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Biomedical subjects

B Beghé

Publications and source records attributed to B Beghé.

14 recordsLinked to original sources
PubMed2006

The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma.

BACKGROUND: The cysteinyl-leukotriene receptor type 1 (CysLT1) mediates the bronchoconstrictor and pro-inflammatory actions of cysteinyl-leukotrienes (LTC4, LTD4, LTE4) in asthma and is the molecular target of the lukast class of oral anti-leukotriene drugs. We screened the CYSLTR1 gene on chromosome Xq13-21 for coding region polymorphisms, and investigated their associations with allergy and asthma. METHODS: Solid-phase chemical cleavage was used to screen polymorphisms in the coding region of CYSLTR1. A TaqMan allelic discrimination assay was used to genotype a 927T/C SNP and oligonucleotide ligation assays were used to genotype the previously reported 617T/C and 898G/A SNPs of CYSLTR1 in 341 asthmatic families from the UK. Associations with asthma diagnosis, atopic status, serum-specific IgE and severity of allergy and asthma were examined. RESULTS: Family-based association tests showed that the 927 T allele was associated with atopy severity, especially in female subjects, but not with asthma diagnosis or severity, atopic status, bronchial hyper-responsiveness to methacholine or forced expiratory volume in 1 s. CONCLUSION: Mutation screening identified only one polymorphism, 927T/C, in the coding region of the CysLT1 receptor. This polymorphsim is predictive of atopy severity, but not associated with asthma.

Adolescent↗
PubMed2005

Decreased expression of TGF-beta type II receptor in bronchial glands of smokers with COPD.

BACKGROUND: The role of transforming growth factor-beta1 (TGF-beta1) in chronic obstructive pulmonary disease is still controversial, but it has been proposed that it may protect from mucus hypersecretion since it is able to downregulate mucin production. A study was undertaken to investigate the expression of TGF-beta1 and its type II receptor (TGF-beta RII) in the bronchial glands of smokers with COPD. METHODS: The expression of TGF-beta(1) and TGF-beta RII were examined immunohistochemically in the bronchial glands of 24 smokers undergoing lung resection for solitary peripheral nodules: 12 with airflow limitation (smokers with COPD) and 12 with normal lung function. RESULTS: The expression of TGF-beta1 in bronchial glands was similar in the two groups of subjects while that of TGF-beta RII was lower in smokers with COPD than in smokers with normal lung function (p=0.004). TGF-beta RII expression was inversely correlated with the values of Reid's index, a measure of gland size (p=0.02, r=-0.50). CONCLUSIONS: In the bronchial glands of smokers with COPD there is decreased expression of TGF-beta RII which is associated with bronchial gland enlargement. These findings support the view that the absence of TGF-beta signalling may induce structural changes in the bronchial glands which, in turn, may promote mucus hypersecretion.

Aged↗
PubMed2004

Lack of association of HLA class I genes and TNF alpha-308 polymorphism in toluene diisocyanate-induced asthma.

BACKGROUND: Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational asthma and it affects 5-15% of the exposed population suggesting an underlying genetic susceptibility. METHODS: To investigate the role of genetic factors in the development of TDI-induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)-alpha A-308G polymorphism in 142 patients with TDI-induced asthma and in 50 asymptomatic exposed subjects. RESULTS: Neither the distribution of HLA class I antigens nor the distribution of TNF-alpha A-308G polymorphism was different between patients with TDI-induced asthma and asymptomatic exposed subjects. CONCLUSIONS: These results suggest that HLA class I antigens and TNF-alpha A-308G are not associated with susceptibility or resistance to the development of TDI-induced asthma.

Adult↗
PubMed2004

Neutrophilic infiltration within the airway smooth muscle in patients with COPD.

BACKGROUND: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. METHODS: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. RESULTS: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). CONCLUSIONS: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation.

Aged↗
PubMed2003

Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population.

BACKGROUND: IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype. OBJECTIVE: To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Ralpha chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma. METHODS: Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Ralpha chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England. RESULTS: Case-control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006). CONCLUSION: Our data suggest that polymorphisms in the IL-4 and IL-4Ralpha chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.

