2022/10/26 更新

写真a

カネマツ タケシ
兼松 毅
KANEMATSU Takeshi
所属
医学部附属病院 検査部 病院助教
職名
病院助教

学位 2

  1. 博士(医学) ( 2022年3月   名古屋大学 ) 

  2. 学士(医学) ( 2006年3月   名古屋大学 ) 

研究分野 3

  1. その他 / その他  / 血栓・止血学

  2. ライフサイエンス / 血液、腫瘍内科学

  3. ライフサイエンス / 血液、腫瘍内科学

経歴 1

  1. 名古屋大学   医学部附属病院 検査部   病院助教

    2018年4月 - 現在

学歴 1

  1. 名古屋大学   医学部   医学科

    2000年4月 - 2006年3月

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    国名: 日本国

所属学協会 7

  1. 日本検査血液学会

  2. 日本輸血・細胞治療学会

  3. 日本臨床腫瘍学会

  4. 国際血栓止血学会

  5. 日本血栓止血学会

  6. 日本血液学会

  7. 日本内科学会

▼全件表示

 

論文 34

  1. VWF-Gly2752Ser, a novel non-cysteine substitution variant in the CK domain, exhibits severe secretory impairment by hampering C-terminal dimer formation 査読有り 国際誌

    Okamoto Shuichi, Tamura Shogo, Sanda Naomi, Odaira Koya, Hayakawa Yuri, Mukaide Masato, Suzuki Atsuo, Kanematsu Takeshi, Hayakawa Fumihiko, Katsumi Akira, Kiyoi Hitoshi, Kojima Tetsuhito, Matsushita Tadashi, Suzuki Nobuaki

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS   20 巻 ( 8 ) 頁: 1784 - 1796   2022年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Thrombosis and Haemostasis  

    Background: Von Willebrand factor (VWF) is a multimeric glycoprotein that plays important roles in hemostasis and thrombosis. C-terminal interchain-disulfide bonds in the cystine knot (CK) domain are essential for VWF dimerization. Previous studies have reported that missense variants of cysteine in the CK domain disrupt the intrachain-disulfide bond and cause type 3 von Willebrand disease (VWD). However, type 3 VWD-associated noncysteine substitution variants in the CK domain have not been reported. Objective: To investigate the molecular mechanism of a novel non-cysteine variant in the CK domain, VWF c.8254 G>A (p.Gly2752Ser), which was identified in a patient with type 3 VWD as homozygous. Methods: Genetic analysis was performed by whole exome sequencing and Sanger sequencing. VWF multimer analysis was performed using SDS-agarose electrophoresis. VWF production and subcellular localization were analyzed using ex vivo endothelial colony forming cells (ECFCs) and an in vitro recombinant VWF (rVWF) expression system. Results: The patient was homozygous for VWF-Gly2752Ser. Plasma VWF enzyme-linked immunosorbent assay showed that the VWF antigen level of the patient was 1.2% compared with healthy subjects. A tiny amount of VWF was identified in the patient's ECFC. Multimer analysis revealed that the circulating VWF-Gly2752Ser presented only low molecular weight multimers. Subcellular localization analysis of VWF-Gly2752Ser-transfected cell lines showed that rVWF-Gly2752Ser was severely impaired in its ER-to-Golgi trafficking. Conclusion: VWF-Gly2752Ser causes severe secretory impairment because of its dimerization failure. This is the first report of a VWF variant with a noncysteine substitution in the CK domain that causes type 3 VWD.

    DOI: 10.1111/jth.15746

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  2. 血液凝固第IX因子濃縮製剤へのアレルギーに対する減感作療法の有効性 査読有り 国際誌

    鈴木 伸明, 兼松 毅, 岸本 磨由子, 鈴木 奈瑠子, 岡本 修一, 田村 彰吾, 清井 仁, 松下 正

    日本輸血細胞治療学会誌   68 巻 ( 3 ) 頁: 422 - 427   2022年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:一般社団法人 日本輸血・細胞治療学会  

    <p>血液凝固第IX因子(FIX)濃縮製剤に対する重度なアレルギーに対し,減感作療法が有効であった血友病B 2例を報告する.【症例1】9カ月男児.重症.遺伝子組換え血液凝固第IX因子(rFIX)製剤の定期補充開始後,10回投与目にアナフィラキシーを発症.【症例2】55歳男性.中等症.出血症状に対して,通算4回目の血漿由来血液凝固第IX因子濃縮製剤を投与したところ,アナフィラキシーを発症.以上の2症例に対し,rFIXによる減感作療法を実施した.【結果】2症例とも減感作療法により,FIXに対するアレルギーが消失した.減感作療法中はアレルギー反応を始めとする有害事象を認めなかった.【考察】症例2は中等症であり,アレルギーの発症リスクが低い症例であったが,アナフィラキシーを発症し,中等症でも注意が必要であると考えられた.2症例共にアナフィラキシー発症前後に感度以下の弱力価インヒビターの存在が疑われたことから,インヒビターの発症に注意することはアナフィラキシーの発症予測につながる可能性が示唆された.減感作療法の治療プロトコールについては最適化されておらず,更なる検討が必要であると考えられた.</p>

    DOI: 10.3925/jjtc.68.422

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  3. F9mRNA splicing aberration due to a deep Intronic structural variation in a patient with moderate hemophilia B 査読有り 国際誌

    Odaira Koya, Kawashima Fumika, Tamura Shogo, Suzuki Nobuaki, Tokoro Mahiru, Hayakawa Yuri, Suzuki Atsuo, Kanematsu Takeshi, Okamoto Shuichi, Takagi Akira, Katsumi Akira, Matsushita Tadashi, Shima Midori, Nogami Keiji, Kojima Tetsuhito, Hayakawa Fumihiko

    THROMBOSIS RESEARCH   213 巻   頁: 91 - 96   2022年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Thrombosis Research  

    Introduction: Hemophilia B (HB) is a hereditary bleeding disorder caused by the genetic variation of the coagulation factor IX (FIX) gene (F9). Several F9 structural abnormalities, including large deletion and/or insertion, have been observed to cause HB development. However, there is limited information available on F9 deep intronic variations. In this study, we report about a novel large deletion/insertion observed in a deep region of F9 intron 1 that causes mRNA splicing abnormalities. Patient and methods: The patient was a Japanese male diagnosed with moderate HB (FIX:C = 3.0 IU/dL). The genomic DNA of the patient was isolated from peripheral blood leukocytes. DNA sequences of F9 exons and splice donor/acceptor sites were analyzed via polymerase chain reaction and Sanger sequencing. Variant-affected F9 mRNA aberration and FIX protein production, secretion, and coagulant activity were analyzed by cell-based exon trap and splicing-competent FIX expression vector systems. Results: A 28-bp deletion/476-bp insertion was identified in the F9 intron 1 of a patient with moderate HB. A DNA sequence identical to a part of the inverted HNRNPA1 exon 12 was inserted. Cell-based transcript analysis revealed that this large intronic deletion/insertion disrupted F9 mRNA splicing pattern, resulting in reduction of protein-coding F9 mRNA. Conclusion: A novel deep intronic F9 rearrangement was identified in a Japanese patient with moderate HB. Abnormal F9 mRNA splicing pattern due to this deep intronic structural variation resulted in a reduction of protein-coding F9 mRNA, which probably caused the moderate HB phenotype.

