2022/05/12 更新

写真a

マツシタ タダシ
松下 正
MATSUSHITA, Tadashi
所属
医学部附属病院 輸血部 教授
大学院担当
大学院医学系研究科
職名
教授

学位 1

  1. 医学博士 ( 1992年3月   名古屋大学 ) 

研究分野 3

  1. その他 / その他  / 血液内科学

  2. その他 / その他  / 病態検査学

  3. その他 / その他  / 内科学一般

現在の研究課題とSDGs 1

  1. von Willebrand因子の生体・病態機能

経歴 2

  1. 名古屋大学医学部附属病院 講師

    2005年4月 - 2010年2月

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    国名:日本国

  2. 名古屋大学医学部附属病院 助手

    1999年4月 - 2005年3月

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    国名:日本国

学歴 2

  1. 名古屋大学   医学研究科   内科学第一

    - 1992年3月

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    国名: 日本国

  2. 名古屋大学   医学部   医学科

    - 1985年

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    国名: 日本国

所属学協会 9

  1. 日本輸血・細胞治療学会

  2. 日本血栓止血学会   理事、評議員、血友病部会員、VWD/TTP部副会長

  3. 日本臨床検査医学会

  4. 日本検査血液学会   理事

  5. American Society of Hematolohy

  6. American Association of Blood Banks

  7. International Society in Thrombosis and Hemostasis

  8. 日本臨床検査自動化学会

  9. American Society for Biochemistry and Molecular Biology

▼全件表示

委員歴 2

  1. 男女共同参画専門委員会   委員  

    2010年4月 - 現在   

  2. 情報連携統括本部会議   委員  

    2010年4月 - 現在   

受賞 1

  1. 日本血栓止血学会 第1回学術奨励賞

    1994年11月   日本血栓止血学会  

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    受賞国:日本国

 

論文 197

  1. Use of cyclophosphamide and total lymphoid irradiation combined with cyclosporine in bone marrow transplantation for transfused severe aplastic anemia. 査読有り

    "K. Miyamura, S. Kojima, K. Takeyama, T. Matsushita, M. Fukuda, K. Horibe, S. Minami, Y. Morishima, K. Matsuyama and Y. Kodera"

    Bone Marrow Transplantation   3 巻   頁: 457-461   1988年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  2. Comparison between bone marrow transplantation and immuno-suppressive therapy in treatment of patients younger than 20 years with severe aplastic anemia 査読有り

    "Kojima, S., Fukuda, M., Horibe, K., Matsuyama, K., Takeyama, K., Matsushita, T., Miyamura, K., Kimura, Y., Minami, S. and Kodera, Y."

    Acta. Haematol. Jpn.   51 巻 ( 1 ) 頁: 28-35   1988年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  3. Allogeneic bone marrow transplantation for Burkitt's lymphoma (stage IV). 査読有り

    "Miyamura, K., Takeyama, K., Matsushita, T., Kimura, M., Minami, S., Yoshida, J., Matsuyama, K., Kodera, Y., Yamauchi, T. and Hiraiwa, A., et al."

    "Jpn. J. Clin. Hematol. 29, 149-55, 1988"   29 巻 ( 2 ) 頁: 149-55   1988年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  4. Cyclosporine as prophylaxis for graft versus host disease in adults undergoing allogeneic bone marrow transplantation 査読有り

    "Matsushita, T., Akatsuka, Y., Towatari, M., Takeyama, K., Miyamura, K., Sugihara, T., Minami, S., & Kodera, Y."

    Jpn. J. Clin. Hematol.   30 巻 ( 4 ) 頁: 429-436   1989年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  5. Effects of ceftriaxone on severe infectious complications in hematological disorders. Tohkai Research Group on Infections in Hematological Disorders 査読有り

    "Mitomo, Y., Nitta, M., Kodama, H., Kobayashi, M., Ikeda, Y., Kodera, Y., Matsushita, T., Ohara, K., Kamiya, O. and Shirakawa, S., et al."

    Jpn J Antibiot   42 巻 ( 4 ) 頁: 938-47   1989年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Ceftriaxone (CTRX), a new long acting antibiotic in the 3rd generation cephem group, was administered intravenously once or twice a day in daily doses of 1-6 g for at least 3 days to 86 patients with severe infections complicating hematopoietic disorders. Underlying diseases were acute leukemia in 41 cases, chronic leukemia in 3 cases, malignant lymphoma in 19 cases, myeloma in 7 cases and others. Most patients (55 cases) suffered from sepsis or suspected sepsis. As for efficacy rates classified by underlying diseases, the treatment was effective in 61.0% of patients with acute leukemia. As for efficacy rates classified by infections, the treatment was effective in 60.0% of patients with sepsis. No side effects were noted except rash in 2 patients. Abnormal hepatic functions were recognized in 3 patients but were not attributed to the agent in any case. The results indicate that CTRX is a safe and useful antibiotic for the treatment of severe infections accompanied by hematopoietic disorders."

  6. Prolonged thrombocytopenia after autologous bone marrow transplantation 査読有り

    "Kojima, S., Fukuda, M., Horibe, K., Matsuyama, T., Takeyama, K., Matsushita, T., Miyamura, K., Sugihara, T., Minami, S., & Kodera, Y."

    Jpn. J. Clin. Hematol.   30 巻 ( 2 ) 頁: 175-80   1989年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Thirty two patients with hematologic malignancies and solid tumors were treated with intensive therapy and autologous bone marrow transplantation. In nine out of 32 patients, it took more than 50 days to achieve a sustained platelet count of 50,000/microliter or greater. Significant associations with poor platelet recovery were found for patient age, diseases, period of cryopreservation, the kinds of eradicative therapy and in vitro purging. But most of these factors overlapped each other in the same patients. No correlation was found between platelet recovery and number of cells or CFU-GM infused."

  7. Severe aplastic anemia remarkably improved by a treatment with antilymphocyte globulin, high-dose methylprednisolone and danazol 査読有り

    Miyamura, K., Kojima, S., Takeyama, K., Matsushita, T., Minami, S., & Kodera, Y.

    Jpn. J. Clin. Hematol.   30 巻 ( 1 ) 頁: 72-77   1989年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Sixteen-years-old female with severe aplastic anemia received a therapy combined with antilymphocyte globulin (ALG), high-dose methylprednisolone (m-PSL) and danazol. At the hospitalization, hematological examination demonstrated as follows; reticulocyte 21,000/microliters, granulocyte 350/microliters, platelet 10,000/microliters and hypocellular bone marrow. Treatment schedule were 1) m-PSL 1,000 mg (day 1-4), 500 mg (5-8)--then tapered. 2) ALG lg/day (day 4-8) 3) danazol 600 mg/day. During ALG administration, leukocytopenia and thrombocytopenia appeared but thereafter hematological recovery was obtained and the patient was free from supportive care. She developed mild diabetes mellitus and moderate liver dysfunction, nevertheless, both of which were controlled. At 3 months after the beginning of the treatment, hematological examination demonstrated as follows; reticulocyte 236,000/microliters, granulocyte 1,900/microliters, platelet 56,000/microliters and normocellular bone marrow. Although this immunosuppressive therapy was remarkably effective to this patient, immunological relation to the onset of aplastic anemia was not demonstrated in in vitro examination. This combined therapy seems to be effective one for patients with severe aplastic anemia.

  8. The analysis of mutant factor IX gene responsible for the development of inhibitor in hemophilia B. 査読有り

    "Matsushita, T."

    Hematology & Oncology   21 巻 ( 4 ) 頁: 472-477   1990年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  9. Gene diagnosis of hereditary bloodcoagulation factor disorders 査読有り

    "Matsushita, T., Sugiura, I."

    Jpn. J. Clin. Pathol.   85 巻   頁: 114-122   1990年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  10. Molecular diagnosis of inherited coagulation disorders--sequence analysis of hemophilia B patients with anti-factor IX antibodies 査読有り

    "Tanimoto, M., Matsushita, T., Takamatsu, J. and Saito, H."

    "J. Clin. Pathol. 38, 1041-1046, 1990"   38 巻 ( 9 ) 頁: 1041-1046   1990年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Seven hemophilia B patients with anti-factor IX antibodies are studied with molecular means. A total factor IX gene deletion was detected in four patients from three distinct families. Three other patients without detectable gene arrangements were investigated at the DNA sequence level. Enzymatic amplification of the factor IX gene and subsequent DNA sequencing revealed four novel nucleotide mutations in these patients. Patient HB 5 had two point mutations in his factor IX gene. One is located at nucleotide -793 from the translation start (G-A) and the other (C-T) was found in the codon for 191-Gln changing to a termination codon. Patient HB6 had a point mutation (G-A) in the splicing junction of intron g. A2 bp nucleotide deletion was detected in the third exon of the patient HB7 yielding 8 frameshifted amino acids and a stop codon. These results suggested that not only a large deletion of the factor IX gene but also point mutations or small deletion of the gene which may cause the substantial loss of the coding information for the mature protein are involved in the development of anti-factor IX antibodies in hemophilia B patients.

  11. DNA sequence analysis of three inhibitor-positive hemophilia B patients without gross gene deletion. Identification of four novel mutations in factor IX gene. 査読有り

    "Matsushita, T., Tanimoto, M., Yamamoto, K., Sugiura, I., Hamaguchi, M., Takamatsu, J., Kamiya, T. and Saito, H."

    J Lab Clin Med.   116 巻   頁: 492-497   1990年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  12. Cytomegalovirus-induced gastritis in a bone marrow transplant patient. 査読有り

    "Minami, H., Matsushita, T., Sugihara, T., Kodera, Y., Sakai, S. and Shimokata, K."

    INTERNAL MEDICINE   29 巻   頁: 433-435   1990年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  13. Molecular genetics of hemophiliacs 査読有り

    "Matsushita, T. and Saito, H."

    Hematology & Oncology   22 巻 ( 1 ) 頁: 129-140   1991年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  14. Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C. 査読有り

    "Yamamoto, K., Matsushita, T., Sugiura, I., Takamatsu, J., Iwasaki, E., Wada, H., Deguchi, K., Shirakawa, S. and Saito, H."

    J. Lab. Clin. Med.   119 巻   頁: 682-689   1991年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  15. "Three distinct point mutations in the factor IX gene of three CRM+ hemophilia B patients (Factor IX BMNagoya 2, B+ Nagoya 3 and 4)." 査読有り

    "Hamaguchi, M., Tanimoto, M., Matsushita, T., Yamamoto, K., Sugiura, I., Takamatsu, J., Ogata, T., Kamiya, T. and H., S."

    Thromb. Haemost.   65 巻   頁: 514-520   1991年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  16. Genotype establishments for protein C deficiency by use of a DNA polymorphism in the gene. 査読有り

    "Yamamoto, K., Tanimoto, M., Matsushita, T., Kagami, K., Sugiura, I., Hamaguchi, M., Takamatsu, J. and Saito, H."

    Blood   77 巻   頁: 2633-2636   1991年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  17. Direct carrier detection in hemophilia B kindreds: Use of modified primers (mutagenic primers) for enzymatic amplification of the factor IX gene. 査読有り

    "Matsushita, T., Tanimoto, M., Yamamoto, K., Sugiura, I., Takamatsu, J., Kamiya, T. and Saito, H."

    Thromb. Res.   63 巻   頁: 355-361   1991年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  18. A female hemophilia A combined with hereditary coagulation factor XII deficiency: a case report. 査読有り

    "Matsushita, T., Takamatsu, J., Kagami, K., Takahashi, I., Sugiura, I., Hamaguchi, M., Kamiya, T. and Saito, H."

    Am. J. Hematol   39 巻   頁: 137-141   1991年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  19. Mammalian expression systems of human blood coagulation factors. 査読有り

    "Matsushita, T. and Emi, N."

    Jpn. J. Thromb. Hemost.     頁: 546-549   1991年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  20. Elevation of factor VII activity and mass in coronary artery disease of varying severity 査読有り

    "Suzuki, T., Yamauchi, K., Matsushita, T., Furumachi, T., Furui, H., Tsuzuki, J. and Saito, H."

    Clin. Cardiol.   14 巻   頁: 731-736   1991年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  21. Three distinct candidate point mutatations of the von Willebrand factor gene in four patients with type IIA von Willebrand disease 査読有り

    "Sugiura, I., Matsushita, T., Tanimoto, M., Takahashi, I., Yamazaki, T., Yamamoto, K., Takamatsu, J., Kamiya, T. and Saito, H."

    Thromb. Haemost.   67 巻 ( 6 ) 頁: 612-617   1992年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  22. Impaired secretion of the elongated mutant of protein C (protein C-Nagoya). Molecular and celluler basis for hereditary protein C deficiency. 査読有り

    "Yamamoto, K., Tanimoto, M., Emi, N., Matsushita, T., Takamatsu, J. and Saito, H."

    J. Clin. Invest.   90 巻   頁: 2439-2446   1992年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  23. Construction and its expression of a new retroviral vector containing a human blood coagulation factor IX cDNA 査読有り

    "Matsushita, T., Emi, N., Takahashi, I., Takamatsu, J. and Saito, H."

    Thromb. Res.   69 巻   頁: 387-393   1993年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  24. A phenotypically neutral dimorphism of protein S: the substitution of Lys155 by Glu in the second EGF domain predicted by an A to G base exchange in the gene 査読有り

    "Yamazaki, T., Sugiura, I., Matsushita, T., Kojima, T., Kagami, K., Takamtsu, J. and Saito, H."

    Thromb. Res   70 巻   頁: 395-403   1993年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  25. *Impaired human tissue factor-mediated activity in blood clotting factor VIINagoya (Arg304 -> Trp). Evidence that a region in the catalytic domain of factor VII is important for the association with tissue factor) 査読有り

    "Matsushita, T., Kojima, T., Emi, N., Takahashi, I. and Saito, H."

    J. Biol. Chem.   269 巻 ( 10 ) 頁: 7355-7363   1994年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  26. von Willebrand's factor and von Willebrand's diesease 査読有り

    "Matsushita, T., Dong, Z. and Sadler, J. E."

    Current Opinion in Hematology   1 巻   頁: 362-368   1994年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  27. *Identification of amino acid residues essential for von Willebrand factor binding to platelet glycoprotein Ib. Charged-to-alanine scanning mutagenesis of the A1 domain of human von willebrand factor. 査読有り

    "Matsushita, T. and Sadler, J."

    J. Biol. Chem.   270 巻 ( 22 ) 頁: 13406-13414   1995年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  28. Molecular mechanism and classification of von Willebrand disease 査読有り

    "Sadler, J. E., Matsushita, T., Dong, Z., Tuley, E. and Westfield, L. A."

    Thromb. Haemost.   74 巻 ( 1 ) 頁: 161-166   1995年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  29. Diagnosis of hemophilia B carriers using two novel dinucleotide polymorphisms and Hha I RFLP of the factor IX gene in Japanese subjects 査読有り

    "Toyozumi, H., Kojima, T., Matsushita, T., Hamaguchi, M., Tanimoto, M. and Saito, H."

    Thrombosis & Haemostasis   74 巻 ( 4 ) 頁: 1009-1014   1995年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "We identified two novel dinucleotide polymorphisms in intron A at nucleotide 192 (FIX192) and in the 5' flanking region at nucleotide -793 (FIX-793) of the factor IX gene, which are present in normal Japanese. The Hha I restriction fragment length polymorphism (FIX-HhaI) located 8 kb 3' to the factor IX gene was also found to be an efficient marker for detecting carriers in a Japanese family with hemophilia B. Each of these polymorphisms was able to be rapidly ascertained by the polymerase chain reaction (PCR) technique. In 22 Japanese families with hemophilia B, 18 families (81.8%) were heterozygous for at least one of these polymorphisms, whereas 11 (50%) were informative for the extragenic DXS99/Sac I RFLP which was previously reported as a useful gene marker for Japanese hemophilia B. Using all 4 polymorphisms together, the informative rate improved to 86.4%. Carrier detection and, possibly, the prenatal diagnosis of hemophilia B can be achieved effectively and rapidly in Japanese with these polymorphisms."

  30. Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor. 査読有り

    "Eikenboom, J. C. J., Matsushita, T., Reitsma, P. H., Tuley, E. A., Castman, G., Briテゥt, E. and Sadler, J. E."

    Blood   88 巻 ( 7 ) 頁: 2433-2441   1996年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  31. Identification of the five hydrophilic residues (Lys-217, Lys-218, Arg- 359, His-360, and Arg-513) essential for the structure and activity of vitamin K-dependent carboxylase 査読有り

    "Shimizu, A., Sugiura, I., Matsushita, T., Kojima, T., Hirai, M. and Saito, H."

