bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of β2‐adrenergic receptor polymorphisms with severe asthma
Authors: Holloway  , Dunbar  , Riley  , Sawyer  , Fitzharris  , Pearce  , Le Gros  , Beasley  
Published: March 2003

BackgroundThere is considerable interest in the role of different candidate loci in the development of asthma. This study investigates the association between asthma severity and previously identified polymorphisms at two sites within the β2‐adrenergic receptor (β2AR) gene: the Arg16→Gly16 and Gln27→Glu27 alleles.MethodsRestriction enzyme analysis of amplified β2AR gene products (PCR‐RFLP) was used to analyse the frequency of the Arg16→Gly16 and Gln27→Glu27 polymorphisms within the β2AR gene in 95 severe asthmatic patients (with a markedly increased risk of death from asthma), 59 mild asthmatic patients, and a control group of 92 nonasthmatic subjects.ResultsThe Gly16 polymorphism was significantly associated with asthma severity with odds ratios (95% CI) for the Gly16 allele being 1.56 (1.02–2.40, P = 0.04) and 0.98 (0.61–1.57, P = 0.92) for the severe and mild asthma groups, respectively. The corresponding odds ratios (95% CI) for Gly16 homozygotes were 1.91 (0.82–4.41, P = 0.13) and 0.82 (0.35–1.92, P = 0.65) for the severe and mild asthma groups, respectively. There was no significant association between either polymorphism at amino acid 27 and asthma or asthma severity.ConclusionsWe conclude that the polymorphisms of amino acids 16 and 27 of the β2AR gene are not associated with the development of asthma per se, but that the Gly16 polymorphism may play a role in the pathogenesis of asthma severity.
Uptake of the yeast Malassezia furfur and its allergenic components by human immature CD1a+ dendritic cells
Authors: Buentke E. , Zargari A. , Heffler L. C. , Avila‐Cariño J. , Savolainen J. , Scheynius A. 
Published: March 2003

Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing prevalence, though still little is known of the pathomechanisms and the causes of the disease. Patients with AD often have specific IgE reactivity to the yeast Malassezia furfur (M. furfur), present in the normal microflora on human skin.To investigate the possible interaction of immature and mature antigen‐presenting dendritic cells with the yeast M. furfur and its allergenic components.Monocyte‐derived dendritic cells (MDDCs) generated from human peripheral blood were allowed to interact with FITC‐labelled whole M. furfur yeast cells, M. furfur extract, a recombinant allergen from M. furfur designated rMal f 5 and M. furfur mannan, in the absence of IgE antibodies. Interaction and uptake were detected using flow cytometry and confocal laser scanning microscopy.Internalization of M. furfur yeast cells and yeast components by immature MDDCs was found using confocal laser scanning microscopy. Results from flow cytometric studies showed that a median of 94% (range, 65–98%) of the immature CD1a+ MDDCs were M. furfur extract positive, 81% (75–97%) rMal f 5 positive and 93% (62–98%) mannan positive. Mature CD1a+ MDDCs were significantly less efficient in this respect, with the corresponding figures only 26% (6–37%, P < 0.01), 6% (2–15%, P < 0.05) and 32% (9–50%, P < 0.01), respectively. Uptake of the non‐glycosylated rMal f 5 by immature CD1a+ MDDCs was decreased to 27% (15–38%) by inhibition of pinocytosis. The binding of M. furfur extract and mannan was inhibited in a dose‐dependent manner by methyl‐α‐d‐mannopyranoside, suggesting uptake via the mannose receptor.Human immature CD1a+ MDDCs can efficiently take up M. furfur and allergenic components from the yeast in the absence of IgE antibodies, implying that sensitization of AD patients to M. furfur can be mediated by immature dendritic cells in the skin.
Interleukin‐2 inhibits eosinophil migration but is counteracted by IL‐5 priming
Authors: Lampinen M. , Håkansson L. , Venge P. 
Published: March 2003

Conflicting data on the role of interleukin‐2 in the recruitment of eosinophil granulocytes (EOS) to sites of inflammation have been presented. The objective of the present study was to investigate the effect of recombinant human IL‐2 and anti‐IL‐2 on the migration of purified blood EOS.Neutralizing antibodies to IL‐2 were added to a cytokine mixture with significant eosinophil chemotactic activity (ECA), and afterwards the ECA was tested on EOS from both normal and allergic donors. EOS migration was measured by a modification of the Boyden technique, using a 48‐well microchemotaxis chamber. Recombinant human IL‐2 was either added to the lower compartment of the chemotaxis chamber, or to the EOS for a pre‐incubation period of 20 min, before migration assays towards the chemotaxins were performed.Anti‐IL‐2 caused a significant increase of EOS migration towards the cytokine mixture. Pre‐incubation of the EOS with rhIL‐2 inhibited the chemotaxis towards RANTES, PAF, IL‐8 and eotaxin, and EOS migration towards IL‐2 was lower than that towards buffer. These effects were more pronounced on EOS from normal than from allergic donors. Priming of the EOS with IL‐5 prevented the inhibitory effect of IL‐2.We hypothesize that IL‐2 acts as an autocrine regulator of EOS migration, and that this inhibitory effect may be downregulated in allergy, allowing an increased migration of EOS towards chemotactic factors.
Occupational asthma as identified by the Surveillance of Work‐related and Occupational Respiratory Diseases programme in South Africa
Authors: Hnizdo E. , Esterhuizen T. M. , Rees D. , Lalloo U. G. 
Published: March 2003

