MASS SPECTROMETRY ANALYSIS OF THE HUMAN CSF PROTEOME

描述：（改编自申请人的摘要）我们假设 从人脑脊液（CSF）中获得的蛋白质组在对照组之间存在差异 而那些被诊断为特发性腰痛的患者， 初步数据清楚地表明，这两个方面存在显著差异 特定阿片样物质和特定速激肽的量的组 神经肽我们将把研究范围扩大到蛋白质和酶。我们将 首先从定性和定量的角度来实验性地检验我们的假设 分析CSF中阿片和速激肽神经肽能系统 蛋白质组，包括每种神经肽前体和相关酶。 内吗啡肽和其他相关的神经肽系统也将进行研究。的 蛋白质组将用电泳和质谱法分析。 我们将分析代谢级联中的含神经肽蛋白质 在神经元中合成每一种神经肽：DNA -> RNA -> 中等大小的蛋白质->神经肽->代谢物。这一级联涉及到 几种不同的酶（激素原转化酶、氨肽酶、肽基 甘氨酸酰胺化单加氧酶、脑啡肽酶等）。 使用利多卡因的脊柱鉴别诊断很容易区分 三种不同的腰痛患者群体-对照（疼痛;非疼痛 患者）、生理反应者（需要手术）和非生理反应者 响应者。非生理反应者包括两个亚组： 和特发性下背部患者。伪装者很容易识别（> CA。百分之九十五 准确性）通过心理测试（MMPI），并很容易被排除在外， study.我们的假设只集中在特发性腰痛组， 不知道他们的痛苦的原因。

DESCRIPTION: (adapted from applicant's abstract) We hypothesize that the proteome obtained from human cerebrospinal fluid (CSF) differs between controls and those patients who are diagnosed with idiopathic low back pain because our preliminary data clearly demonstrate significant differences in those two groups in the amount of a specific opioid and a specific tachykinin neuropeptide. We will expand our study to include proteins and enzymes. We will experimentally test our hypothesis by first qualitatively and quantitatively analyzing the opioid and tachykinin neuropeptidergic systems in the CSF proteome, including each neuropeptide precursor and associated enzymes. Endomorphins and other pertinent neuropeptide systems will also be studied. The proteome will be analyzed with electrophoresis and mass spectrometry. We will analyze the neuropeptide-containing proteins in the metabolic cascade that synthesizes each neuropeptide in the neuron: DNA -> RNA -> intermediate-sized proteins-> neuropeptide ->metabolites. That cascade involves several different enzymes (prohormone convertases, aminopeptidases, peptidyl glycine-amidating monooxygenase, enkephalinase, and others). A differential spinal diagnosis with lidocaine readily differentiates among the three different low back pain patient populations-controls (pain; non-pain patients), physiologic responders (require surgery), and nonphysiologic responders. The non-physiologic responders contain two subgroups: malingerers and idiopathic low back patients. Malingerers are readily identified (> ca. 95% accuracy) by a psychological test (MMPI), and are readily excluded from this study. Our hypothesis focuses only on the idiopathic low back pain group, which has no known reason for their pain.