Updated on 2023/06/21

写真a

 
NAKAGAMA YU
 
Organization
Graduate School of Medicine Department of Basic Medical Science Associate Professor
School of Medicine Department of Medical Science
Title
Associate Professor
Affiliation
Institute of Medicine
Affiliation campus
Abeno Campus

Position

  • Graduate School of Medicine Department of Basic Medical Science 

    Associate Professor  2022.10 - Now

  • Graduate School of Medicine Department of Basic Medical Science 

    Lecturer  2022.04 - 2022.09

  • School of Medicine Department of Medical Science 

    Associate Professor  2022.10 - Now

  • School of Medicine Department of Medical Science 

    Lecturer  2022.04 - 2022.09

Degree

  • Doctor of Philosophy (Medicine) ( The University of Tokyo ) (   The University of Tokyo )

Research Areas

  • Life Science / Embryonic medicine and pediatrics

  • Life Science / Cardiology

  • Life Science / Parasitology

Research Interests

  • グローバルヘルス

  • 心臓病学

  • 小児科学

  • 寄生虫学

Professional Memberships

  • 日本熱帯医学会

    2019.10 - Now

  • 日本臨床薬理学会

    2019.08 - Now

  • 日本寄生虫学会

    2019.01 - Now

  • 日本小児遺伝学会

    2018.09 - Now

  • 国際心臓研究学会

    2015.09 - Now

  • 日本小児循環器学会

    2011.07 - Now

  • 日本小児科学会

    2010.04 - Now

▼display all

Committee Memberships (off-campus)

  • 学術委員会   日本小児科学会  

    2020 - Now 

  • Echocardiography Writing Group on Chagas Disease   World Heart Federation  

    2021 - Now 

Awards

▼display all

Job Career (off-campus)

  • 大阪市立大学大学院 医学研究科

    2019.04 - Now

Education

  • The University of Tokyo   Doctor's Course   Graduated/Completed

    2015.04 - 2019.03

  • The University of Tokyo   School of Medicine   Bachelor's Course   Graduated/Completed

    2002.04 - 2008.03

Papers

  • Nitric Oxide Derived from Cytoglobin-Deficient Hepatic Stellate Cells Causes Suppression of Cytochrome c Oxidase Activity in Hepatocytes

    Okina Y.

    Antioxidants and Redox Signaling   38 ( 7-9 )   463 - 479   2023.03( ISSN:15230864

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  • Successful treatment of proven coronavirus disease 2019-associated pulmonary aspergillosis with liposomal amphotericin B in a patient with bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation(タイトル和訳中)

    Nakaya Yosuke, Nakashima Yasuhiro, Harada Naonori, Yamada Koichi, Makuuchi Yosuke, Kuno Masatomo, Takakuwa Teruhito, Okamura Hiroshi, Nanno Satoru, Nishimoto Mitsutaka, Koh Hideo, Nakagama Yu, Kido Yasutoshi, Kanno Takayuki, Suzuki Tadaki, Nakamae Hirohisa, Kakeya Hiroshi, Hino Masayuki

    Journal of Infection and Chemotherapy   29 ( 2 )   223 - 227   2023.02( ISSN:1341-321X

  • Successful treatment of proven coronavirus disease 2019-associated pulmonary aspergillosis with liposomal amphotericin B in a patient with bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation

    Nakaya Y.

    Journal of Infection and Chemotherapy   29 ( 2 )   223 - 227   2023.02( ISSN:1341321X

  • Age-adjusted impact of prior COVID-19 on SARS-CoV-2 mRNA vaccine response

    Nakagama S.

    Frontiers in Immunology   14   1087473   2023.01

  • Patients with B-cell malignancies experience reduced antibody responses with class switching defect following BNT162b2 SARS-CoV-2 vaccination

    Nakagama Y.

    Journal of Infection and Chemotherapy   29 ( 1 )   112 - 114   2023.01( ISSN:1341321X

  • クラススイッチ異常を有するB細胞性腫瘍患者はSARS-CoV-2 BNT162b2ワクチン接種後に抗体応答減少を経験する(Patients with B-cell malignancies experience reduced antibody responses with class switching defect following BNT162b2 SARS-CoV-2 vaccination)

    Nakagama Yu, Chi Sung-Gi, Minami Yosuke, Watanabe Reiko, Yamagishi Michiteru, Uno Atsuko, Kido Yasutoshi

    Journal of Infection and Chemotherapy   29 ( 1 )   112 - 114   2023.01( ISSN:1341-321X

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    B細胞標的治療を受けたリンパ球系腫瘍患者におけるSARS-CoV-2ワクチンの免疫原性を前向きに監視した。2回目のBNT162b2 mRNAワクチン接種を受けた参加者から血清を採取し、抗スパイクIgGとIgAの抗体陽転率と抗体保有率を調べた。リンパ腫/白血病の患者12例中11例はリツキシマブを含むレジメン(RTX)、1例はブルトン型チロシンキナーゼ阻害薬(BTKi)によるB細胞標的療法を受けた。RTX/BTKi治療群は他のリンパ球系腫瘍患者(他群、n=5)と比べて有意に減弱した抗スパイク抗体を示した。RTX/BTKi群と他群の間の幾何平均抗スパイクIgG抗体価には280倍の差があった。RTX/BTKi群のIgG抗体陽転率33%(4/12)は他群の100%(5/5)より有意に低かった。更に、他群のIgG抗体保有率が20%(1/5)であったのに対してRTX/BTKi群では0%(0/12)であった。RTX/BTKi群のIgA抗体陽転率が8%(1/12)まで減少したことから、RTX/BTKi曝露患者におけるIgGからIgAへのクラススイッチ異常が示唆された。直近のRTX/BTKi投与からワクチン接種までの期間中央値は5.3ヵ月であった。ワクチン接種時にRTX/BTKi群で推奨リンパ球数を超えたのは抗体陽転者が75%(3/4)、非抗体陽転者は63%(5/8)であった。

  • WHF Recommendations for the Use of Echocardiography in Chagas Disease.

    Ralston K, Zaidel E, Acquatella H, Barbosa MM, Narula J, Nakagama Y, Molina GR, Sliwa K, Zamorano JL, Pinto FJ, Piñeiro DJ, Corneli M

    Global heart   18 ( 1 )   27   2023( ISSN:2211-8160

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  • Antibody avidity maturation, following recovery from infection or the booster vaccination, grants breadth in SARS-CoV-2 neutralizing capacity.

    Yu Nakagama, Katherine Candray, Natsuko Kaku, Yuko Komase, Maria-Virginia Rodriguez-Funes, Rhina Dominguez, Tomoya Tsuchida, Hiroyuki Kunishima, Etsuko Nagai, Eisuke Adachi, Dieudonné Mumba Ngoyi, Mari Yamasue, Kosaku Komiya, Kazufumi Hiramatsu, Naoto Uemura, Yuki Sugiura, Mayo Yasugi, Yuka Yamagishi, Hiroshige Mikamo, Satoshi Shiraishi, Takehiro Izumo, Sachie Nakagama, Chihiro Watanabe, Yuko Nitahara, Evariste Tshibangu-Kabamba, Hiroshi Kakeya, Yasutoshi Kido

    The Journal of infectious diseases   227 ( 6 )   780 - 787   2022.12( ISSN:0022-1899

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    BACKGROUND: Cross-neutralizing capacity of antibodies against SARS-CoV-2 variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. METHODS: Sera from SARS-CoV-2 convalescents at 2-, 6-, or 10-months post-recovery, and BNT162b2 vaccine recipients at 3- or 25-weeks post-vaccination, were analyzed. Anti-spike IgG avidity was measured on urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. RESULTS: Compared with early-convalescence, avidity indices of late-convalescent sera were significantly higher (median 37.7 (interquartile range 28.4-45.1) vs. 64.9 (57.5-71.5), p < 0.0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman's r = 0.49 vs. 0.67 (wild-type); 0.18-0.52 vs. 0.48-0.83 (variants)). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (p < 0.001 (Alpha); p < 0.01 (Delta and Omicron)). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week-25. CONCLUSIONS: Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the two building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

    DOI: 10.1093/infdis/jiac492

    PubMed

  • Re-emerging threat of Trypanosoma cruzi vector transmission in El Salvador, update from 2018 to 2020

    Rodríguez M.S.

