Background: Most patients with cystic fibrosis (CF) have a DF508 mutation resulting in abnormal retention of mutant gene protein (DF508-CFTR) within the cell. This study was undertaken to investigate DF508-CFTR trafficking in native cells from patients with CF with the aim of discovering pharmacological agents that can move DF508-CFTR to its correct location in the apical cell membrane. Method:...

Choo-Kang, Lee R., and Pamela L. Zeitlin. Induction of HSP70 promotes DF508 CFTR trafficking. Am J Physiol Lung Cell Mol Physiol 281: L58–L68, 2001.— The DF508 cystic fibrosis transmembrane conductance regulator (CFTR) is a temperature-sensitive trafficking mutant that is detected as an immature 160-kDa form (band B) in gel electrophoresis. The goal of this study was to test the hypothesis that...

Background. Cystic fibrosis is a recessive disorder mainly characterized by lung disease. We tested the hypothesis that individuals heterozygous for the common cystic fibrosis DF508 mutation are at risk of obstructive pulmonary disease. Methods. We studied a cross-sectional sample from the general population of Copenhagen, Denmark, aged 20 years and older. We did spirometry to measure forced ex...

The most prevalent cystic fibrosis transmembrane conductance regulator (CFTR) mutation causing cystic fibrosis, DF508, impairs folding of nucleotide binding domain (NBD) 1 and stability of the interface between NBD1 and the membranespanning domains. The interfacial stability defect can be partially corrected by the investigational drug VX-809 (3-[6-[[[1-(2,2difluoro-1,3-benzodioxol-5-yl)cyclopr...

OBJECTIVE To determine the effects that mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and deletion of the glutathione S-transferase (GST) genes mu-1 (GSTM1) and theta-1 (GSTT1) have on the clinical course of cystic fibrosis (CF) in patients residing in the southeastern region of Brazil. METHODS The study sample consisted of all consecutive CF patients treated...

To define mutations present in 23 exons and flanking intronic sequences of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 95 patients from Rio de Janeiro, Brazil, we carried out single-strand conformation polymorphism analysis and automated direct sequencing. Mutation detection was achieved in 45% of the alleles presented, and complete genotyping (two mutated alleles) wa...

The cause of insulin insufficiency remains unknown in many diabetic cases. Up to 50% adult patients with cystic fibrosis (CF), a disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), develop CF-related diabetes (CFRD) with most patients exhibiting insulin insufficiency. Here we show that CFTR is a regulator of glucose-dependent electrical acitivitie...

significant difference in the cystic fibrosis transmembrane regulator DF508 allele prevalence, the number of patients should be increased dramatically. Hopefully, the worldwide existing large collections of DNA specimens from osteoporotic patients will provide an opportunity to enlighten the possible implication of a cystic fibrosis transmembrane regulator mutation in the development of osteopo...