A5089009870- Hemophilia Treatment and Research
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Cancer-related gene regulation
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Chronic Myeloid Leukemia Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Hemostasis and retained surgical items
- Blood properties and coagulation
- HIV/AIDS Research and Interventions
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- HIV-related health complications and treatments
- Pneumocystis jirovecii pneumonia detection and treatment
- Hepatitis C virus research
- Blood groups and transfusion
- Venous Thromboembolism Diagnosis and Management
- Lymphoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Heparin-Induced Thrombocytopenia and Thrombosis
- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- Chronic Lymphocytic Leukemia Research
- Protease and Inhibitor Mechanisms
- Blood donation and transfusion practices
Tokyo Medical University
2015-2024
Ogikubo Hospital
2002-2024
Tokyo Medical University Hospital
2006-2023
University Medical Center Utrecht
2023
Utrecht University
2023
Laboratory of Molecular Genetics
2016
Hyogo Medical University
2011
University of Occupational and Environmental Health Japan
2011
Nara Medical University
2001-2006
Japanese Red Cross Society, Japan
1999-2006
In patients with severe hemophilia A, standard treatment is regular prophylactic and episodic intravenous infusions of factor VIII. However, these treatments are burdensome, especially for children, may lead to the formation anti–factor VIII alloantibodies (factor inhibitors). Emicizumab (ACE910), a humanized bispecific antibody mimicking cofactor function VIII, was developed abate problems.
RANTES (regulated on activation normal T cell expressed and secreted) is one of the natural ligands for chemokine receptor CCR5 potently suppresses in vitro replication R5 strains HIV-1, which use as a coreceptor. Previous studies showed that peripheral blood mononuclear cells or CD4 + lymphocytes obtained from different individuals had wide variations their ability to secrete RANTES. These findings prompted us analyze upstream noncoding region gene, contains cis-acting elements involved...
Emicizumab (ACE910), a recombinant humanized bispecific monoclonal antibody, provides factor VIII (FVIII) cofactor bridging function to restore hemostasis in people with hemophilia A. In phase 1 trial involving 18 Japanese patients severe A, once-weekly subcutaneous administration of emicizumab 0.3, 1, or 3 mg/kg (cohorts 2, and 3, respectively) was well tolerated substantially reduced annualized bleeding rates (ABRs) the presence absence FVIII inhibitors. The current study represents an...
Platelet glycoprotein VI (GPVI), a 62kD membrane protein, has been identified as one of the platelet receptors for collagen, since GPVI-deficient platelets exhibit abnormal responses to collagen and an bleeding tendency. We report female patient with mild history whose expressed 10% GPVI normal platelets. Shape change, aggregation ATP release patient's were completely absent in response 1-5 micrograms/ml but present normally ADP Ca2+ ionophore A23187. Adhesion coated was mildly affected...
Recommendation for Measurement of Erythrocyte Sedimentation Rate Human Blood: International Committee For Standardization in Haematology K. G. Von Boroviczeny, (Berlin), (Berlin) The late Dr. A. Westergren was a foundation member the Panel. Search other works by this author on: Oxford Academic Google Scholar L. E. Böttiger, (Stockholm), (Stockholm) B. S. Bull, (Loma Linda; Consultant), Consultant) Chattas, (Buenos Aires), Aires) J. Dawson, (Rochester), (Rochester) Fukutake, (Tokyo), (Tokyo)...
BAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression optimize clinical performance.To demonstrate superiority of prophylaxis vs. on demand therapy patients severe hemophilia A.In this multinational,randomized, open-label crossover study (LEOPOLD II;ClinicalTrials.gov identifier: NCT01233258), males aged 12–65 years A were randomized twice-weekly (20-30 IU kg(-1)), 3-times-weekly (30-40 or...
Summary In order to clarify the potential role of von Willebrand factor (vWf) in attenuating inactivation VIII (fVIII) by those antibodies with C2 domain specificity, we investigated a panel 14 human fVIII. Immunoblotting analysis localized light chain (C2 domain) epitopes for four cases, heavy (A2 five while remaining cases were both and chains. The inhibitor titer was considerably higher Kogenate, recombinant fVIII concentrate, than Haemate P, fVIII/vWf complex all plasmas that had...
Summary Patients with congenital haemophilia inhibitors or acquired are at risk of bleeding complications during surgery. In these patients, replacement therapy for the missing coagulation factor is ineffective, and a bypassing agent such as recombinant activated VII (rFVIIa) required to manage bleeding. To evaluate safety haemostatic efficacy rFVIIa treatment in Japanese patients FVIII/FIX undergoing Postmarketing surveillance data from May 2000 March 2010 were analysed assess 38 procedures...
