Updated on 2026/03/28

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写真a

 
Hideaki Nakajima
 
Organization
Graduate School of Medicine Department of Medicine Internal Medicine and Clinical Immunology Professor
School of Medicine Medical Course
Title
Professor
Homepage
http://www-user.yokohama-cu.ac.jp/~naika1/index.html
External link

Degree

  • 博士（医学） ( 慶應義塾大学 )

Research Interests

  • アンチセンス

  • Robo4

  • 胎盤

  • トランスジェニックマウス

  • 血液幹細胞

  • レチノイン酸レセプター

  • 細胞増殖

  • レチノイン酸

  • ISF

  • 骨髄異形成症候群

  • FACS

  • ShIF

  • 5q-症候群

  • EBPα

  • ATOX1

  • 自己複製

  • 造血

  • フローサイトメトリー

  • ストローマ

  • immune suppressor factor

  • Magic roundabout

  • 血液内科学

  • 血球分化

  • 転写因子

  • 幹細胞

  • C

  • 細胞分化

  • 造血幹細胞

  • PU.1

Research Areas

  • Life Science / Hematology and medical oncology

Papers

  • Successful treatment of relapsed FLT3-mutated donor cell-derived MDS/AML with FLT3 inhibitor gilteritinib

    Mana Kawano, Hiroyoshi Kunimoto, Akihiko Izumi, Akiko Adachi, Ayaka Miura, Chiaki Yokoyama, Kodai Hasegawa, Mayoko Shirafuta, Marika Tanaka, Takayuki Sakuma, Takuma Ohashi, Hiroyuki Takahashi, Takuya Miyazaki, Takayoshi Tachibana, Maki Hagihara, Kenji Matsumoto, Hideaki Nakajima

    Annals of Hematology   105 ( 4 )   2026.2

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.1007/s00277-026-06896-3

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    Other Link： https://link.springer.com/article/10.1007/s00277-026-06896-3

  • Two Cases of Human Immunodeficiency Virus Infection Mimicking Rheumatic Disease with a Literature Review

    Yutaro SOEJIMA, Sei SAMUKAWA, Hideaki KATO, Ryusuke YOSHIMI, Yohei KIRINO, Hideaki NAKAJIMA

    Kansenshogaku Zasshi   2026

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    Publishing type：Research paper (scientific journal)   Publisher：The Japanese Association for Infectious Diseases  

    DOI： 10.11150/kansenshogakuzasshi.e25008

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  • Characteristics of Late-Onset Systemic Lupus Erythematosus: Clinical Manifestations and Diagnostic and Treatment Challenges

    Natsuki Sakurai, Ryusuke Yoshimi, Hideaki Nakajima

    Drugs & Aging   42 ( 11 )   1001 - 1009   2025.9

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.1007/s40266-025-01245-x

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    Other Link： https://link.springer.com/article/10.1007/s40266-025-01245-x/fulltext.html

  • PRC2‐mediated apoptosis evasion is a therapeutic target of MDS/AML harboring inv(3)/t(3;3) and monosomy 7

    Hiroyoshi Kunimoto, Ayaka Miura, Maiko Sagisaka, Mieko Ito, Ryoichi Maenosono, Hirofumi Yamauchi, Kazuki Nishimura, Daisuke Honma, Shinji Tsutsumi, Akiko Adachi, Takayuki Sakuma, Takuma Ohashi, Hiroshi Teranaka, Junji Ikeda, Sei Samukawa, Takashi Toya, Yuka Harada, Noriko Doki, Sheng F. Cai, Hiroaki Maki, Hiroaki Goto, Akihide Yoshimi, Hideaki Nakajima

    HemaSphere   9 ( 7 )   2025.7

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    Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Abstract

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) harboring both inv(3)/t(3;3) and monosomy 7 (−7) are highly aggressive myeloid cancers of which molecular pathogenesis and therapeutic vulnerability remain elusive. High throughput drug screens, CUT&Tag/RNA sequence, and functional assays using human MDS/AML cells revealed that EZH2 inhibitors efficiently induce apoptosis preferentially in MDS/AML with inv(3)/t(3;3) and −7 through the activation of GADD45γ‐p38‐p53 axis. EVI1 activated in 3q‐rearranged MDS/AML was responsible for GADD45γ silencing by direct binding to its consensus sequence within GADD45γ promoter and recruitment of PRC2 complex via interaction with EZH2, which can be therapeutically targeted by EZH2 inhibition. MDS/AML with inv(3)/t(3;3) and −7 showed preferential sensitivity to EZH2 inhibition in both mouse model and patient samples. Thus, MDS/AML cells with inv(3)/t(3;3) and −7 possess apoptosis evasion mechanism through EVI1‐PRC2‐mediated repression of GADD45γ‐p38‐p53 axis, which is a potential therapeutic vulnerability in MDS/AML patients with these high‐risk cytogenetic lesions.

    DOI： 10.1002/hem3.70149

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  • 全身性エリテマトーデスに対するCAR-T細胞療法

    吉見 竜介, 中島 秀明

    リウマチ科   73 ( 4 )   462 - 468   2025.4

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    Language：Japanese   Publisher：(有)科学評論社  

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  • 自己炎症病態を伴う骨髄異形成症候群患者の臨床像と予後に関する後方視的解析

    中山 裕太, 長沢 有真, 安達 聡一郎, 市川 健斗, 前田 彩花, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   69回   910 - 910   2025.3

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  • 成人移行後にAicardi-Goutieres症候群と診断された小児期発症全身性エリテマトーデスの一例

    松尾 康平, 小宮 孝章, 濱田 直樹, 前田 彩花, 平原 理紗, 副島 裕太郎, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   69回   905 - 905   2025.3

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  • 当院におけるJAK阻害薬使用中の関節リウマチ患者における帯状疱疹ワクチンの使用経験

    張田 佳代, 峯岸 薫, 松本 未於, 市川 健斗, 櫻井 菜月, 小宮 孝章, 濱田 直樹, 前田 彩花, 平原 理紗, 副島 裕太郎, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   69回   894 - 894   2025.3

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  • 縦隔腫瘤で発症したIgG4関連大動脈周囲炎の一例

    松本 未於, 張田 佳代, 市川 健斗, 櫻井 菜月, 小宮 孝章, 濱田 直樹, 前田 彩花, 平原 理紗, 副島 裕太郎, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   69回   842 - 842   2025.3

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  • 経胸壁心臓超音波で診断,経過フォローを行ったSLEとAPSに合併したLibman Sacks型心内膜炎の一例

    濱田 直樹, 張田 佳代, 松本 未於, 小宮 孝章, 前田 彩花, 平原 理紗, 副島 裕太郎, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   69回   729 - 729   2025.3

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  • VEXAS症候群の経過中に播種性非定型抗酸菌感染症を合併した一例

    村井 郁, 松本 未於, 張田 佳代, 市川 健斗, 櫻井 菜月, 小宮 孝章, 濱田 直樹, 前田 彩花, 平原 理紗, 副島 裕太郎, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   69回   905 - 905   2025.3

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  • The Characteristics and Management Considerations of Late-onset Rheumatoid Arthritis.

    Ryusuke Yoshimi, Hideaki Nakajima

    Internal medicine (Tokyo, Japan)   63 ( 24 )   3267 - 3269   2024.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.2169/internalmedicine.3786-24

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  • Successful treatment of two cases with Philadelphia-chromosome positive acute lymphoblastic leukemia who relapsed after allogeneic stem cell transplantation and the treatments with novel immunotherapies and ponatinib. International journal

    Takayoshi Tachibana, Masatsugu Tanaka, Yuma Noguchi, Yuho Najima, Daichi Sadato, Yuka Harada, Yotaro Tamai, Noriko Doki, Hideaki Nakajima

    Hematology (Amsterdam, Netherlands)   29 ( 1 )   2360843 - 2360843   2024.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    The outcomes of relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant to new drugs such as tyrosine kinase inhibitors, inotuzumab ozogamicin (InO) and blinatumomab are dismal. We treated two cases of Ph+ALL resistant to these drugs that achieved long-term survival after treatment with chimeric antigen receptor (CAR)-T cell therapy or a second allogeneic hematopoietic stem cell transplantation (HCT) with a sequential conditioning regimen. Case 1: A 15-year-old boy was diagnosed with Ph+ALL. Despite the second HCT after the treatment of ponatinib and blinatumomab, hematological relapse occurred. InO was ineffective and he was transferred to a CAR-T center. After the CAR-T cell therapy, negative measurable residual disease (MRD) was achieved and maintained for 38 months without maintenance therapy. Case 2: A 21-year-old man was diagnosed with Ph+ALL. Hematological relapse occurred after the first HCT. Despite of the treatment with InO, ponatinib, and blinatumomab, hematological remission was not achieved. The second HCT was performed using a sequential conditioning regimen with clofarabine. Negative MRD was subsequently achieved and maintained for 42 months without maintenance therapy. These strategies are suggestive and helpful to treat Ph+ALL resistant to multiple immunotherapies.

    DOI： 10.1080/16078454.2024.2360843

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  • Idiopathic Multicentric Castleman's Disease as a Mimicker of IgG4-related Disease.

    Ryusuke Yoshimi, Hideaki Nakajima

    Internal medicine (Tokyo, Japan)   2024.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.2169/internalmedicine.4793-24

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  • Characteristic features of late-onset systemic lupus erythematosus: An observational study of data from the Lupus Registry of Nationwide Institutions. International journal

    Natsuki Sakurai, Ryusuke Yoshimi, Nobuyuki Yajima, Chiharu Hidekawa, Yosuke Kunishita, Daiga Kishimoto, Yumiko Kawahara Sugiyama, Noriko Kojitani, Naoki Suzuki, Yuji Yoshioka, Takaaki Komiya, Kaoru Takase-Minegishi, Yohei Kirino, Ken-Ei Sada, Yoshia Miyawaki, Kunihiro Ichinose, Shigeru Ohno, Hiroshi Kajiyama, Shuzo Sato, Yasuhiro Shimojima, Michio Fujiwara, Hideaki Nakajima

    Lupus   9612033241281507 - 9612033241281507   2024.9

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    OBJECTIVE: Late-onset systemic lupus erythematosus (LoSLE) is known to possess characteristics different from those of early-onset SLE (EoSLE), thereby making their diagnosis difficult. This study aimed to assess the characteristic features of LoSLE in Japan, a model country with a super-aged society. METHODS: Data were obtained from the Lupus Registry of Nationwide Institutions, which includes a multicenter cohort of patients with SLE in Japan who satisfied the 1997 American College of Rheumatology revised classification criteria for SLE. Data were compared between patients with LoSLE (≥50 years old at onset) and EoSLE (<50 years old at onset). To identify factors associated with LoSLE, binary logistic regression was used for the multivariate analysis, and missing values were complemented by multiple imputations. We also conducted a sub-analysis for patients diagnosed within 5 years of onset. RESULTS: Out of 929 enrolled patients, 34 were excluded owing to a lack of data regarding onset age. Among the 895 remaining patients, 100 had LoSLE, whereas 795 had EoSLE. The male-to-female ratio was significantly higher in the LoSLE group than in the EoSLE group (0.32 vs 0.11, p < 0.001). With respect to SLEDAI components at onset, patients with LoSLE exhibited a higher frequency of myositis (11.9% vs 3.75%, p = 0.031), lower frequency of skin rash (33.3% vs 67.7%, p < 0.001), and lower frequency of alopecia (7.32% vs 24.7%, p = 0.012). No significant differences in overall disease activity at onset were observed between the two groups. Regarding medical history, immunosuppressants were more commonly used in EoSLE. A multivariate analysis revealed that a higher male proportion and a lower proportion of new rash at onset were independent characteristic features of LoSLE. We also identified late onset as an independent risk factor for a high SDI score at enrollment and replicated the result in a sub-analysis for the population with a shorter time since onset. CONCLUSIONS: We clarified that LoSLE was characterized by a higher male proportion, a lower frequency of skin rash and a tendency to organ damage. Now that the world is faced with aging, our results may be helpful at diagnosis of LoSLE.

    DOI： 10.1177/09612033241281507

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  • Effect of Shared Decision‐Making on Trust in Physicians in the Management of Systemic Lupus Erythematosus: The Trust Measurement for Physicians and Patients With Systemic Lupus Erythematosus Prospective Cohort Study

    Ryusuke Yoshimi, Nobuyuki Yajima, Chiharu Hidekawa, Natsuki Sakurai, Nao Oguro, Kenta Shidahara, Keigo Hayashi, Takanori Ichikawa, Dai Kishida, Yoshia Miyawaki, Ken‐ei Sada, Yasuhiro Shimojima, Yuichi Ishikawa, Yuji Yoshioka, Yosuke Kunishita, Daiga Kishimoto, Kaoru Takase‐Minegishi, Yohei Kirino, Shigeru Ohno, Noriaki Kurita, Hideaki Nakajima

    Arthritis Care &amp; Research   76 ( 12 )   1597 - 1605   2024.8

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    Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Objective

    Few studies have explored whether the involvement of patients in shared decision‐making (SDM) is beneficial to the management of systemic lupus erythematosus (SLE). Therefore, this study investigated the relationship between patient participation in SDM and their trust in physicians using data from the Trust Measurement in Physicians and Patients With SLE (TRUMP2‐SLE) study.

    Methods

    Data regarding the nine‐item Japanese version of the Shared Decision‐Making Questionnaire (SDM‐Q‐9) scores, Trust in Physician Scale (TIPS) scores, and Abbreviated Wake Forest Physician Trust Scale (A‐WFPTS) scores for interpersonal trust in a physician and trust in the medical profession were collected from patients with SLE who visited the outpatient clinics of five facilities in Japan through a self‐administered questionnaire. The relationships among these scores were analyzed by general linear models with cluster‐robust variance.

    Results

    This study included 433 patients with SLE. The median baseline TIPS and A‐WFPTS (attending physician version) scores were 82 (73–93) and 80 (70–95), respectively. A higher baseline SDM‐Q‐9 score was correlated with an increase in the TIPS score at one year (coefficient per 10‐point [pt] increase, 0.94 pts, 95% confidence interval [CI] 0.16–1.72). A higher baseline SDM‐Q‐9 score was correlated with a higher A‐WFPTS score for interpersonal trust (coefficient per 10‐pt increase, 2.20 pts, 95% CI 1.44–2.96). The baseline SDM‐Q‐9 score was also correlated with an increase in the general physician version of the A‐WFPTS score at one year (coefficient per 10‐pt increase, 1.29 pts, 95% CI 0.41–2.18).

    Conclusion

    Engagement of patients with SLE in SDM elevates their trust in the attending physicians and health care providers, potentially enhancing doctor–patient relationships and overall health care trust.

    DOI： 10.1002/acr.25409

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  • Distinct features of trisomy 8-associated autoinflammatory disease from Behçet's disease: case series and systematic review

    Kento Ichikawa, Soichiro Adachi, Kaoru Takase-Minegishi, Yuta Nakayama, Yuma Nagasawa, Yuki Iizuka, Ayaka Maeda, Lisa Hirahara, Yutaro Soejima, Takuma Ohashi, Hiroyoshi Kunimoto, Nobuyuki Horita, Ryusuke Yoshimi, Yohei Kirino, Hideaki Nakajima

    Clinical and Experimental Rheumatology   2024.8

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    Publishing type：Research paper (scientific journal)   Publisher：Clinical and Experimental Rheumatology  

    DOI： 10.55563/clinexprheumatol/8j7rbr

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  • 感染症を繰り返し治療に難渋したTAFRO症候群の一例

    市川 健斗, 渡辺 武俊, 佐藤 雄一郎, 峯岸 薫, 吉見 竜介, 北堀 弘大, 本多 主悦, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 桐野 洋平, 中島 秀明

    関東リウマチ   56   97 - 100   2024.5

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  • 感染症を繰り返し治療に難渋したTAFRO症候群の一例

    市川 健斗, 渡辺 武俊, 佐藤 雄一郎, 峯岸 薫, 吉見 竜介, 北堀 弘大, 本多 主悦, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 桐野 洋平, 中島 秀明

    関東リウマチ   56   97 - 100   2024.5

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  • A case of Bloom syndrome manifesting with therapy-related myelodysplastic syndromes harboring a novel BLM gene variant

    Takuma Ohashi, Hiroyoshi Kunimoto, Jun Nukui, Haruka Teshigawara, Satoshi Koyama, Takuya Miyazaki, Maki Hagihara, Kenji Matsumoto, Eriko Koshimizu, Naomi Tsuchida, Haruka Hamanoue, Satoko Miyatake, Akihiro Yachie, Naomichi Matsumoto, Hideaki Nakajima

    International Journal of Hematology   2024.3

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.1007/s12185-024-03751-x

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    Other Link： https://link.springer.com/article/10.1007/s12185-024-03751-x/fulltext.html

  • 当院におけるトリソミー8を伴う自己炎症症候群の診療状況

    中山 裕太, 北堀 弘大, 本多 主税, 市川 健斗, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   907 - 907   2024.3

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  • トシリズマブが奏功した肝障害を伴うTAFRO症候群 1症例報告と文献レビュー

    北堀 弘大, 本多 主税, 市川 健人, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   782 - 782   2024.3

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  • シェーグレン症候群に合併した巨大腎結石の1例

    仲野 寛人, 北堀 弘大, 本多 主税, 市川 健斗, 濱田 直樹, 副島 裕太郎, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   780 - 780   2024.3

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  • 幽門部狭窄で発症したIgG4関連疾患の一例

    本多 主税, 北堀 弘大, 市川 健斗, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   892 - 892   2024.3

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  • 当院における大型血管炎に対するトシリズマブの有用性の検討

    濱田 直樹, 市川 健斗, 北堀 弘大, 副島 裕太郎, 仲野 寛人, 平原 理紗, 前田 彩花, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   880 - 880   2024.3

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  • リウマチ性疾患の多様な側面を検討する 膠原病診療での地域医療連携における障壁に関する意識調査

    吉見 竜介, 佐藤 雄一郎, 前田 彩花, 平原 理紗, 小宮 孝章, 副島 裕太郎, 濱田 直樹, 土田 奈緒美, 峯岸 薫, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   606 - 606   2024.3

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  • 経過中にマクロファージ活性化症候群を示した成人スティル病の再燃にトシリズマブの再投与が有効であった一例

    長沢 有真, 北堀 弘大, 本多 主税, 市川 健斗, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   913 - 913   2024.3

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  • 当院におけるトリソミー8を伴う自己炎症症候群の診療状況

    中山 裕太, 北堀 弘大, 本多 主税, 市川 健斗, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   907 - 907   2024.3

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  • シェーグレン症候群に合併した巨大腎結石の1例

    仲野 寛人, 北堀 弘大, 本多 主税, 市川 健斗, 濱田 直樹, 副島 裕太郎, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   780 - 780   2024.3

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  • ベーチェット病・成人スチル病 ベーチェット病における高疾患活動性および血清IL-6濃度と重症病変の関連

    平原 理紗, 桐野 洋平, 飯塚 友紀, 副島 裕太郎, 吉見 竜介, 藤枝 雄一郎, 渥美 達也, 東野 俊洋, 小林 大介, 岳野 光洋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   526 - 526   2024.3

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  • ループス腎炎等に対する治療 全身性エリテマトーデスにおける実臨床におけるベリムマブの効果について 当科における使用成績調査

    櫻井 菜月, 吉見 竜介, 秀川 智春, 鈴木 直樹, 吉岡 裕二, 東谷 佳奈, 安達 聡一郎, 飯塚 友紀, 前田 彩花, 平原 理紗, 本多 主税, 北堀 弘大, 市川 健斗, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   588 - 588   2024.3

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  • ベーチェット病・成人スチル病 ベーチェット病における高疾患活動性および血清IL-6濃度と重症病変の関連

    平原 理紗, 桐野 洋平, 飯塚 友紀, 副島 裕太郎, 吉見 竜介, 藤枝 雄一郎, 渥美 達也, 東野 俊洋, 小林 大介, 岳野 光洋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   526 - 526   2024.3

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  • 幽門部狭窄で発症したIgG4関連疾患の一例

    本多 主税, 北堀 弘大, 市川 健斗, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   892 - 892   2024.3

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  • トシリズマブが奏功した肝障害を伴うTAFRO症候群 1症例報告と文献レビュー

    北堀 弘大, 本多 主税, 市川 健人, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   782 - 782   2024.3

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  • 経過中にマクロファージ活性化症候群を示した成人スティル病の再燃にトシリズマブの再投与が有効であった一例

    長沢 有真, 北堀 弘大, 本多 主税, 市川 健斗, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   68回   913 - 913   2024.3

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  • Effect of shared decision-making on trust in physicians in the management of systemic lupus erythematosus: The TRUMP2-SLE prospective cohort study

    Ryusuke Yoshimi, Nobuyuki Yajima, Chiharu Hidekawa, Natsuki Sakurai, Nao Oguro, Kenta Shidahara, Keigo Hayashi, Takanori Ichikawa, Dai Kishida, Yoshia Miyawaki, Ken-ei Sada, Yasuhiro Shimojima, Yuichi Ishikawa, Yuji Yoshioka, Yosuke Kunishita, Daiga Kishimoto, Kaoru Takase-Minegishi, Yohei Kirino, Shigeru Ohno, Noriaki Kurita, Hideaki Nakajima

    2024.1

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    DOI： 10.1101/2024.01.05.24300886

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  • ベーチェット病様症状を契機に診断に至ったトリソミー8を伴う自己炎症症候群の一例

    市川 健斗, 北堀 弘大, 本多 主悦, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会関東支部学術集会プログラム・抄録集   33回   79 - 79   2023.12

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  • トシリズマブが奏効したステロイド抵抗性TAFRO症候群の一例

    北堀 弘大, 市川 健斗, 本多 主悦, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会関東支部学術集会プログラム・抄録集   33回   80 - 80   2023.12

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  • ベーチェット病様症状を契機に診断に至ったトリソミー8を伴う自己炎症症候群の一例

    市川 健斗, 北堀 弘大, 本多 主悦, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会関東支部学術集会プログラム・抄録集   33回   79 - 79   2023.12

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  • トシリズマブが奏効したステロイド抵抗性TAFRO症候群の一例

    北堀 弘大, 市川 健斗, 本多 主悦, 濱田 直樹, 副島 裕太郎, 仲野 寛人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会関東支部学術集会プログラム・抄録集   33回   80 - 80   2023.12

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  • Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia

    Katherine Knorr, Jahan Rahman, Caroline Erickson, Eric Wang, Mara Monetti, Zhuoning Li, Juliana Ortiz-Pacheco, Andrew Jones, Sydney X. Lu, Robert F. Stanley, Maria Baez, Nina Fox, Cynthia Castro, Alessandra E. Marino, Caroline Jiang, Alex Penson, Simon J. Hogg, Xiaoli Mi, Hideaki Nakajima, Hiroyoshi Kunimoto, Koutarou Nishimura, Daichi Inoue, Benjamin Greenbaum, David Knorr, Jeffrey Ravetch, Omar Abdel-Wahab

    Nature Cancer   2023.10

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    Abstract

    Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique expression of a variety of antigens, including the RNA helicase U5 snRNP200, on the surface of AML cells but not on normal hematopoietic precursors and skewed Fc receptor distribution in the AML immune microenvironment. Cell membrane localization of U5 snRNP200 was linked to surface expression of the Fcγ receptor IIIA (FcγIIIA, also known as CD32A) and correlated with expression of interferon-regulated immune response genes. Anti-U5 snRNP200 antibodies engaging activating Fcγ receptors were efficacious across immunocompetent AML models and were augmented by combination with azacitidine. These data provide a roadmap of AML-associated antigens with Fc receptor distribution in AML and highlight the potential for targeting the AML cell surface using Fc-optimized therapeutics.

    DOI： 10.1038/s43018-023-00656-2

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    Other Link： https://www.nature.com/articles/s43018-023-00656-2

  • <i>O</i>-Linked <i>N</i>-Acetylglucosamine Transferase Ensures Survival of Mouse Fetal Liver Hematopoietic Progenitors Partly by Regulating <i>Bcl-xL</i> and Oxidative Phosphorylation

    Shunsuke Soma, Koichi Murakami, Yumi Fukuchi, Hiroyoshi Kunimoto, Hideaki Nakajima

    Stem Cells   2023.10

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    Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    Abstract

    O-linked N-acetylglucosamine transferase (OGT) critically regulates wide variety of biological processes such as gene expression, metabolism, stress response, signaling and proteostasis. In adult hematopoiesis, OGT is crucial for differentiation of B and T cells and the maintenance of hematopoietic stem cells (HSCs). However, a role for OGT in fetal liver (FL) hematopoiesis remains unknown. To investigate a role for OGT in FL hematopoiesis, we conditionally disrupted OGT in hematopoietic cells in developing FLs. Hematopoietic specific disruption of OGT resulted in embryonic lethality in late stage of gestation due to severe anemia and growth retardation. OGT loss led to profound reduction of differentiating erythroid cells and erythroid progenitors in FLs due to massive apoptosis. In addition, clonogenic capacity of FL cells was severely impaired by OGT loss. Interestingly, expression of BCL-XL, a well-known inhibitor of apoptosis in FL cells, dramatically decreased, and the levels of reactive oxygen species (ROS) were increased in OGT-deficient FL cells. Overexpression of Bcl-xL and reduction of ROS significantly restored the colony formation of OGT-deficient FL cells. This study revealed a novel role for OGT during embryogenesis, which ensures survival of FL hematopoietic cells partly by regulating Bcl-xL and oxidative phosphorylation.

    DOI： 10.1093/stmcls/sxad076

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  • 関節リウマチにおける抗RANKL抗体製剤の骨密度および骨代謝マーカーに対する効果

    副島 裕太郎, 小宮 孝章, 吉見 竜介, 峯岸 薫, 桐野 洋平, 中島 秀明

    日本骨粗鬆症学会雑誌   9 ( Suppl.1 )   440 - 440   2023.9

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  • 関節リウマチにおける抗RANKL抗体製剤の骨密度および骨代謝マーカーに対する効果

    副島 裕太郎, 小宮 孝章, 吉見 竜介, 峯岸 薫, 桐野 洋平, 中島 秀明

    日本骨粗鬆症学会雑誌   9 ( Suppl.1 )   440 - 440   2023.9

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  • COVID-19 Vaccination and the Development of Autoimmune Diseases.

    Ryusuke Yoshimi, Hideaki Nakajima

    Internal medicine (Tokyo, Japan)   62 ( 10 )   1387 - 1388   2023.5

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    DOI： 10.2169/internalmedicine.1490-22

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  • 肺多発結節影を呈したVEXAS症候群の一例

    加藤 浩之, 水野 広輝, 東谷 佳奈, 佐藤 雄一郎, 永井 秀人, 濱田 直樹, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    関東リウマチ   55   62 - 65   2023.5

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    症例は54歳男性で、労作時呼吸困難を主訴とした。下腿の紅斑、大球性貧血を認め、骨髄検査よりMDSと診断した。両側肺多発結節影、多発リンパ節腫脹を認め、高拍出性心不全が出現した。炎症所見、皮膚・肺・眼の病変、骨髄検査で空砲像を認め、末梢血の遺伝子解析よりVEXAS症候群と診断した。炎症に伴う貧血・心不全のコントロールが困難であったが利尿剤、プレドニゾロン投与が奏効し、心不全の改善・CRPの改善傾向、貧血の改善を認めた。胸部CTで胸水・肺鬱血像の消失、多発肺結節影の縮小を認めた。

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  • Clinical and genetic features of Japanese cases of MDS associated with VEXAS syndrome.

    Hiroyoshi Kunimoto, Ayaka Miura, Ayaka Maeda, Naomi Tsuchida, Yuri Uchiyama, Yosuke Kunishita, Yuki Nakajima, Kaoru Takase-Minegishi, Ryusuke Yoshimi, Takuya Miyazaki, Maki Hagihara, Etsuko Yamazaki, Yohei Kirino, Naomichi Matsumoto, Hideaki Nakajima

    International journal of hematology   2023.4

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    VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a new disease entity with autoinflammatory disorders (AID) driven by somatic variants in UBA1 that frequently co-exists with myelodysplastic syndromes (MDS). Clinicopathological and molecular features of Japanese cases with VEXAS-associated MDS remain elusive. We previously reported high prevalence of UBA1 variants in Japanese patients with relapsing polychondritis, in which 5 cases co-occurred with MDS. Here, we report clinicopathological and variant profiles of these 5 cases and 2 additional cases of MDS associated with VEXAS syndrome. Clinical characteristics of these cases included high prevalence of macrocytic anemia with marked cytoplasmic vacuoles in myeloid/erythroid precursors and low bone marrow (BM) blast percentages. All cases were classified as low or very low risk by the revised international prognostic scoring system (IPSS-R). Notably, 4 out of 7 cases showed significant improvement of anemia by treatment with prednisolone (PSL) or cyclosporin A (CsA), suggesting that an underlying inflammatory milieu induced by VEXAS syndrome may aggravate macrocytic anemia in VEXAS-associated MDS. Targeted deep sequencing of blood samples suggested that MDS associated with VEXAS syndrome tends to involve a smaller number of genes and lower risk genetic lesions than classical MDS.