    Biochem Biophys Res Commun   251 巻 ( 1 ) 頁: 16285-94   1998年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Vitamin K-dependent carboxylase catalyzes the posttranslational conversion of glutamic acid to gamma-carboxyglutamic acid in vitamin K- dependent proteins. The clustered charged-to-alanine scanning mutagenesis of bovine carboxylase has identified five distinct candidate regions (I. Sugiura et al., J. Biol. Chem. 271, 17837-17844, 1996) with significant loss-of-function phenotype. To further specify the residues essential for the structure and function of the enzyme, Lys-217, Lys-218, Arg-359, His-360, Lys-361, Arg-513, and Lys-515 were analyzed by substituting to alanine individually. All the mutants except for K217A were expressed in Chinese hamster ovary cells. The carboxylase activities of R359A, H360A, and R513A decreased in parallel with the vitamin K epoxidase activities. Both carboxylations by R359A and H360A were stimulated saturatively at 1 microM factor IX propeptide (proFIX18) concentration, but that by R513A was not at a concentration up to 128 microM. K218A completely lost the enzyme activities but it cross-linked to the propeptide, suggesting that Lys-218 is critical for enzyme activity without affecting propeptide binding. We conclude that Lys-218, Arg-359, and His-360 are involved in the catalytic event, and Arg-513 participates in propeptide binding. Copyright 1998 Academic Press."

  32. ERGIC-53 Gene Structure and Mutation Analysis in 19 Combined Factors V and VIII Deficiency Families 査読有り

    "Nichols, W. C., Terry, V. H., Wheatley, M. A., Yang, A., Zivelin, A., Ciavarella, N., Stefanile, C., Matsushita, T., Saito, H., de Bosch, N. B., Ruiz-Saez, A., Torres, A., Thompson, A. R., Feinstein, D. I., White, G. C., Negrier, C., Vinciguerra, C., Aktan, M., Kaufman, R. J., Ginsburg, D. and Seligsohn, U."

    Blood   93 巻 ( 7 ) 頁: 2261-2266   1999年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Combined factors V and VIII deficiency is an autosomal recessive bleeding disorder associated with plasma levels of coagulation factors V and VIII approximately 5% to 30% of normal. The disease gene was recently identified as the endoplasmic reticulum-Golgi intermediate compartment protein ERGIC-53 by positional cloning, with the detection of two founder mutations in 10 Jewish families. To identify mutations in additional families, the structure of the ERGIC-53 gene was determined by genomic polymerase chain reaction (PCR) and sequence analysis of bacterial artificial chromosome clones containing the ERGIC- 53 gene. Nineteen additional families were analyzed by direct sequence analysis of the entire coding region and the intron/exon junctions. Seven novel mutations were identified in 10 families, with one additional family found to harbor one of the two previously described mutations. All of the identified mutations would be predicted to result in complete absence of functional ERGIC-53 protein. In 8 of 19 families, no mutation was identified. Genotyping data indicate that at least two of these families are not linked to the ERGIC-53 locus. Taken together, these results suggest that a significant subset of combined factors V and VIII deficiency is due to mutation in one or more additional genes."

  33. Severe factor VII deficiency caused by a novel mutation His348 to Gln in the catalytic domain 査読有り

    "Katsumi, A., Matsushita, T., Yamazaki, T., Sugiura, I., Kojima, T. and Saito, H."

    Thromb Haemost   83 巻 ( 2 ) 頁: 239-43   2000年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Factor VII is a vitamin K-dependent zymogen that plays a key role in the initiation of the extrinsic pathway. A severe factor VII deficiency was identified in a 45-year old male whose plasma factor VII antigen was less than 60 ng/ml and expressed 5.2% of normal factor VII activity. DNA sequence analysis of the patient's factor VII gene showed a thymidine to guanine transversion at nucleotide 10968 in exon VIII that results in a novel amino acid substitution of His348 to Gln. The patient was homozygous for this mutation, whereas some of his family members were heterozygous. Both wild type and mutant factor VII were transiently expressed in COS-1 cells. The level of secreted mutant factor VII antigen was only 11.0% of the level of wild type factor VII. In CHO cells stably transfected with the mutant factor VII, only 37.3% of the total labeled FVII was secreted into the conditioned media and the remainder was retained inside the cells. These data suggest this mutation leads to factor VII deficiency due to the impaired secretion of the molecule."

  34. Complete antithrombin deficiency in mice results in embryonic lethality 査読有り

    "Ishiguro, K., Kojima, T., Kadomatsu, K., Nakayama, Y., Takagi, A., Suzuki, M., Takeda, N., Ito, M., Yamamoto, K., Matsushita, T., Kusugami, K., Muramatsu, T. and Saito, H."

    J Clin Invest   106 巻 ( 7 ) 頁: 873-878   2000年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Antithrombin is a plasma protease inhibitor that inhibits thrombin and contributes to the maintenance of blood fluidity. Using targeted gene disruption, we investigated the role of antithrombin in embryogenesis. Mating mice heterozygous for antithrombin gene (ATIII) disruption, ATIII(+/-), yielded the expected Mendelian distribution of genotypes until 14.5 gestational days (gd). However, approximately 70% of the ATIII(-/-) embryos at 15.5 gd and 100% at 16.5 gd had died and showed extensive subcutaneous hemorrhage. Histological examination of those embryos revealed extensive fibrin(ogen) deposition in the myocardium and liver, but not in the brain or lung. Furthermore, no apparent fibrin(ogen) deposition was detected in the extensive hemorrhagic region, suggesting that fibrinogen might be decreased due to consumptive coagulopathy and/or liver dysfunction. These findings suggest that antithrombin is essential for embryonic survival and that it plays an important role in regulation of blood coagulation in the myocardium and liver."

  35. Short report: A case of purpura fulminans is caused by homozygous delta8857 mutation (protein C-nagoya) and successfully treated with activated protein C concentrate 査読有り

    "Nakayama, T., Matsushita, T., Hidano, H., Suzuki, C., Hamaguchi, M., Kojima, T. and Saito, H."

    Br J Haematol   110 巻 ( 3 ) 頁: 727-30   2000年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "We report a Japanese patient who developed purpura fulminans and disseminated intravascular coagulation (DIC) shortly after birth. The patient was diagnosed to be homozygous for protein C deficiency and was treated with an activated protein C (APC) concentrate. Intravenous infusions of APC markedly improved the necrotic skin lesions and the anticoagulation by APC enabled successful DIC control. The identified mutation (Delta8857) results in impaired intracellular transport and protein maturation and would be the cause of the complete protein C deficiency. This is the seventh case of the mutation that has been exclusively reported in Japan, but is the first report of a homozygous case. Our findings propose new therapeutic and diagnostic tools for the management of this fatal thrombotic disease."

  36. Identification of plasma antibody epitopes and gene abnormalities in Japanese hemophilia A patients with factor VIII inhibitor 査読有り

    "Sugihara, T., Takahashi, I., Kojima, T., Okamoto, Y., Yamamoto, K., Kamiya, T., Matsushita, T. and Saito, H."

    Nagoya J Med Sci   63 巻   頁: 25-39   2000年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Eleven Japanese hemophilia A patients with anti-factor VIII (FVIII) inhibitors were studied to localize both their inhibitory antibody epitopes and their genotypes. The inhibitor epitopes were studied in nine severe hemophilia A patients by means of a scanning method using the oligopeptide panel covering the FVIII polypeptides without the B domain. The 107 15 mer-peptides were synthesized on solid-phase pins and analyzed for their reactivity with diluted patient plasma. As indicated previously, a series of peptides corresponding to the A2 and C2 domains were recognized by plasma antibodies from 2 patients and 4 patients, respectively. In contrast, all the antibodies bound to several epitopes in the A3 domain, while an epitope 1809-1821 covering the putative factor IX binding site was found in 3 patients. Southern blotting analysis showed that 8 out of 11 patients had either gene deletions or inversions of the FVIII gene, indicating a higher proportion of gross gene alterations in inhibitor-positive hemophilia A patients. However, the correlation of gene abnormality type with epitope location was not fully established."

  37. DNA sequence analysis of protein S deficiency--identification of four point mutations in twelve Japanese subjects 査読有り

    "Iwaki, T., Mastushita, T., Kobayashi, T., Yamamoto, Y., Nomura, Y., Kagami, K., Nakayama, T., Sugiura, I., Kojima, T., Takamatsu, J., Kanayama, N. and Saito, H."

    Semin Thromb Hemost   27 巻 ( 2 ) 頁: 155-60   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "The molecular basis for the hereditary type I protein S (PS) deficiency was investigated. DNA sequence analysis of 12 patients with PS deficiency in Japan identified four point mutations and three of them were novel. Nonsense mutations found in two unrelated patients resulted in termination of the PS polypeptide chains at Gln 238 and Lys 392, respectively. Two novel missense mutations were also found in two other patients substituting Asp 202 for Asn and Leu 298 for Pro, respectively. Comparison of the PS amino acid sequences from several mammalians indicated that Asp 202 and Leu 298 were preserved and thus appeared to be responsible for the pathogenesis of PS deficiency."

  38. Localization of von willebrand factor-binding sites for platelet glycoprotein Ib and botrocetin by charged-to-alanine scanning mutagenesis 査読有り

    Matsushita, T., Meyer, D. and Sadler, J. E.

    J Biol Chem   275 巻 ( 15 ) 頁: 11044-9   2000年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    At sites of vascular injury, von Willebrand factor (VWF) mediates platelet adhesion through binding to platelet glycoprotein Ib (GPIb). Previous studies identified clusters of charged residues within VWF domain A1 that were involved in binding GPIb or botrocetin. The contribution of 28 specific residues within these clusters was analyzed by mutating single amino acids to alanine. Binding to a panel of six conformation-dependent monoclonal antibodies was decreased by mutations at Asp(514), Asp(520), Arg(552), and Arg(611) (numbered from the N- terminal Ser of the mature processed VWF), suggesting that these residues are necessary for domain A1 folding. Binding of (125)I- botrocetin was decreased by mutations at Arg(629), Arg(632), Arg(636), and Lys(667). Ristocetin-induced and botrocetin-induced binding to GPIb both were decreased by mutations at Lys(599), Arg(629), and Arg(632); among this group the K599A mutant was unique because (125)I-botrocetin binding was normal, suggesting that Lys(599) interacts directly with GPIb. Ristocetin and botrocetin actions on VWF were dissociated readily by mutagenesis. Ristocetin-induced binding to GPIb was reduced selectively by substitutions at positions Lys(534), Arg(571), Lys(572), Glu(596), Glu(613), Arg(616), Glu(626), and Lys(642), whereas botrocetin-induced binding to GPIb was decreased selectively by mutations at Arg(636) and Lys(667). The binding of monoclonal antibody B724 involved Lys(660) and Arg(663), and this antibody inhibits (125)I- botrocetin binding to VWF. The crystal structure of the A1 domain suggests that the botrocetin-binding site overlaps the monoclonal antibody B724 epitope on helix 5 and spans helices 4 and 5. The binding of botrocetin also activates the nearby VWF-binding site for GPIb that involves Lys(599) on helix 3.

  39. Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome) 査読有り

    "Kunishima, S., Kojima, T., Matsushita, T., Tanaka, T., Tsurusawa, M., Furukawa, Y., Nakamura, Y., Okamura, T., Amemiya, N., Nakayama, T., Kamiya, T. and Saito, H."

    Blood   97 巻 ( 4 ) 頁: 1147-9.   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Macrothrombocytopenia with leukocyte inclusions is a rare autosomal dominant platelet disorder characterized by a triad of giant platelets, thrombocytopenia, and characteristic Dohle body-like leukocyte inclusions. A previous study mapped a locus for the disease on chromosome 22q12.3-q13.2 by genome-wide linkage analysis. In addition, the complete DNA sequence of human chromosome 22 allowed a positional candidate approach, and results here indicate that the gene encoding nonmuscle myosin heavy chain-A, NMMHC-A, is mutated in this disorder. Mutations were found in 6 of 7 Japanese families studied: 3 missense mutations, a nonsense mutation, and a one-base deletion resulting in a premature termination. Immunofluorescence studies revealed that NMMHC-A distribution in neutrophils appeared to mimic the inclusion bodies. These results provide evidence for the involvement of abnormal NMMHC-A in the formation of leukocyte inclusions and also in platelet morphogenesis."

  40. Cloning and characterization of the murine antithrombin gene 査読有り

    "Nakayama, Y., Kojima, T., Takagi, A., Yanada, M., Yamamoto, K., Matsushita, T. and Saito, H."

    Thromb Res   100 巻 ( 3 ) 頁: 179-83   2000年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  41. Syndecan-4 deficiency leads to high mortality of lipopolysaccharide- injected mice 査読有り

    "Ishiguro, K., Kadomatsu, K., Kojima, T., Muramatsu, H., Iwase, M., Yoshikai, Y., Yanada, M., Yamamoto, K., Matsushita, T., Nishimura, M., Kusugami, K., Saito, H. and Muramatsu, T."

    J Biol Chem   3 巻   頁: 3   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the syndecan family. Following intraperitoneal injection of lipopolysaccharide (LPS), syndecan-4-deficient mice exhibited high mortality compared to wild-type controls. Severe endotoxin shock was observed in the deficient mice: systolic blood pressure and left ventricular fractional shortening were lower in the deficient mice than in the wild-type controls 9 h after LPS injection. Although histological examinations revealed no apparent differences between two groups, the plasma level of interleukin (IL)-1b was higher in the deficient mice than in the wild-type controls 9 h after LPS injection. Consistent with the regulatory roles of syndecan-4, its expression in monocytes and endothelial cells of microvasculature increased in the wild-type mice after LPS administration. Although IL-1b was produced to the same extent by macrophages from syndecan-4-deficient and wild-type mice after LPS stimulation, inhibition of its production by transforming growth factor (TGF)-b1 was impaired in the syndecan-4- deficient macrophages. These results indicate that syndecan-4 could be involved in prevention of endotoxin shock, at least partly through the inhibitory action of TGF-b1 on IL-1b production."

  42. Plasma levels of syndecan-4 (ryudocan) are elevated in patients with acute myocardial infarction 査読有り

    "Kojima, T., Takagi, A., Maeda, M., Segawa, T., Shimizu, A., Yamamoto, K., Matsushita, T. and Saito, H."

    Thromb Haemost   85 巻 ( 5 ) 頁: 793-9   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Syndecan-4 (ryudocan) is a cell-surface heparan sulfate proteoglycan, which plays an important role in a variety of biological functions including regulation of blood coagulation. cell adhesion, and cell growth. In this study, we measured plasma levels of syndecan-4 in patients with acute myocardial infarction using an enzyme-immunoassay, and found that they were extremely high, with a peak of average (10.5 +/- 5.6 ng/ml, 2 weeks after onset), as compared with those in normal subjects (0.078 +/- 0.030 ng/ml) (p < 0.001). We also observed a distinct expression of syndecan-4 in the repair region of the damaged cardiac tissues with infarction, but not in intact region, by immunohistochemical analysis. To clarify the mechanism of syndecan-4 induction, we investigated the hypoxia effect on its expression, and found that hypoxia treatment up-regulated the gene expression of syndecan-4 in various types of cells. Taken together, it is suggested that syndecan-4 is induced by hypoxia stimuli in ischemic heart tissues, and may function as a tissue-repair molecule via biological mediators such as heparin-binding growth factors."

  43. Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions 査読有り

    "Kunishima, S., Matsushita, T., Kojima, T., Amemiya, N., Choi, Y. M., Hosaka, N., Inoue, M., Jung, Y., Mamiya, S., Matsumoto, K., Miyajima, Y., Zhang, G., Ruan, C., Saito, K., Song, K. S., Yoon, H. J., Kamiya, T. and Saito, H."

    J Hum Genet   46 巻 ( 12 ) 頁: 722-9   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "The autosomal dominant macrothrombocytopenia with leukocyte inclusions, May-Hegglin anomaly (MHA), Sebastian syndrome (SBS), and Fechtner syndrome (FTNS), are rare platelet disorders characterized by a triad of giant platelets, thrombocytopenia, and characteristic Dohle body-like leukocyte inclusions. The locus for these disorders was previously mapped on chromosome 22q12.3-q13.2 and the disease gene was recently identified as MYH9, the gene encoding the nonmuscle myosin heavy chain-A. To elucidate the spectrum of MYH9 mutations responsible for the disorders and to investigate genotypephenotype correlation, we examined MYH9 mutations in an additional 11 families and 3 sporadic patients with the disorders from Japan. Korea, and China. All 14 patients had heterozygous MYH9 mutations, including three known mutations and six novel mutations (three missense and three deletion mutations). Two cases had Alport manifestations including deafness, nephritis, and cataracts and had R1165C and E1841K mutations, respectively. However, taken together with three previous reports, including ours, the data do not show clear phenotype-genotype relationships. Thus, MHA, SBS, and FTNS appear to represent a class of allelic disorders with variable phenotypic diversity."

