD11c(+) DCs, injection of EP3-deficient CD11c(+) DCs dramatically reduced accumulation of SDF-1(+)CD11c(+) DCs in regional LNs and LNM in LLC-injected mice. Accumulation of Tregs and lymph node lymphangiogenesis, which may influence the fate of metastasized tumor cells, was also COX-2/EP3-dependent. These results indicate that DCs induce a premetastatic niche during LNM via COX-2/EP3-dependent induction of SDF-1 and suggest that inhibition of this signaling axis may be an effective strategy to suppress premetastatic niche formation and LNM.

    添付ファイル: JCI73530.pdf

    DOI: 10.1172/JCI73530

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  • Enhancing clinical reasoning skills in medical students through team-based learning: a mixed-methods study. 国際誌

    Kosuke Ishizuka, Kiyoshi Shikino, Naoko Takada, Yohei Sakai, Yasushi Ototake, Takashi Kobayashi, Tetsuhiko Inoue, Ryosuke Jikuya, Yuri Iwata, Kenichi Nishimura, Ryusuke Yoshimi, Yasufumi Oi, Yuko Watanabe, Yu Togashi, Fumihiro Ogawa, Daisuke Sano, Takeshi Asami, Yuichi Imai, Ichiro Takeuchi, Kengo Funakoshi, Mitsuyasu Ohta, Masahiko Inamori, Akihiko Kusakabe

    BMC medical education   25 ( 1 )   221 - 221   2025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: Clinical reasoning skills are essential competencies for medical students; therefore, effective, evidence-informed teaching methodologies are needed worldwide. This study investigated the benefits of team-based learning (TBL) for developing the skills in medical students. METHOD: A mixed-methods sequential explanatory design was used to investigate the effectiveness of TBL for medical students acquiring clinical reasoning skills. The study participants comprised 92 fourth-year medical students at Yokohama City University School of Medicine, participating in TBL sessions that covered 10 major clinical symptoms identified in the core curriculum. Each session lasted 240 min. Before and after the educational intervention, student performance was measured using the script concordance test (SCT) on a 30-point scale, and self-assessed clinical reasoning competency was measured on a 7-point Likert scale. The SCT included pre-tests and post-tests of 30 questions each, with students randomly assigned to one of two test sets. Following the quantitative evaluation, a qualitative content analysis was conducted to explore the advantages of TBL for learning clinical reasoning skills. The analytic categories were set according to the six levels of Fink's taxonomy of significant learning. RESULT: Student performance improved significantly after the educational intervention (A test: 16.5 ± 4.4 to 18.7 ± 4.5, p = 0.019; B test: 18.1 ± 3.7 to 19.8 ± 4.4, p = 0.028). After the educational intervention, self-assessed clinical reasoning competency was significantly higher in "recalling appropriate physical examination and tests on clinical hypothesis generation," "recalling appropriate differential diagnosis from patient's chief complaint," "verbalizing points that fit/don't fit the recalled differential diagnosis appropriately," "verbalizing and reflecting appropriately on own mistakes," "selecting keywords from the whole aspect of the patient," and "practicing the appropriate clinical reasoning process" (all p < 0.001). The content analysis extracted 23 subcategories and 233 codes of the advantages of TBL for learning clinical reasoning skills, covering all six levels of Fink's taxonomy of significant learning: Foundational knowledge (7 codes); Application (40 codes); Integration (69 codes); Human dimension (89 codes); Caring (8 codes); and Learning how to learn (20 codes). CONCLUSION: This study demonstrates that TBL supports the acquisition of critical clinical reasoning skills among medical students.

    DOI: 10.1186/s12909-025-06784-w

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  • Retrospective Study for Safer Management for Citizen’s Marathon: A Medical Support Perspective

    Fumihiro Ogawa, Riichiro Nakayama, Yusuke Nakayama, Yoji Yuasa, Tomohiro Kamagata, Kohei Takahashi, Ryosuke Furuya, Shohei Imaki, Ichiro Takeuchi

    2025年2月

  • A Screening Tool to Predict Sepsis in Patients With Suspected Infection in the Emergency Department. 国際誌

    Yasufumi Oi, Fumihiro Ogawa, Hiroshi Honzawa, Takeru Abe, Shouhei Imaki, Ichiro Takeuchi

    Cureus   17 ( 2 )   e78728   2025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 and objective Sepsis is a life-threatening condition associated with high morbidity and mortality, and hence early recognition and treatment are crucial. The 2016 Sepsis-3 guidelines introduced the quick Sequential Organ Failure Assessment (qSOFA), but its low sensitivity limits early detection. The 2021 Surviving Sepsis Campaign Guidelines (SSCG) discourage relying solely on qSOFA and recommend additional tools such as the systemic inflammatory response syndrome (SIRS) score, the National Early Warning Score (NEWS), and the Modified Early Warning Score (MEWS) along with lactate measurement. This study assessed whether combining qSOFA with quantitative capillary refill time (Q-CRT) or lactate levels enhances early sepsis diagnosis in emergency departments. Methods This retrospective, multi-facility observational study was conducted at two hospitals in Yokohama, Japan. Patients with suspected infections who underwent Q-CRT measurement were included. Q-CRT was measured using a pulse oximeter-based device that records the time taken for blood flow to return to 90% after compression. Receiver operating characteristic (ROC) curves determined the area under the curve (AUC), sensitivity, and specificity. Statistical significance was set at p<0.05. Results Of the 357 patients who underwent Q-CRT measurement, 75 (21%) were suspected of having an infection, with 48 (64%) classified as having sepsis with organ dysfunction. Patients in the sepsis group had higher age, heart rate, lactate level, creatinine level, NEWS, MEWS, and Sequential Organ Failure Assessment (SOFA) scores compared to those without organ dysfunction. Among individual tools, the qSOFA, NEWS, and MEWS scores showed high AUCs (>0.8), while Q-CRT and lactate levels demonstrated moderate predictive accuracy with AUCs exceeding 0.7. The SIRS score had the lowest predictive ability, with an AUC of approximately 0.6. Combining qSOFA with Q-CRT or lactate levels significantly improved sensitivity and specificity. The qSOFA+Q-CRT combination resulted in an AUC of 0.821, sensitivity of 83.3%, and specificity of 81.4%, while the qSOFA+lactate combination yielded an AUC of 0.844, sensitivity of 87.5%, and specificity of 81.4%. These combinations exceeded 80% in both sensitivity and specificity, unlike the SIRS-based combinations, which showed limited improvement and specificity below 40%. While the qSOFA score alone demonstrated limited sensitivity, combining it with Q-CRT or lactate levels enhanced its predictive performance for early sepsis detection. This approach improved sensitivity without compromising specificity. The increase in sensitivity and specificity is likely due to Q-CRT and lactate identifying sepsis cases not detected by qSOFA, thereby making the combined approach more reliable for clinical use. Lactate levels are well-established markers associated with sepsis severity, and Q-CRT offers a non-invasive means of assessing peripheral perfusion. Conclusions Combining qSOFA with Q-CRT or lactate levels significantly improves early sepsis detection by enhancing both sensitivity and specificity. These combinations offer superior diagnostic accuracy compared to standalone tools, supporting their potential integration into clinical protocols for better patient outcomes. Further prospective studies are needed to validate these findings across diverse clinical settings.

    DOI: 10.7759/cureus.78728

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  • Rivaroxaban as a protector of Oxidative Stress-induced Vascular Endothelial Glycocalyx Damage via The IQGAP1/PAR1-2/PI3K/Akt Pathway. 国際誌

    Lisa Kitasato, Minako Yamaoka-Tojo, Toshiyuki Iwaya, Yusuke Murayama, Yuki Ikeda, Takehiro Hashikata, Jun Oikawa, Machika Suzuki, Nonoka Misawa, Rei Kawashima, Fumihiro Ogawa, Junya Ako

    Journal of vascular research   62 ( 1 )   1 - 24   2024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)  

    INTRODUCTION: The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a FXa inhibitor, on the glycocalyx under oxidative stress condition. METHODS: We examined the impact of rivaroxaban on human umbilical vein endothelial cells (HUVECs) exposed to acute and chronic H₂O₂-induced oxidative stress. RESULTS: Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/ phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx. CONCLUSION: We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.

    DOI: 10.1159/000542419

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  • Combining blood glucose and SpO2/FiO2 ratio facilitates prediction of imminent ventilatory needs in emergency room COVID-19 patients. 国際誌

    Kazuya Sakai, Kai Okoda, Mototsugu Nishii, Ryo Saji, Fumihiro Ogawa, Takeru Abe, Ichiro Takeuchi

    Scientific reports   13 ( 1 )   22718 - 22718   2023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)  

    The increasing requirement of mechanical ventilation (MV) due to the novel coronavirus disease (COVID-19) is still a global threat. The aim of this study is to identify markers that can easily stratify the impending use of MV in the emergency room (ER). A total of 106 patients with COVID-19 requiring oxygen support were enrolled. Fifty-nine patients were provided MV 0.5 h (interquartile range: 0.3 to 1.4) post-admission. Clinical and laboratory data before intubation were collected. Using a multivariate logistic regression model, we identified four markers associated with the impending use of MV, including the ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 ratio), alanine aminotransferase, blood glucose (BG), and lymphocyte counts. Among these markers, SpO2/FiO2 ratio and BG, which can be measured easily and immediately, showed higher accuracy (AUC: 0.88) than SpO2/FiO2 ratio alone (AUC: 0.84), despite no significant difference (DeLong test: P = 0.591). Moreover, even in patients without severe respiratory failure (SpO2/FiO2 ratio > 300), BG (> 138 mg/dL) was predictive of MV use. Measuring BG and SpO2/FiO2 ratio may be a simple and versatile new strategy to accurately identify ER patients with COVID-19 at high risk for the imminent need of MV.