    DOI： 10.1007/s12185-023-03598-8

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  • Incidence and Risk of Hematological Adverse Events Associated With Immune Checkpoint Inhibitors: A Systematic Literature Review and Meta-Analysis. International journal

    Takuma Ohashi, Kaoru Takase-Minegishi, Ayaka Maeda, Naoki Hamada, Ryusuke Yoshimi, Yohei Kirino, Hiroshi Teranaka, Hiroyoshi Kunimoto, Maki Hagihara, Kenji Matsumoto, Ho Namkoong, Nobuyuki Horita, Hideaki Nakajima

    Journal of hematology   12 ( 2 )   66 - 74   2023.4

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    BACKGROUND: Immune checkpoint inhibitors (ICIs) have been a breakthrough in cancer therapy. ICI therapy is generally better tolerated than cytotoxic chemotherapy; however, hematological adverse events (AEs) have not been fully analyzed. Hence, we performed a meta-analysis to evaluate the incidence and risk of ICI-related hematological AEs. METHODS: A systematic literature search was performed using PubMed, EMBASE, Cochrane Library, and the Web of Science Core Collection. Phase III randomized controlled trials (RCTs) involving ICI combination regimens were selected. The experimental group received ICIs with systemic treatment, and the control group received only the same systemic treatment. Odds ratios (ORs) for anemia, neutropenia, and thrombocytopenia were calculated using a random-model meta-analysis. RESULTS: We identified 29 RCTs with 20,033 patients. The estimated incidence rates for anemia of all grades and grades III-V were 36.5% (95% confidence interval (CI) 30.23 - 42.75) and 4.1% (95% CI 3.85 - 4.42), respectively. The incidence of neutropenia (all grades 29.7%, grades III-V 5.3%) and thrombocytopenia (all grades 18.0%, grades III-V 1.6%) was also calculated. CONCLUSION: Treatment with ICIs seemed unlikely to increase the incidence of anemia, neutropenia, and thrombocytopenia in all grades. However, programmed cell death-1 receptor ligand inhibitors significantly increased the risk of grades III-V thrombocytopenia (OR 1.53; 95% CI 1.11 - 2.11). Further research is needed to examine the potential risk factors.

    DOI： 10.14740/jh1090

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  • VEXAS症候群などの後天性自己炎症症候群 UBA1バリアント解析に基づく,本邦におけるVEXAS症候群疑い症例の多施設共同前向きコホート研究

    前田 彩花, 土田 奈緒美, 桐野 洋平, 國下 洋輔, 岸本 大河, 峯岸 薫, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   67回   733 - 733   2023.3

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  • 膠原病に伴う間質性肺疾患に対するニンテダニブの継続率と有効性の検討

    佐藤 雄一郎, 渡辺 武俊, 峯岸 薫, 吉見 竜介, 三木 智代, 小宮 孝章, 濱田 直樹, 桐野 洋平, 副島 裕太郎, 櫻井 菜月, 平原 理紗, 前田 彩花, 秀川 智春, 飯塚 友紀, 吉岡 裕二, 安達 聡一郎, 土田 奈緒美, 東谷 佳奈, 鈴木 直樹, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   67回   851 - 851   2023.3

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  • VEXAS症候群を疑う症状を認めたが末梢血UBA1バリアントが陰性であった一例

    三木 智代, 桐野 洋平, 前田 彩花, 土田 奈緒美, 渡辺 武俊, 小宮 孝章, 佐藤 雄一郎, 濱田 直樹, 副島 裕太郎, 峯岸 薫, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   67回   795 - 795   2023.3

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  • ベーチェット病患者における超音波検査による腱付着部の評価

    西崎 碧, 峯岸 薫, 平原 理紗, 飯塚 友紀, 副島 裕太郎, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   67回   910 - 910   2023.3

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  • ベーチェット病 ベーチェット病患者における新型コロナウイルスワクチンの有効性・安全性

    副島 裕太郎, 桐野 洋平, 平原 理紗, 飯塚 友紀, 峯岸 薫, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   67回   649 - 649   2023.3

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  • 家族性地中海熱・成人自己炎症性疾患 家族性地中海熱に伴うコルヒチン治療抵抗性の髄膜炎に対してカナキヌマブが奏効した一例

    渡辺 武俊, 峯岸 薫, 吉見 竜介, 岸田 大, 前田 彩花, 土田 奈緒美, 三木 智代, 佐藤 雄一郎, 小宮 孝章, 濱田 直樹, 副島 裕太郎, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   67回   735 - 735   2023.3

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  • Protective effect of hydroxychloroquine on infections in patients with systemic lupus erythematosus: an observational study using the LUNA registry. International journal

    Chiharu Hidekawa, Ryusuke Yoshimi, Yusuke Saigusa, Jun Tamura, Noriko Kojitani, Naoki Suzuki, Natsuki Sakurai, Yuji Yoshioka, Yumiko Sugiyama-Kawahara, Yosuke Kunishita, Daiga Kishimoto, Kana Higashitani, Yuichiro Sato, Takaaki Komiya, Hideto Nagai, Naoki Hamada, Ayaka Maeda, Naomi Tsuchida, Lisa Hirahara, Yutaro Soejima, Kaoru Takase-Minegishi, Yohei Kirino, Nobuyuki Yajima, Ken-Ei Sada, Yoshia Miyawaki, Kunihiro Ichinose, Shigeru Ohno, Hiroshi Kajiyama, Shuzo Sato, Yasuhiro Shimojima, Michio Fujiwara, Hideaki Nakajima

    Frontiers in immunology   14   1227403 - 1227403   2023

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    OBJECTIVES: Infection is a leading cause of death in patients with systemic lupus erythematosus (SLE). Alt hough hydroxychloroquine (HCQ) has been reported to inhibit infection, evidence from Asian populations remains insufficient. We investigated this effect in Japanese SLE patients. METHODS: Data from the Lupus Registry of Nationwide Institutions were used in this study. The patients were ≥20 years old and met the American College of Rheumatology (ACR) classification criteria revised in 1997. We defined "severe infections" as those requiring hospitalization. We analyzed the HCQ's effect on infection suppression using a generalized estimating equation (GEE) logistic regression model as the primary endpoint and performed a survival analysis for the duration until the first severe infection. RESULTS: Data from 925 patients were used (median age, 45 [interquartile range 35-57] years; female, 88.1%). GEE analysis revealed that severe infections were significantly associated with glucocorticoid dose (odds ratio [OR] 1.968 [95% confidence interval, 1.379-2.810], p<0.001), immunosuppressants (OR 1.561 [1.025-2.380], p=0.038), and baseline age (OR 1.043 [1.027-1.060], p<0.001). HCQ tended to suppress severe infections, although not significantly (OR 0.590 [0.329-1.058], p=0.077). Survival time analysis revealed a lower incidence of severe infections in the HCQ group than in the non-HCQ group (p<0.001). In a Cox proportional hazards model, baseline age (hazard ratio [HR] 1.029 [1.009-1.050], p=0.005) and HCQ (HR 0.322 [0.142-0.728], p=0.006) were significantly related to incidence. CONCLUSION: HCQ may help extend the time until the occurrence of infection complications and tends to decrease infection rates.

    DOI： 10.3389/fimmu.2023.1227403

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  • Subcutaneous Edema in Polymyositis and Dermatomyositis.

    Ryusuke Yoshimi, Hideaki Nakajima

    Internal medicine (Tokyo, Japan)   62 ( 15 )   2161 - 2162   2023

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  • Clinical risk factors for patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplantation

    Haruka Teshigawara-Tanabe, Maki Hagihara, Jun Aoki, Satoshi Koyama, Hiroyuki Takahashi, Yuki Nakajima, Hiroyoshi Kunimoto, Takayoshi Tachibana, Takuya Miyazaki, Kenji Matsumoto, Masatsugu Tanaka, Etsuko Yamazaki, Shin Fujisawa, Heiwa Kanamori, Masataka Taguri, Hideaki Nakajima

    Hematology   27 ( 1 )   620 - 628   2022.12

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    DOI： 10.1080/16078454.2022.2052601

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  • Cryptococcal meningitis with atypical paradoxical inflammatory reactions after antifungal treatment in acquired immune deficiency syndrome: A case report. Reviewed International journal

    Sei Samukawa, Ryusuke Yoshimi, Noriko Kojitani, Yuji Uzawa, Kaoru Takase-Minegishi, Yohei Kirino, Yutaro Soejima, Hideaki Kato, Hideaki Nakajima

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2022.11

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    Cryptococcal meningitis (CM) is a life-threatening disease that primarily affects patients with human immunodeficiency virus (HIV). Antifungal therapy with antiretroviral treatment (ART) usually leads to the clinical remission of CM; however, in some cases, these treatments exacerbate intracranial inflammation because of paradoxical inflammatory reaction or immune reconstitution inflammatory syndrome (IRIS). Here we report two CM cases that presented atypical clinical courses attributed to paradoxical inflammatory reactions. The first case was a 43-year-old man with headache and vertigo diagnosed with CM and HIV. The patient's CM not only was refractory to the antifungal combination therapy of liposomal amphotericin B (L-AMB) and fluconazole (FLCZ) but suddenly worsened because of a paradoxical inflammatory reaction after 18 days of treatment. He passed away from brain herniation on day 23. The second case was a 43-year-old man diagnosed with CM and HIV. After receiving antifungal therapy and ART, the patient's status was stable for more than 3 years with undetectable HIV-RNA. He suddenly presented with brain inflammation and was diagnosed with IRIS due to CM (CM-IRIS). His brain lesions were migratory and refractory to various antifungal therapies such as L-AMB, FLCZ, flucytosine, and intrathecal amphotericin B. Although the cryptococcal antigen in the patient's cerebrospinal fluid gradually diminished after continuous antifungal therapies, his cognitive function declined, and right hemiparesis persisted. These two cases of CM presented atypical clinical courses, presumably because of paradoxical inflammatory reactions. It should be noted that the onset of CM-IRIS may not necessarily depend on the timing of ART initiation.

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  • CAR-T細胞療法の全身性エリテマトーデス治療への応用

    吉見 竜介, 中島 秀明

    リウマチ科   68 ( 4 )   455 - 461   2022.10

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  • Immune checkpoint inhibitor-induced arthralgia is tightly associated with improved overall survival in cancer patients. International journal

    Ayaka Maeda, Kaoru Takase-Minegishi, Yohei Kirino, Naoki Hamada, Yosuke Kunishita, Ryusuke Yoshimi, Akira Meguro, Ho Namkoong, Nobuyuki Horita, Hideaki Nakajima

    Rheumatology (Oxford, England)   2022.9

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    OBJECTIVES: With the increased use of immune checkpoint inhibitors (ICIs), arthralgia has been the most commonly reported musculoskeletal immune-related adverse events (irAEs). We aimed to characterise arthralgia and its association with overall survival (OS). METHODS: Randomised controlled trials (RCTs) reporting data for ICI-induced arthralgia from four online databases were comprehensively investigated. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for arthralgia using a random effects model meta-analysis. Individual patient data were reconstructed from RCTs, assessing OS in patients with or without ICI-induced arthralgia. We also retrospectively collected data on the clinical features and outcomes of ICI-induced arthralgia in the Yokohama City University (YCU) registry. RESULTS: We analysed 14,377 patients from 24 RCTs. The OR of ICI-induced arthralgia was 1.37 (95% CI 1.20-1.56). Of the 369 patients in YCU registry, 50 (13.6%) developed ICI-induced arthralgia. Among them, 30 had other grade ≥2 irAEs; noticeably more frequently vs. those without arthralgia (OR 1.92, 95% CI 1.04-3.52). By irAE types, a significant difference was found for relative adrenal insufficiency (OR 3.88, 95% CI 1.80-8.39). In the YCU registry, patients with (vs. without) ICI-induced arthralgia had better OS (log-rank, P < 0.001). OS results were validated from RCT patients with matched cancer types, drugs, and time to arthralgia onset (hazard ratio 0.34, 95% CI 0.17-0.65, P < 0.001). CONCLUSION: If arthralgia develops after ICIs, another irAE, such as relative adrenal insufficiency, may have developed. The incidence of arthralgia was associated with better OS and patients' condition must be carefully evaluated to determine optimal management.

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  • Anti-interferon-γ Antibody-seropositive Disseminated Nontuberculous Mycobacterial Infection Mimicking POEMS and TAFRO Syndromes.

    Chiharu Hidekawa, Ryusuke Yoshimi, Daiga Kishimoto, Hideaki Kato, Masaki Mitsuhashi, Natsuki Sakurai, Yuichiro Sato, Takeaki Uehara, Yuki Iizuka, Takaaki Komiya, Naoki Hamada, Hideto Nagai, Yutaro Soejima, Reikou Kamiyama, Kaoru Takase-Minegishi, Yohei Kirino, Takuro Sakagami, Hideaki Nakajima

    Internal medicine (Tokyo, Japan)   61 ( 15 )   2377 - 2385   2022.8

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    Disseminated nontuberculous mycobacterial infection (DNTM) is typically observed in immunocompromised hosts. Recently, it has been reported that healthy individuals with serum neutralizing autoantibodies for interferon (IFN)-γ can also develop DNTM. We herein report a case of anti-IFN-γ antibody-seropositive DNTM caused by Mycobacterium kansasii with symptoms mimicking TAFRO or POEMS syndrome, including anasarca, organomegaly, skin pigmentation, polyneuropathy, osteosclerotic change, thrombocytopenia, serum M protein, high C-reactive protein level, and reticulin fibrosis. The combination of antimicrobial chemotherapy with glucocorticoid and intravenous immunoglobulin improved his symptoms. Glucocorticoids may be an effective method of suppressing the production of anti-IFN-γ antibodies in DNTM.

    DOI： 10.2169/internalmedicine.8366-21

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  • Clinical impact of cigarette smoking on the outcomes of allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study. International journal

    Takuma Ohashi, Jun Aoki, Taiki Ando, Yasufumi Ishiyama, Yoshimi Ishii, Kazuho Miyashita, Yuki Nakajima, Takayoshi Tachibana, Maki Hagihara, Kenji Matsumoto, Masatsugu Tanaka, Heiwa Kanamori, Shin Fujisawa, Hideaki Nakajima

    Bone marrow transplantation   57 ( 7 )   1124 - 1132   2022.7

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    Smoking is associated with a high risk for different diseases including respiratory tract infections in immunocompetent patients. However, data about the effects of cigarette smoking on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are limited. Therefore, we retrospectively investigated 608 patients aged ≥20 years with hematological disorders who received their first allo-HSCT at our group of hospitals between 2000 and 2015, and evaluated the impact of cigarette smoking before allo-HSCT on clinical outcomes by dividing patients into two groups according to the Brinkman index (BI) (nonsmokers or light smokers [BI: 0-500] and heavy smokers [BI: ≥ 500]). Multivariate analyses showed that heavy smoking was associated with a high 5-year cumulative incidence of chronic graft-versus-host disease (cGVHD) (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.15-2.61, p < 0.01). The 5-year overall survival (HR: 1.16, 95% CI: 0.86-1.58, p = 0.33) and disease-free survival (HR: 1.12, 95% CI: 0.83-1.52, p = 0.45) were similar between the two groups. Hence, cigarette smoking is correlated with cGVHD, although prospective studies must be conducted to further verify this result.

    DOI： 10.1038/s41409-022-01678-7

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  • Aberrant <i>EVI1</i> splicing contributes to <i>EVI1</i>-rearranged leukemia

    Atsushi Tanaka, Taizo A Nakano, Masaki Nomura, Hiromi Yamazaki, Jan Philipp Bewersdorf, Roger Mulet-Lazaro, Simon Hogg, Bo Liu, Alex Vincent Penson, Akihiko Yokoyama, Weijia Zang, Marije Havermans, Miho Koizumi, Yasutaka Hayashi, Hana Cho, Akinori Kanai, Stanley C Lee, Muran Xiao, Yui Koike, Yifan Zhang, Miki Fukumoto, Yumi Aoyama, Tsuyoshi Konuma, Hiroyoshi Kunimoto, Toshiya Inaba, Hideaki Nakajima, Hiroaki Honda, Hiroshi Kawamoto, Ruud Delwel, Omar Abdel-Wahab, Daichi Inoue

    Blood   140 ( 8 )   875 - 888   2022.6

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    Detailed genomic and epigenomic analyses of MECOM (the MDS1 and EVI1 complex locus) have revealed that inversion or translocation of chromosome 3 drive inv(3)/t(3;3) myeloid leukemias via structural rearrangement of an enhancer which upregulates transcription of EVI1. Here we identify a novel, previously unannotated oncogenic RNA-splicing derived isoform of EVI1 which is frequently present in inv(3)/t(3;3) AML and directly contributes to leukemic transformation. This EVI1 isoform is generated by oncogenic mutations in the core RNA splicing factor SF3B1, which is mutated in &amp;gt;30% of inv(3)/t(3;3) myeloid neoplasm patients and thereby represents the single most commonly co-occurring genomic alteration in inv(3)/t(3;3) patients. SF3B1 mutations are statistically uniquely enriched in inv(3)/t(3;3) myeloid neoplasm patients and patient-derived cell lines compared with other forms of AML and promote mis-splicing of EVI1 generating an in-frame insertion of six amino acids at the 3' end of the second Zinc finger domain of EVI1. Expression of this EVI1 splice variant enhanced the self-renewal of hematopoietic stem cells and introduction of mutant SF3B1 in mice bearing the humanized inv(3)(q21q26) allele resulted in generation of this novel EVI1 isoform in mice and hastened leukemogenesis in vivo. The mutant SF3B1 spliceosome depends upon an exonic splicing enhancer within EVI1 exon 13 to promote usage of a cryptic branch point and aberrant 3' splice site within intron 12 resulting in the generation of this isoform. These data provide a mechanistic basis for the frequent co-occurrence of SF3B1 mutations as well as new insights into the pathogenesis of myeloid leukemias harboring inv(3)/t(3;3).

    DOI： 10.1182/blood.2021015325

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  • Benefits and risks of Hematopoietic Stem Cell Transplantation for Systemic Sclerosis: A Systematic Review and Meta-Analysis. International journal

    Kana Higashitani, Kaoru Takase-Minegishi, Ryusuke Yoshimi, Yohei Kirino, Naoki Hamada, Hideto Nagai, Maki Hagihara, Kenji Matsumoto, Ho Namkoong, Nobuyuki Horita, Hideaki Nakajima

    Modern rheumatology   2022.3

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    OBJECTIVES: We aimed to evaluate the efficacy and safety of hematopoietic stem cell transplantation (HSCT) in patients with systemic sclerosis (SSc). METHODS: A systematic literature review and meta-analysis were carried out. We compared survival outcomes using the Kaplan-Meier method with patient-level data between HSCT and intravenous pulse cyclophosphamide (IVCY). Additionally, the incidence rate of treatment-related deaths with HSCT was pooled using a random-effect model. RESULTS: Of the 2,091 articles screened, 22 were included: 3 randomized controlled trials and 19 observational studies. HSCT studies showed significant improvement in the skin thickness score and lung function. Despite treatment-related deaths being higher in HSCT than in IVCY, the Kaplan-Meier analysis showed a high survival rate 2 years post-transplant (log-rank, P=0.004). The pooled frequency of transplant-related death from 700 SSc patients was 6.30% (95% confidence interval 4.21-8.38). However, the estimated frequency of treatment-related deaths has been reducing over the last decade. CONCLUSION: HSCT is an effective treatment for SSc, but the optimal indications must be carefully determined by balancing the risks.

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  • 横浜市立大学附属病院のVEXAS症候群4症例の治療経過

    星 美希, 桐野 洋平, 土田 奈緒美, 前田 彩花, 峯岸 薫, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   752 - 752   2022.3

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  • The Roles of Monocytes and Macrophages in Behçet's Disease With Focus on M1 and M2 Polarization. Invited Reviewed International journal

    Lisa Hirahara, Kaoru Takase-Minegishi, Yohei Kirino, Yuki Iizuka-Iribe, Yutaro Soejima, Ryusuke Yoshimi, Hideaki Nakajima

    Frontiers in immunology   13   852297 - 852297   2022.3

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    Behçet's disease (BD) is a systemic inflammatory disease characterized by recurrent oral ulcers, genital ulcers, cutaneous inflammation, and uveitis. In addition, other potentially life-threatening lesions may occur in the intestinal tract, blood vessels, and central nervous system. This heterogeneity of the BD phenotype hampers development of a targeted treatment strategy. The pathogenesis of BD is not fully elucidated, but it is likely that genetically susceptible people develop BD in response to environmental factors, such as microbiome factors. Genetic analyses have identified various BD susceptibility loci that function in HLA-antigen presentation pathways, Th1 and Th17 cells, and autoinflammation related to monocytes/macrophages, or that increase levels of pro-inflammatory cytokines, reduce levels of anti-inflammatory cytokines, or act in dysfunctional mucous barriers. Our functional analyses have revealed that impairment of M2 monocyte/macrophage-mediated anti-inflammatory function through IL-10 is crucial to BD pathogenesis. We, therefore, propose that BD is an M1-dominant disease. In this review, we describe the roles of monocytes and macrophages in BD and consider the potential of these cells as therapeutic targets.

    DOI： 10.3389/fimmu.2022.852297

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  • ベーチェット病の難治性口腔潰瘍に対するアプレミラストの実臨床における1年間の治療成績

    中山 裕太, 平原 理紗, 桐野 洋平, 飯塚 友紀, 副島 裕太郎, 峯岸 薫, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   750 - 750   2022.3

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  • 当院における好酸球性多発血管炎性肉芽腫症40例の検討

    佐藤 雄一郎, 峯岸 薫, 吉見 竜介, 水野 広輝, 桐野 洋平, 永井 秀人, 濱田 直樹, 東谷 佳奈, 副島 裕太郎, 小宮 孝章, 櫻井 菜月, 平原 理紗, 前田 彩花, 秀川 智春, 飯塚 友紀, 吉岡 裕二, 安達 聡一郎, 土田 奈緒美, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   687 - 687   2022.3

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  • 大動脈周囲炎と間質性肺炎を合併したIgG4陰性自己免疫性膵炎の一例

    本多 主税, 峯岸 薫, 水野 広輝, 佐藤 雄一郎, 吉見 竜介, 東谷 佳奈, 永井 秀人, 濱田 直樹, 桐野 洋平, 中島 秀明

    関東リウマチ   54   9 - 11   2022.3

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    73歳男性。造影CTで膵尾部腫大、大動脈周囲の腫瘤性病変を認め、IgG4関連疾患を疑った。臨床検査、画像所見、病理組織所見で大動脈周囲炎、間質性肺炎、自己免疫膵炎を認めたが、血清IgG4は正常範囲で、病理所見はIgG4関連疾患の分類基準を満たさなかった。第19病日の造影CT、血液検査、臨床経過よりIgG4関連疾患で、大動脈周囲炎と間質性肺炎を合併したIgG4陰性自己免疫性膵炎と診断した。プレドニゾロンを開始した結果、膵酵素は速やかに改善し、膵炎および大動脈周囲炎も改善した。

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  • Current State and Issues of Regenerative Medicine for Rheumatic Diseases. Invited Reviewed International journal

    Ryusuke Yoshimi, Hideaki Nakajima

    Frontiers in medicine   9   813952 - 813952   2022.1

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    The prognosis of rheumatic diseases is generally better than that of malignant diseases. However, some cases with poor prognoses resist conventional therapies and cause irreversible functional and organ damage. In recent years, there has been much research on regenerative medicine, which uses stem cells to restore the function of missing or dysfunctional tissues and organs. The development of regenerative medicine is also being attempted in rheumatic diseases. In diseases such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and rheumatoid arthritis, hematopoietic stem cell transplantation has been attempted to correct and reconstruct abnormalities in the immune system. Mesenchymal stem cells (MSCs) have also been tried for the treatment of refractory skin ulcers in SSc using the ability of MSCs to differentiate into vascular endothelial cells and for the treatment of systemic lupus erythematosus SLE using the immunosuppressive effect of MSCs. CD34-positive endothelial progenitor cells (EPCs), which are found in the mononuclear cell fraction of bone marrow and peripheral blood, can differentiate into vascular endothelial cells at the site of ischemia. Therefore, EPCs have been used in research on vascular regeneration therapy for patients with severe lower limb ischemia caused by rheumatic diseases such as SSc. Since the first report of induced pluripotent stem cells (iPSCs) in 2007, research on regenerative medicine using iPSCs has been actively conducted, and their application to rheumatic diseases is expected. However, there are many safety issues and bioethical issues involved in regenerative medicine research, and it is essential to resolve these issues for practical application and spread of regenerative medicine in the future. The environment surrounding regenerative medicine research is changing drastically, and the required expertise is becoming higher. This paper outlines the current status and challenges of regenerative medicine in rheumatic diseases.

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  • Case Report: Tocilizumab Treatment for VEXAS Syndrome With Relapsing Polychondritis: A Single-Center, 1-Year Longitudinal Observational Study In Japan. Reviewed International journal

    Yosuke Kunishita, Yohei Kirino, Naomi Tsuchida, Ayaka Maeda, Yuichiro Sato, Kaoru Takase-Minegishi, Ryusuke Yoshimi, Hideaki Nakajima

    Frontiers in immunology   13   901063 - 901063   2022

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    Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an autoinflammatory disease caused by somatic variants in the UBA1 gene that lead to severe systemic inflammation and myelodysplastic syndrome. Although no standard therapy has been established yet, azacitidine and bone marrow transplantation have been reported to be promising possibilities; however, the indications for these treatments are problematic and not necessarily applicable to all patients. We previously reported the results of short-term treatment with tocilizumab (TCZ) and glucocorticoids in three patients with VEXAS syndrome. In this paper, we report that the combination of TCZ and glucocorticoids allowed the patients to continue treatment for at least one year without significant disease progression. Glucocorticoids were able to be reduced from the start of TCZ. Adverse events were herpes zoster, skin ulceration after cellulitis, and decreased blood counts. The results suggest the significance of this treatment as a bridge therapy for the development of future therapies.

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  • The Treatment of Systemic Sclerosis-related Pericarditis

    Ryusuke Yoshimi, Hideaki Nakajima

    Internal Medicine   2022

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    Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

    DOI： 10.2169/internalmedicine.9471-22

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  • The PRY/SPRY domain of pyrin/TRIM20 interacts with β2-microglobulin to promote inflammasome formation. Reviewed International journal

    Sei Samukawa, Ryusuke Yoshimi, Yohei Kirino, Hideaki Nakajima

    Scientific reports   11 ( 1 )   23613 - 23613   2021.12

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    Pyrin/TRIM20 is expressed in the neutrophils and monocytes/macrophages and regulates caspase-1 activation and interleukin-1β maturation. Although the mutations in the PRY/SPRY domain of pyrin cause familial Mediterranean fever (FMF), the mechanism of how mutated pyrin provokes excessive inflammation in FMF patients is not well understood. The present study investigated the role of pyrin/TRIM20 in inflammation and the pathogenesis of FMF. β2-Microglobulin (β2MG) was identified as the novel pyrin ligand binding to the PRY/SPRY domain by yeast two-hybrid screenings and co-immunoprecipitation analysis. β2MG was co-localized with pyrin not only in the HEK293 cells overexpressing these proteins but also in the monosodium urate-stimulated human neutrophils in the speck-like structures. The pyrin-β2MG interaction triggered the binding of pyrin and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) and then the subsequent recruitment of apoptosis-associated speck-like protein containing caspase recruitment domain (ASC). Caspase-1 p20 subunit, produced by pyrin inflammasome, also interacted with the pyrin PRY/SPRY domain and inhibited the pyrin-β2MG interaction. FMF-associated pyrin mutation M694V did not affect pyrin-β2MG interaction but weakened this inhibition. Our findings suggest that β2MG functions as the pyrin ligand inducing pyrin inflammasome formation and that the FMF-associated pyrin mutations weakened negative feedback of caspase-1 p20 subunit.

