CAMP STIMULATED SWEAT RATE IN CYSTIC FIBROSIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。该项目的目标是开发一种环磷酸腺苷(CAMP)刺激的“出汗率”测试，该测试将区分囊性纤维化跨膜电导调节器(CFTR)的全功能、部分功能和非功能形式。胆碱能和肾上腺素能激动剂都能刺激汗液的产生。收集胆碱能刺激汗液并随后测量汗液氯化物浓度是囊性纤维化(CF)标准诊断试验--匹罗卡品离子导入汗液试验的基础。毛果芸香碱刺激汗液的产生，会导致汗腺产生等渗性分泌物。在非CF患者中，当分泌物穿过汗管时，氯化物被重新吸收，导致皮肤上出现的汗液中的氯化物浓度较低。这种氯再吸收依赖于功能性CFTR的存在。在缺乏功能性CFTR的CF患者中，汗氯化物浓度仍然很高，这是CF与非CF患者的最大区别，但不是全部。然而，这项技术不能区分CFTR突变的杂合子携带者和非携带者，汗液氯浓度也不与疾病严重程度相关。假设cAMP介导的出汗率的测量将区别于CF受试者、非CF受试者和CFTR突变的未受影响的携带者。第二个假设是，CFTR活性和出汗率之间存在相关性，因此CFTR突变的未受影响的携带者与CF和非CF对照组受试者的出汗率处于中等水平。另一个次要假设是，不同类别的cftr突变可能与不同程度的出汗率有关。所有年龄和性别的科目都有资格参赛。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is the development of a cyclic-AMP(cAMP)-stimulated "sweat rate" test that will discriminate between fully functional, partially functional, and non-functional forms of the Cystic Fibrosis Transmembrane Conductance Regulator(CFTR). Sweat production can be stimulated by both cholinergic amp; adrenergic agonists. Collection of cholinergic stimulated sweat amp; the subsequent measurement of sweat chloride concentration is the basis of a standard diagnostic test for cystic fibrosis (CF), the pilocarpine iontophoresis sweat test. Stimulation of sweat production with pilocarpine leads to initial production of an isotonic secretion in the sweat gland. In non-CF patients, as the secretion traverses the sweat duct, chloride is reabsorbed leading to low concentrations of chloride in sweat as it appears on the skin. This chloride resorption is dependent on the presence of functional CFTR. In CF patients, who lack functional CFTR, the sweat chloride concentration remains high, amp; distinguishes most, but not all, CF from non-CF patients. However, this technique does not distinguish heterozygote carriers of CFTR mutations from non-carriers, nor does the sweat chloride concentration correlate with disease severity. The hypothesis is that measurement of cAMP-mediated sweat rates will distinguish among CF subjects, non-CF subjects, and non-affected carriers of CFTR mutations. A secondary hypothesis is that there will be a correlation between CFTR activity and sweat rate such that non-affected carriers of CFTR mutations will have intermediate sweat rates to CF and non-CF control subjects. Another secondary hypothesis is that different classes of CFTR mutations can be associated with different levels of sweat rate. Subjects of both genders and all ages are eligible for entry.