EFFECT OF BETA S HAPLOTYPES ON THE RHEOLOGICAL CHARACTERISTICS OF SICKLE RBCS

β S 单倍型对镰状红细胞流变特性的影响

基本信息

  • 批准号:
    5213645
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

This study is primarily designed to determine beta-haplotypes and RBC deformability on our current patients with sickle cell anemia. A major specific objective is to determine if the beta haplotype (Benin, CAR, Senegal) has an effect on RBC deformability or not. In addition the alpha-gene number and Hb F level will also be determined. Another major objective is to determine the rheological properties of sickle RBC in the steady state and during painful crises in patients with different beta-- haplotypes and alpha-gene number. A third objective is to determine the effect of hydroxyurea on the rheological properties of sickle erythrocytes in vivo. This part of the study will be a parallel project to the Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia. Genomic DNA will be prepared from peripheral white blood cells from patients with sickle cell anemia. The alpha-gene number and beta-haplotypes will be determined by the Southern blotting technique or by polymerase chain reaction (PCR). Rheological properties of RBC will include: 1) RBC deformability determined by Ektacytometry; 2) number of dense cells determined by centrifugation on discontinuous Stractan density gradient and 3) RBC cations (Na+ and K+) determined by flame photometry. The rheological studies will be performed on unfractionated cells as well as on density-defined cells. It is projected that at least 15 of our patients will enroll in the HU study. Multiple base line studies (at least three determined at monthly intervals) will be performed before the initiation of drug therapy. Rheological studies will be done monthly after the initiation of drug therapy for the period of the study and for a minimum of four months after the discontinuation of drug therapy. In addition, survival of 51Cr-labeled autologous erythrocytes, 51Fe uptake by the bone marrow, plasma iron turnover and iron utilization will also be determined. These erythrokinetic studies will be done before the initiation of Hydroxyurea/placebo therapy and every six months thereafter. They will also be determined 4-6 months after the discontinuation of drug therapy. It must be emphasized that during the course of the study the principal investigator will have no access to any data such as the MCV, deformability index, etc. which may break the double-blind nature of the study. We hope this study will generate data which will: 1) clarify the factors which affect the clinical phenotype of sickle cell anemia; 2) elucidate the pathophysiologic changes that occur during the painful sickle cell crisis; and 3) provide insight into the mechanism of action of HU and its cellular effects which are not secondary to the increased level of Hb F. Moreover, determination of the rheological properties of RBC may be of value in monitoring the response to HU.
这项研究主要是为了确定β-单倍型和红细胞 我们目前的镰状细胞性贫血患者的变形性。一位少校 具体目标是确定Beta单倍型(贝宁,Car, 塞内加尔)对红细胞变形性是否有影响。此外, 还将测定α-基因数量和Hb-F水平。另一大专业 目的:测定高血压病患者镰状红细胞的流变学特性。 有不同β-的患者在稳定期和痛苦的危象中- 单倍型和α基因数目。第三个目标是确定 羟基脲对镰刀流变学特性的影响 体内的红细胞。研究的这一部分将是一个平行项目 对镰状细胞性贫血患者羟基尿素(HU)的多中心研究 基因组DNA将从以下来源的外周白细胞中提取 镰状细胞性贫血患者。阿尔法基因数量和 β单倍型将通过Southern blotting技术或 通过聚合酶链式反应(PCR)检测。红细胞的流变性将 包括:1)红细胞变形性测定;2)红细胞变形性 不连续斯特拉坦离心法测定致密细胞 密度梯度和3)火焰测定的RBC阳离子(Na+和K+) 测光学。流变学研究将在未分馏的基础上进行 单元格以及密度定义的单元格。据预测,至少 我们的15名患者将参加HU研究。多基线 研究(至少每月确定三次)将是 在药物治疗开始前进行的。流变学研究 将在药物治疗开始后每月进行一次 并在停止后至少四个月内 关于药物治疗的问题。此外,~(51)Cr标记的自体移植的存活率 红细胞、骨髓对~(51)Fe的摄取、血浆铁周转率和 还将确定铁的利用率。这些红血球动力学研究 将在羟基脲/安慰剂治疗开始前完成 此后每六个月举行一次。它们还将在4-6个月内确定 在停止药物治疗后。 必须强调的是,在研究过程中,校长 调查员将无法访问任何数据,如MCV, 可变形性指数等,可打破材料的双盲性 学习。 我们希望这项研究将产生以下数据:1)澄清因素 哪些因素影响镰状细胞性贫血的临床表型;2)阐明 在痛苦的镰状细胞期间发生的病理生理变化 危机;3)洞察胡的作用机制及其 细胞效应并不次于Hb-F水平的升高。 此外,测定红细胞的流变性可能是 在监测对胡的反应方面的价值。

项目成果

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SAMIR BALLAS其他文献

SAMIR BALLAS的其他文献

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{{ truncateString('SAMIR BALLAS', 18)}}的其他基金

CORE--CLINICAL RESEARCH UNIT, JEFFERSON UNIVERSITY HOSPITAL
核心--杰斐逊大学医院临床研究单位
  • 批准号:
    6241959
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
EFFECT OF BETA S HAPLOTYPES ON THE RHEOLOGICAL CHARACTERISTICS OF SICKLE RBCS
β S 单倍型对镰状红细胞流变特性的影响
  • 批准号:
    6241951
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
DIAGNOSIS AND COUNSELING FOR HEMOGLOBIN ABNORMALITIES
血红蛋白异常的诊断和咨询
  • 批准号:
    6241946
  • 财政年份:
    1997
  • 资助金额:
    --
  • 项目类别:
CORE--CLINICAL RESEARCH UNIT, JEFFERSON UNIVERSITY HOSPITAL
核心--杰斐逊大学医院临床研究单位
  • 批准号:
    3758621
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
DIAGNOSIS AND COUNSELING FOR HEMOGLOBIN ABNORMALITIES
血红蛋白异常的诊断和咨询
  • 批准号:
    3758608
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
EFFECT OF BETA S HAPLOTYPES ON THE RHEOLOGICAL CHARACTERISTICS OF SICKLE RBCS
β S 单倍型对镰状红细胞流变特性的影响
  • 批准号:
    3780632
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
CORE--CLINICAL RESEARCH UNIT, JEFFERSON UNIVERSITY HOSPITAL
核心--杰斐逊大学医院临床研究单位
  • 批准号:
    3736625
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
CLINICAL RESEARCH UNIT CORE--JEFFERSON UNIVERSITY HOSPITAL
临床研究单位核心--杰斐逊大学医院
  • 批准号:
    3880535
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
DIAGNOSIS AND COUNSELING FOR HEMOGLOBIN ABNORMALITIES
血红蛋白异常的诊断和咨询
  • 批准号:
    3780627
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
DIAGNOSIS AND COUNSELING FOR HEMOGLOBIN ABNORMALITIES
血红蛋白异常的诊断和咨询
  • 批准号:
    5213640
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
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