    Infectious Diseases of Poverty   11 ( 1 )   89   2022.12( ISSN:20955162

  • 唾液カチオン性蛋白質によるACE2受容体のクローキングはSARS-CoV-2の侵入を阻止する(Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry)

    Yoshizato Katsutoshi, Taira Toshio, Sato-Matsubara Misako, Sekiguchi Shizuko, Yabunaka Yoriko, Kira Yukimi, Ohashi Tetsu, Daikoku Atsuko, Ofusa Ken, Kadono Chiho, Oikawa Daisuke, Matsubara Tsutomu, Nakagama Yu, Kido Yasutoshi, Tokunaga Fuminori, Ikeda Kazuo, Kaneko Akira, Kawada Norifumi

    The Journal of Biochemistry   172 ( 4 )   205 - 216   2022.10( ISSN:0021-924X

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    健康人の唾液蛋白質(SP)がアンジオテンシン変換酵素2(ACE2)に結合する能力を評価し、新型コロナウイルス(SARS-CoV-2)スパイク蛋白質S1(S1)受容体結合ドメインとACE2の間の結合に及ぼすSPの影響を測定した。SPはACE2に結合し、S1のACE2への結合を妨害し、S1-ACE2相互作用を阻害するカチオン性ヒストンH2Aと好中球エラスターゼを含む4種類のACE2結合性SPを同定した。ウシ胸腺ヒストン(CTH)もH2Aと同じく効果的に結合を阻害した。CTHはACE2発現宿主細胞へのSARS-CoV-2偽ウイルス性侵入を抑制した。ε-ポリ-L-リジンなどの合成ポリペプチドもS1-ACE2結合を妨害し、ACE2結合におけるSPの重要性が示された。以上より、正荷電のSPはACE2の負荷電表面をクローキングしてSARS-CoV-2の侵入に対する障壁になり、カチオン性ポリペプチドは新型コロナウイルス感染症に対する予防的・治療的手法になり得ると考えられた。

  • BNT162b2 COVID-19ワクチン接種後に温式自己免疫性溶血性貧血とIgM-M蛋白血症を発症した脾辺縁帯リンパ腫

    曽我部 信広, 久野 雅智, 中釜 悠, 幕内 陽介, 原田 尚憲, 高桑 輝人, 岡村 浩史, 廣瀬 朝生, 西本 光孝, 中嶋 康博, 康 秀男, 中前 美佳, 城戸 康年, 中前 博久, 日野 雅之

    臨床血液   63 ( 10 )   1379 - 1385   2022.10( ISSN:0485-1439

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    新型コロナウイルス(SARS-CoV-2)に対するmRNA COVID-19ワクチン接種後に自己免疫性血球減少を発症することが知られているが,成熟B細胞腫瘍患者のワクチン接種が腫瘍随伴症状へ与える影響を調べた報告はない。症例は71歳男性。数年前に成熟B細胞腫瘍を疑う症状があったが自然軽快し経過観察されていた。BNT162b2 mRNA COVID-19ワクチン2回目接種10日後に温式自己免疫性溶血性貧血を発症した。貧血はステロイドで改善したが,脾腫,IgM-M蛋白血症,腎障害が増悪した。診断・治療目的に脾臓摘出術を施行し,脾辺縁帯リンパ腫と診断され,M蛋白血症,腎障害は改善した。本症例でSARS-CoV-2特異的抗体の獲得は障害されていた。ワクチン接種後の非特異的な免疫賦活が,成熟B細胞腫瘍の腫瘍随伴症状を増悪させる可能性が示唆されたが,病態解明のためにさらなる症例集積が必要である。(著者抄録)

  • Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan

    Matsuura T.

    Vaccine   40 ( 38 )   5631 - 5640   2022.09( ISSN:0264410X

  • 今月の特集1 感染防御-免疫とワクチンの基本 ワクチン誘導免疫を評価する

    中釜 悠

    臨床検査   66 ( 8 )   924 - 931   2022.08( ISSN:04851420

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  • Detecting Waning Serological Response with Commercial Immunoassays: 18-Month Longitudinal Follow-up of Anti-SARS-CoV-2 Nucleocapsid Antibodies.

    Yu Nakagama, Yuko Komase, Natsuko Kaku, Yuko Nitahara, Evariste Tshibangu-Kabamba, Tomoyo Tominaga, Hiroko Tanaka, Tomoaki Yokoya, Minako Hosokawa, Yasutoshi Kido

    Microbiology spectrum   10 ( 4 )   e0098622   2022.07

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an important determinant of protection from reinfection and of postvaccine immune responses. Herein, we conducted a follow-up analysis of health care workers previously infected with coronavirus disease 2019 (COVID-19) with the aim of evaluating different immunoassays for their capability in detecting the waning anti-SARS-CoV-2 immune responses and accuracy in documenting past SARS-CoV-2 infections. We evaluated serum antinucleocapsid antibody levels in convalescent individuals following a 1.5-year interval from SARS-CoV-2 infection. Three different commercial immunoassays that qualitatively measure serum antibodies targeting the SARS-CoV-2 nucleocapsid protein, namely, the Abbott Architect SARS-CoV-2 IgG, the Euroimmun anti-SARS-CoV-2 NCP enzyme-linked immunosorbent assay (ELISA) IgG, and the Roche Elecsys anti-SARS-CoV-2, were tested for comparison of detectability. A total of 38 individuals consented to participating in this follow-up analysis. From assay to assay, seropositivity rate at 18 months from infection varied from lowest at 42% to highest at 92%. The Roche Elecsys immunoassay, dependent on the dual-antigen antibody detection method and tuned for the detection of high avidity antibodies, was most capable of accurately documenting past SARS-CoV-2 infections. Different immunoassays showed variable capability of determining previous infection status under waning antibody concentrations. Immunoassays with lower detection limits are to be selected, and adjusted thresholds are to be considered in order to maximize the tests' performance. IMPORTANCE Past SARS-CoV-2 infection is an important determinant of protection from reinfection and of postvaccine immune responses. Our results show that different immunoassays, by design, harbor variable capability of tracking SARS-CoV-2 infection under waning antibody concentrations. With each recovered patient standing at a unique time point along the decline curve of antibodies, precise estimation of COVID-19 cumulative incidence remains a challenge. Since future surveillance studies will be targeting more than ever heterogenous cohorts, selecting the appropriate immunoassay is crucial in order to assure reliable decisions about an individual's previous infection status.

    DOI: 10.1128/spectrum.00986-22

    PubMed

  • Title: Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry.

    Yoshizato K, Taira T, Sato-Matsubara M, Sekiguchi S, Yabunaka Y, Kira Y, Ohashi T, Daikoku A, Ofusa K, Kadono C, Oikawa D, Matsubara T, Nakagama Y, Kido Y, Tokunaga F, Ikeda K, Kaneko A, Kawada N

    Journal of biochemistry   172 ( 4 )   205 - 216   2022.07( ISSN:0021-924X

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  • Cumulative seroprevalence among healthcare workers after the first wave of the COVID-19 pandemic in El Salvador, Central America.

    Yu Nakagama, Maria-Virginia Rodriguez-Funes, Rhina Dominguez, Katherine-Sofia Candray-Medina, Naoto Uemura, Evariste Tshibangu-Kabamba, Yuko Nitahara, Natsuko Kaku, Akira Kaneko, Yasutoshi Kido

    Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases   28 ( 11 )   1508 - 1510   2022.06( ISSN:1198-743X

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    International / domestic magazine:International journal  

    DOI: 10.1016/j.cmi.2022.06.020

    PubMed

  • Low SARS-CoV-2 antibody titers may be associated with poor clinical outcomes for patients with severe COVID-19.