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  • Genetic and chemical inhibition of IRF5 suppresses pre-existing mouse lupus-like disease

    Tatsuma Ban, Masako Kikuchi, Go R. Sato, Akio Manabe, Noriko Tagata, Kayo Harita, Akira Nishiyama, Kenichi Nishimura, Ryusuke Yoshimi, Yohei Kirino, Hideyuki Yanai, Yoshiko Matsumoto, Shuichi Suzuki, Hiroe Hihara, Masashi Ito, Kappei Tsukahara, Kentaro Yoshimatsu, Tadashi Yamamoto, Tadatsugu Taniguchi, Hideaki Nakajima, Shuichi Ito, Tomohiko Tamura

    Nature Communications   12 ( 1 )   2021.12

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    <title>Abstract</title>The transcription factor IRF5 has been implicated as a therapeutic target for the autoimmune disease systemic lupus erythematosus (SLE). However, IRF5 activation status during the disease course and the effects of IRF5 inhibition after disease onset are unclear. Here, we show that SLE patients in both the active and remission phase have aberrant activation of IRF5 and interferon-stimulated genes. Partial inhibition of IRF5 is superior to full inhibition of type I interferon signaling in suppressing disease in a mouse model of SLE, possibly due to the function of IRF5 in oxidative phosphorylation. We further demonstrate that inhibition of IRF5 via conditional <italic>Irf5</italic> deletion and a newly developed small-molecule inhibitor of IRF5 after disease onset suppresses disease progression and is effective for maintenance of remission in mice. These results suggest that IRF5 inhibition might overcome the limitations of current SLE therapies, thus promoting drug discovery research on IRF5 inhibitors.

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    Other Link： http://www.nature.com/articles/s41467-021-24609-4

  • Population Pharmacokinetic Analysis and Dosing Optimization of Prophylactic Fluconazole in Japanese Patients with Hematological Malignancy

    Yasutaka Sakamoto, Hikaru Isono, Yuki Enoki, Kazuaki Taguchi, Takuya Miyazaki, Hiroyoshi Kunimoto, Hirofumi Koike, Maki Hagihara, Kenji Matsumoto, Hideaki Nakajima, Yukiko Sahashi, Kazuaki Matsumoto

    Journal of Fungi   7 ( 11 )   975 - 975   2021.11

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    We conducted population pharmacokinetic (PPK) analysis and Monte Carlo simulations to determine the appropriate prophylactic dose of fluconazole to prevent invasive candidiasis in patients with hematological malignancies. Patients receiving chemotherapy or hematopoietic stem cell transplantation at Yokohama City University Hospital between November 2018 and March 2020 were included. Additionally, patients receiving oral fluconazole for prophylaxis were recruited. We set the free area under the curve/minimum inhibitory concentration (MIC) = 50 as the target and determined the largest MIC (breakpoint MIC) that could achieve more than 90% probability of target attainment. The blood fluconazole concentration of 54 patients (119 points) was used for PPK analysis. The optimal model was the one-compartment model with first-order administration and first-order elimination incorporating creatinine clearance (CLcr) as a covariate of clearance and body weight as a covariate of distribution volume. We conducted Monte Carlo simulation with fluconazole at 200 mg/day or 400 mg/day dosing schedules and patient body weight and CLcr ranging from 40 to 70 kg and 40–140 mL/min, respectively. The breakpoint MICs on the first dosing day and at steady state were 0.5–1.0 μg/mL and 1.0–2.0 μg/mL for 200 mg/day and 1.0–2.0 μg/mL and 2.0–4.0 μg/mL for 400 mg/day, respectively. The recommended dose was 400–700 mg/day for the loading dose and 200–400 mg/day for the maintenance dose. Our findings suggest that the optimal prophylactic dose of fluconazole in hematological malignancy patients depends on CLcr and body weight, and a sufficient loading and maintenance dose may be needed to completely prevent invasive candidiasis.

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  • Beneficial Effects of Apremilast on Genital Ulcers, Skin Lesions, and Arthritis in Patients With Behçet's Disease: A Systematic Review and Meta-Analysis. International journal

    Yuki Iizuka, Kaoru Takase-Minegishi, Lisa Hirahara, Yohei Kirino, Yutaro Soejima, Ho Namkoong, Nobuyuki Horita, Ryusuke Yoshimi, Masaki Takeuchi, Mitsuhiro Takeno, Nobuhisa Mizuki, Hideaki Nakajima

    Modern rheumatology   32 ( 6 )   1153 - 1162   2021.11

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    OBJECTIVE: This study aimed to determine the clinical efficacy of apremilast for oral ulcers, extra-oral manifestations, and overall disease activity in patients with Behçet's disease (BD). METHODS: A systematic literature search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science Core Collection. Studies assessing the treatment effects of apremilast in BD were included. The odds ratios (ORs) of being symptom free for individual manifestations and mean difference (MD) of Behçet's Disease Current Activity Form (BDCAF) scores were calculated with 95% confidence intervals (CIs) at 12 and 24 weeks using a random-model meta-analysis. RESULTS: Of 259 screened articles, eight were included. After 12 weeks of apremilast treatment the OR of symptom-free was as followings: oral ulcers, 45.76 (95% CI, 13.23-158.31); genital ulcers, 4.56 (95% CI, 2.47-8.44); erythema nodosum, 3.59 (95% CI, 1.11-11.61); pseudofolliculitis, 2.81 (95% CI, 1.29-6.15); and arthritis, 3.55 (95% CI, 1.71-7.40). Furthermore, BDCAF scores at 12 weeks were significantly reduced (MD=-1.38; -1.78 to -0.99). However, the proportion of oral-ulcer free patients increased at 24 weeks (OR=14.88; 4.81 to 46.07). CONCLUSION: The currently accumulated data indicates an improvement in mucocutaneous and articular symptoms by short-term apremilast treatment in patients with BD.

    DOI： 10.1093/mr/roab098

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  • Tocilizumab in VEXAS relapsing polychondritis: a single-center pilot study in Japan

    Yohei Kirino, Kaoru Takase-Minegishi, Naomi Tsuchida, Lisa Hirahara, Yosuke Kunishita, Ryusuke Yoshimi, Hideaki Nakajima

    Annals of the Rheumatic Diseases   annrheumdis - 2021   2021.6

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    DOI： 10.1136/annrheumdis-2021-220876

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  • Detection of residual disease in chronic myeloid leukemia utilizing genomic next generation sequencing reveals persistence of differentiated Ph+ B cells but not bone marrow stem/progenitors

    Daiki Karigane, Hidenori Kasahara, Kouhei Shiroshita, Shinya Fujita, Hiroshi Kobayashi, Shinpei Tamaki, Rie Yamazaki, Kaori Yahagi, Yoko Yatabe, Naomi Kondoh, Tomoko Arai, Hisako Katagiri, Nobuko Shimizu, Masatoshi Sakurai, Taku Kikuchi, Jun Kato, Takayuki Shimizu, Taeko Hayakawa, Tomonori Yaguchi, Maiko Matsushita, Hideaki Nakajima, Yutaka Kawakami, Mitsuru Murata, Takehiko Mori, Takashi Sasaki, Shinichiro Okamoto, Keiyo Takubo

    Leukemia & Lymphoma   62 ( 3 )   679 - 687   2021.2

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    DOI： 10.1080/10428194.2020.1837366

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  • TET2: A cornerstone in normal and malignant hematopoiesis

    Hiroyoshi Kunimoto, Hideaki Nakajima

    Cancer Science   112 ( 1 )   31 - 40   2021.1

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    DOI： 10.1111/cas.14688

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  • OGT Regulates Hematopoietic Stem Cell Maintenance via PINK1-Dependent Mitophagy.

    Murakami K, Kurotaki D, Kawase W, Soma S, Fukuchi Y, Kunimoto H, Ryusuke Yoshimi, Shuhei Koide, Oshima M, Hishiki T, Hayakawa N, Matsuura T, Oda M, Yanagisawa K, Kobayashi H, Haraguchi M, Atobe Y, Funakoshi K, Iwama A, Keiyo Takubo, Okamoto S, Tamura T, Hideaki Nakajima

    Cell reports   2021.1

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    O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is a unique enzyme introducing O-GlcNAc moiety on target proteins, and it critically regulates various cellular processes in diverse cell types. However, its roles in hematopoietic stem and progenitor cells (HSPCs) remain elusive. Here, using Ogt conditional knockout mice, we show that OGT is essential for HSPCs. Ogt is highly expressed in HSPCs, and its disruption induces rapid loss of HSPCs with increased reactive oxygen species and apoptosis. In particular, Ogt-deficient hematopoietic stem cells (HSCs) lose quiescence, cannot be maintained in vivo, and become vulnerable to regenerative and competitive stress. Interestingly, Ogt-deficient HSCs accumulate defective mitochondria due to impaired mitophagy with decreased key mitophagy regulator, Pink1, through dysregulation of H3K4me3. Furthermore, overexpression of PINK1 restores mitophagy and the number of Ogt-deficient HSCs. Collectively, our results reveal that OGT critically regulates maintenance and stress response of HSCs by ensuring mitochondrial quality through PINK1-dependent mitophagy.

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  • Anti-TRIM21 antibody is associated with aberrant B-cell function and type I interferon production in systemic lupus erythematosus

    Yosuke Kunishita, Ryusuke Yoshimi, Reikou Kamiyama, Daiga Kishimoto, Takaaki Komiya, Natsuki Sakurai, Yumiko Sugiyama, Kaoru Takase-Minegishi, Yohei Kirino, Shouhei Nagaoka, Hideaki Nakajima

    Lupus   2021

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    DOI： 10.1177/09612033211042293

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  • Efficacy and safety of apremilast for 3 months in Behçet’s disease: A prospective observational study

    Lisa Hirahara, Yohei Kirino, Yutaro Soejima, Mitsuhiro Takeno, Kaoru Takase-Minegishi, Ryusuke Yoshimi, Masaki Takeuchi, Nobuhisa Mizuki, Hideaki Nakajima

    Modern Rheumatology   31 ( 4 )   856 - 861   2021

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    DOI： 10.1080/14397595.2020.1830504

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  • Incidence and Distinct Features of Immune Checkpoint Inhibitor-Related Myositis From Idiopathic Inflammatory Myositis: A Single-Center Experience With Systematic Literature Review and Meta-Analysis. International journal

    Naoki Hamada, Ayaka Maeda, Kaoru Takase-Minegishi, Yohei Kirino, Yumiko Sugiyama, Ho Namkoong, Nobuyuki Horita, Ryusuke Yoshimi, Hideaki Nakajima

    Frontiers in immunology   12   803410 - 803410   2021

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    Immune checkpoint inhibitor (ICI)-related myositis is a rare, potentially fatal condition that warrants further studies. Its incidence, clinical features, and prognosis remain poorly understood. To address these gaps, we conducted a systematic review and meta-analysis to evaluate the risk of myositis associated with ICI for solid tumors by analyzing phase III randomized controlled trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4). To complement this analysis with clinical data, we evaluated published ICI case reports along with cases from our institutional registry. This registry comprised 422 patients treated with ICIs alone or in combination from September 2014 to June 2021. The analysis revealed an incidence of ICI-related myositis in 6,838 patients in 18 randomized controlled trials of 0.38% (odds ratio 1.96; 95% confidence interval 1.02-3.75) for patients receiving ICIs compared with controls. Detailed analysis of 88 cases from the literature search and our registry showed that myositis induced by PD-1 inhibitors was more frequent than that induced by anti-CTLA-4 agents, revealing a clinically diverse trend including myasthenia gravis and myocarditis. Importantly, having ptosis at the time of onset was significantly associated with the development of concomitant myocarditis (odds ratio 3.81; 95% CI 1.48-9.83), which is associated with poor prognosis. Regarding treatment, most patients received glucocorticoids, and some received immunosuppressants. Our study revealed the incidence of ICI-mediated myositis and the clinical features of myocarditis, highlighting the need for recognition and early intervention.

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  • 当院におけるチェックポイント阻害剤による炎症性関節炎発症の実態と遺伝学的検討

    濱田 直樹, 桐野 洋平, 吉見 竜介, 山口 由衣, 寺尾 知可史, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   64回   690 - 690   2020.8

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  • TRIM21 dysfunction enhances aberrant B-cell differentiation in autoimmune pathogenesis. Reviewed

    Yosuke Kunishita, Ryusuke Yoshimi, Reikou Kamiyama, Daiga Kishimoto, Koji Yoshida, Eijin Hashimoto, Takaaki Komiya, Natsuki Sakurai, Yumiko Sugiyama, Yohei Kirino, Keiko Ozato, Hideaki Nakajima

    Front Immunol.   11   98   2020.2

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  • Refractory optic perineuritis related to granulomatosis with polyangiitis treated with intensive immunosuppressive therapy combined with plasma exchange. Reviewed

    Masaki Mitsuhashi, Ryusuke Yoshimi, Daiga Kishimoto, Chiharu Hidekawa, Yuki Iizuka, Natsuki Sakurai, Reikou Kamiyama, Yohei Kirino, Yukiho Kondo, Nobuhisa Mizuki, Hideaki Nakajima

    Mod Rheumatol Case Reports.   4 ( 1 )   84 - 89   2020.1

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    DOI： 10.1080/24725625.2019.1649857

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  • Dose down-titration of biological disease-modifying antirheumatic drugs in daily clinical practice: Shared decision-making and patient treatment preferences in Japanese patients with rheumatoid arthritis. Reviewed

    Takaaki Komiya, Kaoru Takase-Minegishi, Natsuki Sakurai, Hideto Nagai, Naoki Hamada, Yutaro Soejima, Yumiko Sugiyama, Naomi Tsuchida, Yosuke Kunishita, Daiga Kishimoto, Kouji Kobayashi, Reikou Kamiyama, Ryusuke Yoshimi, Yohei Kirino, Shigeru Ohno, Hideaki Nakajima

    Int J Rheum Dis.   22 ( 11 )   2009 - 2016   2019.11

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    DOI： 10.1111/1756-185X.13692

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  • Haploinsufficiency of A20 caused by a novel nonsense variant or entire deletion of TNFAIP3 is clinically distinct from Behçet's disease. Reviewed International journal

    Naomi Tsuchida, Yohei Kirino, Yutaro Soejima, Masafumi Onodera, Katsuhiro Arai, Eiichiro Tamura, Takashi Ishikawa, Toshinao Kawai, Toru Uchiyama, Shigeru Nomura, Daisuke Kobayashi, Masataka Taguri, Satomi Mitsuhashi, Takeshi Mizuguchi, Atsushi Takata, Noriko Miyake, Hideaki Nakajima, Satoko Miyatake, Naomichi Matsumoto

    Arthritis research & therapy   21 ( 1 )   137 - 137   2019.6

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    BACKGROUND: Haploinsufficiency of A20 (HA20) is caused by loss-of-function TNFAIP3 variants. Phenotypic and genetic features of HA20 remain uncertain; therefore, the clinical distinction between HA20 and Behçet's disease (BD) requires clarification. METHODS: We have collected 12 Japanese BD-like families. Probands of these families were analyzed by whole exome sequencing (WES) and subsequent Sanger sequencing. Clinical features were compared between 54 HA20 patients (including previously reported and new cases) and 520 Japanese BD patients. RESULTS: We identified c.1434C>A:p.(Cys478*) in one family and a 236 kb deletion at 6q23.3 containing TNFAIP3 in another family. Four HA20 patients in the two families presented with childhood-onset recurrent oral and genital ulcers and were initially diagnosed and treated as BD. Consistent with the clinical features of HA20, recurrent, refractory fever attacks (three of four patients), and digestive ulcers (two of the four patients) were observed. A comparison of clinical features between HA20 patients and cohorts of BD patients revealed several critical features specific to HA20. These were early-onset, familial occurrence, recurrent fever attacks, gastrointestinal involvement, and infrequent ocular involvement. CONCLUSIONS: We identified a novel nonsense variant and deletion of the entire TNFAIP3 gene in two unrelated Japanese HA20 families. Genetic screening of TNFAIP3 should be considered for familial BD-like patients with early-onset recurrent fevers.

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  • Impact of therapeutic angiogenesis using autologous bone marrow-derived mononuclear cells implantation in critical limb ischemia with scleroderma - subanalysis of the long-term clinical outcomes survey. Reviewed

    Keisuke Shoji, Kenji Yanishi, Ryusuke Yoshimi, Naoki Hamada, Kazuhisa Kondo, Kazuteru Fujimoto, Hideaki Nakajima, Koichiro Kuwahara, Yukihito Higashi, Yoshihiro Fukumoto, Toyoaki Murohara, Satoaki Matoba, TACT Follow u, Study Investigators

    Circ J.   83 ( 3 )   662 - 671   2019.2

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  • miR-1 is a novel biomarker for polymyositis/dermatomyositis-associated interstitial lung disease. Reviewed

    Yumiko Sugiyama, Ryusuke Yoshimi, Mitsuhiro Takeno, Yosuke Kunishita, Daiga Kishimoto, Reikou Kamiyama, Yohei Kirino, Shigeru Ohno, Hideaki Nakajima

    Mod Rheumatol.   In press   2019

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    DOI： 10.1080/14397595.2019.1661584

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  • Dysfunction of TRIM21 in interferon signature of systemic lupus erythematosus. Reviewed

    Reikou Kamiyama, Ryusuke Yoshimi, Mitsuhiro Takeno, Yasuhiro Iribe, Toshinori Tsukahara, Daiga Kishimoto, Yosuke Kunishita, Yumiko Sugiyama, Naomi Tsuchida, Hiroto Nakano, Kaoru Minegishi, Maasa Tamura, Yukiko Asami, Yohei Kirino, Yoshiaki Ishigatsubo, Keiko Ozato, Hideaki Nakajima

    Mod Rheumatol.   28 ( 6 )   993 - 1003   2018.11

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    DOI： 10.1080/14397595.2018.1436028

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  • Successful treatment of extensive venous thrombosis with combination of immunosuppressants and a direct Xa inhibitor in Behçet’s disease. Reviewed

    Chiharu Hidekawa, Kaoru Minegishi, Kouji Kobayashi, Ryusuke Yoshimi, Yohei Kirino, Shigeru Ohno, Mitsuhiro Takeno, Hideaki Nakajima

    Mod Rheumatol Case Reports.   2 ( 2 )   204 - 208   2018.7

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    DOI： 10.1007/978-3-540-75387-2_66

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  • GWAS-identified CCR1 and IL10 loci contribute to M1 macrophage-predominant inflammation in Behçet's disease. Reviewed

    Hiroto Nakano, Yohei Kirino, Mitsuhiro Takeno, Kana Higashitani, Hideto Nagai, Ryusuke Yoshimi, Yukie Yamaguchi, Ikuma Kato, Ichiro Aoki, Hideaki Nakajima

    Arthritis Res Ther.   20 ( 1 )   124   2018.6

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  • Dysregulated heme oxygenase-1low M2-like macrophages augment lupus nephritis via Bach1 induced by type I interferons. Reviewed

    Daiga Kishimoto, Yohei Kirino, Maasa Tamura, Mitsuhiro Takeno, Yosuke Kunishita, Kaoru Takase-Minegishi, Hiroto Nakano, Ikuma Kato, Kiyotaka Nagahama, Ryusuke Yoshimi, Kazuhiko Igarashi, Ichiro Aoki, Hideaki Nakajima

    Arthritis Res Ther.   20 ( 1 )   64   2018.4

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  • Angiotensin receptor-binding molecule in leukocytes in association with the systemic and leukocyte inflammatory profile. Reviewed International journal

    Kotaro Haruhara, Hiromichi Wakui, Kengo Azushima, Daisuke Kurotaki, Wataru Kawase, Kazushi Uneda, Sona Haku, Ryu Kobayashi, Kohji Ohki, Sho Kinguchi, Masato Ohsawa, Shintaro Minegishi, Tomoaki Ishigami, Miyuki Matsuda, Akio Yamashita, Hideaki Nakajima, Tomohiko Tamura, Nobuo Tsuboi, Takashi Yokoo, Kouichi Tamura

    Atherosclerosis   269   236 - 244   2018.2

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    BACKGROUND AND AIMS: The components of the renin-angiotensin system in leukocytes is involved in the pathophysiology of non-communicable diseases (NCDs), including hypertension, atherosclerosis and chronic kidney disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) is an AT1R-specific binding protein, and is able to inhibit the pathological activation of AT1R signaling in certain animal models of NCDs. The aim of the present study was to investigate the expression and regulation of ATRAP in leukocytes. METHODS: Human leukocyte ATRAP mRNA was measured with droplet digital polymerase chain reaction system, and analyzed in relation to the clinical variables. We also examined the leukocyte cytokines mRNA in bone-marrow ATRAP-deficient and wild-type chimeric mice after injection of low-dose lipopolysaccharide. RESULTS: The ATRAP mRNA was abundantly expressed in leukocytes, predominantly granulocytes and monocytes, of healthy subjects. In 86 outpatients with NCDs, leukocyte ATRAP mRNA levels correlated positively with granulocyte and monocyte counts and serum C-reactive protein levels. These positive relationships remained significant even after adjustment. Furthermore, the leukocyte ATRAP mRNA was significantly associated with the interleukin-1β, tumor necrosis factor-α and monocyte chemotactic protein-1 mRNA levels in leukocytes of NCDs patients. In addition, the leukocyte interleukin-1β mRNA level was significantly upregulated in bone marrow ATRAP-deficient chimeric mice in comparison to wild-type chimeric mice after injection of lipopolysaccharide. CONCLUSIONS: These results suggest that leukocyte ATRAP is an emerging marker capable of reflecting the systemic and leukocyte inflammatory profile, and plays a role as an anti-inflammatory factor in the pathophysiology of NCDs.

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  • Diagnostic test accuracy of ultrasound for synovitis in rheumatoid arthritis: systematic review and meta-analysis. Reviewed

    Kaoru Takase-Minegishi, Nobuyuki Horita, Kouji Kobayashi, Ryusuke Yoshimi, Yohei Kirino, Shigeru Ohno, Takeshi Kaneko, Hideaki Nakajima, Richard J. Wakefield, Paul Emery

    Rheumatology (Oxford)   57 ( 1 )   49 - 58   2018.1

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    DOI： 10.1093/rheumatology/kex036

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  • The predictive prognostic factors for polymyositis/dermatomyositis-associated interstitial lung disease. Reviewed

    Yumiko Sugiyama, Ryusuke Yoshimi, Maasa Tamura, Mitsuhiro Takeno, Yosuke Kunishita, Daiga Kishimoto, Yuji Yoshioka, Kouji Kobayashi, Kaoru Takase-Minegishi, Toshiyuki Watanabe, Naoki Hamada, Hideto Nagai, Naomi Tsuchida, Yutaro Soejima, Hiroto Nakano, Reikou Kamiyama, Takeaki Uehara, Yohei Kirino, Akiko Sekiguchi, Atsushi Ihata, Shigeru Ohno, Shouhei Nagaoka, Hideaki Nakajima

    Arthritis Res Ther.   20 ( 1 )   7   2018.1

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  • Epigenetic dysregulation of hematopoietic stem cells and preleukemic state Invited Reviewed

    Hiroyoshi Kunimoto, Hideaki Nakajima

    INTERNATIONAL JOURNAL OF HEMATOLOGY   106 ( 1 )   34 - 44   2017.7

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  • Outcome and prognostic factors among patients who underwent a second transplantation for disease relapse post the first allogeneic cell transplantation Reviewed

    Takayoshi Tachibana, Kenji Matsumoto, Masatsugu Tanaka, Maki Hagihara, Kenji Motohashi, Wataru Yamamoto, Eriko Ogusa, Satoshi Koyama, Ayumi Numata, Naoto Tomita, Jun Taguchi, Shin Fujisawa, Heiwa Kanamori, Hideaki Nakajima

    LEUKEMIA & LYMPHOMA   58 ( 6 )   1403 - 1411   2017.6

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  • Body mass index is a prognostic factor in adult patients with acute myeloid leukemia Reviewed

    Taiki Ando, Etsuko Yamazaki, Eriko Ogusa, Yoshimi Ishii, Wataru Yamamoto, Kenji Motohashi, Takayoshi Tachibana, Maki Hagihara, Kenji Matsumoto, Masatsugu Tanaka, Chizuko Hashimoto, Hideyuki Koharazawa, Katsumichi Fujimaki, Jun Taguchi, Hiroyuki Fujita, Heiwa Kanamori, Shin Fujisawa, Hideaki Nakajima

    INTERNATIONAL JOURNAL OF HEMATOLOGY   105 ( 5 )   623 - 630   2017.5

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  • Musculoskeletal ultrasonography delineates ankle symptoms in rheumatoid arthritis. Reviewed

    Yukihiro Toyota, Maasa Tamura, Yohei Kirino, Yumiko Sugiyama, Naomi Tsuchida, Yosuke Kunishita, Daiga Kishimoto, Reikou Kamiyama, Miura Yasushi, Kaoru Minegishi, Ryusuke Yoshimi, Atsuhisa Ueda, Hideaki Nakajima

    Mod Rheumatol.   27 ( 3 )   425 - 429   2017.5

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  • On-demand ultrasonography assessment in the most symptomatic joint supports the 8-joint score system for management of rheumatoid arthritis patients Reviewed

    Ryusuke Yoshimi, Mitsuhiro Takeno, Yukihiro Toyota, Naomi Tsuchida, Yumiko Sugiyama, Yosuke Kunishita, Daiga Kishimoto, Reikou Kamiyama, Kaoru Minegishi, Maasa Hama, Yohei Kirino, Yoshiaki Ishigatsubo, Shigeru Ohno, Atsuhisa Ueda, Hideaki Nakajima

    MODERN RHEUMATOLOGY   27 ( 2 )   257 - 265   2017.3

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  • CTD-4 ベーチェット病におけるマクロファージの機能的な分析 C-Cケモカイン受容体1型(CCR1)とインターロイキン(IL)-10は本疾患の病状形成に関与する(CTD Functional Analysis of Macrophages in Behcet's Disease: C-C Chemokine Receptor Type 1(CCR1) and IL-10 are Implicated in Pathogenesis of the Disease)

    Nakano Hiroto, Kirino Yohei, Ohno Momoko, Higashitani Kana, Takeno Mitsuhiro, Yoshimi Ryusuke, Ueda Atsuhisa, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   398 - 398   2017.3

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  • Successful treatment of a patient with refractory haemophagocytic syndrome in systemic lupus erythematosus with mycophenolate mofetil. Reviewed

    Yumiko Sugiyama, Kaoru Minegishi, Naoki Hamada, Hideto Nagai, Yuko Tatekabe, Naomi Tsuchida, Yutaro Soejima, Yosuke Kunishita, Daiga Kishimoto, Hiroto Nakano, Reikou Kamiyama, Maasa Tamura, Ryusuke Yoshimi, Yukiko Asami, Yohei Kirino, Atsuhisa Ueda, Hideaki Nakajima

    Modern Rheumatology Case Reports   1 ( 2 )   79 - 83   2017.2

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  • Outcome of Newly Diagnosed Acute Myeloid Leukemia with Hyperleukocytosis: Retrospective Study of JALSG AML201 Reviewed

    Kenji Matsumoto, Shin Fujisawa, Maki Hagihara, Sumihisa Honda, Shigeki Ohtake, Shuichi Miyawaki, Toru Sakura, Dobashi Nobuaki, Kinya Ohata, Yukiyasu Ozawa, Iekuni Ou, Asao Hirose, Tomoya Maeda, Yoshikazu Ito, Noriko Doki, Hitoshi Kiyoi, Kazunori Ohnishi, Tomoki Naoe, Yasushi Miyazaki, Hideaki Nakajima

    BLOOD   128 ( 22 )   2016.12

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  • Residual Blast Cells in Bone Marrow on Day 15 Following Remission Induction Therapy for Acute Myeloid Leukemia Is Associated with Long-Term Prognosis: A Retrospective Analysis of the JALSG AML201 Study Reviewed

    Maki Hagihara, Shin Fujisawa, Sumihisa Honda, Shigeki Ohtake, Shuichi Miyawaki, Nobuaki Dobashi, Toru Sakura, Yukiyasu Ozawa, Yoshikazu Ito, Katsumichi Fujimaki, Asao Hirose, Hiroyuki Fujita, Kinya Ohata, Tomoya Maeda, Toshi Imai, Hitoshi Kiyoi, Yasushi Miyazaki, Kazunori Ohnishi, Tomoki Naoe, Hideaki Nakajima

    BLOOD   128 ( 22 )   2016.12

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  • Continuous evolution of clinical phenotype in 578 Japanese Behçet's disease patients: a retrospective observational study. Reviewed