Adolescent↗
PubMed2003

Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population.

BACKGROUND: 5-Lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) are essential for cysteinyl-leukotriene (cys-LT) production, critical mediators in asthma. OBJECTIVE: We sought to identify novel promoter polymorphisms within the FLAP (ALOX5AP) gene promoter and test the role of these and the previously identified 5-LO (ALOX5) Sp1 promoter polymorphism in asthma susceptibility. METHODS: To assess genetic association with asthma phenotypes, we genotyped 341 Caucasian families (containing two asthmatic siblings) and non-asthmatic control subjects (n=184). Genetic association was determined by case-control and transmission disequilibrium test (TDT) analyses. To determine the functional role of polymorphisms on basal transcription, we generated ALOX5AP-promoter-luciferase constructs and transiently transfected human HeLa cells. RESULTS: A novel G/A substitution at -336 bp and a poly(A) repeat (n=19 or 23) at position -169 to -146 bp were identified in the ALOX5AP promoter. Genotyping found the -336 A and poly(A19) alleles at frequencies of q=0.06 and 0.12, respectively. No ALOX5AP allele was associated with asthma or asthma-related phenotypes in case-control or TDT analyses. ALOX5AP-promoter-luciferase analyses did not support a functional role of the -336 or poly(A) polymorphism in determining basal transcription. The ALOX5 Sp1 polymorphism was predominantly homozygous wild-type 5/5 (frequency q=0.70) and heterozygous 4/5 (q=0.23) genotypes and no allele was associated with asthma or asthma-related phenotypes. CONCLUSION: Taken together, these data do not support a significant role for these polymorphisms in genetic susceptibility to asthma in the Caucasian population.

5-Lipoxygenase-Activating Proteins↗
PubMed2003

Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma.

BACKGROUND: LTC4 synthase is essential for the production of cysteinyl leukotrienes (Cys-LT), critical mediators in asthma. We have identified a novel promoter polymorphism at position -1072 (G/A) and a -444 (A/C) polymorphism has previously been reported. The role of these polymorphisms in the genetic susceptibility to asthma was examined. METHODS: To test for genetic association with asthma phenotypes, 341 white families (two asthmatic siblings) and 184 non-asthmatic control subjects were genotyped. Genetic association was assessed using case control and transmission disequilibrium test (TDT) analyses. LTC4S promoter luciferase constructs and transiently transfected human HeLa and KU812F cells were generated to determine the functional role of these polymorphisms on basal transcription. RESULTS: No associations were observed in case control analyses (-1072 A, q=0.09; -444 C, q=0.29); the TDT identified a borderline association between the -444 C allele and bronchial responsiveness to methacholine (p=0.065). Asthmatic children with the -444 C allele had a lower mean basal forced expiratory volume in 1 second (97.4 v 92.7% predicted, p=0.005). LTC4S promoter luciferase analyses provided no evidence for a functional role of either polymorphism in determining basal transcription. CONCLUSION: This study does not support a role for these polymorphisms in genetic susceptibility to asthma but provides evidence to suggest a role in determining lung function parameters.

Adolescent↗
PubMed2001

Linkage analysis of the 5q31-33 candidate region for asthma in 240 UK families.

Atopy and asthma are complex genetic diseases resulting from the interactions of a number of genetic and environmental factors. We had previously reported allelic association between the IL9 marker on chromosome 5q31-33 and atopy. In order to further investigate the role of susceptibility genes on 5q31-33 in the development of atopy and asthma we have studied 240 UK families comprising 131 families selected at random, 60 multiplex families with affected sib pairs, and 49 single proband nuclear families. Polymorphic markers on 5q31-33 were genotyped and both single and multipoint linkage analysis was undertaken using the BETA program. We have used both affection status and quantitative scores for atopy and asthma for phenotypic variables, combining data into scores for asthma and atopy. The strongest suggestion of linkage using multipoint analysis was centred around D5S410 with a maximum Lod of 1.946 at location 171.3 cM and a standard error of 3.3 for the asthma quantitative score. There was no evidence of linkage with atopy, the atopy quantitative score or total serum IgE.