  44. "Binding site on human von Willebrand factor of bitiscetin, a snake venom-derived platelet aggregation inducer" 査読有り

    "Matsui, T., Hamako, J., Matsushita, T., Nakayama, T., Fujimura, Y. and Titani, K."

    Biochemistry   41 巻 ( 25 ) 頁: 7939-46.   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Bitiscetin, a C-type lectin-like heterodimeric snake venom protein purified from Bitis arietans, binds to human von Willebrand factor (VWF) and induces the platelet membrane glycoprotein (GP) Ib-dependent platelet agglutination in vitro similar to botrocetin. In contrast with botrocetin which binds to the A1 domain of VWF, the A3 domain, a major collagen-binding site of VWF, was proposed to be a bitiscetin-binding site. In the competitive binding assay, neither bitiscetin nor botrocetin had an inhibitory effect on the VWF binding to the immobilized type III collagen on a plastic plate. The anti-VWF monoclonal antibody NMC-4, which inhibits VWF-induced platelet aggregation by binding to alpha4 helix of the A1 domain, also inhibited bitiscetin binding to the VWF. Binding of VWF to the immobilized bitiscetin was competitively inhibited by a high concentration of botrocetin. A panel of recombinant VWF, in which alanine-scanning mutagenesis was introduced to the charged amino acid residues in the A1 domain, showed that the bitiscetin-binding activity was reduced in mutations at Arg632, Lys660, Glu666, and Lys673 of the A1 domain. Those substituted at Arg629, Arg636, and Lys667, which decreased the botrocetin binding, showed no effect on the bitiscetin binding. These results indicate that bitiscetin binds to a distinct site in the A1 domain of VWF spanning over alpha4a, alpha5 helices and the loop between alpha5 and beta6 but close to the botrocetin- and NMC-4-binding sites. Monoclonal antibodies recognizing the alpha-subunit of bitiscetin specifically inhibited bitiscetin-induced platelet agglutination without affecting the binding between VWF and bitiscetin, suggesting that the alpha-subunit of bitiscetin is located on VWF closer to the GPIb-binding site than the beta-subunit is. Bitiscetin and botrocetin might modulate VWF by binding to the homologous region of the A1 domain to induce a conformational change leading to an increased accessibility to platelet GPIb."

  45. Identification of the regulatory elements of the human von Willebrand factor for binding to platelet GPIb. Importance of structural integrity of the regions flanked by the CYS1272-CYS1458 disulfide bond 査読有り

    "Nakayama, T., Matsushita, T., Dong, Z., Sadler, J. E., Jorieux, S., Mazurier, C., Meyer, D., Kojima, T. and Saito, H."

    J Biol Chem   277 巻 ( 24 ) 頁: 22063-72.   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "In vitro platelet glycoprotein Ib (GPIb) binding of the human von Willebrand factor (VWF) increases markedly by exogenous modulators such as ristocetin or botrocetin, and the binding does not occur in normal circulation. GPIb binding sites have been assigned in the VWF A1 domain, which consists of a disulfide loop Cys1272(509)-Cys1458(695) where amino acid residues are numbered from the starting methionine as +1. The previous numbering from the N-terminal Ser of the mature processed VWF is indicated in parentheses. In contrast, several gain-of- function mutations have been found in two regions comprised of the disulfide loop and its N- and C-terminal flanking regions. In this study, Cys1222(459)-Tyr1271(508), Gln1238(475)-Tyr1271(508), Glu1260(497)-Tyr1271(508), and Asp1459(696)-Asp1472(709) were sequentially deleted of full-length multimeric recombinant VWF. Deletions at either side resulted in normal GPIb binding, indicating that the flanking regions are not GPIb binding sites. However, the addition of a mutation at Arg1308(545) on each deletion mutant resulted in spontaneous GPIb binding without requiring modulators, suggesting that both regions are important for the inhibition of GPIb binding. Spontaneous binding was completely inhibited by monoclonal antibodies that recognize the GPIb binding sites. Interestingly, mutant proteins with N-terminal but not C-terminal deletions lost binding to monoclonal antibodies B328, B710, and 23C7, which selectively inhibit ristocetin- induced GPI binding. Their epitopes were found at His1268(505) or Asp1269(506). The crystallographic structure of the A1 domain suggests that GPIb binding is influenced by the molecular interface between the two regions and that the antibody binding to the interface inhibits binding."

  46. Impact of antithrombin deficiency in thrombogenesis: lipopolysaccharide and stress-induced thrombus formation in heterozygous antithrombin- deficient mice 査読有り

    "Yanada, M., Kojima, T., Ishiguro, K., Nakayama, Y., Yamamoto, K., Matsushita, T., Kadomatsu, K., Nishimura, M., Muramatsu, T. and Saito, H."

    Blood   99 巻 ( 7 ) 頁: 2455-8.   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Antithrombin (AT) deficiency is an autosomal disorder associated with venous thromboembolism. However, a diagnosis of homozygous AT deficiency is seldom made. Most patients are heterozygous and have approximately 50% AT activities, and they are at higher risk for the development of thromboembolism. Through gene targeting we generated AT- deficient mice and previously reported that completely AT-deficient mice could not survive the prenatal period because of extensive thrombosis in the myocardium and liver sinusoids. In contrast, heterozygous AT-deficient mice with 50% AT activities have not shown spontaneous thromboembolic episodes. To demonstrate a thrombotic tendency in heterozygous AT deficiency, we challenged heterozygous AT- deficient mice (AT+/- mice) with the administration of lipopolysaccharide (LPS) or with restraint stress by immobilization. LPS injection markedly induced fibrin deposition in the kidney glomeruli, myocardium, and liver sinusoids in AT+/- mice compared with wild-type mice (AT+/+ mice). Restraint stress tests were performed by placing mice in 50-mL conical centrifuge tubes for 20 hours. Fibrin deposition was observed in the kidney of AT+/+ and AT+/- mice, but AT+/- mice exhibited more extensive fibrin deposition than AT+/+ mice. After prophylactic administration of human AT concentrates to increase plasma AT activities of AT+/- mice, LPS-induced fibrin deposition was effectively prevented. These results suggest that heterozygous AT deficiency is significantly associated with a tendency toward thrombosis formation in the kidney. The AT+/- mouse thus is a useful model for studying the effect of environmental or genetic risk factors on thrombogenesis."

  47. Increased expression of plasminogen activator inhibitor-1 with fibrin deposition in a murine model of aging, ""Klotho"" mouse 査読有り

    "Takeshita, K., Yamamoto, K., Ito, M., Kondo, T., Matsushita, T., Hirai, M., Kojima, T., Nishimura, M., Nabeshima, Y., Loskutoff, D. J., Saito, H. and Murohara, T.

    Semin Thromb Hemost   28 巻 ( 6 ) 頁: 545-54   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Although aging accompanies specific pathological changes, including thrombosis and organ sclerosis, the underlying mechanisms of these processes remain to be elucidated. In the present study, we analyzed the gene expression of plasminogen activator inhibitor-1 (PAI-1), a key molecule in the development of thrombosis, in a murine model of aging, klotho mutant (kl/kl) mice. Active PAI-1 antigen in plasma and PAI-1 mRNA in several tissues were strikingly elevated in kl/kl mice as compared with wild-type mice. This increased PAI-1 expression was age dependent and linked to the development of ectopic calcification and glomerular fibrin deposition in the kidneys. In situ hybridization analysis of kl/kl mice demonstrated that strong signals for PAI-1 mRNA were localized in renal tubular epithelial cells, cardiomyocytes, adrenal medullar cells, and smooth muscle and endothelial cells in Monckeberg's arteriosclerotic vessels. Renal glomerular fibrin deposition, as evaluated immunohistochemically, was occasionally observed only in kl/kl mice, and the number of fibrin-positive glomeruli increased as the kl/kl mice aged. These observations suggest that in the process of aging the PAI-1 gene expression is increased, contributing to the development of thrombosis.

  48. Novel nonsense mutation in the platelet glycoprotein Ibbeta gene associated with Bernard-Soulier syndrome 査読有り

    "Kunishima, S., Matsushita, T., Ito, T., Kamiya, T. and Saito, H."

    Am J Hematol   71 巻 ( 4 ) 頁: 279-84   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder caused by quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex, the platelet receptor for von Willebrand factor. This complex is composed of four subunits, GPIbalpha, GPIbbeta, GPIX, and GPV, and the coordinated assembly of GPIbalpha, GPIbbeta, and GPIX is required for the efficient surface expression of a functional complex. We report here a novel nonsense mutation of the GPIbbeta gene associated with BSS. Flow cytometric analysis of the patient's platelets showed markedly reduced GPIbalpha and absent GPIX surface expression. Immunoblot analysis of solubilized platelets showed that a small amount of GPIbalpha was detected; however, GPIbbeta and GPIX were undetectable. DNA sequencing analysis revealed a novel nonsense mutation of the GPIbbeta gene that converts Trp (TGG) to a stop codon (TAG) at residue 123. Transient transfection studies revealed that the mutant GPIbbeta polypeptide was not detected in the transfected 293T cells, suggesting that null expression of the mutant GPIbbeta impairs expression of the GPIbalpha and GPIX subunits and results in a BSS phenotype in the patient."

  49. Immunofluorescence analysis of neutrophil nonmuscle myosin heavy chain-A in MYH9 disorders: association of subcellular localization with MYH9 mutations 査読有り

    "Kunishima, S., Matsushita, T., Kojima, T., Sako, M., Kimura, F., Jo, E. K., Inoue, C., Kamiya, T. and Saito, H."

    Lab Invest   83 巻 ( 1 ) 頁: 115-22   2003年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "In this study, a total of 24 cases with MYH9 disorders and suspected cases were subjected to immunofluorescence analysis by a polyclonal antibody against human platelet NMMHCA. Abnormal subcellular localization of NMMHCA was observed in every neutrophil from individuals with MYH9 mutations. Comparison with May-Grunwald-Giemsa staining revealed that the NMMHCA always coexisted with the neutrophil inclusion bodies, suggesting that NMMHCA is associated with such bodies. In three cases, neutrophil inclusions were not detected on conventional May-Grunwald-Giemsa-stained blood smears but immunofluorescence analysis revealed the abnormal NMMHCA localization. In contrast, cases with Epstein syndrome and the isolated macrothrombocytopenia with normal NMMHCA localization had no MYH9 mutations. An antibody that recognizes the C-terminal 12 mer peptides showed similar immunoreactivity from the patients heterozygous for truncated mutations that abolished the C-terminal epitope, suggesting that normal NMMHCA dimerizes with abnormal NMMHCA to form inclusion bodies. We further propose that the localization pattern can be classified into three groups according to the number, size, and shape of the fluorescence-labeled NMMHCA granule. Immunofluorescence analysis of neutrophil NMMHCA is useful as a screening test for the clear hematopathologic classification of MYH9 disorders."

  50. Compound heterozygosity for two novel mutations in a severe factor XI deficiency 査読有り

    "Tsukahara, A., Yamada, T., Takagi, A., Murate, T., Matsushita, T., Saito, H. and Kojima, T."

    Am J Hematol   73 巻 ( 4 ) 頁: 279-84   2003年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "We identified two novel mutations in an asymptomatic 25-year-old Japanese patient with severe factor XI deficiency. Direct sequencing analysis of PCR products from his factor XI gene revealed a G to T transversion in exon 12, resulting in the nonsense mutation (Glu447Stop) and a G insertion in five consecutive guanine nucleotides ((501)Trp(TGG)-(502)Gly(GGG)) in exon 13 that is expected to lead to the substitution of the last 105 amino acids ((503)Tyr-(607)Val) with 32 abnormal amino acid residues ((503)Val-(534)Thr) followed by stop codon. We also demonstrated that two mutations are associated with the separate alleles in this patient, indicating compound heterozygosity for these mutations. Both mutations lead to the disruption of the catalytic domain structure of the FXI molecule and thus are responsible for his deficiency of factor XI."

  51. "Enzyme immunoassay for measurement of murine plasminogen activator inhibitor-1, employing a specific antibody produced by the DNA vaccine method" 査読有り

    "Yamada, T., Takagi, A., Takeshita, K., Yamamoto, K., Ito, M., Matsushita, T., Murate, T., Saito, H. and Kojima, T."

    Thromb Res   111 巻   頁: 285-91   2003年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "We developed a sensitive immunoassay to determine the concentration of mouse plasminogen activator inhibitor-1. The assay was a non-competitive sandwich enzyme-linked immunosorbent assay (ELISA) based on the production of a specific polyclonal antibody against mouse plasminogen activator inhibitor type-1 (PAI-1) used both as a trapping and detecting antibody. This antibody was raised in a rabbit by direct introduction of the expression vector plasmid DNA encoding mouse PAI-1, instead of conventional immunization with the purified protein. The standard curve was constructed with a recombinant glutathione S-transferase (GST)-mouse PAI-1 fusion protein (GST-mPAI-1) and dose-response of the assay was linear for GST-mPAI-1 between 6.25 and 100 pM. In order to assess the consistency of the assay, we measured PAI-1 antigen in normal mouse pooled plasma several times. We found that the intra-assay and inter-assay coefficients of variation (CV) were 4.8% and 9.2%, respectively, indicating that the ELISA would be sufficiently repeatable and reproducible. In this assay, lipopolysaccharide (LPS)-injected mice showed substantially higher levels (22-fold) of plasma PAI-1 antigen than did control mice (12.5+/-2.4 vs. 0.58+/-0.16 nM), similar to results reported elsewhere. Taken together, the DNA vaccine method is extremely useful for preparing specific antibodies against mouse PAI-1, which can be utilized to establish the ELISA and analyze the profile of PAI-1 distributions in mice under various conditions. This approach might also be useful for immunological investigation of other coagulation factors and related proteins."

  52. *Identification of the Amino Acid Residues of the Platelet Glycoprotein Ib (GPIb) Essential for the von Willebrand Factor Binding by Clustered Charged-to-Alanine Scanning Mutagenesis 査読有り

    "Shimizu, A., Matsushita, T., Kondo, T., Inden, Y., Kojima, T., Saito, H. and Hirai, M."

    J Biol Chem   279 巻 ( 16 ) 頁: 16285-94   2004年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    At the site of vascular injury, von Willebrand factor (VWF) mediates platelet adhesion to subendothelial connective tissue through binding to the N-terminal domain of the alpha chain of platelet glycoprotein Ib (GPIbalpha). To elucidate the molecular mechanisms of the binding, we have employed charged-to-alanine scanning mutagenesis of the soluble fragment containing the N-terminal 287 amino acids of GPIbalpha. Sixty-two charged amino acids were changed singly or in small clusters, and 38 mutant constructs were expressed in the supernatant of 293T cells. Each mutant was assayed for binding to several monoclonal antibodies for human GPIbalpha and for ristocetin-induced and botrocetin-induced binding of (125)I-labeled human VWF. Mutations at Glu(128), Glu(172), and Asp(175) specifically decreased both ristocetin- and botrocetin-induced VWF binding, suggesting that these sites are important for VWF binding of platelet GPIb. Monoclonal antibody 6D1 inhibited ristocetin- and botrocetin-induced VWF binding, and a mutation at Glu(125) specifically reduced the binding to 6D1. In contrast, antibody HPL7 had no effect for VWF binding, and mutant E121A reduced the HPL7 binding. Mutations at His(12) and Glu(14) decreased the ristocetin-induced VWF binding with normal botrocetin-induced binding. Crystallographic modeling of the VWF-GPIbalpha complex indicated that Glu(128) and Asp(175) form VWF binding sites; the binding of 6D1 to Glu(125) interrupts the VWF binding of Glu(128), but HPL7 binding to Glu(121) has no effect on VWF binding. Moreover, His(12) and Glu(14) contact with Glu(613) and Arg(571) of VWF A1 domain, whose mutations had shown similar phenotype. These findings indicated the novel binding sites required for VWF binding of human GPIbalpha.

  53. Identification of protein Salpha gene mutations including four novel mutations in eight unrelated patients with protein S deficiency 査読有り

    "Okada, H., Takagi, A., Murate, T., Adachi, T., Yamamoto, K., Matsushita, T., Takamatsu, J., Sugita, K., Sugimoto, M., Yoshioka, A., Yamazaki, T., Saito, H. and Kojima, T."

    Br J Haematol   126 巻 ( 2 ) 頁: 219-25   2004年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Eight distinct and potentially causative mutations were identified in eight unrelated Japanese patients with protein S (PS) deficiency, by direct DNA sequencing of the protein Salpha (PSalpha) gene-specific polymerase chain reaction products of all 15 exons and exon/intron boundaries. There were five missense mutations, including two novel mutations (Cys80Tyr and Arg314His), and three showed a major impact on the expected gene products: novel mutations of a 5-bp deletion (delCTCTG887:Cys206Stop) and a nonsense mutation (Glu208Stop), as well as a previously reported splice site (exon 10 +5 A-->G) mutation. One of the patients showed compound heterozygosity for delCTCTG887 and 732A-->G. Investigation for the cosegregation state of these two mutations with PS deficiency in the patient's family suggested that the delCTCTG887 mutation was responsible for the abnormal phenotype and that the 732A-->G (Lys155Glu) mutation did not appear to play a key role. However, we also identified the same 732A-->G (Lys155Glu) mutation in an unrelated patient with apparent PS deficiency with severe pulmonary embolism, and found that this mutation seemed to cosegregate with a PS-deficient state in her family members. These data implied that unknown factor(s) other than the 732A-->G mutation itself might influence phenotypic expression of PS status in different individuals."

