A5021731392- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Erythrocyte Function and Pathophysiology
- Blood groups and transfusion
- Blood properties and coagulation
- Heme Oxygenase-1 and Carbon Monoxide
- Platelet Disorders and Treatments
- Bone and Joint Diseases
- Hemoglobin structure and function
- Pharmacological Effects and Toxicity Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Advanced Glycation End Products research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Folate and B Vitamins Research
- Cell Adhesion Molecules Research
- Biochemical effects in animals
- Antiplatelet Therapy and Cardiovascular Diseases
- Extracellular vesicles in disease
- Heparin-Induced Thrombocytopenia and Thrombosis
- Neonatal Health and Biochemistry
- Hematological disorders and diagnostics
- Ion Channels and Receptors
- Blood donation and transfusion practices
- Ion channel regulation and function
- Blood Coagulation and Thrombosis Mechanisms
Medical College of Wisconsin
2011-2025
University of Pittsburgh
2015-2025
Children's Hospital of Pittsburgh
2015-2024
University of Pittsburgh Medical Center
2015-2020
Versiti Blood Center of Wisconsin
2005-2017
Children's Hospital of Wisconsin
2001-2014
Children’s Institute
2014
Pulmonary Associates
2014
Blood Systems Research Institute
2013
Queen Mary University of London
2012
Objective. Alloimmunization in patients with sickle cell disease (SCD) has a reported incidence of 5% to 36%. One complication alloimmunization is delayed hemolytic transfusion reaction/hyperhemolysis (DHTR/H) syndrome, which 11%. In SCD, clinical findings DHTR/H syndrome occur approximately 1 week after the red blood (RBC) and include onset increased hemolysis associated pain profound anemia. The hemoglobin (Hb) often drops below pretransfusion levels. many adult cases, direct antiglobulin...
Pulmonary hypertension (PHT) is common in sickle cell disease (SCD). The purpose of this study was to determine whether markers coagulation activation and inflammation are associated with PHT SCD.This cross-sectional performed using a cohort patients followed at an adult Sickle Cell Clinic. artery systolic pressure determined by Doppler echocardiography, the diagnosis defined age, sex body mass index-adjusted reference ranges. Clinical laboratory examinations, including hematologic studies...
Sickle cell disease (SCD) pain is associated with colder temperatures and touch described as "cold," "hot," "shooting" suggesting hypersensitivity to tactile stimuli. mice exhibit thermal (cold, heat) mechanical stimuli compared controls. It unknown whether humans experience this same hypersensitivity. Thus, we quantified sensitivity differences between patients SCD Our primary hypothesis was that will race-matched secondary be older female subjects, frequent hemolysis in SCD. A total of 55...
Background— Hypercholesterolemia and sickle cell disease (SCD) impair endothelium-dependent vasodilation by dissimilar mechanisms. impairs a low-density lipoprotein (LDL)–dependent mechanism. SCD has been characterized as chronic state of inflammation in which xanthine oxidase (XO) from ischemic tissues increases vascular superoxide anion (O 2 · − ) generation. Recent reports indicate that apolipoprotein (apo) A-1 mimetics inhibit atherosclerosis LDL receptor–null ( Ldlr −/− mice fed Western...
PECAM-1 is a recently described member of the immunoglobulin gene (Ig) superfamily that expressed on surface platelets, several leukocyte subsets, and at endothelial cell intracellular junction. Recent studies have shown extracellular domain PECAM-1, which comprised 6 Ig-like homology units, participates in mediating cell-cell adhesion, plays role initiating contact, may later serve to stabilize monolayer. also has relatively large 108 amino acid cytoplasmic domain, with potential sites for...
The adhesion of sickle erythrocytes to the vascular endothelium and subendothelial matrix probably contributes pathogenesis vaso‐occlusive disease. chemotherapeutic agent hydroxyurea (HU) decreases frequency crises in patients with cell However, exact mechanism(s) HU's effect on is not fully understood. goal this study was determine HU therapy proteins thrombospondin (TSP) laminin under conditions flow vitro . Erythrocytes from severe disease ( n = 14) had significantly less TSP (687 ± 92...
As a measure of morbidity vaso-occlusive crises (VOC) in sickle cell disease, we used national hospital discharge database, the Kids' Inpatient Database (KID), to determine number hospitalizations and length stay (LOS) by age.Nationally weighted discharges for VOC children with disease were analyzed using data from 2,500 hospitals Healthcare Cost Utilization Project (HCUP) KID. Number LOS age group analyzed. Multiple linear regression was performed analyze effect on LOS.There 20,271 VOC....
Thrombosis and inflammation are intimately linked synergistically contribute to the pathogenesis of numerous thromboinflammatory diseases, including sickle cell disease (SCD). While platelets central thrombogenesis inflammation, molecular mechanisms crosstalk between 2 remain elusive. High-mobility group box 1 (HMGB1) regulates stimulates platelet activation through Toll-like receptor 4. However, it remains unclear whether HMGB1 modulates other thrombotic agonists regulate activation....
To assess the role of partial splenectomy for symptomatic children with various congenital hemolytic anemias.The use total anemias is restricted by concern postsplenectomy sepsis. A an alternative procedure, although its utility remains incompletely defined.This longitudinal cohort study followed 25 who underwent splenectomy. Sixteen had hereditary spherocytosis (HS), and nine other erythrocyte disorders. Outcome measures were clinical laboratory hemolysis, splenic phagocytic immune...
Asthma is characterized by oxidative stress and inflammation of the airways. Although proinflammatory lipids are involved in asthma, therapies targeting them remain lacking. Ac-DWFKAFYDKVAEKFKEAFNH(2) (4F) an apolipoprotein (apo)A-I mimetic that has been shown to preferentially bind oxidized improve HDL function. The objective present study was determine effects 4F on stress, inflammation, airway resistance established murine model asthma. We show here ovalbumin (OVA)-sensitization increased...
Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. In addition, both humans mice SCD experience heightened cold sensitivity. However, studies have not addressed the mechanism(s) underlying sensitization or its progression age. Here we measured thermotaxis behavior in young aged severe SCD. had a marked increase sensitivity by preference test. Furthermore, hypersensitivity worsened advanced We...
Vaso-occlusive events are the major source of morbidity and mortality in sickle cell disease (SCD); however, pathogenic mechanisms driving these remain unclear. Using hypoxia to induce pulmonary injury, we investigated by which hemoglobin increases susceptibility lung injury a murine model SCD, where mice either exclusively express human alpha/sickle beta-globin (halphabetaS) transgene (SCD mice) or heterozygous for normal gene halphabetaS (mbeta+/-, halphabetaS+/-; heterozygote SCD mice)....
Glycoprotein IIb-IIIa (GPIIb-IIIa) is the fibrinogen receptor on activated platelets. GPIIIa phosphorylated in resting platelets and incorporation of 32Pi increases with platelet activation. To address functional significance this modification, stoichiometry phosphorylation was determined by estimating specific activity metabolic [gamma-32P]ATP from phosphatidic acid. Approximately 0.01 mol P/mol 0.03 thrombin-, phorbol ester-, or U46619-treated Myosin light chain (MLC) served as a positive...