    DOI: 10.1016/j.thromres.2022.03.010

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  4. Periosteum-derived podoplanin-expressing stromal cells regulate nascent vascularization during epiphyseal marrow development 査読有り 国際誌

    Tamura Shogo, Mukaide Masato, Katsuragi Yumi, Fujii Wataru, Odaira Koya, Suzuki Nobuaki, Tsukiji Nagaharu, Okamoto Shuichi, Suzuki Atsuo, Kanematsu Takeshi, Katsumi Akira, Takagi Akira, Ikeda Katsuhide, Ueyama Jun, Hirayama Masaaki, Suzuki-Inoue Katsue, Matsushita Tadashi, Kojima Tetsuhito, Hayakawa Fumihiko

    JOURNAL OF BIOLOGICAL CHEMISTRY   298 巻 ( 5 ) 頁: 101833   2022年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Biological Chemistry  

    Bone marrow development and endochondral bone formation occur simultaneously. During endochondral ossification, periosteal vasculatures and stromal progenitors invade the primary avascular cartilaginous anlage, which induces primitive marrow development. We previously determined that bone marrow podoplanin (PDPN)-expressing stromal cells exist in the perivascular microenvironment and promote megakaryopoiesis and erythropoiesis. In this study, we aimed to examine the involvement of PDPN-expressing stromal cells in postnatal bone marrow generation. Using histological analysis, we observed that periosteum-derived PDPN-expressing stromal cells infiltrated the cartilaginous anlage of the postnatal epiphysis and populated on the primitive vasculature of secondary ossification center. Furthermore, immunophenotyping and cellular characteristic analyses indicated that the PDPN-expressing stromal cells constituted a subpopulation of the skeletal stem cell lineage. In vitro xenovascular model cocultured with human umbilical vein endothelial cells and PDPN-expressing skeletal stem cell progenies showed that PDPN-expressing stromal cells maintained vascular integrity via the release of angiogenic factors and vascular basement membrane-related extracellular matrices. We show that in this process, Notch signal activation committed the PDPN-expressing stromal cells into a dominant state with basement membrane-related extracellular matrices, especially type IV collagens. Our findings suggest that the PDPN-expressing stromal cells regulate the integrity of the primitive vasculatures in the epiphyseal nascent marrow. To the best of our knowledge, this is the first study to comprehensively examine how PDPN-expressing stromal cells contribute to marrow development and homeostasis.

    DOI: 10.1016/j.jbc.2022.101833

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  5. Protein S-Leu17Pro disrupts the hydrophobicity of its signal peptide causing a proteasome-dependent degradation 査読有り 国際誌

    Okada Kentaro, Tamura Shogo, Suzuki Nobuaki, Odaira Koya, Mukaide Masato, Fujii Wataru, Katsuragi Yumi, Suzuki Atsuo, Kanematsu Takeshi, Okamoto Shuichi, Suzuki Naruko, Katsumi Akira, Matsushita Tadashi, Kojima Tetsuhito, Hayakawa Fumihiko

    THROMBOSIS RESEARCH   210 巻   頁: 26 - 32   2022年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Thrombosis Research  

    Introduction: Protein S is a vitamin K-dependent glycoprotein with important anticoagulant, fibrinolytic, anti-inflammatory, anti-apoptotic, and cytoprotective functions. Congenital protein S deficiency is an autosomal dominant thrombophilia due to protein S gene (PROS1) variations. Our group identified a variation in PROS1 that translates into protein S deficiency: c.50 T > C (p.Leu17Pro). Here, we investigated the mechanisms by which this variation results in protein S deficiency. Materials and methods: The effect of L17P substitution on protein S signal peptide was predicted by in silico (a computational prediction technique) analysis of hydrophobicity and signal peptide cleavage. Recombinant protein S was overexpressed in HEK293 and COS-7 cells. Intracellular kinetics and extracellular secretion of recombinant protein S-L17P were analyzed by western blotting and immunocytochemistry. Results: In silico hydrophobicity analysis showed that protein S-L17P had disrupted hydrophobic status in the h-region of its signal peptide. Under normal culture conditions, recombinant protein S -L17P was not detected in either transfectant cell lysates or medium. Upon treatment with a proteasome inhibitor, recombinant protein S-L17P was clearly detected in the cell lysate, but not in the culture medium. Recombinant protein S-L17P did not undergo post-translational modification with N-glycosylation, suggesting that the nascent polypeptide of recombinant protein S-L17P is not transported to the endoplasmic reticulum lumen, but is mislocalized to the cytosol. Conclusion: PROS1-L17P variation translates into protein S deficiency. Protein S-L17P causes its cytosolic mislocalization resulting in its proteasome-dependent degradation.

    DOI: 10.1016/j.thromres.2021.12.014

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  6. Development and validation of a novel qualitative test for plasma fibrinogen utilizing clot waveform analysis 査読有り 国際誌

    Suzuki Atsuo, Suzuki Nobuaki, Kanematsu Takeshi, Shinohara Sho, Kurono Hiroshi, Arai Nobuo, Okamoto Shuichi, Suzuki Naruko, Tamura Shogo, Kikuchi Ryosuke, Katsumi Akira, Kojima Tetsuhito, Matsushita Tadashi

    SCIENTIFIC REPORTS   12 巻 ( 1 ) 頁: 434   2022年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    Plasma fibrinogen is commonly examined by Clauss fibrinogen assay, which cannot distinguish between quantitative and qualitative fibrinogen anomalies. However, our previously reported Clauss fibrinogen assay utilizing clot waveform analysis (Clauss-CWA) provides additional information that contributes to the classification of fibrinogen anomalies. In this study, we adopted the Clauss-CWA method for an autoanalyzer to automatically measure the antigenic estimate (eAg) of fibrinogen in addition to the functional amount (Ac), and to thus provide the Ac/eAg ratio as a qualitative indicator. Performance was validated by receiver operating characteristics (ROC) and precision recall (PR) curve analyses using a patient cohort, consisting of a training cohort (n = 519) and a validation cohort (n = 523), both of which contained cases of congenital (hypo)dysfibrinogenemia as qualitative defects. We obtained an optimal cutoff of 0.65 for Ac/eAg by ROC curve analysis of the training cohort, offering superior sensitivity (> 0.9661) and specificity (1.000). This cutoff was validated in the validation cohort, providing positive predictive value > 0.933 and negative predictive value > 0.998. PR curve analysis also showed that Clauss-CWA provided excellent performance for detecting qualitative fibrinogen anomalies. The Clauss-CWA method may represent a useful approach for detecting qualitative fibrinogen abnormalities in routine laboratory testing.

    DOI: 10.1038/s41598-021-04464-5

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  7. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia HCC after HCV eradication in hemophilia 査読有り 国際誌

    Inukai Yosuke, Imai Norihiro, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Honda Takashi, Okamoto Shuichi, Kanematsu Takeshi, Suzuki Nobuaki, Matsushita Tadashi, Ishigami Masatoshi, Fujishiro Mitsuhiro

    ANNALS OF HEPATOLOGY   27 巻 ( 1 ) 頁: 100545   2022年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Annals of Hepatology  

    Introduction and objectives: Hepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. Patients and methods: The study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. Results: Compared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years. Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. Conclusion: Hemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.