  54. *Targeted disruption of mouse ortholog of the human MYH9 responsible for macrothrombocytopenia with different organ involvement: hematological, nephrological, and otological studies of heterozygous KO mice 査読有り

    Matsushita, T., Hayashi, H., Kunishima, S., Hayashi, M., Ikejiri, M., Takeshita, K., Yuzawa, Y., Adachi, T., Hirashima, K., Sone, M., Yamamoto, K., Takagi, A., Katsumi, A., Kawai, K., Nezu, T., Takahashi, M., Nakashima, T., Naoe, T., Kojima, T. and Saito, H.

    Biochem Biophys Res Commun   325 巻 ( 4 ) 頁: 1163-71   2004年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Among three different isoforms of non-muscle myosin heavy chains (NMMHCs), only NMMHCA is associated with inherited human disease, called MYH9 disorders, characterized by macrothrombocytopenia and characteristic granulocyte inclusions. Here targeted gene disruption was performed to understand fundamental as well as pathological role of the gene for NMMHCA, MYH9. Heterozygous intercrosses yielded no homozygous animals among 552 births, suggesting that MYH9 expression is required for embryonic development. In contrast, MYH9+/- mice were viable and fertile without gross anatomical, hematological, and nephrological abnormalities. Immunofluorescence analysis also showed the normal cytoplasmic distribution of NMMHCA. We further measured the auditory brainstem response and found two of six MYH9+/- mice had hearing losses, whereas the remaining four were comparable to wild-type mice. Such observation may parallel the diverse expression of Alport's manifestations of human individuals with MYH9 disorders and suggest the limited requirement of the gene for maintenance and function of specific organs.

  55. First description of somatic mosaicism in MYH9 disorders 査読有り

    "Kunishima, S., Matsushita, T., Yoshihara, T., Nakase, Y., Yokoi, K., Hamaguchi, M. and Saito, H."

    Br J Haematol   128 巻 ( 3 ) 頁: 360-5   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "MYH9 disorders are characterized by giant platelets, thrombocytopenia, and Dohle body-like cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, which encodes non-muscle myosin heavy chain-A (NMMHCA). These disorders are known to be transmitted in an autosomal dominant manner, although about 20% of cases are considered to be sporadic. We report here the first case of a MYH9 disorder because of somatic mosaicism. The patient was the father of a male with typical May-Hegglin anomaly. The father had normal platelet counts, however, both normal-sized and giant platelets were observed on his peripheral blood smears. In addition, 14% of neutrophils contained inclusion bodies and the rest showed a normal morphology. Quantitative fluorescent polymerase chain reaction analysis showed that only 6% of DNA from peripheral blood leucocytes harboured the mutation. The mosaicism was demonstrated at a similar rate in different tissues, buccal mucosa cells and hair bulb cells, implying that the mutation had occurred before gastrulation. Mosaicism might account for some de novo mutations in MYH9 disorders."

  56. Detection of unique neutrophil non-muscle myosin heavy chain-A localization by immunofluorescence analysis in MYH9 disorder presented with macrothrombocytopenia without leukocyte inclusions and deafness 査読有り

    "Kunishima, S., Matsushita, T., Shiratsuchi, M., Ikuta, T., Nishimura, J., Hamaguchi, M., Naoe, T. and Saito, H."

    Eur J Haematol   74 巻 ( 1 ) 頁: 1-5   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "MYH9 disorders are autosomal-dominant macrothrombocytopenias with leukocyte inclusions caused by mutations in the MYH9 gene, which encodes the non-muscle myosin heavy chain-A (NMMHCA). We report a patient with an MYH9 disorder who presented with macrothrombocytopenia without leukocyte inclusions and severe bilateral sensory deafness. Conventional May-Grunwald-Giemsa staining failed to detect granulocyte cytoplasmic inclusions, whereas immunofluorescence analysis clearly demonstrated abnormal neutrophil NMMHCA localization. Genetic analyses revealed a novel heterozygous 18 base deletion in MYH9, leading to a six-amino acid in-frame deletion (N76_S81del) in NMMHCA. These results further support the usefulness of immunofluorescence analysis in differential diagnosis of MYH9 disorders."

  57. Obesity enhances the induction of plasminogen activator inhibitor-1 by restraint stress: a possible mechanism of stress-induced renal fibrin deposition in obese mice 査読有り

    "Yamamoto, K., Kojima, T., Adachi, T., Hayashi, M., Matsushita, T., Takamatsu, J., Loskutoff, D. J. and Saito, H."

    Journal of Thrombosis and Haemostasis   3 巻 ( 7 ) 頁: 1495-1502   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Summary. Background and objectives: Cardiovascular/thrombotic diseases are frequently induced by a variety of stressors. Obese patients are susceptible to thrombotic diseases associated with stress, but the underlying mechanism is still unknown. We have begun to investigate the expression of a primary inhibitor of fibrinolysis, plasminogen activator inhibitor-1 (PAI-1), in association with tissue thrombosis, using restraint-stressed obese mice. Methods and results: We analyzed the expression of PAI-1 after restraint (immobilization) stress in genetically obese mice in comparison with their lean counterparts. Dramatic increases in PAI-1 antigen in plasma and in tissue extracts were observed in the obese mice exposed to restraint stress. The induction of PAI-1 mRNA by stress in the tissues was also pronounced in the stressed obese mice as compared with the lean mice, especially in the hearts and adipose tissues. In situ hybridization analysis revealed that strong signals for PAI-1 mRNA were localized in the adipocytes, cardiovascular endothelial cells, and renal glomerular cells of the stressed obese mice. Histological examination revealed that renal glomerular fibrin deposition was detected only in the obese mice after 2 h of restraint stress. Conclusions: Obesity enhances the stress-mediated PAI-1 induction in the blood and tissues. This phenomenon may be associated with the increased risk of stress-induced renal fibrin deposition in obese subjects."

  58. Integrin activation and matrix binding mediate cellular responses to mechanical stretch 査読有り

    "Katsumi, A., Naoe, T., Matsushita, T., Kaibuchi, K. and Schwartz, M. A."

    J Biol Chem   280 巻 ( 17 ) 頁: 16546-9   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Mechanical tension is a critical determinant of cell growth, differentiation, apoptosis, migration, and development. Integrins have been implicated in sensing force but little is known about how forces are transduced to biochemical signals. We now show that mechanical strain stimulates conformational activation of integrin alphavbeta3 in NIH3T3 cells. Integrin activation is mediated by phosphoinositol 3-kinase and is followed by an increase in integrin binding to extracellular matrix proteins. Mechanical stretch stimulation of JNK was dependent on new integrin binding to extracellular matrix. These data define a molecular mechanism for the role of integrins in mechanotransduction."

  59. Giant platelet syndrome 査読有り

    "Saito, H., Matsushita, T., Yamamoto, K., Kojima, T. and Kunishima, S."

    Hematology   10 Suppl 1 巻   頁: 41-6   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  60. Identification of amino acid residues essential for heparin binding by the A1 domain of human von Willebrand factor 査読有り

    "Adachi, T., Matsushita, T., Dong, Z., Katsumi, A., Nakayama, T., Kojima, T., Saito, H., Sadler, J. E. and Naoe, T."

    Biochem Biophys Res Commun   339 巻 ( 4 ) 頁: 1178-83   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Platelet adhesion is mediated by von Willebrand factor (VWF) that binds platelet glycoprotein Ib (GPIb). Previous observations suggested that heparin competitively inhibits the binding of VWF to GPIb and may down-regulate platelet adhesion. We performed charged-to-alanine scanning mutagenesis of domain A1 and studied dose-dependent binding to heparin-Sepharose beads. Mutations at Lys1362 and Arg1395, at which the GPIb binding was markedly decreased, showed 41% and 42% binding, respectively. Clustered mutations in the segments 1332KDRKR1336 and 1405KKKK1408, which have been proposed as heparin binding sequences, showed 72% and 52% binding, respectively. However, single alanine substitutions within these clusters showed normal binding. Our findings suggest that heparin may inhibit the binding of VWF to GPIb by interacting with GPIb binding and interpret why some hemorrhagic complications of heparin therapy are not predictable based on techniques for monitoring the conventional anticoagulant effects of heparin."

  61. *Fatal thrombosis of antithrombin-deficient mice is rescued differently in the heart and liver by intercrossing with low tissue factor mice 査読有り

    Hayashi, M., Matsushita, T., Mackman, N., Ito, M., Adachi, T., Katsumi, A., Yamamoto, K., Takeshita, K., Kojima, T., Saito, H., Murohara, T. and Naoe, T.

    Journal of Thrombosis and Haemostasis   4 巻 ( 1 ) 頁: 177-185   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Summary. Background: We previously reported that the targeted disruption of murine antithrombin (AT) gene resulted in embryonic lethality before 16.5 gestational days (gd) because of severe cardiac and hepatic thrombosis. Objective and Methods: To investigate the influences of lowered tissue factor (TF) activity upon hypercoagulation of AT-/- embryos, we crossed AT+/- with low TF (mTF-/-hTF+) mice to yield homozygous AT-deficient mice with the extremely low TF activity, that is expressed from the inserted human TF mini gene. Results: AT-/- embryos either with 50% TF (AT-/-mTF+/-hTF+) or with low (~1% TF, AT-/-mTF-/-hTF+) were not born, although the survival was prolonged until 18.5 gd. In both genotypes, histological examination showed disseminated thrombosis in hepatic sinusoidal space or in the portal veins, suggesting that the thrombogenesis caused loss of hepatic blood flow. As in original AT-/-, AT-/-mTF+/-hTF+ showed subcutaneous (s.c.) bleeding and also suffered from the myocardial degeneration apparently because of coronary thrombus formation. However, AT-/-mTF-/-hTF+ had no skin hemorrhage and the thrombosis and degeneration were completely abolished in the heart. Myocardium of adult low TF mice had exhibited fibrosis secondary to hemorrhage; however, it was significantly decreased in low TF mice with AT+/-. Conclusions: Our current model suggests that, in the heart, TF plays an important role in the thrombogenesis and it counterbalances AT-dependent anticoagulation. AT may be a potent anticoagulant during mice development and the activation and subsequent regulation of TF-procoagulant activity take place differently between the liver and the heart. These differences appear to point to local regulatory mechanisms in murine hemostasis.

  62. Anti-HCV agent, ribavirin, elevates the activity of clotting factor VII in patients with hemophilia: a possible mechanism of decreased events of bleeding in patients with hemophilia by ribavirin 査読有り

    "Yamamoto, K., Honda, T., Matsushita, T., Kojima, T. and Takamatsu, J."

    J Thromb Haemost   4 巻 ( 2 ) 頁: 469-70   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  63. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? No, but they need a careful look 招待有り

    Matsushita, T. and Saito, H.

    J Thromb Haemost   4 巻 ( 9 ) 頁: 2066-7   2006年9月

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

  64. "[Approaches to anemia, thrombocytopenia, and DIC in cancer patients]" 査読有り

    "Matsushita, T."

    Gan To Kagaku Ryoho   33 巻 ( 1 ) 頁: 6-12   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    "Patients with cancer-related anemia have an inadequate Epo response that is further impaired by cancer treatments such as chemotherapy. Significant number of studies have demonstrated that treatment of anemia in cancer patients using recombinant human EPO(rHuEPO, epoetin alfa) significantly increases hemoglobin(Hb) levels,reduces transfusion requirements,and improves quality of life,particularly by relieving fatigue. However,the findings of several studies have raised the possibility of an adverse effect of thromboembolism. The American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. In cancer patients, the risk of bleeding depends not only on the platelet count, but also on the underlying disease, in accordance with coagulation defects. The cause of thrombocytopenia must be established prior to platelet transfusion since platelet transfusions may be relatively contraindicated in certain conditions e. g., heparin-induced thrombocytopenia(HIT), and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome(TTP/HUS)."

  65. Classic polyarteritis nodosa presenting rare clinical manifestations in a hemophilia A patient 査読有り

    "Matsushita, T., Adachi, H., Watanabe, H., Shimoyama, Y., Adachi, T., Sobue, G., Ito, M., Kojima, T., Saito, H. and Naoe, T."

    Int. J. Hematol   83 巻   頁: 420-425   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  66. Recurrent Intramural Hematoma of the Small Intestine in a Severe Hemophilia A Patient with a High Titer of Factor VIII Inhibitor: A Case Report and Review of the Literature 査読有り

    Katsumi, A., Matsushita, T., Hirashima, K., Iwasaki, T., Adachi, T., Yamamoto, K., Kojima, T., Takamatsu, J., Saito, H. and Naoe, T.

    Int J Hematol   84 巻 ( 2 ) 頁: 166-9   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  67. Identification of amino acid residues essential for heparin binding by the A1 domain of human von Willebrand factor. 査読有り

    Adachi T, Matsushita T, Dong Z, Katsumi A, Nakayama T, Kojima T, Saito H, Sadler JE, Naoe T.

    Biochem Biophys Res Commun   339 巻   頁: 1178-83   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  68. In vitro characterization of missense mutations associated with quantitative protein S deficiency 査読有り

    Okada, H., Yamazaki, T., Takagi, A., Murate, T., Yamamoto, K., Takamatsu, J., Matsushita, T., Naoe, T., Kunishima, S., Hamaguchi, M., Saito, H. and Kojima, T.

    Journal of Thrombosis and Haemostasis   4 巻 ( 9 ) 頁: 2003-2009   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  69. High titer of ADAMTS13 inhibitor associated with thrombotic microangiopathy of the gut and skeletal muscle after allogenic hematopoietic stem cell transplantation 査読有り

    "Adachi, T., Matsushita, T., Ichihashi, R., Hirashima, K., Ito, M., Inukai, A., Yokozawa, T., Nishida, T., Murata, M., Hayashi, M., Katsumi, A., Kojima, T., Saito, H. and Naoe, T."

    Int. J. Hematol.   83 巻   頁: 415-419   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  70. Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome. 査読有り

    1. Yanada M, Matsushita T, Asou N, Kishimoto Y, Tsuzuki M, Maeda Y, Horikawa K, Okada M, Ohtake S, Yagasaki F, Matsumoto T, Kimura Y, Shinagawa K, Iwanaga M, Miyazaki Y, Ohno R, Naoe T.

    Eur J Haematol   78 巻   頁: 213-219   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  71. Molecular basis of antithrombin deficiency in four Japanese patients with antithrombin gene abnormalities including two novel mutations. 査読有り

    Kyotani M, Okumura K, Takagi A, Murate T, Yamamoto K, Matsushita T, Sugimura M, Kanayama N, Kobayashi T, Saito H, Kojima T.

    Am J Hematol.   82 巻 ( 8 ) 頁: 702-705   2007年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  72. Pitavastatin attenuates the upregulation of tissue factor in restraint-stressed mice. 査読有り

    Yamamoto K, Kojima T, Takeshita K, Matsushita T, Takamatsu J.

    Thromb Res 2007   2007 巻   頁: 143-144   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  73. An Sp1 binding site mutation of the PROS1 promoter in a patient with protein S deficiency. 査読有り

    Sanda N, Fujimori Y, Kashiwagi T, Takagi A, Murate T, Mizutani E, Matsushita T, Naoe T, Kojima T.

    Br J Haematol 2007   138 巻   頁: 663-666   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  74. Haematological characteristics of MYH9 disorders due to MYH9 R702 mutations. 査読有り

    Kunishima S, Yoshinari M, Nishio H, Ida K, Miura T, Matsushita T, Hamaguchi M, Saito H.

    Eur J Haematol.   78 巻 ( 3 ) 頁: 220-226   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  75. Prognostic analysis of aberrant somatic hypermutation of RhoH gene in diffuse large B cell lymphoma. 査読有り

    Hiraga J, Katsumi A, Iwasaki T, Abe A, Kiyoi H, Matsushita T, Kinoshita T, Naoe T.

    Leukemia.   21 巻 ( 8 ) 頁: 1846-1847   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  76. Paratope and epitope mapping of the antithrombotic antibody 6B4 in complex with platelet glycoprotein Ibalpha. 査読有り

    Fontayne A, De Maeyer B, De Maeyer M, Yamashita M, Matsushita T, Deckmyn H.

