A5066832003- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Blood groups and transfusion
- Erythrocyte Function and Pathophysiology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Heme Oxygenase-1 and Carbon Monoxide
- Hemoglobin structure and function
- Folate and B Vitamins Research
- Bone and Joint Diseases
- Pregnancy and preeclampsia studies
- Neonatal Health and Biochemistry
- Kruppel-like factors research
- Pulmonary Hypertension Research and Treatments
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Liver Disease Diagnosis and Treatment
- Cardiovascular Function and Risk Factors
- Ubiquitin and proteasome pathways
- Transplantation: Methods and Outcomes
- Erythropoietin and Anemia Treatment
- Blood properties and coagulation
- Prenatal Screening and Diagnostics
- Cancer-related molecular mechanisms research
- Hematological disorders and diagnostics
- Genomics and Chromatin Dynamics
CSL (United States)
2020-2025
University of Pittsburgh
2015-2024
Scientific Consulting Group
2024
CSL (Switzerland)
2020-2024
University of Mississippi Medical Center
2019-2022
University Physicians
2017-2022
Mach I (United States)
2022
University of Pittsburgh Medical Center
2015-2021
National Heart Lung and Blood Institute
2007-2019
Juntendo University
2019
Sickle cell disease is characterized by a state of nitric oxide resistance and limited bioavailability l-arginine, the substrate for synthesis. We hypothesized that increased arginase activity dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary hypertension, patient outcomes.To explore role in sickle pathogenesis, mortality.Plasma amino acid levels, plasma erythrocyte activities, hypertension status as measured Doppler echocardiogram were prospectively obtained...
The product of the c-myc proto-oncogene is a nuclear phosphoprotein whose normal cellular function has not yet been defined. c-Myc number biochemical properties, however, that suggest it may as potential regulator gene transcription. Specifically, DNA-binding protein with short half-life, high proline content, segments are rich in glutamine and acidic residues, carboxyl-terminal oligomerization domain containing leucine zipper helix-loop-helix motifs serve domains known regulators...
Sickle cell disease has been very well characterized as a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, with resulting red rigidity that causes poor microvascular blood flow, consequent tissue ischemia and infarction. More recently, an independent spectrum pathophysiology vessel function demonstrated, involving abnormal vascular tone activated, adhesive endothelium. These vasculopathic abnormalities are attributable pathways...
Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionMethodsHow to Use These Guidelin...Definition PH in SCDDiagnosis SCDEstimating Mortality Risk...Treatment Patients wit...Future DirectionsReferencesCITING ARTICLES
The product of the c-myc proto-oncogene is a DNA-binding protein, deregulated expression which associated with variety malignant neoplasms. cDNA for max gene was recently cloned as result ability its protein to interact c-Myc protein. We studied bacterially produced Max, c-Myc, and series truncated proteins. Full-length alone cannot bind DNA. However, comprising basic, helix-loop-helix, leucine zipper regions can specifically DNA bearing sequence GGGCAC(G/A)TGCCC. Max either or in...
Summary Pulmonary hypertension is a frequent complication of sickle cell disease that associated with haemolysis, impaired nitric oxide bioavailability and high mortality. We sought to evaluate the safety efficacy selective pulmonary vasodilators antiproliferative agents in this at‐risk population. After optimising therapy stabilise haemoglobin fetal levels, we evaluated sildenafil 12 patients hypertension. Sildenafil (mean duration 6 ± 1 months) decreased estimated artery systolic pressure...
To the Editor: Dr Olshansky's research letter on accelerated aging of US presidents concluded that do not age faster than other men. 1 That may be true, but this study cannot demonstrate it due to a faulty comparison.Olshansky compared presidents' actual at death (adjusted for by subtracting 2 days every day in office) against average life expectancy men matched date inauguration.However, correct comparison is with who have same profile risk factors premature death.For example, as Olshansky...
The intensity of hemolytic anemia has been proposed as an independent risk factor for the development certain clinical complications sickle cell disease, such pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A composite variable derived from several individual markers hemolysis could facilitate studies underlying mechanisms hemolysis. In this study, we assessed association with outcomes in anemia. component was calculated by principal analysis reticulocyte count, serum lactate...
Summary Endothelial cell adhesion molecules orchestrate the recruitment and binding of inflammatory cells to vascular endothelium. With endothelial dysfunction injury, levels bound soluble increase. Such expression is modulated by nitric oxide (NO), in patients with sickle disease (SCD), these are inversely associated measures NO bioavailability. To further evaluate role a population study SCD, we have measured endothelium‐derived plasma specimens 160 adult SCD during steady state....
ContextThirty percent of patients with sickle cell disease (SCD) develop pulmonary hypertension, a major risk factor for death in this population. A validated blood biomarker hypertension SCD could provide important prognostic and diagnostic information allow the exploration prevalence participants 1996 Multicenter Study Hydroxyurea Sickle Cell Anemia (MSH) Patients' Follow-up Study. Levels N-terminal pro-brain natriuretic peptide (NT-proBNP) such idiopathic arterial hypertension.ObjectiveTo...
Elevation of echocardiography-determined tricuspid regurgitant jet velocity predicts high systolic pulmonary artery pressure and early mortality in adults with sickle cell disease. The definition, prevalence clinical correlates elevated have not been established pediatric patients. present study tested the hypotheses that affects 10% patients, is associated both hemolysis hypoxia, has acute chest syndrome, stroke, transfusion requirement abnormal 6-minute walk test results.A prospective...
BackgroundIntravascular hemolysis in sickle cell anemia could contribute to complications associated with nitric oxide deficiency, advancing age, and increased mortality. We have previously reported that intense is risk of vascular a small cohort adults disease. These observations not been validated other populations.MethodsThe distribution serum lactic dehydrogenase (LDH) values was used as surrogate measure intravascular contemporaneous patient group an historical adult population from the...
Background— Noninvasively assessed pulmonary pressure elevations and left ventricular (LV) diastolic dysfunction are associated with increased mortality in adults sickle cell disease, but their relationship to exercise intolerance has not been evaluated prospectively. Methods Results— Echocardiography, 6-minute walk distance, hemolytic rate, serum concentrations of ferritin erythropoietin were a cohort 483 subjects homozygous hemoglobin S the US UK Walk–Treatment Pulmonary Hypertension...
Background: Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated early mortality, but no prior studies have evaluated quantitative relationships of mortality to physiological measures pre- and postcapillary PH.Objectives: To identify risk factors estimate the expected survival a cohort patients SCD PH documented by right heart catheterization.Methods: Nine-year follow-up data (median, 4.7 yr) from National Institutes Health screening study are reported. A total...
Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates multicellular functions through interactions with its receptors on cell surfaces. S1P enriched and stored in erythrocytes; however, it not clear whether alterations are involved the prevalent debilitating hemolytic disorder sickle disease (SCD). Here, using metabolomic screening, we found highly elevated blood of mice humans SCD. In murine models SCD, demonstrated erythrocyte sphingosine kinase 1 (SPHK1) underlies sickling...
Background The role of pulmonary hypertension as a cause mortality in sickle cell disease (SCD) is controversial. Methods and Results We evaluated the relationship between an elevated estimated artery systolic pressure patients with SCD. followed from walk-PHaSST screening cohort for median 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has 67–75% positive predictive value mean ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. 582 measured NT-proBNP,...