PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “CYSTIC FIBROSIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1999

Abnormal expression of the cystic fibrosis transmembrane regulator in chronic sinusitis in cystic fibrosis and non-cystic fibrosis patients.

Cystic fibrosis (CF) patients commonly suffer from chronic sinusitis. Mutations of a single gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, have been associated with CF. Functional CFTR protein is localized to the apical cell membrane, while dysfunctional CFTR is commonly found in the cytoplasm. We undertook a preliminary immunocytochemical study of CFTR subcellular localization in CF and non-CF pediatric and adult patients using a newly developed murine monoclonal antibody, TAM. Immunostaining was evaluated for subcellular localization (cytoplasmic versus membranous) and for epithelial layer (basal versus luminal). Analysis of the predominant CFTR distribution patterns demonstrated significant differences in adult versus pediatric groups independent of whether the latter were CF or non-CF (p<.0001 and p<.008, respectively), and no significant difference between the 2 pediatric groups (p = .70). This suggests that the pathophysiology of pediatric sinusitis differs from that of adult sinusitis at the level of secretion production.

Adolescent↗
PubMed2000

Newborn screening for cystic fibrosis.

BACKGROUND: This review was performed to test the hypothesis that presymptomatic diagnosis, for example by newborn screening, and early treatment may prevent or reduce irreversible organ damage and thereby improve outcome and quality of life in patients with cystic fibrosis. OBJECTIVES: To determine whether there is evidence that early diagnosis of cystic fibrosis by means of neonatal screening, followed by current treatment, improves survival and long term morbidity, without unacceptable adverse effects. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Trials Register. Additional studies were identified by one of the reviewers from handsearching conference proceedings not included in the Cochrane Register. Pharmaceutical companies manufacturing screening tests for cystic fibrosis were also contacted to identify any trials of neonatal screening for cystic fibrosis. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudorandomised controlled trials, published and unpublished, comparing screening followed by early treatment to clinical diagnosis and later treatment in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Four reviewers independently assessed trial eligibility and methodological quality and two of these reviewers independently extracted data. MAIN RESULTS: Two trials involving a total of 1,124,483 neonates met inclusion criteria. A total of 210 patients with cystic fibrosis aged from zero to 11 years with a maximum follow-up of eleven years are included. Concealment of allocation was unclear in both studies. Sequence generation was adequate in one study and unclear in the other. Method to ascertain cases was similar in one study and not similar in the other. An intention-to-screen-analysis was possible in one study, but could not be made due to lack of data and was not performed in the other. Differences in study design, variation in outcomes reported and their summary measures precluded calculation of pooled screening estimates. Only data from one study could be analysed in this review. This study reported a reduced risk of weight and height below the fifth percentile among screened patients (odds ratio control compared with screened group for: weight 6.16, 95% Confidence Interval (CI) 2.44, 15.57 and height 5.03, 95% CI 1. 63, 15.63). Adverse effects among parents in the screened and control populations were examined, but it is difficult to assess how meaningful these results are as the timing of the administration of the questionnaire to each group was not clear. Estimation of direct medical costs of screening suggested it was cheaper to diagnose cystic fibrosis by screening rather than other methods. The costing methods used however were not fully described and costs have not been related to effect. REVIEWER'S CONCLUSIONS: There are few randomised controlled trials assessing the effectiveness of neonatal screening in cystic fibrosis. From the data available at this time, there is little evidence suggesting benefit from screening for cystic fibrosis in the neonatal period, although there is similarly little evidence of harm. This systematic review has identified the need for individual patient data from both included studies. Although we have not been able to perform a meta-analysis, this review provides a summary of all the information currently available from randomised controlled trials on the effectiveness of neonatal screening for cystic fibrosis.

Cystic Fibrosis↗
PubMed2004

Cystic fibrosis -- therapeutic challenge in cystic fibrosis children.

Cystic fibrosis (CF) is the most common autosomal recessive disease with fatal outcome in Caucasians with a frequency of 1 in 2500 life births. It is caused by mutations in a single gene on the long arm of chromosome 7 encoding a protein called the cystic fibrosis transmembrane regulator (CFTR). The defect in CFTR leads to pathological changes in all organs with mucus-secretory glands, e.g. airways, pancreas, gut, biliary tract, vas deferens and sweat glands. Despite impressive advances in understanding the molecular basis of the disease, life expectancy is still limited in CF and chronic infection of the lung resulting in fibrosis and bronchiectasis followed by respiratory insufficiency is still the main factor in morbidity and the leading cause of death. Poor nutritional status is one of the major problems in the vicious cycle of chronic inflammation and lung destruction and its impact on outcome in lung function has been demonstrated. The possible role of growth hormone treatment in this context will be discussed.

