oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Update of Faecal Markers of Inflammation in Children with Cystic Fibrosis  [PDF]
Jung M. Lee,Steven T. Leach,Tamarah Katz,Andrew S. Day,Adam Jaffe,Chee Y. Ooi
Mediators of Inflammation , 2012, DOI: 10.1155/2012/948367
Abstract: There is evidence of intestinal inflammation in patients with CF. Intestinal inflammation may negatively impact the nutritional status of patient with CF, which adversely affects pulmonary function and survival. This paper provides an up-to-date review of intestinal inflammation in CF and an evaluation of utility of two specific faecal inflammatory markers (S100A12 and calprotectin). 1. Introduction Cystic fibrosis (CF) is the most common, life-shortening, recessive disease in Caucasians with an average life expectancy of 40 years [1]. In the majority of cases, mortality in CF is due to respiratory failure. CF is caused by mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein [2, 3]. The CFTR protein functions on the apical surface of epithelial cells as a cyclic AMP-dependent chloride and a bicarbonate channel [4, 5]. Absent or defective CFTR leads to viscous luminal secretions in affected organs particularly in the lungs, intestines, and pancreas. The nutritional status of CF patients is a major determinant of pulmonary and survival outcomes. Longitudinal cohort studies in CF report a distinct survival advantage among patients with better nutritional status [6–8]. More specifically, poor nutritional status is not only strongly linked to poorer lung function but was also an independent risk factor for early death in children with CF. Several factors contribute to impaired nutritional status in CF. These include malabsorption, recurrent sinopulmonary infections, increased energy expenditure, and suboptimal intake [9]. The malabsorptive state in CF is likely multifactorial. The primary cause of malabsorption is due to maldigestion from pancreatic exocrine insufficiency. However, children with CF can continue to have malabsorption despite pancreatic enzyme replacement therapy (PERT) administration. It has been previously suggested that the presence of an acidic intestinal milieu, that impairs enzyme activity, contributes to the failure of PERT in nutrient assimilation in CF. More recently, intestinal inflammation has been hypothesized as another contributing factor. 2. Intestinal Inflammation in Cystic Fibrosis There is increasing evidence of intestinal inflammation in CF. Although the exact underlying mechanism is unknown, there have been several pathogenic mechanisms proposed (Figure 1). As a primary consequence of a defective CFTR, intestinal mucus secretions are viscid and inspissated due to dehydration, are in an acidic milieu, and have altered glycosylation of mucins [10, 11]. Such
The Cystic Fibrosis Transmembrane Regulator (CFTR) in the kidney
MORALES, MARCELO M.;FALKENSTEIN, DORIS;LOPES, ANíBAL GIL;
Anais da Academia Brasileira de Ciências , 2000, DOI: 10.1590/S0001-37652000000300013
Abstract: the cystic fibrosis transmembrane regulator (cftr) is a cl - channel. mutations of this transporter lead to a defect of chloride secretion by epithelial cells causing the cystic fibrosis disease (cf). in spite of the high expression of cftr in the kidney, patients with cf do not show major renal dysfunction, but it is known that both the urinary excretion of drugs and the renal capacity to concentrate and dilute urine is deficient. cftr mrna is expressed in all nephron segments and its protein is involved with chloride secretion in the distal tubule, and the principal cells of the cortical (ccd) and medullary (imcd) collecting ducts. several studies have demonstrated that cftr does not only transport cl - but also secretes atp and, thus, controls other conductances such as na+ (enac) and k+ (romk2) channels, especially in ccd. in the polycystic kidney the secretion of chloride through cftr contributes to the cyst enlargement. this review is focused on the role of cftr in the kidney and the implications of extracellular volume regulators, such as hormones, on its function and expression.
The Cystic Fibrosis Transmembrane Regulator (CFTR) in the kidney  [cached]
MORALES MARCELO M.,FALKENSTEIN DORIS,LOPES ANíBAL GIL
Anais da Academia Brasileira de Ciências , 2000,
Abstract: The cystic fibrosis transmembrane regulator (CFTR) is a Cl- channel. Mutations of this transporter lead to a defect of chloride secretion by epithelial cells causing the Cystic Fibrosis disease (CF). In spite of the high expression of CFTR in the kidney, patients with CF do not show major renal dysfunction, but it is known that both the urinary excretion of drugs and the renal capacity to concentrate and dilute urine is deficient. CFTR mRNA is expressed in all nephron segments and its protein is involved with chloride secretion in the distal tubule, and the principal cells of the cortical (CCD) and medullary (IMCD) collecting ducts. Several studies have demonstrated that CFTR does not only transport Cl- but also secretes ATP and, thus, controls other conductances such as Na+ (ENaC) and K+ (ROMK2) channels, especially in CCD. In the polycystic kidney the secretion of chloride through CFTR contributes to the cyst enlargement. This review is focused on the role of CFTR in the kidney and the implications of extracellular volume regulators, such as hormones, on its function and expression.
