NASAL ELECTRIC POTENTIAL DIFFERENCE IN NORMAL AND CYSTIC FIBROSIS PATIENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 囊性纤维化是高加索人最常见的致死性遗传病。囊性纤维化是由囊性纤维化跨膜传导调节基因突变引起的，该基因在受影响的上皮细胞顶膜上形成氯离子通道。由于CFTR功能的缺陷，受影响的上皮细胞有异常的跨上皮电解质转运。在呼吸道上皮细胞，包括鼻黏膜上皮，囊性纤维化缺陷被测量为异常升高的电压和对调节氯离子运输的试剂的异常反应。缺乏氯离子转运是诊断CF的一个标准。此外，基础Vt的增加和阿米洛利灌流后Vt的变化也被认为与CF的发病机制有关。然而，先前的数据表明，这可能对该病的发病机制没有意义。因此，这些研究人员提出了三个假设：a)鼻腔Vt测量可以作为评估CFTR功能和CFTR基因转移到体内呼吸道上皮细胞的终点；b)根据鼻腔Vt方案，没有CFT但有支气管扩张的患者将有异常的钠或氯转运；以及c)增加VtAmil的干预不会导致囊性纤维性肺部疾病。

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. Cystic fibrosis (CF) is the most common lethal genetic disease of Caucasians. CF is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) which forms a chloride channel in the apical membrane of affected epithelia. As a result of the defective function of the CFTR, affected epithelia have abnormal transepithelial electrolyte transport. In airway epithelia, including the nasal epithelium, the cystic fibrosis defect is measured as an abnormally increased voltage and an abnormal response to agents that modulate chloride transport. The lack of chloride transport is a diagnostic criteria for CF. In addition, an increase in basal Vt and the change in Vt after perfusion with amiloride have been implicated by others in the pathogenesis of CF. However, previous data suggest this may not be of significance for the pathogenesis of the disease. Thus, these investigators have developed three hypotheses: a) nasal Vt measurement can be used as an end point for evaluating CFTR function and CFTR gene transfer to airway epithelia in vivo; b) people wihout CF but with bronchiectasis will have an abnormal sodium or chloride transport as measured by the nasal Vt protocol; and c) interventions that increase the VtAmil will not result in cystic fibrosis lung disease.