    DOI: 10.1038/s41598-023-50075-7

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  • ECPRを施行された院外心停止患者に対する予防的下肢送血と退院時生存との関連 SAVE-J2 studyの二次解析

    本澤 大志, 谷口 隼人, 安部 猛, 大井 康史, 小川 史洋, 竹内 一郎

    日本救急医学会雑誌   34 ( 12 )   705 - 705   2023年12月

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    記述言語:日本語   出版者・発行元:(一社)日本救急医学会  

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  • 働き方改革にむけた救急診療と集中治療の並行診療における遠隔病態把握システムの有用性の検討

    小川 史洋, 大井 康史, 本澤 大志, 三澤 菜穂, 四宮 祥恵, 水上 紗緒里, 丸岩 伯章, 貞広 智瑛梨, 高木 俊介, 竹田 美希, 竹内 一郎

    日本救急医学会雑誌   34 ( 12 )   715 - 715   2023年12月

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    記述言語:日本語   出版者・発行元:(一社)日本救急医学会  

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  • 敗血症を予測するスクリーニングツールの検討

    大井 康史, 小川 史洋, 本澤 大志, 四宮 祥恵, 水上 紗緒里, 貞広 智瑛梨, 安部 猛, 竹内 一郎

    日本救急医学会雑誌   34 ( 12 )   698 - 698   2023年12月

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    記述言語:日本語   出版者・発行元:(一社)日本救急医学会  

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  • Prediction of prognosis in patients with severe COVID-19 pneumonia using CT score by emergency physicians: a single-center retrospective study. 国際誌

    Yasufumi Oi, Fumihiro Ogawa, Tsuneo Yamashiro, Shoichiro Matsushita, Ayako Oguri, Shusuke Utada, Naho Misawa, Hiroshi Honzawa, Takeru Abe, Ichiro Takeuchi

    Scientific reports   13 ( 1 )   4045 - 4045   2023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 aimed to develop a method to determine the CT score that can be easily obtained from CT images and examine its prognostic value for severe COVID pneumonia. Patients with COVID pneumonia who required ventilatory management by intubation were included. CT score was based on anatomical information in axial CT images and were divided into three sections of height from the apex to the bottom. The extent of pneumonia in each section was rated from 0 to 5 and summed. The primary outcome was the prediction of patients who died or were managed on extracorporeal membrane oxygenation (ECMO) based on the CT score at admission. Of the 71 patients included, 12 (16.9%) died or required ECMO management, and the CT score predicted death or ECMO management with ROC of 0.718 (0.561-0.875). The death or ECMO versus survival group (median [quartiles]) had a CT score of 17.75 (14.75-20) versus 13 (11-16.5), p = 0.017. In conclusion, a higher score on our generated CT score could predict the likelihood of death or ECMO management. A CT score at the time of admission allows for early preparation and transfer to a hospital that can manage patients who may need ECMO.

    DOI: 10.1038/s41598-023-31312-5

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  • Association of obesity paradox with prognosis of veno-venous-extracorporeal membrane oxygenation in patients with coronavirus disease 2019. 国際誌

    Hiroshi Honzawa, Hayato Taniguchi, Fumihiro Ogawa, Yasufumi Oi, Takeru Abe, Ichiro Takeuchi

    Acute medicine & surgery   10 ( 1 )   e871   2023年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: Although the obesity paradox is known for various diseases, including cancer and acute respiratory distress syndrome, little is known about veno-venous extracorporeal membrane oxygenation (VV-ECMO) in patients with coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the association between body mass index (BMI) and prognosis in critical patients with COVID-19 requiring VV-ECMO. METHODS: We conducted a retrospective observational single-center study at Yokohama City University Civic General Medical Center between March 2020 and October 2021. Participants were patients with COVID-19 who required VV-ECMO. They were classified into two groups: BMI ≤30 kg/m2 and >30 kg/m2. RESULTS: In total, 23 patients were included in the analysis, with a median BMI of 28.7 kg/m2. Overall, 22 patients were successfully weaned from the ECMO. When comparing the two groups, there was a trend toward fewer days from onset to ECMO induction in the BMI >30 kg/m2 group. Moreover, the two groups had a similar prognosis. There were no statistically significant differences in the number of days from onset to hospitalization or the duration of ECMO induction between the groups. CONCLUSION: VV-ECMO induction for patients with COVID-19 may lead to earlier indications in patients with BMI >30 kg/m2 than in those with BMI ≤30 kg/m2.

    DOI: 10.1002/ams2.871

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  • The microsomal prostaglandin E synthase-1/PGE2 axis induces recovery from ischemia via recruitment of regulatory T cells. 国際誌

    Hideki Amano, Koji Eshima, Yoshiya Ito, Masaki Nakamura, Hidero Kitasato, Fumihiro Ogawa, Kanako Hosono, Kazuya Iwabuchi, Satoshi Uematsu, Shizuo Akira, Shuh Narumiya, Masataka Majima

    Cardiovascular research   119 ( 5 )   1218 - 1233   2022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)  

    AIMS: Microsomal prostaglandin E synthase-1 (mPGES-1)/prostaglandin E2 (PGE2) induces angiogenesis through the prostaglandin E2 receptor (EP1-4). Among immune cells, regulatory T cells (Tregs), which inhibit immune responses, have been implicated in angiogenesis, and PGE2 is known to modulate function and differentiation of Tregs. We hypothesized that mPGES-1/PGE2-EP signaling could contribute to recovery from ischemic conditions by promoting the accumulation of Tregs. METHODS AND RESULTS: Wild-type (WT), mPGES-1-deficient (mPges-1-/-), and EP4 receptor-deficient (Ep4-/-) male mice 6-8 weeks old were used. Hindlimb ischemia was induced by femoral artery ligation. Recovery from ischemia was suppressed in mPges-1-/- mice and compared with WT mice. The number of accumulated forkhead box protein P3 (FoxP3)+ cells in ischemic muscle tissue was decreased in mPges-1-/- mice compared with that in WT mice. Expression levels of transforming growth factor-β (TGF-β) and stromal cell derived factor-1 (SDF-1) in ischemic tissue were also suppressed in mPges-1-/- mice. The number of accumulated FoxP3+ cells and blood flow recovery were suppressed when Tregs were depleted by injecting antibody against folate receptor 4 (FR4) in WT mice but not in mPges-1-/- mice. Recovery from ischemia was significantly suppressed in Ep4-/- mice compared with WT mice. Furthermore, mRNA levels of Foxp3 and Tgf-β were suppressed in Ep4-/- mice. Moreover, the numbers of accumulated FoxP3+ cells in ischemic tissue were diminished in Ep4-/- mice compared with Ep4+/+ mice. CONCLUSIONS: These findings suggested that mPGES-1/PGE2 induced neovascularization from ischemia via EP4 by promoting accumulation of Tregs. Highly selective EP4 agonists could be useful for treatment of peripheral artery disease (PAD). TRANSLATIONAL PERSPECTIVE: Although surgical treatment for PAD in patients improved, some patients with advanced disease have no other option for treatments other than amputation. In the present study, we revealed that endogenous mPGES-1/PGE2-EP4 signaling induced recovery from ischemia by promoting Tregs accumulation at the ischemic site. In addition, we showed that selective EP4 agonist, or transplantation of Tregs, induced recovery from ischemic conditions. These results indicate that the use of selective EP4 agonist, or cell therapy of Tregs, may be a potential treatment option for severe critical limb ischemia patients.

    DOI: 10.1093/cvr/cvac137

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  • 機械学習を用いた重症COVID-19の層別化における臨床的有用性の予備的検討

    酒井 和也, 西井 基継, 佐治 龍, 松村 玲生, 小川 史洋, 安部 猛, 豊田 洋, 小山 洋史, 竹内 一郎

    日本臨床救急医学会雑誌   25 ( 2 )   397 - 397   2022年5月

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    記述言語:日本語   出版者・発行元:(一社)日本臨床救急医学会  

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  • Differential diagnosis of dysosmia and dysgeusia in COVID-19 pandemic setting

    Kenji Minowa, Fumihiro Ogawa, Mitsuru Takahashi, Hideto Yokoi, Masayasu Gakumazawa, Tomoki Doi, Ichiro Takeuchi

    Medicine: Case Reports and Study Protocols   3 ( 2 )   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)   出版者・発行元:Ovid Technologies (Wolters Kluwer Health)  

    DOI: 10.1097/md9.0000000000000210

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  • Peripheral venous lactate levels substitute arterial lactate levels in the emergency department. 国際誌

    Yasufumi Oi, Kosuke Mori, Hidehiro Yamagata, Ayako Nogaki, Tomoaki Takeda, Chikara Watanabe, Yusuke Sakaguchi, Fumihiro Ogawa, Takeru Abe, Shouhei Imaki, Ichiro Takeuchi

    International journal of emergency medicine   15 ( 1 )   7 - 7   2022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)  

    BACKGROUND: Arterial lactate (AL) level is an important predictor of patient prognosis. AL and peripheral venous lactate (PVL) in blood gas analysis have a low concordance rate, and PVL cannot be used as a substitute for AL. However, if the AL range can be predicted from PVL, PVL may be an alternative method for predicting patient prognosis, and the risk of arterial puncture complications with AL may be reduced. This could be a safe and rapid test method. METHODS: This was a retrospective observational study of 125 cases in which blood gas analysis was performed on both arterial and venous blood with an infectious disease in an emergency department. Spearman's rank correlation coefficient (r) and Bland-Altman analyses were performed. Sensitivity, specificity, and area under the curve (AUC) were calculated for PVL to predict AL < 2 mmol/L or < 4 mmol/L. RESULTS: The median [interquartile range] AL and PVL were 1.82 [1.25-2.46] vs. 2.08 [1.57-3.28], respectively, r was 0.93 (p < 0.0001), and a strong correlation was observed; however, Bland-Altman analysis showed disagreement. When AL < 2 mmol/L was used as the outcome, AUC was 0.970, the PVL cutoff value was 2.55 mmol/L, sensitivity was 85.71%, and specificity was 96.05%. If PVL < 2 mmol/L was the outcome, the sensitivity for AL < 2mmol/L was 100%, and for PVL levels ≥ 3 mmol/L, the specificity was 100%. When AL < 4 mmol/L was used as the outcome, AUC was 0.967, the PVL cutoff value was 3.4 mmol/L, sensitivity was 100%, and specificity was 85.84%. When PVL < 3.5 mmol/L was the outcome, the sensitivity for AL < 4 mmol/L was 100%, and for PVL levels ≥ 4 mmol/L, the specificity was 93.81%. CONCLUSIONS: This study revealed that PVL and AL levels in the same critically ill patients did not perfectly agree with each other but were strongly correlated. Furthermore, the high accuracy for predicting AL ranges from PVL levels explains why PVL levels could be used as a substitute for AL level ranges.

    DOI: 10.1186/s12245-022-00410-y

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  • Severity predictors of COVID-19 in SARS-CoV-2 variant, delta and omicron period; single center study. 国際誌

    Fumihiro Ogawa, Yasufumi Oi, Hiroshi Honzawa, Naho Misawa, Tomoaki Takeda, Yushi Kikuchi, Ryosuke Fukui, Katsushi Tanaka, Daiki Kano, Hideaki Kato, Takeru Abe, Ichiro Takeuchi

    PloS one   17 ( 10 )   e0273134   2022年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The outcomes of coronavirus disease 2019 (COVID-19) treatment have improved due to vaccination and the establishment of better treatment regimens. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, and the corresponding changes in the characteristics of the disease present new challenges in patient management. This study aimed to analyze predictors of COVID-19 severity caused by the delta and omicron variants of SARS-CoV-2. METHODS: We retrospectively analyzed the data of patients who were admitted for COVID-19 at Yokohama City University Hospital from August 2021 to March 2022. RESULTS: A total of 141 patients were included in this study. Of these, 91 had moderate COVID-19, whereas 50 had severe COVID-19. There were significant differences in sex, vaccination status, dyspnea, sore throat symptoms, and body mass index (BMI) (p <0.0001, p <0.001, p <0.001, p = 0.02, p< 0.0001, respectively) between the moderate and severe COVID-19 groups. Regarding comorbidities, smoking habit and renal dysfunction were significantly different between the two groups (p = 0.007 and p = 0.01, respectively). Regarding laboratory data, only LDH level on the first day of hospitalization was significantly different between the two groups (p<0.001). Multiple logistic regression analysis revealed that time from the onset of COVID-19 to hospitalization, BMI, smoking habit, and LDH level were significantly different between the two groups (p<0.03, p = 0.039, p = 0.008, p<0.001, respectively). The cut-off value for the time from onset of COVID-19 to hospitalization was four days (sensitivity, 0.73; specificity, 0.70). CONCLUSIONS: Time from the onset of COVID-19 to hospitalization is the most important factor in the prevention of the aggravation of COVID-19 caused by the delta and omicron SARS-CoV-2 variants. Appropriate medical management within four days after the onset of COVID-19 is essential for preventing the progression of COVID-19, especially in patients with smoking habits.

