Bronx Comprehensive Sickle Cell Center

布朗克斯综合镰状细胞中心

• 批准号: 7463050
• 负责人: Mary E Fabry
• 金额: $ 7.54万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7463050
• 关键词: Adhesions; Adverse effects; Affect; Animal Model; Arginine; Arts; Basic Science; Blood; Blood Platelets; Blood Vessels; Blood Volume; Brain; Calcium-Activated Potassium Channel; Cell Adhesion; Cell Volumes; Cells; Characteristics; Citrulline; Clinical; Complement; Condition; Development; Disease; Enzymes; Epigenetic Process; Erythrocytes; Evaluation; Factor VIII-Related Antigen; Family suidae; Finding of Mean Corpuscular Hemoglobin; Gene Cluster; Genes; Globin; Haplotypes; Hospitalization; Housing; Human; Integrins; Kidney; Knowledge; Laminin; Learning; Length of Stay; Leukocytes; Link; Measurement; Measures; Microarray Analysis; Microcirculation; Molecular; Monitor; Mus; Muscle; Near-Infrared Spectroscopy; Nitric Oxide; Nitric Oxide Synthase; Numbers; Obstruction; Osmolar Concentration; Oxides; Oxygen; P-Selectin; Pain; Patients; Pensions; Performance; Phenotype; Plasma; Platelet Aggregation Inhibition; Play; Polymers; Potassium Channel; Process; Production; Property; Purpose; Rate; Recovery; Reporting; Research Project Grants; Risk; Role; Services; Severities; Sickle Cell; Sickle Cell Anemia; Structure; Supplementation; Sus scrofa; Technology; Testing; Therapeutic Intervention; Toxic effect; Transgenic Mice; Transgenic Organisms; Urine; VWF gene; Work; base; concept; density; desire; follow-up; gamma Globin; improved; interest; liver function; mouse model; novel; polymerization; pre-clinical; quantum; sickling; vasoconstriction; von Willebrand Factor

This proposal includes: one clinical Project l_Proje-t 2: PI: Dr. Fabry) that builds on the pioneering work of the Pi in the .: la cycle on the development of BOLD-MRI and now near infrared spectroscopy (NIRS) to measure oxygenation:. pension and blood volume it, sickle cell patients and novel sickle transgenic mice. The objective is to determine if these state-of-the-art technologies can help in the evaluation ofsicMe damage to brain, kidney and muscle. In addition, there are three Translationa! Research projects, that aim at finding potentially helpful therapeutic interventions in SCD by the pre-clinical development of several basic research strategies. They are: Project I (PI: Dr. Acharya) who is interested in generating a globin chain that has more polymerization inhibitory potential than the paradigmane HbF, based on the pioneering f'mding, in the previous cycle, that pig-sigma-chain completely neurralizes human B5-polymerization.The follow-up to define the minimum number of pig-gamma-chain sequences that are sufficient to confer the desired properties on the human Gamma globin chain. In the process, we will learn about the quinary structure of sickle polymer as well as the refinement of semisynthesis. Project 3 (PI: Dr. Kaul), also builds on work done in the previous cycle, but the present proposal aims at a quantum leap of knowledge as it pertains to: testing the hypotheses that a heterogenous array of red cell integrins and vWF, P-selectin, laminin, and NO are involved in sickle adhesion, and testing the hypothesis that gamma, beta3, anionic polysacharides, and hydroxyur, can be useful in blocking sickle cell adhesion. Project 4 (PI; Dr. Nagel), builds on a long interest in ti,.emulfigene involvement in the sickle phenotype. This project aims at defining, by state-of-the art microarray technology, the genes responsible for the pleiotropic effects in sickle cell anemia, as well as which of these have epistatic (modifier) capability to define severity risk and to explore potential epigenetic effects in B-gene cluster haplotypes linked to the sickle gene. The projects are supported by an Administrative Core, Transgecnic Core (in the forefront of developing sickle animal models), by a micro-CHIP Core (supposed also by our in-house Microarray Facility), a strong Clinical and Patient Services Core, that have pioneered the Day Hospital concept into reality, with the purpose of treating sickle cell anemia patients with uncomplicated painful crises in a way that greatly improves their rate of recovery, their hospitalization rates that also favorably affects the in house hospitalization length of stay. This proposal is complemented by two above-the caplemented by two above -the-cap Clinical Project Proposals, both based on last cycle accomplishments.

该提案包括：一个临床项目l_Proje-t 2：PI：Dr. Fabry），该项目建立在Pi在以下领域的开创性工作基础上： 在BOLD-MRI和现在的近红外光谱（NIRS）的发展周期，以测量氧合： 养老金和血容量它，镰状细胞患者和新型镰状转基因小鼠。目的是确定这些 最先进的技术可以帮助评估sicMe对大脑、肾脏和肌肉的损害。此外还有 有三个翻译！研究项目，旨在寻找SCD的潜在有用的治疗干预措施， 临床前发展的几个基础研究策略。他们是：项目I（PI：Acharya博士）， 基于所述聚合物，产生具有比所述范式HbF更大的聚合抑制潜力的球蛋白链。 在前一个周期中，开创性的发现，猪sigma链完全神经化人类B5聚合。 以限定足以赋予人所需性质的猪-γ-链序列的最小数目 伽马珠蛋白链。在这个过程中，我们将了解镰刀形聚合物的五元结构以及 半合成项目3（主要参与者：Kaul博士）也是在上一周期所做工作的基础上开展的，但本提案的目的是 在知识的飞跃，因为它涉及：测试假设，一个异质阵列的红细胞整合素和 vWF、P-选择素、层粘连蛋白和NO参与镰状细胞粘附，并检验γ、β 3、阴离子 多糖和羟基脲可用于阻断镰状细胞粘附。项目4（PI;内格尔博士）建立在 长期以来，人们一直对镰状表型中的乳化基因的参与感兴趣。该项目旨在通过最先进的技术， 微阵列技术，负责镰状细胞性贫血多效性效应的基因，以及这些基因中的哪一个， 具有上位（修饰）能力，以定义严重风险并探索B基因簇中潜在的表观遗传效应 与镰刀基因相关的单倍型这些项目得到行政核心-跨性别核心（在 开发镰状动物模型的最前沿），通过微芯片核心（也应该是我们内部的微阵列 设施），一个强大的临床和病人服务中心，率先将日间医院的概念变成现实， 治疗镰状细胞性贫血患者的目的是以一种大大提高其发病率的方式， 的恢复，他们的住院率，也有利地影响在内部住院住院时间。这项建议 由两个以上的临床项目建议书补充，两者都是基于上一个周期的成就。