    DOI: 10.1016/j.aohep.2021.100545

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  8. Tolerability of Molecular-targeted Agents for Hepatocellular Carcinoma Treatment in Haemophiliacs 査読有り 国際誌

    Yamamoto Takafumi, Imai Norihiro, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Honda Takashi, Okamoto Shuichi, Kanematsu Takeshi, Suzuki Nobuaki, Matsushita Tadashi, Ishigami Masatoshi, Fujishiro Mitsuhiro

    ANTICANCER RESEARCH   41 巻 ( 5 ) 頁: 2569 - 2573   2021年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Anticancer Research  

    Background: Hepatocellular carcinoma (HCC) is considered a leading cause of death in patients with haemophilia. Recent advances in the treatment of unresectable HCC with molecular-Targeted agents (MTAs) have led to better clinical outcomes. However, the tolerability of MTAs by haemophilic patients with HCC remains unclear. Aim: This study aimed to compare the tolerability of MTAs in such patients. Patients and Methods: From January 2011 to October 2020, five haemophilic patients with HCC were treated with MTAs. Adverse events were assessed in comparison with 265 non-haemophilic patients with HCC. Results: The prevalence of hand foot skin reaction was not higher in the haemophiliacs than in the non-haemophiliacs, whereas the rate of haemorrhagic events was higher in the haemophiliacs (6.0% versus 40.0%, p=0.037). Conclusion: Haemophiliacs tolerate long-Term MTA use, without the occurrence of life-Threatening complications. However, careful observation and prevention are needed for MTA-related gastrointestinal bleeding in haemophiliacs.

    DOI: 10.21873/anticanres.15035

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  9. Essential role of a carboxyl-terminal alpha-helix motif in the secretion of coagulation factor XI 査読有り 国際誌

    Hayakawa Yuri, Tamura Shogo, Suzuki Nobuaki, Odaira Koya, Tokoro Mahiru, Kawashima Fumika, Hayakawa Fumihiko, Takagi Akira, Katsumi Akira, Suzuki Atsuo, Okamoto Shuichi, Kanematsu Takeshi, Matsushita Tadashi, Kojima Tetsuhito

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS   19 巻 ( 4 ) 頁: 920 - 930   2021年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Thrombosis and Haemostasis  

    Background: Coagulation factor XI (FXI) is a plasma serine protease zymogen that contributes to hemostasis. However, the mechanism of its secretion remains unclear. Objective: To determine the molecular mechanism of FXI secretion by characterizing a novel FXI mutant identified in a FXI-deficient Japanese patient. Patient/Methods: The FXI gene (F11) was analyzed by direct sequencing. Mutant recombinant FXI (rFXI) was overexpressed in HEK293 or COS-7 cells. Western blotting and enzyme-linked immunosorbent assay were performed to examine the FXI extracellular secretion profile. Immunofluorescence microscopy was used to investigate the subcellular localization of the rFXI mutant. Results: We identified a novel homozygous frameshift mutation in F11 [c.1788dupC (p.E597Rfs*65)], resulting in a unique and extended carboxyl-terminal (C-terminal) structure in FXI. Although rFXI-E597Rfs*65 was intracellularly synthesized, its extracellular secretion was markedly reduced. Subcellular localization analysis revealed that rFXI-E597Rfs*65 was abnormally retained in the endoplasmic reticulum (ER). We generated a series of C-terminal–truncated rFXI mutants to further investigate the role of the C-terminal region in FXI secretion. Serial rFXI experiments revealed that a threonine at position 622, the fourth residue from the C-terminus, was essential for secretion. Notably, Thr622 engages in the formation of an α-helix motif, indicating the importance of the C-terminal α-helix in FXI intracellular behavior and secretion. Conclusion: FXI E597Rfs*65 results in the pathogenesis of a severe secretory defect resulting from aberrant ER-to-Golgi trafficking caused by the lack of a C-terminal α-helix motif. This study demonstrates the impact of the C-terminal structure, especially the α-helix motif, on FXI secretion.

    DOI: 10.1111/jth.15242

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  10. Impact of variation in reagent combinations for one-stage clotting assay on assay discrepancy in nonsevere haemophilia A 査読有り 国際誌

    Suzuki Atsuo, Suzuki Nobuaki, Kanematsu Takeshi, Okamoto Shuichi, Tamura Shogo, Kikuchi Ryosuke, Katsumi Akira, Kiyoi Hitoshi, Kojima Tetsuhito, Matsushita Tadashi

    INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY   43 巻 ( 1 ) 頁: 131 - 138   2021年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Laboratory Hematology  

    Introduction: Factor VIII activity (FVIII:C) is measured by one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). Significant differences in FVIII:C between OSA (FVIII:C1st) and CSA (FVIII:CChr) are described as assay discrepancy in nonsevere haemophilia A (HA). A large number of reagent combinations (APTT reagent and FVIII-deficient plasma) are used for OSA, but the impact of variations in reagent combinations on assay discrepancy has not been fully characterized. Aim: To clarify the variations in FVIII:C1st/FVIII:CChr ratios according to OSA reagent combination in HA subjects with/without assay discrepancy. Methods: Thirty-nine patients previously diagnosed with nonsevere HA were enrolled, and their FVIII genes were investigated and FVIII:C levels were assessed by a single CSA reagent and 11 OSA reagent combinations. Receiver operating characteristic (ROC) curve analysis was used to predict possible cut-off values of the FVIII:C1st/FVIII:CChr ratio to define FVIII assay discrepancy for each reagent combination. Results: Patients were categorized into nondiscrepant (n = 25), discrepant (n = 5) and unclassified (n = 9) groups according to their genotypes and information in the database. The FVIII:C1st/FVIII:CChr ratio in nondiscrepant HA varied widely, depending on the APTT reagents and FVIII-deficient plasma used. The ratio in discrepant HA patients differed with respect to their genotype and the reagent combination used. ROC curve analyses revealed that cut-off values to distinguish the assay discrepancy differed depending on the reagents used, but revealed two novel genotype variants, p.Cys573Gly and p.Gly582Arg, associated with FVIII assay discrepancy. Conclusion: Our findings showed that the FVIII:C1st/FVIII:CChr ratio is dependent on the reagent combination used for OSA.