    DOI: 10.1371/journal.pone.0273134

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  • Prostaglandin-E2 receptor-4 stimulant rescues cardiac malfunction during myocarditis and protects the heart from adverse ventricular remodeling after myocarditis. 国際誌

    Akira Takakuma, Mototsugu Nishii, Alan Valaperti, Haruto Hiraga, Ryo Saji, Kazuya Sakai, Reo Matsumura, Yasuo Miyata, Nozomu Oba, Fumiya Nunose, Fumihiro Ogawa, Kouichi Tamura, Ichiro Takeuchi

    Scientific reports   11 ( 1 )   20961 - 20961   2021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)  

    Cardioprotective effect of prostaglandin-E2 receptor-4 (EP4) stimulation on the ischemic heart has been demonstrated. Its effect on the heart affected by myocarditis, however, remains uncertain. In this study, we investigated therapeutic effect of EP4 stimulant using a mouse model of autoimmune myocarditis (EAM) that progresses to dilated cardiomyopathy (DCM). EP4 was present in the hearts of EAM mice. Treatment with EP4 agonist (ONO-0260164: 20 mg/kg/day) improved an impaired left ventricular (LV) contractility and reduction of blood pressure on day 21, a peak myocardial inflammation. Alternatively, DCM phenotype, characterized by LV dilation, LV systolic dysfunction, and collagen deposition, was observed on day 56, along with activation of matrix metalloproteinase (MMP)-2 critical for myocardial extracellular matrix disruption, indicating an important molecular mechanism underlying adverse ventricular remodeling after myocarditis. Continued treatment with ONO-0260164 alleviated the DCM phenotype, but this effect was counteracted by its combination with a EP4 antagonist. Moreover, ONO-0260164 inhibited in vivo proteolytic activity of MMP-2 in association with up-regulation of tissue inhibitor of metalloproteinase (TIMP)-3. EP4 stimulant may be a promising and novel therapeutic agent that rescues cardiac malfunction during myocarditis and prevents adverse ventricular remodeling after myocarditis by promoting the TIMP-3/MMP-2 axis.

    DOI: 10.1038/s41598-021-99930-5

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  • Evaluation of a combination protocol of CT-first triage and active telemedicine methods by a selected team tackling COVID-19: An experimental research study

    Shigeta Miyake, Takuma Higurashi, Hideaki Kato, Yutaro Yamaoka, Takaomi Kessoku, Shingo Kato, Fumihiro Ogawa, Yasufumi Oi, Atsushi Nakajima, Tetsuya Yamamoto, Ichiro Takeuchi, Akihide Ryo, Shin Maeda

    Journal of Infection and Public Health   14 ( 9 )   1212 - 1217   2021年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.jiph.2021.08.016

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  • Author Correction: The U‑shaped association of serum iron level with disease severity in adult hospitalized patients with COVID‑19. 国際誌

    Kentaro Tojo, Yoh Sugawara, Yasufumi Oi, Fumihiro Ogawa, Takuma Higurashi, Yukihiro Yoshimura, Nobuyuki Miyata, Hajime Hayami, Yoshikazu Yamaguchi, Yoko Ishikawa, Ichiro Takeuchi, Natsuo Tachikawa, Takahisa Goto

    Scientific reports   11 ( 1 )   16949 - 16949   2021年8月

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  • The U-shaped association of serum iron level with disease severity in adult hospitalized patients with COVID-19. 国際誌

    Kentaro Tojo, Yoh Sugawara, Yasufumi Oi, Fumihiro Ogawa, Takuma Higurashi, Yukihiro Yoshimura, Nobuyuki Miyata, Hajime Hayami, Yoshikazu Yamaguchi, Yoko Ishikawa, Ichiro Takeuchi, Natsuo Tachikawa, Takahisa Goto

    Scientific reports   11 ( 1 )   13431 - 13431   2021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)  

    Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.

    DOI: 10.1038/s41598-021-92921-6

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  • Real-world evaluation of a computed tomography-first triage strategy for suspected Coronavirus disease 2019 in outpatients in Japan: An observational cohort study. 国際誌

    Shigeta Miyake, Takuma Higurashi, Takashi Jono, Taisuke Akimoto, Fumihiro Ogawa, Yasufumi Oi, Katsushi Tanaka, Yu Hara, Nobuaki Kobayashi, Hideaki Kato, Tsuneo Yamashiro, Daisuke Utsunomiya, Atsushi Nakajima, Tetsuya Yamamoto, Shin Maeda, Takeshi Kaneko, Ichiro Takeuchi

    Medicine   100 ( 22 )   e26161   2021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)  

    ABSTRACT: The Coronavirus disease 2019 pandemic continues to spread worldwide. Because of the absence of reliable rapid diagnostic systems, patients with symptoms of Coronavirus disease 2019 are treated as suspected of the disease. Use of computed tomography findings in Coronavirus disease 2019 are expected to be a reasonable method for triaging patients, and computed tomography-first triage strategies have been proposed. However, clinical evaluation of a computed tomography-first triage protocol is lacking.The aim of this study is to investigate the real-world efficacy and limitations of a computed tomography-first triage strategy in patients with suspected Coronavirus disease 2019.This was a single-center cohort study evaluating outpatients with fever who received medical examination at Yokohama City University Hospital, prospectively registered between 9 February and 5 May 2020. We treated according to the computed tomography-first triage protocol. The primary outcome was efficacy of the computed tomography-first triage protocol for patients with fever in an outpatient clinic. Efficacy of the computed tomography-first triage protocol for outpatients with fever was evaluated using sensitivity, specificity, positive predictive value, and negative predictive value. We conducted additional analyses of the isolation time of feverish outpatients and final diagnoses.In total, 108 consecutive outpatients with fever were examined at our hospital. Using the computed tomography-first triage protocol, 48 (44.9%) patients were classified as suspected Coronavirus disease 2019. Nine patients (18.8%) in this group were positive for severe acute respiratory syndrome coronavirus 2 using polymerase chain reaction; no patients in the group considered less likely to have Coronavirus disease 2019 tested positive for the virus. The protocol significantly shortened the duration of isolation for the not-suspected versus the suspected group (70.5 vs 1037.0 minutes, P < .001).Our computed tomography-first triage protocol was acceptable for screening patients with suspected Coronavirus disease 2019. This protocol will be helpful for appropriate triage, especially in areas where polymerase chain reaction is inadequate.

    DOI: 10.1097/MD.0000000000026161

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  • Long Term Decreased Exercise Capacity of COVID-19 Patients Who Received Mechanical Ventilation in Japan: A Case Series. 国際誌

    Takuya Saeki, Fumihiro Ogawa, Mina Matsumiya, Mei Yamamura, Hideyuki Oritsu, Manabu Nonogaki, Jo Uesugi, Ichiro Takeuchi, Takeshi Nakamura

    American journal of physical medicine & rehabilitation   2021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)  

    ABSTRACT: The long-term exercise capacity of coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS) is not clear. The 6-minute walking distance (6MWD) of four patients with COVID-19-associated ARDS was followed for 6 months after admission to the hospital. These four patients were admitted to the intensive care unit (ICU) of our hospital and received mechanical ventilation. Rehabilitation therapy (positioning, postural drainage, and passive range of motion exercises) was started after ICU admission. Mobilization therapy, including muscle power training, sitting on the edge of the bed, and endurance training, was performed after the end of sedation. The Medical Research Council sum scores and Barthel Indexes for the patients improved after ICU discharge and completely recovered 6 months after admission to the hospital. However, the 6MWD of the four patients remained shorter than those of healthy persons of the same age at 6 months after admission to the hospital. Furthermore, the minimum SpO2 during the 6-minute walking test remained below 96%. It is possible that patients who receive mechanical ventilation due to COVID-19-associated ARDS have decreased long-term exercise capacity, despite muscle power and activities of daily living recovering completely.

    DOI: 10.1097/PHM.0000000000001803

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  • An evaluation of venous thromboembolism by whole-body enhanced CT scan for critical COVID-19 pneumonia with markedly rises of coagulopathy related factors: a case series study. 国際誌

    Fumihiro Ogawa, Yasufumi Oi, Kento Nakajima, Reo Matsumura, Tomoki Nakagawa, Takao Miyagawa, Takeru Abe, Ichiro Takeuchi

    Thrombosis journal   19 ( 1 )   26 - 26   2021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)  

    BACKGROUND: Coronavirus disease (COVID-19) pneumonitis associated with severe respiratory failure has a high mortality rate. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently observed. Coagulopathy has emerged as a significant contributor to thrombotic complications. Although recommendations have been made for anticoagulant use for COVID-19, no guidelines have been specified. We describe four cases of critical COVID-19 with thrombosis detected by enhanced CT scan. The CT findings of all cases demonstrated typical findings of COVID-19 and pulmonary embolism or deep venous thrombus without critical exacerbation. Two patients died of respiratory failure due to COVID-19. DISCUSSION: Previous reports have suggested coagulopathy with thrombotic signs as the main pathological feature of COVID-19, but no previous reports have focused on coagulopathy evaluated by whole-body enhanced CT scan. Changes in hemostatic biomarkers, represented by an increase in D-dimer and fibrin/fibrinogen degradation products, indicated that the essence of coagulopathy was massive fibrin formation. Although there were no clinical symptoms related to their prognosis, critical COVID-19-induced systemic thrombus formation was observed. CONCLUSIONS: Therapeutic dose anticoagulants should be considered for critical COVID-19 because of induced coagulopathy, and aggressive follow-up by whole body enhanced CT scan for systemic venous thromboembolism (VTE) is necessary.

    DOI: 10.1186/s12959-021-00280-z

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  • The U-shaped association of serum iron level with COVID-19 severity: Is iron a potential therapeutic target?

    Kentaro Tojo, Yoh Sugawara, Yasufumi Oi, Fumihiro Ogawa, Takuma Higurashi, Yukihiro Yoshimura, Nobuyuki Miyata, Hajime Hayami, Yoshikazu Yamaguchi, Yoko Ishikawa, Ichiro Takeuchi, Natsuo Tachikawa, Takahisa Goto

    2021年2月

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    出版者・発行元:Cold Spring Harbor Laboratory  

    <title>Abstract</title><sec><title>Objective</title>To evaluate the association between iron metabolism indicators and disease severity in hospitalized patients with coronavirus disease 2019 (COVID-19).

    </sec><sec><title>Design</title>Two-center observational study

    </sec><sec><title>Setting</title>A university hospital and a core hospital in Yokohama, Japan

    </sec><sec><title>Patients</title>Adults with COVID-19 whose serum iron levels were measured within the first 5 days of hospitalization were included. Patients who refused mechanical ventilation were excluded from the study.