    Mumon Takita, Toru Yoshida, Tomoya Tsuchida, Yu Nakagama, Yasutoshi Kido, Shotaro Suzuki, Mitsuru Imamura, Kimito Kawahata, Goji Shimizu, Hideki Yoshida, Daiki Morikawa, Takeshi Kawaguchi, Shuichi Fujii, Jumpei Tsukuda, Takako Motohashi, Shigeki Fujitani

    Scientific reports   12 ( 1 )   9147 - 9147   2022.06

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    Recently, immune response to coronavirus disease (COVID-19) has attracted attention where an association between higher antibody titer and worsening disease severity has been reported. However, our experiences with severe COVID-19 patients with low antibody titers led to hypothesizing that suppressed humoral immune response may be associated with poorer prognosis in severe COVID19. In this study, antibody titers in severe COVID19 patients were measured at 7, 10, 12, and 14 days after onset. Patients were divided into survivors and non-survivors. SARS-CoV-2 IgM in survivors and non-survivors were 0.06 AU and 0.02 AU (P = 0.048) at 10 days, 0.1 AU and 0.03 AU (P = 0.02) at 12 days, and 0.17 AU and 0.06 AU (P = 0.02) at 14 days. IgG in survivors and non-survivors were 0.01 AU and 0.01 AU (P = 0.04) at 7 days, 0.42 AU and 0.01 AU (P = 0.04) at 12 days, and 0.42 AU and 0.01 AU (P = 0.02) at 14 days. Multivariate analysis showed better survival among patients with IgM positivity at 12 days (P = 0.04), IgG positivity at 12 days (P = 0.04), IgM positivity at 14 days (P = 0.008), and IgG positivity at 14 days (P = 0.005). In severe COVID-19, low antibody titers on days 12 and 14 after onset were associated with poorer prognosis.

    DOI: 10.1038/s41598-022-12834-w

    PubMed

  • Neutralizing Type I Interferon Autoantibodies in Japanese Patients With Severe COVID-19.

    Eto S, Nukui Y, Tsumura M, Nakagama Y, Kashimada K, Mizoguchi Y, Utsumi T, Taniguchi M, Sakura F, Noma K, Yoshida Y, Ohshimo S, Nagashima S, Okamoto K, Endo A, Imai K, Kanegane H, Ohnishi H, Hirata S, Sugiyama E, Shime N, Ito M, Ohge H, Kido Y, Bastard P, Casanova JL, Tanaka J, Morio T, Okada S

    Research square   2022.03

  • Inflammatory cardiomyopathy of possibly overlapping aetiology: a case posing treatment dilemma and potential association

    Nakagama S.

    ESC Heart Failure   9 ( 1 )   761 - 765   2022.02

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  • COVID-19重症化とI型インターフェロン中和抗体の保有状況との関連性の検討

    江藤 昌平, 津村 弥来, 永島 慎太郎, Bastard Paul, 岡本 圭祐, 鹿島田 健一, 遠藤 明史, 溝口 洋子, 田中 純子, 中釜 悠, 城戸 康年, 貫井 陽子, 今井 耕輔, 金兼 弘和, 森尾 友宏, Casanova Jean-Laurent, 岡田 賢

    日本小児科学会雑誌   126 ( 2 )   320 - 320   2022.02( ISSN:0001-6543

  • Neutralizing Type I Interferon Autoantibodies in Japanese Patients with Severe COVID-19

    Eto S.

    Journal of Clinical Immunology   42 ( 7 )   1360 - 1370   2022( ISSN:02719142

  • Antibody testing as the guide to our living with COVID-19

    KAKU Natsuko, NAKAGAMA Yu, NITAHARA Yuko, KIDO Yasutoshi

    Japanese Journal of Thrombosis and Hemostasis   33 ( 3 )   338 - 346   2022( ISSN:09157441

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  • Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study

    Nakashima K.

    Human Vaccines and Immunotherapeutics   18 ( 6 )   2140549   2022( ISSN:21645515

  • Warm autoimmune hemolytic anemia and IgM-monoclonal gammopathy following BNT162b2 COVID-19 vaccine in a patient with splenic marginal zone lymphoma

    SOGABE Nobuhiro, KUNO Masatomo, NAKAGAMA Yu, MAKUUCHI Yosuke, HARADA Naonori, TAKAKUWA Teruhito, OKAMURA Hiroshi, HIROSE Asao, NISHIMOTO Mitsutaka, NAKASHIMA Yasuhiro, KOH Hideo, NAKAMAE Mika, KIDO Yasutoshi, NAKAMAE Hirohisa, HINO Masayuki

    Rinsho Ketsueki   63 ( 10 )   1379 - 1385   2022( ISSN:04851439

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    <p>There is currently no evidence that a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine might be associated with the development of autoimmune hemolytic anemia or disease progression in patients with mature B-cell neoplasm. Our patient was a 71-year-old man with indolent mature B-cell neoplasm who had been monitored for many years without treatment. After receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine, he developed severe warm autoimmune hemolytic anemia. Although steroid therapy improved his anemia, he continued to develop IgM-monoclonal gammopathy, renal insufficiency, and splenomegaly. He was diagnosed with splenic marginal zone lymphoma after undergoing splenectomy. The splenectomy improved the patient’s symptoms. We assessed his SARS-CoV-2 specific antibody response, but the patient’s serologic response to the vaccine was impaired. In patients with mature B-cell neoplasm, a non-specific immune response after vaccination might be associated with paraneoplastic syndromes.</p>

    DOI: 10.11406/rinketsu.63.1379

    PubMed

  • Towards Deeper Phenotyping of the Dilated Cardiomyopathies in Children ― Where Are We Now, and Where Are We Heading? ―

    Nakagama Yu, Ito Masamichi

    Circulation Journal   86 ( 1 )   116 - 117   2021.12( ISSN:13469843

  • Discrepant Antigen-specific Antibody Responses Causing SARS-CoV-2 Persistence in a Patient Receiving B-cell-targeted Therapy with Rituximab

    Takakuwa Teruhito, Nakagama Yu, Yasugi Mayo, Maeda Toshiki, Matsuo Kenji, Kiritoshi Ayako, Deguchi Ryo, Hagawa Naohiro, Shibata Wataru, Oshima Kazuhiro, Yamamoto Katsumi, Uchida Kenichiro, Noda Tomohiro, Yamada Koichi, Nishimura Tetsuro, Yamamoto Hiromasa, Kido Yasutoshi, Hino Masayuki, Kakeya Hiroshi, Mizobata Yasumitsu

    Internal Medicine   60 ( 23 )   3827 - 3831   2021.12( ISSN:09182918

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    <p>A 73-year-old man previously treated with rituximab for his mucosa-associated lymphoid tissue lymphoma suffered a suboptimal humoral immune response against an acquired SARS-CoV-2 infection. A detailed serological description revealed discrepant antigen-specific humoral immune responses. The titer of spike-targeting, "viral-neutralizing" antibodies remained below the detection level, in contrast to the anti-nucleocapsid, "binding" antibody response, which was comparable in both magnitude and kinetics. Accordingly, viral neutralizability and clearance was delayed, leading to prolonged RNAemia and persistent pneumonia. The present case highlights the need to closely monitor this unique population of recipients of B-cell-targeted therapies for their neutralizing antibody responses against SARS-CoV-2. </p>

    DOI: 10.2169/internalmedicine.7884-21

    PubMed

    CiNii Article

  • A Dual-Antigen SARS-CoV-2 Serological Assay Reflects Antibody Avidity.

    Yu Nakagama, Yuko Nitahara, Natsuko Kaku, Evariste Tshibangu-Kabamba, Yasutoshi Kido

    Journal of clinical microbiology   60 ( 2 )   JCM0226221   2021.12( ISSN:00951137

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    International / domestic magazine:International journal  

    Serial antibody measurements using an array of SARS-CoV-2 immunoassays have demonstrated differing kinetics among assay platforms (1).….

    DOI: 10.1128/JCM.02262-21

    PubMed

  • High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients

    Nitahara Y.