    DOI: 10.1111/ijlh.13335

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  11. Myh9 R702C is associated with erythroid abnormality with splenomegaly in mice 査読有り 国際誌

    Kanematsu Takeshi, Suzuki Nobuaki, Tamura Shogo, Suzuki Atsuo, Ishikawa Yuichi, Katsumi Akira, Kiyoi Hitoshi, Saito Hidehiko, Kunishima Shinji, Kojima Tetsuhito, Matsushita Tadashi

    NAGOYA JOURNAL OF MEDICAL SCIENCE   83 巻 ( 1 ) 頁: 75 - 86   2021年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nagoya Journal of Medical Science  

    MYH9 disorders are characterized by giant platelets, thrombocytopenia, and Döhle body-like cytoplasmic inclusion bodies in granulocytes. However, whether these disorders cause any changes in erythroid cells has yet to be determined. This study analyzed the influence of Myh9 R702C, as one of the most commonly detected MYH9 disorders, on erythroid cells in a mouse model. Knock-in mice expressing Myh9 R702C mutation either systemically or specific to hematological cells (R702C and R702C vav1 mice, respectively) were used in this study. Both displayed lower hemoglobin and higher erythropoietin levels than wild-type (WT) mice, along with significant splenomegaly. Flow cytometric analysis revealed erythroblasts present at a higher rate than WT mice in the spleen. However, no obvious abnormalities were seen in erythroid differentiation from megakaryocyte/erythroid progenitor to erythrocyte. Cell culture assay by fetal liver and colony assay also showed normal progression of erythroid differentiation from erythroid burst-forming unit to red blood cell. In conclusion, R702C and R702C vav1 mice displayed erythroid abnormality with splenomegaly. However, erythroid differentiation showed no obvious abnormality. Further research is required to elucidate the underlying mechanisms.

    DOI: 10.18999/nagjms.83.1.75

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  12. Safety and efficacy of percutaneous radiofrequency ablation for hepatocellular carcinoma patients with haemophilia 査読有り 国際誌

    Yamamoto Takafumi, Imai Norihiro, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Honda Takashi, Okamoto Shuichi, Kanematsu Takeshi, Suzuki Nobuaki, Matsushita Tadashi, Ishigami Masatoshi, Fujishiro Mitsuhiro

    HAEMOPHILIA   27 巻 ( 1 ) 頁: 100 - 107   2021年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Haemophilia  

    Haemophilia is an X-linked inherited bleeding disorder caused by coagulation factor deficiency. Hepatocellular carcinoma (HCC) is a major complication associated with the disease. No study thus far has investigated the safety and efficacy of percutaneous radiofrequency ablation (RFA) for HCC in patients with haemophilia. Aim: This study aimed to evaluate the safety and efficacy of RFA for HCC in haemophilia patients. Methods: From July 2008 to June 2019, 217 patients with HCC underwent 300 RFA sessions. Of these, 18 sessions were performed in ten haemophilia patients (H group) and 282 in 207 non-haemophilia patients (NH group). The patients' characteristics, incidence of haemorrhagic complications and rates of local tumour recurrence were compared between the groups. Results: A majority of the haemophilia patients received clotting factor concentrate replacement therapy before and after RFA treatment, with the aim of reaching a plasma clotting factor level of higher than 60%–80%. Twelve haemorrhagic complications were observed in the NH group (4.2%; 12/282). Major bleeding requiring control procedures was observed in two patients and minor bleeding with careful observation was noted in ten patients. No bleeding complications were observed in the H group (0/18). There were no significant differences in the 5-year local tumour recurrence rates after RFA treatment between the groups (35.0% in the H group and 32.1% in the NH group). Conclusion: RFA could be an effective and a safe method for HCC treatment in patients with haemophilia.

    DOI: 10.1111/hae.14220

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  13. Bursitis, Bacteremia, and Disseminated Infection of Mycobacteroides (Mycobacterium) abscessus subsp. massiliense 国際誌

    Oka Keisuke, Morioka Hiroshi, Eguchi Motoki, Sato Yoshitaka, Tetsuka Nobuyuki, Iguchi Mitsutaka, Kanematsu Takeshi, Fukano Hanako, Hoshino Yoshihiko, Kiyoi Hitoshi, Yagi Tetsuya

    INTERNAL MEDICINE   60 巻 ( 18 ) 頁: 3041 - 3045   2021年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Internal Medicine  

    We herein report a 59-year-old woman with a 2-year history of chronic bursitis of the hand who took 50 mg/day prednisolone for several autoimmune diseases. Mycobacteroides abscessus subsp. massiliense was isolated from the abscess and blood culture. Combination therapy (imipenem/cilastatin, amikacin, and clarithromycin) was administered for a month. Two months later, M. massiliense was detected from a blood culture again, and disseminated lesions were found. Clarithromycin and sitafloxacin were administered following eight weeks of the same regimen. Six months after the diagnosis, M. massiliense was isolated from a blood culture, and she expired due to multiple organ failure.

    DOI: 10.2169/internalmedicine.6189-20

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  14. Aberrant X chromosomal rearrangement through multi-step template switching during sister chromatid formation in a patient with severe hemophilia A 査読有り 国際誌

    Tokoro Mahiru, Tamura Shogo, Suzuki Nobuaki, Kakihara Misaki, Hattori Yuna, Odaira Koya, Suzuki Sachiko, Takagi Akira, Katsumi Akira, Hayakawa Fumihiko, Okamoto Shuichi, Suzuki Atsuo, Kanematsu Takeshi, Matsushita Tadashi, Kojima Tetsuhito

    MOLECULAR GENETICS & GENOMIC MEDICINE   8 巻 ( 9 ) 頁: e1390   2020年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Molecular Genetics and Genomic Medicine  

    Background: Hemophilia A (HA) is an X-linked recessive bleeding disorder caused by pathogenic variants of the coagulation factor VIII gene (F8). Half of the patients with severe HA have a recurrent inversion in the X chromosome, that is, F8 intron 22 or intron 1 inversion. Here, we characterized an abnormal F8 due to atypical complex X chromosome rearrangements in a Japanese patient with severe HA. Methods: Recurrent F8 inversions were tested with inverse shifting-PCR. The genomic structure was investigated using PCR-based direct sequencing or quantitative PCR. Results: The proband's X chromosome had a 119.5 kb insertion, a reverse duplex of an extragenic sequence on the F8 telomere region into the F8 intron 1 with two breakpoints. The telomeric breakpoint was a joining from the F8 intron 1 to the inverted FUNDC2 via a two-base microhomology, and the centromeric breakpoint was a recombination between F8 intron 1 homologous sequences. The rearrangement mechanism was suggested as a multi-step rearrangement with template switching such as fork stalling and template switching (FoSTeS)/microhomology-mediated break-induced replication (MMBIR) and/or homologous sequence-associated recombination during a sister chromatid formation. Conclusion: We identified the aberrant X chromosome with a split F8 due to a multi-step rearrangement in a patient with severe HA.

