11 results on '"Morio Arai"'
Search Results
2. Perioperative safety and hemostatic efficacy of Advate
- Author
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Keiji, Nogami, Hideyuki, Takedani, Midori, Shima, Akira, Yoshioka, Tadashi, Matsushita, Junki, Takamatsu, Masashi, Taki, Katsuyuki, Fukutake, Haruhiko, Uchikawa, Hiroshi, Takagi, Morio, Arai, Werner, Engl, and Akira, Shirahata
- Subjects
Adult ,Male ,Factor VIII ,Adolescent ,Infant ,Middle Aged ,Hemophilia A ,Hemostatics ,Recombinant Proteins ,Young Adult ,Treatment Outcome ,Japan ,Child, Preschool ,Product Surveillance, Postmarketing ,Humans ,Female ,Child ,Infusions, Intravenous ,Aged - Abstract
Rurioctocog alfa (recombinant factor VIII: Advate
- Published
- 2017
3. 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
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Midori Shima, Tadashi Matsushita, Haruhiko Uchikawa, Teruhisa Fujii, Katsuyuki Fukutake, Tetsuji Sato, Michio Sakai, Werner Engl, Brigitt E. Abbuehl, Barbara A. Konkle, Masashi Taki, Morio Arai, Keiji Nogami, and Satoshi Higasa
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Population ,Hemorrhage ,030204 cardiovascular system & hematology ,Hemophilia A ,Recombinant factor viii ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Japan ,Internal medicine ,Post-hoc analysis ,medicine ,Humans ,education ,Child ,Aged ,education.field_of_study ,Hematology ,Factor VIII ,business.industry ,Half-life ,Middle Aged ,Surgery ,Tolerability ,030220 oncology & carcinogenesis ,Female ,Previously treated ,business - Abstract
Rurioctocog alfa pegol (BAX 855) is a novel third-generation recombinant factor VIII whose active ingredient is chemically modified with polyethylene glycol. A global multicenter phase 2/3 study of the product in 137 patients (including 11 patients from Japan) with severe hemophilia A aged 12–65 years, reported an extended half-life and a good tolerability profile, as well as a significantly lower annualized bleeding rate in the prophylactic treatment arm than in the on-demand treatment arm. Using descriptive statistics, a post hoc analysis was performed to compare the pharmacokinetics, safety, and efficacy profiles of the product in the Japanese subpopulation and the overall population. Extended half-life was demonstrated in the Japanese subpopulation. The mean [standard deviation (SD)] annualized bleeding rates in the prophylactic treatment arm were 3.7 (4.7) for the overall population (n = 120) and 4.0 (3.4) for the Japanese subpopulation (n = 11). The proportion of bleeds reported as excellent or good was 94.9% (149/157) in the overall population, whereas that in the Japanese subpopulation was 92.3% (12/13). No FVIII inhibition or anaphylactic reaction was reported in the Japanese subpopulation. The post hoc comparisons demonstrated similar pharmacokinetic, safety, and efficacy profiles between the overall population and the Japanese subpopulation.