    Yohei Kirino, Haruko Ideguchi, Mitsuhiro Takeno, Akiko Suda, Kana Higashitani, Yosuke Kunishita, Kaoru Takase-Minegishi, Maasa Tamura, Toshiyuki Watanabe, Yukiko Asami, Ryusuke Yoshimi, Takeaki Uehara, Tetsu Yamazaki, Akiko Sekiguchi, Atsushi Ihata, Shigeru Ohno, Atsuhisa Ueda, Toshihisa Igarashi, Shohei Nagaoka, Yoshiaki Ishigatsubo, Hideaki Nakajima

    Arthritis Res Ther.   18 ( 1 )   217   2016.10

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  • Non-IgG4-related multifocal fibrosclerosis. Reviewed

    Yosuke Kunishita, Ryusuke Yoshimi, Mitsuhiro Takeno, Shoji Yamanaka, Yumiko Sugiyama, Naomi Tsuchida, Daiga Kishimoto, Reikou Kamiyama, Kaoru Minegishi, Maasa Hama, Yohei Kirino, Yoshiaki Ishigatsubo, Atsuhisa Ueda, Hideaki Nakajima

    Intern Med.   55 ( 17 )   2497 - 2502   2016.9

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  • Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan Reviewed

    A. Yoshimi, T. Toya, Y. Nannya, K. Takaoka, K. Kirito, E. Ito, H. Nakajima, Y. Hayashi, T. Takahashi, A. Moriya-Saito, K. Suzuki, H. Harada, N. Komatsu, K. Usuki, M. Ichikawa, M. Kurokawa

    ANNALS OF ONCOLOGY   27 ( 5 )   887 - 895   2016.5

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  • Favorable prognosis in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia patients following hematopoietic stem cell transplantation Reviewed

    Ayumi Numata, Shin Fujisawa, Megumi Itabashi, Yoshimi Ishii, Wataru Yamamoto, Kenji Motohashi, Kenji Matsumoto, Maki Hagihara, Hideaki Nakajima

    CLINICAL TRANSPLANTATION   30 ( 5 )   485 - 486   2016.5

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  • Genetic basis of myeloid transformation in familial platelet disorder/acute myeloid leukemia patients with haploinsufficient RUNX1 allele Reviewed

    M. Sakurai, H. Kasahara, K. Yoshida, A. Yoshimi, H. Kunimoto, N. Watanabe, Y. Shiraishi, K. Chiba, H. Tanaka, Y. Harada, H. Harada, T. Kawakita, M. Kurokawa, S. Miyano, S. Takahashi, S. Ogawa, S. Okamoto, H. Nakajima

    BLOOD CANCER JOURNAL   6   e392   2016.2

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  • RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity Reviewed

    D. W. L. Chin, M. Sakurai, G. S. S. Nah, L. Du, B. Jacob, T. Yokomizo, T. Matsumura, T. Suda, G. Huang, X-Y Fu, Y. Ito, H. Nakajima, M. Osato

    BLOOD CANCER JOURNAL   6   e379   2016.1

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  • RUNX1制御破綻による骨髄異形成/骨髄増殖性腫瘍発症機序の解明

    櫻井 弘子, 原田 結花, 松井 啓隆, 中島 秀明, 土岐 典子, 垣花 和彦, 大橋 一輝, 北村 俊雄, 小松 則夫, 原田 浩徳

    日本癌学会総会記事   74回   E - 1005   2015.10

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  • Unfavorable outcome of chronic myelogenous leukemia in adolescent and young adults treated with tyrosine kinase inhibitors Reviewed

    Masatoshi Sakurai, Takehiko Mori, Daiki Karigane, Keiichi Tozawa, Eri Matsuki, Takayuki Shimizu, Kenji Yokoyama, Hideaki Nakajima, Yoshinobu Kanda, Shinichiro Okamoto

    INTERNATIONAL JOURNAL OF HEMATOLOGY   102 ( 3 )   342 - 348   2015.9

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  • A phase II study of bendamustine plus rituximab in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma previously treated with rituximab: BRB study Reviewed

    Kimihiro Matsumoto, Nobuyuki Takayama, Yoshinobu Aisa, Hironori Ueno, Masao Hagihara, Kentaro Watanabe, Aya Nakaya, Kenko Chen, Takayuki Shimizu, Yuiko Tsukada, Yuji Yamada, Tomonori Nakazato, Akaru Ishida, Yoshitaka Miyakawa, Kenji Yokoyama, Hideaki Nakajima, Yoshihiro Masuda, Takahiro Yano, Shinichiro Okamoto

    INTERNATIONAL JOURNAL OF HEMATOLOGY   101 ( 6 )   554 - 562   2015.6

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    DOI： 10.1007/s12185-015-1767-3

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  • Immune-mediated Neuropathy with Anti-disialosyl IgM Antibodies in Diffuse Large B-cell Lymphoma: A Case Report and Literature Review Reviewed

    Gen Shihashi, Takuya Yagi, Shigeaki Suzuki, Morinobu Seki, Sumiko Kohashi, Tomoki Ueda, Kaori Kameyama, Susumu Kusunoki, Hideaki Nakajima, Shinichiro Okamoto, Norihiro Suzuki

    INTERNAL MEDICINE   54 ( 13 )   1647 - 1651   2015

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    DOI： 10.2169/internalmedicine.54.4451

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  • Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD/AML patients Reviewed

    M. Sakurai, H. Kunimoto, N. Watanabe, Y. Fukuchi, S. Yuasa, S. Yamazaki, T. Nishimura, K. Sadahira, K. Fukuda, H. Okano, H. Nakauchi, Y. Morita, I. Matsumura, K. Kudo, E. Ito, Y. Ebihara, K. Tsuji, Y. Harada, H. Harada, S. Okamoto, H. Nakajima

    LEUKEMIA   28 ( 12 )   2344 - 2354   2014.12

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    DOI： 10.1038/leu.2014.136

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  • Gossypol induces apoptosis in multiple myeloma cells by inhibition of interleukin-6 signaling and Bcl-2Mcl-1 pathway Reviewed

    Ken Sadahira, Morihiko Sagawa, Tomonori Nakazato, Hideo Uchida, Yasuo Ikeda, Shinichiro Okamoto, Hideaki Nakajima, Masahiro Kizaki

    INTERNATIONAL JOURNAL OF ONCOLOGY   45 ( 6 )   2278 - 2286   2014.12

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    DOI： 10.3892/ijo.2014.2652

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  • TET2 as an epigenetic master regulator for normal and malignant hematopoiesis Reviewed

    Hideaki Nakajima, Hiroyoshi Kunimoto

    CANCER SCIENCE   105 ( 9 )   1093 - 1099   2014.9

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  • Recurrent CDC25C mutations drive malignant transformation in FPD/AML Reviewed

    Akihide Yoshimi, Takashi Toya, Masahito Kawazu, Toshihide Ueno, Ayato Tsukamoto, Hiromitsu Iizuka, Masahiro Nakagawa, Yasuhito Nannya, Shunya Arai, Hironori Harada, Kensuke Usuki, Yasuhide Hayashi, Etsuro Ito, Keita Kirito, Hideaki Nakajima, Motoshi Ichikawa, Hiroyuki Mano, Mineo Kurokawa

    NATURE COMMUNICATIONS   5   4770   2014.8

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    DOI： 10.1038/ncomms5770

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  • Tet2-mutated myeloid progenitors possess aberrant in vitro self-renewal capacity Reviewed

    Hiroyoshi Kunimoto, Yumi Fukuchi, Masatoshi Sakurai, Keiyo Takubo, Shinichiro Okamoto, Hideaki Nakajima

    BLOOD   123 ( 18 )   2897 - 2899   2014.5

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  • [Hydroxyurea (hydroxycarbamide)-induced hepatic dysfunction confirmed by drug-induced lymphocyte stimulation test]. Reviewed

    Shimizu T, Mori T, Karigane D, Kikuchi T, Koda Y, Toyama T, Nakajima H, Okamoto S

    [Rinsho ketsueki] The Japanese journal of clinical hematology   55 ( 1 )   125 - 129   2014.1

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    A 62-year-old man with refractory leukemia transformed from myelodysplastic syndrome was placed on hydroxyurea (hydroxycarbamide) at a daily dose of 500 mg. Because of insufficient cytoreductive efficacy, the dose was increased to 1,500 mg five days later. Eight days after the initiation of hydroxyurea, the patient started complaining of chills, fever, and vomiting. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly elevated to 5,098 and 3,880 IU/l from 44 and 59 IU/l in one day, respectively. Tests for hepatitis viruses were all negative. With the discontinuation of hydroxyurea, AST and ALT returned to their former levels within two weeks. A drug-induced lymphocyte stimulation test for hydroxyurea was positive with a stimulating index of 2.0. Hepatic dysfunction has been recognized as one of the side effects of hydroxyurea. However, there have been only a limited number of reports demonstrating drug allergy to have a role in hepatic dysfunction accompanied by fever and gastrointestinal symptoms. The findings of our case strongly suggest that all presentations could be explained by drug allergy. Physicians should be mindful of the potential for acute and severe hepatic dysfunction due to allergic reaction against hydroxyurea.

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  • The Genetic Landscape Of FPD/AML Revealed CDC25C Mutation As a Driver That Promotes Malignant Transformation

    Akihide Yoshimi, Takashi Toya, Masahiro Nakagawa, Masahito Kawazu, Yasuhito Nannya, Motoshi Ichikawa, Shunya Arai, Hironori Harada, Kensuke Usuki, Yasuhide Hayashi, Etsuro Ito, Keita Kirito, Hideaki Nakajima, Hiroyuki Mano, Mineo Kurokawa

    Blood   122 ( 21 )   739 - 739   2013.11

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    Abstract

    Familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML) is an autosomal dominant disorder and is characterized by inherited thrombocytopenia and a lifelong risk of development of hematological malignancies. Although inherited RUNX1 mutation is the cause of thrombocytopenia, additional genetic events may be responsible for the tumor development as only 40 % of FPD/AML patients develop leukemia. Because of the rarity of this disorder, underlying mechanisms for malignant transformation in FPD/AML have not been elucidated. Thus we conducted a nationwide survey in Japan to collect samples and make a diagnosis of patients with familial thrombocytopenia or hematological malignancies. As a result, 56 pedigrees were extracted, and seven pedigrees with RUNX1 mutation were diagnosed as having FPD/AML, in which eight out of 14 patients had developed hematological malignancies. To systematically identify additional genetic alterations, we utilized whole exome sequencing in two patients with FPD/AML who had RUNX1_F303fsX566 mutation and developed MDS (Patient 1) or myelofibrosis (Patient 2) followed by AML. We identified 12 and 10 somatically acquired nonsynonymous mutations in these patients, respectively. Intriguingly, the two patients had common CDC25C mutation at codon 234 (D234G). Further genomic screening of other pedigrees revealed that four out of eight FPD/AML patients who developed hematological malignancy harbored somatic mutations in CDC25C (CDC25C_D234G in three patients and CDC25C_H437N in one patient). Recurrent CDC25C mutation in FPD/AML with subsequent hematological malignancy implies that it forms common genetic foundation of transformation in this disease. CDC25C is a phosphatase that prevents premature mitosis in response to DNA damage at the G2/M checkpoint, while it is constitutively phosphorylated at Ser216 throughout the interphase by c-TAK1. When phosphorylated at Ser216, CDC25C binds to 14-3-3 protein, which sequestrates CDC25C in the cytoplasm and inactivates it. In all of the mutated forms of CDC25C that we found in FPD/AML, their binding capacity with c-TAK1 and 14-3-3 protein was reduced, resulting in decreased phosphorylation status of CDC25C at Ser216. As a consequence, those CDC25C mutants led to enhanced mitosis entry, which was exaggerated by radiation-induced DNA damage. These results demonstrate that CDC25C mutation results in disruption of DNA checkpoint machinery. It is known that FPD/AML-associated RUNX1 mutations evokes DNA damage and induces cell cycle arrest in hematopoietic cells, suggesting that the DNA checkpoint mechanism is activated in the presence of those types of RUNX1 mutation. We found, however, that introduction of CDC25C mutation results in the marked enhancement of mitosis entry in spite of co-expression of RUNX1 mutation in Ba/F3 cells. Thus, premature mitosis by loss of DNA checkpoint mechanisms in the presence of mutated CDC25C may contribute to malignant transformation of RUNX1-mutated cells. Interestingly, analysis of clonal evolution during leukemic transformation revealed that a clone defined by CDC25C mutation was dominant in the early phase of disease progression in both patients, which supports the idea that CDC25C mutation is associated with establishment of the founder clone during the leukemic progression of FPD/AML. In Patient 1, the founder clone with CDC25C mutation acquired FAM22G and COL9A1 (group 1) mutations, followed by occurrence of GATA2 and LPP (group 2) mutations to become a dominant clone in the AML phase, whereas another subclone of the founder defined by CHEK2 and DTX2 (group 3) mutations regressed. Similar hierarchical progression was observed in Patient 2. An additional single cell genomic sequencing of bone marrow cells from Patient 1 in the AML phase revealed that group 1/2 mutations and group 3 mutations were mutually exclusive, which supports our predicted model. Collectively, these results indicate that somatic mutation in CDC25C is a recurrent event in the early phase of leukemic progression of FPD/AML, which induces premature mitosis and genetic instability in hematopoietic cells with germline RUNX1 mutation.

    Disclosures:

    Usuki: Alexion Pharmaceuticals, Inc.: Speakers Bureau. Kurokawa:Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Research Funding.

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  • Plzf drives MLL-fusion-mediated leukemogenesis specifically in long-term hematopoietic stem cells Reviewed

    Ryoichi Ono, Masahiro Masuya, Hideaki Nakajima, Yutaka Enomoto, Eri Miyata, Akihide Nakamura, Satomi Ishii, Kei Suzuki, Fumi Shibata-Minoshima, Naoyuki Katayama, Toshio Kitamura, Tetsuya Nosaka

    BLOOD   122 ( 7 )   1271 - 1283   2013.8

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  • Robo4 Plays a Role in Bone Marrow Homing and Mobilization, but Is Not Essential in the Long-Term Repopulating Capacity of Hematopoietic Stem Cells Reviewed

    Yuko Goto-Koshino, Yumi Fukuchi, Fumi Shibata, Daichi Abe, Kana Kuroda, Shinichiro Okamoto, Toshio Kitamura, Hideaki Nakajima

    PLOS ONE   7 ( 11 )   e50849   2012.11

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  • Direct reprogramming of terminally differentiated B cells into erythroid lineage Reviewed

    Ken Sadahira, Yumi Fukuchi, Hiroyoshi Kunimono, Masatoshi Sakurai, Yasuo Ikeda, Shinichiro Okamoto, Hideaki Nakajima

    FEBS LETTERS   586 ( 20 )   3645 - 3652   2012.10

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    DOI： 10.1016/j.febslet.2012.08.019

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  • [B-cell acute lymphoblastic leukemia developed 5 years after autologous stem cell transplantation for multiple myeloma]. Reviewed

    Tsukada Y, Hattori Y, Nakajima H, Yokoyama K, Murata M, Shimizu N, Kondo N, Okamoto S

    [Rinsho ketsueki] The Japanese journal of clinical hematology   53 ( 2 )   219 - 223   2012.2

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  • Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells Reviewed

    Hiroyoshi Kunimoto, Yumi Fukuchi, Masatoshi Sakurai, Ken Sadahira, Yasuo Ikeda, Shinichiro Okamoto, Hideaki Nakajima

    SCIENTIFIC REPORTS   2   273   2012.2

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    DOI： 10.1038/srep00273

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  • [Signaling pathways regulating hematopoiesis and their roles in hematopoietic malignancies]. Reviewed

    Nakajima H

    [Rinsho ketsueki] The Japanese journal of clinical hematology   52 ( 10 )   1677 - 1686   2011.10

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  • The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress Reviewed

    Jo Ishizawa, Shinji Kuninaka, Eiji Sugihara, Hideaki Naoe, Yusuke Kobayashi, Tatsuyuki Chiyoda, Arisa Ueki, Kimi Araki, Ken-ichi Yamamura, Yumi Matsuzaki, Hideaki Nakajima, Yasuo Ikeda, Shinichiro Okamoto, Hideyuki Saya

    CANCER SCIENCE   102 ( 5 )   967 - 974   2011.5

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    Various key cell cycle components, especially G0/G1 regulators, have effects not only on cell proliferation but also on cell differentiation. Cdh1, one of the co-activators that maintain anaphase-promoting complex/cyclosome activity, plays a crucial role in the mitotic phase, but has recently been identified as a G0/G1 regulator, suggesting that the role of Cdh1 in cell differentiation. Here, we generated Cdh1 conditional gene-trap mice to examine Cdh1 functions in adult tissues by overcoming the embryonic lethality of Cdh1 homozygous gene-trap mice. We focused on the hematopoietic system and found that Cdh1-deficient mice exhibited a general decrease in mature lineage progenitor cells and a significant increase in short-term hematopoietic stem cells. This phenomenon became conspicuous by irradiation shortly after Cdh1 downregulation, suggesting that Cdh1 regulates the pool sizes of the hematopoietic stem cells and mature lineage progenitor cells by protecting cells from genotoxic stress. We also found that the irradiation-induced G2/M checkpoint was defective in Cdh1-deficient BM cells, causing the loss of stem/progenitor cells. This is the first report revealing Cdh1 function in adult hematopoiesis and showing a role of Cdh1 in a G2/M checkpoint regulation in vivo. (Cancer Sci 2011; 102: 967-974).

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  • The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress

    Ishizawa, J, Kuninaka, S, Sugihara, E, Naoe, H, Kobayashi, Y, Chiyoda, T, Ueki, A, Araki, K, Yamamura, K, Matsuzaki, Y, Nakajima, H, Ikeda, Y, Okamoto, S, Saya, H

    Cancer Sci   102 ( 5 )   967 - 74   2011.5

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    Various key cell cycle components, especially G0/G1 regulators, have effects not only on cell proliferation but also on cell differentiation. Cdh1, one of the co-activators that maintain anaphase-promoting complex/cyclosome activity, plays a crucial role in the mitotic phase, but has recently been identified as a G0/G1 regulator, suggesting that the role of Cdh1 in cell differentiation. Here, we generated Cdh1 conditional gene-trap mice to examine Cdh1 functions in adult tissues by overcoming the embryonic lethality of Cdh1 homozygous gene-trap mice. We focused on the hematopoietic system and found that Cdh1-deficient mice exhibited a general decrease in mature lineage progenitor cells and a significant increase in short-term hematopoietic stem cells. This phenomenon became conspicuous by irradiation shortly after Cdh1 downregulation, suggesting that Cdh1 regulates the pool sizes of the hematopoietic stem cells and mature lineage progenitor cells by protecting cells from genotoxic stress. We also found that the irradiation-induced G2/M checkpoint was defective in Cdh1-deficient BM cells, causing the loss of stem/progenitor cells. This is the first report revealing Cdh1 function in

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  • Two types of C/EBP alpha mutations play distinct but collaborative roles in leukemogenesis: lessons from clinical data and BMT models Reviewed

    Naoko Kato, Jiro Kitaura, Noriko Doki, Yukiko Komeno, Naoko Watanabe-Okochi, Katsuhiro Togami, Fumio Nakahara, Toshihiko Oki, Yutaka Enomoto, Yumi Fukuchi, Hideaki Nakajima, Yuka Harada, Hironori Harada, Toshio Kitamura

    BLOOD   117 ( 1 )   221 - 233   2011.1

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    DOI： 10.1182/blood-2010-02-270181

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  • Role of transcription factors in differentiation and reprogramming of hematopoietic cells Reviewed

    Hideaki Nakajima

    Keio Journal of Medicine   60 ( 2 )   47 - 55   2011

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    DOI： 10.2302/kjm.60.47

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  • TIMP-3 recruits quiescent hematopoietic stem cells into active cell cycle and expands multipotent progenitor pool Reviewed

    Hideaki Nakajima, Miyuki Ito, David S. Smookler, Fumi Shibata, Yumi Fukuchi, Yoshihiro Morikawa, Yuichi Ikeda, Fumio Arai, Toshio Suda, Rama Khokha, Toshio Kitamura

    BLOOD   116 ( 22 )   4474 - 4482   2010.11

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    DOI： 10.1182/blood-2010-01-266528

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  • Wnt modulators, SFRP-1, and SFRP-2 are expressed in osteoblasts and differentially regulate hematopoietic stem cells Reviewed

    Hideaki Nakajima, Miyuki Ito, Yoshihiro Morikawa, Tadasuke Komori, Yumi Fukuchi, Fumi Shibata, Shinichiro Okamoto, Toshio Kitamura

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   390 ( 1 )   65 - 70   2009.12

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    DOI： 10.1016/j.bbrc.2009.09.067

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  • Possible involvement of RasGRP4 in leukemogenesis Reviewed

    Naoko Watanabe-Okochi, Toshihiko Oki, Yukiko Komeno, Naoko Kato, Koichiro Yuji, Ryoichi Ono, Yuka Harada, Hironori Harada, Yasuhide Hayashi, Hideaki Nakajima, Tetsuya Nosaka, Jiro Kitaura, Toshio Kitamura

    INTERNATIONAL JOURNAL OF HEMATOLOGY   89 ( 4 )   470 - 481   2009.5

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    DOI： 10.1007/s12185-009-0299-0

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  • Mixed-lineage-leukemia (MLL) fusion protein collaborates with Ras to induce acute leukemia through aberrant Hox expression and Raf activation.

    Ono R, Kumagai H, Nakajima H, Hishiya A, Taki T, Horikawa K, Takatsu K, Satoh T, Hayashi Y, Kitamura T, Nosaka T

    Leukemia   23   2197 - 2209   2009.1

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    DOI： 10.1038/leu.2009.177

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  • SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription Reviewed

    Hideaki Nakajima, Toshiki Tamura, Miyuki Ito, Fumi Shibata, Kana Kuroda, Yumi Fukuchi, Naohide Watanabe, Toshio Kitamura, Yasuo Ikeda, Makoto Handa

    BLOOD   113 ( 5 )   1027 - 1036   2009.1

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    DOI： 10.1182/blood-2008-01-133405

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  • Roundabout 4 Is Expressed on Hematopoietic Stem Cells and Potentially Involved in the Niche-Mediated Regulation of the Side Population Phenotype Reviewed

    Fumi Shibata, Yuko Goto-Koshino, Yoshihiro Morikawa, Tadasuke Komori, Miyuki Ito, Yumi Fukuchi, Jeffrey P. Houchins, Monica Tsang, Dean Y. Li, Toshio Kitamura, Hideaki Nakajima

    STEM CELLS   27 ( 1 )   183 - 190   2009

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    DOI： 10.1634/stemcells.2008-0292

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  • C/EBP alpha and C/EBP epsilon induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene Reviewed

    H. Matsushita, H. Nakajima, Y. Nakamura, H. Tsukamoto, Y. Tanaka, G. Jin, M. Yabe, S. Asai, R. Ono, T. Nosaka, K. Sugita, A. Morimoto, Y. Hayashi, T. Hotta, K. Ando, H. Miyachi

    ONCOGENE   27 ( 53 )   6749 - 6760   2008.11

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    DOI： 10.1038/onc.2008.285

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  • AML1 mutations induced MDS and MDS/AML in a mouse BMT model Reviewed

    Naoko Watanabe-Okochi, Jiro Kitaura, Ryoichi Ono, Hironori Harada, Yuka Harada, Yukiko Komeno, Hideaki Nakajima, Tetsuya Nosaka, Toshiya Inaba, Toshio Kitamura

    BLOOD   111 ( 8 )   4297 - 4308   2008.4

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    DOI： 10.1182/blood-2007-01-068346

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  • Concise review: Isolation and characterization of cells from human term placenta: Outcome of the first international workshop on placenta derived stem cells Reviewed

    Ornella Parolini, Francesco Alviano, Gian Paolo Bagnara, Grozdana Bilic, Hans-Joerg Buehring, Marco Evangelista, Simone Hennerbichler, Bing Liu, Marta Magatti, Ning Mao, Toshio Miki, Fabio Marongiu, Hideaki Nakajima, Toshio Nikaido, C. Bettina Portmann-Lanz, Venkatachalam Sankar, Maddalena Soncini, Guido Stadler, Daniel Surbek, Tsuneo A. Takahashi, Heinz Redl, Norio Sakuragawa, Susanne Wolbank, Steffen Zeisberger, Andreas Zisch, Stephen C. Strom

    STEM CELLS   26 ( 2 )   300 - 311   2008.2

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  • Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells. Reviewed International journal

    Yoshinori Yamanishi, Jiro Kitaura, Kumi Izawa, Takayuki Matsuoka, Toshihiko Oki, Yang Lu, Fumi Shibata, Satoshi Yamazaki, Hidetoshi Kumagai, Hideaki Nakajima, Mari Maeda-Yamamoto, Victor L J Tybulewicz, Toshiyuki Takai, Toshio Kitamura

    Blood   111 ( 2 )   688 - 98   2008.1

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    We have analyzed leukocyte mono-Ig-like receptor 5 (LMIR5) as an activating receptor among paired LMIRs. Mouse LMIR5 (mLMIR5) is expressed in myeloid cells such as mast cells, granulocytes, macrophages, and dendritic cells. Cross-linking of transduced mLMIR5 in bone marrow-derived mast cells (BMMCs) caused activation events, including cytokine production, cell survival, degranulation, and adhesion to the extracellular matrix. mLMIR5 associated with DAP12 and to a lesser extent with DAP10, and mLMIR5-mediated functions of BMMCs were strongly inhibited by DAP12 deficiency. Importantly, cross-linking of endogenous mLMIR5 induced Syk-dependent activation of fetal liver-derived mast cells. Unlike mLMIR5, cross-linking of human LMIR5 (hLMIR5) induced cytokine production of BMMCs even in the absence of both DAP12 and DAP10, suggesting the existence of unidentified adaptors. Interestingly, hLMIR5 possessed a tyrosine residue (Y188) in the cytoplasmic region. Signaling via Y188 phosphorylation played a predominant role in hLMIR5-mediated cytokine production in DAP12-deficient, but not wild-type BMMCs. In addition, experiments using DAP10/DAP12 double-deficient BMMCs suggested the existence of Y188 phoshorylation-dependent and -independent signals from unidentified adaptors. Collectively, although both mouse and human LMIR5 play activatory roles in innate immunity cells, the functions of LMIR5 were differentially regulated in mouse versus human cells.

    DOI： 10.1182/blood-2007-04-085787

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  • Activation of CCAAT/Enhancer-Binding Protein alpha or PU.1 in Hematopoietic Stem Cells Leads to Their Reduced Self-Renewal and Proliferation Reviewed

    Yumi Fukuchi, Miyuki Ito, Fumi Shibata, Toshio Kitamura, Hideaki Nakajima

    STEM CELLS   26 ( 12 )   3172 - 3181   2008

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    DOI： 10.1634/stemcells.2008-0320

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  • Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD. Reviewed

    Lu Y, Kitaura J, Oki T, Komeno Y, Ozaki K, Kiyono M, Kumagai H, Nakajima H, Nosaka T, Aburatani H, Kitamura T

    Leukemia   21 ( 11 )   2246 - 2257   2007.11

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  • Functional analysis of activating receptor LMIR4 as a counterpart of inhibitory receptor LMIR3. Reviewed International journal

    Kumi Izawa, Jiro Kitaura, Yoshinori Yamanishi, Takayuki Matsuoka, Toshihiko Oki, Fumi Shibata, Hidetoshi Kumagai, Hideaki Nakajima, Mari Maeda-Yamamoto, Jeffrey P Hauchins, Victor L J Tybulewicz, Toshiyuki Takai, Toshio Kitamura

    The Journal of biological chemistry   282 ( 25 )   17997 - 8008   2007.6

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    The leukocyte mono-Ig-like receptor (LMIR) belongs to a new family of paired immunoreceptors. In this study, we analyzed activating receptor LMIR4/CLM-5 as a counterpart of inhibitory receptor LMIR3/CLM-1. LMIR4 is expressed in myeloid cells, including granulocytes, macrophages, and mast cells, whereas LMIR3 is more broadly expressed. The association of LMIR4 with Fc receptor-gamma among immunoreceptor tyrosine-based activation motif-bearing molecules was indispensable for LMIR4-mediated functions of bone marrow-derived mast cells, but dispensable for its surface expression. Cross-linking of LMIR4 led to Lyn- and Syk-dependent activation of bone marrow-derived mast cells, resulting in cytokine production and degranulation, whereas that of LMIR3 did not. The triggering of LMIR4 and TLR4 synergistically caused robust cytokine production in accordance with enhanced activation of ERK, whereas the co-ligation of LMIR4 and LMIR3 dramatically abrogated cytokine production. Notably, intraperitoneal administration of lipopolysaccharide strikingly up-regulated LMIR3 and down-regulated LMIR4, whereas that of granulocyte colony-stimulating factor up-regulated both LMIR3 and LMIR4 in granulocytes. Cross-linking of LMIR4 in bone marrow granulocytes also resulted in their activation, which was enhanced by lipopolysaccharide. Collectively, these results suggest that the innate immune system is at least in part regulated by the qualitative and quantitative balance of the paired receptors LMIR3 and LMIR4.