    </sec><sec><title>Measurements and Main Results</title>One hundred thirty-six patients were included in this study. We analyzed the association between COVID-19 severity and serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT) levels. Disease severity was defined as the worst respiratory status during hospitalization. Serum iron levels were significantly lower in patients with mild respiratory failure (RF) (n=55, median serum iron level: 24 [interquartile range: 19–42] mg/dL) than in the non-RF group (n=44, 40 [24–80] mg/dL) and the severe RF group (n=37, 60 [23.5–87] mg/dL); however, there were no significant differences in iron levels between the non-RF and severe RF groups (non-RF <italic>vs</italic>. mild RF: p=0.019, non-RF <italic>vs</italic>. severe RF: p&gt;0.999, and mild RF <italic>vs</italic>. severe RF: p=0.009). That is, there was a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron or TSAT levels were independently associated with development of severe RF.

    </sec><sec><title>Conclusions</title>A U-shaped association between serum iron level and RF severity in hospitalized COVID-19 patients was observed. Higher serum iron levels in COVID-19 patients with RF are associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.

    </sec>

    DOI: 10.1101/2021.02.19.21252061

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  • A Case of Central Pontine Myelinolysis Occurred During Treatment of Hyperosmolar Hyperglycemic Syndrome. 国際誌

    Shoko Niida, Fumihiro Ogawa, Kento Nakajima, Kazuya Sakai, Munehito Uchiyama, Takeru Abe, Ichiro Takeuchi

    International medical case reports journal   14   407 - 412   2021年

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    記述言語:英語  

    Central pontine myelinolysis (CPM) is a rare demyelinating condition which has been reported to occur in a variety of clinical settings, but most commonly in association with a rapid rise in plasma osmolality during correction of chronic hyponatremia. The clinical consequences can vary from a mild motor weakness that resolves completely over time to the devastating locked-in syndrome. In this presentation, we report a case of hyperosmolar hyperglycemic syndrome (HHS) with ponto-occipital disintegration. A 71-year-old female was transferred to our ER by an ambulance due to consciousness disorder and continuous fever for 10 days. We diagnosed septic shock caused by urinary tract infection (UTI), cerebral multiple infarctions, acute kidney injury (AKI) and HHS without treatment for diabetes. Then, we started therapeutic interventions for them based on the guideline with severe control for blood sugar (BS; primary 1635 mg/dl) under insulin therapy and hypernatremia (primary 153 mEq/l) under crystal infusion control in advanced care unit, apparently on routine lab data. However, the initial serum sodium value of 153 mEq/l was slowly compensated to 148 mEq/l in 60 hours under guideline on routine lab data, the initial compensated sodium value with osmolality was changed from 178 mEq/l to 150 mEq/l in the period. She recovered from her primary diagnosis and unconsciousness. After stabilized sepsis and HHS, we detected CPM on brain MRI due to following up multiple cerebral infarctions with left leg paralysis and verbal disorder. She gradually recovered over several months with intensive rehabilitation and eventually regained near normal functional capacity with stabilized BS. When we consider HHS with hypernatremia, it may be necessary to pay attention to not only to BS control and sodium control according to the guideline but also to osmolality changes to prevent CPM.

    DOI: 10.2147/IMCRJ.S316943

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  • Serum cholinesterase associated with COVID-19 pneumonia severity and mortality. 査読 国際誌

    Kento Nakajima, Takeru Abe, Ryo Saji, Fumihiro Ogawa, Hayato Taniguchi, Keishi Yamaguchi, Kazuya Sakai, Tomoki Nakagawa, Reo Matsumura, Yasufumi Oi, Mototsugu Nishii, Ichiro Takeuchi

    The Journal of infection   82 ( 2 )   282 - 327   2020年8月

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  • Rehabilitation Therapy for A COVID-19 Patient who Received Mechanical Ventilation in Japan 査読 国際誌

    Takuya Saeki, Fumihiro Ogawa, Ryosuke Chiba, Manabu Nonogaki, Jo Uesugi, Ichiro Takeuchi, Takeshi Nakamura

    American Journal of Physical Medicine & Rehabilitation   Publish Ahead of Print ( 10 )   873 - 875   2020年7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:Ovid Technologies (Wolters Kluwer Health)  

    A 65-yr-old man visited a primary care hospital with a continued fever of 38°C for 3 days. As his fever did not improve until 8 days after, he was admitted into another acute care hospital, where his respiratory condition rapidly worsened. Therefore, the patient was transferred to our hospital. On the day of transfer (day 1), he was started on mechanical ventilation. COVID-19 was diagnosed using a polymerase chain reaction assay 6 days after admission (day 6). The rehabilitation therapy was begun on day 6. The initial rehabilitation programs focused on positioning and postural drainage. The patient was extubated on day 19, and he began standing and stepping on the same day. Gait exercises began on day 22, and endurance training was initiated on day 28. The patient was discharged from our hospital on day 34 as he met the physical function milestones. One month after discharge, the Medical Research Council sum score and Barthel Index had each improved; therefore, muscle strength and daily activities had returned to normal. It was assumed that mobilization should be performed as soon as possible after the end of sedation during the acute phase of severe COVID-19 infection in patients receiving mechanical ventilation.

    DOI: 10.1097/phm.0000000000001545

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  • Serum cholinesterase on admission as a predictor of COVID-19 pneumonia severity and mortality

    Nakajima K, Abe T, Saji R, Ogawa F, Taniguchi H, Yamaguchi K, Sakai K, Nakagawa T, Matsumura R, Oi Y, Nishii M, Takeuchi I

    2020年7月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.21203/rs.3.rs-47469/v1

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  • A Case of Coronavirus Disease 2019 Treated With Ciclesonide. 査読 国際誌

    Kento Nakajima, Fumihiro Ogawa, Kazuya Sakai, Munehito Uchiyama, Yutaro Oyama, Hideaki Kato, Ichiro Takeuchi

    Mayo Clinic proceedings   95 ( 6 )   1296 - 1297   2020年6月

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  • A climate‐change vulnerability and adaptation assessment for Brazil's protected areas

    Lapola DM, Silva JMCd, Braga DR, Carpigiani L, Ogawa F, Torres RR, Barbosa LCF, Ometto JPHB, Joly CA

    Conservation biology : the journal of the Society for Conservation Biology   2020年4月

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    掲載種別:研究論文(学術雑誌)  

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  • O抗原と敗血症性ショック

    酒井 和也, 西井 基継, 佐治 龍, 廣見 太郎, 小川 史洋, 竹内 一郎

    感染症学雑誌   94 ( 臨増 )   291 - 291   2020年3月

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    記述言語:日本語   出版者・発行元:(一社)日本感染症学会  

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  • Veno‐venous extracorporeal membrane oxygenation for severe pneumonia: COVID‐19 case in Japan 査読 国際誌

    Hayato Taniguchi, Fumihiro Ogawa, Hiroshi Honzawa, Keishi Yamaguchi, Shoko Niida, Mafumi Shinohara, Kohei Takahashi, Masayuki Iwashita, Takeru Abe, Sousuke Kubo, Makoto Kudo, Ichiro Takeuchi

    Acute Medicine & Surgery   7 ( 1 )   e509   2020年1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)   出版者・発行元:Wiley  

    BACKGROUND: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is one of the ultimate treatments for acute respiratory failure. However, the effectiveness of ECMO in patients with novel coronavirus disease (COVID-19) is unknown. CASE PRESENTATION: A 72-year-old woman who was a passenger of a cruise ship tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) while in quarantine on board using throat swab. Three days after admission, her condition deteriorated, and she was subsequently intubated. On day 6, VV-ECMO was introduced. Lopinavir/ritonavir was given; continuous renal replacement therapy was also introduced. On day 10, her chest radiography and lung compliance improved. She was weaned off ECMO on day 12. CONCLUSION: Treatment of severe pneumonia in COVID-19 by ECMO should recognize lung plasticity considering time to ECMO introduction and interstitial biomarkers. In Japan, centralization of ECMO patients has not been sufficient. Thus, we suggest nationwide centralization and further research to respond to the crisis caused by COVID-19.

    DOI: 10.1002/ams2.509

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ams2.509

  • Therapeutic strategy for severe COVID-19 pneumonia from clinical experience

    Fumihiro Ogawa, Hideaki Kato, Kento Nakajima, Tomoki Nakagawa, Reo Matsumura, Yasufumi Oi, Kazuya Sakai, Munehito Uchiyama, Yutaro Ohyama, Takeru Abe, Ichiro Takeuchi

    European Journal of Inflammation   18   2020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:SAGE PUBLICATIONS INC  

    Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first identified in December 2019 in Wuhan, China, and has resulted in global pandemic. There is currently no effective therapeutic strategy for the management of mechanical ventilation or antiviral drugs for the treatment of this disease. As such, the development of a therapeutic strategy is urgently needed and should be established as soon as possible. In this case series, a therapeutic strategy was initially developed based on previous treatment methods used for the treatment of SARS and MERS in the absence of treatment options for COVID-19 due to a lack of information. During the search for a potential treatment, clinical findings were obtained from patients with severe COVID-19, and one therapeutic strategy was established. This therapeutic strategy was then applied to severe COVID-19 patients. In addition, we can require some interesting clinical features and characteristics of COVID-19 from blood analysis and physical findings. Here, we reported on the clinical features and characteristics of a therapeutic strategy for the treatment of severe COVID-19 pneumonia at our institution.