- Published
- 2017
4. Novel Bernard-Soulier syndrome variants caused by compound heterozygous mutations (case I) or a cytoplasmic tail truncation (case II) of GPIbα
- Author
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Naomasa Yamamoto, Kohji Kasahara, Susumu Mitsuyama, Hitoshi Sakuraba, Haruo Nogami, Noriko Akamatsu, Kazuhiko Matsuno, Ryota Hosoya, and Morio Arai
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Adult ,Blood Platelets ,Heterozygote ,Nonsense mutation ,Platelet membrane glycoprotein ,Bernard–Soulier syndrome ,Young Adult ,chemistry.chemical_compound ,medicine ,Humans ,Platelet ,Amino Acid Sequence ,Platelet activation ,Ristocetin ,Sequence Deletion ,Genetics ,Chemistry ,Ristocetin-induced platelet aggregation ,Bernard-Soulier Syndrome ,Hematology ,medicine.disease ,Molecular biology ,GP1BA ,Platelet Glycoprotein GPIb-IX Complex ,Mutation ,Female - Abstract
A defective platelet glycoprotein (GP) Ib/IX/V complex [von Willebrand factor (VWF) receptor] results in Bernard-Soulier syndrome (BSS), which is characterized by macrothrombocytopenia and impaired ristocetin- and thrombin-induced platelet aggregation. We found 2 independent BSS-variant families: Case I [compound heterozygous mutations, p.Glu331X and a frame shift by a deletion at c.1444delA of GPIbα (GP1BA) terminating at a premature stop codon (p.Thr452ProfsX58)], and case II [homozygous nonsense mutation at c.1723C > T, p.Gln545X]. Case I platelets expressed no GPIbα, resulting in absence of ristocetin-induced platelet aggregation (RIPA) and 50% reduction in thrombin-induced aggregation with no shape change. The mother's platelets had 50% the expression level of A-type GPIbα (4-repeated VNTR: variable number of tandem repeats, p.[Thr145Met; Ser399_Pro411[4]]); the father's platelets had the same expression level of C-type GPIbα (2-repeated VNTR, p.Ser399_Pro411dup) as the mother's platelets. The mother's RIPA was significantly higher than the father's. Thrombin-induced aggregation was normal in both parents. Case II platelets expressed a GPIbα with an abnormal cytoplasmic tail, p.Gln545X-truncated GPIbα, which complexed with GPIX and GPV on the cell surface; its expression level of the complex was normal. Case II platelets had reversible RIPA, with no ATP release, and weak thrombin-induced aggregation without shape change. These results suggest that a signaling process through the GPIbα cytoplasmic tail required for full platelet activation is defective in BSS variant case II and a length polymorphism of GPIbα is associated with a modified level of RIPA heterozygous BSS case I.
- Published
- 2013
5. Five Novel and four recurrent point mutations in the antithrombin gene causing venous thrombosis
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Midori Suzuki, Katsuyuki Fukutake, Morio Arai, Keiko Nagaizumi, Hiroshi Inaba, and Kagehiro Amano
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Adult ,Male ,Adolescent ,Genotype ,Protein Conformation ,Antithrombin III ,DNA Mutational Analysis ,Mutation, Missense ,Biology ,medicine.disease_cause ,law.invention ,Exon ,Japan ,law ,medicine ,Humans ,Point Mutation ,Missense mutation ,Allele ,Gene ,Polymerase chain reaction ,Venous Thrombosis ,Genetics ,Mutation ,Antithrombin III Deficiency ,Point mutation ,Antithrombin ,Hematology ,Middle Aged ,Molecular biology ,Pedigree ,Phenotype ,Female ,medicine.drug - Abstract
We analyzed the antithrombin (AT) gene in 9 unrelated Japanese patients with thrombotic disease. All 7 exons, the splice junctions, and the 5'-flanking region of the AT gene were amplified by polymerase chain reaction and sequenced directly. Nine different point mutations, all in the heterozygous state, were identified. Five novel (M-32T, M89K, L146H, Q159X, and L409P) and 2 previously reported (R132X and R359X) point mutations were identified in patients with type 1 deficiency. Two different missense mutations, R393C and R393H, located in the protease reactive site were detected in patients with type 2 deficiency. No other sequence abnormalities in the AT gene were detected by direct sequencing. None of the mutations was present in 100 alleles from 50 unrelated Japanese control subjects Although type 1 deficiency was diagnosed in patient 7 on the basis of approximately 50% AT antigen and activity levels, the data indicated that the novel L409P mutation is a type 2 pleiotropic effects (PE) deficiency because its location in the C-terminal portion of the reactive site is similar to the locations of reported PE type mutations, and it is highly conserved among other serpins.
