A5067192657- Platelet Disorders and Treatments
- Antiplatelet Therapy and Cardiovascular Diseases
- Venous Thromboembolism Diagnosis and Management
- Acute Myocardial Infarction Research
- Cell Adhesion Molecules Research
- Blood groups and transfusion
- Blood properties and coagulation
- Hemoglobinopathies and Related Disorders
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Diabetes Treatment and Management
- Heparin-Induced Thrombocytopenia and Thrombosis
- Inflammatory mediators and NSAID effects
- Inflammatory Biomarkers in Disease Prognosis
- Blood Coagulation and Thrombosis Mechanisms
- Atrial Fibrillation Management and Outcomes
- Monoclonal and Polyclonal Antibodies Research
- Blood disorders and treatments
- Lipoproteins and Cardiovascular Health
- Adenosine and Purinergic Signaling
- Renal Diseases and Glomerulopathies
- Wound Healing and Treatments
- Periodontal Regeneration and Treatments
- Neuroscience of respiration and sleep
- Glycosylation and Glycoproteins Research
- Erythrocyte Function and Pathophysiology
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2017-2025
Harvard University
2016-2025
Boston Children's Hospital
2013-2024
Dana-Farber Cancer Institute
2011-2024
Boston Children's Museum
2009-2023
Medical University of Vienna
2016
Wayne State University
2016
Glsynthesis
2016
University of Massachusetts Chan Medical School
2005-2015
Harvard University Press
2012-2015
Background— The increasing use of higher-than-approved doses clopidogrel in clinical practice is based part on the desire for greater levels inhibition platelet aggregation (IPA). Prasugrel a new thienopyridine that more potent than standard-dose healthy subjects and patients with stable coronary artery disease. relative antiplatelet effects prasugrel versus high-dose percutaneous intervention are unknown. Methods Results— Comparison to Clopidogrel Inhibition Platelet Activation...
The ligand-binding function of integrin adhesion receptors depends on divalent cations. A mutant α IIb β 3 (platelet gpIIb/IIIa) that lacks ligand recognition shows immunologic evidence a perturbed interaction with This was found to be caused by G → T mutation resulted in an Asp 119 Tyr substitution the subunit. residue is proximal bound and conserved region among integrins are enriched oxygenated residues. spacing these residues aligns calcium-binding EF hand proteins, suggesting...
<h3>Context</h3>Variants in the CYP2C19 gene influence pharmacologic and clinical response to standard 75-mg daily maintenance dose of antiplatelet drug clopidogrel.<h3>Objective</h3>To test whether higher doses (up 300 mg daily) improve clopidogrel setting loss-of-function genotypes.<h3>Design, Setting, Patients</h3>ELEVATE-TIMI 56 was a multicenter, randomized, double-blind trial that enrolled genotyped 333 patients with cardiovascular disease across 32 sites from October 2010 until...
Occupancy of integrin receptors induces conformational changes in the receptor, resulting exposure novel interactive sites termed ligand-induced binding (LIBS). We report here that Fab fragments certain antibodies against LIBS on alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) block platelet aggregation. Thus, or regions surrounding them may participate events required for In addition, anti-alpha stimulated This was due to induction fg 3, apparently by shifting a equilibrium between...
We have hypothesized that ligand-induced binding sites (LIBS), i.e. expressed on cell surface receptors only after ligand causes the receptor to change shape, mediate subsequent biological events. To test this hypothesis, we raised monoclonal antibodies preferentially react with an integrin (platelet glycoprotein (GP) IIb-IIIa) it bind Arg-Gly-Asp-containing ligands. The 13 anti-LIBS obtained define at least three distinct GPIIb-IIIa epitopes; one of these epitopes is also following...
Thrombotic events still occur in aspirin-treated patients with coronary artery disease.To better understand aspirin "resistance," serum thromboxane B2 (TXB2) and flow cytometric measures of arachidonic acid-induced platelet activation (before after the ex vivo addition indomethacin) were analyzed 700 consecutive undergoing cardiac catheterization. In 680 682 evaluable patients, TXB2 concentrations reduced compared nonaspirinated healthy donors. Twelve had that was lower than donors but >10...
Binding of ligands that contain Arg-Gly-Asp to adhesion receptors induces cell spreading and aggregation alters gene expression, possibly due conformational changes within occupied receptors. PMI-1 is a monoclonal antibody which reacts with the platelet fibrinogen receptor, glycoprotein IIb-IIIa, reports such change. ADP stimulation platelets results in fibrinogen-dependent increase binding antibody. Peptides containing also reversibly this cells purified IIb-IIIa. The inhibits on certain...
To examine the extent of platelet inhibition by prasugrel vs. clopidogrel in a TRITON-TIMI 38 substudy. randomized acute coronary syndrome (ACS) patients undergoing percutaneous intervention (PCI) to or standard dose clopidogrel. Selected sites prospectively enrolled evaluate adenosine diphosphate (ADP)-attenuated phosphorylation vasodilator-stimulated phosphoprotein (VASP) (n = 125 patients) and, subset 31 patients), ADP-stimulated aggregation. VASP reactivity index (PRI) was lower...
Platelets are involved in the thromboses that central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks morning (~9 AM), potentially related endogenous circadian clock control of platelet activation. The objective was test if human system influences (1) function (2) response standardized behavioral stressors. We also aimed compare magnitude any effects on caused by varied stressors, including mental arithmetic, passive...
Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced response to clopidogrel compared patients without DM. Prasugrel, a more potent antiplatelet agent, is associated greater reductions in ischaemic events clopidogrel, particularly The aim of this study was perform serial pharmacodynamic assessments prasugrel high-dose Optimizing anti-Platelet Therapy In MellitUS (OPTIMUS)-3 prospective, randomized, double-blind, crossover type 2 DM coronary artery disease...
Poor clinical outcome in aspirin-treated patients has been termed aspirin resistance and may result from inadequate inhibition of platelet cyclooxygenase-1 (COX-1) by aspirin. The objectives this study were to determine prospectively whether COX-1-dependent other function assays correlate with outcomes patients.Blood was collected before percutaneous coronary intervention 700 consecutive (81 or 325 mg for > =3 days) patients. Platelet tested (1) serum thromboxane B(2); (2) arachidonic...
The vascular endothelium and shear stress are critical determinants of physiological hemostasis platelet function in vivo, yet current diagnostic monitoring devices do not fully incorporate endothelial under flow their assessment and, therefore, they can be unreliable inaccurate. It is challenging to include the assays for clinical laboratories or point-of-care settings because living cell cultures sufficiently robust. Here, we describe a microfluidic device that lined by human chemically...