- Platelet Disorders and Treatments
- Antiplatelet Therapy and Cardiovascular Diseases
- Cellular transport and secretion
- Venous Thromboembolism Diagnosis and Management
- Autoimmune and Inflammatory Disorders Research
- Cell Adhesion Molecules Research
- Mechanical Circulatory Support Devices
- Protein Kinase Regulation and GTPase Signaling
- Heparin-Induced Thrombocytopenia and Thrombosis
- Immune Cell Function and Interaction
- Inflammatory mediators and NSAID effects
- Atrial Fibrillation Management and Outcomes
- Coronary Interventions and Diagnostics
- Blood properties and coagulation
- Endoplasmic Reticulum Stress and Disease
- Lipid Membrane Structure and Behavior
- Cardiac Valve Diseases and Treatments
- Ubiquitin and proteasome pathways
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cellular Mechanics and Interactions
- Cardiovascular Function and Risk Factors
- Microtubule and mitosis dynamics
- Diabetes Treatment and Management
- Pulmonary Hypertension Research and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Tohoku University
2016-2025
Methodist Hospital
2023
Tenri Hospital
2023
International University of Health and Welfare
2023
University of Miyazaki
2023
University of Tokyo Hospital
2023
Nihon Pharmaceutical University
2016
Kyoto University Hospital
2013
Kyoto University
2003-2012
The University of Tokyo
2010
Abstract Proinflammatory cytokines such as TNF-α and IFN-γ induce cell adhesion molecules in endothelial cells promote transmigration of leukocytes across cells. However, when those two were administered together, leukocyte paradoxically decreased. We cloned a human bovine homologue the junctional molecule (JAM), novel at tight junction, examined effects proinflammatory on JAM HUVECs. The combined treatment plus caused disappearance from intercellular junctions. flow cytometry, ELISA,...
Percutaneous transvenous mitral commissurotomy was performed in 106 consecutive patients. Significant symptomatic improvement achieved 97 patients (92%). Mean left atrial pressure decreased (from 18 +/- 8 to 11 mm Hg, p less than 0.00001), mean diastolic gradient 12 7 6 and valve area increased 1.40 0.40 2.00 0.50 cm2, 0.00001). Based on echocardiographic characteristics of the apparatus, were grouped retrospectively three categories: pliable (group 1, n = 37), semipliable 2, 59), rigid 3,...
Platelets store self-agonists such as ADP and serotonin in dense core granules. Although exocytosis of these granules is crucial for hemostasis thrombosis, the underlying mechanism not fully understood. Here, we show that incubation permeabilized platelets with unprenylated active mutant Rab27A-Q78L, wild type Rab27A, Rab27B inhibited secretion, whereas inactive Rab27A-T23N other GTPases had no effects. Furthermore, affinity-purified a GTP-Rab27A-binding protein identified it Munc13-4,...
Metformin is the first-line drug in treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) alarmin that released from necrotic cells and induces inflammatory responses by cytokine-like is, therefore, a target therapies. Here we identified HMGB1 as novel metformin-binding protein affinity purification using biotinylated analogue. directly...
Perforin gene (PRF1) mutations cause the primary form of hemophagocytic lymphohistiocytosis (HLH). We report a genetic defect PRF1 in 62-year-old Japanese man with recurrent episodes HLH. Sequencing from both peripheral blood mononuclear cells and nail clippings showed compound heterozygous mutation, including deletion two base pairs at codons 1090 1091 (1090–1091delCT) guanine-to-adenine conversion nucleotide position 916 (916G→A). Although HLH has been detected infants children, mutation...
Background: The P2Y12 adenosine diphosphate (ADP) receptor blocker, clopidogrel, an essential drug for the prevention of stent thrombosis after percutaneous coronary intervention (PCI), is a prodrug that requires CYP2C19- and CYP3A4-mediating activation. CYP2C19*2 *3 polymorphisms are known to lack enzymatic activity. CYP2C19 have been reported exhibit weaker antiplatelet response clopidogrel in healthy subjects. effect CYP2C19, CYP3A4 on clinical patients was examined present study. Methods...
Munc13-4 is a widely expressed member of the CAPS/Munc13 protein family proposed to function in priming secretory granules for exocytosis. contains N- and C-terminal C2 domains (C2A C2B) predicted bind Ca(2+), but Ca(2+)-dependent regulation activity has not been described. The bracket SNARE-binding domain, whether interacts with SNARE proteins unknown. We report that bound Ca(2+) restored granule exocytosis permeable cells (platelets, mast, neuroendocrine cells) dependent on putative...
Upon stimulation, neutrophils release their nuclear contents called neutrophil extracellular traps (NETs), which contain unfolded chromatin and lysosomal enzymes. NETs have been demonstrated to play a critical role in host defence, although the of PGE2 , bioactive substance generated inflammatory tissues, formation remains unclear.The effects agonists antagonists its receptors, modulators cAMP-PKA pathway on were examined vitro isolated vivo newly established mouse model.PGE2 inhibited...
Aim: Severe gastrointestinal bleeding sometimes occurs in patients with aortic stenosis (AS), known as Heyde's syndrome. This syndrome is thought to be caused by acquired von Willebrand and characterized reduced large factor (vWF) multimers. However, the relationship between severity of AS loss vWF multimers unclear.Methods: We examined 31 consecutive severe AS. Quantitative evaluation for was performed using conventional ratio novel multimer index. index defined those controls.Results: Loss...
Weibel-Palade bodies (WPBs) are endothelial-specific organelles, which, upon fusion with the plasma membrane, release cargo molecules that essential in critical blood vessel functions such as thrombosis, inflammation and angiogenesis. Despite importance of WPBs, basic mechanisms mediate their secretion only poorly understood. Rab GTPases play fundamental role trafficking intracellular organelles. Yet, known WPB-associated Rabs Rab27a Rab3d. Here, to determine full spectrum WPB-Rabs we...
A questionnaire on COVID-19-related thrombosis in patients hospitalized before Aug 31, 2020, was sent to 399 hospitals throughout Japan. Responses were received from 111 (27.8%) with information 6,202 COVID-19 patients. Of these, 333 and 56 required ventilation or extracorporeal membrane oxygenation (ECMO), respectively, 212 died (3.4%). D-dimer levels measured 75.0% of the patients, revealing that 9.2% 7.6% exhibited increases 3-8-fold ≥8-fold reference value, respectively. Thrombotic...
The smg-25A/rab3A protein (smg p25A) is a small GTP-binding implicated in intracellular vesicle traffic, particularly neurotransmitter release from the presynapse. In present study, we attempted to identify target bovine brain crude membranes that might be interacted with GTP-bound form of smg p25A. When guanosine-5'-(3-O-thio)triphosphate (GTP gamma S)-bound radioiodinated p25A and membrane fraction were incubated cross-linker, disuccinimidyl suberate, sample was subjected sodium dodecyl...