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  • Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors Reviewed

    Toshiyuki Kawashima, Ying Chun Bao, Yasushi Nomura, Yuseok Moon, Yukio Tonozuka, Yukinori Minoshima, Tomonori Hatori, Akiho Tsuchiya, Mari Kiyono, Tetsuya Nosaka, Hideaki Nakajima, David A. Williams, Toshio Kitamura

    JOURNAL OF CELL BIOLOGY   175 ( 6 )   937 - 946   2006.12

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  • Overexpression of interleukin 21 induces expansion of hematopoietic progenitor cells Reviewed

    Katsutoshi Ozaki, Ai Hishiya, Keiko Hatanaka, Hideaki Nakajima, Gang Wang, Patrick Hwu, Toshio Kitamura, Keiya Ozawa, Warren J. Leonard, Tetsuya Nosaka

    INTERNATIONAL JOURNAL OF HEMATOLOGY   84 ( 3 )   224 - 230   2006.10

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  • Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3 Reviewed

    Hideaki Nakajima, Fumi Shibata, Hidetoshi Kumagai, Kazuya Shimoda, Toshio Kitamura

    INTERNATIONAL JOURNAL OF HEMATOLOGY   84 ( 1 )   54 - 59   2006.7

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    DOI： 10.1532/IJH97.06016

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  • Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBP alpha Reviewed

    Yumi Fukuchi, Fumi Shibata, Miyuki Ito, Yuko Goto-Koshino, Yusuke Sotomaru, Mamoru Ito, Toshio Kitamura, Hideaki Nakajima

    EMBO JOURNAL   25 ( 14 )   3398 - 3410   2006.7

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    DOI： 10.1038/sj.emboj.7601199

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  • N-terminal Region of CCAAT/Enhancer-binding Protein epsilon Is Critical for Cell Cycle Arrest, Apoptosis, and Functional Maturation during Myeloid Differentiation Reviewed

    Hideaki Nakajima, Naohide Watanabe, Fumi Shibata, Toshio Kitamura, Yasuo Ikeda, Makoto Handa

    JOURNAL OF BIOLOGICAL CHEMISTRY   281 ( 20 )   14494 - 14502   2006.5

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  • Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells Reviewed

    H Nakajima, F Shibata, Y Fukuchi, Y Goto-Koshino, M Ito, A Urano, T Nakahata, H Aburatani, T Kitamura

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   340 ( 1 )   35 - 42   2006.2

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    DOI： 10.1016/j.bbrc.2005.11.146

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  • Integrin alpha(IIb)beta(3) induces the adhesion and activation of mast cells through interaction with fibrinogen Reviewed

    T Oki, J Kitaura, K Eto, Y Lu, M Maeda-Yamamoto, Inagaki, I, H Nagai, Y Yamanishi, H Nakajima, H Kumagai, T Kitamura

    JOURNAL OF IMMUNOLOGY   176 ( 1 )   52 - 60   2006.1

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  • Disruption of Sept6, a fusion partner gene of MLL, does not affect ontogeny, leukemogenesis induced by MLL-SEPT6, or phenotype induced by the loss of Sept4 Reviewed

    R Ono, M Ihara, H Nakajima, K Ozaki, Y Kataoka-Fujiwara, T Taki, K Nagata, M Inagaki, N Yoshida, T Kitamura, Y Hayashi, M Kinoshita, T Nosaka

    MOLECULAR AND CELLULAR BIOLOGY   25 ( 24 )   10965 - 10978   2005.12

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  • Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia Reviewed

    A Urano, M Endoh, T Wada, Y Morikawa, M Itoh, Y Kataoka, T Taki, H Akazawa, H Nakajima, Komuro, I, N Yoshida, Y Hayashi, H Handa, T Kitamura, T Nosaka

    MOLECULAR AND CELLULAR BIOLOGY   25 ( 15 )   6834 - 6845   2005.8

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    DOI： 10.1128/MCB.25.15.6834-6845.2005

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  • [Immunological tests: Red cell autoantibodies]. Reviewed

    Nakajima H, Handa M

    Nihon rinsho. Japanese journal of clinical medicine   63 Suppl 7   618 - 620   2005.7

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  • [Cytokine receptors and signal transduction]. Reviewed

    Nakajima H, Kitamura T

    Nihon rinsho. Japanese journal of clinical medicine   63 Suppl 4   178 - 186   2005.4

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  • Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple-lineage leukemogenesis Reviewed

    R Ono, H Nakajima, K Ozaki, H Kumagai, T Kawashima, T Taki, T Kitamura, Y Hayashi, T Nosaka

    JOURNAL OF CLINICAL INVESTIGATION   115 ( 4 )   919 - 929   2005.4

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    DOI： 10.1172/JCI200522725

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  • Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway Reviewed

    A Numata, K Shimoda, K Kamezaki, T Haro, H Kakumitsu, K Shide, K Kato, T Miyamoto, Y Yamashita, Y Oshima, H Nakajima, A Iwama, K Aoki, K Takase, H Gondo, H Mano, M Harada

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 13 )   12621 - 12629   2005.4

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  • AGTPase-activating protein binds STAT3 and is required for IIL-6-induced STAT3 activation and for differentiation of a leukemic cell line Reviewed

    Y Tonozuka, Y Minoshima, YC Bao, Y Moon, Y Tsubono, T Hatori, H Nakajima, T Nosaka, T Kawashima, T Kitamura

    BLOOD   104 ( 12 )   3550 - 3557   2004.12

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    DOI： 10.1182/blood-2004-03-1066

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  • Identification of the molecular requirements for an RAR alpha-mediated cell cycle arrest during granulocytic differentiation Reviewed

    CR Walkley, LE Purton, HJ Snelling, YD Yuan, H Nakajima, P Chambon, RAS Chandraratna, GA McArthur

    BLOOD   103 ( 4 )   1286 - 1295   2004.2

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    DOI： 10.1182/blood-2003-07-2391

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  • Human placenta-derived cells have mesenchymal stem/progenitor cell potential Reviewed

    Y Fukuchi, H Nakajima, D Sugiyama, Hirose, I, T Kitamura, K Tsuji

    STEM CELLS   22 ( 5 )   649 - 658   2004

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    DOI： 10.1634/stemcells.22-5-649

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  • The lipocalin 24p3, which is an essential molecule in IL-3 withdrawal-induced apoptosis, is not involved in the G-CSF withdrawal-induced apoptosis Reviewed

    K Kamezaki, K Shimoda, A Numata, K Aoki, K Kato, K Takase, H Nakajima, K Ihara, T Haro, F Ishikawa, R Imamura, T Miyamoto, K Nagafuji, H Gondo, T Hara, M Harada

    EUROPEAN JOURNAL OF HAEMATOLOGY   71 ( 6 )   412 - 417   2003.12

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    DOI： 10.1046/j.0902-4441.2003.00160.x

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  • Retrovirus-mediated gene transfer and expression cloning: Powerful tools in functional genornics Reviewed

    T Kitamura, Y Koshino, F Shibata, T Oki, H Nakajima, T Nosaka, H Kumagai

    EXPERIMENTAL HEMATOLOGY   31 ( 11 )   1007 - 1014   2003.11

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  • Identification and characterization of a new pair of immunoglobulin-like receptors LMIR1 and 2 derived from murine bone marrow-derived mast cells Reviewed

    H Kumagai, T Oki, K Tamitsu, SZ Feng, M Ono, H Nakajima, YC Bao, Y Kawakami, K Nagayoshi, NG Copeland, DJ Gilbert, NA Jenkins, T Kawakami, T Kitamura

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   307 ( 3 )   719 - 729   2003.8

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    DOI： 10.1016/S0006-291X(03)01245-2

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  • Selective cytotoxic mechanism of GTP-14564, a novel tyrosine kinase inhibitor in leukemia cells expressing a constitutively active Fms-like tyrosine kinase 3 (FLT3) Reviewed

    K Murata, H Kumagai, T Kawashima, K Tamitsu, M Irie, H Nakajima, S Suzu, M Shibuya, S Kamihira, T Nosaka, S Asano, T Kitamura

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 35 )   32892 - 32898   2003.8

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  • Functional phenotype of phosphoinositide 3-kinase p85 alpha-null platelets characterized by an impaired response to GP VI stimulation Reviewed

    N Watanabe, H Nakajima, H Suzuki, A Oda, Y Matsubara, M Moroi, Y Terauchi, T Kadowaki, H Suzuki, S Koyasu, Y Ikeda, M Handa

    BLOOD   102 ( 2 )   541 - 548   2003.7

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    DOI： 10.1182/blood-2002-11-3327

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  • Mammalian twisted gastrulation is essential for skeleto-lymphogenesis Reviewed

    T Nosaka, S Morita, H Kitamura, H Nakajima, F Shibata, Y Morikawa, Y Kataoka, Y Ebihara, T Kawashima, T Itoh, K Ozaki, E Senba, K Tsuji, F Makishima, N Yoshida, T Kitamura

    MOLECULAR AND CELLULAR BIOLOGY   23 ( 8 )   2969 - 2980   2003.4

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    DOI： 10.1128/MCB.23.8.2969-2980.2003

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  • CCAAT/enhancer binding proteins repress the leukemic phenotype of acute myeloid leukemia Reviewed

    BTH Truong, YJ Lee, TA Lodie, DJ Park, D Perrotti, N Watanabe, HP Koeffler, H Nakajima, DG Tenen, SC Kogan

    BLOOD   101 ( 3 )   1141 - 1148   2003.2

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  • Identification, cDNA cloning, and targeted deletion of p70, a novel, ubiquitously expressed SH3 domain-containing protein Reviewed

    N Carpino, R Kobayashi, H Zang, Y Takahashi, ST Jou, J Feng, H Nakajima, JN Ihle

    MOLECULAR AND CELLULAR BIOLOGY   22 ( 21 )   7491 - 7500   2002.11

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  • Twisted gastrulation欠損マウスにおける矮小発育症とリンパ球形成不全

    野阪 哲哉, 森田 純代, 北村 秀智, 中島 秀明, 柴田 文, 片岡 由起, 森川 吉博, 川島 敏行, 海老原 康博, 牧島 房夫, 吉田 進昭, 北村 俊雄

    臨床血液   43 ( 8 )   91 - 91   2002.8

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  • Novel variant isoform of G-CSF receptor involved in induction of proliferation of FDCP-2 cells: Relevance to the pathogenesis of myelodysplastic syndrome Reviewed

    N Awaya, H Uchida, Y Miyakawa, K Kinjo, H Matsushita, H Nakajima, Y Ikeda, M Kizaki

    JOURNAL OF CELLULAR PHYSIOLOGY   191 ( 3 )   327 - 335   2002.6

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    DOI： 10.1002/jcp.10102

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  • A novel polymorphism, (70)Leu/Phe, disrupts a consensus Leu residue within the leucine-rich repeat sequence of platelet glycoprotein Ib alpha Reviewed

    Y Matsubara, M Murata, T Moriki, K Yokoyama, N Watanabe, H Nakajima, M Handa, K Kawano, N Aoki, H Yoshino, Y Ikeda

    THROMBOSIS AND HAEMOSTASIS   87 ( 5 )   867 - 872   2002.5

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  • The centrosomal protein TACC3 is essential for hematopoietic stem cell function and genetically interfaces with p53-regulated apoptosis Reviewed

    RP Piekorz, A Hoffmeyer, CD Duntsch, C McKay, H Nakajima, Sexl, V, L Snyder, J Rehg, JN Ihle

    EMBO JOURNAL   21 ( 4 )   653 - 664   2002.2

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  • Granulocyte colony-stimulating factor regulates myeloid differentiation through CCAAT/enhancer-binding protein epsilon Reviewed

    H Nakajima, JN Ihle

    BLOOD   98 ( 4 )   897 - 905   2001.8

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    DOI： 10.1182/blood.V98.4.897

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  • The distal region and receptor tyrosines of the Epo receptor are non-essential for in vivo erythropoiesis Reviewed

    HS Zang, K Sato, H Nakajima, C McKay, PA Ney, JN Ihle

    EMBO JOURNAL   20 ( 12 )   3156 - 3166   2001.6

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  • [Red cell autoantibodies]. Reviewed

    Nakajima H, Handa M

    Nihon rinsho. Japanese journal of clinical medicine   57 Suppl   539 - 541   1999.11

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  • All-trans and 9-cis retinoic acid enhance 1,25-dihydroxyvitamin D-3-induced monocytic differentiation of U937 cells Reviewed

    H Nakajima, M Kizaki, H Ueno, A Muto, N Takayama, H Matsushita, A Sonoda, Y Ikeda

    LEUKEMIA RESEARCH   20 ( 8 )   665 - 676   1996.8

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  • [Proposals for the objective indices for evaluating the differentiation of leukemic cells by all-trans retinoic acid in the patients with acute promyelocytic leukemia]. Reviewed

    Nakajima H, Kizaki M, Takayama N, Kawai Y, Watanabe K, Okamoto S, Ikeda Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   37 ( 3 )   208 - 213   1996.3

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  • Mechanisms of retinoid resistance in leukemic cells: Possible role of cytochrome P450 and P-glycoprotein Reviewed

    M Kizaki, H Ueno, Y Yamazoe, M Shimada, N Takayama, A Muto, H Matsushita, H Nakajima, M Morikawa, HP Koeffler, Y Ikeda

    BLOOD   87 ( 2 )   725 - 733   1996.1

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  • CD7 positive acute lymphoblastic leukemia successfully treated with high dose cytosine arabinoside and mitoxantrone: A case report Reviewed

    Hideaki Nakajima, Masahiro Kizaki, Yohko Kawai, Akaru Ishida, Michihide Tokuhira, Kiyoaki Watanabe, Yasuo Ikeda

    Keio Journal of Medicine   45 ( 2 )   114 - 117   1996

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  • [A randomized controlled study of rG.CSF in patients with neutropenia after induction therapy for acute myelogenous leukemia. (rG.CSF Clinical Study Group)]. Reviewed

    Nakajima H, Ikeda Y, Hirashima K, Toyama K, Okuma M, Saito H, Ohno R, Tomonaga M, Asano S

    [Rinsho ketsueki] The Japanese journal of clinical hematology   36 ( 6 )   597 - 605   1995.6

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    A randomized treated/non-treated study of rG&middot;CSF (5 &mu;g/kg/d, d.i.v.) in patients with acute myelogenous leukemia was conducted to assess its efficacy on fever (&ge;38&deg;C) or documented infection after induction therapy. Of 95 patients enrolled, 46 patients were evaluable for safety and 43 for efficacy in the treated group of 47 patients while 37 of 48 patients were eligible for data analysis in the untreated group. Mare patients showed a recovery in the blood neutrophil count (to >1,000/&mu;<i>l</i>) during rG&middot;CSF treatment (14 days) than in the non-treated group (p=0.039) while the number of febrile patients and duration of fever did not significantly differ between the two groups. The treatment with rG&middot;CSF enabled an early recovery in neutrophil count in the patients with neutropenia and overt signs of infection after induction therapy, but there was no hastened allevistion of symptoms of infection in these patients.

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  • SPONTANEOUS RESOLUTION OF TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE Reviewed

    S MORI, H MATSUSHITA, K OZAKI, A ISHIDA, M TOKUHIRA, H NAKAJIMA, M KIZAKI, H SUGIURA, A KIKUCHI, M HANDA, Y KAWAI, S YAMAMORI, Y IKEDA

    TRANSFUSION   35 ( 5 )   431 - 435   1995.5

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  • RETINOIDS (ALL-TRANS AND 9-CIS RETINOIC ACID) STIMULATE PRODUCTION OF MACROPHAGE-COLONY-STIMULATING FACTOR AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR BY HUMAN BONE-MARROW STROMAL CELLS Reviewed

    H NAKAJIMA, M KIZAKI, A SONODA, S MORI, K HARIGAYA, Y IKEDA

    BLOOD   84 ( 12 )   4107 - 4115   1994.12

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  • RAPID IMPROVEMENT OF COAGULOPATHY BY ALL-TRANS-RETINOIC ACID IN ACUTE PROMYELOCYTIC LEUKEMIA Reviewed

    Y KAWAI, K WATANABE, M KIZAKI, M MURATA, T KAMATA, H UCHIDA, T MORIKI, K YOKOYAMA, M TOKUHIRA, H NAKAJIMA, M HANDA, Y IKEDA

    AMERICAN JOURNAL OF HEMATOLOGY   46 ( 3 )   184 - 188   1994.7

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  • NOVEL RETINOIC ACID, 9-CIS RETINOIC ACID, IN COMBINATION WITH ALL-TRANS-RETINOIC ACID IS AN EFFECTIVE INDUCER OF DIFFERENTIATION OF RETINOIC ACID-RESISTANT HL-60 CELLS Reviewed

    M KIZAKI, H NAKAJIMA, S MORI, T KOIKE, M MORIKAWA, M OHTA, M SAITO, HP KOEFFLER, Y IKEDA

    BLOOD   83 ( 11 )   3289 - 3297   1994.6

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  • [Effects of 9-cis retinoic acid on hematopoiesis in vitro]. Reviewed

    Kizaki M, Nakajima H, Ikeda Y

    [Rinsho ketsueki] The Japanese journal of clinical hematology   35 ( 3 )   256 - 260   1994.3

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  • EFFECTS OF NOVEL RETINOIC ACID COMPOUND, 9-CIS-RETINOIC ACID, ON PROLIFERATION, DIFFERENTIATION, AND EXPRESSION OF RETINOIC ACID RECEPTOR-ALPHA AND RETINOID-X RECEPTOR-ALPHA RNA BY HL-60 CELLS Reviewed

    M KIZAKI, Y IKEDA, R TANOSAKI, H NAKAJIMA, M MORIKAWA, A SAKASHITA, HP KOEFFLER

    BLOOD   82 ( 12 )   3592 - 3599   1993.12

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  • A CASE OF CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA WITH A HIGH TITRE OF PLATELET MEMBRANE‐ASSOCIATED ANTIPHOSPHOLIPID ANTIBODIES Reviewed

    Hideaki Nakajima, Hiroshi Murakami, Yohko Araki, Hironobu Ambo, Shinichiro Okamoto, Makoto Handa, Yasuo Ikeda

    British Journal of Haematology   78 ( 3 )   456 - 457   1991

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    DOI： 10.1111/j.1365-2141.1991.tb04464.x

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  • Chronic Immune Thrombocytopenia in Sarcoidosis Reviewed

    Michie Hisada, Hideaki Nakajima, Shigeru Nogawa, Yohsuke Shigeta, Ken Kawamura, Shinichiro Okamoto

    The Keio Journal of Medicine   39 ( 4 )   261 - 264   1990

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MISC

  • 後腹膜腫瘍を合併したIgA血管炎の一例

    張田佳代, 北堀弘大, 仲野寛人, 高瀬宙希, 村岡枝里香, 加藤生真, 松本未於, 本多主税, 市川健人, 櫻井菜月, 小宮孝章, 濱田直樹, 前田彩花, 平原理紗, 副島裕太郎, 峯岸薫, 吉見竜介, 桐野洋平, 山中正二, 中島秀明

    関東リウマチ   57   2025

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  • 疫学2:SLE、DM/PM、PMRの観察研究 全身性エリテマトーデスにおける共同意思決定と医師への信頼度の関連についての前向きコホート研究 TRUMP2-SLE研究

    吉見 竜介, 矢嶋 宣幸, 栗田 宜明, 秀川 智春, 櫻井 菜月, 小黒 奈緒, 志田原 健太, 林 啓悟, 市川 貴規, 岸田 大, 宮脇 義亜, 佐田 憲映, 下島 恭弘, 石川 雄一, 吉岡 裕二, 國下 洋輔, 岸本 大河, 峯岸 薫, 桐野 洋平, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   67回   539 - 539   2023.3

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  • CAR-T細胞療法の全身性エリテマトーデス治療への応用

    吉見 竜介, 中島 秀明

    リウマチ科   68 ( 4 )   455 - 461   2022.10

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  • Effect of Shared Decision-making on Trust in Physician in the Clinical Practice of Systemic Lupus Erythematosus: The TRUMP<SUP>2</SUP>-SLE Study

    Ryusuke Yoshimi, Chiharu Hidekawa, Natsuki Sakurai, Nobuyuki Yajima, Noriaki Kurita, Naoki Suzuki, Yuji Yoshioka, Daiga Kishimoto, Noriko Kojitani, Yumiko Sugiyama, Yosuke Kunishita, Kana Higashitani, Yuji Uzawa, Yuichiro Sato, Soichiro Adachi, Yuki Iizuka, Ayaka Maeda, Lisa Hirahara, Takaaki Komiya, Yutaro Soejima, Naoki Hamada, Hideto Nagai, Naomi Tsuchida, Kaoru Takase-Minegishi, Yohei Kirino, Nao Oguro, Keigo Hayashi, Kenta Shidahara, Yoshia Miyawaki, Ken-ei Sada, Dai Kishida, Takanori Ichikawa, Yasuhiro Shimojima, Yuichi Ishikawa, Shigeru Ohno, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   74   359 - 360   2022.9

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  • Association of Hydroxychloroquine with the Incidence of Infectious Disease in Systemic Lupus Erythematosus: Data from the LUNA Registry

    Chiharu Hidekawa, Ryusuke Yoshimi, Yusuke Saigusa, Jun Tamura, Nobuyuki Yajima, Naoki Suzuki, Noriko Kojitani, Yuji Yoshioka, Natsuki Sakurai, Yumiko Sugiyama, Yosuke Kunishita, Daiga Kishimoto, Kana Higashitani, Yuichiro Sato, Takaaki Komiya, Hideto Nagai, Naoki Hamada, Ayaka Maeda, Naomi Tsuchida, Lisa Hirahara, Yutaro Soejima, Kaoru Takase-Minegishi, Yohei Kirino, Ken-ei Sada, Yoshia Miyawaki, Kunihiro Ichinose, Shigeru Ohno, Hiroshi Kajiyama, Shuzo Sato, Yasuhiro Shimojima, Michio Fujiwara, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   74   4059 - 4061   2022.9

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  • 免疫チェックポイント阻害剤誘発性関節症状の発生率と臨床的特徴 単施設での経験と文献の系統的考察(Incidence and clinical features of immune checkpoint inhibitor-induced joint symptoms: a single center experience and systematic review of the literature)

    Maeda Ayaka, Minegishi Kaoru, Hamada Naoki, Yoshimi Ryusuke, Kirono Yohei, Yamaguchi Yukie, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   745 - 745   2022.3

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  • 横浜市立大学附属病院のVEXAS症候群4症例の治療経過

    星 美希, 桐野 洋平, 土田 奈緒美, 前田 彩花, 峯岸 薫, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   752 - 752   2022.3

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  • ベーチェット病の難治性口腔潰瘍に対するアプレミラストの実臨床における1年間の治療成績

    中山 裕太, 平原 理紗, 桐野 洋平, 飯塚 友紀, 副島 裕太郎, 峯岸 薫, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   750 - 750   2022.3

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  • 全身性エリテマトーデス患者の疾患活動性と血清ヘムオキシゲナーゼ-1の関連

    岸本 大河, 桐野 洋平, 鈴木 直樹, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   653 - 653   2022.3

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  • SLEの患者特性と臨床的意義 全身性エリテマトーデス診療における医師への信頼度に対して共同意思決定が与える影響 TRUMP2-SLE研究

    吉見 竜介, 秀川 智春, 櫻井 菜月, 矢嶋 宣幸, 吉岡 裕二, 岸本 大河, 麹谷 典子, 杉山 裕美子, 國下 洋輔, 水野 広輝, 東谷 佳奈, 佐藤 雄一郎, 安達 聡一郎, 飯塚 友紀, 前田 彩花, 平原 理紗, 小宮 孝章, 副島 裕太郎, 濱田 直樹, 永井 秀人, 土田 奈緒美, 峯岸 薫, 桐野 洋平, 栗田 宜明, 小黒 奈緒, 宮脇 義亜, 佐田 憲映, 下島 恭弘, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   365 - 365   2022.3

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  • 当院における好酸球性多発血管炎性肉芽腫症40例の検討

    佐藤 雄一郎, 峯岸 薫, 吉見 竜介, 水野 広輝, 桐野 洋平, 永井 秀人, 濱田 直樹, 東谷 佳奈, 副島 裕太郎, 小宮 孝章, 櫻井 菜月, 平原 理紗, 前田 彩花, 秀川 智春, 飯塚 友紀, 吉岡 裕二, 安達 聡一郎, 土田 奈緒美, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   687 - 687   2022.3

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  • Adult-onset Still's disease and autoinflammatory diseases 生物学的治療を受けている成人発症スティル病患者におけるマクロファージ活性化症候群の発生率 単施設での経験および文献のメタアナリシス(The incidence of macrophage activation syndrome in patients with adult-onset Still's disease receiving biological therapy: a single center experience and meta-analysis of the literature)

    Adachi Soichiro, Nagai Hideto, Minegishi Kaoru, Kirino Yohei, Yoshimi Ryusuke, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   498 - 498   2022.3

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  • 巨細胞性動脈炎の診断・治療 当院における巨細胞性動脈炎31例の検討

    水野 広輝, 峯岸 薫, 東谷 佳奈, 佐藤 雄一郎, 前田 彩花, 濱田 直樹, 永井 秀人, 桐野 洋平, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   66回   339 - 339   2022.3

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  • 皮膚筋炎に自己免疫性溶血性貧血を合併した1例

    水野 広輝, 東谷 佳奈, 佐藤 雄一郎, 濱田 直樹, 永井 秀人, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会関東支部学術集会プログラム・抄録集   31回   46 - 46   2021.12

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  • O-GlcNAcylation: Implications in normal and malignant hematopoiesis

    Hideaki Nakajima, Koichi Murakami

    Experimental Hematology   101-102   16 - 24   2021.9

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    DOI： 10.1016/j.exphem.2021.07.003

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  • Pathogenic UBA1 Variants in Japanese Patients with Relapsing Polychondritis

    Naomi Tsuchida, Yosuke Kunishita, Yuri Uchiyama, Yohei Kirino, Kaoru Takase-Minegishi, Ryusuke Yoshimi, Hideaki Nakajima, Naomichi Matsumoto

    ARTHRITIS & RHEUMATOLOGY   73   2292 - 2293   2021.9

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  • 難治性の成人発症スティル病様症状を示しトシリズマブが有効であった全身性エリテマトーデスの1例

    松本 佳子, 吉見 竜介, 水野 広輝, 佐藤 雄一郎, 峯岸 薫, 東谷 佳奈, 濱田 直樹, 永井 秀人, 桐野 洋平, 中島 秀明

    日本内科学会関東地方会   671回   42 - 42   2021.9

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  • Anti-TRIM21 antibody seropositivity is related to B -cell abnormalities in systemic lupus erythematosus

    Yosuke Kunishita, Ryusuke Yoshimi, Takaaki Komiya, Natsuki Sakurai, Yumiko Sugiyama, Kaoru Takase-Minegishi, Yohei Kirino, Shouhei Nagaoka, Hideaki Nakajima

    JOURNAL OF IMMUNOLOGY   206   2021.5

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  • 妊娠・移行期医療 横浜市立大学関連2施設におけるベーチェット病合併妊娠症例の検討

    飯塚 友紀, 桐野 洋平, 副島 裕太郎, 平原 理紗, 杉山 裕美子, 吉見 竜介, 大野 滋, 長岡 章平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   455 - 455   2021.3

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  • 全身性エリテマトーデス 全身性エリテマトーデス患者における抗SS-A抗体陽性率とループス低疾患活動性(LLDAS)の達成の関係性(Systemic Lupus Erythematosus Relationships between anti-SS-A antibody and Achievement of Lupus Low Disease Activity State(LLDAS) in patients with systemic lupus erythematosus: A cross-sectional analysis using the LUNA registry)