    DOI: 10.1177/2058739220961591

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  • SARS-CoV-2 PCR検査が長期陽性持続した新型コロナウイルス感染症(COVID-19)の2例 査読

    加藤英明, 加藤英明, 渡邊弘樹, 小林信明, 原悠, 酒井和也, 中嶋賢人, 小川史洋, 佐野加代子, 佐野加代子, 山崎悦子, 宇宿修三, 田中伸子, 竹内一郎, 中島秀明, 金子猛

    感染症学雑誌   94 ( 4 )   591 - 595   2020年

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    記述言語:日本語   出版者・発行元:(一社)日本感染症学会  

    症例1(66歳男)は酸素投与を要する中等症、症例2(39歳男)は軽症であり、症例1は入院から30日後、症例2は25日後までPCR陽性が持続した。検査反応の1ウェル中のウイルス量の概数を用いて評価した結果、2例とも入院初期にウイルス量が増加し、症状改善に遅れてウイルス量が減少したが、喀痰からのPCR検査は咽頭や鼻咽頭拭い液よりも長期間陽性が持続した。また、2型糖尿病の既往のある症例1は症例2よりも症状が強く、ウイルス量も多かった。

    J-GLOBAL

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00276&link_issn=&doc_id=20200812300021&doc_link_id=10.11150%2Fkansenshogakuzasshi.94.591&url=https%3A%2F%2Fdoi.org%2F10.11150%2Fkansenshogakuzasshi.94.591&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • Role of KRAS in regulating normal human airway basal cell differentiation 査読

    Fumihiro Ogawa, Matthew S. Walters, Afrah Shafquat, Sarah L. O’Beirne, Robert J. Kaner, Jason G. Mezey, Haijun Zhang, Philip L. Leopold, Ronald G. Crystal

    Respiratory Research   20 ( 1 )   2019年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1186/s12931-019-1129-4

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  • The role of vascular endothelial growth factor receptor 1 tyrosine kinase signaling in bleomycin-induced pulmonary fibrosis. 査読 国際誌

    Hideki Amano, Yoshio Mastui, Yoshiya Ito, Yusaku Shibata, Tomohiro Betto, Koji Eshima, Fumihiro Ogawa, Yukitoshi Satoh, Masabumi Shibuya, Masataka Majima

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   117   109067 - 109067   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with a poor prognosis. Fibroblast proliferation amplifies extracellular matrix deposition and increases angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors. VEGF interacts with VEGF receptors (VEGFR1 and VEGFR2). A previous study showed that VEGFR1 tyrosine kinase (TK) signaling induced blood flow recovery mediated by bone marrow (BM)-derived stem cells. We hypothesized that VEGFR1-TK signaling might be related to pulmonary fibrosis. MATERIAL AND METHODS: Six-week-old male C57Bl/6 wild-type (WT) mice and VEGFR1 TK knockout mice (TKKO mice) were treated with a single intratracheal injection of bleomycin (BLM; 0.1 μg in 50 μl saline) or vehicle (saline; 50 μl). Lung fibrosis was evaluated by histology, real-time PCR and ELISA for pro-fibrotic factors, and assessment of lung mechanics. RESULTS: The fibrotic area in the lung and the lung elastance were significantly reduced in TKKO mice (P < 0.01). The expression of the fibrosis-related factors type I collagen, S100A4, and transforming growth factor (TGF)-β was also significantly reduced in TKKO mice on day 21 after BLM injection. TKKO mice also had significantly lower levels of stromal cell-derived factor (SDF)-1 in the lungs and plasma on days 14 and 21 after BLM treatment (P < 0.05). Moreover, the expression of C-X-C chemokine receptor type 7 (CXCR7) and CXCR4, the receptors for SDF-1, was also suppressed in TKKO mice. Immunohistochemical analysis showed that treatment with a CXCR4 antibody decreased the accumulation of VEGFR1+ cells in the lung in WT mice but not in TKKO mice. CONCLUSION: These results suggest that VEGFR1 TK signaling promotes BLM-induced pulmonary fibrosis by activating the SDF-1/CXCR4 axis in infiltrating VEGFR1+ cells.

    DOI: 10.1016/j.biopha.2019.109067

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  • Erroneously Analyzed F-Wave of Bradycardic Atrial Fibrillation as Ventricular Fibrillation for a Cardiac Arrest Patient 査読

    Chikara Watanabe, Kento Nakajima, Kosuke Mori, Masayasu Gakumazawa, Naoki Nakayama, Makoto Kato, Fumihiro Ogawa, Kouhei Takahashi, Masayuki Iwashita, Takeru Abe, Ichiro Takeuchi

    Case Reports in Acute Medicine   25   2019年6月

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    出版者・発行元:S. Karger {AG}  

    DOI: 10.1159/000500880

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  • A case report: Veno-venous extracorporeal membrane oxygenation for severe blunt thoracic trauma. 査読 国際誌

    Fumihiro Ogawa, Takuma Sakai, Ko Takahashi, Makoto Kato, Keishi Yamaguchi, Sayo Okazaki, Takeru Abe, Masayuki Iwashita, Ichiro Takeuchi

    Journal of cardiothoracic surgery   14 ( 1 )   88 - 88   2019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)  

    INTRODUCTION: The use of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in trauma patients has been controversial, but VV-ECMO plays a crucial role when the lungs are extensively damaged and when conventional management has failed. VV-ECMO provides adequate tissue oxygenation and an opportunity for lung recovery. However, VV-ECMO remains contraindicated in patients with a risk of bleeding because of systemic anticoagulation during the treatment. The most important point is controlling the bleeding from severe trauma. CASE: A 32-year-old male experienced blunt trauma due to a traffic accident. He presented with bilateral hemopneumothorax and bilateral flail chest. We performed emergency thoracotomy for active bleeding and established circulatory stability. After surgery, the oxygenation deteriorated under mechanical ventilation, so we decided to establish VV-ECMO. However, bleeding from the bilateral lung contusions increased after VV-ECMO was established, and the patient was switched to heparin-free ECMO. After conversion, we could control the bronchial bleeding, especially the lung hematomas, and the oxygenation recovered. The patient was discharged without significant complications. VV-ECMO and mechanical ventilation were stopped on days 10 and 11, respectively. He was discharged from the ICU on day 15. CONCLUSION: When we consider the use of ECMO for patients with uncontrollable, severe bleeding caused by blunt trauma, it may be necessary to use a higher flow setting for heparin-free ECMO than typically used for patients without trauma to prevent thrombosis.

    添付ファイル: Ogawa_et_al-2019-Journal_of_Cardiothoracic_Surgery.pdf

    DOI: 10.1186/s13019-019-0908-9

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  • Suppression of lymphangiogenesis by soluble vascular endothelial growth factor receptor-2 in a mouse lung cancer model 査読 国際誌

    Shotaro Maehana, Masaki Nakamura, Fumihiro Ogawa, Rimika Imai, Rei Murakami, Fumiaki Kojima, Masataka Majima, Hidero Kitasato

    Biomedicine & Pharmacotherapy   84   660 - 665   2016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:Elsevier {BV}  

    The vascular endothelial growth factor (VEGF) family has a key role in the formation of blood vessels and lymphatics. Among the members of this family, VEGF-C is one of the most important factors involved in lymphangiogenesis via binding with two receptors (vascular endothelial growth factor receptor-2 and -3: VEGFR-2 and VEGFR-3). Soluble VEGFR-2 (sVEGFR-2) has a role in maintaining the alymphatic state of the cornea associated with binding to VEGF-C, and selectively inhibits lymphangiogenesis but not angiogenesis. In this study, we introduced sVEGFR-2 into lung cancer cells and evaluated the influence on tumor progression and on genes regulating lymphatic formation and metastasis in vivo. A retroviral vector was used to introduce the sVEGFR-2 gene into Lewis lung carcinoma cells (LLC), which were designated as LLC-sVEGFR-2 cells. Proteins secreted into the culture supernatant by these cells were detected by western blotting using specific antibodies. To examine lymphangiogenesis by primary lung cancer in vivo, LLC-sVEGFR-2 cells were subcutaneously injected into C57BL/6 mice. At 14days after injection, immunohistochemistry was performed using an antibody directed against lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a marker of lymphatics. Expression of mRNA for VEGFR-2, VEGFR-3 and matrix metalloproteinases (MMPs) was also determined by real-time PCR. Furthermore, LLC-sVEGFR-2 cells were directly inoculated into the left lung in C57BL/6 mice and the number of micro-metastases in pulmonary lymph nodes was determined. Introduction of sVEGFR-2 into LLC cells resulted in secretion of sVEGFR-2 protein into the culture supernatant. There were fewer LYVE-1 positive lymphatics after inoculation of LLC-sVEGFR-2 into mice compared with the control group. In addition, VEGFR-2, VEGFR-3, and MMPs gene expression was suppressed in the primary tumors of the LLC-sVEGFR-2 group compared with the control group. Furthermore, there were fewer micro-metastases in the pulmonary lymph nodes of the LLC-sVEGFR-2 group compared with the control group after cells were directly inoculated into the lung. These findings indicate that introduction of sVEGFR-2 suppressed lymphangiogenesis in primary lung cancer and also suppressed lymphogenic metastasis by inhibiting VEGF-C, followed by down-regulation of VEGFR-2, VEGFR-3 and MMPs. Accordingly, sVEGFR-2 might be a promising target for treatment of cancer by regulating lymphangiogenesis and lymphogenic metastasis.

    DOI: 10.1016/j.biopha.2016.09.083

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  • Thromboxane A2 induces blood flow recovery via platelet adhesion to ischaemic regions. 査読 国際誌

    Hideki Amano, Yoshiya Ito, Koji Eshima, Shintaro Kato, Fumihiro Ogawa, Kanako Hosono, Kazuhito Oba, Hideaki Tamaki, Hiroyuki Sakagami, Masabumi Shibuya, Shuh Narumiya, Masataka Majima

    Cardiovascular research   107 ( 4 )   509 - 21   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: Thromboxane A2 (TXA2) induces platelet adhesion through thromboxane prostanoid (TP) receptor. Platelets contain many pro-angiogenic factors and are recruited to the site of vascular injury. However, the cellular and molecular mechanisms of platelet-dependent angiogenesis, especially the involvement of TP signalling, have not been fully elucidated. The present study hypothesized that TP-dependent platelet adhesion would contribute to angiogenesis in a mouse hindlimb ischaemic model. METHODS AND RESULTS: Blood flow recovery was suppressed by the TXA2 receptor antagonist (S-1452) and the TXA2 synthase inhibitor (OKY-046) compared with control mice. TP knockout mice (TP(-/-)) showed delayed blood flow recovery from ischaemia and impaired angiogenesis compared with wild-type (WT) mice and prostacyclin receptor knockout mice (IP(-/-)). Selective platelet adhesion to ischaemic endothelial cells (ECs) via P-selectin was identified in WT and IP(-/-), but not in TP(-/-), via in vivo microscopy. IF analysis showed that P-selectin glycoprotein ligand-1 (PSGL-1) co-localized with endothelial CD31 in ischaemic muscle in WT and IP(-/-) but not diminished in TP(-/-). Platelet-rich plasma levels of stromal cell-derived factor-1 and VEGF were increased after ischaemia in WT, and suppressed by antibody against P-selectin in WT but not in TP(-/-). Furthermore, the blood flow recovery was suppressed by neutralizing antibodies against VEGF or C-X-C chemokine receptor type 4 in WT and IP(-/-) but not in TP(-/-). CONCLUSION: These results indicated that TP signalling facilitates ischaemia-induced angiogenesis via P-selectin-mediated platelet adhesion to PSGL-1 on the ECs at ischaemic sites and the supply of pro-angiogenic factors by the adherent platelets.

    DOI: 10.1093/cvr/cvv139

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  • The role of vascular endothelial growth factor receptor-1 signaling in compensatory contralateral lung growth following unilateral pneumonectomy 査読 国際誌

    Yoshio Matsui, Hideki Amano, Yoshiya Ito, Koji Eshima, Hideaki Tamaki, Fumihiro Ogawa, Akira Iyoda, Masafumi Shibuya, Yuji Kumagai, Yukitoshi Satoh, Masataka Majima

    Laboratory Investigation   95 ( 5 )   456 - 468   2015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:Springer Science and Business Media {LLC}  

    Compensatory lung growth models have been widely used to investigate alveolization because the remaining lung can be kept intact and volume loss can be controlled. Vascular endothelial growth factor (VEGF) plays an important role in blood formation during lung growth and repair, but the precise mechanisms involved are poorly understood; therefore, the aim of this study was to investigate the role of VEGF signaling in compensatory lung growth. After left pneumonectomy, the right lung weight was higher in VEGF transgenic mice than wild-type (WT) mice. Compensatory lung growth was suppressed significantly in mice injected with a VEGF neutralizing antibody and in VEGF receptor-1 tyrosine kinase-deficient mice (TK(-/-) mice). The mobilization of progenitor cells expressing VEGFR1(+) cells from bone marrow and the recruitment of these cells to lung tissue were also suppressed in the TK(-/-) mice. WT mice transplanted with bone marrow from TK(-/-)transgenic GFP(+) mice had significantly lower numbers of GFP(+)/aquaporin 5(+), GFP(+)/surfactant protein A(+), and GFP(+)/VEGFR1(+) cells than WT mice transplanted with bone marrow from WTGFP(+) mice. The GFP(+)/VEGFR1(+) cells also co-stained for aquaporin 5 and surfactant protein A. Overall, these results suggest that VEGF signaling contributes to compensatory lung growth by mobilizing VEGFR1(+) cells.

