ETIOLOGIC FACTORS IN FOCAL GLOMERULAR SCLEROSIS
局灶性肾小球硬化的病因
基本信息
- 批准号:2143253
- 负责人:
- 金额:$ 16.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-12-15 至 1996-11-30
- 项目状态:已结题
- 来源:
- 关键词:bioassay blood proteins endopeptidases gel filtration chromatography glomerular filtration glomerulosclerosis high performance liquid chromatography human subject ion exchange chromatography kidney transplantation laboratory rat method development plasmapheresis protein sequence proteinuria renal glomerulus serum albumin vascular endothelium permeability
项目摘要
The presence of a circulating factor that increases glomerular
macromolecular permeability in patients with focal sclerosing
glomerulonephritis (FSGS) is supported by recurrence of proteinuria in
the immediate post-transplant period and by the observation that
plasmapheresis is often effective in reversing this proteinuria.
Attempts to identify the factor responsible for glomerular injury in FSGS
have been largely unsuccessful. We have developed a sensitive in vitro
assay for glomerular protein permeability and have employed this assay
to demonstrate the presence of a factor in serum or plasma of patients
with FSGS which increases glomerular macromolecular permeability.
Incubation of glomeruli in media containing active sera increases albumin
permeability from a normal value of 0 to as high as 0.9. The presence
of this activity prior to transplantation is strongly associated with
early recurrence of proteinuria and progressive renal insufficiency
following renal transplantation. Preliminary studies suggest that the
active component is a protein of molecular weight 110-120 kD. Its
activity is rapid in onset and is concentration dependent. Activity is
neutralized by the presence of normal serum; this finding may explain the
difficulty that others have had in demonstrating its presence by infusion
into intact animals. The goals of the proposed studies are: 1) to purify
and characterize the albumin permeability enhancing factor from sera of
FSGS patients using ammonium sulphate precipitation, gel filtration, ion
exchange column chromatography, HPLC, gel electrophoresis and, if
necessary, isoelectric focusing and capillary electrophoresis; 2) to
determine the amino acid composition and amino acid sequence of the
factor in order to compare it to known proteins. The availability of a
bioassay for activity provides a unique opportunity to identify and
characterize the factor responsible for proteinuria and, in later
studies, to develop an immunologic assay for the factor, to identify its
source, to define its targets and mechanism of action, and, finally, to
develop rational and effective treatment for patients with FSGS.
一种循环因子的存在,
局灶性硬化患者的大分子渗透性
肾小球肾炎(FSGS)是由蛋白尿的复发支持,
移植后即刻,并观察到
血浆除去法通常能有效逆转这种蛋白尿。
FSGS中肾小球损伤因子的鉴定
基本上都不成功。 我们已经开发了一种敏感的体外
用于肾小球蛋白渗透性的测定,并已使用该测定
证明患者血清或血浆中存在某种因子
FSGS增加肾小球大分子渗透性。
在含有活性血清的培养基中孵育肾小球可增加白蛋白
渗透率从正常值0到高达0.9。 存在
移植前的这种活性与
蛋白尿和进行性肾功能不全的早期复发
肾移植后。 初步研究表明,
活性成分是分子量为110-120 kD的蛋白质。 其
活性是快速起效的并且是浓度依赖性的。 活动是
被正常血清的存在所中和;这一发现可以解释
其他人在通过输液证明其存在时遇到的困难
变成了完整的动物 本研究的目的是:1)纯化
并表征来自以下患者血清的白蛋白通透性增强因子:
FSGS患者使用硫酸铵沉淀,凝胶过滤,离子
交换柱层析、HPLC、凝胶电泳,如果
必要时,等电聚焦和毛细管电泳; 2)
测定了该蛋白的氨基酸组成和氨基酸序列,
将其与已知蛋白质进行比较。 的可用性
活性的生物测定提供了一个独特的机会,
描述了蛋白尿的原因,
研究,以开发一种免疫测定的因素,以确定其
来源,确定其目标和作用机制,最后,
为FSGS患者制定合理有效的治疗方案。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Virginia J. Savin其他文献
Virginia J. Savin的其他文献
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{{ truncateString('Virginia J. Savin', 18)}}的其他基金
Cytokine based murine focal glomerulosclerosis model a prelude to novel therapy
基于细胞因子的鼠局灶性肾小球硬化模型是新疗法的前奏
- 批准号:
8696811 - 财政年份:2011
- 资助金额:
$ 16.5万 - 项目类别:
Cytokine based murine focal glomerulosclerosis model a prelude to novel therapy
基于细胞因子的鼠局灶性肾小球硬化模型是新疗法的前奏
- 批准号:
8143226 - 财政年份:2011
- 资助金额:
$ 16.5万 - 项目类别:
Cytokine based murine focal glomerulosclerosis model a prelude to novel therapy
基于细胞因子的鼠局灶性肾小球硬化模型是新疗法的前奏
- 批准号:
8255321 - 财政年份:2011
- 资助金额:
$ 16.5万 - 项目类别:
Cytokine based murine focal glomerulosclerosis model a prelude to novel therapy
基于细胞因子的鼠局灶性肾小球硬化模型是新疗法的前奏
- 批准号:
8398954 - 财政年份:2011
- 资助金额:
$ 16.5万 - 项目类别:
Cardiotrophin-Like Cytokine 1, a Candidate Molecule for the FSGS Factor
心肌营养素样细胞因子 1,FSGS 因子的候选分子
- 批准号:
7988466 - 财政年份:2009
- 资助金额:
$ 16.5万 - 项目类别:
Cardiotrophin-Like Cytokine 1, a Candidate Molecule for the FSGS Factor
心肌营养素样细胞因子 1,FSGS 因子的候选分子
- 批准号:
7803655 - 财政年份:2009
- 资助金额:
$ 16.5万 - 项目类别:
Cardiotrophin-Like Cytokine 1, a Candidate Molecule for the FSGS Factor
心肌营养素样细胞因子 1,FSGS 因子的候选分子
- 批准号:
7588208 - 财政年份:2009
- 资助金额:
$ 16.5万 - 项目类别:
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