    DOI: 10.1002/mgg3.1390

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  15. Higher FVIII:C measured by chromogenic substrate assay than by one-stage assay is associated with silent hemophilic arthropathy 査読有り 国際誌

    Ogawa Mika, Suzuki Nobuaki, Takahashi Nobunori, Tamura Shogo, Suzuki Atsuo, Suzuki Sachiko, Hattori Yuua, Kakihara Misaki, Kanematsu Takeshi, Kojima Toshihisa, Katsumi Akira, Hayakawa Fumihiko, Kojima Tetsuhito, Ishiguro Naoki, Kiyoi Hitoshi, Matsushita Tadashi

    THROMBOSIS RESEARCH   188 巻   頁: 103 - 105   2020年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Thrombosis Research  

    DOI: 10.1016/j.thromres.2020.01.003

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  16. [Lupus anticoagulant-hypoprothrombinemia syndrome associated with follicular lymphoma]. 査読有り 国際誌

    Koyama D, Hanajiri R, Kanematsu T, Ito R, Yamamoto S, Imoto N, Suzuki N, Kurahashi S, Sugiura I

    [Rinsho ketsueki] The Japanese journal of clinical hematology   61 巻 ( 7 ) 頁: 745 - 749   2020年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:一般社団法人 日本血液学会  

    <p>56歳女性。繰り返す四肢の腫脹,疼痛,紫斑を主訴に受診した。PTとAPTTの延長を認め,クロスミキシング試験で凝固阻害因子の存在が疑われた。ループスアンチコアグラント(LA)陽性かつプロトロンビン活性著減を認め,ループスアンチコアグラント低プロトロンビン血症症候群(LAHPS)と診断した。基礎疾患の検索にて胸骨背面の腫瘤を認め生検を予定したが,新鮮凍結血漿の投与で凝固異常を補正できず断念した。Prednisolone(PSL)1 mg/kgの投与により凝固異常は正常化し,LAと腫瘤も消失した。LAHPSの再発なくPSLを漸減したが,経過観察のCTで多発リンパ節腫大を認め,生検により濾胞性リンパ腫と診断した。LAHPSが再発する可能性を考慮しbendamustine+rituximab療法を6サイクル行った。濾胞性リンパ腫は完全寛解となりLAHPSの再発も認めない。LAHPSはLA陽性だが出血傾向を来しうる稀な後天性凝固異常である。診断時はリンパ性腫瘍を含む基礎疾患の検索を要する。</p>

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  17. 血小板膜糖蛋白質GPIb変異体を用いたvon Willebrand因子活性測定試薬「INNOVANCE<sup>®</sup> VWF Ac」の基本性能評価 国際誌

    鈴木 敦夫, 鈴木 伸明, 兼松 毅, 岡本 修一, 田村 彰吾, 篠原 翔, 新井 信夫, 菊地 良介, 安藤 善孝, 小嶋 哲人, 松下 正

    日本血栓止血学会誌   31 巻 ( 4 ) 頁: 409 - 419   2020年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:一般社団法人 日本血栓止血学会  

    <p>INNOVANCE<sup>®</sup> VWF Acは血小板膜糖蛋白質GPIbの変異体を用いるフォンヴィレブランド因子(von Willebrand factor: VWF)活性(VWF:GPIbM)測定試薬である.本研究では本邦で初めてその基本性能評価を行った.併行精度はCVが3%未満,室内再現性はCVが2%未満と良好な成績であった.希釈直線性も良好であり,最小検出感度は1.3 IU/dLであった.また,干渉物質や未分画ヘパリン混入による明らかな影響は見られなかった.正常検体100例を用いた相関性試験ではVWF抗原量およびVWFリストセチンコファクター活性(VWF:RCo)と良好な相関性を示した.フォンヴィレブランド病患者検体においてもVWF:RCoとの測定値に大きな差はなく,VWF:GPIbMでは特に低濃度域を評価することが可能であった.INNOVANCE<sup>®</sup> VWF AcはVWF:RCo測定試薬と比べても高い性能を有することが明らかとなった.</p>

    DOI: 10.2491/jjsth.31.409

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  18. Performance evaluation of Revohem((TM)) FVIII chromogenic and Revohem((TM)) FIX chromogenic in the CS-5100 autoanalyser 査読有り 国際誌

    Suzuki Atsuo, Suzuki Nobuaki, Kanematsu Takeshi, Shinohara Sho, Arai Nobuo, Kikuchi Ryosuke, Matsushita Tadashi

    INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY   41 巻 ( 5 ) 頁: 664 - 670   2019年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Laboratory Hematology  

    Introduction: Chromogenic substrate assay (CSA) reagents Revohem™ FVIII and Revohem™ FIX are now available as in vitro diagnostic reagents for autoanalysers in Japan. In this study, we evaluated the performance of these reagents in the CS-5100 automated coagulation analyser. Methods: We assessed within-run and between-day imprecision, on-board stability and frozen-storage stability of Revohem FVIII and FIX. Sensitivity to lupus anticoagulant (LA) was examined using LA-positive patient plasma. Correlations were analysed using plasma samples from normal individuals and patients with haemophilia A (HA) or B (HB) or von Willebrand disease (VWD). Results: Imprecision was <2% for Revohem FVIII and <6.5% for Revohem FIX. On-board storage of Revohem FVIII resulted in a <10% decrease in FVIII levels from baseline at 24 hours, whereas Revohem FIX showed a >10% decrease at 8 hours. Revohem FVIII showed good stability while frozen for 22 days. Although Revohem FIX showed degradation due to freeze-thawing, a new calibration improved stability up to 22 days. Interference from LA was not observed with Revohem FVIII or FIX. The FVIII CSA-CSA correlation was excellent in normal (r = 0.9924), HA (r = 0.9945) and VWD (r = 0.9914). The FVIII CSA-OSA correlation was good in normal (r = 0.8468) and excellent in HA (r = 0.975) and VWD (r = 0.9936). The FIX CSA-OSA correlation was fair in normal (r = 0.4791) and excellent in HB (r = 0.9501). Conclusion: Revohem FVIII and FIX both showed excellent performance in the CS-5100 analyser. These reagents could be useful in routine laboratory testing for diagnosing and treating haemophilia.

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  19. Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors. 査読有り 国際誌

    Okamoto S, Suzuki N, Suzuki A, Suzuki S, Tamura S, Suzuki M, Takahashi N, Kojima T, Kanematsu T, Kojima T, Kiyoi H, Ishiguro N, Matsushita T

    TH open : companion journal to thrombosis and haemostasis   3 巻 ( 4 ) 頁: e364 - e366   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1055/s-0039-3401001

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  20. Apparent synonymous mutation F9 c.87A > G causes secretion failure by in-frame mutation with aberrant splicing 査読有り 国際誌

    Odaira Koya, Tamura Shogo, Suzuki Nobuaki, Kakihara Misaki, Hattori Yuna, Tokoro Mahiru, Suzuki Sachiko, Takagi Akira, Katsumi Akira, Hayakawa Fumihiko, Okamoto Shuichi, Suzuki Atsuo, Kanematsu Takeshi, Matsushita Tadashi, Kojima Tetsuhito

    THROMBOSIS RESEARCH   179 巻   頁: 95 - 103   2019年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Thrombosis Research  

    Introduction: Hemophilia B is an X-linked recessive bleeding disorder caused by coagulation factor IX (FIX) gene (F9) mutations. Several F9 synonymous mutations have been known to cause hemophilia B; however, the deleterious mechanisms underlying the development of hemophilia B have not been completely understood. To elucidate the molecular pathogenesis causing hemophilia B, we investigated the synonymous F9 mutation: c.87A>G, p.(Thr29=). Materials and methods: The influence of F9 c.87A>G on mRNA splicing was analyzed by exon-trap assay and in silico prediction. We prepared FIX expression vectors using mutant F9 cDNA and transfected HepG2 cells to investigate intracellular transport and extracellular secretion of FIX. Intracellular kinetics of the expressed FIX was examined by treatment with the proteasome inhibitor MG132. Results: Exon-trap analysis revealed that F9 c.87A>G resulted in almost (99.1%) aberrant splicing (r.83_88del). In silico analysis predicted that F9 c.87A>G influenced the splicing pattern by generating an available aberrant 5′ splice site. The aberrant F9 mRNA (r.83_88del) was translated to a mutant FIX p.Cys28_Val30delinsPhe with an in-frame mutation at the signal peptide cleavage site. Simultaneously, a small amount (0.9%) of mutant F9 r.87A>G translating into WT FIX p.Thr29 = was also observed. The mutant FIX was abnormally retained in the endoplasmic reticulum (ER) and was not extracellularly secreted. It appeared to be intracellularly degraded via proteasome-dependent degradation machinery. Conclusion: F9 c.87A>G was found to cause abnormal mRNA splicing, r.83_88del, and produce the mutant FIX p.Cys28_Val30delinsPhe. The mutant FIX is an abnormal protein with extracellular secretory defects and is intracellularly eliminated via proteasome-dependent ER-associated degradation.