Child↗
PubMed1981

Effect of cystic fibrosis and non-cystic fibrosis plasma on the movement and retention of 45Ca2+ and 35SO42- in guinea-pig stomach and small intestine.

The effect of cystic fibrosis plasma on the net fluxes of 45Ca2+ and 35SO42- across the guinea-pig stomach and small intestine was investigated, using an automatic short-circuit current apparatus. A significant increase in net fluxes across the stomach and small intestine for 45Ca2+ in the presence of cystic fibrosis plasma compared with non-cystic fibrosis plasma was observed. There was an increase in net flux for 35SO42- across the stomach in the presence of cystic fibrosis plasma when compared with non-cystic fibrosis plasma. However, there was a more highly significant increase in net fluxes for 35SO42- across the small intestine in the presence of cystic fibrosis plasma when compared with non-cystic fibrosis plasma. The amount of 45Ca2+ activity retained by the stomach and small intestine is more highly significant in the presence of cystic fibrosis plasma than in the presence of non-cystic fibrosis plasma. The retention of 35SO42- activity by the stomach and small intestine in the presence of cystic fibrosis plasma when compared with non-cystic fibrosis plasma was also highly significant. These findings indicate that cystic fibrosis plasma increases the net fluxes and raises retention of 45Ca2+ and 35SO42- in guinea-pig stomach and small intestine.

Animals↗
PubMed1998

Membrane trafficking of the cystic fibrosis gene product, cystic fibrosis transmembrane conductance regulator, tagged with green fluorescent protein in madin-darby canine kidney cells.

The mechanism by which cAMP stimulates cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride (Cl-) secretion is cell type-specific. By using Madin-Darby canine kidney (MDCK) type I epithelial cells as a model, we tested the hypothesis that cAMP stimulates Cl- secretion by stimulating CFTR Cl- channel trafficking from an intracellular pool to the apical plasma membrane. To this end, we generated a green fluorescent protein (GFP)-CFTR expression vector in which GFP was linked to the N terminus of CFTR. GFP did not alter CFTR function in whole cell patch-clamp or planar lipid bilayer experiments. In stably transfected MDCK type I cells, GFP-CFTR localization was substratum-dependent. In cells grown on glass coverslips, GFP-CFTR was polarized to the basolateral membrane, whereas in cells grown on permeable supports, GFP-CFTR was polarized to the apical membrane. Quantitative confocal fluorescence microscopy and surface biotinylation experiments demonstrated that cAMP did not stimulate detectable GFP-CFTR translocation from an intracellular pool to the apical membrane or regulate GFP-CFTR endocytosis. Disruption of the microtubular cytoskeleton with colchicine did not affect cAMP-stimulated Cl- secretion or GFP-CFTR expression in the apical membrane. We conclude that cAMP stimulates CFTR-mediated Cl- secretion in MDCK type I cells by activating channels resident in the apical plasma membrane.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Islet autoantibodies and insulin dependent diabetes mellitus in cystic fibrosis.

Cystic fibrosis-related diabetes mellitus (CF-DM) is thought to be secondary to beta-cell destruction by fibrous tissue replacing the exocrine pancreas. The aim of this study was to investigate the hypothesis that other factors may also be responsible. Glutamic acid decarboxylase (GAD) and islet cell (IA-2) antibodies were measured by quantitative ELISA in a group of patients with CF (n=30) in comparison to a group of newly diagnosed DM type 1 (IDDM) patients (n=30) and normal subjects (n=30). GAD antibodies were positive (>32 ng/ml) in 50% of the CF, 93% of the IDDM and 0% of the control group. IA-2 antibodies were detected (>0.9 U/ml) in 40% of the CF, 93% of the IDDM and 0% of the control group. Among the fifteen CF patients with positive GAD and IA-2 antibodies, four already had IDDM and another five abnormally low (<45 mU/l) first phase insulin response (FPIR) indicating a prediabetic state. We conclude that factors other than mechanical may be involved in the development of CFDM. The presence of autoantibodies predicting IDDM supports the hypothesis that CF-DM may have a multifactorial pathogenesis.

Adolescent↗
PubMed1993

Cystic fibrosis--V. Does cystic fibrosis alter the values of dynamic parameters of erythrocyte membrane ghosts?