      282 巻 ( 32 ) 頁: 23517-23524   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  77. A neonate with homozygous protein C deficiency with a homozygous Arg178Trp mutation. 査読有り

    Ozlu F, Kyotani M, Taskin E, Ozcan K, Kojima T, Matsushita T, Yapicioğlu H, Takagi A, Saşmaz I, Satar M, Narli N

    J Pediatr Hematol Oncol   30 巻   頁: 608-611   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  78. A new binding assay of von Willebrand factor and glycoprotein Ib using solid-phase biotinylated platelets.

    Hayata K, Nakayama T, Matsushita T, Sakano K

    J Pharmacol Sci.   108 巻   頁: 217-221   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  79. Mutational analysis of SOS1 gene in acute myeloid leukemia. 査読有り

    Tanizaki R, Katsumi A, Kiyoi H, Kunishima S, Iwasaki T, Ishikawa Y, Kobayashi M, Abe A, Matsushita T, Watanabe T, Kojima T, Kaibuchi K, Kojima S, Naoe T.

    Int J Hematol.   88 巻   頁: 460-462   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  80. Identification and characterization of the first large deletion of the MYH9 gene associated with MYH9 disorders. 査読有り

    Kunishima S, Matsushita T, Hamaguchi M, Saito H

    Eur J Haematol.   80 巻   頁: 540-544   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  81. Identification of amino acid residues responsible for von Willebrand factor binding to sulfatide by charged-to-alanine-scanning mutagenesis. 査読有り

    Nakayama T, Matsushita T, Yamamoto K, Mutsuga N, Kojima T, Katsumi A, Nakao N, Sadler JE, Naoe T, Saito H

    Int J Hematol   87 巻   頁: 363-370   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  82. Prognostic implication and biological roles of RhoH in acute myeloid leukaemia. 査読有り

    Iwasaki T, Katsumi A, Kiyoi H, Tanizaki R, Ishikawa Y, Ozeki K, Kobayashi M, Abe A, Matsushita T, Watanabe T, Amano M, Kojima T, Kaibuchi K, Naoe T

    Eur J Haematol.   81 巻   頁: 454-460   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  83. Ablation of angiotensin IV receptor attenuates hypofibrinolysis via PAI-1 downregulation and reduces occlusive arterial thrombosis. 査読有り

    Numaguchi Y, Ishii M, Kubota R, Morita Y, Yamamoto K, Matsushita T, Okumura K, Murohara T

    Arterioscler Thromb Vasc Biol.   29 巻   頁: 2102-2108   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  84. A novel missense mutation causing abnormal LMAN1 in a Japanese patient with combined deficiency of factor V and factor VIII. 査読有り

    Yamada T, Fujimori Y, Suzuki A, Miyawaki Y, Takagi A, Murate T, Sano M, Matsushita T, Saito H, Kojima T

    Am J Hematol.   84 巻   頁: 738-742   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  85. Definite diagnosis in Japanese patients with protein C deficiency by identification of causative PROC mutations. 査読有り

    Takagi A, Tanaka R, Nakashima D, Fujimori Y, Yamada T, Okumura K, Murate T, Yamada M, Horikoshi Y, Yamamoto K, Katsumi A, Matsushita T, Naoe T, Kojima T.

    Int J Hematol.   89 巻   頁: 555-557   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  86. A novel splice site mutation in intron C of PROS1 leads to markedly reduced mutant mRNA level, absence of thrombin-sensitive region, and impaired secretion and cofactor activity of mutant protein S. 査読有り

    Okada H, Kunishima S, Hamaguchi M, Takagi A, Yamamoto K, Takamatsu J, Matsushita T, Saito H, Kojima T, Yamazaki T.

    Thromb Res.   125 巻   頁: e246-250   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  87. Irrespective of CD34 expression, lineage-committed cell fraction reconstitutes and re-establishes transformed Philadelphia chromosome-positive leukemia in NOD/SCID/IL-2Rgammac-/- mice. 査読有り

    Tanizaki R, Nomura Y, Miyata Y, Minami Y, Abe A, Hanamura A, Sawa M, Murata M, Kiyoi H, Matsushita T, Naoe T.

    Cancer Sci.   101 巻   頁: 631-638   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  88. Heterozygous antithrombin deficiency improves in vivo haemostasis in factor VIII-deficient mice. 査読有り

    Bolliger D, Szlam F, Suzuki N, Matsushita T, Tanaka KA

    Thromb Haemost.   103 巻   頁: 1233-1238   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  89. Severe hemophilia A in a Japanese female caused by an F8-intron 22 inversion associated with skewed X chromosome inactivation. 査読有り

    Miyawaki Y, Suzuki A, Fujimori Y, Takagi A, Murate T, Suzuki N, Katsumi A, Naoe T, Yamamoto K, Matsushita T, Takamatsu J, Kojima T.

    Int J Hematol.   92 巻   頁: 405-408   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  90. Impaired secretion of carboxyl-terminal truncated factor VII due to an F7 nonsense mutation associated with FVII deficiency. 査読有り

    Tanaka R, Nakashima D, Suzuki A, Miyawaki Y, Fujimori Y, Yamada T, Takagi A, Murate T, Yamamoto K, Katsumi A, Matsushita T, Naoe T, Kojima T.

    Thromb Res.   125 巻   頁: 262-266   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  91. Successful fertility management of a patient with factor V deficiency: planned transfusion of fresh frozen plasma under infertility treatment. 査読有り

    Iwase A, Goto M, Manabe S, Hirokawa W, Kobayashi H, Nakahara T, Takikawa S, Kotani T, Sumigama S, Tsuda H, Nakayama T, Suzuki N, Matsushita T, Kikkawa F.

    Fertil Steril.   95 巻   頁: 2124.e5-7   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  92. Pitavastatin-induced angiogenesis and arteriogenesis is mediated by Notch1 in a murine hindlimb ischemia model without induction of VEGF. 査読有り

    Kikuchi R, Takeshita K, Uchida Y, Kondo M, Cheng XW, Nakayama T, Yamamoto K, Matsushita T, Liao JK, Murohara T.

    Lab Invest.   91 巻   頁: 691-703   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  93. Virus-associated hemophagocytic syndrome caused by pandemic swine-origin influenza A (H1N1) in a patient after unrelated bone marrow transplantation. 査読有り

    Katsumi A, Nishida T, Murata M, Terakura S, Shimada K, Saito S, Kobayashi M, Kodaira A, Shibata S, Oda I, Yagi T, Kiyoi H, Matsushita T, Kojima T, Naoe T.

    J Clin Exp Hematop.   51 巻   頁: 63-65   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  94. FLT/ITD regulates leukemia cell adhesion thruough α4β1 integrin ando Pyk2 signalling. 査読有り

    Katsumi A, Kiyoi H, Abe A, Tanizaki R, Iwasaki T, Kobayashi M, Matsushita T, Kaibuchi K, Senga T, Kojima T, Kohno T, Hamaguchi M, Naoe T.

    Eur J Haematol.   86 巻   頁: 191-198   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  95. A novel ENG mutation causing impaired co-translational processing of endoglin associated with hereditary hemorrhagic telangiectasia. 査読有り

    Suzuki A, Nakashima D, Miyawaki Y, Fujita J, Maki A, Fujimori Y, Takagi A, Murate T, Teranishi M, Matsushita T, Saito H, Kojima T.

    Thromb Res.   129 巻   頁: e200-208   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  96. Increased von Willebrand Factor to ADAMTS13 ratio as a predictor of thrombotic complications following a major hepatectomy. 査読有り

    Kobayashi S, Yokoyama Y, Matsushita T, Kainuma M, Ebata T, Igami T, Sugawara G, Takahashi Y, Nagino M.

    Arch Surg.   147 巻   頁: 909-917   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  97. Thrombosis from a prothrombin mutation conveying antithrombin resistance. 査読有り

    Miyawaki Y, Suzuki A, Fujita J, Maki A, Okuyama E, Murata M, Takagi A, Murate T, Kunishima S, Sakai M, Okamoto K, Matsushita T, Naoe T, Saito H, Kojima T.

    N Engl J Med.   366 巻   頁: 2390-2396   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  98. Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: a randomized controlled trial. 査読有り

    de Paula EV, Kavakli K, Mahlangu J, Ayob Y, Lentz SR, Morfini M, Nemes L, Šalek SZ, Shima M, Windyga J, Ehrenforth S, Chuansumrit A

    J Thromb Haemost.   10 巻   頁: 81-89   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  99. Stress augments insulin resistance and prothrombotic state: role of visceral adipose-derived monocyte chemoattractant protein-1. 査読有り

    Uchida Y, Takeshita K, Yamamoto K, Kikuchi R, Nakayama T, Nomura M, Cheng XW, Egashira K, Matsushita T, Nakamura H, Murohara T.

    Diabetes.   61 巻   頁: 1552-1561   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  100. VWF-Gly2752Ser, a novel non-cysteine substitution variant in the CK domain, exhibits severe secretory impairment by hampering C-terminal dimer formation.

    Okamoto S, Tamura S, Sanda N, Odaira K, Hayakawa Y, Mukaide M, Suzuki A, Kanematsu T, Hayakawa F, Katsumi A, Kiyoi H, Kojima T, Matsushita T, Suzuki N

    Journal of thrombosis and haemostasis : JTH     2022年5月

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    記述言語:英語  

    DOI: 10.1111/jth.15746

    PubMed

  101. F9 mRNA splicing aberration due to a deep Intronic structural variation in a patient with moderate hemophilia B.

    Odaira K, Kawashima F, Tamura S, Suzuki N, Tokoro M, Hayakawa Y, Suzuki A, Kanematsu T, Okamoto S, Takagi A, Katsumi A, Matsushita T, Shima M, Nogami K, Kojima T, Hayakawa F

    Thrombosis research   213 巻   頁: 91 - 96   2022年5月

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    記述言語:英語  

    DOI: 10.1016/j.thromres.2022.03.010

    PubMed

  102. Medical Management of a Mural Thrombus Inducing Repeated Ischemic Strokes in a Patient with Congenital Afibrinogenemia.

    Nishihori M, Araki Y, Suzuki N, Tamura S, Hattori M, Izumi T, Goto S, Yokoyama K, Uda K, Matsushita T, Saito R

    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association   31 巻 ( 7 ) 頁: 106526   2022年4月

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  103. Indoxyl Sulfate Activates NLRP3 Inflammasome to Induce Cardiac Contractile Dysfunction Accompanied by Myocardial Fibrosis and Hypertrophy

    Yamaguchi Kazutoshi, Yisireyili Maimaiti, Goto Sumie, Cheng Xian Wu, Nakayama Takayuki, Matsushita Tadashi, Niwa Toshimitsu, Murohara Toyoaki, Takeshita Kyosuke

    CARDIOVASCULAR TOXICOLOGY   22 巻 ( 4 ) 頁: 365 - 377   2022年4月

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  104. International consensus recommendations on the management of people with haemophilia B

    Hart Daniel P., Matino Davide, Astermark Jan, Dolan Gerard, d'Oiron Roseline, Hermans Cedric, Jimenez-Yuste Victor, Linares Adriana, Matsushita Tadashi, McRae Simon, Ozelo Margareth C., Platton Sean, Stafford Darrel, Sidonio Robert F. Jr., Tiede Andreas

    THERAPEUTIC ADVANCES IN HEMATOLOGY   13 巻   頁: 20406207221085202   2022年4月

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  105. Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors.

    Shapiro AD, Angchaisuksiri P, Astermark J, Benson G, Castaman G, Eichler H, Jiménez-Yuste V, Kavakli K, Matsushita T, Poulsen LH, Wheeler AP, Young G, Zupancic-Salek S, Oldenburg J, Chowdary P

    Blood advances     2022年3月

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    記述言語:英語  

    DOI: 10.1182/bloodadvances.2021006403

    PubMed

  106. Periosteum-derived podoplanin-expressing stromal cells regulate nascent vascularization during epiphyseal marrow development.

    Tamura S, Mukaide M, Katsuragi Y, Fujii W, Odaira K, Suzuki N, Tsukiji N, Okamoto S, Suzuki A, Kanematsu T, Katsumi A, Takagi A, Ikeda K, Ueyama J, Hirayama M, Suzuki-Inoue K, Matsushita T, Kojima T, Hayakawa F

    The Journal of biological chemistry   298 巻 ( 5 ) 頁: 101833   2022年3月

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    記述言語:英語  

    DOI: 10.1016/j.jbc.2022.101833

    PubMed

  107. International Society of Blood Transfusion survey of experiences of blood banks and transfusion services during the COVID-19 pandemic

    Al-Riyami Arwa Z., Burnouf Thierry, Wood Erica M., Devine Dana V., Oreh Adaeze, Apelseth Torunn Oveland, Goel Ruchikha, Bloch Evan M., van den Berg Karin, Getshen Mahrukh, Louw Vernon, Ang Ai Leen, Lee Cheuk Kwong, Rahimi-Levene Naomi, Stramer Susan L., Vassallo Ralph, Schulze Torsten J., Patidar Gopal Kumar, Pandey Hem Chandra, Dubey Rounak, Badawi Maha, Hindawi Salwa, Meshi Abdullah, Matsushita Tadashi, Sorrentino Enrico, Grubovic Rastvorceva Rada M., Bazin Renee, Vermeulen Marion, Nahirniak Susan, Tsang Hamilton C., Vrielink Hans, Triyono Teguh, Addas-Carvalho Marcelo, Hecimovic Ana, Torres Oscar W., Mutindu Samclide M., Bengtsson Jesper, Dominguez Diego, Sayedahmed Ahmed, Hanisa Musa Rozi, Gautam Bipul, Herczenik Eszter, So-Osman Cynthia

    VOX SANGUINIS     2022年3月

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    記述言語:日本語  

    DOI: 10.1111/vox.13256

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  108. AKATSUKI study: a prospective, multicentre, phase IV study evaluating the safety of emicizumab under and immediately after immune tolerance induction therapy in persons with congenital haemophilia A with factor VIII inhibitors

    Matsushita Tadashi, Suzuki Nobuaki, Nagao Azusa, Nagae Chiai, Yamaguchi-Suita Haruko, Kyogoku Yui, Ioka Akiko, Nogami Keiji

    BMJ OPEN   12 巻 ( 3 ) 頁: e057018   2022年3月

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  109. Assessment of global coagulation function under treatment with emicizumab concomitantly with bypassing agents in haemophilia A with inhibitor (UNEBI Study): multicentre open-label non-randomised clinical trial

    Ogiwara Kenichi, Taki Masashi, Suzuki Takashi, Takedani Hideyuki, Matsushita Tadashi, Amano Kagehiro, Matsumoto Masanori, Nishio Kenji, Shima Midori, Kasahara Masato, Nogami Keiji

    BMJ OPEN   12 巻 ( 2 ) 頁: e056922   2022年2月

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  110. SURGERIES AND DIAGNOSTIC PROCEDURES IN HAEMOPHILIA PATIENTS ON CONCIZUMAB PROPHYLAXIS IN PHASE 2 CLINICAL TRIALS

    Wheeler A., Benson G., Eichler H., Tonder S. M., Cepo K., Jimenez-Yuste V., Kavakli K., Wong L. L., Matsushita T.

    HAEMOPHILIA   28 巻   頁: 92 - 92   2022年2月

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    記述言語:日本語  

    Web of Science

  111. SECOND INTERIM ANALYSIS OF THE PHASE IV HEM-POWR STUDY EVALUATING THE REAL-WORLD EFFECTIVENESS AND SAFETY OF DAMOCTOCOG ALFA PEGOL IN PREVIOUSLY TREATED PATIENTS WITH HAEMOPHILIA A

    Reding M. T., Roman M. T. Alvarez, Sanabria M., Castaman G., Janbain M., Matsushita T., Meijer K., Schmidt K., Oldenburg J.

    HAEMOPHILIA   28 巻   頁: 89 - 90   2022年2月

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    記述言語:日本語  

    Web of Science

  112. Protein S-Leu17Pro disrupts the hydrophobicity of its signal peptide causing a proteasome-dependent degradation.

    Okada K, Tamura S, Suzuki N, Odaira K, Mukaide M, Fujii W, Katsuragi Y, Suzuki A, Kanematsu T, Okamoto S, Suzuki N, Katsumi A, Matsushita T, Kojima T, Hayakawa F

    Thrombosis research   210 巻   頁: 26 - 32   2022年2月

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    記述言語:英語  

    DOI: 10.1016/j.thromres.2021.12.014

    PubMed

  113. DOSE OPTIMISATION AND RISK MITIGATION DURING CONCIZUMAB PROPHYLAXIS IN PATIENTS WITH HAEMOPHILIA A/B WITH AND WITHOUT INHIBITORS IN PHASE 3 CLINICAL TRIALS

    Chowdary P., Eichler H., Matsushita T., Rose T. H., Ruzanski C., Seremetis S.