- Published
- 2003
6. Clinical Trial to Investigate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Recombinant Factor VIIa in Japanese Patients With Hemophilia With Inhibitors
- Author
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Yoko Minamoto, Tetsuhito Kojima, Midori Shima, Shigeru Fujita, Hideji Hanabusa, Katsuyuki Fukutake, Morio Arai, Akira Shirahata, Hiroyuki Naka, Hidehiko Saito, Junki Takamatsu, H. Tagami, Tadashi Kamiya, Akira Yoshioka, and Junji Kamizono
- Subjects
Adult ,Adolescent ,Factor VIIa ,Hemophilia A ,Japan ,Pharmacokinetics ,Isoantibodies ,medicine ,Coagulopathy ,Humans ,Adverse effect ,Prothrombin time ,medicine.diagnostic_test ,biology ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Therapeutic Equivalency ,Consumer Product Safety ,Recombinant factor VIIa ,Anesthesia ,Pharmacodynamics ,Hemostasis ,biology.protein ,business ,Partial thromboplastin time - Abstract
A multicenter and open-labeled clinical trial of human recombinant factor VIIa (rFVIIa) was conducted in Japanese patients with severe hemophilia A or B with inhibitors. The trial consisted of 2 parts. In study 1, the pharmacokinetics, pharmacodynamics, and safety of a single dose of 120 microg/kg of rFVIIa were investigated in 8 patients. In the subsequent study 2, the hemostatic effect and safety of rFVIIa were evaluated during a 24-week period in 10 patients. In study 1, the mean maximum FVII-coagulant activity (FVII:C) was found to occur after 10 minutes; activity then decreased rapidly and returned to the baseline within 24 hours after a single intravenous infusion of rFVIIa. The mean half-life of FVII:C was 3.5 hours. The activated partial thromboplastin time and prothrombin time in the patients were immediately shortened but returned to the baseline within 24 hours after dosing. In study 2, 86 microg/kg to 120 microg/kg of rFVIIa (mean, 97 microg/kg) was administered 1 to 85 times to 10 patients. A total of 58.0% (91/157) of bleeding episodes were treated excellently or effectively, with 5 (3.2%) ineffective episodes. There was no apparent trend in the relationship of the hemostatic effect with bleeding sites, mean dose, or number of injections. The efficacy rate, however, was significantly higher (90.0%) in bleeding episodes treated within 3 hours than in those treated at longer intervals (31.0%). No treatment-related adverse events were observed, and there was no evidence of antibody formation to rFVIIa. In conclusion. rFVIIa is an effective and well-tolerated option for treatment of bleeding episodes in hemophilia patients with inhibitors.
- Published
- 2001
7. Autoantibody to factor VIII that has less reactivity to factor Vlll/von Willebrand Factor Complex
- Author
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Kazuhiko Kagawa, Kagehiro Amano, Yasuharu Nishida, Morio Arai, Kimihito Koshihara, Katsuyuki Fukutake, and Takashi Suzuki
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Adult ,Hemolytic anemia ,Anemia, Hemolytic ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,animal diseases ,Immunoglobulin light chain ,law.invention ,Von Willebrand factor ,law ,hemic and lymphatic diseases ,Internal medicine ,von Willebrand Factor ,medicine ,Humans ,Autoantibodies ,Factor VIII ,biology ,Chemistry ,Autoantibody ,Hematology ,medicine.disease ,Endocrinology ,Monoclonal ,biology.protein ,Recombinant DNA ,Female ,Immunoglobulin Light Chains ,Antibody ,Autoimmune hemolytic anemia - Abstract
To determine the difference in reactivity of factor VIII (FVIII) inhibitor to FVIII/von Willebrand Factor (vWF) complex and FVIII free of vWF, an autoantibody to FVIII light chain was tested. A patient (1-3) suffered from autoimmune hemolytic anemia with autoantibody to FVIII. Epitope specificity of the patient's IgG (I-3 IgG) was shown to be the C2 domain of FVIII light chain (2170-2332) by Western blotting using recombinant FVIII deletions expressed in Escherichia coli. The inhibitory effect on FVIII procoagulant activity (VIII:C) of I-3 IgG was tested against a conventional FVIII concentrate; Haemate P, a monoclonal antibody-purified FVIII concentrate; Hemofil M, and a recombinant FVIII (rFVIII); Kogenate. I-3 IgG showed only 1.3 BU/mgIgG for Haemate P, in contrast to 20 BU/mgIgG for both Hemofil M and Kogenate. The ratio of VIII:C/vWF:Ag in Haemate P and Hemofil M was 1/3.43 and 1/0.01, respectively, while Kogenate did not contain vWF. The inhibitory effect of the I-3 IgG was then compared with Kogenate and its complex with vWF. The inhibitory effect was decreased against the rFVIII by forming a complex with vWF from 22 BU/mgIgG to 0.5 BU/mgIgG. Fab from the I-3 IgG had the same effect. In addition, vWF showed a protective effect on FVIII inactivation by the I-3 IgG in a dose dependent manner. Fifty-nine percent of residual VIII:C was retained in the presence of 8 U/ml of vWF after 1 hr incubation with I-3 IgG. These results suggested that vWF could compete with the I-3 IgG for binding to FVIII.