    DOI: 10.1038/labinvest.2014.159

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  • The Role of Vascular Endothelial Growth Factor Receptor-1 Signaling in the Recovery from Ischemia. 査読 国際誌

    Hideki Amano, Shintaro Kato, Yoshiya Ito, Koji Eshima, Fumihiro Ogawa, Ryo Takahashi, Kazuki Sekiguchi, Hideaki Tamaki, Hiroyuki Sakagami, Masabumi Shibuya, Masataka Majima

    PloS one   10 ( 7 )   e0131445   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Vascular endothelial growth factor (VEGF) is one of the most potent angiogenesis stimulators. VEGF binds to VEGF receptor 1 (VEGFR1), inducing angiogenesis through the receptor's tyrosine kinase domain (TK), but the mechanism is not well understood. We investigated the role of VEGFR1 tyrosine kinase signaling in angiogenesis using the ischemic hind limb model. Relative to control mice, blood flow recovery was significantly impaired in mice treated with VEGFA-neutralizing antibody. VEGFR1 tyrosine kinase knockout mice (TK-/-) had delayed blood flow recovery from ischemia and impaired angiogenesis, and this phenotype was unaffected by treatment with a VEGFR2 inhibitor. Compared to wild type mice (WT), TK-/- mice had no change in the plasma level of VEGF, but the plasma levels of stromal-derived cell factor 1 (SDF-1) and stem cell factor, as well as the bone marrow (BM) level of pro-matrix metalloproteinase-9 (pro-MMP-9), were significantly reduced. The recruitment of cells expressing VEGFR1 and C-X-C chemokine receptor type 4 (CXCR4) into peripheral blood and ischemic muscles was also suppressed. Furthermore, WT transplanted with TK-/- BM significantly impaired blood flow recovery more than WT transplanted with WT BM. These results suggest that VEGFR1-TK signaling facilitates angiogenesis by recruiting CXCR4+VEGFR1+ cells from BM.

    DOI: 10.1371/journal.pone.0131445

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  • Report of a rare case: occult hemothorax due to blunt trauma without obvious injury to other organs 査読

    Fumihiro Ogawa, Masahito Naito, Akira Iyoda, Yukitoshi Satoh

    Journal of Cardiothoracic Surgery   8 ( 1 )   2013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:Springer Science and Business Media {LLC}  

    DOI: 10.1186/1749-8090-8-205

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    その他リンク: http://link.springer.com/content/pdf/10.1186/1749-8090-8-205.pdf

  • LUNG VOLUME ASSESSMENT ON 3D-CT AND PREDICTED POSTOPERATIVE PULMONARY FUNCTION FOR LUNG CANCER PATIENTS

    Masanori Yokoba, Tsuyoshi Ichikawa, Akira Takakura, Masaru Kubota, Shinichiro Ryuge, Sachiyo Maki, Yasuhiro Hiyoshi, Masashi Kasajima, Kazu Shiomi, Fumihiro Ogawa, Masashi Mikubo, Masahito Naito, Yukitoshi Sato, Nobuo Yanase, Noriyuki Masuda, Masato Katagiri

    RESPIROLOGY   18   147 - 147   2013年11月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

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  • VALIDATION STUDY OF POSTOPERATIVE PLATINUM-BASED ADJUVANT CHEMOTHERAPY FOR JAPANESE PATIENTS WITH COMPLETELY RESECTED PATHOLOGICAL STAGEIIIA NON-SMALL CELL LUNG CANCER

    Kazu Shiomi, Noriyuki Takakura, Shinichiro Ryuge, Syoko Hayashi, Dai Ishii, Hirotsugu Yamazaki, Masahito Naito, Yoshio Matsui, Masashi Mikubo, Fumihiro Ogawa, Jiichiro Sasaki, Hiroyasu Nakashima, Noriyuki Masuda, Yukitoshi Satoh

    JOURNAL OF THORACIC ONCOLOGY   8   S585 - S585   2013年11月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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  • Risk factors for postoperative complications in the elderly with lung cancer 査読

    Fumihiro Ogawa, Guoqin Wang, Yoshio Matsui, Hidenori Hara, Akira Iyoda, Yukitoshi Satoh

    Asian Cardiovascular and Thoracic Annals   21 ( 3 )   313 - 318   2013年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE Publications  

    DOI: 10.1177/0218492312457359

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    その他リンク: http://journals.sagepub.com/doi/full-xml/10.1177/0218492312457359

  • Clinicopathological features and the impact of the new TNM classification of malignant tumors in patients with pulmonary large cell neuroendocrine carcinoma

    AKIRA IYODA, SHI-XU JIANG, WILLIAM D. TRAVIS, NAOMI KUROUZU, FUMIHIRO OGAWA, HIDEKI AMANO, YUICHI SATO, VALERIE W. RUSCH, MAKOTO SAEGUSA, YUKITOSHI SATOH

    Molecular and Clinical Oncology   1 ( 3 )   437 - 443   2013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:Spandidos Publications  

    DOI: 10.3892/mco.2013.80

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  • Clinicopathological features and the impact of the new TNM classification of malignant tumors in patients with pulmonary large cell neuroendocrine carcinoma. 査読 国際誌

    Akira Iyoda, Shi-Xu Jiang, William D Travis, Naomi Kurouzu, Fumihiro Ogawa, Hideki Amano, Yuichi Sato, Valerie W Rusch, Makoto Saegusa, Yukitoshi Satoh

    Molecular and clinical oncology   1 ( 3 )   437 - 443   2013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)  

    The prognosis of patients with large-cell neuroendocrine carcinoma (LCNEC) of the lung is extremely poor and the optimal treatment for these patients has yet to be determined. In this study, we described the clinicopathological characteristics of LCNECs and compared the prognoses of corresponding stages determined by the guidelines of the 6th and 7th editions of the TNM classification of malignant tumors. Clinical data from 42 patients diagnosed with primary LCNEC who underwent treatment at Kitasato University Hospital between 1991 and 2009 were retrospectively analyzed. On follow-up of 42 patients, 22 (52.4%) had confirmed recurrent tumors, including 8 patients with mediastinal lymph node recurrences and 19 with distant metastases. The sites of distant metastases included the brain in 8, bone in 8, liver in 7, lungs in 5 and adrenal glands in 4 patients. For all the patients, the 5-year overall survival rate was 34.7% and the 5-year disease-free survival rate was 32.9%. The 5-year overall survival rates of patients with stage I cancers according to the 6th and 7th staging editions was 51.3% (6th n=18, 7th n=16). Thirteen of 42 patients (31.0%) also had metachronous or synchronous primary cancers. Patients with LCNEC had poor outcomes, even those with stage I tumors classified according to the 7th edition of the TNM classification. Therefore, frequent recurrences in addition to metachronous or synchronous primary cancers in patients with LCNEC should be treated.

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  • Surgical removal of pulmonary arteriovenous malformations subsequent to total cavopulmonary connection conversion long after a Björk procedure 査読

    Fumihiro Ogawa, Kagami Miyaji, Masahiro Ishii, Akira Iyoda, Yukitoshi Satoh

    Pediatric Cardiology   34 ( 3 )   739 - 742   2013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)  

    Because the cavopulmonary shunt procedure is widely used for palliation of complex congenital heart diseases, pulmonary arteriovenous malformations (PAVMs) are relatively well-known complications. The reported patient was a 23-year-old woman who experienced PAVMs in the right lower lobe after a classical Glenn anastomosis and Björk procedure for tricuspid atresia. Her arterial oxygen saturation (SaO2) 14 years after the Björk procedure was ~80 %. She then underwent a total cavopulmonary connection (TCPC) conversion to reduce her PAVMs in the right lower lobe using the "hepatic factor." However, her situation remained unchanged, and she experienced severe systemic cyanosis (SaO2, 70 %) and dyspnea during physical exertion without hemoptysis due to increased blood flow to the PAVMs. Although interventional embolization was considered, it was impossible due to considerable dilation of the main PAVM. Thus, right lower lung lobectomy was performed. After surgery, the patient's SaO2 increased to 90 %. To the authors' knowledge, this is the first case report of a lung resection for residual PAVMs after TCPC conversion. © 2012 Springer Science+Business Media, LLC.

    DOI: 10.1007/s00246-012-0336-2

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  • Angiotensin II Type 1A receptor signaling facilitates tumor metastasis formation through p-selectin-mediated interaction of tumor cells with platelets and endothelial cells 査読

    Hideki Amano, Yoshiya Ito, Fumihiro Ogawa, Koji Eshima, Tatsunori Suzuki, Kazuhito Oba, Yoshio Matsui, Shintaro Kato, Tomoya Fukui, Masaki Nakamura, Hidero Kitasato, Akiyoshi Fukamizu, Masataka Majima

    American Journal of Pathology   182 ( 2 )   553 - 564   2013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)  

    Angiotensin II is involved in tumor growth
    however, the precise mechanism is not known. Platelets also contribute to tumor growth, and angiotensin II type 1 receptor (AT1) is expressed on the platelet surface. We hypothesized that interaction of platelets with tumor cells through AT1 receptor signaling promotes tumor metastasis. B16F1 melanoma cells were intravenously injected into Agtr1a knockout mice (AT1a-/-) and wild-type littermates (WT)
    the AT1a-/- mice exhibited a reduction in lung colonies. Angiotensin II induced expression of P-selectin on platelets in WT but not in AT1a -/- mice. A selective P-selectin neutralizing antibody decreased lung colony numbers in WT but not in AT1a-/- mice. Levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1) receptor in platelets at metastatic locus were lower in AT1a-/- mice. Treatment of neutralizing antibodies against VEGF and CXCR4 decreased lung colony numbers in WT but not in AT1a-/- mice. In AT1a-/- mice, and both mobilization of progenitor cells expressing CXCR4 +VEGFR1+ cells from bone marrow and their recruitment to lung tissues were suppressed. These results suggest that AT1A signaling plays a critical role in tumor metastasis through P-selectin-mediated interactions of platelets with tumor and endothelial cells and through the AT1A signaling-dependent production of VEGF and SDF-1, which may be involved in mobilization of CXCR4+VEGFR1+ cells. © 2013 American Society for Investigative Pathology.