    Microbiology Spectrum   9 ( 3 )   e0096521   2021.12

  • Discrepant Antigen-specific Antibody Responses Causing SARS-CoV-2 Persistence in a Patient Receiving B-cell-targeted Therapy with Rituximab(和訳中)

    Takakuwa Teruhito, Nakagama Yu, Yasugi Mayo, Maeda Toshiki, Matsuo Kenji, Kiritoshi Ayako, Deguchi Ryo, Hagawa Naohiro, Shibata Wataru, Oshima Kazuhiro, Yamamoto Katsumi, Uchida Kenichiro, Noda Tomohiro, Yamada Koichi, Nishimura Tetsuro, Yamamoto Hiromasa, Kido Yasutoshi, Hino Masayuki, Kakeya Hiroshi, Mizobata Yasumitsu

    Internal Medicine   60 ( 23 )   3827 - 3831   2021.12( ISSN:0918-2918

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    症例は73歳男性で、食道の粘膜関連リンパ組織リンパ腫と診断され、リツキシマブを8回投与後、局所照射を行った。最終リツキシマブ投与の12週後、発熱と呼吸症状が出現し、SARS-CoV-2陽性が判明した。呼吸検体だけでなく血清もSARS-CoV-2陽性であったことから、SARS-CoV-2播種によるRNA血症が示唆された。胸部CT所見から、新型コロナウイルス感染症(COVID-19)H型が示唆された。重度呼吸障害のために機械的換気を行い、ファビピラビルとクロロキンによる併用療法を行ったが、明らかな有効性は得られなかった。高用量メチルプレドニゾロンにより換気パラメータが軽度に改善したが、一過性であった。イベルメクチン単回投与を行ったが、発症24日目の喀痰PCRは、依然としてSARS-CoV-2陽性であった。発症25日目の血清SARS-CoV-2特異的抗体検査では矛盾した結果が得られ、スパイク標的ウイルス中和抗体は検出レベル未満であったが、抗ヌクレオカプシド結合抗体の程度と動態は他の免疫正常重度COVID-19患者と同等であった。発症29日目、酸素化不良により死亡した。

  • 新興感染症:新型コロナウイルスに即応する生化学〜診断・治療・疫学への越境 COVID-19 mRNAワクチン接種者におけるSARS-CoV-2スパイクタンパク質受容体結合ドメインの高解像度線形エピトープマッピング解析

    仁田原 裕子, 中釜 悠, 加来 奈津子, Tshibangu-Kabamba Evariste, 金子 明, 安木 真世, 城戸 康年

    日本生化学会大会プログラム・講演要旨集   94回   [1S10a - 03]   2021.11

  • Serological Testing Reveals the Hidden COVID-19 Burden among Health Care Workers Experiencing a SARS-CoV-2 Nosocomial Outbreak.

    Yu Nakagama, Yuko Komase, Katherine Candray, Sachie Nakagama, Fumiaki Sano, Tomoya Tsuchida, Hiroyuki Kunishima, Takumi Imai, Ayumi Shintani, Yuko Nitahara, Natsuko Kaku, Yasutoshi Kido

    Microbiology spectrum   9 ( 2 )   e0108221   2021.09

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    We describe the results of testing health care workers, from a tertiary care hospital in Japan that had experienced a coronavirus disease 2019 (COVID-19) outbreak during the first peak of the pandemic, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing revealed that a surprising 42% of overlooked COVID-19 diagnoses (27/64 cases) occurred when case detection relied solely on SARS-CoV-2 nucleic acid amplification testing (NAAT). Our results suggest that the NAAT-positive population is only the tip of the iceberg and the portion left undetected might potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures (i.e., noninvasive ventilation and airway suctioning) having mediated transmission and served as the origins of the outbreak. Our observations are supportive of a multitiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum. IMPORTANCE We describe the results of testing frontline health care workers, from a hospital in Japan that had experienced a COVID-19 outbreak, for SARS-CoV-2-specific antibodies. Antibody testing revealed that a surprising 42% of overlooked COVID-19 diagnoses occurred when case detection relied solely on PCR-based viral detection. COVID-19 clusters have been continuously striking the health care system around the globe. Our findings illustrate that such clusters are lined with hidden infections eluding detection with diagnostic PCR and that the cluster burden in total is more immense than actually recognized. The mainstays of diagnosing infectious diseases, including COVID-19, generally consist of two approaches, one aiming to detect molecular fragments of the invading pathogen and the other to measure immune responses of the host. Considering antibody testing as one trustworthy option to test our way through the pandemic can aid in the exhaustive case detection of COVID-19 patients with variable presentations.

    DOI: 10.1128/Spectrum.01082-21

    PubMed

  • Physical health complaints among healthcare workers engaged in the care of critically ill COVID-19 patients: A single tertiary-care center prospective study from Japan

    Namikawa H.

    Journal of Infection and Public Health   14 ( 9 )   1263 - 1267   2021.09( ISSN:18760341

  • 嗅覚障害患者におけるSARS-CoV-2の感染状況

    河相 裕子, 寺西 裕一, 橋本 孝佑, 吉田 充裕, 角南 貴司子, 城戸 康年, 中釜 悠

    日本鼻科学会会誌   60 ( 3 )   358 - 358   2021.09( ISSN:0910-9153

  • Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

    Bastard P.

    Science Immunology   6 ( 62 )   2021.08

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  • X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

    Asano T.

    Science Immunology   6 ( 62 )   2021.08

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  • Back to normal; serological testing for COVID-19 diagnosis unveils missed infections.

    Tomoya Tsuchida, Yuko Nitahara, Shotaro Suzuki, Yuko Komase, Katherine Candray, Yasutoshi Kido, Yu Nakagama, Yukitaka Yamasaki, Mitsuru Imamura, Kimito Kawahata, Hiroyuki Kunishima, Shigeki Fujitani, Masamichi Mineshita, Takahide Matsuda

    Journal of medical virology   93 ( 7 )   4549 - 4552   2021.07( ISSN:01466615

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    BACKGROUND: The gold standard for coronavirus disease (COVID-19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID-19 may offer advantages in detecting possibly overlooked infections by NAAT. METHODS: To evaluate seroconversion of NAAT-negative pneumonia patients, immunoglobulin M (IgM) and IgG targeting the spike protein of SARS-CoV-2 were semiquantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein. RESULTS: Eight suspected but unconfirmed COVID-19 pneumonia patients (median age, 39 years; range, 21-55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2-27 days). None of them had tested positive for SARS-CoV-2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS-CoV-2. The median period between onset and blood sampling was 26.5 days (7-51 days). CONCLUSION: Eight patients with COVID-19 pneumonia, initially tested negative for SARS-CoV-2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multitiered diagnostic algorithm for COVID-19.

    DOI: 10.1002/jmv.26949

    PubMed

  • COVID-19患者の従事者に対する身体的健康管理の取り組み

    並川 浩己, 栩野 吉弘, 岡田 明子, 太田 恵子, 岡田 恵代, 藤岡 一也, 山田 康一, 渡辺 徹也, 中釜 悠, 城戸 康年, 竹本 恭彦, 溝端 康光, 掛屋 弘, 桑鶴 由美子, 柴田 利彦, 首藤 太一

    日本プライマリ・ケア連合学会学術大会   12回   np427 - np427   2021.05

  • Poor Myocardial Compaction in a Patient with Recessive <i>MYL2</i> Myopathy

    Tamamitsu Ayaka Monoi, Nakagama Yu, Domoto Yukako, Yoshida Kenichi, Ogawa Seishi, Hirono Keiichi, Shindo Takahiro, Ogawa Yosuke, Nakano Katsutoshi, Asakai Hiroko, Hirata Yoichiro, Matsui Hikoro, Inuzuka Ryo

    International Heart Journal   62 ( 2 )   445 - 447   2021.03( ISSN:13492365

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:Domestic journal  

    <p>Recessive mutations in the Myosin regulatory light chain 2 (<i>MYL2</i>) gene are the cause of an infantile-onset myopathy, associated with fatal myocardial disease of variable macromorphology. We here present the first Japanese family affected with recessive <i>MYL2</i> myopathy. Affected siblings manifested typical features and the proband's autopsy findings were compatible with the diagnosis of noncompaction cardiomyopathy. The rapidly progressive clinical course of this recessive <i>MYL2</i> cardiomyopathy highlights the crucial role of c-terminal tails in MYL2 protein in maintaining cardiac morphology and function.</p>

    DOI: 10.1536/ihj.20-639

    PubMed

    CiNii Article

  • MYL2遺伝子の劣性変異によるMYL2ミオパチー患者における心筋緻密化障害(Poor Myocardial Compaction in a Patient with Recessive MYL2 Myopathy)

    Monoi Tamamitsu Ayaka, Nakagama Yu, Domoto Yukako, Yoshida Kenichi, Ogawa Seishi, Hirono Keiichi, Shindo Takahiro, Ogawa Yosuke, Nakano Katsutoshi, Asakai Hiroko, Hirata Yoichiro, Matsui Hikoro, Inuzuka Ryo

    International Heart Journal   62 ( 2 )   445 - 447   2021.03( ISSN:1349-2365

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    症例は生後4ヵ月の女児で、ミオパチーの疑いで精査を目的に当院へ紹介された。生後1ヵ月に不規則な不随意運動が間歇的に出現し、神経学的検査で筋緊張低下を示唆するスカーフ徴候と踵耳徴候が陽性を呈した。顔面筋に異常はなかった。深部腱反射消失と定頸の遅れを認めた。臨床検査または骨格筋画像で異常は見られなかった。1ヵ月後の臨床検査で脳性ナトリウム利尿ペプチド(BNP)は149.2pg/mLであった。心エコー検査で左室駆出率は49%で、拡張不全を認めた。心電図で右脚ブロックを認めた。生後11ヵ月でBNPは5186pg/mLに増加し、左室駆出率は27%に低下した。心不全の増悪に対して集中治療管理を施行したが、治療の甲斐なく1ヵ月後に死亡した。遺伝学的検査でMYL2遺伝子の劣性変異(c.431_432del:p.P144Rfs*57)を認め、MYL2ミオパチーと診断した。姉も同様の遺伝子変異を有しており、生後8ヵ月で拡張型心筋症のため死亡していた。剖検で骨格筋にMYL2ミオパチーに典型的な所見を認めた。心臓は乳頭筋の形成が不明瞭で、肉柱層(NC)に比べて緻密層(C)が菲薄化しており、NC/Cは1.6であった。

  • Antibody response to SARS-CoV-2 in people living with HIV.