CFTR and Ca2+ Signaling in Cystic Fibrosis  [PDF]
Caroline Norez,Frédéric Becq,Clarisse Vandebrouck
Frontiers in Pharmacology , 2011, DOI: 10.3389/fphar.2011.00067
Abstract: Among the diverse physiological functions exerted by calcium signaling in living cells, its role in the regulation of protein biogenesis and trafficking remains incompletely understood. In cystic fibrosis (CF) disease the most common CF transmembrane conductance regulator (CFTR) mutation, F508del-CFTR generates a misprocessed protein that is abnormally retained in the endoplasmic reticulum (ER) compartment, rapidly degraded by the ubiquitin/proteasome pathway and hence absent at the plasma membrane of CF epithelial cells. Recent studies have demonstrated that intracellular calcium signals consequent to activation of apical G-protein-coupled receptors by different agonists are increased in CF airway epithelia. Moreover, the regulation of various intracellular calcium storage compartments, such as ER is also abnormal in CF cells. Although the molecular mechanism at the origin of this increase remains puzzling in epithelial cells, the F508del-CFTR mutation is proposed to be the onset of abnormal Ca2+ influx linking the calcium signaling to CFTR pathobiology. This article reviews the relationships between CFTR and calcium signaling in the context of the genetic disease CF.
Molecular Chaperones as Targets to Circumvent the CFTR Defect in Cystic Fibrosis  [PDF]
Ronald C. Rubenstein
Frontiers in Pharmacology , 2012, DOI: 10.3389/fphar.2012.00137
Abstract: Cystic Fibrosis (CF) is the most common autosomal recessive lethal disorder among Caucasian populations. CF results from mutations and resulting dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). CFTR is a cyclic AMP-dependent chloride channel that is localized to the apical membrane in epithelial cells where it plays a key role in salt and water homeostasis. An intricate network of molecular chaperone proteins regulates CFTR’s proper maturation and trafficking to the apical membrane. Understanding and manipulation of this network may lead to therapeutics for CF in cases where mutant CFTR has aberrant trafficking.
Mutation Analysis of CFTR Gene in 70 Iranian Cystic Fibrosis Patients
Reza Alibakhshi,Mahdi Zamani
Iranian Journal Of Allergy, Asthma and Immunology , 2006,
Abstract: Cystic fibrosis (CF) is the most common inherited disorder in Caucasian populations, with over 1400 cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The type of mutations and their distributions varies widely between different countries and/or ethnic groups. Seventy Iranian cystic fibrosis patients were screened for the CFTR gene mutation using ARMS/PCR (amplification refractory mutation system) for the following mutations: F508, N1303K, G542X, 1717-1G>A, R553X, W1282X, G551D, 621+1G>T, I507 and R560T. Single strand conformation polymorphism (SSCP) analysis of exons 3, 7, 10, 11 and 17b, including both the exon/intron junctions, of the CFTR gene was performed in patients in whom no mutation could be identified on one or both CFTR genes. As a result of this screening, only three mutations were found: F508 mutation was found in 25 (17.8%) alleles, N1303K in six (4.3%) alleles and G542X in five (3.6%) alleles. Thus, a total of 3 mutations cover 25.7% of CF alleles. These finding will be used for planning future screening and appropriate genetic counseling programs in Iranian CF patients.
Defective CFTR Expression and Function Are Detectable in Blood Monocytes: Development of a New Blood Test for Cystic Fibrosis  [PDF]
Claudio Sorio,Mario Buffelli,Chiara Angiari,Michele Ettorre,Jan Johansson,Marzia Vezzalini,Laura Viviani,Mario Ricciardi,Genny Verzè,Baroukh Maurice Assael,Paola Melotti
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0022212
Abstract: Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes.