1. The dynamic properties of erythrocyte membranes in CF children have been investigated by means of fluorescence and ESR techniques. 2. It has been revealed that the apparent distance separating the membrane protein tryptophan and bound 1-anilino-8-naphthalenesulphonate (ANS) molecules is decreased in CF children which results in a significant increase of the maximum energy transfer efficiency. 3. The slight increase in the ratio hw/hs of maleimide bound to membrane protein-SH groups of erythrocytes in cystic fibrosis may ensue the lowered membrane protein immobilization in the plane of lipid bilayer, especially at the intrinsic, more slowly reacting thiol groups.

Anilino Naphthalenesulfonates↗
PubMed2006

Proteomic analysis of nasal cells from cystic fibrosis patients and non-cystic fibrosis control individuals: search for novel biomarkers of cystic fibrosis lung disease.

Potential biological markers for cystic fibrosis (CF) lung disease were identified by comparative proteomics profiling of nasal cells from deletion of phenylalanine residue 508 (F508del)-homozygous CF patients and non-CF controls. From the non-CF 2-DE gels, 65 spots were identified by MS, and a reference 2-DE map was thus established. The majority of those correspond to ubiquitously expressed proteins. Consistent with the epithelial origin of this tissue, some of the identified proteins are epithelial markers (e.g. cytokeratins, palate lung and nasal epithelium clone protein (PLUNC), and squamous cell carcinoma antigen 1). Comparison of this protein profile with the one similarly obtained for CF nasal cells revealed a set of differentially expressed proteins. These included proteins related to chronic inflammation and some others involved in oxidative stress injury. Alterations were also observed in the levels of cytoskeleton proteins, being probably implicated with cytoskeleton organization changes described to occur in CF-airways. Lower levels were found for some mitochondrial proteins suggesting an altered mitochondrial metabolism in CF. Differential expression was also found for two more enzymes that have not been previously associated to CF. Further studies will clarify the involvement of such proteins in CF pathophysiology and whether they are targets for CF therapy.

Adolescent↗
PubMed2006

Relationships between cystic fibrosis transmembrane conductance regulator, extracellular nucleotides and cystic fibrosis.

Cystic fibrosis (CF) is one of the most common lethal autosomal recessive genetic diseases in the Caucasian population, with a frequency of about 1 in 3000 livebirths. CF is due to a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding the CFTR protein, a cyclic adenosine 5'-monophosphate (cAMP)-regulated chloride channel localized in the apical membrane of epithelial cells. CFTR is a multifunctional protein which, in addition to be a Cl-channel, is also a regulator of multiple ion channels and other proteins. In particular CFTR has been reported to play a role in the outflow of adenosine 5'-triphosphate (ATP) from cells, but this remains controversial. Extracellular nucleotides are signaling molecules that regulate ion transport and mucociliary clearance by acting on P2 nucleotide receptors, in particular the P2Y(2) receptor. Nucleotides activating the P2Y(2) receptor represent thus one pharmacotherapeutic strategy to treat CF disease, via improvement of mucus hydration and mucociliary clearance in airways. Phase II clinical trials have recently shown that aerosolized denufosol (INS37217, Inspire(R)) improves pulmonary function in CF patients: denufosol was granted orphan drug status and phase III trials are planned. Here, we review what is known about the relationship between extracellular nucleotides and CFTR, the role of extracellular nucleotides in epithelial pathophysiology and their putative role as therapeutic agents.

Animals↗
PubMed1986

Effect of cystic fibrosis and non-cystic fibrosis plasma on 45Ca and 35SO4 uptake and retention by the small intestine at the cellular level in the guinea pig.

A highly significant increase in net fluxes across the guinea-pig small intestine for both 45Ca2+ and 35SO4(2-), in the presence of cystic fibrosis plasma compared with non-cystic fibrosis plasma, was observed (p less than 0.001). In the presence of cystic fibrosis plasma, the nuclear, mitochondrial, microsomal and soluble fractions retained greater activity when compared with non-cystic fibrosis plasma. Of all the fractions, the nuclear fraction retained the highest activity both for 45Ca2+ and 35SO4(2-). These findings indicate that cystic fibrosis plasma increases the net fluxes and raises the retention of 45Ca2+ and 35SO4(2-) in guinea-pig small intestine at the cellular level.

Animals↗
PubMed2000

Nebulised hypertonic saline for cystic fibrosis.

BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance, recurrent bronchial infection and airway inflammation. Hypertonic saline has been shown to enhance mucociliary clearance in-vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To determine if nebulised hypertonic saline treatment improved lung function, exercise tolerance, quality of life and decreased the incidence of exacerbations of respiratory infections in patients with cystic fibrosis. SEARCH STRATEGY: Studies were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register. Titles and abstracts were reviewed to identify all controlled trials. Review articles and bibliographies identified from this process were surveyed for additional citations & RCTs. Identification of unpublished work was obtained from abstract books from the three major Cystic Fibrosis conferences (International Cystic Fibrosis Conference, The European Cystic Fibrosis Conference and the North American Cystic Fibrosis Conference). Trial authors were contacted for additional information when only abstracts were available to review. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All controlled trials that assessed the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in subjects with cystic fibrosis of any age or severity were reviewed. Studies in languages other than English were included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: Twelve controlled trials of hypertonic saline were identified. Seven trials met the inclusion criteria; these involved 143 subjects with an age range of 6 to 46 years. Of these, six were published studies and one in abstract form. The durations of the trials were limited to immediate effects on mucociliary clearance to a maximum of three weeks. In two studies, involving thirty five subjects, a score for the feeling of cleared chest was made using visual analogue scales. This analysis showed a weighted mean difference of -0.98 (95% confidence Interval -1.6, -0.34), favouring hypertonic saline over isotonic saline. In two trials with 22 subjects hypertonic saline improved mucociliary clearance as measured by isotope clearance from the lungs in 90 minutes demonstrating a weighted mean difference of -11.3 (95% confidence Interval -18.6, -4.0), and as area under the clearance time curve; weighted mean difference of -212 (95%CI -272, -152), also favouring hypertonic saline over isotonic saline. Lung function as measured by improvement in FEV1 was observed in one study of 27 subjects. The percentage increase in FEV1 at two weeks increased by a mean 15.0% with hypertonic saline and 2.8% with isotonic saline (p=0.004). Adverse events were adequately described in only one trial and none were serious. REVIEWER'S CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance immediately after administration which may have a longer term beneficial effect in cystic fibrosis. The maximum time data were recorded for was only three weeks. Most of the patients had mild to moderate lung disease and the effect on severe lung disease remains unclear. Further studies of hypertonic saline should be carried out to determine the effect on pulmonary function tests, quality of life, frequency of exacerbations of respiratory disease and efficacy comparisons with nebulised deoxyribonuclease, with larger numbers and for longer duration. At this stage there is insufficient evidence to support the use of hypertonic saline in routine treatment for patients with cystic fibrosis.

Administration, Inhalation↗
PubMed1977

Studies on cystic fibrosis using isoelectric focusing. IV. Distinction between ciliary dyskinesia activity in cystic fibrosis and asthmatic sera and association of cystic fibrosis protein with the activity in cystic fibrosis serum.

The cystic fibrosis protein (CFP) and ciliary dyskinesia activities (CDA) in sera from CF homozygotes, heterozygote carriers, and individuals with bronchial asthma have been partially purified. Concurrently, the CDA's in sera from patients with cystic fibrosis (CF) or bronchial asthma were shown to be different substances by ion-exchange or gel permeation chromatographic procedures. Sephadex G-200 chromatography indicated that the CF-CDA eluted with a protein fraction of molecular weight (MW) 68,000-150,000 and that the asthma CDA was found in a protein fraction of MV greater than 150,000. The two activities could also be separated by DEAE-cellulose chromatography. Prior acidification of whole normal, CF homozygote, obligate heterozygote, or asthmatic sera to pH 3.7 using EDTA, followed by fractionation of Sephadex G-200 removed all the CDA's from fractions of highermolecular weight and shifted the activities to a protein fraction of MW 1,100-13,700. This procedure afforded a 200-fold purification of the CDA's in sera from patients with asthma or CF. EDTA treatment, however, also generated a CDA in previously nonreactive normal sera. Subsequent fractionation of the various active G-200 fractions on Bio-Gel P10 allowed for the separation of three separate activities (Bio-Gel Fractions I, II-IV, and V). Fraction I was shown to represent the activity in sera from patients with asthma and was determined to be C3a (MW 9,000). Fraction I was also found in normal, CF, and carrier sera and therefore is not a specific CDA. Fraction II-IV is thought to represent a CF-specific CDA (MW 5,000) since it could not be demonstrated in either normal or asthmatic sera but was found in sera of obligate heterozygotes. Fraction III-IV also did not react with antisera to human C3a. Fraction V was generated from all serum types upon acidification of the serum with EDTA and is thought to be a nonspecific CDA. Bio-Gel P10 filtration of Sephadex G-200 fractions provided 823-fold and 650-fold purification of the asthmatic and CF CDA's, respectively. Concurrent analysis of column fractions for CDA's by bioassay and for CFP by electrofocusing showed CFP only in fractions that contained the CF-CDA. Combined analyses employing acid disc gel electrophoresis, isoelectric focusing, and EDTA treatment of active CF-immunoglobulin (Ig) G and Sephadex G-200 column fractions, followed by Bio-Gel P10 chromatography, provided evidence that CFP was associated with the CF-CDA. It is unknown as yet whether CFP itself is responsible for the CF-CDA activity.