    Shinya Yamamoto, Makoto Saito, Etsuko Nagai, Keiko Toriuchi, Hiroyuki Nagai, Hiroshi Yotsuyanagi, Yu Nakagama, Yasutoshi Kido, Eisuke Adachi

    Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi   54 ( 1 )   144 - 146   2021.02( ISSN:16841182

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    International / domestic magazine:International journal  

    DOI: 10.1016/j.jmii.2020.09.005

    PubMed

  • Seroconversion against SARS-CoV-2 occurred after the recovery in patients with COVID-19.

    Shinya Yamamoto, Makoto Saito, Etsuko Nagai, Keiko Toriuchi, Hiroyuki Nagai, Hiroshi Yotsuyanagi, Yu Nakagama, Yasutoshi Kido, Eisuke Adachi

    Journal of medical virology   93 ( 2 )   692 - 694   2021.02( ISSN:01466615

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    International / domestic magazine:International journal  

    DOI: 10.1002/jmv.26495

    PubMed

  • Prevalence of SARS-CoV-2-Specific Antibodies, Japan, June 2020.

    Takashi Yoshiyama, Yasuki Saito, Kunitsugu Masuda, Yoshiko Nakanishi, Yasutoshi Kido, Kazuhiro Uchimura, Satoshi Mitarai, Tadaki Suzuki, Yu Nakagama, Hiroshi Kubota, Maki Satomi, Sana Uchikoba, Makoto Ohnishi, Takaji Wakita, Seiya Kato, Katsunobu Kato

    Emerging infectious diseases   27 ( 2 )   628 - 631   2021.02( ISSN:10806040

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    We used 2 commercially available antibody tests to estimate seroprevalence of severe acute respiratory syndrome coronavirus 2 infection in Japan during June 2020. Of 7,950 samples, 8 were positive by both assays. Using 2 reliable antibody tests in conjunction is an effective method for estimating seroprevalence in low prevalence settings.

    DOI: 10.3201/eid2702.204088

    PubMed

  • Noonan syndrome-associated biallelic LZTR1 mutations cause cardiac hypertrophy and vascular malformations in zebrafish. Reviewed

    Yu Nakagama, Norihiko Takeda, Seishi Ogawa, Hiroyuki Takeda, Yoshiyuki Furutani, Toshio Nakanishi, Tatsuyuki Sato, Yoichiro Hirata, Akira Oka, Ryo Inuzuka

    Molecular genetics & genomic medicine   8 ( 3 )   e1107   2020.03

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    BACKGROUND: Variants in the LZTR1 (leucine-zipper-like transcription regulator 1) gene (OMIM #600574) have been reported in recessive Noonan syndrome patients. In vivo evidence from animal models to support its causative role is lacking. METHODS: By CRISPR-Cas9 genome editing, we generated lztr1-mutated zebrafish (Danio rerio). Analyses of histopathology and downstream signaling were performed to investigate the pathogenesis of cardiac and extracardiac abnormalities in Noonan syndrome. RESULTS: A frameshift deletion allele was created in the zebrafish lztr1. Crosses of heterozygotes obtained homozygous lztr1 null mutants that modeled LZTR1 loss-of-function. Histological analyses of the model revealed ventricular hypertrophy, the deleterious signature of Noonan syndrome-associated cardiomyopathy. Further, assessment for extracardiac abnormalities documented multiple vascular malformations, resembling human vascular pathology caused by RAS/MAPK activation. Due to spatiotemporal regulation of LZTR1, its downstream function was not fully elucidated from western blots of adult tissue. CONCLUSION: Our novel zebrafish model phenocopied human recessive Noonan syndrome and supported the loss-of-function mechanism of disease-causing LZTR1 variants. The discovery of vascular malformations in mutants calls for the clinical follow-up of patients to monitor for its emergence. The model will serve as a novel platform for investigating the pathophysiology linking RAS/MAPK signaling to cardiac and vascular pathology.

    DOI: 10.1002/mgg3.1107

    PubMed

  • 日本由来梅毒(Treponema pallidum)のMulti Locus Sequencing Typing(MLST)法による分子疫学解析

    市村 裕菜, 安達 英輔, 古賀 道子, 菊地 正, 四柳 宏, 城戸 康年, 中釜 悠, 仁田原 裕子, 金子 明

    感染症学雑誌   94 ( 臨増 )   317 - 317   2020.03( ISSN:0387-5911

  • アフリカトリパノソーマ症治療薬開発に向けた、First in Human試験の立案・実施への取り組み

    中釜 悠, 城戸 康年, 仁田原 裕子, 中谷 大作, 北 潔, 上村 尚人

    臨床薬理   50 ( Suppl. )   S258 - S258   2019.11( ISSN:0388-1601

  • Therapeutic targeting of mitochondrial ROS ameliorates murine model of volume overload cardiomyopathy. Reviewed

    Kenichi Okamura, Yu Nakagama, Norihiko Takeda, Katsura Soma, Tatsuyuki Sato, Takayuki Isagawa, Yasutoshi Kido, Masaya Sakamoto, Ichiro Manabe, Yasutaka Hirata, Issei Komuro, Minoru Ono

    Journal of pharmacological sciences   141 ( 1 )   56 - 63   2019.09( ISSN:13478613

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:Domestic journal  

    Concomitant heart failure is associated with poor clinical outcome in dialysis patients. The arteriovenous shunt, created as vascular access for hemodialysis, increases ventricular volume-overload, predisposing patients to developing cardiac dysfunction. The integral function of mitochondrial respiration is critically important for the heart to cope with hemodynamic overload. The involvement, however, of mitochondrial activity or reactive oxygen species (ROS) in the pathogenesis of ventricular-overload-induced heart failure has not been fully elucidated. We herein report that disorganization of mitochondrial respiration increases mitochondrial ROS production in the volume-overloaded heart, leading to ventricular dysfunction. We adopted the murine arteriovenous fistula (AVF) model, which replicates the cardinal features of volume-overload-induced ventricular dysfunction. Enzymatic assays of cardiac mitochondria revealed that the activities of citrate synthase and NADH-quinone reductase (complex Ⅰ) were preserved in the AVF heart. In contrast, the activity of NADH oxidase supercomplex was significantly compromised, resulting in elevated ROS production. Importantly, the antioxidant N-acetylcysteine prevented the development of ventricular dilatation and cardiac dysfunction, suggesting a pathogenic role for ROS in dialysis-related cardiomyopathy. A cardioprotective effect was also observed in metformin-treated mice, illuminating its potential use in the management of heart failure complicating diabetic patients on dialysis.