Summary Haemophilia A is caused by various genetic mutations in the factor VIII gene ( F8 ). However, after conventional analysis, no candidate mutation could be identified of about 2% haemophilia patients. The a patient with mild congenital A, whom was found exons or their flanking regions, analysed detail to identify patient's aetiological abnormality. We also characterized anti‐FVIII antibody (inhibitor) development this patient. Genomic DNA analysis revealed an adenine guanine transition...
MC710, a mixture of plasma-derived activated factor VII and X at protein weight ratio 1:10, is novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In Phase II trial, we evaluated the haemostatic efficacy safety single doses investigated pharmacokinetic pharmacodynamic parameters nine joint bleeding episodes six male This trial was multi-centre, open-label, non-randomized study two (60 120 μg kg−1 as FVIIa dose), allowing re-administration different MC710 dosages to...
Introduction MC 710, a 1:10 protein weight ratio mixture of plasma‐derived activated factor VII ( FVII a) and X FX ), is novel bypassing agent for haemostasis in haemophilia patients with inhibitors. We evaluated the haemostatic efficacy safety one to two administrations 710 21 joint, muscle, subcutaneous bleeding episodes 14 male patients, multi‐centre, open‐label, non‐randomized clinical trial. Methods Subjects were intravenously administered or doses 60 120 μg kg −1 (as once twice (to...
Recombinant factor XIII-A2 (rFXIII-A2) was developed for prophylaxis and treatment of bleeds in patients with congenital FXIII A-subunit deficiency. mentor™2 (NCT00978380), a multinational, open-label, single-arm, multiple-dosing extension to the pivotal mentor™1 trial, assessed long-term safety efficacy rFXIII-A2 eligible (patients severe [<0.05 IU/mL] subunit A deficiency) aged ≥6 years. Patients received 35 IU/kg (exact dosing) every 28 ± 2 days ≥52 weeks. Primary endpoint (adverse events...
Summary We reported the results of a clinical pharmacological study MC 710 (a mixture plasma‐derived FVII and FX ) in haemophilia patients with inhibitors during non‐haemorrhagic state. This report provides clot waveform analysis ( CWA thrombin generation test TGT using blood samples obtained this study. were conducted from pharmacokinetic pharmacodynamic which (five dose rates: 20, 40, 80, 100 120 μg kg −1 was compared NovoSeven (120 FEIBA (two 50 75 U as control drugs 11 without...
Patients with haematological diseases occasionally exhibit liver dysfunction during treatment. This can have various causes such as therapy-related drugs and hepatitis B C infections, although the cause is unclear in some cases. It was recently reported that patients initially diagnosed drug-induced actually had E1. Several cases of transfusion-transmitted E infections also been reported1,2. In Japan, screening for does not appear to be performed at initial examination acute hepatitis. might...
No genetic defects are found in the coagulation factor VIII gene (F8) of approximately 2% patients with hemophilia A. Recently, genomic variants causative A that were located deep within introns have been reported.We aimed to establish a comprehensive method analysis F8 using next-generation sequencing (NGS) and investigate F8.Forty-five male A, including 31 previously identified mutations, investigated.Our NGS allowed for identification roughly 99% F8. We confirmed our can detect single...
Summary. MC710, a combined product of plasma‐derived activated factor VII (FVIIa) and X (FX) at protein weight ratio 1:10, is novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In this study, pharmacokinetic (PK), pharmacodynamic (PD) parameters safety single doses MC710 were investigated 11 male inhibitors non‐bleeding state. This was multi‐centre, open‐labelled, non‐randomized, active controlled crossover, dose‐escalation study five (20–120 μg kg −1 FVIIa)...
Summary Activated protein C ( APC ) inactivates activated factor V FV a) and moderates FVIIIa by restricting cofactor function. Emicizumab is a humanized anti‐FIXa/FX bispecific monoclonal antibody that mimicks In recent clinical trials in haemophilia A patients, once‐weekly subcutaneous administration of emicizumab was remarkably effective preventing bleeding events, but the mechanisms controlling regulation emicizumab‐mediated haemostasis remain to be explored. We investigated role...
The recombinant full‐length FVIII product Kogenate ® has been reformulated using sucrose (rFVIII–FS) instead of human serum albumin as a stabiliser in purification and formulation. vivo recovery, haemostatic efficacy, safety rFVIII–FS were investigated 20 previously treated patients with severe or moderate haemophilia A for ≥ 24 weeks. In recoveries 73.5 ± 16.3%, 78.4 16.1%, 82.8 23.9% after the initial infusion 50 IU kg −1 at weeks 12 24, respectively, showed no significant changes over...