    HAEMOPHILIA   28 巻   頁: 27 - 27   2022年2月

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    記述言語:日本語  

    Web of Science

  114. Development and validation of a novel qualitative test for plasma fibrinogen utilizing clot waveform analysis

    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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  115. International Forum on the Management of Major Haemorrhage: Responses

    Green Laura, Stanworth Simon, McQuilten Zoe, Lin Victor, Tucker Harriet, Jackson Bryon, Badawi Maha, Hindawi Salwa, Chaurasia Rahul, Patidar Gopal, Pandey Hem Chandra, Fasola Foluke, Miyata Shigeki, Matsumoto Masanori, Matsushita Tadashi, Rahimi-Levene Naomi, Peer Victoria, Pavenski Katerina, Callum Jeannie, Thompson Troy, Murphy Michael, Staves Julie, Maegele Marc, Abeyakoon Chathuri, Rushford Kylie, Wood Erica, Nunez Maria Antonieta, Mellado Sandra, Saa Edgardo, Triyono Teguh, Pratomo Bhirowo, Apelseth Torunn Oveland, Dunbar Nancy

    VOX SANGUINIS     2022年1月

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    記述言語:日本語  

    DOI: 10.1111/vox.13243

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  116. International Forum on the Management of Major Haemorrhage: Summary.

    Green L, Stanworth S, McQuilten Z, Lin V, Tucker H, Jackson B, Badawi M, Hindawi S, Chaurasia R, Patidar G, Pandey HC, Fasola F, Miyata S, Matsumoto M, Matsushita T, Rahimi-Levene N, Peer V, Pavenski K, Callum J, Thompson T, Murphy M, Staves J, Maegele M, Abeyakoon C, Rushford K, Wood E, Nuñez MA, Mellado S, Saa E, Triyono T, Pratomo B, Apelseth TO, Dunbar N

    Vox sanguinis     2022年1月

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    記述言語:英語  

    DOI: 10.1111/vox.13244

    PubMed

  117. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia HCC after HCV eradication in hemophilia

    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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  118. Feasibility of the automated column agglutination technique for titration of anti-A/B antibodies in ABO-incompatible living kidney transplantation

    Matsuura Hideaki, Sugiura Yukari, Matsuno Takahiro, Tomiya Yume, Shiraki Mari, Kato Chiaki, Ishihara Keiko, Fukami Harue, Niwa Reiko, Hayashi Megumi, Matsushita Tadashi, Kato Hidefumi, Watarai Yoshihiko, Ito Taihei, Kenmochi Takashi, Fujii Sumie, Miura Yasuo

    THERAPEUTIC APHERESIS AND DIALYSIS     2021年12月

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    記述言語:日本語  

    DOI: 10.1111/1744-9987.13764

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  119. A POST-HOC ANALYSIS OF TEMPORARILY DECREASED INCREMENTAL RECOVERY (IR) OBSERVED IN A SUBSET OF PREVIOUSLY UNTREATED PATIENTS (PUPS) WITH HAEMOPHILIA A TREATED WITH N8-GP

    Male C., Konigs C., Dey S., Matsushita T., Millner Holm A., Sonnergren H., Young G., Kenet G.

    HAEMATOLOGICA   106 巻 ( 9 ) 頁: 13 - 13   2021年9月

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    記述言語:日本語  

    Web of Science

  120. THE SAFETY AND EFFICACY OF N8-GP IN PREVIOUSLY UNTREATED PATIENTS (PUPS) WITH SEVERE HAEMOPHILIA A: INTERIM RESULTS FROM THE MAIN AND EXTENSION PHASES OF PATHFINDER6

    Kenet G., Konigs C., Dey S., Matsushita T., Millner Holm A., Sonnergren H., Young G., Male C.

    HAEMATOLOGICA   106 巻 ( 9 ) 頁: 6 - 7   2021年9月

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    記述言語:日本語  

    Web of Science

  121. Notch1 haploinsufficiency in mice accelerates adipogenesis

    Yamaguchi Kazutoshi, Hayashi Motoharu, Uchida Yasuhiro, Cheng Xian Wu, Nakayama Takayuki, Matsushita Tadashi, Murohara Toyoaki, Takeshita Kyosuke

    SCIENTIFIC REPORTS   11 巻 ( 1 ) 頁: 16761   2021年8月

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  122. Anemia in older adults as a geriatric syndrome: A review

    Katsumi Akira, Abe Akihiro, Tamura Shogo, Matsushita Tadashi

    GERIATRICS & GERONTOLOGY INTERNATIONAL   21 巻 ( 7 ) 頁: 549 - 554   2021年7月

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    記述言語:日本語  

    DOI: 10.1111/ggi.14183

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  123. Concomitant use of bypassing agents with emicizumab for people with haemophilia A and inhibitors undergoing surgery

    Jimenez-Yuste Victor, Carlos Rodriguez-Merchan E., Matsushita Tadashi, Andre Holme Pal

    HAEMOPHILIA   27 巻 ( 4 ) 頁: 519 - 530   2021年7月

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    記述言語:日本語  

    DOI: 10.1111/hae.14322

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  124. Clopidogrel response predicts thromboembolic events associated with coil embolization of unruptured intracranial aneurysms: A prospective cohort study

    Higashi Eiji, Matsumoto Shoji, Nakahara Ichiro, Hatano Taketo, Ishii Akira, Sadamasa Nobutake, Ohta Tsuyoshi, Ishihara Takuma, Tokunaga Keisuke, Ando Mitsushige, Chihara Hideo, Furuta Konosuke, Hashimoto Tetsuya, Tanaka Koji, Sonoda Kazutaka, Koge Junpei, Takita Wataru, Hashikawa Takuro, Funakoshi Yusuke, Kondo Daisuke, Kamata Takahiko, Tsujimoto Atsushi, Matsushita Takuya, Murai Hiroyuki, Matsuo Keitaro, Kitazono Takanari, Kira Junichi

    PLOS ONE   16 巻 ( 4 )   2021年4月

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    記述言語:日本語  

    DOI: 10.1371/journal.pone.0249766

    Web of Science

  125. Essential role of a carboxyl-terminal alpha-helix motif in the secretion of coagulation factor XI

    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  

    DOI: 10.1111/jth.15242

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  126. Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation

    Goto Tatsunori, Murata Makoto, Nishida Tetsuya, Terakura Seitaro, Kamoshita Sonoko, Ishikawa Yuichi, Ushijima Yoko, Adachi Yoshiya, Suzuki Satoshi, Kato Katsuyoshi, Hirakawa Akihiro, Nishiwaki Satoshi, Nishio Nobuhiro, Takahashi Yoshiyuki, Kodera Yoshihisa, Matsushita Tadashi, Kiyoi Hitoshi

    STEM CELLS TRANSLATIONAL MEDICINE   10 巻 ( 4 ) 頁: 542 - 553   2021年4月

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    記述言語:日本語  

    DOI: 10.1002/sctm.20-0381

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  127. Vascular endothelial growth factor (VEGF)-A and VEGF-A(165)b are associated with time to remission of granulomatosis with polyangiitis in a nationwide Japanese prospective cohort study

    Kikuchi Ryosuke, Tsuboi Naotake, Sada Ken-Ei, Nakatochi Masahiro, Yokoe Yuki, Suzuki Atsuo, Maruyama Shoichi, Murohara Toyoaki, Matsushita Tadashi, Amano Koichi, Atsumi Tatsuya, Takasaki Yoshinari, Ito Satoshi, Hasegawa Hitoshi, Dobashi Hiroaki, Ito Takafumi, Makino Hirofumi, Matsuo Seiichi

    ANNALS OF CLINICAL BIOCHEMISTRY   58 巻 ( 2 ) 頁: 86 - 94   2021年3月

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  128. Impact of variation in reagent combinations for one-stage clotting assay on assay discrepancy in nonsevere haemophilia A

    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  

    DOI: 10.1111/ijlh.13335

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  129. SAFETY AND LONGER-TERM EFFICACY OF CONCIZUMAB PROPHYLAXIS IN PATIENTS WITH HAEMOPHILIA A OR B WITH INHIBITORS: RESULTS FROM THE EXTENSION PART OF THE PHASE 2 EXPLORER4 TRIAL

    Shapiro A., Castaman G., Cepo K., Tonder S. M., Matsushita T., Poulsen L. Hvitfeldt, Young G., Zupancic-Salek S., Jimenez Yuste V.

    HAEMOPHILIA   27 巻   頁: 128 - 128   2021年2月

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    記述言語:日本語  

    Web of Science

  130. Myh9 R702C is associated with erythroid abnormality with splenomegaly in mice

    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  

    DOI: 10.18999/nagjms.83.1.75

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  131. Long-term safety and efficacy of emicizumab for up to 5.8 years and patients' perceptions of symptoms and daily life: A phase 1/2 study in patients with severe haemophilia A

    Shima Midori, Nagao Azusa, Taki Masashi, Matsushita Tadashi, Oshida Koichi, Amano Kagehiro, Nagami Sayaka, Okada Norihiro, Maisawa Shingo, Nogami Keiji

    HAEMOPHILIA   27 巻 ( 1 ) 頁: 81 - 89   2021年1月

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  132. Safety and efficacy of percutaneous radiofrequency ablation for hepatocellular carcinoma patients with haemophilia

    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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  133. Design of the HEM-POWR study: a prospective, observational study of real-world treatment with damoctocog alfa pegol in patients with haemophilia A

    Sanabria Martin, Alvarez Roman Maria Teresa, Castaman Giancarlo, Janbain Maissaa, Matsushita Tadashi, Meijer Karina, Oldenburg Johannes, Friedl Sabine, Reding M. T.

    BMJ OPEN   11 巻 ( 9 ) 頁: e044997   2021年

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  134. [The diagnosis and management of von Willebrand disease].

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    [Rinsho ketsueki] The Japanese journal of clinical hematology   62 巻 ( 8 ) 頁: 1205 - 1212   2021年

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    DOI: 10.11406/rinketsu.62.1205

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  135. [The management strategy for von Willebrand disease].

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    [Rinsho ketsueki] The Japanese journal of clinical hematology   62 巻 ( 5 ) 頁: 435 - 444   2021年

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    DOI: 10.11406/rinketsu.62.435

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  136. Long-term safety and sustained efficacy for up to 5 years of treatment with recombinant factor IX Fc fusion protein in subjects with haemophilia B: Results from the B-YOND extension study

    Pasi K. John, Fischer Kathelijn, Ragni Margaret, Kulkarni Roshni, Ozelo Margareth C., Mahlangu Johnny, Shapiro Amy, P'Ng Stephanie, Chambost Herve, Nolan Beatrice, Bennett Carolyn, Matsushita Tadashi, Winding Bent, Fruebis Joachim, Yuan Huixing, Rudin Dan, Oldenburg Johannes

    HAEMOPHILIA   26 巻 ( 6 ) 頁: E262 - E271   2020年11月

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    DOI: 10.1111/hae.14036

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  137. Theory for High-Angular-Resolution Photoelectron Holograms Considering the Inelastic Mean Free Path and the Formation Mechanism of Quasi-Kikuchi Band

    Matsushita Tomohiro, Muro Takayuki, Yokoya Takayoshi, Terashima Kensei, Kato Yukako, Matsui Hirosuke, Maejima Naoyuki, Hashimoto Yusuke, Matsui Fumihiko

    PHYSICA STATUS SOLIDI B-BASIC SOLID STATE PHYSICS   257 巻 ( 11 )   2020年11月

  138. Aberrant X chromosomal rearrangement through multi-step template switching during sister chromatid formation in a patient with severe hemophilia A

    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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    DOI: 10.1002/mgg3.1390

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  139. An overview of the pathfinder clinical trials program: Long-term efficacy and safety of N8-GP in patients with hemophilia A

    Matsushita Tadashi, Mangles Sarah

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS   18 巻   頁: 26 - 33   2020年9月

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    DOI: 10.1111/jth.14958

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  140. A Japanese multi-institutional collaborative study of antigen-positive red blood cell (RBC) transfusions in patients with corresponding RBC antibodies

    Yamada Chiaki, Takeshita Akihiro, Ohto Hitoshi, Ishimaru Ken, Kawabata Kinuyo, Nomaguchi Yuriko, Haraguchi Yasue, Abe Misao, Sobue Koki, Takenouchi Hiroyuki, Takadate Junko, Kamimura Masami, Katai Akiko, Kasai Daisuke, Minami Yumiko, Sugimoto Tatsuya, Michino Junko, Nagai Kazuhiro, Kumagai Mikako, Hasegawa Yuichi, Ishizuka Keiko, Ohtomo Naoki, Yamada Naotomo, Muroi Kazuo, Matsushita Tadashi, Takahashi Koki

    VOX SANGUINIS   115 巻 ( 5 ) 頁: 456 - 465   2020年7月

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    DOI: 10.1111/vox.12906

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  141. A survey of blood transfusion errors in Aichi Prefecture in Japan: Identifying major lapses threatening the safety of transfusion recipients

    Ri Masaki, Kasai Masanobu, Kohno Akio, Kondo Masaru, Sawa Masashi, Kinoshita Tomohiro, Sugiura Isamu, Miura Yasuo, Yamamoto Kazuhito, Saito Toshiki I, Ozawa Yukiyasu, Matsushita Tadashi, Kato Hidefumi

    TRANSFUSION AND APHERESIS SCIENCE   59 巻 ( 3 ) 頁: 102735   2020年6月

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  142. Higher FVIII:C measured by chromogenic substrate assay than by one-stage assay is associated with silent hemophilic arthropathy

    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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  143. An experimental setup for creating and imaging He-4(2)* excimer cluster tracers in superfluid helium-4 via neutron-He-3 absorption reaction

    Sonnenschein V, Tsuji Y., Kokuryu S., Kubo W., Suzuki S., Tomita H., Kiyanagi Y., Iguchi T., Matsushita T., Wada N., Kitaguchi M., Shimizu H. M., Hirota K., Shinohara T., Hiroi K., Hayashida H., Guo W., Ito D., Saito Y.

    REVIEW OF SCIENTIFIC INSTRUMENTS   91 巻 ( 3 )   2020年3月

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  144. REAL-WORLD EFFECTIVENESS AND SAFETY OF BAY 94-9027 ( DAMOCTOCOG ALFA PEGOL) IN PREVIOUSLY TREATED PATIENTS WITH HAEMOPHILIA A (HEM-POWR): ONLINE PATIENT PORTAL AND LIFE-ACTIVE SUB-STUDY

    Oldenburg J., Roman M. T. Alvarez, Castaman G., Janbain M., Matsushita T., Meijer K., Friedl S., Sanabria M., Reding M.

    HAEMOPHILIA   26 巻   頁: 100 - 101   2020年2月

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    記述言語:日本語  

    Web of Science

  145. Safety and efficacy of turoctocog alfa in the prevention and treatment of bleeds in previously untreated paediatric patients with severe haemophilia A: Results from the guardian 4 multinational clinical trial

    Yaish Hassan, Matsushita Tadashi, Belhani Meriem, Jimenez-Yuste Victor, Kavakli Kaan, Korsholm Lars, Matytsina Irina, Philipp Claire, Reichwald Kirsten, Wu Runhui

    HAEMOPHILIA   26 巻 ( 1 ) 頁: 64 - 72   2020年1月

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    記述言語:日本語  

    DOI: 10.1111/hae.13883

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  146. Indoxyl Sulfate-induced Vascular Calcification is mediated through Altered Notch Signaling Pathway in Vascular Smooth Muscle Cells

    Yamaguchi Kazutoshi, Yisireyili Maimaiti, Goto Sumie, Kato Katsuhiro, Cheng Xian Wu, Nakayama Takayuki, Matsushita Tadashi, Niwa Toshimitsu, Murohara Toyoaki, Takeshita Kyosuke

    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES   17 巻 ( 17 ) 頁: 2703 - 2717   2020年

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    記述言語:日本語  

    DOI: 10.7150/ijms.43184

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  147. Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results

    Shapiro Amy D., Angchaisuksiri Pantep, Astermark Jan, Benson Gary, Castaman Giancarlo, Chowdary Pratima, Eichler Hermann, Jimenez-Yuste Victor, Kavakli Kaan, Matsushita Tadashi, Poulsen Lone Hvitfeldt, Wheeler Allison P., Young Guy, Zupancic-Salek Silva, Oldenburg Johannes

    BLOOD   134 巻 ( 22 ) 頁: 1973 - 1982   2019年11月

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  148. Efficacy and Safety of Subcutaneous Prophylaxis with Concizumab in Patients with Hemophilia a or B with Inhibitors: Results from explorer4, a Phase 2, Randomized, Open-Label, Controlled Trial

    Shapiro Amy, Castaman Giancarlo, Cepo Katarina, Poulsen Lone Hvitfeldt, Hollensen Christian, Matsushita Tadashi, Young Guy, Zupancic-Salek Silva, Jimenez-Yuste Victor

    BLOOD   134 巻   2019年11月

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    記述言語:日本語  

    DOI: 10.1182/blood-2019-122809

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  149. Phase I Study of Cord Blood Transplantation with Intra-Bone Marrow Injection of Mesenchymal Stem Cells

    Goto Tatsunori, Murata Makoto, Nishida Tetsuya, Terakura Seitaro, Kamoshita Sonoko, Ishikawa Yuichi, Ushijima Yoko, Adachi Yoshiya, Kato Katsuyoshi, Hirakawa Akihiro, Nishiwaki Satoshi, Nishio Nobuhiro, Takahashi Yoshiyuki, Kodera Yoshihisa, Matsushita Tadashi, Kiyoi Hitoshi

    BLOOD   134 巻   2019年11月

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    記述言語:日本語  

    DOI: 10.1182/blood-2019-122101

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  150. Real-World Effectiveness and Safety of BAY 94-9027 (Damoctocog Alfa Pegol) in Previously Treated Patients with Hemophilia A (HEM-POWR): Online Patient Portal and LIFE-ACTIVE Sub-Study

    Oldenburg Johannes, Roman Maria Teresa Alvarez, Castaman Giancarlo, Janbain Maissaa, Matsushita Tadashi, Meijer Karina, Friedl Sabine, Sanabria Martin, Reding Mark

    BLOOD   134 巻   2019年11月

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    記述言語:日本語  

    DOI: 10.1182/blood-2019-128140

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  151. Systematic review and analysis of efficacy of recombinant factor IX products for prophylactic treatment of hemophilia B in comparison with rIX-FP

    Davis Joanna, Yan Songkai, Matsushita Tadashi, Alberio Lorenzo, Bassett Paul, Santagostino Elena

    JOURNAL OF MEDICAL ECONOMICS   22 巻 ( 10 ) 頁: 1014 - 1021   2019年10月

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  152. Performance evaluation of Revohem((TM)) FVIII chromogenic and Revohem((TM)) FIX chromogenic in the CS-5100 autoanalyser

    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  

    DOI: 10.1111/ijlh.13083

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  153. Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors.