- Published
- 1995
8. Substantial expression of glycoproteins IX and V on the platelet surface from a patient with Bernard-Soulier syndrome
- Author
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Naomasa Yamamoto, Yasuharu Nishida, Atsumi Yamaguchi, Katsuyuki Fukutake, Noriko Akamatsu, Kenjiro Tanoue, Morio Arai, and Hidenori Suzuki
- Subjects
Adult ,Blood Platelets ,chemistry.chemical_classification ,medicine.medical_specialty ,business.industry ,Immunoblotting ,Bernard-Soulier Syndrome ,Platelet Membrane Glycoproteins ,Hematology ,Flow Cytometry ,medicine.disease ,Bernard–Soulier syndrome ,Endocrinology ,chemistry ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Female ,Platelet ,Glycoprotein ,business - Abstract
Summary. Flow cytometric studies demonstrated that the platelets from a patient with Bernard-Soulier syndrome expressed substantial amounts of both GPIX and GPV, although in reduced amounts.
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- 1994
9. Involvement of glycoprotein VI in platelet thrombus formation on both collagen and von Willebrand factor surfaces under flow conditions
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Noriko Tamura, Shunnosuke Handa, Morio Arai, Kumi Kodama, Hiroshi Takayama, and Shinya Goto
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Adult ,Blood Platelets ,Male ,Platelet Membrane Glycoproteins ,Platelet membrane glycoprotein ,chemistry.chemical_compound ,Von Willebrand factor ,Physiology (medical) ,von Willebrand Factor ,Medicine ,Humans ,Platelet ,Platelet activation ,Thrombus ,Phosphorylation ,Ristocetin ,Whole blood ,biology ,business.industry ,Receptors, IgG ,Thrombosis ,medicine.disease ,Platelet Activation ,Molecular biology ,chemistry ,Immunology ,biology.protein ,Female ,Collagen ,Stress, Mechanical ,Cardiology and Cardiovascular Medicine ,business ,Type I collagen - Abstract
Background — We studied the role of glycoprotein (GP) VI in platelet adhesion and thrombus formation on the immobilized collagen and von Willebrand factor (vWF) surface under flow conditions. Methods and Results — Whole blood obtained from 2 patients with GP VI–deficient platelets and the effects of the Fab of anti–GP VI antibody (Fab/anti–GP VI) were tested. Blood containing platelets rendered fluorescent by mepacrine was perfused on immobilized type I collagen or vWF under controlled wall shear rate. Platelet adhesion and thrombus formation were detected by epifluorescent videomicroscopy. The percentage of surface coverage by the platelets was calculated. Fc receptor γ-chain and spleen tyrosine kinase (Syk) were immunoprecipitated from the lysate of platelets stimulated by vWF plus ristocetin and then analyzed by antiphosphotyrosine immunoblotting. No platelet attachment was seen on the surface of collagen even after 9 minutes of perfusion of blood at relatively low (100 s −1 ) or high (1500 s −1 ) wall shear rate, either in the case of blood containing GP VI–deficient platelets or in the presence of Fab/anti–GP VI, whereas significant platelet thrombus formation was noted after control blood perfusion. Such interference with the actions of GP VI also reduced firm platelet adhesion on immobilized vWF. vWF-induced tyrosine phosphorylation of GP VI–associated Fc receptor γ-chain followed by Syk activation occurred in normal platelets, but little activation of Syk occurred in GP VI–deficient platelets. Conclusions — GP VI plays crucial roles in platelet thrombus formation on the surface of collagen under flow conditions in humans and is also involved in the process of firm platelet adhesion on the surface of vWF.