Correcting the Cystic Fibrosis Disease Mutant, A455E CFTR  [PDF]
Liudmila Cebotaru, Daniele Rapino, Valeriu Cebotaru, William B. Guggino
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0085183
Abstract: Cystic fibrosis is caused by more than 1000 mutations, the most common being the ΔF508 mutation. These mutations have been divided into five classes [1], with ΔF508 CFTR in class II. Here we have studied the class V mutation A455E. We report that the mature and immature bands of A455E are rapidly degraded primarily by proteasomes; the short protein half-life of this mutant therefore resembles that of ΔF508 CFTR. A455E could be rescued by treatment of the cells with proteasome inhibitors. Furthermore, co-transfection of A455E with the truncation mutant Δ264 CFTR also rescued the mature C band, indicating that A455E can be rescued by transcomplementation. We found that Δ264 CFTR bound to A455E, forming a bimolecular complex. Treatment with the compound correctors C3 and C4 also rescued A455E. These results are significant because they show that although ΔF508 belongs to a different class than A455E, it can be rescued by the same strategies, offering therapeutic promise to patients with Class V mutations.
CFTR Mutations Spectrum and the Efficiency of Molecular Diagnostics in Polish Cystic Fibrosis Patients  [PDF]
Ewa Zi?tkiewicz, Ewa Rutkiewicz, Andrzej Pogorzelski, Barbara Klimek, Katarzyna Voelkel, Micha? Witt
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089094
Abstract: Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane regulator gene (CFTR). In light of the strong allelic heterogeneity and regional specificity of the mutation spectrum, the strategy of molecular diagnostics and counseling in CF requires genetic tests to reflect the frequency profile characteristic for a given population. The goal of the study was to provide an updated comprehensive estimation of the distribution of CFTR mutations in Polish CF patients and to assess the effectiveness of INNOLiPA_CFTR tests in Polish population. The analyzed cohort consisted of 738 patients with the clinically confirmed CF diagnosis, prescreened for molecular defects using INNOLiPA_CFTR panels from Innogenetics. A combined efficiency of INNOLiPA CFTR_19 and CFTR_17_TnUpdate tests was 75.5%; both mutations were detected in 68.2%, and one mutation in 14.8% of the affected individuals. The group composed of all the patients with only one or with no mutation detected (109 and 126 individuals, respectively) was analyzed further using a mutation screening approach, i.e. SSCP/HD (single strand conformational polymorphism/heteroduplex) analysis of PCR products followed by sequencing of the coding sequence. As a result, 53 more mutations were found in 97 patients. The overall efficiency of the CF allele detection was 82.5% (7.0% increase compared to INNOLiPA tests alone). The distribution of the most frequent mutations in Poland was assessed. Most of the mutations repetitively found in Polish patients had been previously described in other European populations. The most frequent mutated allele, F508del, represented 54.5% of Polish CF chromosomes. Another eight mutations had frequencies over 1%, 24 had frequencies between 1 and 0.1%; c.2052-2053insA and c.3468+2_3468+3insT were the most frequent non-INNOLiPA mutations. Mutation distribution described herein is also relevant to the Polish diaspora. Our study also demonstrates that the reported efficiency of mutation detection strongly depends on the diagnostic experience of referring health centers.
Analysis of CFTR gene mutations and Cystic Fibrosis incidence in the Ecuatorian population
Valle,édison Patricio; Burgos,Ramiro Israel; Valle,José Rubén; Béjar,Daniela Egas; Ruiz-Cabezas,Juan-Carlos;
Investigación Clínica , 2007,
Abstract: ecuador is one of the latin american countries where cystic fibrosis has not been thoroughly studied. the goal of this study was to establish the incidence of this specific pathology and the incidence of the 29 most common european cf mutations in ecuador′s population.we performed a prospective-descriptive study with the intention of including patients registered at the ecuadorian cystic fibrosis foundation as well as the main pediatric hospitals in ecuador. the inclusion criteria were clinical manifestations of cystic fibrosis plus two positive pilocarpine iontophoresis sweat tests (ci > 60 meq/l). we tested f508del mutation by heteroduplex method and then, we confirmed these results and searched for other 28 frequent european mutations aside from f508del by a reverse dot blot technique (inno-lipa cftr 29 + tn). sixty two unrelated patients were included. both heteroduplex and reverse dot blot methods identified 53.22% of all mutations. the estimated ecuadorian cystic fibrosis incidence was 1:11,252. the mutations found and their incidence were f508del (37.1%), g85e (8.9%), g542x (2.4%), n1303k (2.4%), g551d (1.6%) and r334w (0.8%). the incidence of cystic fibrosis in ecuador is closely similar to other latin american countries where there is a large ?mestizo? population. we are reporting one of the highest incidences of g85e in the world.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.