Optimizing Primary Stroke Prevention in Children with Sickle Cell Anemia (STOP II)
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PROVIDER: PRJNA715788 | ENA |
REPOSITORIES: ENA
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Project description:Optimizing Primary Stroke Prevention in Children with Sickle Cell Anemia (STOP II)
| PRJNA715787 | ENA
Project description:Genetic differences in endothelial biology could underlie development of phenotypic heterogeneity amongst individuals afflicted with vascular diseases. We obtained BOEC (blood outgrowth endothelial cells) from 20 subjects with sickle cell anemia (age 4-19) shown to be either at-risk (n=11) or not-at-risk (n=9) for ischemic stroke due to, respectively, having or not having occlusive disease at the Circle of Willis (CoW). Gene expression profiling identified no significant single gene differences between the two groups, as expected. However, analysis of Biological Systems Scores, using gene sets that were pre-determined to survey each of nine biological systems, showed that only changes in inflammation signaling are characteristic of the at-risk subjects, as supported by multiple statistical approaches Experiment Overall Design: We obtained BOEC (blood outgrowth endothelial cells) from 20 subjects with sickle cell anemia (age 4-19) shown to be either at-risk (n=11) or not-at-risk (n=9) for ischemic stroke due to, respectively, having or not having occlusive disease at the Circle of Willis (CoW). To allow power calculations to be done, we performed microarray analysis on BOEC from 27 normal subjects of diverse ages. Gene expression profilings were obtained by using Affymetrix U133A chips
2008-06-17 | E-GEOD-9877 | biostudies-arrayexpress
Project description:We hypothesized that miRNA regulation may be invloved in hydroxyurea-mediated fetal hemoglobin induction. Microarray analysis was utilized as an initial screening tool to determine differential miRNA expression in CD71+ erythroid cells comparing cells from control individuals without sickle cell anemia to patients with sickle cell anemia prior to treatment with hydroxyurea and patients receiving the maximum tolerated dose (MTD) of hydroxurea.
2011-11-21 | GSE32035 | GEO
Project description:We hypothesized that miRNA regulation may be invloved in hydroxyurea-mediated fetal hemoglobin induction. Microarray analysis was utilized as an initial screening tool to determine differential miRNA expression in CD71+ erythroid cells comparing cells from control individuals without sickle cell anemia to patients with sickle cell anemia prior to treatment with hydroxyurea and patients receiving the maximum tolerated dose (MTD) of hydroxurea. CD71+ cells were isolated from whole blood of control individuals (n=2), pediatric patients without hydroxyurea treatment (n=3) and pediatric patients at hydroxyurea MTD (n=3). All 8 samples were analyzed for miRNA expression.
2011-11-21 | E-GEOD-32035 | biostudies-arrayexpress
Project description:Genetic differences in endothelial biology could underlie development of phenotypic heterogeneity amongst individuals afflicted with vascular diseases. We obtained BOEC (blood outgrowth endothelial cells) from 20 subjects with sickle cell anemia (age 4-19) shown to be either at-risk (n=11) or not-at-risk (n=9) for ischemic stroke due to, respectively, having or not having occlusive disease at the Circle of Willis (CoW). Gene expression profiling identified no significant single gene differences between the two groups, as expected. However, analysis of Biological Systems Scores, using gene sets that were pre-determined to survey each of nine biological systems, showed that only changes in inflammation signaling are characteristic of the at-risk subjects, as supported by multiple statistical approaches Keywords: disease status analysis
2007-12-18 | GSE9877 | GEO
Project description:Sickle cell disease is the most common genetic disorder in African-Americans. The opioid analgesic, morphine, has long been the treatment for the severe pain associated with this disease. Here we reveal that the opioid antagonist, naloxone, possesses potent analgesic activity in two strains of sickle cell mice (NY1DD and hBERK1) and not in their respective controls (ICR-CD1 and C57BL/6J) when administered by three parenteral routes. In the NY1DD sickle mice, naloxone (i.c.v.) possessed ~300-fold greater potency than morphine (i.c.v.). Other opioid antagonists (naltrexone, norbinaltorphimine, naltrindole) were substantially less effective in producing analgesia. Naloxone and morphine were synergistic in NY1DD mice, suggesting that analgesia was mediated via different receptor systems. Since microarray analysis suggested naloxone-induced down-regulation of the CCR5 chemokine receptor in NY1DD mice but not in control mice, the role of its endogenous ligand, CCL5 (RANTES), was investigated. Keywords: Comparison of drug induced gene expression
2007-03-14 | GSE6578 | GEO
Project description:The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (?200 cm/s) received moderate fixed-dose hydroxyurea therapy (?20 mg/kg/day). A comparison group of children with TCD measurements?<200 cm/s was followed prospectively. Approximately 88% (330 of 375) of families agreed to be screened, while 87% (29 of 33) of those with abnormal TCD measurements, enrolled in the trial. No participant elected to withdraw from the trial. The average mean corpuscular volume increased from 85.7 fl at baseline to 95.5 fl at 24 months (not all of the children who crossed over had a 24 month visit), demonstrating adherence to hydroxyurea. The comparison group consisted of initially 210 children, of which four developed abnormal TCD measurements, and were started on hydroxyurea. None of the monthly research visits were missed (n?=?total 603 visits). Two and 10 deaths occurred in the treatment and comparison groups, with mortality rates of 2.69 and 1.81 per 100 patient-years, respectively (P?=?.67). Our results provide strong evidence, for high family recruitment, retention, and adherence rates, to undertake the first randomized controlled trial with hydroxyurea therapy for primary stroke prevention in children with SCA living in Africa.
| S-EPMC5523858 | biostudies-literature
Project description:Ischemic Stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2,469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. Thus, these exploratory results may contribute to a better understanding of the role of endothelial cells in SCA ischemic stroke recovery, and promote new insights to further studies on therapeutic strategies for this severe complication.
2024-04-08 | GSE248760 | GEO
Project description:Transcriptional profiling of the antennae of adult honeybee workers with a dsx stop/stop mutation and wild-type workers was performed by RNA-Seq. Gene expression of the dsx stop/stop and wild type female workers was compared.
2024-07-10 | GSE270222 | GEO
Project description:Rationale. Sickle cell cardiomyopathy is characterized by prolonged QTc, myocardial fibrosis, diastolic dysfunction, and vulnerability to ventricular tachycardia (VT). Based on previous reports, IL-18 mediates cardiac fibrosis and its promoter SNPs are associated with sudden cardiac death in a non-sickle population. We, therefore, hypothesized that IL-18 may mediate cardiomyopathy and VT in sickle cell disease. Findings. Sickle cell patients with evidence of myocardial fibrosis demonstrated greater IL18 expression. Patients with higher IL18 gene expression levels also exhibited increased QTc intervals and overall mortality. A novel SNP within IL-18, rs5744285, was associated with both QTc and IL-18 expression levels. Similar to sickle cell patients, sickle mice demonstrated increased cardiac fibrosis and prolonged action potential duration (APD) associated with higher VT inducibility. Administration of exogenous IL-18 acutely ex vivo to hearts resulted in increased triggered activity and VTs while inhibition of IL-18 resulted in reduced cardiac NFkB expression, fibrosis, and dysfunction in sickle mice. Conclusions. IL-18 is associated with prolonged QTc, myocardial fibrosis, and mortality in sickle cell patients, and prolonged APD associated with heightened VT susceptibility in sickle mice. Inhibition of IL-18 improves cardiac function, in part, via NFκB. Inflammatory cytokines contribute to the development of sickle cardiomyopathy and inducible VT.
2018-10-31 | GSE89373 | GEO