Molecular Analysis of Ureteric Reflux

输尿管反流的分子分析

基本信息

  • 批准号:
    6793191
  • 负责人:
  • 金额:
    $ 11.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-08-20 至 2008-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Reflux nephropathy (RN) is a syndrome of renal scarring associated with primary vesico-ureteral reflux (VUR). Primary VUR is known to exhibit autosomal dominant inheritance. However, the genetic defect of primary VUR and its molecular pathogenesis are not well understood. The current diagnosis of VUR and RN involves radiologic tests which are invasive and costly. Therefore VUR screening in siblings and offspring and RN screening in patients with primary VUR are not routinely practised. Early detection of VUR is valuable for the prevention of RN since the incidence of scarring can be reduced effectively by antiobiotic prophylaxis. The long-term goals of this proposal are to develop less-invasive tests for early diagnosis and monitoring of VUR and RN as well as to develop therapeutic strategies based on a better understanding of the molecular pathogenesis. The hypothesis is that characteristic gene and protein expression patterns exist in ureteric tissue as well as in urine of patients with primary VUR and RN. Custom-spotted cDNA microarrays will be used to study differential gone expression. Surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy coupled with tandem mass spectroscopy will be used to study differential protein expression. This latter method is however limited to molecules smaller than 70 kD. For larger molecules, two-dimensional gel electrophoresis will be employed. Ureteric tissue from patients with primary VUR will be compared with those from patients with secondary VUR and normal controls from renal transplant donors. Urine samples from patients with primary and secondary VUR with and without RN will be compared with age- and gender-matched normal children. State-of-the-art bioinformatics methodologies will be used for data analysis. Confounding variables, including age, gender and presence of glomerular proteinuria will be considered. Identification of specific urinary biomarkers in patients with VUR and RN may lead to further understanding of the molecular pathogenesis, as well as the development of less-invasive screening tests for primary VUR and RN. A clinical database of primary VUR and RN will be set up to establish correlations between biomarkers and phenotype and to test the sensitivity and specificity of these markers for detecting primary VUR and RN.
描述(由申请人提供): 反流性肾病(RN)是一种与原发性膀胱输尿管反流(VUR)相关的肾脏瘢痕形成综合征。已知原发VUR表现为常染色体显性遗传。然而,原发性输尿管返流的遗传缺陷及其分子发病机制尚不清楚。目前VUR和RN的诊断涉及到具有侵入性和昂贵的放射学检查。因此,在兄弟姐妹和子女中进行输尿管返流筛查以及对原发输尿管返流患者进行肾小球肾炎筛查并不是常规做法。早期发现VUR对预防RN有重要价值,因为抗菌药物预防可有效降低瘢痕形成的发生率。这项建议的长期目标是开发侵入性较小的检测方法,用于VUR和RN的早期诊断和监测,并基于对分子发病机制的更好理解来开发治疗策略。假设输尿管和肾炎患者的输尿管组织和尿液中存在特有的基因和蛋白表达模式。定制斑点基因芯片将被用来研究差异表达的Gone。表面增强激光解吸/电离飞行时间质谱仪将与串联质谱仪联用来研究差异蛋白质的表达。然而,后一种方法仅限于小于70kD的分子。对于较大的分子,将采用双向凝胶电泳法。来自原发输尿管返流患者的输尿管组织将与来自肾移植供者的继发性输尿管返流患者和正常对照的输尿管组织进行比较。有和没有RN的原发和继发性VUR患者的尿样将与年龄和性别匹配的正常儿童进行比较。将使用最先进的生物信息学方法进行数据分析。混杂变量,包括年龄、性别和肾小球蛋白尿的存在将被考虑。在VUR和RN患者中识别特定的尿液生物标志物可能有助于进一步了解其分子发病机制,以及开发对原发VUR和RN进行更少侵入性的筛查试验。将建立原发VUR和RN的临床数据库,以建立生物标记物与表型之间的相关性,并测试这些标记物检测原发VUR和RN的敏感性和特异性。

项目成果

期刊论文数量(0)
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会议论文数量(0)
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ROBERT H MAK其他文献

ROBERT H MAK的其他文献

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{{ truncateString('ROBERT H MAK', 18)}}的其他基金

Targeting NLRP3 inflammasome for treating muscle complications of chronic kidney disease
靶向 NLRP3 炎性体治疗慢性肾病的肌肉并发症
  • 批准号:
    10399639
  • 财政年份:
    2020
  • 资助金额:
    $ 11.65万
  • 项目类别:
Targeting NLRP3 inflammasome for treating muscle complications of chronic kidney disease
靶向 NLRP3 炎性体治疗慢性肾病的肌肉并发症
  • 批准号:
    10034754
  • 财政年份:
    2020
  • 资助金额:
    $ 11.65万
  • 项目类别:
Targeting NLRP3 inflammasome for treating muscle complications of chronic kidney disease
靶向 NLRP3 炎性体治疗慢性肾病的肌肉并发症
  • 批准号:
    10240309
  • 财政年份:
    2020
  • 资助金额:
    $ 11.65万
  • 项目类别:
International Symposium on Growth and Nutrition in Chronic Kidney Disease
慢性肾脏病生长与营养国际研讨会
  • 批准号:
    8319197
  • 财政年份:
    2012
  • 资助金额:
    $ 11.65万
  • 项目类别:
Urinary Biomarkers for Steroid Resistant Nephrotic Syndr
类固醇抵抗性肾病综合征的尿液生物标志物
  • 批准号:
    6877282
  • 财政年份:
    2004
  • 资助金额:
    $ 11.65万
  • 项目类别:
Urinary Biomarkers for Steroid Resistant Nephrotic Syndr
类固醇抵抗性肾病综合征的尿液生物标志物
  • 批准号:
    6951059
  • 财政年份:
    2004
  • 资助金额:
    $ 11.65万
  • 项目类别:
Molecular Analysis of Ureteric Reflux
输尿管反流的分子分析
  • 批准号:
    7095325
  • 财政年份:
    2003
  • 资助金额:
    $ 11.65万
  • 项目类别:
Molecular Analysis of Ureteric Reflux
输尿管反流的分子分析
  • 批准号:
    6611870
  • 财政年份:
    2003
  • 资助金额:
    $ 11.65万
  • 项目类别:
Molecular Analysis of Ureteric Reflux
输尿管反流的分子分析
  • 批准号:
    6938668
  • 财政年份:
    2003
  • 资助金额:
    $ 11.65万
  • 项目类别:
GROWTH RETARDATION IN CHRONIC RENAL FAILURE
慢性肾衰竭的生长迟缓
  • 批准号:
    2701198
  • 财政年份:
    1997
  • 资助金额:
    $ 11.65万
  • 项目类别:

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Identification and characterization of genes in patients with severe mental retardation caused by autosomal dominant trait.
常染色体显性遗传性重度智力低下患者基因的鉴定和特征分析。
  • 批准号:
    13670158
  • 财政年份:
    2001
  • 资助金额:
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  • 项目类别:
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