Asthma↗
PubMed2002

Tyrosine kinase c-Src constitutes a bridge between cystic fibrosis transmembrane regulator channel failure and MUC1 overexpression in cystic fibrosis.

Cystic fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) chloride channel, is associated in the respiratory system with the accumulation of mucus and impaired lung function. The role of the CFTR channel in the regulation of the intracellular pathways that determine the overexpression of mucin genes is unknown. Using differential display, we have observed the differential expression of several mRNAs that may correspond to putative CFTR-dependent genes. One of these mRNAs was further characterized, and it corresponds to the tyrosine kinase c-Src. Additional results suggest that c-Src is a central element in the pathway connecting the CFTR channel with MUC1 overexpression and that the overexpression of mucins is a primary response to CFTR malfunction in cystic fibrosis, which occurs even in the absence of bacterial infection.

Base Sequence↗
PubMed2004

Impaired regulatory volume decrease in freshly isolated cholangiocytes from cystic fibrosis mice: implications for cystic fibrosis transmembrane conductance regulator effect on potassium conductance.

Various K(+) and Cl(-) channels are important in cell volume regulation and biliary secretion, but the specific role of cystic fibrosis transmembrane conductance regulator in cholangiocyte cell volume regulation is not known. The goal of this research was to study regulatory volume decrease (RVD) in bile duct cell clusters (BDCCs) from normal and cystic fibrosis (CF) mouse livers. Mouse BDCCs without an enclosed lumen were prepared as described (Cho, W. K. (2002) Am. J. Physiol. 283, G1320-G1327). The isotonic solution consisted of HEPES buffer with 40% of the NaCl replaced with isomolar amounts of sucrose, whereas hypotonic solution was the same as isotonic solution without sucrose. The cell volume changes were indirectly assessed by measuring cross-sectional area (CSA) changes of the BDCCs using quantitative videomicroscopy. Exposure to hypotonic solutions increased relative CSAs of normal BDCCs to 1.20 +/- 0.01 (mean +/- S.E., n = 50) in 10 min, followed by RVD to 1.07 +/- 0.01 by 40 min. Hypotonic challenge in CF mouse BDCCs also increased relative CSA to 1.20 +/- 0.01 (n = 53) in 10 min but without significant recovery. Coadministration of the K(+)-selective ionophore valinomycin restored RVD in CF mouse BDCCs, suggesting that the impaired RVD was likely from a defect in K(+) conductance. Moreover, this valinomycin-induced RVD in CF mice was inhibited by 5-nitro-2'-(3-phenylpropylamino)-benzoate, indicating that it is not from nonspecific effects. Neither cAMP nor calcium agonists could reverse the impaired RVD seen in CF cholangiocytes. Our conclusion is that CF mouse cholangiocytes have defective RVD from an impaired K(+) efflux pathway, which could not be reversed by cAMP nor calcium agonists.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Cystic fibrosis mortality: registry data of cystic fibrosis.

BACKGROUND: The Cystic Fibrosis Foundation has been collecting mortality and other data on cystic fibrosis patients from over 100 U.S. clinical centers since 1966, and publishes annual reports of the data. Cystic fibrosis is an important autosomal recessive genetic disease, affecting multiple body systems, with disability and early mortality as very common complications. RESULTS: Observed data by age in the 1994 and 1995 REports are compared with the earliest Registry experience. 1966-1972, after age-matching observed with expected mortality in the U.S. population. Observed and expected results are given in four tables of comparative mortality. CONCLUSION: Excess mortality as a rate difference has shown a marked decrease during this time period, ranging from 96% at age 0-1 to 52% at ages 20-25 years. This can be attributed to improvements in medical treatment.

Adolescent↗