Asthma↗
PubMed1999

Comparison of three methods for single nucleotide polymorphism typing for DNA bank studies: sequence-specific oligonucleotide probe hybridisation, TaqMan liquid phase hybridisation, and microplate array diagonal gel electrophoresis (MADGE).

In the near future the number of SNPs identified and mapped will increase and the need for high throughput SNP typing will be paramount for comprehensive examination by association of the role of genomic regions in disease traits. A range of higher throughput methods for typing SNPs is now in routine use in many laboratories worldwide. In this report, we analyse the relative advantages and disadvantages of three such methods, TaqMan, PCR-SSOP, and ARMS-MADGE, currently in use in our laboratories. Throughputs achievable are similar, but there are major differences in cost and time for set-up, equipment, consumables, and staff time, which may determine the choice for individual laboratories.

Costs and Cost Analysis↗
PubMed1998

Comparison of two methods of processing induced sputum: selected versus entire sputum.

Sputum analysis is increasingly used to assess airway inflammation in asthma. The analysis of sputum is currently performed with two techniques, i.e., analysis of selected sputum (plugs) and analysis of entire sputum. To investigate the diagnostic value of these two methods, we compared total and differential cell counts and supernatant eosinophil cationic protein (ECP) in selected and entire sputum collected on two occasions in a group of healthy and asthmatic subjects. We induced sputum with hypertonic saline in 18 asthmatics and in eight healthy subjects. On one occasion we analyzed selected sputum, and on another occasion we analyzed entire sputum. In each sample we measured total and differential cell counts and ECP concentration in supernatant. We found a higher percentage of eosinophils (15.3 versus 8.3%; p < 0.01), more viable nonsquamous cells (80.6 versus 71.8%; p < 0.01), and higher levels of ECP (548 versus 105 microg/L; p < 0.001) in selected sputum as compared with entire sputum, whereas the percentage of neutrophils was higher in the entire sputum (42.7 versus 33.3%; p < 0.05). The percentage of eosinophils and ECP concentration were significantly and similarly increased in both selected and entire sputum of asthmatic subjects, i.e., independent of the method of sputum analysis. In conclusion, the selected sputum method may indeed provide more viable cells, more eosinophils, and a higher concentration of ECP. However, both the selected sputum and the entire sputum method have the same diagnostic value in distinguishing asthmatics from healthy subjects.

Adult↗
PubMed1995

Tissue polypeptide specific antigen (tps) and cytokeratin 19 fragment (CYFRA 21.1) immunoradiometric assay in non small cell lung cancer evaluation.

The aim of our work was the evaluation of the immunoradiometric assay (IRMA) of two cytokeratinic markers, TPS and CYFRA 21.1, in clinical setting on non small cell lung cancer (NSCLC). Serum samples were obtained from 148 untreated NSCLC patients, 60 patients with non malignant lung diseases and 100 healthy subjects: TPS and CYFRA 21.1 serum levels were assayed by IRMA methods. Diagnostic performance of the markers was evaluated and the TPS and CYFRA 21.1 distribution analysed according to some different clinical and biological variables as histological subtypes, stage and survival time by using the Mann-Whitney "U"-test. Sensitivity, specificity and accuracy were 0.54 (80/148), 0.47 (28/60), 0.52 (108/208) and 0.73 (108/148), 0.74 (44/60), and 0.73 (152/208) for TPS and CYFRA 21.1 respectively. CYFRA 21.1 demonstrate a higher sensitivity than TPS in all stages of the disease and in the spinocellular and adenocarcinoma histological subtypes while TPS sensibility is higher in large cell carcinoma. The CYFRA 21.1 specificity is better than TPS probably by reason of its preferential distribution in respiratory epithelium. Both markers serum levels differ significantly between Stage I-II and IV and between Stage I-II-IIIa and IIIb-IV but neither TPS nor CYFRA 21.1 can discriminate Stage IIIa from IIIb. No significant differences were found in the serum expression of the markers by the different histological subtypes. A value of both markers less than the selected cut-off is related to a longer survival of the patients apart from therapy (p < 0.05). Our conclusion supports similar behaviour of these markers in NSCLC and indicates CYFRA 21.1 as the more needed biochemical index to evaluate NSCLC patients.

Adult↗