    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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  154. LIFE-ACTIVE: OBSERVATIONAL STUDY EVALUATING THE PHYSICAL ACTIVITY IN A SUBSET OF DAM OCT OCOG ALFA PEGOL TREATED HEMOPHILIA A PATIENTS WHO ARE ENROLLED IN THE HEM- POWR STUDY

    Musi E., Sanabria M., Alvarez Roman M. T., Castaman G., Janbain M., Matsushita T., Meijer K., Oldenburg J., Friedl S., Reding M.

    HAEMATOLOGICA   104 巻   頁: 16 - 16   2019年9月

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    記述言語:日本語  

    Web of Science

  155. Management of Neonatal Alloimmune Thrombocytopenia in Type 1 CD36 Deficiency Pregnant Women

    Matsushita Tadashi, Sanda Naomi, Watanabe Tomomi, Endo Hiroko, Kato Chiaki

    TRANSFUSION   59 巻   頁: 130A - 130A   2019年9月

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    記述言語:日本語  

    Web of Science

  156. Apolipoprotein E binds to and reduces serum levels of DNA-mimicking, pyrrolated proteins

    Hirose Sayumi, Hioki Yusuke, Miyashita Hiroaki, Hirade Naoya, Yoshitake Jun, Shibata Takahiro, Kikuchi Ryosuke, Matsushita Tadashi, Chikazawa Miho, Itakura Masanori, Zhang Mimin, Nagata Koji, Uchida Koji

    JOURNAL OF BIOLOGICAL CHEMISTRY   294 巻 ( 28 ) 頁: 11035 - 11045   2019年7月

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  157. Apparent synonymous mutation F9 c.87A > G causes secretion failure by in-frame mutation with aberrant splicing

    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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  158. Ischaemic events are rare, and the prevalence of hypertension is not high in Japanese adults with haemophilia: First multicentre study in Asia

    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  

    DOI: 10.1111/hae.13749

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  159. Postmarketing safety and effectiveness of recombinant factor IX (nonacog alfa) in Japanese patients with haemophilia B

    Fukutake Katsuyuki, Taki Masashi, Matsushita Tadashi, Sakai Michio, Takata Ami, Yamaguchi Hiromi, Karumori Toshiyuki

    HAEMOPHILIA   25 巻 ( 4 ) 頁: E247 - E256   2019年7月

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    記述言語:日本語  

    DOI: 10.1111/hae.13783

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  160. Molecular basis of SERPINC1 mutations in Japanese patients with antithrombin deficiency

    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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  161. Factor VIII: Long-established role in haemophilia A and emerging evidence beyond haemostasis

    Bannow Bethany Samuelson, Recht Michael, Negrier Claude, Hermans Cedric, Berntorp Erik, Eichler Hermann, Mancuso Maria Elisa, Klamroth Robert, O'Hara Jamie, Santagostino Elena, Matsushita Tadashi, Kessler Craig

    BLOOD REVIEWS   35 巻   頁: 43 - 50   2019年5月

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  162. Inhibitor development, safety and efficacy of Advate((R)) among previously treated patients with hemophilia A in a postmarketing surveillance in Japan

    Fukutake Katsuyuki, Taki Masashi, Matsushita Tadashi, Nogami Keiji, Shima Midori, Yoshioka Akira, Takamatsu Junki, Uchikawa Haruhiko, Takagi Hiroshi, Arai Morio, Engl Werner, Shirahata Akira

    INTERNATIONAL JOURNAL OF HEMATOLOGY   109 巻 ( 3 ) 頁: 336 - 345   2019年3月

  163. Clot waveform analysis in Clauss fibrinogen assay contributes to classification of fibrinogen disorders

    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

  164. Inhibitor development, safety, and efficacy of Advate (R) in previously untreated patients with hemophilia A in a postmarketing surveillance in Japan (vol 109, pg 70, 2019)

    Taki Masashi, Fukutake Katsuyuki, Matsushita Tadashi, Nogami Keiji, Shima Midori, Yoshioka Akira, Takamatsu Junki, Arai Morio, Takagi Hiroshi, Uchikawa Haruhiko, Engl Werner, Shirahata Akira

    INTERNATIONAL JOURNAL OF HEMATOLOGY   109 巻 ( 2 ) 頁: 241 - 241   2019年2月

  165. Inhibitor development, safety, and efficacy of Advate((R)) in previously untreated patients with hemophilia A in a postmarketing surveillance in Japan

    Taki Masashi, Fukutake Katsuyuki, Matsushita Tadashi, Nogami Keiji, Shima Midori, Yoshioka Akira, Takamatsu Junki, Arai Morio, Takagi Hiroshi, Uchikawa Haruhiko, Engl Werner, Shirahata Akira

    INTERNATIONAL JOURNAL OF HEMATOLOGY   109 巻 ( 1 ) 頁: 70 - 78   2019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)  

    DOI: 10.1007/s12185-018-2499-y

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  166. B-YOND Final Results Confirm Established Safety, Sustained Efficacy, and Extended Dosing Interval for Up to 4 Years of Treatment With rFIXFc in Previously Treated Subjects With Severe Hemophilia B

    Ragni Margaret, Kulkarni Roshni, Pasi K. John, Fischer Kathelijn, Mahlangu Johnny, Shapiro Amy, Nolan Beatrice, Oldenburg Johannes, Matsushita Tadashi, Willemze Annemieke, Yuan Huixing, Rudin Dan

    BLOOD   132 巻   2018年11月

  167. Chronic Inflammatory Demyelinating Polyneuropathy With Concurrent Membranous Nephropathy: An Anti-paranode and Podocyte Protein Antibody Study and Literature Survey

    Hashimoto Yu, Ogata Hidenori, Yamasaki Ryo, Sasaguri Takakazu, Ko Senri, Yamashita Kenichiro, Xu Zhang, Matsushita Takuya, Tateishi Takahisa, Akiyama Shin'ichi, Maruyama Shoichi, Yamamoto Akifumi, Kira Jun-ichi

    FRONTIERS IN NEUROLOGY   9 巻   2018年11月

  168. Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15% in patients with haemophilia B: Pooled data from the paradigm (TM) trials

    Oldenburg Johannes, Carcao Manuel, Lentz Steven R., Mahlangu Johnny, Mancuso Maria Elisa, Matsushita Tadashi, Negrier Claude, Clausen Wan Hui Ong, Ehrenforth Silke, Young Guy

    HAEMOPHILIA   24 巻 ( 6 ) 頁: 911 - 920   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/hae.13608

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  169. Characterization of lntraoperative Motor Evoked Potential Monitoring for Surgery of the Pediatric Population with Brain Tumors

    Motomura Kazuya, Sumita Kayo, Chalise Lushun, Nishikawa Tomohide, Tanahashi Kuniaki, Ohka Fumiharu, Aoki Kosuke, Hirano Masaki, Nakamura Tomohiko, Matsushita Tadashi, Wakabayashi Toshihiko, Natsume Atsushi

    WORLD NEUROSURGERY   119 巻   頁: E1052 - E1059   2018年11月

  170. Identification of the novel deletion-type PML-RARA mutation associated with the retinoic acid resistance in acute promyelocytic leukemia

    Hattori Hikaru, Ishikawa Yuichi, Kawashima Naomi, Akashi Akimi, Yamaguchi Yohei, Harada Yasuhiko, Hirano Daiki, Adachi Yoshiya, Miyao Kotaro, Ushijima Yoko, Terakura Seitaro, Nishida Tetsuya, Matsushita Tadashi, Kiyoi Hitoshi

    PLOS ONE   13 巻 ( 10 ) 頁: e0204850   2018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: 10.1371/journal.pone.0204850

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  171. The Japanese Immune Tolerance Induction (J-ITI) study in haemophilia patients with inhibitor: Outcomes and successful predictors of ITI treatment

    Nogami K., Taki M., Matsushita T., Ohga S., Oka T., Horikoshi Y., Amano K., Shima M.

    HAEMOPHILIA   24 巻 ( 5 ) 頁: E328 - E337   2018年9月

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  172. Perioperative safety and hemostatic efficacy of Advate(A (R)) in patients with hemophilia A in a postmarketing surveillance in Japan

    Nogami Keiji, Takedani Hideyuki, Shima Midori, Yoshioka Akira, Matsushita Tadashi, Takamatsu Junki, Taki Masashi, Fukutake Katsuyuki, Uchikawa Haruhiko, Takagi Hiroshi, Arai Morio, Engl Werner, Shirahata Akira

    INTERNATIONAL JOURNAL OF HEMATOLOGY   108 巻 ( 1 ) 頁: 22 - 29   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12185-018-2434-2

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  173. Changes in bleeding and daily life with emicizumab prophylaxis: a questionnaire in patients with hemophilia A with inhibitors (PwHAwI) and their families in a long-term phase 1/2 study

    Suzuki Takashi, Taki Masashi, Matsushita Tadashi, Sato Tetsuji, Fukutake Katsuyuki, Kasai Ryu, Okada Norihiro, Maisawa Shingo, Nogami Keiji, Shima Midori

    HAEMOPHILIA   24 巻   頁: 32-32   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)  

    Web of Science

  174. Surgical Experience in Two Multicentre, Open-label Phase 3 Studies of Emicizumab in Persons with Haemophilia A with Inhibitors (HAVEN 1 and HAVEN 2)

    Kruse-Jarres R., Callaghan M., Croteau S. E., Jimenez-Yuste V., Khoo L., Liesner R., Matsushita T., Recht M., Young G., Chang T., Dhalluin C., Mu Y., Xu J., Devenport J., Ko R., Solari P., Oldenburg J.

    BRITISH JOURNAL OF HAEMATOLOGY   181 巻   頁: 128-128   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Web of Science

  175. Angiotensin receptor blocker irbesartan reduces stress-induced intestinal inflammation via AT1a signaling and ACE2-dependent mechanism in mice

    Yisireyili Maimaiti, Uchida Yasuhiro, Yamamoto Koji, Nakayama Takayuki, Cheng Xian Wu, Matsushita Tadashi, Nakamura Shigeo, Murohara Toyoaki, Takeshita Kyosuke

    BRAIN BEHAVIOR AND IMMUNITY   69 巻   頁: 167 - 179   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbi.2017.11.010

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

    Sanda N, Suzuki N, Suzuki A, Kanematsu T, Kishimoto M, Hasuwa H, Takagi A, Kojima T, Matsushita T, Nakamura S

    International journal of hematology     2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12185-017-2394-y

    PubMed

  177. Guardian (TM) 4: safety and efficacy of turoctocog alfa in prevention and treatment of bleeds in previously untreated patients with hemophilia A

    Ozelo M., Wu R., Belhani M., Lebedev V., Yaish H., Korsholm L., Matytsina I., Matsushita T.

    HAEMOPHILIA   24 巻   頁: 101-102   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Web of Science

  178. Structural and functional insights into S-thiolation of human serum albumins

    Nakashima Fumie, Shibata Takahiro, Kamiya Kohei, Yoshitake Jun, Kikuchi Ryosuke, Matsushita Tadashi, Ishii Isao, Gimenez-Bastida Juan A., Schneider Claus, Uchida Koji

    SCIENTIFIC REPORTS   8 巻 ( 1 ) 頁: 932   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)  

    DOI: 10.1038/s41598-018-19610-9

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  179. 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

    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)  

    DOI: 10.1111/hae.13360

    Web of Science

  180. Efficacy and safety of full-length pegylated recombinant factor VIII with extended half-life in previously treated patients with hemophilia A: comparison of data between the general and Japanese study populations (vol 106, pg 704, 2017)

    Nogami Keiji, Shima Midori, Fukutake Katsuyuki, Fujii Teruhisa, Taki Masashi, Matsushita Tadashi, Higasa Satoshi, Sato Tetsuji, Sakai Michio, Arai Morio, Uchikawa Haruhiko, Engl Werner, Abbuehl Brigitt, Konkle Barbara A.

    INTERNATIONAL JOURNAL OF HEMATOLOGY   107 巻 ( 1 ) 頁: 123 - 124   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)  

    DOI: 10.1007/s12185-017-2369-z

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    PubMed

  181. Pyrometallurgical Separation of Indium Phosphide through the Phosphorous Removal by Iron and the Chlorination Process Utilizing Ammonium Chloride

    Terakado Osamu, Matsushita Taishi, Tani Haruki, Hirasawa Masahiro

    MATERIALS TRANSACTIONS   59 巻 ( 6 ) 頁: 984 - 988   2018年

  182. Efficacy of Early Fusion With Local Bone Graft and Platelet-Rich Plasma in Lumbar Spinal Fusion Surgery FollowedOver 10 Years

    Imagama Shiro, Ando Kei, Kobayashi Kazuyoshi, Ishikawa Yoshimoto, Nakamura Hiroshi, Hida Tetsuro, Ito Kenyu, Tsushima Mikito, Matsumoto Akiyuki, Morozumi Masayoshi, Tanaka Satoshi, Machino Masaaki, Ota Kyotaro, Nakashima Hiroaki, Takamatsu Junki, Matsushita Tadashi, Nishida Yoshihiro, Ishiguro Naoki, Matsuyama Yukihiro

    GLOBAL SPINE JOURNAL   7 巻 ( 8 ) 頁: 749 - 755   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1177/2192568217696690

    Web of Science

    PubMed

  183. Urinary and circulating levels of the anti-angiogenic isoform of vascular endothelial growth factor-A in patients with chronic kidney disease

    Kikuchi Ryosuke, Yasuda Yoshinari, Nakatochi Masahiro, Shibata Yohei, Hara Toshiaki, Suzuki Atsuo, Imaizumi Takahiro, Suzuki Susumu, Ishii Hideki, Takeshita Kyosuke, Matsushita Tadashi, Maruyama Shoichi, Murohara Toyoaki

    CLINICA CHIMICA ACTA   475 巻   頁: 102 - 108   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.cca.2017.10.014

    Web of Science

    PubMed

  184. Efficacy and safety of full-length pegylated recombinant factor VIII with extended half-life in previously treated patients with hemophilia A: comparison of data between the general and Japanese study populations

    Nogami Keiji, Shima Midori, Fukutake Katsuyuki, Fujii Teruhisa, Taki Masashi, Matsushita Tadashi, Higasa Satoshi, Sato Tetsuji, Sakai Michio, Arai Morio, Uchikawa Haruhiko, Engl Werner, Abbuehl Brigitt, Konkle Barbara A.

    INTERNATIONAL JOURNAL OF HEMATOLOGY   106 巻 ( 5 ) 頁: 704 - 710   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12185-017-2265-6

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    PubMed

  185. Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors

    Shima Midori, Hanabusa Hideji, Taki Masashi, Matsushita Tadashi, Sato Tetsuji, Fukutake Katsuyuki, Kasai Ryu, Yoneyama Koichiro, Yoshida Hiroki, Nogami Keiji

    BLOOD ADVANCES   1 巻 ( 22 ) 頁: 1891 - 1899   2017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: 10.1182/bloodadvances.2017006684

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    PubMed

  186. Successful Blood Transfusion Management of a Living Donor Liver Transplant Recipient in the Presence of Anti-Jr(a): A Case Report

    Kurata N., Onishi Y., Kamei H., Hori T., Komagome M., Kato C., Matsushita T., Ogura Y.