    Kishimoto Daiga, Yoshimi Ryusuke, Kojitani Noriko, Hidekawa Chiharu, Sakurai Natsuki, Sugiyama Yumiko, Kunishita Yosuke, Okubo Tomohiko, Uzawa Yuji, Hirahara Lisa, Maeda Ayaka, Komiya Takaaki, Soejima Yutaro, Nagai Hideto, Hamada Naoki, Tsuchida Naomi, Takase-Minegishi Kaoru, Kirino Yohei, Yajima Nobuyuki, Sada Ken-ei, Miyawaki Yoshia, Ichinose Kunihiro, Ohno Shigeru, Kajiyama Hiroshi, Sato Shuzo, Shimojima Yasuhiro, Fujiwara Michio, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   508 - 508   2021.3

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  • SLE患者における低補体血症と感染症の関連 LUNAレジストリを用いた後向き観察研究(第一報)

    麹谷 典子, 吉見 竜介, 秀川 智春, 櫻井 菜月, 杉山 裕美子, 國下 洋輔, 岸本 大河, 大久保 智彦, 鵜澤 侑司, 前田 彩花, 平原 理紗, 小宮 孝章, 副島 裕太郎, 濱田 直樹, 永井 秀人, 土田 奈緒美, 峯岸 薫, 桐野 洋平, 矢嶋 宣幸, 佐田 憲映, 宮脇 義亜, 一瀬 邦弘, 大野 滋, 梶山 浩, 佐藤 秀三, 下島 恭弘, 藤原 道雄, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   620 - 620   2021.3

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  • 椎骨硬膜動静脈瘻からのくも膜下出血を合併した顕微鏡的多発血管炎の1例

    大久保 智彦, 桐野 洋平, 麹谷 典子, 鵜澤 侑司, 濱田 直樹, 永井 秀人, 峯岸 薫, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   656 - 656   2021.3

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  • 胸水および心嚢水を合併した抗SRP抗体陽性の炎症性筋疾患の1例

    鵜澤 侑司, 吉見 竜介, 麹谷 典子, 大久保 智彦, 濱田 直樹, 永井 秀人, 峯岸 薫, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   649 - 649   2021.3

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  • SLE・抗リン脂質抗体症候群(臨床):ヒドロキシクロロキン SLE患者におけるHCQ使用によるステロイド減量効果について LUNAを用いた縦断観察研究

    櫻井 菜月, 杉山 裕美子, 吉見 竜介, 麹谷 典子, 秀川 智春, 國下 洋輔, 岸本 大河, 大久保 智彦, 鵜澤 侑司, 前田 彩花, 平原 理紗, 小宮 孝章, 副島 裕太郎, 濱田 直樹, 永井 秀人, 土田 奈緒美, 峯岸 薫, 桐野 洋平, 矢嶋 宣幸, 佐田 憲映, 宮脇 義亜, 一瀬 邦弘, 大野 滋, 梶山 浩, 佐藤 秀三, 下島 恭弘, 藤原 道雄, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   382 - 382   2021.3

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  • 成人スティル病に対して寛解導入目的にトシリズマブを投与した4例

    逸見 莉子, 永井 秀人, 桐野 洋平, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   720 - 720   2021.3

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  • 自己炎症症候群 本邦初のUBA1遺伝子変異を有する新規自己炎症性疾患VEXAS・再発性多発軟骨炎患者の報告

    土田 奈緒美, 桐野 洋平, 國下 洋輔, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   447 - 447   2021.3

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  • 成人スチル病の特性 AOSD・sJIAにおける単球/マクロファージのPyroptosisと新規バイオマーカーとしてのGSDMDに関する機能解析

    永井 秀人, 桐野 洋平, 仲野 寛人, 國下 洋輔, 吉岡 裕二, 杉山 裕美子, 吉見 竜介, 大久保 忠信, 大野 滋, 長岡 章平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   429 - 429   2021.3

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  • SLE病状形成 全身性エリテマトーデスにおいて抗TRIM21抗体はI型インターフェロンおよびB細胞異常と関連している(SLE Pathogenesis Anti-TRIM21 antibody is associated with type I interferon and B-cell abnormalities in systemic lupus erythematosus)

    Kunishita Yosuke, Yoshimi Ryusuke, Suzuki Naoki, Iizuka Yuki, Mitsuhashi Masaki, Komiya Takaaki, Sakurai Natsuki, Sugiyama Yumiko, Kishimoto Daiga, Kamiyama Reikou, Kirino Yohei, Nagaoka Shouhei, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   65回   476 - 476   2021.3

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  • Clonal hematopoiesis: Molecular basis and clinical relevance

    Hiroyoshi Kunimoto, Hideaki Nakajima

    Leukemia Research   98   2020.11

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    DOI： 10.1016/j.leukres.2020.106457

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  • 全身性エリテマトーデスにおいて抗TRIM21抗体はTRIM21機能不全及びB細胞機能異常と関連する

    國下 洋輔, 吉見 竜介, 鈴木 直樹, 飯塚 友紀, 三橋 正季, 小宮 孝章, 櫻井 菜月, 杉山 裕美子, 桐野 洋平, 長岡 章平, 中島 秀明

    日本臨床免疫学会総会プログラム・抄録集   48回   105 - 105   2020.10

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  • ベーチェット病 ベーチェット病患者における疾患活動性残存と医師の過小評価の現状

    平原 理紗, 桐野 洋平, 副島 裕太郎, 鈴木 直樹, 日高 優香, 櫻井 菜月, 小宮 孝章, 永井 秀人, 濱田 直樹, 前田 彩花, 土田 奈緒美, 國下 洋輔, 岸本 大河, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   64回   416 - 416   2020.8

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  • 成人スティル病における予後予測因子の検討

    逸見 莉子, 永井 秀人, 桐野 洋平, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   64回   791 - 791   2020.8

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  • 急性膵炎を発症したSLEの一例

    鈴木 直樹, 國下 洋輔, 桐野 洋平, 土田 奈緒美, 日高 優香, 前田 彩花, 岸本 大河, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   64回   743 - 743   2020.8

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  • 全身性エリテマトーデス 臨床 全身性エリテマトーデス患者の重症感染症に対するヒドロキシクロロキンの予防効果に関する検討 LUNA registryから得られたデータ(Systemic lupus erythematosus: Clinical Examination about the prevention effect of hydroxychloroquine toward severe infectious disease in patients with systemic lupus erythematosus: date from the LUNA registry)

    Hidekawa Chiharu, Kunishita Yosuke, Yoshimi Ryusuke, Sakurai Natsuki, Sugiyama Yumiko, Kishimoto Daiga, Komiya Takaaki, Soejima Yutaro, Nagai Hideto, Hamada Naoki, Tsuchida Naomi, Kirino Yohei, Yajima Nobuyuki, Sada Ken-ei, Ichinose Kunihiro, Ohno Shigeru, Kajiyama Hiroshi, Sato Shuzo, Shimojima Yasuhiro, Fujiwara Michio, Nagaoka Shohei, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   64回   328 - 328   2020.8

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  • SLE・抗リン脂質抗体症候群(臨床) SLE患者におけるHCQ使用によるステロイド減量効果について LUNAレジストリを用いた横断研究

    飯塚 友紀, 杉山 裕美子, 吉見 竜介, 國下 洋輔, 秀川 智春, 櫻井 菜月, 小林 幸司, 岸本 大河, 小宮 孝章, 永井 秀人, 濱田 直樹, 土田 奈緒美, 副島 裕太郎, 桐野 洋平, 矢嶋 宣幸, 佐田 憲映, 一瀬 邦弘, 梶山 浩, 佐藤 秀三, 下島 恭弘, 藤原 道雄, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   64回   380 - 380   2020.8

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  • Association between macrophage cell death and hyperferritinemia in adult-onset Still’s disease

    永井秀人, 桐野洋平, 仲野寛人, 吉見竜介, 濱田直樹, 副島裕太郎, 小宮孝章, 櫻井菜月, 平原理紗, 岸本大河, 國下洋輔, 土田奈緒美, 前田彩花, 日高優香, 鈴木直樹, 吉岡裕二, 小林幸司, 大野滋, 長岡章平, 中島秀明, 中島秀明

    日本免疫不全・自己炎症学会総会・学術集会プログラム・抄録集   64回   704 - 704   2020.8

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  • 当科にてヒドロキシクロロキン単剤で治療を開始した全身性エリテマトーデス症例の検討

    市川 健斗, 桐野 洋平, 國下 洋輔, 岸本 大河, 小林 幸司, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   64回   783 - 783   2020.8

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  • 全身性エリテマトーデスに伴う治療抵抗性の重症自己免疫性好中球減少症に対してベリムマブが奏功した一例

    永石 妙美, 岸本 大河, 吉見 竜介, 秀川 智春, 三橋 正季, 日高 優香, 前田 彩花, 鈴木 直樹, 國下 洋輔, 土田 奈緒美, 桐野 洋平, 中島 秀明

    日本リウマチ学会関東支部学術集会プログラム・抄録集   30回   72 - 72   2019.12

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  • Novel Nonsense Variant and Entire Deletion of TNFAIP3 Cause Haploinsufficiency of A20 Clinically Distinct from Behcet's Disease

    Naomi Tsuchida, Yohei Kirino, Yutaro Soejima, Hideaki Nakajima, Satoko Miyatake, Naomichi Matsumoto

    ARTHRITIS & RHEUMATOLOGY   71   2019.10

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  • MicroRNA-27a Can Contribute to Interferon Signatures in Systemic Lupus Erythematosus via the Suppression of Tripartite Motif-containing Protein 27

    Daiga Kishimoto, Ryusuke Yoshimi, Yosuke Kunishita, Yumiko Sugiyama, Takaaki Komiya, Natsuki Sakurai, Reikou Kamiyama, Yohei Kirino, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   71   2019.10

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  • Identification of a Distinct Intestinal Behcet's Disease Cluster in Japan: A Nationwide Retrospective Observational Study

    Yutaro Soejima, Yohei Kirino, Mitsuhiro Takeno, Michiko Kurosawa, Ryusuke Yoshimi, Nobuhisa Mizuki, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   71   2019.10

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  • Dysfunction of TRIM21 Promotes Aberrant Plasmablast Differentiation in Systemic Lupus Erythematosus Due to the Reduction of TRIM21-mediated Ubiquitylation of IRF5

    Yosuke Kunishita, Ryusuke Yoshimi, Reikou Kamiyama, Daiga Kishimoto, Koji Yoshida, Eijin Hashimoto, Yumiko Sugiyama, Takaaki Komiya, Natsuki Sakurai, Yohei Kirino, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   71   2019.10

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  • リウマチ性疾患における幹細胞移植医療の現状と課題． Invited

    吉見竜介, 中島秀明

    リウマチ科.   61 ( 5 )   503 - 509   2019.5

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  • SLE(臨床)-2 全身性エリテマトーデスにおいてLLDAS達成に影響を与える因子の探索 LUNAレジストリを用いた横断研究

    岸本 大河, 吉見 竜介, 國下 洋輔, 秀川 智春, 櫻井 菜月, 三橋 正季, 杉山 裕美子, 飯塚 友紀, 小宮 孝章, 永井 秀人, 濱田 直樹, 土田 奈緒美, 副島 裕太郎, 神山 玲光, 小林 幸司, 浅見 由希子, 桐野 洋平, 矢嶋 宣幸, 佐田 憲映, 一瀬 邦弘, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   476 - 476   2019.3

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  • トシリズマブ投与中に高安動脈炎の再燃が疑われた一例

    張田 佳代, 桐野 洋平, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   832 - 832   2019.3

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  • 全身性エリテマトーデスにおける感染症既往の実態について LUNAレジストリによる横断研究

    秀川 智春, 國下 洋輔, 吉見 竜介, 櫻井 菜月, 三橋 正季, 杉山 裕美子, 岸本 大河, 飯塚 友紀, 小宮 孝章, 永井 秀人, 濱田 直樹, 土田 奈緒美, 副島 裕太郎, 神山 玲光, 小林 幸司, 浅見 由希子, 桐野 洋平, 矢嶋 宣幸, 佐田 憲映, 一瀬 邦弘, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   730 - 730   2019.3

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  • 肺胞出血と腎障害を認め顕微鏡的多発血管炎との鑑別を要したIgA血管炎の症例報告および文献的考察

    飯塚 友紀, 桐野 洋平, 秀川 智春, 櫻井 菜月, 三橋 正季, 岸本 大河, 神山 玲光, 吉見 竜介, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   788 - 788   2019.3

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  • エドキサバン内服中に多臓器で血栓症を来した抗リン脂質抗体症候群の一例

    櫻井 菜月, 吉見 竜介, 三宅 暁夫, 飯塚 友紀, 秀川 智春, 三橋 正季, 小宮 孝章, 副島 裕太郎, 濱田 直樹, 永井 秀人, 國下 洋輔, 土田 奈緒美, 岸本 大河, 神山 玲光, 桐野 洋平, 杉山 裕美子, 大野 滋, 大橋 健一, 中島 秀明

    関東リウマチ   52   136 - 140   2019.3

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    54歳女性。抗リン脂質抗体症候群(APS)に対するエドキサバン内服中に腹痛、発熱、意識障害が出現した。前医ではAPSによる両側副腎出血性梗塞、副腎不全に伴う低ナトリウム血症として加療を受けたが、経過中に微小脳梗塞を認め、精査加療目的に当科転院となった。入院時検査では副腎梗塞、左前頭葉皮質下・後頭葉皮質の微小脳梗塞、APS腎症を認め、APSに対する抗凝固療法としてワルファリン投与を継続し、第63病日よりアスピリンを追加したところ、良好な経過が得られ、第96病日に退院となった。

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  • ベーチェット病 本邦ベーチェット病患者の臨床像に基づく亜群分類 腸管型は異なる亜群を形成する

    副島 裕太郎, 桐野 洋平, 岳野 光洋, 黒澤 美智子, 飯塚 友紀, 上原 武晃, 吉見 竜介, 浅見 由希子, 関口 章子, 井畑 淳, 大野 滋, 五十嵐 俊久, 長岡 章平, 石ヶ坪 良明, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   561 - 561   2019.3

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  • SLEの病状形成 全身性エリテマトーデスに対するタクロリムス治療において高い血清トラフ値を維持することは重要なのか(SLE Treatment Is it important to maintain the high serum trough level in the treatment with tacrolimus for systemic lupus erythematosus?)

    Komiya Takaaki, Kunishita Yosuke, Yoshimi Ryusuke, Iizuka Yuki, Hidekawa Chiharu, Mitsuhashi Masaki, Sakurai Natsuki, Nagai Hideto, Hamada Naoki, Soejima Yutaro, Tsuchida Naomi, Kishimoto Daiga, Kamiyama Reikou, Kirino Yohei, Ohno Shigeru, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   369 - 369   2019.3

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  • 全身性エリテマトーデスにおけるヒドロキシクロロキン使用患者の臨床像について LUNAレジストリを用いた横断研究

    杉山 裕美子, 吉見 竜介, 國下 洋輔, 秀川 智春, 櫻井 菜月, 三橋 正季, 岸本 大河, 飯塚 友紀, 小宮 孝章, 永井 秀人, 濱田 直樹, 土田 奈緒美, 副島 裕太郎, 神山 玲光, 小林 幸司, 浅見 由希子, 桐野 洋平, 矢嶋 宣幸, 佐田 憲映, 一瀬 邦弘, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   707 - 707   2019.3

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  • LUNAレジストリを用いた全身性エリテマトーデスにおけるタクロリムス使用患者の臨床像の検討

    三橋 正季, 國下 洋輔, 吉見 竜介, 秀川 智春, 櫻井 菜月, 杉山 裕美子, 岸本 大河, 飯塚 友紀, 小宮 孝章, 永井 秀人, 濱田 直樹, 土田 奈緒美, 副島 裕太郎, 神山 玲光, 小林 幸司, 浅見 由希子, 桐野 洋平, 矢嶋 宣幸, 佐田 憲映, 一瀬 邦弘, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   641 - 641   2019.3

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  • 全身性エリテマトーデスにおけるニューモシスチス肺炎予防の現状 多施設共同レジストリLUNAより

    吉見 竜介, 國下 洋輔, 秀川 智春, 櫻井 菜月, 三橋 正季, 杉山 裕美子, 岸本 大河, 飯塚 友紀, 小宮 孝章, 永井 秀人, 濱田 直樹, 土田 奈緒美, 副島 裕太郎, 神山 玲光, 小林 幸司, 浅見 由希子, 桐野 洋平, 矢嶋 宣幸, 佐田 憲映, 一瀬 邦弘, 宮本 俊明, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   729 - 729   2019.3

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  • SLEの病状形成 全身性エリテマトーデスにおいてTrim21の機能障害は異常B細胞分化を促進する(SLE Pathogenesis Dysfunction of Trim21 promotes aberrant B cell differentiation in systemic lupus erythematosus)

    Kunishita Yosuke, Yoshimi Ryusuke, Kamiyama Reikou, Kishimoto Daiga, Komiya Takaaki, Sugiyama Yumiko, Kirino Yohei, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   364 - 364   2019.3

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  • 免疫チェックポイント阻害薬により引き起こされた免疫関連有害事象に関する遺伝学的分析についての中間報告(Preliminary report on genetic analysis for an immune-related adverse event caused by immune checkpoint inhibitors)

    Hamada Naoki, Kirino Yohei, Yoshimi Ryusuke, Yamaguchi Yukie, Aihara Michiko, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   580 - 580   2019.3

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  • AOSDにおけるM1/M2マクロファージ産生サイトカイン解析

    永井 秀人, 桐野 洋平, 仲野 寛人, 吉見 竜介, 國下 洋輔, 土田 奈緒美, 濱田 直樹, 副島 裕太郎, 小宮 孝章, 神山 玲光, 岸本 大河, 櫻井 菜月, 三橋 正季, 飯塚 友紀, 秀川 智春, 吉岡 裕二, 杉山 裕美子, 小林 幸司, 上原 武晃, 大野 滋, 長岡 章平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   63回   604 - 604   2019.3

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  • 再生医療の最前線 膠原病疾患における再生医療の現状について

    吉見 竜介, 濱田 直樹, 桐野 洋平, 中島 秀明

    日本フットケア学会年次学術集会プログラム・抄録集   17回   129 - 129   2019.2

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  • 肺胞出血をきたしたIgA血管炎の一例

    飯塚 友紀, 桐野 洋平, 秀川 智春, 櫻井 菜月, 三橋 正季, 岸本 大河, 神山 玲光, 吉見 竜介, 中島 秀明

    日本リウマチ学会関東支部学術集会プログラム・抄録集   29回   76 - 76   2018.12

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  • Regulation of Mitophagy By O-Linked N-Acetylglucosamine Transferase Is Essential for Hematopoietic Stem Cell Maintenance

    Koichi Murakami, Daisuke Kurotaki, Wataru Kawase, Shunsuke Soma, Yumi Fukuchi, Hiroyoshi Kunimoto, Ryusuke Yoshimi, Shuhei Koide, Motohiko Oshima, Takako Hishiki, Noriyo Hayakawa, Tomomi Matsuura, Minoru Ko, Mayumi Oda, Kiichi Yanagisawa, Hiroshi Kobayashi, Yoshitoshi Atobe, Kengo Funakoshi, Atsushi Iwama, Keiyo Takubo, Shinichiro Okamoto, Tomohiko Tamura, Hideaki Nakajima

    BLOOD   132   2018.11

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    DOI： 10.1182/blood-2018-171

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  • The Predictive Risk Factors for Opportunistic Infection during Immunosuppressive Therapy for Polymyositis/Dermatomyositis

    Yumiko Sugiyama, Ryusuke Yoshimi, Maasa Tamura, Mitsuhiro Takeno, Yohei Kirino, Shigeru Ohno, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   70   2018.9

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  • O-GlcNAc化による造血幹細胞ミトコンドリアダイナミクスの制御(O-GlcNAcylation is critical for mitochondrial dynamics in hematopoietic stem cells)

    村上 紘一, 黒滝 大翼, 川瀬 航, 相馬 俊介, 福地 由美, 國本 博義, 吉見 竜介, 小出 周平, 大島 基彦, 小田 真由美, 洪 実, 菱木 貴子, 早川 典代, 松浦 友美, 柳澤 輝一, 小林 央, 原口 美帆, 跡部 好敏, 船越 健吾, 岩間 厚志, 田久保 圭誉, 岡本 真一郎, 田村 智彦, 中島 秀明

    臨床血液   59 ( 9 )   1483 - 1483   2018.9

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  • METABOLIC REGULATION OF HEMATOPOIETIC STEM CELLS BY O-LINKED N-ACETYLGLUCOSAMINE TRANSFERASE

    Koichi Murakami, Daisuke Kurotaki, Wataru Kawase, Shunsuke Soma, Yumi Fukuchi, Hiroyoshi Kunimoto, Ryusuke Yoshimi, Shuhei Koide, Motohiko Oshima, Mayumi Oda, Minoru Ko, Takako Hishiki, Noriyo Hayakawa, Tomomi Matsuura, Kiichi Yanagisawa, Miho Haraguchi, Hiroshi Kobayashi, Yoshitoshi Atobe, Kengo Funakoshi, Atsushi Iwama, Keiyo Takubo, Shinichiro Okamoto, Tomohiko Tamura, Hideaki Nakajima

    EXPERIMENTAL HEMATOLOGY   64   S89 - S89   2018.8

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  • 関節リウマチの治療中に縦隔炎を呈して発症した侵襲性髄膜炎菌感染症の一例

    吉見 竜介, 加藤 英明, 杉山 裕美子, 國下 洋輔, 副島 裕太郎, 岸本 大河, 仲野 寛人, 酒井 梨紗, 寒川 整, 太田 嘉, 松本 裕子, 中島 秀明

    日本化学療法学会雑誌   66 ( Suppl.A )   292 - 292   2018.4

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  • 皮膚筋炎・多発筋炎患者における日和見感染症合併の予測因子の検討

    杉山 裕美子, 吉見 竜介, 國下 洋輔, 副島 裕太郎, 岸本 大河, 仲野 寛人, 中島 秀明

    日本化学療法学会雑誌   66 ( Suppl.A )   292 - 292   2018.4

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  • 関節リウマチの治療効果判定におけるEULAR改善基準と関節超音波所見の比較

    吉見 竜介, 櫻井 菜月, 佐藤 雄一郎, 小宮 孝章, 濱田 直樹, 永井 秀人, 杉山 裕美子, 土田 奈緒美, 副島 裕太郎, 國下 洋輔, 岸本 大河, 仲野 寛人, 神山 玲光, 峯岸 薫, 桐野 洋平, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   62回   615 - 615   2018.3

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  • ベーチェット病 臨床像に基づく主成分分析によるベーチェット病患者の亜群分類の試み

    副島 裕太郎, 桐野 洋平, 岳野 光洋, 渡邉 俊幸, 上原 武晃, 峯岸 薫, 吉見 竜介, 山崎 哲, 浅見 由希子, 関口 章子, 井畑 淳, 大野 滋, 五十嵐 俊久, 長岡 章平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   62回   442 - 442   2018.3

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  • RA bDMARDs 実社会におけるRA患者に対する生物学的DMARDs漸減投与成功の解析(RA bDMARDs The Analysis of Successful Down-titration of Biological DMARDs among RA Patients in the real world)

    Komiya Takaaki, Sugiyama Yumiko, Minegishi Kaoru, Kunisita Yousuke, Sakurai Natuki, Sato Yuichiro, Nagai Hideto, Hamada Naoki, Soejima Yutaro, Tsuchida Naomi, Nakano Hiroto, Kishimoto Daiga, Kobayashi Kouji, Kamiyama Reikou, Yoshimi Ryusuke, Asami Yukiko, Kirino Yohei, Ohno Shigeru, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   62回   346 - 346   2018.3

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  • 合成免疫抑制剤/DMARDs 全身性エリテマトーデスにおける用量とトラフに基づくtacrolimusの有効性 横断的研究(Synthetic immunosuppressants/DMARDs Efficacy of tacrolimus based on dosage and trough in systemic lupus erythematosus: a cross-sectional study)

    Kunishita Yosuke, Yoshimi Ryusuke, Sakurai Natsuki, Kishimoto Daiga, Komiya Takaaki, Sato Yuichiro, Nagai Hideto, Hamada Naoki, Sugiyama Yumiko, Tsuchida Naomi, Soejima Yutaro, Nakano Hiroto, Kamiyama Reikou, Kirino Yohei, Ohno Shigeru, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   62回   390 - 390   2018.3

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  • PM/DM 血清microRNA-1は多発性筋炎/皮膚筋炎関連間質性肺疾患の治療反応を予測する新規バイオマーカーである(PM/DM Serum MicroRNA-1 is a Novel Biomarker for Predicting Therapeutic Responses of Polymyositis/dermatomyositis-associated Interstitial Lung Disease)

    Sugiyama Yumiko, Yoshimi Ryusuke, Tamura Maasa, Kunishita Yosuke, Kishimoto Daiga, Kirino Yohei, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   62回   380 - 380   2018.3

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  • 本院における移行期医療の現状 内科の立場から

    神山 玲光, 吉見 竜介, 小宮 孝章, 櫻井 菜月, 佐藤 雄一郎, 副島 裕太郎, 岸本 大河, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   62回   844 - 844   2018.3

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  • 多発性筋炎・皮膚筋炎3 皮膚筋炎・多発筋炎の治療中に生じる日和見感染症の予測因子の検討

    佐藤 雄一郎, 杉山 裕美子, 吉見 竜介, 田村 真麻, 國下 洋輔, 岸本 大河, 吉岡 裕二, 小林 幸司, 峯岸 薫, 渡邉 俊幸, 小宮 孝章, 櫻井 菜月, 濱田 直樹, 永井 秀人, 土田 奈緒美, 副島 裕太郎, 仲野 寛人, 神山 玲光, 上原 武晃, 桐野 洋平, 関口 章子, 井畑 淳, 大野 滋, 長岡 章平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   62回   492 - 492   2018.3

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  • SLE・抗リン脂質抗体症候群3 高齢発症SLEの臨床的特徴の検討

    櫻井 菜月, 國下 洋輔, 吉見 竜介, 岸本 大河, 小宮 孝章, 佐藤 雄一郎, 永井 秀人, 濱田 直樹, 副島 裕太郎, 杉山 裕美子, 土田 奈緒美, 仲野 寛人, 神山 玲光, 桐野 洋平, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   62回   468 - 468   2018.3

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  • SLE・抗リン脂質抗体症候群4 間質炎症細胞浸潤と血栓を有するループス腎炎患者は横断時血清Creが有意に高い

    岸本 大河, 吉見 竜介, 櫻井 菜月, 國下 洋輔, 小宮 孝章, 佐藤 雄一郎, 副島 裕太郎, 神山 玲光, 桐野 洋平, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   62回   471 - 471   2018.3

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  • 家族性地中海熱が疑われた二症例

    大津 佑希子, 桐野 洋平, 濱田 直樹, 永井 秀人, 副島 裕太郎, 神山 玲光, 浅見 由希子, 吉見 竜介, 中島 秀明

    関東リウマチ   51   49 - 52   2018.2

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    症例1は34歳男性で、4年前より2〜3ヵ月ごとに数週間続く腹痛が出現し、前医消化器内科で精査を受けるも原因不明であった。今回、炎症高値の精査目的に当科紹介となった。当科受診以降も2ヵ月に1回程度の腹痛発作を認めていた。発作時は37.9℃程度の発熱を認めており、それに伴いCRPの上昇も認められた。その後、コルヒチン投与を開始したところ、症状は速やかに消失し、CRP陰性化を認めた。症例2は41歳男性で、3年前より1ヵ月に2回程度、38℃台の発熱や腹痛を自覚していた。その後、当院外科紹介となり、遺残胆石摘出術が施行された。術後、抗菌薬加療をされていたが、40℃台の発熱、CRP高値が遷延したため当科併診となった。コルヒチンを開始したところ、初めて解熱や症状消失、CRPの陰性化を認め、以降、発熱、腹痛ともに認めていない。

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  • 消化管出血および穿孔をきたした多発血管炎性肉芽腫症に対し、リツキシマブ投与と血漿交換療法が奏効した一例

    野本 芽衣, 副島 裕太郎, 小宮 孝章, 神山 玲光, 櫻井 菜月, 佐藤 雄一郎, 岸本 大河, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会関東支部学術集会プログラム・抄録集   28回   71 - 71   2017.12

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  • Corynebacterium blood stream infection among hematological malignancy patients with neutropenia: a case series analysis

    Hiroyuki Takahashi, Hideaki Kato, Ayako Matsumura, Kazuho Miyashita, Sei Samukawa, Yuki Nakajima, Maki Hagihara, Etsuko Yamazaki, Shin Fujisawa, Hideaki Nakajima

    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS   50   S60 - S60   2017.11

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  • Predictive Factors Associated with Successful Down-Titration of Biologics for Rheumatoid Arthritis Patients in Clinical Practice