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  21. Ischaemic events are rare, and the prevalence of hypertension is not high in Japanese adults with haemophilia: First multicentre study in Asia 査読有り 国際誌

    Nagao Azusa, Suzuki Nobuaki, Takedani Hideyuki, Yamasaki Naoya, Chikasawa Yushi, Sawada Akihiro, Kanematsu Takeshi, Nojima Masanori, Higasa Satoshi, Amano Kagehiro, Fukutake Katsuyuki, Fujii Teruhisa, Matsushita Tadashi, Suzuki Takashi

    HAEMOPHILIA   25 巻 ( 4 ) 頁: E223 - E230   2019年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Haemophilia  

    Introduction: With the increasing life expectancy of patients with haemophilia (PWH), the number of PWH with age-related comorbidities, such as ischaemic events, is increasing. Aim: We conducted this multicentre observational study to identify the risk factors for major ischaemic events in PWH. Methods: This study was the first multicentre observational study, conducted with the participation of five haemophilia treatment centres in Japan, conducted in ≥30-year-old adult PWH. The latest data recorded in the medical charts between 1 January and 31 December 2016 were reviewed. Healthcare data collected from the National Health and Nutrition Survey were used as the control data. Results: Data of a total of 711 patients were collected. Only two PWH (0.3%) had a history of ischaemic events. Age-adjusted analysis indicated that the prevalence of hypertension defined as a blood pressure of 140/90 mm Hg or over was similar in the PWH to that in the males of the general population. However, when hypertension was defined more strictly (≥130/85 mm Hg), the prevalence was significantly lower in PWH than in the general male population. The hypertension in PWH was associated with the age, BMI, CKD, HIV infection and inhibitors. In particular, the odds ratio for the presence of inhibitors was high (odds ratio = 7.529). Conclusion: Whether the present results can be attributed to Japanese ethnicity or to the presence of haemophilia per se remains uncertain. We propose to initiate a prospective study for further investigation.

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  22. Thalidomide maintenance therapy in Japanese myeloma patients: a multicenter, phase II clinical trial (COMET study) (vol 109, pg 409, 2019) 査読有り 国際誌

    Murakami Hirokazu, Kasamatsu Tetsuhiro, Murakami Jun, Kiguchi Toru, Kanematsu Takeshi, Ogawa Daisuke, Takamatsu Hiroyuki, Handa Hiroshi, Ozaki Shuji, Miki Hirokazu, Takahashi Takeshi, Takeo Takaaki, Yamauchi Tatsuya, Morishita Takanobu, Kosugi Hiroshi, Shimizu Kazuyuki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   110 巻 ( 1 ) 頁: 125 - 126   2019年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Hematology  

    The authors would like to correct the errors in the publication of the original article. The correction details are given below.

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  23. Molecular basis of SERPINC1 mutations in Japanese patients with antithrombin deficiency 査読有り 国際誌

    Tamura Shogo, Hashimoto Erika, Suzuki Nobuaki, Kakihara Misaki, Odaira Koya, Hattori Yuna, Tokoro Mahiru, Suzuki Sachiko, Takagi Akira, Katsumi Akira, Hayakawa Fumihiko, Suzuki Atsuo, Okamoto Shuichi, Kanematsu Takeshi, Matsushita Tadashi, Kojima Tetsuhito

    THROMBOSIS RESEARCH   178 巻   頁: 159 - 170   2019年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Thrombosis Research  

    Background: Congenital antithrombin (AT) deficiency, which arises from various SERPINC1 defects, is an autosomal-dominant thrombophilic disorder associated with a high risk of recurrent venous thromboembolism. Patients/methods: We investigated SERPINC1 defects in Japanese patients with congenital AT deficiency who developed venous thromboembolism or had a family history of deep vein thrombosis. We analyzed the full DNA sequences of SERPINC1 exons and exon-intron junctions by PCR-mediated direct sequencing. If no mutation was found, multiplex ligation-dependent probe amplification (MLPA) was conducted for the relative quantification of the copy number of all exons in SERPINC1. If splice-site mutations were detected, mRNA splicing abnormalities were further investigated using an in vitro cell-based exontrap assay. Results: We identified 19 different SERPINC1 abnormalities, including 8 novel mutations, in 21 Japanese patients with AT deficiency. These abnormalities were distributed as follows: 9 missense mutations (42.9%), 3 nonsense mutations (14.3%), 1 splice-site mutation (4.8%), 2 small insertions (9.5%), 2 deletion mutations (9.5%) and 4 large deletions (19.0%). Cases with large deletions of SERPINC1 included Alu-mediated gene rearrangements and non-Alu-mediated complex gene rearrangements; the latter could conceivably be explained using the fork stalling and template switching (FoSTeS) model. Conclusions: We identified a variety of SERPINC1 defects in Japanese patients with AT deficiency. The SERPINC1 mutations detected in patients with type I AT deficiency included single nucleotide missense or nonsense mutations, small intragenic insertions or deletions, and large genomic structural deletions. Large deletions of SERPINC1 were caused by various recurrent or non-recurrent complex genomic rearrangement mutations.

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  24. The first case of antithrombin-resistant prothrombin Belgrade mutation in Japanese 査読有り 国際誌

    Kishimoto Mayuko, Suzuki Nobuaki, Murata Moe, Ogawa Mika, Kanematsu Takeshi, Takagi Akira, Kiyoi Hitoshi, Kojima Tetsuhito, Matsushita Tadashi

    ANNALS OF HEMATOLOGY   95 巻 ( 3 ) 頁: 541 - 542   2016年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Annals of Hematology  

    DOI: 10.1007/s00277-015-2533-6

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  25. A case of MYH9 disorders caused by a novel mutation (p.K74E) 査読有り 国際誌

    Kanematsu Takeshi, Suzuki Nobuaki, Yoshida Tadao, Kishimoto Mayuko, Aoki Tomohiro, Ogawa Mika, Kagami Yoshitoyo, Kiyoi Hitoshi, Matsushita Tadashi, Kunishima Shinji

    ANNALS OF HEMATOLOGY   95 巻 ( 1 ) 頁: 161 - 163   2016年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Annals of Hematology  