- Published
- 2002
10. Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI
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Morio Arai, Hiroshi Takayama, Naomasa Yamamoto, Tatsuo Ichinohe, Yasuharu Ezumi, Minoru Okuma, and Hoyu Takahashi
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Adult ,Integrins ,Receptors, Collagen ,Platelet Aggregation ,Integrin ,Proto-Oncogene Proteins pp60(c-src) ,Syk ,Cell Cycle Proteins ,macromolecular substances ,Platelet Membrane Glycoproteins ,Platelet membrane glycoprotein ,Biochemistry ,Collagen receptor ,chemistry.chemical_compound ,Proto-Oncogene Proteins ,Humans ,Syk Kinase ,Phosphotyrosine ,Proto-Oncogene Proteins c-vav ,Molecular Biology ,Cells, Cultured ,Enzyme Precursors ,biology ,Chemistry ,Phospholipase C gamma ,Microfilament Proteins ,Intracellular Signaling Peptides and Proteins ,Tyrosine phosphorylation ,Cell Biology ,Protein-Tyrosine Kinases ,Phosphoproteins ,Cell biology ,Enzyme Activation ,Isoenzymes ,Focal Adhesion Kinase 1 ,Focal Adhesion Protein-Tyrosine Kinases ,Type C Phospholipases ,Cancer research ,biology.protein ,Phosphorylation ,Collagen ,GPVI ,Cell Adhesion Molecules ,Cortactin ,Proto-oncogene tyrosine-protein kinase Src ,Signal Transduction - Abstract
Activation of circulating platelets by subendothelial collagen is an essential event in vascular hemostasis. In human platelets, two membrane glycoprotein (GP) abnormalities, integrin alpha2 beta1 deficiency and GPVI deficiency, have been reported to result in severe hyporesponsiveness to fibrillar collagen. Although it has been well established that integrin alpha2 beta1, also known as the GPIa-IIa complex, functions as a primary platelet adhesion receptor for collagen, the mechanism by which GPVI contributes to collagen-platelet interaction has been ill defined to date. However, our recent observation that GPVI cross-linking couples to cyclic AMP-insensitive activation of c-Src and Syk tyrosine kinases suggested a potential role for GPVI in regulating protein-tyrosine phosphorylation by collagen (Ichinohe, T., Takayama, H., Ezumi, Y., Yanagi, S., Yamamura, H., and Okuma, M. (1995) J. Biol. Chem. 270, 28029-28036). To further investigate this hypothesis, here we examined the collagen-induced protein-tyrosine phosphorylation in GPVI-deficient platelets expressing normal amounts of alpha2 beta1. In response to collagen, these platelets exhibited alpha2 beta1-dependent c-Src activation accompanied by tyrosine phosphorylation of several substrates including cortactin. In contrast, severe defects were observed in collagen-stimulated Syk activation and tyrosine phosphorylation of phospholipase C-gamma2, Vav, and focal adhesion kinase, implicating a specific requirement of GPVI for recruiting these molecules to signaling cascades evoked by collagen-platelet interaction.
- Published
- 1997
11. Influences of strenuous exercise (triathlon) on blood coagulation and fibrinolytic system
- Author
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Hisashi Yorifuji, Katsuhiro Fukutake, Hiroshi Nagasawa, Michio Fujimaki, Toshihito Katsumura, Hisao Iwane, Shojiro Ikematsu, Morio Arai, and Toshihiko Ishii
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Strenuous exercise ,Physical Exertion ,Running ,Reference Values ,Internal medicine ,Fibrinolysis ,medicine ,Coagulation (water treatment) ,Homeostasis ,Humans ,Blood Coagulation ,Swimming ,Aged ,business.industry ,Hematology ,Middle Aged ,Bicycling ,Clotting time ,Physical therapy ,Cardiology ,Blood Coagulation Tests ,business - Published
- 1990
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