Background The nationwide Surveillance of Work‐related and Occupational Respiratory Diseases in South Africa, SORDSA, was established in 1996 to provide systematic information on occupational respiratory diseases.Objective SORDSA's objectives are to monitor the nature, extent and distribution of occupational respiratory diseases, and to increase awareness of their diagnosis and prevention. This paper describes the programme and results obtained for occupational asthma in the first 2 years, ending in October 1998.Methods SORDSA identifies newly diagnosed cases of occupational respiratory disease through voluntary reporting by pulmonologists, occupational medicine doctors and occupational health nurses. Initially, recruitment of the above health care providers was done through the membership infrastructure of their respective professional societies. Booklets with prescribed monthly reporting forms were distributed annually to all reporting members and a core of reporting providers was established through a proactive method of data collection. Information dissemination and reporting feedback takes place through quarterly newsletters and issue‐specific brochures on certain hazardous agents.Results Over the initial 2‐year period, 3285 cases of occupational respiratory disease were reported to SORDSA by 203 doctors and 97 occupational health nurses. After pneumoconiosis and associated respiratory conditions, occupational asthma was the second most commonly reported disease with 225 cases (6.9%). The average annual incidence for occupational asthma in South Africa was 13.1 per million employed people, with the highest incidence reported from the Western Cape province (37.6 per million). Latex was the most frequently reported agent for occupational asthma, followed by isocyanates and platinum salts. Low molecular weight agents accounted for 59.6% of the cases of occupational asthma.Conclusion The results from this initial phase show that despite some limitations, SORDSA has the potential to obtain useful data on the industries, agents and occupations causing occupational asthma in South Africa.
Atopy, intestinal helminth infection and total serum IgE in rural and urban adult Gambian communities
Authors: Nyan O. A. , Walraven G. E. L. , Banya W. A. S. , Milligan P. , Van Der Sande M. , Ceesay S. M. , Del Prete G. , McAdam K. P. W. J. 
Published: March 2003

Background The rarity of atopy in traditional societies has been attributed to high parasite‐driven blocking IgE concentrations. Information is lacking on the relationship between atopy, IgE and intestinal helminth infection in African populations.Objective To determine the prevalence of atopy and intestinal helminth infection and to relate these to wheeze history and serum total IgE in a community sample of adults from an urban (Banjul) and a rural (Farafenni) area of the Gambia.Methods Six hundred and ninety‐three adults were interviewed about respiratory symptoms using a modified version of the IUTLD questionnaire, and had skin prick testing using four allergens. Stools were examined after formol‐ether concentration. Total serum IgE concentration was measured in a subset of participants.Results The prevalence of atopy (mean weal diameter > = 3 mm) in the urban and rural area was 35.3% and 22.5% (P = 0.05); D. pteronyssinus and Mold mix being the common sensitizing allergens. Prevalence of wheeze in the previous 12 months was 4.4% and 3.5% for the urban and rural areas, respectively. Wheezing was not significantly associated with atopy. Seventeen per cent of urban and 8.2% of rural subjects had helminths detected in stools. There was an inverse association between atopy and intestinal helminth infection; 7% of atopic subjects had helminths, compared to 13% of non‐atopic subjects (unadjusted odds ratio 0.51, 95%CI 0.24–1.1, P = 0.09; adjusted odds ratio 0.37, 95%CI 0.15–0.92, P = 0.03). Non‐atopics had total serum IgE concentrations about 2.5 times the upper limit of the reference range in non‐atopic Western populations. Geometric mean total serum IgE concentration was significantly higher among atopic subjects (570 IU/mL, IQR 91–833) than non‐atopic subjects (259 IU/mL, IQR 274–1303) (P < 0.001). IgE concentration was not associated with the presence of helminth infection.Conclusion Further studies are needed to clarify why asthma is still relatively uncommon in spite of the prevalence of atopy in Gambian adults. Our data are also compatible with the idea that atopy might protect against helminth infection.
Interaction of cigarette smoke and house dust mite allergens on inflammatory mediator release from primary cultures of human bronchial epithelial cells
Authors: Rusznak C. , Sapsford R. J. , Devalia J. L. , Shah S. S. , Hewitt E. L. , Lamont A. G. , Davies R. J. , Lozewicz S. 
Published: March 2003