    DOI: 10.1016/j.jphs.2019.09.005

    PubMed

  • 構造生物学から観た寄生適応の分子戦略 メタボローム解析による薬剤標的の評価とアフリカトリパノソーマ症に対する早期臨床開発

    城戸 康年, 杉浦 悠毅, 中釜 悠, 稲岡 健ダニエル, 志波 智生, 斎本 博之, 山本 雅一, 上村 尚人, 金子 明, 北 潔

    日本生化学会大会プログラム・講演要旨集   92回   [2S06m - 05]   2019.09

  • 哺乳動物の心臓の燃料としての乳酸(Lactate as a fuel for the mammalian heart)

    中釜 悠, 武田 憲彦, 城戸 康年, 佐藤 達之, 犬塚 亮, 小室 一成

    日本生化学会大会プログラム・講演要旨集   92回   [2T02m - 03]   2019.09

  • Volume overload心筋症マウスモデルにて、ミトコンドリアROSを治療ターゲットとすると改善する(Therapeutic targeting of mitochondrial ROS ameliorates murine model of volume overload cardiomyopathy)

    Okamura Kenichi, Nakagama Yu, Takeda Norihiko, Soma Katsura, Sato Tatsuyuki, Isagawa Takayuki, Kido Yasutoshi, Sakamoto Masaya, Manabe Ichiro, Hirata Yasutaka, Komuro Issei, Ono Minoru

    Journal of Pharmacological Sciences   141 ( 1 )   56 - 63   2019.09( ISSN:1347-8613

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    Volume overloadによる心室機能不全モデルを用いて、ミトコンドリア活性酸素種(ROS)産生の分子メカニズムとROSの機能について検討した。VOL誘発性心室機能障害の基本的特徴を再現した動静脈瘻(AVF)マウスモデルを用いた。心臓ミトコンドリアの酵素アッセイにて、クエン酸シンターゼ-NADH-キノンレダクターゼ(complex I)の活性がAVF心臓内では維持されていた。一方、NADHオキシダーゼ超複合体の活性は顕著に障害され、ROS産生が増加していた。また、抗酸化物質のN-アセチルシステインは心室拡張と心機能障害を予防したことから、透析関連心筋症におけるROSの役割が示唆された。心保護効果はメトフォルミン(MET)処置マウスでも観察され、透析糖尿病患者の複合的心不全の管理におけるMETの有用性が示された。

  • Cell Cycle Perturbation Induces Collagen Production in Fibroblasts

    Wake Masaki, Takeda Norihiko, Isagawa Takayuki, Sato Tatsuyuki, Nakagama Yu, Morioka Masaki Suimye, Hirota Yasushi, Asagiri Masataka, Maemura Koji, Manabe Ichiro, Tanabe Kazuaki, Komuro Issei

    International Heart Journal   60 ( 4 )   958 - 963   2019.07( ISSN:13492365

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:Domestic journal  

    <p>Myocardial infarction (MI) occurs when the heart muscle is severely damaged due to a decrease in blood flow from the coronary arteries. During recovery from an MI, cardiac fibroblasts become activated and produce extracellular matrices, contributing to the wound healing process in the damaged heart. Inappropriate activation of the fibroblasts leads to excessive fibrosis in the heart. However, the molecular pathways by which cardiac fibroblasts are activated have not yet been fully elucidated.</p><p>Here we show that serum deprivation, which recapitulates the cellular microenvironment of the MI area, strikingly induces collagen production in C3H/10T1/2 cells. Based on transcriptomic and pharmacological studies, we found that cell cycle perturbation is directly linked to collagen production in fibroblasts. Importantly, collagen synthesis is increased independently of the transcriptional levels of type I collagen genes. These results reveal a novel mode of fibroblast activation in the ischemic area, which will allow us to gain insights into the molecular mechanisms underlying cardiac fibrosis and establish a basis for anti-fibrotic therapy.</p>

    DOI: 10.1536/ihj.18-710

    PubMed

    CiNii Article

  • 細胞周期の攪乱は、線維芽細胞のコラーゲン産生を誘導する(Cell Cycle Perturbation Induces Collagen Production in Fibroblasts)

    Wake Masaki, Takeda Norihiko, Isagawa Takayuki, Sato Tatsuyuki, Nakagama Yu, Morioka Masaki Suimye, Hirota Yasushi, Asagiri Masataka, Maemura Koji, Manabe Ichiro, Tanabe Kazuaki, Komuro Issei

    International Heart Journal   60 ( 4 )   958 - 963   2019.07( ISSN:1349-2365

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    心臓線維芽細胞活性化の分子機序について検討した。マウス線維芽細胞系C3H/10T1/2を、心筋梗塞(MI)後の細胞微小環境を再現した血清枯渇下で培養し、細胞外マトリックス産生に影響する成長因子または栄養素欠乏の影響について検討した。血清枯渇状態では、当該細胞におけるコラーゲン産生が顕著に促進され、血清枯渇線維芽細胞上澄みのコラーゲン含量はTGF-βで刺激した線維芽細胞よりも多かった。また当該細胞の遺伝子発現プロファイルにおよぼす血清枯渇の役割を、トランスクリプトーム解析と遺伝子発現解析により検討した結果、血清枯渇環境では709遺伝子の転写物レベルが減少し、260遺伝子の転写物レベルが情報制御されていた。またサイクリンA2、B2、ゲミニン遺伝子を含む細胞周期関連遺伝子の転写物レベルは、血清枯渇環境で有意に減少していた。さらに当該細胞の細胞周期阻害によるコラーゲン産生の検討から、細胞周期の攪乱は線維芽細胞のコラーゲン産生に直接関連し、特にコラーゲン合成はI型コラーゲン遺伝子の転写レベルとは無関係に増加していることが示された。虚血領域における線維芽細胞活性化の新たな様式が明らかとなった。

  • Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M. Reviewed

    Hajime Abe, Norihiko Takeda, Takayuki Isagawa, Hiroaki Semba, Satoshi Nishimura, Masaki Suimye Morioka, Yu Nakagama, Tatsuyuki Sato, Katsura Soma, Katsuhiro Koyama, Masaki Wake, Manami Katoh, Masataka Asagiri, Michael L Neugent, Jung-Whan Kim, Christian Stockmann, Tomo Yonezawa, Ryo Inuzuka, Yasushi Hirota, Koji Maemura, Takeshi Yamashita, Kinya Otsu, Ichiro Manabe, Ryozo Nagai, Issei Komuro

    Nature communications   10 ( 1 )   2824 - 2824   2019.06

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    The fibrogenic response in tissue-resident fibroblasts is determined by the balance between activation and repression signals from the tissue microenvironment. While the molecular pathways by which transforming growth factor-1 (TGF-β1) activates pro-fibrogenic mechanisms have been extensively studied and are recognized critical during fibrosis development, the factors regulating TGF-β1 signaling are poorly understood. Here we show that macrophage hypoxia signaling suppresses excessive fibrosis in a heart via oncostatin-m (OSM) secretion. During cardiac remodeling, Ly6Chi monocytes/macrophages accumulate in hypoxic areas through a hypoxia-inducible factor (HIF)-1α dependent manner and suppresses cardiac fibroblast activation. As an underlying molecular mechanism, we identify OSM, part of the interleukin 6 cytokine family, as a HIF-1α target gene, which directly inhibits the TGF-β1 mediated activation of cardiac fibroblasts through extracellular signal-regulated kinase 1/2-dependent phosphorylation of the SMAD linker region. These results demonstrate that macrophage hypoxia signaling regulates fibroblast activation through OSM secretion in vivo.

    DOI: 10.1038/s41467-019-10859-w

    PubMed

  • Leaky splicing variant in sepiapterin reductase deficiency: Are milder cases escaping diagnosis? Reviewed

    Yu Nakagama, Kohei Hamanaka, Masakazu Mimaki, Haruo Shintaku, Satoko Miyatake, Naomichi Matsumoto, Koji Hirohata, Ryo Inuzuka, Akira Oka

    Neurology. Genetics   5 ( 2 )   e319   2019.04( ISSN:2376-7839

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    Publishing type:Research paper (scientific journal)   International / domestic magazine:International journal  

    DOI: 10.1212/NXG.0000000000000319

    PubMed

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Books and Other Publications

MISC

  • Usefulness of seasonal malaria chemoprevention in the Sahel

    Kalenda N.K.

    The Lancet Infectious Diseases   23 ( 3 )   269 - 270   2023.03( ISSN:14733099

  • Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan

    Tsuchida T.

    Clinical and Experimental Medicine   1 - 8   2023( ISSN:15918890

  • 【感染防御-免疫とワクチンの基本】ワクチン誘導免疫を評価する

    中釜 悠

    臨床検査   66 ( 8 )   924 - 931   2022.08( ISSN:0485-1420

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    <文献概要>Point ●ワクチンと免疫学的検査は両者が表裏一体となって,感染症に対するpharmaceuticalな(医薬品を用いた)対策の一翼を担う.●ワクチン接種後に獲得免疫の検査を行う目的は,ワクチンが目指すところの防御レベル抗体価が適正に構築されたかを評価することにある.●臨床検査室における免疫学的検査法が多様化するなか,測定結果の標準化(ハーモナイゼーション)はますます重要な課題となっている.