    DOI: 10.1016/j.ajpath.2012.10.026

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  • Thromboxane A2 receptor signaling facilitates tumor colonization through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells 査読

    Yoshio Matsui, Hideki Amano, Yoshiya Ito, Koji Eshima, Tastunori Suzuki, Fumihiro Ogawa, Akira Iyoda, Yukitoshi Satoh, Shintaro Kato, Masaki Nakamura, Hidero Kitasato, Shuh Narumiya, Masataka Majima

    Cancer Science   103 ( 4 )   700 - 707   2012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:Wiley  

    Thromboxane A2 (TXA2) is a prostanoid formed by thromboxane synthase using the cyclooxygenase product, prostaglandin H(2), as the substrate. TXA2 was shown to enhance tumor metastasis, but the underlying mechanism remains unclear. B16F1 melanoma cells were intravenously injected into TXA2 receptor (TP) knockout mice (TP-/-) and wild-type littermates (WT). TP-/- showed a reduction in B16F1 lung colonization and mortality rate, which were associated with a decreased number of platelets. Platelet activation as assessed by P-selectin expression was suppressed in TP-/-. A selective P-selectin neutralizing antibody decreased the lung colonization in WT mice, but not in TP-/-. The expression of P-selectin glycoprotein ligand-1 in B16F1 and HUVEC were enhanced by treatment with U46619, a thromboxane analog. The plasma levels of vascular endothelial growth factor (VEGF) and stromal-derived factor (SDF)-1 were lower in TP-/-. In TP-/-, the mobilization of progenitor cells expressing CXCR4+VEGFR1+ from bone marrow and the recruitment of those cells to lung tissues were suppressed. These results suggest that TP signaling plays a critical role in tumor colonization through P-selectin-mediated interactions between platelets-tumor cells and tumor cells-endothelial cells through the TP signaling-dependent production of VEGF and SDF-1, which might be involved in the mobilization of VEGFR1+CXCR4+ cells. Blockade of TP signaling might be useful in the treatment of tumor metastasis. (Cancer Sci 2012; 103: 700707)

    DOI: 10.1111/j.1349-7006.2012.02200.x

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  • CIRCULATING TUMOR CELLS IN PERIPHERAL VENOUS BLOOD OF PRIMARY NON-SMALL CELL LUNG CANCER PATIENTS: DETECTION USING ADENOVIRUS GFP-LABELING

    Yukitoshi Satoh, Dai Ishii, Hirotsugu Yamazaki, Fumihiro Ogawa, Yoshio Matsui, Kazu Shiomi, Hideki Amano, Naomi Kurouzu, Hidenori Hara, Kenji Nezu, Akira Iyoda, Tomoya Fukui, Satoshi Igawa, Masato Katagiri, Noriyuki Masuda, Akinori Kawai, Jun Sato, Yukio Tsujino

    JOURNAL OF THORACIC ONCOLOGY   6 ( 6 )   S451 - S451   2011年6月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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  • Prediction of postoperative exacerbation of interstitial pneumonia in patients with lung cancer and interstitial lung disease 査読

    AKIRA IYODA, SHI-XU JIANG, HIDEKI AMANO, FUMIHIRO OGAWA, YOSHIO MATUI, NAOMI KUROUZU, HIDENORI HARA, KENJI NEZU, TETSUO MIKAMI, MAKOTO SAEGUSA, YUKITOSHI SATOH

    Experimental and Therapeutic Medicine   2 ( 6 )   1073 - 1076   2011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:Spandidos Publications  

    Postoperative exacerbation of interstitial pneumonia in patients with lung cancer and interstitial lung disease has emerged as a serious problem. Therefore, the risk factors for postoperative exacerbation of interstitial pneumonia in patients with interstitial lung disease must be identified. We analyzed 22 patients diagnosed as having lung cancer with interstitial lung disease who underwent surgical treatment at the Kitasato University Hospital. Among the patients with lung cancer and interstitial lung disease, 5 patients (22.7%) had postoperative exacerbation of interstitial pneumonia. The prognosis of the patients with postoperative exacerbation was significantly poorer than that of patients without. Patients with postoperative exacerbation had a significantly higher age (&gt;= 75 years) and a significantly lower frequency of postoperative administration of steroid than patients without postoperative exacerbation. Almost all patients with postoperative exacerbation underwent lobectomy, had elevated KL-6 levels in the serum pre-operatively, and had significantly advanced stages of disease. Of the 5 patients with postoperative exacerbation, 2 had a history of inflammation prior to their exacerbation: 1 had a common cold and the other pyothorax. In patients with lung cancer and interstitial lung disease, advanced age, advanced stage disease, no postoperative administration of steroid and a pre-operative episode of inflammation are all risk factors for postoperative exacerbation of interstitial pneumonia.

    DOI: 10.3892/etm.2011.342

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  • Thymic large cell neuroendocrine carcinoma: report of a resected case - a case report 査読

    Fumihiro Ogawa, Akira Iyoda, Hideki Amano, Kenji Nezu, Shi-Xu Jiang, Isao Okayasu, Yukitoshi Satoh

    Journal of Cardiothoracic Surgery   5 ( 1 )   2010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:Springer Science and Business Media {LLC}  

    Thymic large cell neuroendocrine carcinomas (LCNECs) are very rare. We here describe a case in which the tumor could be completely resected. A 55-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor found at a regular health check-up. The patient underwent an extended thymectomy of an invasive thymoma of Masaoka&apos;s stage II that had been suspected preoperatively. The tumor was located in the right lobe of the thymus and was completely resected. Final pathological diagnosis of the surgical specimen was thymic LCNEC. The patient underwent adjuvant chemotherapy with irinotecan and cisplatin in accordance with the diagnosis of a lung LCNEC, and is alive without recurrence or metastasis 16 months after surgery.

    DOI: 10.1186/1749-8090-5-115

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  • Roles of a prostaglandin E-type receptor, EP3, in upregulation of matrix metalloproteinase-9 and vascular endothelial growth factor during enhancement of tumor metastasis 査読

    Hideki Amano, Yoshiya Ito, Tastunori Suzuki, Shintaro Kato, Yoshio Matsui, Fumihiro Ogawa, Takahiko Murata, Yukihiko Sugimoto, Robert Senior, Hidero Kitasato, Izumi Hayashi, Yukitoshi Satoh, Shuh Narumiya, Masataka Majima

    CANCER SCIENCE   100 ( 12 )   2318 - 2324   2009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:WILEY-BLACKWELL PUBLISHING, INC  

    Cyclooxygenase (COX)-2 is known to correlate with poor cancer prognosis and to contribute to tumor metastasis. However, the precise mechanism of this phenomenon remains unknown. We have previously reported that host stromal prostaglandin E(2) (PGE(2))-prostaglandin E2 receptor (EP)3 signaling appears critical for tumor-associated angiogenesis and tumor growth. Here we tested whether the EP3 receptor has a critical role in tumor metastasis. Lewis lung carcinoma (LLC) cells were intravenously injected into WT mice and mice treated with the COX-2 inhibitor NS-398. The nonselective COX inhibitor aspirin reduced lung metastasis, but the COX-1 inhibitor SC560 did not. The expression of matrix metalloproteinases (MMP)-9 and vascular endothelial growth factor (VEGF)-A was suppressed in NS-398-treated mice compared with PBS-treated mice. Lungs containing LLC colonies were markedly reduced in EP3 receptor knockout (EP3-/-) mice compared with WT mice. The expression of MMP-9 and VEGF-A was downregulated in metastatic lungs of EP3-/- mice. An immunohistochemical study revealed that MMP-9-expressing endothelial cells were markedly reduced in EP3-/- mice compared with WT mice. When HUVEC were treated with agonists for EP1, EP2, EP3, or EP4, only the EP3 agonist enhanced MMP-9 expression. These results suggested that EP3 receptor signaling on endothelial cells is essential for the MMP-9 upregulation that enhances tumor metastasis and angiogenesis. An EP3 receptor antagonist may be useful to protect against tumor metastasis. (Cancer Sci 2009; 100: 2318-2324).

    DOI: 10.1111/j.1349-7006.2009.01322.x

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  • Thymic neuroblastoma with the syndrome of inappropriate secretion of antidiuretic hormone☆ 査読

    Fumihiro Ogawa, Hideki Amano, Akira Iyoda, Yukitoshi Satoh

    Interactive CardioVascular and Thoracic Surgery   9 ( 5 )   903 - 905   2009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 University Press ({OUP})  

    We describe a rare case of thymic neuroblastoma with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A 60-year-old male patient was admitted to our hospital for further examination and treatment of anterior mediastinal tumor found at a regular health check-up. On examination there was hyponatremia, decrease in plasma osmolarity and elevation of plasma antidiuretic hormone (ADH) level. Thus, he underwent total thymectomy under the diagnosis of thymoma with SIADH. The tumor was located in the right lobe of the thymus and the final diagnosis was thymic neuroblastoma. To our knowledge, this is the first reported case of thymic neuroblastoma in which production of ADH by tumor cells is demonstrated immunohistochemically. This case highlights the need to consider functional activity of thymic neuroblastoma and complete resection of the tumor is warranted for treatment.

    DOI: 10.1510/icvts.2009.210229

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  • Clinical report on a computer-controlled hand-actuated stapling system for general lung surgery: the first application in Japan 査読

    Yukitoshi Satoh, Yoshio Matsui, Fumihiro Ogawa, Hideki Amano, Hidenori Hara, Kenji Nezu, Akira Iyoda

    General Thoracic and Cardiovascular Surgery   57 ( 8 )   402 - 405   2009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:Springer Science and Business Media {LLC}  

    Objective. Computer-controlled stapling systems can improve lung tissue approximation during thoracic surgery. We report our experience with a handy system with computer-controlled placement of staples for lung resection in Japan. Methods. The iDrive system is the improved second version of the SurgAssist stapling system. It comprises a self-contained computer microprocessor and hand-held control unit combined with a digital loading unit (a power linear cutter with a blue or green cartridge) for use in open and minimally invasive thoracic surgery. The mounted control unit has two uses: (1) controlling accurate placement of the cartridge by orientating the tip of the rigid and curved shaft and (2) controlling the closure of the stapler and the firing. Each cartridge contains a programmed electronic device that triggers activation of the appropriate program in the self-contained microprocessor. The compression level on lung tissue is determined by the computer. Results. From March to October 2008, the iDrive system was used 53 times in a consecutive series of 39 patients during open thoracic lung surgery. There were 12 women and 27 men. The following procedures were performed: lobectomy, segmentectomy, and wedge resection. The power linear cutters were used for stapling lung parenchyma for wedge resection in 6 patients, bullectomy in 1, segmentectomy in 2, and fissure division in 33. There were no stapling failures and no complications related to the staplers. Conclusion. The new computer-controlled stapling system may be safe and efficient for lung parenchymal tissue resection during open thoracic surgery. © The Japanese Association for Thoracic Surgery 2009.