    Takaaki Komiya, Kaoru Minegishi-Takase, Natsuki Sakurai, Yuichiro Sato, Hideto Nagai, Naoki Hamada, Yumiko Sugiyama, Naomi Tsuchida, Yutaro Soejima, Yosuke Kunishita, Hiroto Nakano, Daiga Kishimoto, Koji Kobayashi, Reikou Kamiyama, Ryusuke Yoshimi, Yukiko Asami, Yohei Kirino, Shigeru Ohno, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   69   2017.10

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  • Serum Microrna-1 Can be a Predictive Marker for Disease Activity of Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease

    Yumiko Sugiyama, Ryusuke Yoshimi, Yosuke Kunishita, Daiga Kishimoto, Yohei Kirino, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   69   2017.10

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  • The Predictive Risk Factors for Opportunistic Infection during Treatment for Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease

    Yumiko Sugiyama, Ryusuke Yoshimi, Maasa Tamura, Naoki Hamada, Hideto Nagai, Naomi Tsuchida, Yosuke Kunishita, Yutaro Soejima, Daiga Kishimoto, Reikou Kamiyama, Kaoru Minegishi, Yohei Kirino, Shigeru Ohno, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   69   2017.10

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  • The Discrepancy between the EULAR Response Criteria and Ultrasonography Assessment for Monitoring Therapeutic Response in Rheumatoid Arthritis

    Ryusuke Yoshimi, Yuichiro Sato, Natsuki Sakurai, Takaaki Komiya, Naoki Hamada, Hideto Nagai, Naomi Tsuchida, Yumiko Sugiyama, Yutaro Soejima, Yosuke Kunishita, Hiroto Nakano, Daiga Kishimoto, Reikou Kamiyama, Kaoru Minegishi-Takase, Yohei Kirino, Shigeru Ohno, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   69   2017.10

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  • 膠原病と関節リウマチ 関節リウマチの治療効果モニタリングにおける関節超音波検査8関節評価の有用性について

    吉見 竜介, 濱田 直樹, 永井 秀人, 杉山 裕美子, 土田 奈緒美, 副島 裕太郎, 國下 洋輔, 岸本 大河, 神山 玲光, 峯岸 薫, 浅見 由希子, 桐野 洋平, 大野 滋, 中島 秀明

    アレルギー   66 ( 4-5 )   578 - 578   2017.5

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  • SLE-1 M2マクロファージの機能的な変化はループス腎炎の病状形成に寄与する(SLE Functional alteration of M2 Macrophages contributes to pathogenesis of lupus nephritis)

    Kishimoto Daiga, Kirino Yohei, Tamura Maasa, Yoshimi Ryusuke, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   330 - 330   2017.3

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  • リウマチ足変形を考える 内科的側面から外科的治療まで 関節リウマチにおける足関節の関節超音波が教えること

    豊田 行健, 田村 真麻, 桐野 洋平, 杉山 裕美子, 土田 奈緒美, 國下 洋輔, 岸本 大河, 神山 玲光, 峯岸 薫, 吉見 竜介, 上田 敦久, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   232 - 232   2017.3

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  • 成人発症スチル病に対する2016年版ACR/EULARマクロファージ活性化症候群の分類の適応(Application of 2016 ACR/EULAR macrophage activation syndrome classification criteria on adult-onset Still's disease)

    Nagai Hideto, Kirino Yohei, Hamada Naoki, Sugiyama Yumiko, Tsuchida Naomi, Soejima Yutaro, Kunishita Yosuke, Kishimoto Daiga, Kamiyama Reikou, Nakano Hiroto, Yoshimi Ryusuke, Asami Yukiko, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   631 - 631   2017.3

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  • リウマチ性疾患の画像 関節超音波検査による8関節評価は関節リウマチの治療効果のモニタリングに有用である

    吉見 竜介, 濱田 直樹, 永井 秀人, 杉山 裕美子, 土田 奈緒美, 副島 裕太郎, 國下 洋輔, 岸本 大河, 神山 玲光, 峯岸 薫, 浅見 由希子, 桐野 洋平, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   576 - 576   2017.3

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  • 膠原病と妊娠 現行のシクロフォスファミド大量静注療法(IVCY)に対する卵巣保護療法の有用性についてのpreliminary study

    井畑 淳, 峯岸 薫, 吉見 竜介, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   521 - 521   2017.3

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  • SLE-1 当院におけるSLE患者のサブグループ分類のための予備的な試み(SLE Preliminary attempt for subgrouping of patients with systemic lupus erythematosus in our hospital)

    Hamada Naoki, Kirino Yohei, Nagai Hideto, Soejima Yutaro, Sugiyama Yumiko, Tsuchida Naomi, Kunishita Yosuke, Kishimoto Daiga, Nakano Hiroto, Kamiyama Reikou, Minegishi Kaoru, Asami Yukiko, Yoshimi Ryusuke, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   330 - 330   2017.3

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  • 関節リウマチにおけるトシリズマブ療法に対する良好な応答性の予測因子は何か?(What is the predictive factor for good response to tocilizumab in rheumatoid arthritis?)

    Kunishita Yosuke, Yoshimi Ryusuke, Nagai Hideto, Hamada Naoki, Soejima Yutaro, Sugiyama Yumiko, Tsuchida Naomi, Nakano Hiroto, Kishimoto Daiga, Kamiyama Reikou, Asami Yukiko, Kirino Yohei, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   614 - 614   2017.3

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  • CTD-2 多発性筋炎と皮膚筋炎に対する治療中の感染症の合併症に関する予測的な危険因子(CTD The Predictive Risk Factors for Complication of Infection during the Treatment for Polymyositis and Dermatomyositis)

    Sugiyama Yumiko, Yoshimi Ryusuke, Tamura Maasa, Hamada Naoki, Nagai Hideto, Tsuchida Naomi, Soejima Yutaro, Kunishita Yosuke, Kishimoto Daiga, Nakano Hiroto, Kamiyama Reikou, Minegishi Kaoru, Asami Yukiko, Kirino Yohei, Ohno Shigeru, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   371 - 371   2017.3

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  • 免疫抑制治療が奏効した皮膚潰瘍・肺高血圧症の一例

    杉山 裕美子, 濱田 直樹, 永井 秀人, 立壁 裕子, 土田 奈緒美, 副島 裕太郎, 峯岸 薫, 神山 玲光, 吉見 竜介, 浅見 由希子, 桐野 洋平, 中島 秀明

    関東リウマチ   50   119 - 127   2017.3

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    症例は28歳時に関節リウマチの既往があった。5年前よりレイノー症状、頬部紅斑が出現し、今回、労作時呼吸困難と両側下腿浮腫を認めた。心エコーで肺高血圧症が疑われ精査目的に当科入院となった。顔面紅斑、蛋白尿、LAC陽性、心膜炎を疑う所見から、抗ds-DNA抗体、抗核抗体、抗Sm抗体陰性と非典型的であったがSLEと考え、心筋炎、PHの合併例として先行して治療を開始した。入院直後からPSLを増量し、心筋炎、血管炎の合併を考慮し、第10病日にIVCY、続けてステロイドパルスを施行した。また、初診時にNYHA IIIの両心不全を合併しており、血圧コントロールと心不全治療のため、利尿薬に加えACE阻害薬を開始した。心不全治療と免疫抑制治療で自覚症状、データ、エコー所見は改善した。IVCY 2回目施行後、蛋白尿はほぼ陰性化し、NYHAも改善が得られた。

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  • リウマチ性疾患の画像 血管炎症候群におけるPET-CTの有用性の検討

    杉山 裕美子, 吉見 竜介, 井畑 淳, 濱田 直樹, 永井 秀人, 土田 奈緒美, 國下 洋輔, 副島 裕太郎, 岸本 大河, 仲野 寛人, 神山 玲光, 浅見 由希子, 桐野 洋平, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   579 - 579   2017.3

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  • 広範な下大静脈血栓症にて診断された血管Behcet病の一例

    秀川 智春, 月山 秀明, 小宮 孝章, 小林 幸司, 峯岸 薫, 岳野 光洋, 大野 滋, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   694 - 694   2017.3

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  • ベーチェット病 ベーチェット病患者のサブグループ化と個別化医療に向けての展望

    副島 裕太郎, 桐野 洋平, 岳野 光洋, 出口 治子, 須田 昭子, 杉山 裕美子, 土田 奈緒美, 國下 洋輔, 岸本 大河, 神山 玲光, 吉見 竜介, 浅見 由希子, 渡邉 俊幸, 上原 武晃, 峯岸 薫, 山崎 哲, 関口 章子, 井畑 淳, 大野 滋, 上田 敦久, 五十嵐 俊久, 長岡 章平, 石ヶ坪 良明, 中島 秀明

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   442 - 442   2017.3

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  • 関節リウマチにおける滑膜炎の超音波診断検査の正確性 体系的な考察とメタ分析(Diagnostic test accuracy of ultrasonography for synovitis in rheumatoid arthritis: systematic review and meta-analysis)

    Minegishi Kaoru, Horita Nobuyuki, Kobayashi Kouji, Yoshimi Ryusuke, Kirino Yohei, Ohno Shigeru, Nakajima Hideaki

    日本リウマチ学会総会・学術集会プログラム・抄録集   61回   613 - 613   2017.3

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  • Impact of the Difference in Body Mass Index at Transplantation from That at Diagnosis for Graft-Versus-Host Disease-Free, Relapse-Free Survival in Acute Myeloid Leukemia

    Taiki Ando, Etsuko Yamazaki, Haruka Teshigawara, Eriko Ogusa, Yoshimi Ishii, Kazuho Miyashita, Kenji Motohashi, Takuya Miyazaki, Takayoshi Tachibana, Maki Hagihara, Kenji Matsumoto, Masatsugu Tanaka, Chizuko Hashimoto, Hideyuki Koharazawa, Katsumichi Fujimaki, Jun Taguchi, Hiroyuki Fujita, Heiwa Kanamori, Shin Fujisawa, Hideaki Nakajima

    BLOOD   128 ( 22 )   2016.12

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  • Identification of Bone Marrow Involvement of FL: Comparison of PET-CT and Bone Marrow Biopsy.

    Yuki Nakajima, Shin Fujisawa, Chika Nigauri, Teshigawara Haruka, Ayako Matsumura, Taiki Ando, Taisei Suzuki, Eri Yamamoto, Eriko Ogusa, Yoshimi Ishii, Hiroyuki Takahashi, Kazuho Miyashita, Reina Watanabe, Takuya Miyazaki, Kenji Motohashi, Atsuko Fujita, Maki Hagihara, Kenji Matsumoto, Hideaki Nakajima

    BLOOD   128 ( 22 )   2016.12

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  • The Role of Tripartite Motif-Containing 21 in Interferon Signature of Systemic Lupus Erythematosus

    Reikou Kamiyama, Ryusuke Yoshimi, Yumiko Sugiyama, Yosuke Kunishita, Daiga Kishimoto, Toshinori Tsukahara, Yukiko Asami, Yohei Kirino, Mitsuhiro Takeno, Atsuhisa Ueda, Keiko Ozato, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   68   2016.10

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  • The Predictive Risk Factors for Complication of Infection during the Treatment for Inflammatory Myopathies Complicated with Interstitial Lung Disease

    Yumiko Sugiyama, Maasa Tamura, Ryusuke Yoshimi, Naoki Hamada, Hideto Nagai, Yuko Tatekabe, Naomi Tsuchida, Yutaro Soejima, Yosuke Kunishita, Daiga Kishimoto, Hiroto Nakano, Reikou Kamiyama, Kaoru Minegishi, Yukiko Asami, Yohei Kirino, Shigeru Ohno, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   68   2016.10

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  • The 8-Joint Ultrasound Score Is a Useful Marker for Monitoring Therapeutic Response in Rheumatoid Arthritis

    Ryusuke Yoshimi, Yukihiro Toyota, Naomi Tsuchida, Yumiko Sugiyama, Yosuke Kunishita, Daiga Kishimoto, Reikou Kamiyama, Kaoru Minegishi, Maasa Tamura, Yukiko Asami, Yohei Kirino, Shigeru Ohno, Hideaki Nakajima

    ARTHRITIS & RHEUMATOLOGY   68   2016.10

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  • Dysregulation of RUNX1 Plays a Critical Role in the Progression of Myelodysplastic Syndromes

    Hiroko Sakurai, Yuka Harada, Hirotaka Matsui, Hideaki Nakajima, Toshio Kitamura, Norio Komatsu, Hironori Harada

    BLOOD   126 ( 23 )   2015.12

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  • OVEREXPRESSION OF RUNX1 SHORT ISOFORM PLAYS A PIVOTAL ROLE IN THE DEVELOPMENT OF MYELODYSPLASTIC SYNDROMES/MYELOPROLIFERATIVE NEOPLASMS

    Hiroko Sakurai, Yuka Harada, Hirotaka Matsui, Hideaki Nakajima, Toshio Kitamura, Norio Komatsu, Hironori Harada

    EXPERIMENTAL HEMATOLOGY   43 ( 9 )   S93 - S93   2015.9

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  • A CRITICAL ROLE FOR O-GLCNACYLATION IN MURINE FETAL LIVER AND ADULT HEMATOPOIESIS

    S. Soma, Y. Fukuchi, S. Okamoto, H. Nakajima

    HAEMATOLOGICA   100   125 - 126   2015.6

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  • Recurrent CDC25C mutations drive malignant transformation in FPD/AML

    Akihide Yoshimi, Takashi Toya, Masahito Kawazu, Toshihide Ueno, Ayato Tsukamoto, Hiromitsu Iizuka, Masahiro Nakagawa, Yasuhito Nannya, Shunya Arai, Motoshi Ichikawa, Hironori Harada, Kensuke Usuki, Yasuhide Hayashi, Etsuro Ito, Keita Kirito, Hideaki Nakajima, Hiroyuki Mano, Mineo Kurokawa

    CANCER RESEARCH   74 ( 19 )   2014.10

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    DOI： 10.1158/1538-7445.AM2014-3439

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  • 大顆粒リンパ球性白血病とSTAT3変異

    NAKAJIMA HIDEAKI

    最新医学   69 ( 9 )   1889 - 1894   2014.9

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  • C-TERMINAL TRUNCATION TYPE OF RUNX1 MUTANTS INDUCE MDS/AML VIA GAIN-OF-FUNCTION MECHANISMS

    Hironori Harada, Yuka Harada, Daichi Inoue, Goro Sashida, Atsushi Iwama, Hideaki Nakajima, Norio Komatsu, Toshio Kitamura

    EXPERIMENTAL HEMATOLOGY   42 ( 8 )   S37 - S37   2014.8

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  • 骨髄増殖性腫瘍 1.骨髄増殖性腫瘍病態解明の進歩

    NAKAJIMA HIDEAKI

    血液フロンティア   24 ( 7 )   989 - 995   2014.6

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  • がんの新規治療を目指した基礎研究 新しいがん薬物療法への革新技術 iPS細胞を用いた白血病発症機序の研究と臨床応用

    NAKAJIMA HIDEAKI

    日本臨床   72   78 - 83   2014.2

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  • 造血幹細胞 2.造血幹細胞におけるTET2の働き

    NAKAJIMA HIDEAKI

    Annual Review 血液   2014   8 - 14   2014.1

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  • MLL融合遺伝子による造血幹細胞の癌化にはPlzfを介した異常な自己修復機構が重要である

    小埜良一, 桝屋正浩, 中島秀明, 片山直之, 北村俊雄, 野阪哲哉

    がん研究分野の特性等を踏まえた支援活動公開シンポジウムプログラム・抄録集 平成25年度   2014

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  • Chemo-Immunotherapy With Hyper-CVAD/MA and Rituximab For B-Cell Lymphomas Leads To Prolonged Immune Suppression Compared To Conventional Treatment With R-CHOP

    Eri Matsuki, Taku Kikuchi, Norisato Hashimoto, Shunsuke Souma, Sumiko Kohashi, Takaaki Toyama, Masatoshi Sakurai, Daiki Karigane, Daichi Abe, Takayuki Shimizu, Kenji Yokoyama, Hideaki Nakajima, Shinichiro Okamoto

    BLOOD   122 ( 21 )   2013.11

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  • Impaired Hematopoietic Differentiation of iPSCs Derived From Patients with FPD/AML

    Masatoshi Sakurai, Hiroyoshi Kunimoto, Naohide Watanabe, Yumi Fukuchi, Ken Sadahira, Shinsuke Yuasa, Keiichi Fukuda, Satoshi Yamazaki, Hiromitsu Nakauchi, Yasuhiro Ebihara, Kohichiro Tsuji, Etsuro Ito, Yuka Harada, Hironori Harada, Shinichiro Okamoto, Hideaki Nakajima

    BLOOD   120 ( 21 )   2012.11

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  • Tet2 Uniquely Regulates Self-Renewal and Long Term Repopulating Capacity of Fetal Liver and Bone Marrow Hematopoietic Stem Cells

    Hiroyoshi Kunimoto, Yumi Fukuchi, Masatoshi Sakurai, Daichi Abe, Ken Sadahira, Yasuo Ikeda, Shinichiro Okamoto, Hideaki Nakajima

    BLOOD   120 ( 21 )   2012.11

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  • 11q23転座型白血病における自己複製能関連転写因子を介した新規分子メカニズムの解析

    小埜良一, 桝屋正浩, 中島秀明, 榎本豊, 宮田恵里, 上迫努, 伊藤守, 中村彰秀, 鈴木圭, 片山直之, 北村俊雄, 野阪哲哉

    日本小児血液・がん学会学術集会・日本小児がん看護学会・がんの子供を守る会公開シンポジウムプログラム・総会号   53rd-9th-16th ( プログラム・総会号 )   219 - 219   2011.11

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  • Disruption of Tet2 Leads to Enhanced Self-Renewal and Competitive Repopulating Capacity of Fetal Liver Hematopoietic Stem Cells

    Hiroyoshi Kunimoto, Yumi Fukuchi, Masatoshi Sakurai, Ken Sadahira, Yasuo Ikeda, Shinichiro Okamoto, Hideaki Nakajima

    BLOOD   118 ( 21 )   1009 - 1010   2011.11

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  • ANALYSIS OF JAK2 MUTATION IN MYELOPROLIFERATIVE NEOPLASM BY SUPERSENTIVE PCR-INVADER ASSAY AND ITS CLINICAL SIGNIFICANCE

    Yoshitaka Miyakawa, Makoto Suzuki, Toshikazu Yamaguchi, Kenji Yokoyama, Hideaki Nakajima, Yoshinobu Aisa, Yuiko Tsukada, Jun Kato, Tomoki Ueda, Akiko Yamane, Eri Matsuki, Norihiro Awaya, Takehiko Mori, Shinichiro Okamoto

    ANNALS OF ONCOLOGY   21   16 - 16   2010.11

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  • Differential Role of Myeloid Transcription Factors, C/EBP alpha and PU.1 In Leukemogenesis by MLL-Fusion Oncogenes

    Yumi Fukuchi, Kana Kuroda, Ken Sadahira, Ryouichi Ono, Daniel G. Tenen, Toshio Kitamura, Tetsuya Nosaka, Shinichiro Okamoto, Hideaki Nakajima

    BLOOD   116 ( 21 )   664 - 664   2010.11

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  • MLL-ENL融合遺伝子による造血幹細胞を標的とした形質転換における新規分子メカニズムの解析(Analysis of novel molecular mechanism in transformation by MLL-ENL targeting long-term hematopoietic stem cells)

    小埜 良一, 桝屋 正浩, 中島 秀明, 榎本 豊, 宮田 恵里, 上迫 努, 伊藤 守, 鈴木 圭, 片山 直之, 北村 俊雄, 野阪 哲哉

    日本癌学会総会記事   69回   49 - 49   2010.8

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  • DIFFERENTIAL ROLE OF MYELOID TRANSCRIPTION FACTORS, C/EBP alpha AND PU.1 IN LEUKEMOGENESIS BY MLL-FUSION ONCOGENES

    Y. Fukuchi, K. Kuroda, K. Sadahira, T. Kitamura, Y. Ikeda, S. Okamoto, H. Nakajima

    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL   95   12 - 12   2010.6

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  • MLL‐ENL融合遺伝子は造血幹細胞のみを標的として形質転換を生じる

    小埜良一, 桝屋正浩, 宮田恵里, 中島秀明, 上迫努, 伊藤守, 鈴木圭, 片山直之, 北村俊雄, 野阪哲哉

    臨床血液   50 ( 9 )   951 - 951   2009.9

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  • MLL-ENL融合遺伝子による形質転換は造血幹細胞のみを標的として生じる(Malignant transformation by MLL-ENL fusion gene arises selectively from long-term hematopoietic stem cells)

    小埜 良一, 桝屋 正浩, 宮田 恵里, 中島 秀明, 上迫 努, 伊藤 守, 鈴木 圭, 片山 直之, 北村 俊雄, 野阪 哲哉

    日本癌学会総会記事   68回   83 - 84   2009.8

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  • マウス骨髄移植モデルにおいて,Evi1はMDS/AMLを誘発する

    渡辺(大河内, 直子, 北浦次郎, 原田浩徳, 米野由希子, 加藤菜穂子, 小埜良一, 野阪哲哉, 中島秀明, 北村俊雄

    臨床血液   49 ( 9 )   884   2008.9

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  • Robo4の造血幹細胞における生理学的機能

    中島秀明, 越野裕子, 柴田文, 福地由美, LI Dean, 北村俊雄

    臨床血液   49 ( 9 )   2008

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  • TIMP-3 inhibition of angiopoietin-1 signaling recruits hematopoietic stem cells from the bone marrow niche.

    Hideaki Nakajima, Miyuki Ito, David Smookler, Fumi Shibata, Yumi Fukuchi, Yuko Goto-Koshino, Fumio Arai, Toshio Suda, Rama Khokha, Toshio Kitamura

    BLOOD   110 ( 11 )   378A - 378A   2007.11

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  • RasGRP4と変異型AML1はマウスBMTモデルにおいて協調的に働き,T細胞性白血病を誘発する

    渡辺(大河内, 直子, 沖俊彦, 小埜良一, 原田浩徳, 湯地晃一郎, 東條有伸, 中島秀明, 野阪哲哉, 稲葉俊哉, 北浦次郎, 北村俊雄

    臨床血液   48 ( 9 )   859   2007.9

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  • RasGRP4 collaborates with AML1 point mutiation to induce T cell leukemia in a mouse BMT model

    N. Watanabe-Okochi, T. Oki, R. Ono, H. Harada, Y. Komeno, K. Yuji, A. Tojo, H. Nakajima, T. Nosaka, J. Kitaura, T. Kitamura

    EXPERIMENTAL HEMATOLOGY   35 ( 9 )   20 - 21   2007.9

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  • RasGRP4 collaborates with AML1 point mutiation to induce T cell leukemia in a mouse BMT model

    N. Watanabe-Okochi, T. Oki, R. Ono, H. Harada, Y. Komeno, K. Yuji, A. Tojo, H. Nakajima, I. Nosaka, J. Kitaura, T. Kitamura

    EXPERIMENTAL HEMATOLOGY   35 ( 9 )   76 - 76   2007.9

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  • A role of Wnt signaling in hematopoietic stem cell and hematological malignancies

    54 ( 2 )   224 - 230   2007.2

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  • MLL融合蛋白はRas-MAPキナーゼ系の活性化と相乗的に協調して急性白血病を発症する

    小埜良一, 小埜良一, 熊谷英敏, 中島秀明, 殿塚行雄, 菱谷愛, 滝智彦, 林泰秀, 北村俊雄, 野阪哲哉

    臨床血液   48 ( 9 )   2007

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  • A BMT model mice for myelodysplastic syndromes (MDS) and transformation to AML.

    Naoko Watanabe-Okochi, Jiro Kitaura, Hironori Harada, Ryoichi Ono, Hideaki Nakajima, Tetsuya Nosaka, Toshiya Inaba, Toshio Kitamura

    BLOOD   108 ( 11 )   744A - 744A   2006.11

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  • C/EBP alpha and C/EBP epsilon induce monocytic differentiation of myelomonocytic cells with MLL chimeric fusion gene.

    Hiromichi Matsushita, Hideaki Nakajima, Yoshihiko Nakamura, Hideo Tsukamoto, Yumiko Tanaka, Satomi Asai, Tetsuya Nosaka, Kiyoshi Ando, Hayato Miyachi

    BLOOD   108 ( 11 )   548A - 548A   2006.11

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    DOI： 10.1182/blood.V108.11.1938.1938

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  • Robo4/Magic roundabout is a novel surface marker for murine and human hematopoietic stem cells.

    Fumi Shibata, Yuko Goto-Koshino, Miyuki Ito, Yumi Fukuchi, Yoshihiro Morikawa, Hiromichi Matsushita, Hayato Miyachi, Toshio Kitamura, Hideaki Nakajima

    BLOOD   108 ( 11 )   204A - 205A   2006.11

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  • MAP kinase activation is essential for the development of acute leukemia by MLL fusion protein and FLT3 tyrosine kinase mutation.

    Ryoichi Ono, Hidetoshi Kumgai, Hideaki Nakajima, Yukio Tonozuka, Ai Hishiya, Tomohiko Taki, Yasuhide Hayashi, Toshio Kitamura, Tetsuya Nosaka

    BLOOD   108 ( 11 )   586A - 586A   2006.11

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  • AML1点変異はマウスBMTモデルにおいてMDS/AMLを発症させる

    渡辺直子, 北浦次郎, 原田浩徳, 小埜良一, 米野由希子, 佐藤均, 稲葉俊哉, 中島秀明, 野阪哲哉, 北村俊雄

    臨床血液   47 ( 9 )   1037   2006.9

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  • A BMT model mouse for myelodysplastic syndromes (MDS) and MDS/overt leukemia

    N. Watanabe-Okochi, J. Kitaura, H. Harada, R. Ono, T. Inaba, H. Nakajima, T. Nosaka, T. Kitamura

    EXPERIMENTAL HEMATOLOGY   34 ( 9 )   63 - 63   2006.9

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  • Integrin alpha(IIb)beta(3) induces the adhesion and activation of mast cells through interaction with fibrinogen. (vol 176, pg 52, 2006)

    T. Oki, J. Kitaura, K. Eto, Y. Lu, M. Maeda-Yamamoto, N. Inagaki, H. Nagai, Y. Yamanishi, H Nakajima, H. Kumagai, T. Kitamura

    JOURNAL OF IMMUNOLOGY   176 ( 6 )   3841 - 3841   2006.3

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  • 新規造血幹細胞マーカーRobo4の解析

    柴田文, 越野裕子, 伊藤美由紀, 福地由美, 石田明, 半田誠, 川合陽子, 松下弘道, 宮地勇人, 北村俊雄, 中島秀明

    臨床血液   47 ( 9 )   2006

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  • C/EBPαとPU.1は造血幹細胞機能を負に制御する

    福地由美, 伊藤美由紀, 柴田文, 外丸祐介, 伊藤守, 北村俊雄, 中島秀明

    臨床血液   47 ( 9 )   2006

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  • MLL融合蛋白による多段階発癌にはMAPキナーゼ系の活性化が重要である

    小埜良一, 熊谷英敏, 中島秀明, 殿塚行雄, 菱谷愛, 滝智彦, 林泰秀, 北村俊雄, 野阪哲哉

    臨床血液   47 ( 9 )   2006

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  • Activation of C/EBP alpha in hematopoietic stem cells leads to growth suppression and impairment of megakaryocyte differentiation.

    Y Fukuchi, F Shibata, M Ito, Y Goto-Koshino, Y Sotomaru, M Ito, T Kitamura, H Nakajima

    BLOOD   106 ( 11 )   638A - 638A   2005.11

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  • Immune suppressor factor confers enhanced supporting activity for hematopoietic stem cells in bone marrow stroma

    H Nakajima, F Shibata, Y Fukuchi, Y Goto-Koshino, M Ito, H Aburatani, T Kitamura

    EXPERIMENTAL HEMATOLOGY   33 ( 7 )   70 - 70   2005.7

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  • サイトカインとその受容体 サイトカイン受容体とシグナル伝達

    中島秀明, 北村俊雄

    日本臨床   63   2005

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  • TIMP-3,SFRP-1による造血幹細胞機能制御

    中島秀明, 柴田文, 福地由美, 伊藤美由紀, 越野裕子, 新井文用, 須田年生, 北村俊雄

    臨床血液   46 ( 8 )   2005

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  • 11q23転座型白血病発症におけるMLLの転座相手遺伝子の破断効果は重要か?