    TRANSPLANTATION PROCEEDINGS   49 巻 ( 7 ) 頁: 1604-1607   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.transproceed.2017.06.009

    Web of Science

  187. Phase II study of intrabone single unit cord blood transplantation for hematological malignancies

    Murata Makoto, Maeda Yoshinobu, Masuko Masayoshi, Onishi Yasushi, Endo Tomoyuki, Terakura Seitaro, Ishikawa Yuichi, Iriyama Chisako, Ushijima Yoko, Goto Tatsunori, Fujii Nobuharu, Tanimoto Mitsune, Kobayashi Hironori, Shibasaki Yasuhiko, Fukuhara Noriko, Inamoto Yoshihiro, Suzuki Ritsuro, Kodera Yoshihisa, Matsushita Tadashi, Kiyoi Hitoshi, Naoe Tomoki, Nishida Tetsuya

    CANCER SCIENCE   108 巻 ( 8 ) 頁: 1634 - 1639   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/cas.13291

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    PubMed

  188. Pharmacokinetics of a novel extended half-life glycoPEGylated factor IX, nonacog beta pegol (N9-GP) in previously treated patients with haemophilia B: results from two phase 3 clinical trials

    Tiede A., Abdul-Karim F., Carcao M., Persson P., Clausen W. H. O., Kearney S., Matsushita T., Negrier C., Oldenburg J., Santagostino E., Young G.

    HAEMOPHILIA   23 巻 ( 4 ) 頁: 547-555   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/hae.13191

    Web of Science

  189. Adductome-based identification of biomarkers for lipid peroxidation

    Shibata Takahiro, Shimizu Kazuma, Hirano Keita, Nakashima Fumie, Kikuchi Ryosuke, Matsushita Tadashi, Uchida Koji

    JOURNAL OF BIOLOGICAL CHEMISTRY   292 巻 ( 20 ) 頁: 8223 - 8235   2017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)  

    DOI: 10.1074/jbc.M116.762609

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    PubMed

  190. Xanthine oxidase inhibition by febuxostat attenuates stress-induced hyperuricemia, glucose dysmetabolism, and prothrombotic state in mice

    Yisireyili Maimaiti, Hayashi Motoharu, Wu Hongxian, Uchida Yasuhiro, Yamamoto Koji, Kikuchi Ryosuke, Hamrah Mohammad Shoaib, Nakayama Takayuki, Cheng Xian Wu, Matsushita Tadashi, Nakamura Shigeo, Niwa Toshimitsu, Murohara Toyoaki, Takeshita Kyosuke

    SCIENTIFIC REPORTS   7 巻 ( 1 ) 頁: 1266   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-017-01366-3

    Web of Science

    PubMed

  191. Long-term Efficacy of Recombinant Factor IX Fc Fusion Protein (rFIXFc) Prophylaxis in Adults, Adolescents, and Children With Hemophilia B: Longitudinal Analysis of B-LONG, Kids B-LONG, and B-YOND

    Kulkarni R., Ragni M., Mahlangu J., Shapiro A., Oldenburg J., Matsushita T., Nolan B., Feng J., Winding B., Ramirez-Santiago A., Barnowski C.

    HAEMOPHILIA   23 巻   頁: 23-24   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Web of Science

  192. Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B

    Pasi K. John, Fischer Kathelijn, Ragni Margaret, Nolan Beatrice, Perry David J., Kulkarni Roshni, Ozelo Margareth, Mahlangu Johnny, Shapiro Amy D., Baker Ross I., Bennett Carolyn M., Barnes Christopher, Oldenburg Johannes, Matsushita Tadashi, Yuan Huixing, Ramirez-Santiago Alejandra, Pierce Glenn F., Allen Geoffrey, Mei Baisong

    THROMBOSIS AND HAEMOSTASIS   117 巻 ( 3 ) 頁: 508-518   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1160/TH16-05-0398

    Web of Science

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

    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:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/hae.13082

    Web of Science

  194. Individualised Prophylaxis with Recombinant Factor IX FC Fusion Protein (RFIXFC) in Adults/Adolescents With Haemophilia B: Updated Interim Results of the B-YOND Extension Study

    Mahlangu J. N., Shapiro A. D., Pasi K. J., Ragni M. V., Ozelo M. C., Oldenburg J., Matsushita T., Baker R. I., Yuan H., Ferrante F., Ramirez-Santiago A., Lethagen S., Barnowski C.

    HAEMOPHILIA   23 巻   頁: 85-86   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Web of Science

  195. A phase III clinical trial of a mixture agent of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors

    Shinkoda Y., Shirahata A., Fukutake K., Takamatsu J., Shima M., Hanabusa H., Mugishima H., Takedani H., Kawasugi K., Taki M., Matsushita T., Tawa A., Nogami K., Higasa S., Kosaka Y., Fujii T., Sakai M., Migita M., Uchiba M., Kawakami K., Sameshima K., Ohashi Y., Saito H.

    HAEMOPHILIA   23 巻 ( 1 ) 頁: 59-66   2017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)  

    DOI: 10.1111/hae.13050

    Web of Science

  196. [Biomarkers of Leukemia ~Description of the Practical Use and Operation in the Clinical Laboratory~]-.

    Kajiura Y, Yamamoto Y, Okada K, Hattori H, Matsumoto H, Kishimoto M, Matsushita T

    Rinsho byori. The Japanese journal of clinical pathology   65 巻 ( 1 ) 頁: 93 - 99   2017年1月

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  197. Acquired immune-mediated von Willebrand syndrome accompanied by antiphospholipid syndrome.

    Kobayashi N, Ogawa Y, Yanagisawa K, Ishizaki T, Uchiumi H, Suzuki N, Matsushita T, Ichinose A, Handa H

    [Rinsho ketsueki] The Japanese journal of clinical hematology   58 巻 ( 6 ) 頁: 613-618   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.11406/rinketsu.58.613

    PubMed

▼全件表示

科研費 5

  1. 血管増殖におけるVWF-HBDの同定と抑制型VEGFアイソフォームとの相互作用

    研究課題/研究課題番号:20K08711  2020年4月 - 2023年3月

    科学研究費助成事業  基盤研究(C)

    松下 正, 鈴木 伸明, 菊地 良介

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    担当区分:研究代表者 

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

    VWFは、そのヘパリン結合ドメインがGFに結合し、創傷治癒において血管新生を促進するという新しい機能が近年指摘されている。我々はVWFのヘパリン結合部位 (HBD)をin vitroでピンポイント同定しており、本研究ではこの結合部位のVWFの血管新生機能における重要性を検討、一部のVWD患者に見られる血管新生障害の原因としての「血管新生抑制型VEGF-Aアイソフォーム(VEGF-A165b)」の負の影響を検討することにより、血漿・内皮細胞由来のVWFがヘパリンへの結合を介して血管外マトリックスへ結合することにより、どのようにGFの血管新生を調節するか明らかにする。
    フォン・ウィルブランド因子 (VWF)のヘパリン結合ドメインは成長因子(Growth factor: GF)に結合し、創傷治癒において血管新生を促進する。近年、GFの結合による治癒において血漿および内皮細胞から放出されるVWFがヘパリンへの結合様式のもと血管外マトリックスへ結合することにより、血管新生を調節することが示されている。そのため、止血以外のVWFの重要な機能である可能性がある。本研究ではVWFのヘパリン結合部位のVWFの血管新生機能における重要性を検討、続いて当グループが新たに同定した「血管新生抑制型VEGF-Aアイソフォーム(VEGF-A165b)」がどのような影響を持つのかを検討する。
    ECFCの作製
    同意を得て分離したVWD type 1、type 2A、type 3 各typeの患者単核球からBOECs(以後ECFCと改称)を樹立した。
    対象例:・健常・type2A(GroupⅠ): L1503R・type3(Null): E2341X+Y2631X
    単核球はVEGF存在下で培養後典型的なcobblestone形態をとるので、PhenotypeをCD31, CD309等の発現にてフローサイトメトリーにて確認、上清中にVEGF-A165-VWF複合体またはVEGF-A165b-VWF複合体が存在するかを免疫沈降と抗ヒトVWF抗体によるWestern blottingにて確認した。患者血漿についても同様に検討してある。ECFCについてはポリクローナルELISA (DAKO A0082とP226を使用)にて、VWFの細胞学的な発現様式をconfocal immunofluorescenceにて観察中である。これと同時にWeibel-Palade小体に局在するVWF、VEGF-A165、VEGF-A165bの共在につき、抗P-selectin, IL-8, CD63抗体とあわせて検討する。観察を行った細胞はLysateを調整し、Western blottingにてVEGF-A165、165b、VWFのプロセシングを確認、初期実験ではLysateにてVWF:Agが確認された。
    PAD患者のVWF血中濃度については順調に進行しているが、VEGF-A165およびVEGF-A165b のヘパリン結合能については、精製VEGF-A165およびVEGF-A165b蛋白の調達にやや遅れが生じている。
    野生マウス/VWFノックアウトマウスを用いた以下の検討は今回のプロジェクトのポイントであり、今年度は早期にマウス個体数を増加させる。すなわちHBDのアミノ酸をピンポイントで同定する目的でVWFノックアウトマウスに対してhydrodynamic injectionによりヘパリン結合を欠くmutant VWFを発現させる。マウスにwild typeまたはmutant VWF cDNAをコードする発現ベクターpsvVWF1 (Matsushita, T., et al., J Biol Chem, 2000)をhydrodynamic injectionによりマウス肝において強制発現する。PBSに希釈したPlasmid DNA (50mg)溶液はマウス体重の10%となるよう調整する。プラスミドはマウス尾静脈より7秒以内に急速静注することにより肝に一過性に発現される。採血によりヒトVWF蛋白が発現されたことをSandwich ELISAで確認し、検討に用いる。

  2. BOECを用いたvon Willebrand病の細胞科学的的解析と治療への応用

    研究課題/研究課題番号:17K09902  2017年4月 - 2020年3月

    松下 正

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    担当区分:研究代表者 

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

    本研究では、VWD患者末梢血から単離した血管内皮前駆細胞(EPCs)を培養して得た患者に直接由来する血管内皮細胞(Endothelial Colony forming cells (ECFC))を用い、免疫蛍光染色法やELISA法を駆使してDominant遺伝子変異によるVWF発現の影響を免疫蛍光染色法やELISA法等で遺伝子変異によるVWF発現の影響を精査して分子病態的に解明した。ついでECFCにおけるDDAVP刺激によるVWDの放出がおこるが本研究では刺激後の細胞学的なVWFの輸送・分泌状況を観察し、患者ごとに異なるDDAVPに対する反応性の差の細胞学的背景を同定することが可能になった。
    von Willebrand病(VWD)の疾患頻度は血友病に次ぐとされているが、正しく診断されていない症例が多数存在する可能性が高い。また本症は優性遺伝形式を取るが、どのようなdominant-negative mechanismでVWFのmutationが疾患をもたらすのか、細胞遺伝学的に明らかになっていない。本研究により従来のTransfectionによる発現検討より生理的な優性遺伝形式を取るVWDにおけるDominant-negativeな細胞学的な機構を詳細に検討を行うことができた。今回得られたDDAVPの最適な分泌刺激方法により新たなVWD治療の基盤モデルとなることが期待された。

  3. アンチトロンビン・レジスタンスの新規変異探索とマウスモデルによる病態解析研究

    研究課題/研究課題番号:16K09825  2016年4月 - 2019年3月

    小嶋 哲人

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    担当区分:研究分担者 

    新しい血栓性素因・アンチトロンビン・レシスタンス(ATR)を示すプロトロンビン異常症(R596L)を報告、さらにATR検出検査法を確立して異なる変異(R596Q)も同定した。またNa+結合領域アミノ酸での単一塩基置換変異体の凝固活性特性を調べた結果、K599RおよびE592Qでは既報変異と同等のATR残存凝固活性を示した。さらにR593L (ヒトR596Lに相当)ノックインマウスは正常出生してATRを示したものの、プロトロンビンの抗原量70%、凝固一段法活性35%と低値で、ATR残存凝固活性が低値で、ヒトR596L変異と異なりR593L変異ホモマウスでは血栓リスクの可能性は低いと思われた。
    静脈血栓塞栓症の遺伝子異常判明例の約2/3は原因特定に至っていない中、申請者らが世界で初めて報告した新たな血栓性素因概念 アンチトロンビン・レジスタンス(ATR)の遺伝子異常を検索・解析は、従来にない独創的な発想の研究である。
    本研究は、これまで原因特定に至ってない症例でのATR血栓性素因の同定とその詳細な病態解析、遺伝子組換体による新たなATR遺伝子異常の同定解析、ATRマウスの血栓症発症病態解析を行うもので、加齢とともに増加する深部静脈血栓・肺塞栓症の新しい診断法や予防法、治療法の開発に極めて有用な情報を提供することが予想され、超高齢化社会を迎えつつある日本において大きな社会的意義をもつ。

  4. ヒトiPSおよび新規遺伝子改変マウスを用いたネフローゼ症候群の病因解明

    研究課題/研究課題番号:15H04880  2015年4月 - 2018年3月

    関根 孝司

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    担当区分:研究分担者 

    本年度は足細胞特異的にR702変異myosin IIAを発現するマウスの作成を中心に研究を行い、以下のような成果を得た。
    名古屋大学より供与されたMYH9-R702Cneo♂マウス精子と京都大学医学系研究科・横井秀基先生より供与されたNPHS2-CreERT2♀マウスの卵を用いて人工授精し、仮親に移植した。NPHS2-CreERT2/MYH9-R702Cneoダブルヘテロ5匹、MYH9-R702Cneoシングルヘテロ4匹、野生型14匹の♂マウスが得られ、これらをそれぞれ2群に分けた上、生後4週齢にて1群に4-hydroxytamoxifen (4-OHT)腹腔内投与(0.5mg/匹、3日連続投与)を行った(参考文献1)。投与後4週間目より毎週1回、代謝ケージを用いて24時間尿を回収し、SDS-PAGEによりアルブミンのバンドを観察してその濃さによりタンパク尿を評価した。NPHS2-CreERT2/MYH9-R702Cneoダブルヘテロマウス・4-OHT投与群にのみ、投与後5週目より有意な蛋白尿が観察され、10週目には明瞭、17週目には極めて顕著となった。投与後11週目に各群1匹、18週目に残余の動物を屠殺し、腎臓を光学顕微鏡および電子顕微鏡観察のためサンプリングした。11週目に採取した腎臓の組織を用いて免疫組織学的な解析を行い、スリット膜分子(ネフリン)のシグナルの低下とミオシンIIAの糸球体係蹄に沿った束状の集積がNPHS2-CreERT2 / MYH9-R702Cneoダブルヘテロマウス・4-OHT投与群にのみ観察された。同じマウスの腎組織を電子顕微鏡で観察したところ、足突起の消失に伴う足細胞の扁平化とスリット膜の消失が顕著であり、扁平化した細胞の基底側にアクチン線維が束状に集積していた。さらに、一部の細胞では尿腔側で細胞質の断片化が起こっておりアポトーシスに類似した形態変化を示した。以上のことから、足細胞特異的にR702変異myosin IIAの発現を後天的に誘導することにより、細胞骨格系の制御機構が変化することで足細胞の形態変化を引き起こし、糸球体濾過機能が低下した結果、蛋白尿が検出されたと考えられた。
    参考文献1 : Yokoi et al., Nephrol Dial Transplant 2010
    本年度はR702変異myosin IIAが正常な足細胞に発現されることでどのような変化が起こるかを明らかにするために、MYH9-R702Cneo♂マウスとNPHS2-CreERT2♀マウスを掛け合わせてダブルヘテロマウスを作成し、マウスが出生後に変異ミオシンの発現をタモキシフエンで誘導する系を確立することを中心に研究を進めた結果、変異ミオシンの発現を誘導したマウスでのみ蛋白尿が検出され、さらに形態学的な変化を捉えることに成功した。この成果は世界で初めてin vivoで変異ミオシンが足細胞に及ぼす影響を捉えたものである。このモデル動物の系を用いることで変異ミオシンの発現によりin vivo足細胞においてどのような機能上変化が起こっているかを分子レベルで明らかにしていくことが可能となり、病態の詳細な解析と治療薬開発にも多大な貢献をするものと期待される。

  5. モノクローナル抗体によるTMA治療モデルの確立

    2007年

    科学研究費補助金  基盤研究(C)(一般),課題番号:19591104

    松下 正

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    担当区分:研究代表者