    DOI: 10.1007/s11748-009-0407-3

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書籍等出版物

  • 呼吸器診療エッセンシャル

    ( 担当: 分担執筆 範囲: 急性間質性肺炎,ARDS)

    南江堂  2024年4月  ( ISBN:9784524204946

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  • ICU輸液が見えるグリコカリックスアトラス

    小川史洋, 岡田英志, 富田弘之( 担当: 分担執筆 範囲: 微小血管と毛細血管)

    MEDICAL VIEW  2020年12月  ( ISBN:9784758317818

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講演・口頭発表等

  • 特定看護師の活躍に向けた課題―医師の立場から― 招待

    小川史洋, 大井康史, 竹内一郎

    第73回日本救急医学会関東地方会学術集会・第60回救急隊員学術研究会  2024年2月 

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    開催年月日: 2024年2月

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 急性呼吸窮迫症候群の喫煙・炎症因子関連分子メカニズムの解明と新規治療法の 確立~喫煙習慣は肺障害・ARDS を助長するか?~ 招待

    小川史洋

    第48回日本救急医学会総会・学術集会  2020年11月 

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    開催年月日: 2022年11月

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • COVID-19重症例の呼吸管理と感染対策 招待

    第42回日本呼吸療法医学会学術集会  2020年12月 

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    開催年月日: 2020年12月

    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 研究費申請書類の書き方 ~さぁ研究テーマが決まった。次は研究資金を獲得し よう~ 招待

    小川史洋, 竹内一郎

    第48回日本救急医学会総会・学術集会  2020年11月 

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    開催年月日: 2020年11月

    会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • Pre-metastatic niche形成における樹状細胞-PGE2-EP3 signaling,SDF-1/TGF-βの役割

    小川 史洋

    第35回日本炎症・再生医学会  2014年7月 

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    記述言語:日本語   会議種別:ポスター発表  

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  • 肺癌リンパ節転移およびpremetastatic niche形成におけるプロスタグランジンの役割.

    小川 史洋

    第38回日本リンパ学会総会  2014年6月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

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  • Suppression of KRAS Expression in Normal Airway Basal Cells Shifts Differentiation of Squamous/EMT Phenotype. 国際会議

    小川 史洋

    American Thoracic Society 2016  2016年5月 

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    記述言語:英語   会議種別:ポスター発表  

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  • CLINICAL APPLICABILITY OF LUNG AGE FOR POSTOPERATIVE COMPLICATIONS IN NON-SMALL CELL LUNG CANCER PATIENTS MORE THAN 70-YEARS UNDERWENT CURATIVE RESECTION. 国際会議

    小川 史洋

    ASCVTS2013  2013年4月 

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    記述言語:英語   会議種別:口頭発表(一般)  

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  • COX-2-derived PGE2 forms SDF-1-expressing premetastatic niche via EP3 signaling in mediastinal lymph node with accumulation of immature dendritic cells. 国際会議

    小川 史洋

    American Thoracic Society  2013年5月 

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    記述言語:英語   会議種別:ポスター発表  

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  • 縦隔リンパ節内premetastatic niche形成における樹状細胞-PGE2-EP3シグナリングの役割.

    小川 史洋

    第113回日本外科学会  2013年4月 

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    記述言語:日本語   会議種別:ポスター発表  

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  • Src Activation is Critical for KRAS-dependent Regulation of Human Airway Basal Cell Differentiation into Secretory and Ciliated Cells. 国際会議

    小川 史洋

    American Thoracic Society 2018  2018年5月 

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    記述言語:英語   会議種別:ポスター発表  

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  • Function of KRAS in Regulating Differentiation of Normal Human Airway Basal Cells into a Mucociliated Epithelium. 国際会議

    小川 史洋

    American Thoracic Society 2017  2017年5月 

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    記述言語:英語   会議種別:ポスター発表  

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  • A Case Report: Heparin Free Veno-Venous Extracorporeal Membrane Oxygenation for Severe Blunt Thoracic Trauma.

    小川 史洋

    日本呼吸器外科学会総会  2019年5月 

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    記述言語:英語   会議種別:ポスター発表  

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受賞

  • 神奈川県病院学会優秀演題賞

    2024年9月  

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  • 2017 Raymond Sekiguchi MD JMSA Scholarship

    2017年4月   米国日本人医師会ニューヨーク  

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  • 若手奨励賞

    2016年12月   日本肺癌学会  

    小川 史洋

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  • 第18回黒川正治学術奨励賞

    2015年10月   北里大学医学部  

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  • 日本炎症再生医学会奨励賞

    2015年7月   日本炎症再生医学会  

    小川 史洋

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  • Jo Rae Wright Award

    2014年5月   米国呼吸器病学会   Jo Rae Wright Award

    小川 史洋

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  • 第24回北里大学同窓会研究奨励賞

    2014年5月   北里大学同窓会  

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共同研究・競争的資金等の研究課題

  • ARDSの喫煙・炎症因子関連分子メカニズムの解明と新規治療法の確立

    研究課題/領域番号:23K08445  2023年4月 - 2026年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    小川 史洋

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

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  • インターフェロン制御因子5を標的とした急性呼吸窮迫症候群の分子標的治療の開発

    研究課題/領域番号:21K09025  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    竹内 一郎, 西井 基継, 田村 智彦, 小川 史洋

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

    Lipopolysaccharide (LPS)誘発ARDS 動物モデルの作成:これまでに、6-8 週齢(体重20~22g)の雄性C57BL6J マウスを用いて経気道的リポポリサッカライド(LPS)誘発ARDS マウスモデルを作成した。吸入麻酔下で腹側頸部に約5mm の縦皮膚切開を置き、気管露出し、シリンジにてコントロール群は100μl PBS, 実験群はE.coli O111 抗原由来LPS 200μg/100μl PBS を経気道的に注入し、皮膚を閉創し48時間飼育したのちに病理学的に評価した。現在、LPS 誘発ARDS モデルを用いてIRF5 の病態的意義を検討している。

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  • Single-Cell RNA sequenceによるARDS病態の網羅的探索

    研究課題/領域番号:21K09026  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    本澤 大志, 西井 基継, 谷口 隼人, 田村 智彦, 小川 史洋, 竹内 一郎

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

    我々は、気管支肺胞洗浄液血球および末梢血単核球の表現型を分子生物学的に解析することでこれまでにないARDSの新たな病態分子を明らかとすべく本研究を企図した。現時点でARDS症例について16例の検体を収集することに成功し、気管支肺胞洗浄液と末梢血について細胞の保存やRNAの抽出を進めている。その純度および量において安定的に獲得できており、single cell-RNA sequenceを施行する準備を予定どおり進めている。

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  • 新型コロナウイルス 感染症による肺炎を含む急性呼吸窮迫症候群(ARDS)の喫煙・炎症因子関連分子メカニズムの解明と新規治療法の確立

    2020年8月 - 2021年7月

    公益財団法人 横浜学術教育振興財団  公益財団法人横浜学術教育振興財団 研究助成金 

    小川史洋

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    担当区分:研究代表者 

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  • ARDSの喫煙・炎症因子関連分子メカニズムの解明と新規治療法の確立

    研究課題/領域番号:23K08445  2019年4月 - 2022年3月

    日本学術振興会  科学研究費  基盤研究(C)

    小川 史洋

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    担当区分:研究代表者  資金種別:競争的資金

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  • 急性呼吸窮迫症候群(ARDS)の喫煙・炎症因子関連分子メカニズムの解明と新規治療法の確立

    2019年4月 - 2022年3月

    公益財団法人喫煙科学研究財団  2019年度公益財団法人喫煙科学研究財団研究助成 若手助成 

    小川 史洋

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    担当区分:研究代表者  資金種別:競争的資金

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  • 活動性心筋炎による難治性重症心不全に対する新たな治療法の開発

    研究課題/領域番号:18K08922  2018年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    竹内 一郎, 内山 宗人, 西井 基継, 安部 猛, 小川 史洋

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

    背景:活動性心筋炎を基盤とした拡張型心筋症は難治性急性心不全を引き起こし、人工心肺および心移植を必要とする。故に、その治療は世界的課題となっている。病態進展の主要な機序としてウイルス感染後自己免疫応答が考えられている。本検討では、この一連の免疫過程を制御できる治療標的として転写因子インターフェロン制御因子 (IRF)ファミリーに注目した。目的:IRFの拡張型心筋症における治療標的としての意義を明らかとする。研究計画および結果:心筋ミオシン免疫により作成したマウス自己免疫性心筋炎心筋症を用いて、IRFタンパク発現を解析した結果、IRF-7およびIRF-9発現はそのリン酸を含め有意な変動を示さなかった。また、IRF-3発現はそのリン酸化も含めて、ミオシン免疫拡張型心筋症期において低下していた一方、IRF-5発現が心筋炎活動期から心筋症期にかけて持続的に増加していた。さらに、免疫染色にて、心筋組織浸潤免疫細胞においてIRF-5の発現が認められ、特に樹状細胞核内のIRF-5が同定された。心筋症の進展おいてTh17 T細胞が重要な役割を果たしていることが知られており、樹状細胞はTh17活性を制御することが報告されている。本モデルにおいても、ミオシン免疫心筋組織においてIRF-5と共にTh17転写因子の発現が認められた。したがって、IRF-5シグナルの心筋炎後心筋症進展における病原的な役割が推測された。これらの結果に基づいて、現在マウス遺伝子背景をバッククロスしたIRF-5 total 遺伝子欠損マウスおよびcre-loxp systemを用いて、IRF-5 loxpとCD11c creマウスの交配により樹状細胞選択的IRF5遺伝子欠損マウスを作成している。今後はこれらの遺伝子改変マウスを用いて、心筋炎心筋症におけるIRF-5の機能的役割を分子免疫学的および病理形態学的に検討する。

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  • 肺癌個別化医療を目指した肺癌再発予測診断システムの構築

    研究課題/領域番号:21591822  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)  基盤研究(C)

    伊豫田 明, 佐藤 之俊, 天野 英樹, 根津 賢司, 小川 史洋

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

    13例の大細胞神経内分泌癌(以下LCNEC)に関して、分子標的治療となるマーカーの遺伝子変異、蛋白発現解析を行った。c-kit、EGFR、K-rasに関しては遺伝子変異、c-KIT、HER-2、VEGFについては免疫染色により蛋白発現、さらにEGFRとHER2に関してはFISH法による遺伝子発現を解析して、その結果を腺癌症例14例と比較検討した。結果としてVEGFの発現はLCNEC症例で全例認められた。HER2の発現は腺癌症例においてHER2スコア1+の発現が多くみられたが、HER2スコア2+以上の過剰発現についてはLCNEC症例の2例にのみ認められた。EGFR遺伝子変異は、腺癌症例において有意に高頻度に存在しており、LCNEC症例では1例(exon18)しか認められなかった。LCNEC症例では、c-KITの発現を76.9%に認め、腺癌症例と比較して有意に高頻度であったが、c-kit遺伝子変異は認められなかった。LCNEC症例では、VEGF発現とc-KIT発現が高頻度で、一部の症例ではHER2の高発現が認められることから、VEGF、c-KITやHER2を標的とした治療が有効な可能性がある。

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担当経験のある科目(授業)

  • 救急医学

    2018年4月 - 現在 機関名:横浜市立大学

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  • 呼吸器外科学

    機関名:北里大学医学部, 癌研究会有明病院

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  • 外科

    機関名:独立行政法人国立病院機構 相模原病院病院

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