    小埜良一, 中島秀明, 尾崎勝俊, 滝智彦, 吉田進昭, 北村俊雄, 林泰秀, 野阪哲哉

    臨床血液   46 ( 8 )   2005

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  • Phosphoinositide3-kinase independent regulation of Bruton's tyrosine kinase in platelet immunoreceptor signaling.

    N Watanabe, H Nakajima, A Oda, Y Ikeda, M Handa

    BLOOD   104 ( 11 )   963A - 963A   2004.11

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  • Conditional expression of C/EBP alpha in mice reveals developmental plasticity of lymphoid and erythroid/megakaryocyte precursors in vivo.

    Y Fukuchi, F Shibata, M Ito, Y Goto-Koshino, Y Sotomaru, M Ito, T Kitamura, H Nakajima

    BLOOD   104 ( 11 )   193A - 193A   2004.11

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  • Immune suppressor factor confers enhanced supporting activity for hematopoietic stem cells in bone marrow stroma.

    H Nakajima, F Shibata, Y Fukuchi, Y Goto-Koshino, M Ito, T Kitamura

    BLOOD   104 ( 11 )   148A - 148A   2004.11

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  • Immune suppressor factor(ISF)による造血幹細胞増幅のメカニズム

    中島秀明, 柴田文, 福地由美, 越野裕子, 北村俊雄

    臨床血液   45 ( 8 )   2004

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  • 二段階発癌モデル系を用いたMLL融合蛋白による白血病発症の分子機構の解析

    小埜良一, 中島秀明, 尾崎勝俊, 熊谷英敏, 川島敏行, 滝智彦, 北村俊雄, 林泰秀, 野阪哲哉

    臨床血液   45 ( 8 )   2004

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  • 活性誘導型C/EBPalphaを用いた血球分化可塑性の解析

    福地由美, 柴田文, 越野裕子, 北村俊雄, 中島秀明

    臨床血液   45 ( 8 )   2004

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  • MLL-SEPT6 requires both a GTP-binding domain and a coiled-coil region of SEPT6 to transform murine primary bone marrow cells in concert with FLT3 internal tandem duplication.

    R Ono, H Nakajima, H Kumagai, K Ozaki, T Taki, T Kitamura, Y Hayashi, T Nosaka

    BLOOD   102 ( 11 )   845A - 845A   2003.11

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  • CCAAT/enhancer binding protein a is upregulated by signal transducers and activators of transcription 3 in granulocyte colony-stimulating factor signaling pathway.

    A Numata, K Shimoda, K Kamezaki, K Kato, T Miyamoto, Y Yamashita, Y Oshima, H Nakajima, A Iwama, K Aoki, K Takase, TE Tanimoto, F Ishikawa, T Haro, K Nagafuji, H Gondo, H Mano, M Harada

    BLOOD   102 ( 11 )   836A - 836A   2003.11

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  • The centrosomal protein TACC3 is essential for cell expansion and interfaces with p53-regulated apoptosis

    RP Piekorz, A Hoffmeyer, C Duntsch, C McKay, H Nakajima, Sexl, V, JN Ihle

    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY   367   R76 - R76   2003.3

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  • Retinoic acid receptor alpha (RAR alpha) mediated cell cycle arrest requires Mad1 and p27(KIP1).

    CR Walkley, LE Purton, YD Yuan, RAS Chandraratna, H Nakajima, GA McArthur

    BLOOD   100 ( 11 )   300A - 300A   2002.11

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  • Lipocalin (24p3), which is an essential molecule in IL-3-induced anti-apoptosis, is not involved in the prevention of apoptosis by G-CSF

    K Kamezaki, K Shimoda, A Numata, K Aoki, K Kato, K Takase, H Nakajima, K Ihara, T Haro, F Ishikawa, R Imamura, T Miyamoto, K Nagafuji, H Gondo, T Hara, M Harada

    BLOOD   100 ( 11 )   181B - 181B   2002.11

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  • FLT3の傍膜領域の重複変異は傍膜領域のチロシンリン酸化とSTAT5の活性化を引き起こす

    入江真理子, 熊谷英敏, 中島秀明, 野阪哲哉, 北村俊雄

    日本癌学会総会記事   61st   2002

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  • Role of phosphatidylinositol 3-kinase p85 alpha in platelet function.

    N Watanabe, H Nakajima, A Oda, H Suzuki, Y Matsubara, Y Ikeda, M Handa

    BLOOD   98 ( 11 )   752A - 752A   2001.11

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  • Functional interaction of STAT5 and nuclear receptor co-repressor SMRT: implications in negative regulation of STAT5-dependent transcription

    NAKAJIMA H, BRINDLE P K, HANDA M, IHLE J N

    EMBO Journal   20 ( 23 )   6836 - 6844   2001

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  • The AML1/ETO fusion protein represses erythroid cell differentiation, and downregulates a novel hematopoietic-specific transmembrane protein, ART-1.

    H Harada, Y Harada, H Nakajima, Downing, JR, A Kimura

    BLOOD   96 ( 11 )   669A - 669A   2000.11

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  • A critical role for CAAT-enhancer binding protein epsilon in cell cycle arrest and apoptosis during myeloid differentiation.

    N Watanabe, H Nakajima, E Ikeda, M Handa

    BLOOD   96 ( 11 )   284A - 284A   2000.11

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  • A new polymorphism, (70)Leu/Phe, within the leucine-rich repeat sequence of platelet glycoprotein Ib alpha.

    Y Matsubara, M Murata, T Moriki, K Yokoyama, N Watanabe, H Nakajima, M Handa, Y Ikeda

    BLOOD   96 ( 11 )   54B - 54B   2000.11

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  • サイトカインの臨床応用 現状と展望 G-CSFの基礎 up to date

    中島秀明, 北村俊雄

    分子細胞治療   1 ( 6 )   2000

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  • Functional interaction of Stat5 and nuclear receptor corepressor, SMRT: Implications in negative regulation of Stat5-dependent transcription.

    H Nakajima, PK Brindle, M Handa, JN Ihle

    BLOOD   94 ( 10 )   685A - 685A   1999.11

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  • Granulocyte colony-stimulating factor regulates myeloid differentiation through ccaat enhancer binding protein epsilon.

    H Nakajima, JL Cleveland, S Nagata, JN Ihle

    BLOOD   92 ( 10 )   712A - 712A   1998.11

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  • ESTABLISHMENT OF A NEW CELL-LINE CARRYING T(14-18) FROM NON-HODGKINS-LYMPHOMA

    S MORI, A MUTO, H UCHIDA, R WATANABE, H MATSUSHITA, H NAKAJIMA, M KIZAKI, S OKAMOTO, Y KAWAI, Y INATOMI, K WAKASUGI, T ABE, Y IKEDA

    EXPERIMENTAL HEMATOLOGY   23 ( 8 )   919 - 919   1995.8

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  • MECHANISMS OF RETINOID RESISTANCE IN LEUKEMIC-CELLS - ROLE OF CYTOCHROME-P-450 AND P-GLYCOPROTEIN

    M KIZAKI, H UENO, N TAKAYAMA, H NAKAJIMA, M MORIKAWA, Y YAMAZOE, HP KOEFFLER, Y IKEDA

    BLOOD   84 ( 10 )   A380 - A380   1994.11

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  • DIFFERENTIATION OF U937 CELLS BY VITAMIN-D3 IS ENHANCED BY RETINOIC ACIDS AND OLIGONUCLEOTIDES FOR VITAMIN-D3 RESPONSIVE ELEMENTS

    H NAKAJIMA, M KIZAKI, H UENO, A MUTO, H MATSUSHITA, Y IKEDA

    BLOOD   84 ( 10 )   A20 - A20   1994.11

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  • ATYPICAL TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE - DEMONSTRATION OF Y-CHROMOSOME SPECIFIC GENES IN THE SKIN BY PCR

    S MORI, H MATSUSHITA, K OZAKI, A ISHIDA, M TOKUHIRA, H NAKAJIMA, M KIZAKI, M HANDA, Y KAWAI, S OKAMOTO, T YAMAMORI, Y IKEDA

    BLOOD   82 ( 10 )   A403 - A403   1993.11

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  • EFFECTS OF RETINOIC ACID COMPOUNDS(ALL-TRANS AND 9-CIS RETINOIC ACID) ON CYTOKINE PRODUCTION AND EXPRESSION OF RAR AND RXR GENES BY HUMAN BONE-MARROW STROMAL CELLS

    H NAKAJIMA, M KIZAKI, S MORI, K HARIGAYA, Y IKEDA

    BLOOD   82 ( 10 )   A22 - A22   1993.11

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  • NOVEL RETINOIC ACID, 9-CIS RETINOIC ACID, IN COMBINATION WITH ALL-TRANS-RETINOIC ACID IS EFFECTIVE INDUCER OF DIFFERENTIATION OF RETINOIC ACID-RESISTANT HL-60 CELLS - RELATION TO RETINOIC ACID RECEPTOR AND RETINOID X-RECEPTOR EXPRESSION

    M KIZAKI, Y IKEDA, H NAKAJIMA, S MORI, M MORIKAWA, M OHTA, M SAITO, H KOEFFLER

    BLOOD   82 ( 10 )   A251 - A251   1993.11

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Research Projects

  • Elucidating molecular basis of myeloid cancers with epigenetic dysregulation and collapse of protein homeostasis

    Grant number：24K11565  2024.4 - 2027.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • タンパク質恒常性制御による白血病幹細胞生成・維持の分子メカニズム解明

    Grant number：23K27630  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    中島 秀明, 國本 博義

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    Grant amount：\18720000 （ Direct Cost: \14400000 、 Indirect Cost：\4320000 ）

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  • Therapeutic strategies for connective tissue diseases by targeting the autophagy-lysosomal pathway

    Grant number：22K08567  2022.4 - 2025.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

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  • Elucidation of the pathophysiology of systemic sclerosis targeting abnormal sodium metabolism

    Grant number：21K08462  2021.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

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  • Investigating molecular basis of chemoresistance using a novel leukemia cell line harboring high-risk chromosome abnormalities

    Grant number：21K08400  2021.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

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  • ミトコンドリアダイナミックスによる白血病幹細胞制御機構の解明と新規治療への応用

    Grant number：20H03714  2020.4 - 2023.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    中島 秀明, 國本 博義

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    Grant amount：\17680000 （ Direct Cost: \13600000 、 Indirect Cost：\4080000 ）

    白血病幹細胞（LSC）の生成・維持にはミトコンドリア機能が重要とされているが、LSCにおけるミトコンドリア動態、すなわちミトコンドリアダイナミックスがいかに制御されているのかは不明な点が多い。そこで本研究では、ミトコンドリアダイナミックスがLSC制御にいかに関わっているのか、その中でも特にマイトファジーとミトコンドリア融合に焦点をあて、これらの機能異常とLSCバイオロジー・治療反応性との関連について解析した。
    2020年度は、ミトコンドリアダイナミックスがLSC機能をどのように変化させ、また化学療法抵抗性を付与するかどうかを、マウスモデルを用いて解析した。具体的には、MLL融合遺伝子など各種白血病関連遺伝子をレトロウイルスを用いて正常マウス造血幹前駆細胞（HSPC）に発現させてAMLモデルを作成し、これらを用いたミトコンドリア機能解析を行った。またあわせて、ミトコンドリア機能と化学療法抵抗性の関係をFACS、生存解析、継代移植、抗癌剤のin vitro 感受性試験／in vivo 治療モデルなどで明らかにした。さらに、ミトコンドリア状態と化学療法抵抗性との関係、それらの基盤となる分子メカニズムを探るため、上記で作成したAMLモデルから白血病幹細胞を単離し、RNAシーケンスを施行して遺伝子発現の点から解析した。
    一方、急性骨髄性白血病（AML）患者検体の解析については、コロナ禍のため検体収集に遅れを生じており、予定より若干の遅れを見せている。

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  • Generation of evidence through registry construction by genome-wide subtype analysis of Behcet's disease

    Grant number：19H03700  2019.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount：\17290000 （ Direct Cost: \13300000 、 Indirect Cost：\3990000 ）

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  • The pathological role of autoantibodies in systemic lupus erythematosus

    Grant number：19K08914  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YOSHIMI Ryusuke

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    The role of autoantibodies in the pathogenesis of systemic lupus erythematosus is unknown. In this study, we investigated whether serum anti-TRIM21 antibodies are taken up by cells and modulate the function of TRIM21 in cells. The results showed that TRIM21 regulates the differentiation of B cells into plasmablasts and the production of antibodies and that anti-TRIM21 antibodies in serum may be transferred into immune cells and inhibit TRIM21 function. The intracellular trafficking of antibodies was observed to be promoted by stimulation with Toll-like receptor ligands and interferons, suggesting that this phenomenon may be part of the mechanism underlying the onset and exacerbation of systemic autoimmune diseases caused by infectious diseases.

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  • Regulation of normal and malignant hematopoiesis by protein glycosylation with O-GlcNAc

    Grant number：17K09909  2017.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    NAKAJIMA HIDEAKI

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    O-GlcNAc transferase (OGT) confers O-GlcNAc moiety to the serine/ threonine residue of the target proteins. O-GlcNAcylation plays a critical role for regulating protein function and epigenetic modification. We have preformed in-depth functional analysis of OGT in hematopoietic stem cells (HSCs) using Ogt-conditional knockout mice and found that OGT is crucial for HSC maintenance. OGT disruption in vivo led to decreased HSCs and impaired HSC function. Further analysis revealed that OGT is critical for quality control of mitochondria in HSCs through mitophagy regulation.

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  • Specific DNA damage repair mechanisms in leukemic stem cells

    Grant number：17K09935  2017.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Miyazaki Takuya

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    Leukemic stem cell is thought to be a critical factor for chemotherapy resistance or relapse in acute myeloid leukemia (AML). Using flow cytometry, we tried to identify leukemic stem cell population, CD34+/CD38- cells in bone marrow or peripheral blood samples from patients with newly diagnosed or relapsed AML. Leukemic stem cells were sorted based on the CD34+/CD38- expression, which were minor population (1.91% (0.83-3.24%)), and RNA and proteins were extracted for DNA repair analysis. AML-related mutations were also identified by targeted sequencing. The target molecule, which is critical for DNA repair in leukemic stem cells, will be determined in the future study.

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  • Epigenetic Regulation of hematopoietic stem cells by O-GlcNAc transferase

    Grant number：26670469  2014.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    NAKAJIMA Hideaki

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    Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）

    O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase （OGT） is a critical enzyme that catalyzes O-GlcNAcylation of Ser/Thr residues of various proteins. This study examined the physiological role of OGT in hematopoietic system using OGT conditional knockout mice. OGT-deficient fetal liver cells were severely decreased in number and lost colony-forming activity in methylcellulose culture. Moreover, self-renewal and long-term repopulating capacity of OGT-deficient fetal liver hematopoietic stem cells were severely impaired in transplantation assays. These results indicated that OGT played a critical role in fetal liver hematopoiesis.

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  • A role for ATOX1 in 5q- syndrome

    Grant number：24659467  2012.4 - 2014.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    NAKAJIMA Hideaki, OKAMOTO Shinichiro

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    Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）

    5q- syndrome is a subtype of myelodysplastic syndrome characterized by a deletion of chromosome 5q33. To elucidate molecular pathogenesis of 5q- syndrome, we focused on ATOX1, a cupper chaperone located in the common deleted region of 5q33. Frequencies of hematopoietic stem cells (HSCs), multipotent hematopoietic progenitors, and lineage-committed progenitors in the bone marrow were normal in ATOX1-/- mice, and ATOX1-/- HSCs maintained normal self-renewal and long-term repopulating capacities. These results suggest that ATOX1 is not essential for HSC function and hematopoietic differentiation, and that ATOX1 has little, if any, roles in 5q- syndrome.

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  • Differentiation induction of the myelomonocytic cells with C/EBPs and PU.1

    Grant number：19591139  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MATSUSHITA Hiromichi, MIYACHI Hayato, ANDO Kiyoshi, NAKAJIMA Hideaki

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

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  • Regulation of self-renewal of leukemic stem cells by hematopoietic transcription factors

    Grant number：19390259  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    NAKAJIMA Hideaki, KITAMURA Toshio

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    Grant amount：\18720000 （ Direct Cost: \14400000 、 Indirect Cost：\4320000 ）

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  • 新規造血幹細胞マーカーによる新しいヒト造血幹細胞単離技術の開発と再生医療への応用

    Grant number：18659278  2006 - 2007

    日本学術振興会  科学研究費助成事業  萌芽研究

    中島 秀明

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    Grant amount：\3300000 （ Direct Cost: \3300000 ）

    細胞表面マーカーを用いた造血幹細胞(HSC)の同定において、マウスではCD34-c-Kit^+Sca-1^+Lineage(CD34-KSL)細胞が高濃度にHSCを濃縮した分画とされているが、完全なHSCの純化は未だなされていない。またヒトではCD34陽性細胞が且SCと同義に用いられているが、CD34のみに依存した且SC同定法の限界と危険性も指摘されている。以上のことから、マウスおよびヒトHSCをより効率よく同定・純化することができる新たなマーカーが求められている。このような背景から、本研究はHSCに発現する新たな細胞表面マーカーを探索し、さらにその細胞膜蛋白質がHSC機能に果たす役割を明らかにする目的で行われた。Roboファミリーは主に神経細胞に発現する膜受容体で、Slitとよばれる分泌蛋白をリガンドとしている。Robo/Slitシステムは神経のaxon guidanceに重要な役割を果たしているほか、腫瘍血管新生やリンパ球の遊走を制御することが近年報告された。RoboファミリーにはRobo1〜Robo4の4種類が存在するが、このうちRobo4はその発現が内皮細胞特異的であるなど他のメンバーとは異なった性質を持つ。我々はHSC特異的に発現する遺伝子としてRobo4に着目し、新たなHSCマーカーとしてのRobo4の有用性をマウスおよびヒトにおいて検討した。
    本年度は昨年度に引き続きRobo4のHSC同定・純化における有用性について検討をすすめた。Robo4高発現KSLI細胞(Robo4^+KSL、)とRobo4陰性/低発現KSL細胞(Robo4^-KSL)をそれぞれFACSでソーティングし致死量放射線照射したレシピエントマウスに移植したところ、Robo4^+KSLのみが生着と数ケ月にわたる長期骨髄再建能を示した。このことから、長期骨髄再建能と自己複製能をもつlong-termHSCはRobo4^+KSL、に特異的に存在することが示唆された。

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  • Crosstalk between STATs and small GTPases in the control of cell division and differentiation.

    Grant number：16209032  2004 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    KITAMURA Toshio, NOSAKA Tetsuya, NAKAJIMA Hideaki, KAWASHIMA Toshiyuki

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    Grant amount：\48490000 （ Direct Cost: \37300000 、 Indirect Cost：\11190000 ）

    In this research project, we have investigated cross-talk between activation of STAT3/STAT5 and Rho family small GTPases. In 2004-2005, using mouse embryonic fibroblasts where Racl can be conditionally deleted by Cre recombinase as well as a dominant negative Racl and siRNA for Racl, we demonstrated that Racl is essential for nuclear transport of STAT3 and STAT5. However, the underlying molecular mechanisms remained elusive. In 2006, we investigated how Racl controls nuclear transport of STAT3 and STAT5. To this end, we established a nuclear transport assay using permialized cells and recombinant proteins produced in F9 insect cells. The nuclear transport assay revealed that an active form of Racl, MgcRacGAP and importin a/b are required for the nuclear transport of phosphorylated STAT3 and STAT5. Interestingly, STAT/Racl/MgcRacGAP complex binds importin a only when Racl is in its GTP-bound form, indicating that MgcRacGAP plays an important role in the binding and dissociation of STAT and importins (Kawashima et al., J Cell Biol, 2006). We also found that MgcRacGAP harbors nuclear localization signal (NLS). Although STAT3 and 5 do not possess typical NLS, the present results show that MgcRacGAP and Racl works as a nuclear shaperon for the activated STAT3 and 5. In addition, we also found that MgcRacGAP also binds JAK2 that is known to phosphorylate STAT proteins. Knockdown of either MgcRacGAP or Racl not only inhibited nuclear transport of STAT3/5 but also attenuated their phosphorylation. Altogether, the present results suggested that MgcRacGAP and Racl plays critical roles in the nuclear transport of STAT3 and STAT5 as well as transport to the plasma membrane and activation of these transcription factors.

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  • Regulation of self-renewal of hematopoietic stem cells by bone marrow stromal cells

    Grant number：16390274  2004 - 2005

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    NAKAJIMA Hideaki, KITAMURA Toshio, MORIKAWA Yoshihiro

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    Grant amount：\14200000 （ Direct Cost: \14200000 ）

    In order to analyze m Kirre function in vivo, we set out to disrupt m Kirre in mouse genome. We screened BAC library to obtain genomic fragment containing m Kirre gene and isolated several genomic fragments. Restriction mapping of m Kirre genomic fragment combined with the computer data base search completed the genomic map of m Kirre locus. Targeting vector was designed to replace the first exon and large portion of the 5-promoter region with Neomycin cassette to disrupt m Kirre gene. Completed targeting vector was electroporated into E14 embryonic stem (ES) cells, and approximately 400 Neomycin-resistant clones were selected and processed to identify homologously recombinant clones by Southern hybridization. We obtained one correctly targeted clone, which was confirmed by hybridizing with 5'- and 3-probes, together with Neo-probe. We are currently making chimeric mice by injecting this clone into blastcysts from C57BL/6 mice.
    As for ISF, we performed cDNA microarray analysis of bone marrow stromal cell lines overexpressing ISF and ShIF. Comparing expression profiles of MS10 cells expressing ISF, ShIF or mock plasmids revealed that TIMP-3 and SFRP-1 were down-regulated by ISF overexpression. By re-expressing TIMP-3 or SFRP-1 genes in MS10/ ISF cells, the enhanced hematopoietic stem cell (HSC) supporting activity of MS10/ ISF cells reduced a level similar to that of parental MS10 cells. These results indicate that TIMP-3 and SFRP-1 play critical roles in enhanced HSC activity conferred by ISF.

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  • レトロウイルス遺伝子導入系を用いた胎盤由来間葉系幹細胞の分化誘導法の確立

    Grant number：15039212  2003 - 2004

    日本学術振興会  科学研究費助成事業  特定領域研究

    中島 秀明

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    Grant amount：\4800000 （ Direct Cost: \4800000 ）

    本年度は昨年度確立した胎盤由来間葉系幹細胞(mesenchymal stem cell ; MSC)の分離・培養法をさらに確立し、全ての胎盤組織から安定にMSCを培養することを目標に研究を行った。新たにインフォームドコンセントを得た上で取得した20例の胎盤組織から胎盤のexplant培養を施行した。具体的にはこれら胎盤組織を細切し培養皿上で1-2週間培養し、全例で付着細胞群の増殖を認め、全てにおいて限界希釈によりクローナルな均一の細胞群を得た。これらは全て各種培養条件により脂肪細胞・骨芽細胞への分化を示し、多能性をもった幹細胞であることが示された。またRT-PCRによる検討では、これらの細胞はOct-4,Rex-1,GATA-2,AC133,Flt-1などを発現しており、FACSではCD29,CD44,CD54など他のMSCで報告されている細胞表面マーカーを発現していることが確認された。次に、レトロウイルスを用いて遺伝子を導入し各種組織細胞への分化を誘導することを目的として研究を行った。条件検討としてHoxB4の遺伝子導入を試みたところ、約60%の遺伝子導入効率を得ることができ、レトロウイルスを用いて安定かつ高率に遺伝子導入が可能であることを示した。

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  • Analysis of hematopoietic lineage plasticity by using inducible transcription factors

    Grant number：14370298  2002 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    NAKAJIMA Hideaki, KITAMURA Toshio

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    Grant amount：\13900000 （ Direct Cost: \13900000 ）

    In order to investigate the molecular mechanism of differentiation and possible lineage switch or trans-differentiation in various hematopoietic lineages, we generated inducible form of myeloid transcription factors C/EBP α and PU.1 and examined their effect in vitro or in vivo. Full length C/EBP a and PU.1 were fused in frame with ligand binding domain of estrogen receptor (C/EBP α -ER and PU.1-ER) so that they can be activated by 4-hydroxy tamoxifen (4-HT). We subcloned. C/EBP α -ER and PU.1-ER into retrovirus vector, pMX-IRES-GFP and infected virus to BaF3 cells. Interestingly, 4-HT treatment of BaF3/CEBP α -ER, BaF3/PU.1l-ER cells induced growth arrest and apoptosis, indicating that C/EBP α -ER and PU.1-ER are working properly. Next we subcloned Cl EBP α -ER and PU.1-ER in H-2K promoter vector made transgenic mice. We obtained transgene integration in 8 lines for C/ EBP a -ER and 5 lines for PU.1-ER. RT-PCR analysis showed that mRNA is expressed in 5 out of 8 C/EBP α -ER transgenics and only one line expressed C/EBP α -ER protein by western blot. C/EBP α -ER was expressed highly in thymus and spleen, moderately in bone marrow and peripheral blood. Gel-shift assay showed that C/ EBP α -ER protein bound to conserved C/EBP binding sequence in response to 4-HT. With these mice in our hand, we are now planning to investigate how ectopically induced C/ EBP α activity affects differentiation of hematopoietic cells at various developmental stages.

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  • STAT3,C/EBPεによる好中球分化の分子制御機構の解析

    Grant number：12770569  2000 - 2001

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    中島 秀明

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    Grant amount：\1900000 （ Direct Cost: \1900000 ）

    前年度に引き続き、C/EBPεとエストロゲンレセプターのリガンド結合ドメインの融合分子(C/EBPε-ER)を用いてC/EBPεによる好中球分化誘導機構をさらに詳細に検討した。昨年我々は、IL-3依存性マウス骨髄細胞株LGにC/EBPε-ERを導入しその活性を4-hydroxy tamoxifen(4-HT)で誘導すると、細胞増殖の抑制と好中球分化が引き起こされることを報告したが、本年度はC/EBPεの様々な変異体を作製しC/EBPε-ERによる分化誘導効果の詳細な分子メカニズムを検討した。C/EBPεのN末を様々な長さで欠損させた6つの欠失変異体および中央部分の転写抑制領域を欠失させた2種類の変異体を作製し、ERと融合させてLG細胞に導入した。4-HTでこれら細胞株を刺激し細胞増殖・アポトーシス・形態学的分化誘導に与える影響を検討したところ、N末を欠損した変異体はすべて細胞増殖抑制能・アポトーシス/分化誘導能を欠いていることが明らかになった。また中央部の転写抑制領域を欠失させた変異体では、野生型同様に細胞増殖抑制・アポトーシス/分化誘導効果が見られたことから、C/EBPεの細胞増殖抑制・分化誘導作用にはN末部分が重要であり転写抑制領域は関与していないことが示唆された。

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  • 血液幹細胞および白血病細胞の分化増殖におけるレチノイン酸レセプターの役割

    Grant number：06770853  1994

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    中島 秀明

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    Grant amount：\900000 （ Direct Cost: \900000 ）

    本年度は、アンチセンスDNAを導入する予備実験として、RARα,RXRα,PML遺伝子に対するアンチセンスオリゴDNAを用いた転写阻害実験を行った。RARα,RXRα,PML各遺伝子の読みとり開始配列を含むアンチセンスオリゴDNA(AS-DNA)を、DNA合成機を用いて合成した。正常人骨髄単核球からAIS Microcellecterを用いてCD34陽性細胞を分離し、AS-DNA-20μM存在下で8時間培養した。これをメチルセルロース半固形培地にまき、G-CSF,IL-3,erythropoietin,存在下でのコロニー形成を検討した。RXRα,PML遺伝子に対するAS-DNAはコロニー形成に影響を与えなかったが、RARα遺伝子に対するAS-DNAはコロニー形成を著明に抑制した。コントロールとしてRARα遺伝子に対するセンスオリゴDNAを用いて同様の実験を行ったが、コロニー形成は抑制されなかった。現在、実験の追試を行うとともに、AS-DNAの濃度を変化させることによりコロニー形成の抑制が濃度依存的であるか否かを確認する予定である。
    RARα遺伝子の個体発生における役割については、2つのグループがRARα gene targeting mouseを作成し、解析している。これらのマウスでは個体発生はほぼ正常であり、造血系にも異常は見られなかった。このことは、RARα遺伝子は必ずしも個体発生や生体機能の維持に必須ではなく、他のRAR遺伝子(RARβ,RARγ)がその機能を代償しうる可能性を示している。上記の結果はこれらの事実と相反しているが、上記の実験で用いたAS-DNAの塩基配列がRARα特異的ではなく、造血に必須な未知の遺伝子の発現を抑制している可能性もあり、追試の結果が待たれる。

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