    DOI: 10.1007/s00277-015-2506-9

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  26. 病気のはなし ハイド症候群 査読有り 国際誌

    兼松 毅, 松下 正

    検査と技術   42 巻 ( 11 ) 頁: 1188 - 1192   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.1543104485

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  27. Thalidomide maintenance therapy in Japanese myeloma patients: a multicenter, phase II clinical trial (COMET study)

    Murakami Hirokazu, Kasamatsu Tetsuhiro, Murakami Jun, Kiguchi Toru, Kanematsu Takeshi, Ogawa Daisuke, Takamatsu Hiroyuki, Handa Hiroshi, Ozaki Shuji, Miki Hirokazu, Takahashi Takeshi, Takeo Takaaki, Yamauchi Tatsuya, Morishita Takanobu, Kosugi Hiroshi, Shimizu Kazuyuki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   109 巻 ( 4 ) 頁: 409 - 417   2019年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Hematology  

    A prospective, multicenter, phase II study was performed to assess the efficacy and safety of thalidomide maintenance therapy at different doses in Japanese multiple myeloma (MM) patients. This study included 34 patients (median age, 74 years) who were previously treated with not more than three prior therapies and whose response status was evaluated as at least stable disease. They were randomized into Group A (no maintenance; 12 patients), Group B (50 mg thalidomide maintenance; 12 patients), and Group C (100 mg thalidomide maintenance; 10 patients), respectively. Thalidomide maintenance therapy resulted in improved depth of response in three cases (13.6%) and sustained response after induction therapy in eight cases (36.4%). Two-year progression-free survival (PFS) was 25.0%, 33.3%, and 77.8% in Groups A, B, and C, respectively, and was significantly higher in Group C than in Group A (p = 0.005). There was no difference in the incidence of hematological or non-hematological adverse events between Groups B and C. The current study demonstrates that maintenance with daily thalidomide at 100 mg, but not 50 mg, improved depth of response and prolonged PFS, and that this treatment was feasible for use in Japanese MM patients.

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  28. Clot waveform analysis in Clauss fibrinogen assay contributes to classification of fibrinogen disorders 国際誌

    Suzuki Atsuo, Suzuki Nobuaki, Kanematsu Takeshi, Shinohara Sho, Arai Nobuo, Kikuchi Ryosuke, Matsushita Tadashi

    THROMBOSIS RESEARCH   174 巻   頁: 98 - 103   2019年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Thrombosis Research  

    Background: Clauss fibrinogen assay (CFA) is widely used as a screening test to detect fibrinogen disorders. However, CFA alone cannot distinguish quantitative and qualitative defects because it depends on functional fibrinogen activity (Ac), and fibrinogen antigen (Ag) determination is required to classify fibrinogen disorders. Objectives: To establish a novel approach to classify fibrinogen disorders, we investigated the potential of clot waveform analysis (CWA) of CFA and searched for a surrogate marker for fibrinogen Ag. Materials and methods: We analyzed CWA parameters obtained from CFA using plasma from normal patients (n = 91) and those with fibrinogen disorders (n = 27, including 15 hypofibrinogenemia, 6 dysfibrinogenemia and 6 hypodysfibrinogenemia) with a CS-5100 autoanalyzer. Results: We found that maximum coagulation velocity (Min1) levels were most strongly correlated with fibrinogen Ag in both normal and fibrinogen disorders. Hence, Min1 appeared to function as a surrogate for fibrinogen Ag. Although the Ac/Min1 ratio did not simply reflect the measured Ac/Ag ratio, we found that the Ac/Min1 ratio was significantly higher than normal in hypofibrinogenemia and hypodysfibrinogenemia, but not in dysfibrinogenemia. On the other hand, we could distinguish type II deficiency from type I using estimated fibrinogen Ag (eAg) predicted from Min1. The Ac/eAg ratios of dysfibrinogenemia and hypodysfibrinogenemia were significantly lower than those of normal and hypofibrinogenemia. Conclusion: The CWA of CFA could distinguish fibrinogen disorders using a combination of Ac/Min1 and Ac/eAg values. This analysis allows the qualitative detection of fibrinogen disorder easily and represents a novel screening test for fibrinogen disorders.

    DOI: 10.1016/j.thromres.2018.12.018

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  29. Ischemic events are rare among aging patients with hemophilia: Results of a cross-sectional study from at centers treating hemophiliacs in Japan 査読有り

    Suzuki Nobuaki, Takedani Hideyuki, Yamasaki Naoya, Chikasawa Yushi, Sawada Akihiro, Kanematsu Takeshi, Higasa Satoshi, Amano Kagehiro, Fukutake Katsuyuki, Nagao Azusa

    HAEMOPHILIA   24 巻   頁: 13-14   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  30. Ischemic events are rare among aging patients with hemophilia: Results of a cross-sectional study from at centers treating hemophiliacs in Japan 査読有り 国際誌

    Suzuki Nobuaki, Takedani Hideyuki, Yamasaki Naoya, Chikasawa Yushi, Sawada Akihiro, Kanematsu Takeshi, Higasa Satoshi, Amano Kagehiro, Fukutake Katsuyuki, Nagao Azusa

    HAEMOPHILIA   24 巻   頁: 13-14   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  31. Vwf K1362A resulted in failure of protein synthesis in mice

    Sanda Naomi, Suzuki Nobuaki, Suzuki Atsuo, Kanematsu Takeshi, Kishimoto Mayuko, Hasuwa Hidetoshi, Takagi Akira, Kojima Tetsuhito, Matsushita Tadashi, Nakamura Shigeo

    INTERNATIONAL JOURNAL OF HEMATOLOGY   107 巻 ( 4 ) 頁: 428 - 435   2018年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Hematology  

    Von Willebrand factor (VWF) is synthesized in megakaryocytes and endothelial cells (ECs) and has two main roles: to carry and protect coagulation factor VIII (FVIII) from degradation by forming VWF–FVIII complex; and to mediate platelet adhesion and aggregation at sites of vascular injury. Previous research using the HEK293 cell line revealed that the VWF K1362 mutation interacted directly with platelet glycoprotein Ib (GPIb). Vwf K1362A knock-in (KI) mice were therefore generated to verify the in vivo function of residue 1362 in binding to platelet GPIb. The Cre-loxP system was employed to introduce the Vwf K1362A mutation systemically in mice. In blood coagulation analysis, the VWF antigen (VWF:Ag) of Lys1362Ala KI homozygous (homo) mice was below the sensitivity of detection by enzyme-linked immunosorbent assay. FVIII activities (FVIII:C) were 47.9 ± 0.3 and 3.3 ± 0.3% (K1362A heterozygous (hetero) and K1362A KI homo mice, respectively) compared to wild-type mice. Immunohistochemical staining analysis revealed that VWF protein did not exist in ECs of K1362A KI homo mice. These results indicated that VWF protein synthesis of K1362A was impaired after transcription in mice. K1362 seems to represent a very important position not only for VWF function, but also for VWF synthesis in mice.

    DOI: 10.1007/s12185-017-2394-y

    Web of Science

    Scopus

    PubMed

  32. Combined deficiency of factors V and VIII by chance coinheritance of parahaemophilia and haemophilia A, but not by mutations of either LMAN1 or MCFD2, in a Japanese family 査読有り 国際誌

    Suzuki S., Nakamura Y., Suzuki N., Yamazaki T., Takagi Y., Tamura S., Takagi A., Kanematsu T., Matsushita T., Kojima T.