  • 新型コロナウイルス関連シリーズ 新型コロナウイルス感染症との共生社会への羅針盤 SARS-CoV-2抗体検査

    加来 奈津子, 中釜 悠, 仁田原 裕子, 城戸 康年

    日本血栓止血学会誌   33 ( 3 )   338 - 346   2022.06( ISSN:0915-7441

  • Longitudinal ventilatory ratio monitoring for COVID‑19: its potential in predicting severity and assessing treatment response

    Kaku N.

    Critical Care   25 ( 1 )   366   2021.12( ISSN:13648535

  • Towards Deeper Phenotyping of the Dilated Cardiomyopathies in Children: Where Are We Now, and Where Are We Heading?(和訳中)

    Nakagama Yu, Ito Masamichi

    Circulation Journal   86 ( 1 )   116 - 117   2021.12( ISSN:1346-9843

  • 新興感染症:新型コロナウイルスに即応する生化学〜診断・治療・疫学への越境 COVID-19 mRNAワクチン接種者におけるSARS-CoV-2スパイクタンパク質受容体結合ドメインの高解像度線形エピトープマッピング解析

    仁田原 裕子, 中釜 悠, 加来 奈津子, Tshibangu-Kabamba Evariste, 金子 明, 安木 真世, 城戸 康年

    日本生化学会大会プログラム・講演要旨集   94回   [1S10a - 03]   2021.11

  • 新興感染症:新型コロナウイルスに即応する生化学〜診断・治療・疫学への越境 唾液内生理活性物質の抗ウイルス効果

    松原 三佐子, 平 敏夫, 城戸 康年, 中釜 悠, 河田 則文, 吉里 勝利

    日本生化学会大会プログラム・講演要旨集   94回   [1S10a - 05]   2021.11

  • COVID-19患者の従事者に対する身体的健康管理の取り組み

    並川 浩己, 栩野 吉弘, 岡田 明子, 太田 恵子, 岡田 恵代, 藤岡 一也, 山田 康一, 渡辺 徹也, 中釜 悠, 城戸 康年, 竹本 恭彦, 溝端 康光, 掛屋 弘, 桑鶴 由美子, 柴田 利彦, 首藤 太一

    日本プライマリ・ケア連合学会学術大会   12回   np427 - np427   2021.05

  • Biochemical laboratory aspects of low-density, submicroscopic malaria infections(和訳中)

    Candray Katherine, 中釜 悠, 仁田原 裕子, Gitaka Jesse, Kongere James, Okomo Gordon, 加賀谷 渉, Chan Chim, 城戸 康年, 金子 明

    日本寄生虫学会・日本臨床寄生虫学会合同大会プログラム・抄録集   90回・32回   80 - 80   2021.04

  • シャーガス心筋症in vitroモデリングによる病態理解

    中釜 悠, Candray Katherine, 伊藤 正道, 仁田原 裕子, 金子 明, 嶋田 淳子, 城戸 康年

    日本寄生虫学会・日本臨床寄生虫学会合同大会プログラム・抄録集   90回・32回   81 - 81   2021.04

  • シアン耐性呼吸を標的とした抗トリパノソーマ症薬の早期臨床開発計画

    加来 奈津子, 中釜 悠, 仁田原 裕子, 道向 優, 稲岡 健ダニエル, 山本 雅一, 斎本 博之, 上村 尚人, 金子 明, 北 潔, 城戸 康年

    日本寄生虫学会・日本臨床寄生虫学会合同大会プログラム・抄録集   90回・32回   63 - 63   2021.04

  • エルサルバドル国におけるシャーガス病ベクターTriatoma dimidiataの血液供給源解析

    長原 優, Rodoriguez Stanley, 中釜 悠, 仁田原 裕子, Candry Katherine, 金子 明, 嶋田 淳子, 城戸 康年

    日本寄生虫学会・日本臨床寄生虫学会合同大会プログラム・抄録集   90回・32回   74 - 74   2021.04

  • Genetic characteristics of Trypanosoma cruzi in El Salvador(和訳中)

    仁田原 裕子, Rodriguez Stanley, 中釜 悠, Candray Katherine, 嶋田 淳子, 金子 明, 城戸 康年

    日本寄生虫学会・日本臨床寄生虫学会合同大会プログラム・抄録集   90回・32回   50 - 50   2021.04

  • COVID-19患者の従事者に対する身体的健康管理の取り組み

    並川 浩己, 栩野 吉弘, 山田 康一, 掛屋 弘, 岡田 明子, 太田 恵子, 岡田 恵代, 藤岡 一也, 渡辺 徹也, 中釜 悠, 城戸 康年, 竹本 恭彦, 溝端 康光, 柴田 利彦, 首藤 太一

    日本化学療法学会雑誌   69 ( 2 )   214 - 214   2021.03( ISSN:1340-7007 ( eISSN:1884-5886

  • COVID-19患者の従事者に対する身体的健康管理の取り組み

    並川 浩己, 栩野 吉弘, 山田 康一, 掛屋 弘, 岡田 明子, 太田 恵子, 岡田 恵代, 藤岡 一也, 渡辺 徹也, 中釜 悠, 城戸 康年, 竹本 恭彦, 溝端 康光, 柴田 利彦, 首藤 太一

    日本化学療法学会雑誌   69 ( 2 )   214 - 214   2021.03( ISSN:1340-7007 ( eISSN:1884-5886

  • エルサルバドルにおけるシャーガス病、2018年のデータベースに基づいた報告(CHAGAS DISEASE IN EL SALVADOR, A REPORT FROM 2018 DATABASE)

    カンドライ・カテリン, 中釜 悠, 仁田原 裕子, Portillo A, 金子 明, 嶋田 淳子, 城戸 康年

    日本小児循環器学会雑誌   36 ( Suppl.2 )   s2 - 320   2020.11( ISSN:0911-1794 ( eISSN:2187-2988

  • シャーガス慢性心筋炎の病態形成機構

    中釜 悠, 伊藤 正道, 仁田原 裕子, Candray Katherine, Rodriguez Stanley, 武田 憲彦, 嶋田 淳子, 金子 明, 城戸 康年

    日本小児循環器学会雑誌   36 ( Suppl.2 )   s2 - 218   2020.11( ISSN:0911-1794 ( eISSN:2187-2988

  • アカデミア創薬:独創的な創薬研究者達の挑戦 コンゴ民主共和国拠点での新興・再興感染症創薬

    城戸 康年, 中釜 悠, 上村 尚人, Mumba Dieudonne, Muyembe Jean-Jacques

    臨床薬理   51 ( Suppl. )   S244 - S244   2020.10( ISSN:0388-1601 ( eISSN:1882-8272

  • 新型コロナウィルス感染症血清学的診断法の臨床的有用性評価

    中釜 悠, 金子 明, 上村 尚人, 城戸 康年

    臨床薬理   51 ( Suppl. )   S289 - S289   2020.10( ISSN:0388-1601 ( eISSN:1882-8272

  • アフリカトリパノソーマ症治療薬開発に向けた、First in Human試験の立案・実施への取り組み

    中釜 悠, 城戸 康年, 仁田原 裕子, 中谷 大作, 北 潔, 上村 尚人

    臨床薬理   50 ( Suppl. )   S258 - S258   2019.11( ISSN:0388-1601 ( eISSN:1882-8272

  • グローバルヘルス課題克服にむけたコンゴ民主共和国におけるトランスレーショナルリサーチ拠点の形成

    城戸 康年, 中釜 悠, 仁田原 裕子, 北 潔, Mumba Dieudonne, Muyembe JeanJacques, 金子 明, 上村 尚人

    臨床薬理   50 ( Suppl. )   S258 - S258   2019.11( ISSN:0388-1601 ( eISSN:1882-8272

  • グローバルヘルス課題克服にむけたコンゴ民主共和国におけるトランスレーショナルリサーチ拠点の形成

    城戸 康年, 中釜 悠, 仁田原 裕子, 北 潔, Mumba Dieudonne, Muyembe JeanJacques, 金子 明, 上村 尚人

    臨床薬理   50 ( Suppl. )   S258 - S258   2019.11( ISSN:0388-1601 ( eISSN:1882-8272

  • L-dopa反応性のジストニアを呈し、遺伝子解析によりセピアプテリン還元酵素(SR)欠損症と診断した1例(第136回静岡地方会発表症例の続報)

