Disease relevance of Cystic Fibrosis

• In humans, many diseases, such as cystic fibrosis, hyperinsulinemia, and macular dystrophy, are traced to defects in ABC transporters [1].
• BACKGROUND AND METHODS: We conducted two multicenter, double-blind, placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection [2].
• In patients with cystic fibrosis and mild lung disease, high-dose ibuprofen, taken consistently for four years, significantly slows the progression of the lung disease without serious adverse effects [3].
• In patients with cystic fibrosis, mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene typically cause pulmonary and pancreatic insufficiency while rarely causing pancreatitis [4].
• In patients with cystic fibrosis, adenoviral-vector-mediated transfer of the CFTR gene did not correct functional defects in nasal epithelium, and local inflammatory responses limited the dose of adenovirus that could be administered to overcome the inefficiency of gene transfer [5].

Psychiatry related information on Cystic Fibrosis

• The new techniques of molecular genetics have allowed the successful chromosomal localization of mutant genes in disorders that show a simple Mendelian segregation, whether autosomal dominant (e.g. Huntington's disease), autosomal recessive (cystic fibrosis) or X-linked (Duchenne muscular dystrophy) [6].
• A useful model of a disease with abnormal airway epithelial ion transport is cystic fibrosis (CF), a distinct genetic syndrome of altered lung defense mechanisms characterized by chronic bacterial infection and a steady decline in lung function [7].
• Whole-body protein metabolism was studied in 11 undernourished cystic fibrosis (CF) patient (7 female), 12 normally nourished CF patients (3 female), 7 anorexia nervosa (AN) patients (all female), and 15 normal control subjects (9 female) [8].
• BACKGROUND: A study was undertaken to observe the gains in bone mass in children and adolescents with cystic fibrosis (CF) over 24 months and to examine the relationship between areal bone mineral density (aBMD) and associated clinical parameters including physical activity, nutrition, and 25-hydroxyvitamin D (25OHD) [9].
• Pulmonary function, nutrition, and self-concept in cystic fibrosis summer campers [10].

High impact information on Cystic Fibrosis

• As a consequence, mutations in CFTR result in both impaired Cl(-) secretion and enhanced Na(+) absorption in the colon of cystic fibrosis (CF) patients [11].
• An incomplete understanding of the molecular mechanisms by which alterations in an apical membrane chloride conductance could give rise to the various clinical manifestations of cystic fibrosis has prompted the suggestion that CFTR may also play a role in the normal function of certain intracellular compartments [12].
• Current knowledge of CFTR structure and function may help us understand better its mechanism of action, its role in electrolyte transport, its dysfunction in cystic fibrosis, and its relationship to other ABC transporters [13].
• Physiol. Rev. 79, Suppl.: S167-S173, 1999. - Many of the mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that cause cystic fibrosis interfere with the folding and biosynthetic processing of nascent CFTR molecules in the endoplasmic reticulum [14].
• Rad50cd crystal structures identify probable protein and DNA interfaces and reveal an ABC-ATPase fold, linking Rad50 molecular mechanisms to ABC transporters, including P glycoprotein and cystic fibrosis transmembrane conductance regulator [15].

Chemical compound and disease context of Cystic Fibrosis

• Aerosolized tobramycin in patients with cystic fibrosis [16].
• Ibuprofen in patients with cystic fibrosis [17].
• The glycine/taurine ratio of conjugated bile acids were lower in enzyme-treated patients with cystic fibrosis (3.7 +/- 0.6) than in patients off treatment (6.4 +/- 1.0), but was higher (P less than 0.01) than in controls (1.8 +/- 0.2) [18].
• The cystic fibrosis gene was recently cloned, and a three-base deletion removing phenylalanine 508 from the coding region was identified as the mutation on the majority of cystic fibrosis chromosomes [19].
• CFTR, the protein associated with cystic fibrosis, is phosphorylated on serine residues in response to cAMP agonists [20].
• A combination of factors that dissolve DNA/filamentous-actin aggregates together with lipopolysaccharide-binding agents may represent a potential treatment for the chronic infections that occur in cystic fibrosis airways [21].

Biological context of Cystic Fibrosis

• Since mutations with this phenotype represent at least 70% of known CF chromosomes, we argue that the molecular basis of most cystic fibrosis is the absence of mature CFTR at the correct cellular location [22].
• Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice [23].
• Despite an increased understanding of the cellular and molecular biology of the CFTR Cl- channel, it is not known how defective Cl- transport across airway epithelia causes chronic bacterial infections in cystic fibrosis (CF) airways [24].
• Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function, with low systemic toxicity [25].
• The diagnosis is based on the occurrence of chronic sinopulmonary infections, persistent azoospermia, normal spermatogenesis, and characteristic epididymal findings, as well as exclusion of cystic fibrosis and the immotile-cilia syndrome [26].

Anatomical context of Cystic Fibrosis

• Microelectrode studies established that extracellular UTP stimulated a larger increase in PD and chloride secretory current in epithelial cells from patients with cystic fibrosis than in cells from normal subjects, by actions localized to the apical membrane [27].
• We have administered a recombinant adenovirus vector (AdCFTR) containing the normal human CFTR cDNA to the nasal and bronchial epithelium of four individuals with cystic fibrosis (CF) [28].
• Higher bioelectric potentials due to decreased chloride absorption in the sweat glands of patients with cystic fibrosis [29].
• An adenoviral vector containing the normal CFTR complementary DNA in four logarithmically increasing doses (estimated multiplicity of infection, 1, 10, 100, and 1000), or vehicle alone, was administered in a randomized, blinded fashion to the nasal epithelium of 12 patients with cystic fibrosis [5].
• We have used gene targeting in embryonic stem cells to introduce an HPRT mini-gene into the coding sequence of the murine cystic fibrosis gene (cftr) [30].

Gene context of Cystic Fibrosis

• The CLD locus was previously mapped to 7q3 adjacent to the cystic fibrosis gene (CFTR) [31].
• We have generated mice carrying the most common mutation in cystic fibrosis (CF), delta F508, within the cystic fibrosis (Cftr) gene [32].
• It is a member of the ABC (ATP-binding cassette) superfamily of transporters, which includes many bacterial transport systems, the putative peptide transporter from the major histocompatibility locus, and the product of the cystic fibrosis gene (the cystic fibrosis transmembrane regulator, CFTR) [33].
• This localization and the pharmacology, voltage-dependence and stimulation by cyclic AMP of KCNQ1/KCNE3 currents indicate that these proteins may assemble to form the potassium channel that is important for cyclic AMP-stimulated intestinal chloride secretion and that is involved in secretory diarrhoea and cystic fibrosis [34].
• Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line [35].
• Staining for EGFR and for pro-transforming growth factor alpha were increased in the epithelium of patients with cystic fibrosis; positive correlations were found between EGFR-stained volume density and both AB/PAS and IL8-stained volume densities [36].

Analytical, diagnostic and therapeutic context of Cystic Fibrosis

• Gene therapy for cystic fibrosis (CF) will require the safe transfer of CFTR cDNA to airway epithelia in vivo [37].
• The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique [38].
• Birth after preimplantation diagnosis of the cystic fibrosis delta F508 mutation by polymerase chain reaction in human embryos resulting from intracytoplasmic sperm injection with epididymal sperm [39].
• We studied the prevalence of serum antibodies to Legionella pneumophila in patients with cystic fibrosis (CF) by indirect immunofluorescence [40].
• Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model [41].

References