    HAEMOPHILIA   24 巻 ( 1 ) 頁: e13 - e16   2018年1月

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

    DOI: 10.1111/hae.13360

    Web of Science

    Scopus

  33. その他の凝固因子濃縮製剤の使い方(フィブリノゲン製剤など) 国際誌

    兼松 毅

    日本血栓止血学会誌   29 巻 ( 6 ) 頁: 744-747 - 747   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:一般社団法人 日本血栓止血学会  

    DOI: 10.2491/jjsth.29.744

    CiNii Research

  34. Retrospective analysis of in vivo recovery and clearance during continuous infusion of recombinant factor VIII products: a single-institution study 国際誌

    Suzuki N., Hirakawa A., Kishimoto M., Kanematsu T., Ogawa M., Kiyoi H., Matsushita T.

    HAEMOPHILIA   23 巻 ( 2 ) 頁: 215 - 221   2017年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Haemophilia  

    Background: Continuous infusion (CI) of recombinant FVIII (rFVIII) concentrates has been reported as an effective and safe method to achieve haemostasis during major surgeries or severe bleeding events. For more effective and safer CI, better understanding of in vivo recovery (IVR) and clearance (CL) issues is imperative. Objective: We investigated the following factors affecting IVR and CL using univariate and multivariate regression analyses during 47 CIs in 34 patients: rFVIII concentrate type, haemophilia severity, blood type, the presence of hepatitis C virus (HCV) or human immunodeficiency virus (HIV), age and body mass index (BMI). Results: The mean IVR was 1.64 ± 0.49 IU dL−1 per IU kg−1, and the mean CL during CI was 3.56 ± 1.57 mL h−1 kg−1. The univariate and multivariate regression analyses showed that the CL of octocog alfa was significantly lower than that of rurioctocog alfa (P = 0.043 and 0.0034, respectively). There was a significant difference in BMI in the univariate and multivariate regression analyses (P = 0.0403 and 0.0376, respectively). Conclusions: This study indicated that CL during CI was potentially affected by the type of rFVIII concentrate used and BMI.

    DOI: 10.1111/hae.13082

    Web of Science

    Scopus

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講演・口頭発表等 10

  1. Clinical Course and Management of Surgical Emergency in a Severe Hemophilia a Patient Under Weekly Subcutaneous Administration of a Bispecific Antibody to Factors IXa and X (ACE910) 国際会議

    Kanematsu Takeshi, Suzuki Nobuaki, Sanda Naomi, Ogawa Mika, Kishimoto Mayuko, Suzuki Atsuo, Kiyoi Hitoshi, Kasai Ryu, Matsushita Tadashi

    米国血液学会総会  2015年12月3日 

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    記述言語:英語   会議種別:ポスター発表  

    国名:アメリカ合衆国  

  2. A case of MYH9 disorders caused by a novel mutation (p.K74E) 国際会議

    Takeshi KANEMATSU, Nobuaki SUZUKI, Mayuko KISHIMOTO, Tomohiro AOKI, Mika Ogawa, Yoshitoyo KAGAMI, Shinji KUNISHIMA, Hitoshi KIYOI, Tadashi MATSUSHITA

    International Society on Thrombosis and Haemostasis 2015 Congress  2015年6月22日 

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    記述言語:英語   会議種別:ポスター発表  

    国名:カナダ  

  3. MYH9異常症が赤血球造血にもたらす影響の検討

    日本血液学会学術集会  2019年10月13日 

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    記述言語:英語   会議種別:ポスター発表  

    国名:日本国  

  4. Continuous infusion of recombinant factor IX Fc fusion protein during major surgery 国際会議

    Takeshi Kanematsu, Nobuaki Suzuki, Mika Ogawa, Mayuko Kishimoto, Atsuo Suzuki, Hitoshi Kiyoi, Tetsuhito Kojima, Tadashi Matsushita

    XXVI Congress of the International Society on Thrombosis and Haemostasis  2017年7月11日 

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    記述言語:英語   会議種別:ポスター発表  

    国名:ドイツ連邦共和国  

  5. 21か月の経過で自然寛解した高力価インヒビター保有自己免疫性第V因子欠乏症(AiF5D)の1例

    兼松 毅、鈴木 伸明、岡本 修一、尾崎 司、惣宇利 正善、鈴木 敦夫、田村 彰吾、 早川 文彦、小嶋 哲人、清井 仁、一瀬 白帝、松下 正

    第83回日本血液学会学術集会  2021年9月23日  張替 秀郎(東北大学)

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    開催年月日: 2021年9月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:完全Web開催  

  6. 周術期の⽌⾎に難渋した先天性第V因⼦⽋乏症の1例

    兼松 毅、鈴木 伸明、岡本 修一、鈴木 敦夫、田村 彰吾、早川 文彦、小嶋 哲人、清井 仁、松下 正

    第43回日本血栓止血学会学術集会  2021年5月28日  浅田 祐士郎

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    開催年月日: 2021年5月

    記述言語:日本語  

    開催地:宮崎県   国名:日本国  

  7. Genetic Analysis of Von Willebrand Disease By Using the Exome Sequencing Approach 国際会議

    Sanda Naomi, Suzuki Nobuaki, Kanematsu Takeshi, Ogawa Mika, Kishimoto Mayuko, Nakamura Shigeo, Matsushita Tadashi

    米国血液学会総会  2015年12月3日 

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    記述言語:英語   会議種別:ポスター発表  

    国名:アメリカ合衆国  

  8. 当施設における新生児・乳幼児に対するエミシズマブの使用経験

    兼松 毅、鈴木 伸明、岡本 修一、鈴木 敦夫、田村 彰吾、早川 文彦、小嶋 哲人、清井 仁、松下 正

    日本血栓止血学会学術集会  2020年6月 

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    記述言語:日本語  

  9. 特発性血小板減少性紫斑病の病勢に対し、サイトメガロウイルス再活性化の関与が疑われた2例

    兼松 毅、鈴木 伸明、岡本 修一、鈴木 敦夫、川上 萌、三田 直美、田村 彰吾、小嶋 哲人、清井 仁、松下 正

    日本血栓止血学会学術集会  2019年6月20日 

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    記述言語:日本語   会議種別:ポスター発表  

    国名:日本国  

  10. ループスアンチコアグラント低プロトロンビン血症症候群(LAHPS)の2例

    兼松 毅、鈴木 伸明、鈴木 敦夫、高木 明、岸本 磨由子、川上(村田) 萌、三田 直美、小山 大輔、小嶋 哲人、清井 仁、松下 正

    日本血栓止血学会学術集会  2018年6月28日 

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    記述言語:日本語   会議種別:ポスター発表  

    国名:日本国  

▼全件表示

 

社会貢献活動 2

  1. 日本血栓止血学会第8回教育セミナー

    役割:講師, 運営参加・支援

    2020年11月

  2. 日本血栓止血学会第7回教育セミナー

    役割:講師, 運営参加・支援

    2019年10月