    久世 崇史, 中釜 悠, 濱中 耕平, 新宅 治夫, 宮武 聡子, 松本 直通, 安藤 太郎, 高見澤 幸一, 入倉 朋也, 増井 礼子, 柏井 洋文, 清水 信隆, 三牧 正和

    日本小児科学会雑誌   123 ( 9 )   1450 - 1450   2019.09( ISSN:0001-6543

  • 構造生物学から観た寄生適応の分子戦略 メタボローム解析による薬剤標的の評価とアフリカトリパノソーマ症に対する早期臨床開発

    城戸 康年, 杉浦 悠毅, 中釜 悠, 稲岡 健ダニエル, 志波 智生, 斎本 博之, 山本 雅一, 上村 尚人, 金子 明, 北 潔

    日本生化学会大会プログラム・講演要旨集   92回   [2S06m - 05]   2019.09

  • 哺乳動物の心臓の燃料としての乳酸(Lactate as a fuel for the mammalian heart)

    中釜 悠, 武田 憲彦, 城戸 康年, 佐藤 達之, 犬塚 亮, 小室 一成

    日本生化学会大会プログラム・講演要旨集   92回   [2T02m - 03]   2019.09

  • Marfan症候群および類縁疾患の遺伝学的診断における次世代シーケンスの有用性

    森口 駿, 中釜 悠, 武田 憲文, 中野 克俊, 浦田 晋, 中川 良, 朝海 廣子, 平田 陽一郎, 犬塚 亮

    日本小児循環器学会雑誌   35 ( Suppl.1 )   s1 - 208   2019.06( ISSN:0911-1794 ( eISSN:2187-2988

  • 劣性遺伝心筋症の1家系における責任遺伝子単離

    中釜 悠, 古谷 喜幸, 中西 敏雄, 平田 陽一郎, 犬塚 亮

    日本小児循環器学会雑誌   35 ( Suppl.1 )   s1 - 209   2019.06( ISSN:0911-1794 ( eISSN:2187-2988

  • 乳児期発症ミオパチーに合併した心筋緻密化異常の病像

    物井 綾香, 中釜 悠, 中川 良, 中野 克俊, 浦田 晋, 朝海 廣子, 松井 彦郎, 平田 陽一郎, 廣野 恵一, 犬塚 亮

    日本小児循環器学会雑誌   35 ( Suppl.1 )   s1 - 338   2019.06( ISSN:0911-1794 ( eISSN:2187-2988

  • RIT1変異陽性Noonan症候群にみられた、リンパ管異常に伴う合併症の治療経験

    水野 雄太, 中野 克俊, 中釜 悠, 浦田 晋, 朝海 廣子, 中川 良, 平田 陽一郎, 松井 彦郎, 犬塚 亮

    日本小児循環器学会雑誌   35 ( Suppl.1 )   s1 - 286   2019.06( ISSN:0911-1794 ( eISSN:2187-2988

  • L-dopa反応性の眼球運動異常発作を呈し、SPR変異の同定により、セピアプテリン還元酵素欠損症と診断された1例

    中釜 悠, 濱中 耕平, 新宅 治夫, 宮武 聡子, 松本 直通, 久世 崇史, 清水 信隆, 廣畑 晃司, 三牧 正和

    脳と発達   51 ( Suppl. )   S259 - S259   2019.05( ISSN:0029-0831 ( eISSN:1884-7668

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Presentations

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Grant-in-Aid for Scientific Research

  • 熱帯アメリカ地域に流行する新興・再興感染症への免疫疫学アプローチ

    Fund for the Promotion of Joint International Research / Fostering Joint International Research (A)  2023

  • 新型コロナウイルスワクチンの抗体応答の関連因子:メタボロミクスに着目した検討

    Grant-in-Aid for Scientific Research(B)  2022

  • 抗体アビディティー成熟を指標としたSARS-CoV-2防御免疫のレジリエンス評価

    Grant-in-Aid for Early-Career Scientists  2022

  • 小児期発症重症心筋症の変異データベース構築と疾患モデル動物を用いた分子機構の解明

    Grant-in-Aid for Scientific Research(C)  2020

  • 乳酸を基軸とした心臓エネルギー代謝可塑性の理解

    Grant-in-Aid for Research Activity Start-up  2019

  • 内臓錯位、円錐動脈幹異常を伴う先天性心疾患の分子遺伝学的発症機序の解明

    Grant-in-Aid for JSPS Fellows  2017

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Contract research

  • ヌーナン症候群における心筋細胞周期脱制御機構の解明と治療候補薬の探索

    日本医療研究開発機構  再生・細胞医療・遺伝子治療実現加速化プログラム(疾患特異的 iPS 細胞を用いた病態解明・創薬研究課題・分野1)  2023

  • 包括的アプローチに基づく小児 COVID-19 関連多系統炎症性症候群(MISC)の病態解析と臨床像の解明

    日本医療研究開発機構  新興・再興感染症に対する革新的医薬品等開発推進研究事業  2023

  • ヒトiPS心筋を用いたシャーガス病モデリングによる宿主-病原体相互作用解析と創薬プロセス変革

    国立研究開発法人日本医療研究開発機構  新興・再興感染症研究基盤創生事業(多分野融合研究領域)  2021

  • 新型コロナウィルス感染症の血清学的診断法の臨床的有用性評価

    日本医療研究開発機構  地球規模保健課題解決推進のための研究開発事業(低・中所得国の健康・医療改善に向けた、医薬品・医療機器・医療技術等の海外展開推進のための国際共同臨床試験)  2020

  • 日本におけるFirst in Human試験、コンゴ民主共和国との国際共同Proof of Concept試験による、アフリカトリパノソーマ症治療薬開発

    日本医療研究開発機構  革新的医療シーズ実用化研究事業(臨床研究中核病院の機能を活用した若手研究者によるプロトコール作成研究)  2017

Incentive donations / subsidies

  • 妊娠高血圧症発症予測のユニバーサルアクセス化による妊娠予後改善

    パブリックヘルスリサーチセンター  2023年度 パブリックヘルス科学研究助成金  2023

  • 心筋の細胞周期制御および成熟化機構を標的したヌーナン症候群心合併症に対する分子創薬

    宮田心臓病研究振興基金  第9回 Miyata Foundation Award日本小児循環器学会研究奨励賞  2023

  • Mitogenic cardiomyopathyの疾患概念確立と病態解明

    大阪難病研究財団  2023年度 医学研究助成  2023

  • シャーガス病重症化機構の解明に資する新規細胞モデル構築

    大山健康財団  大山健康財団学術研究助成金  2022

  • RASopathy関連心筋症の細胞レベル表現型の理解

    宮田心臓病研究振興基金  第5回 Miyata Foundation Award日本小児循環器学会研究奨励賞  2019

  • 乳児期早期発症の遺伝性心疾患におけるゲノム異常と重症化に関する病態解析

    森永奉仕会  森永奉仕会研究奨励金  2017

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Acceptance of Researcher

  • 2022  Number of researchers:5

Charge of on-campus class subject

  • Parasitology

    2022   Intensive lecture   Undergraduate

Number of papers published by graduate students

  • 2022

    Number of graduate students presentations:2

Visiting Lectures ⇒ Link to the list of Visiting Lectures

  • アボットジャパン主催メディカルジャーニー「ワクチン接種とこれからのSARS-CoV-2抗体検査活用の可能性」

    Category:Medicine (medical care, rehabilitation, health exercise science, physical fitness / training, sports practice science)

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    Audience:College students, Graduate students, Teachers, Researchers, General, Media

  • 第165回 茅ヶ崎小児医療セミナー 教育講演

    Category:Medicine (medical care, rehabilitation, health exercise science, physical fitness / training, sports practice science)

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    Audience:Researchers, General, Scientific organization

  • 第2回 臨床薬理・臨床応用セミナー 教育講演

    Category:Medicine (medical care, rehabilitation, health exercise science, physical fitness / training, sports practice science)

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    Audience:College students, Graduate students, Teachers, Researchers

  • 第31回 大阪小児感染症研究会 教育講演

    Category:Medicine (medical care, rehabilitation, health exercise science, physical fitness / training, sports practice science)

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    Audience:Researchers, Scientific organization