Several studies have shown that exposure to cigarette smoke and/or house dust mite (HDM) can lead to increased airway inflammation in susceptible individuals. The underlying mechanisms, however, are not defined.To investigate the interaction between cigarette smoke and HDM allergen on mediator release from primary cultures of human bronchial epithelial cells.Confluent human bronchial epithelial cell cultures were exposed to cigarette smoke in the absence or presence of HDM allergen and investigated for the release of IL‐8, IL‐1β, and sICAM‐1. Damage to the epithelial cells themselves was assessed by release of 51Cr. On separate occasions, we investigated the effect of PTL11028, a highly potent and selective Der p1 inhibitor, on HDM allergen‐induced release of IL‐8, following activation of HDM allergen by incubation with cysteine. The effect of cigarette smoke exposure on the stability of these released mediators in prepared solutions in the absence/presence of reduced glutathione was also studied.Both HDM allergens and short‐term (20 min) cigarette smoke exposure led to a significantly increased release of IL‐8, IL‐1β and sICAM‐1 from the epithelial cell cultures. Longer exposure (1–6 h) to cigarette smoke led to a dramatic decrease in the amount of these mediators detected in the culture medium. Whilst incubation of epithelial cultures with HDM allergen did not cause any significant change in the release of 51Cr from pre‐loaded cells, cigarette smoke on its own led to a marked, exposure and incubation‐time dependent increase in the release of 51Cr. Incubation with HDM allergen led to a significant, dose and time‐dependent increase in the release of IL‐8, which was further enhanced when the allergen extract was pre‐activated with cysteine. This effect was completely abrogated by PTL11028, a novel Der p1 inhibitor. Prepared solutions of various concentrations of IL‐8, IL‐1β and sICAM‐1 exposed to cigarette smoke demonstrated a dramatic exposure time‐dependent decrease in the detectable amount of these mediators, an effect which was abrogated by GSH.HDM‐induced airway inflammation may include Der p‐mediated release of inflammatory mediators from epithelial cells. Additionally, short‐term cigarette smoke exposure may induce airway inflammation by release of inflammatory mediators from these cells, an effect which may be potentiated by Der p allergens. Longer term cigarette smoke exposure may cause damage to epithelial cells and changes in the structure of inflammatory mediators.
A monoclonal antibody specific for a carbohydrate epitope recognizes an IgE‐binding determinant shared by taxonomically unrelated allergenic pollens
Authors: Iacovacci P. , Pini C. , Afferni C. , Barletta B. , Tinghino R. , Schininà E. , Federico R. , Mari A. , Di Felice G. 
Published: March 2003

Carbohydrate epitopes are capable of binding human IgE from allergic subjects and these epitopes play a role in the cross‐reactivity between allergens from unrelated sources. A monoclonal antibody (5E6), specific for a carbohydrate epitope detectable on components of Cupressus arizonica pollen extract, has been produced and characterized.To study the relationship between the epitopes recognized by the monoclonal antibody and by IgE from allergic subjects. To investigate the presence of such carbohydrate IgE determinant in extracts from 21 pollen species belonging to 16 taxonomically related and unrelated families, by means of the monoclonal antibody.IgG‐depleted fraction from protein G‐purified human allergic serum was obtained. The monoclonal antibody and the IgE from the purified fraction were tested on two glycoproteins, polyamine oxidase and ascorbate oxidase, adsorbed on the ELISA plates. The relationship between the monoclonal‐ and the IgE‐recognized epitopes was investigated by ELISA‐competition experiments. Analysis of the distribution of this carbohydrate epitope was performed by direct binding of the monoclonal antibody onto the various extracts.The monoclonal antibody and the IgE were able to bind carbohydrate epitopes on the two plant glycoproteins, ascorbate oxidase and polyamine oxidase. Polyamine oxidase shows only one N‐glycosilation site whose carbohydrate moiety seems to be composed of a branched chain of seven ordered sugars, i.e. two N‐acetyl‐d‐glucosamine‐, three mannose‐, one fucose‐ and one xylose‐residues. This structure bears the epitope recognized by mAb 5E6. Human IgE from the IgG‐depleted fraction were found capable of inhibiting the monoclonal antibody binding. The allergenic epitope identified was shared by a large number of extracts with different levels of reactivity (OD490 ranging from 0.110 to 2.060).Our data support the finding that a monoclonal antibody specific for a carbohydrate epitope of Cupressus arizonica pollen extract detects an epitope which is also recognized by IgE from allergic subjects. This characterized reagent could be a useful tool for studying distribution of cross‐reactive carbohydrate determinants in allergenic pollen extracts and their components.
Having lived on a farm and protection against allergic diseases in Australia
Authors: Downs S. H. , Marks G. B. , Mitakakis T. Z. , Lëuppi J. D. , Car N. G. , Peat J. K. 
Published: March 2003

Background Farmers' children in northern Europe have a lower prevalence of atopy, hay fever and asthma than other children. Farms in Australia differ in scale and operation from those in Europe and the prevalence of allergic diseases in children is higher.Objective To investigate whether having lived on a farm as a child in Australia is associated with a lower risk of allergic diseases.Methods Cross‐sectional study of children (n = 1500) aged 7–12 years from two rural towns: Wagga Wagga in a mixed farming region, and Moree in a crop farming region. Parents answered a questionnaire and children had a skin prick test for atopy.Results Twenty percent of children had lived on a farm for at least 1 year. The effect of having lived on a farm differed between the towns (P < 0.001). It was associated with a lower risk of atopy in Wagga (adjusted odds ratio (aOR) 0.47, 95% confidence interval (CI) 0.32–0.72) but not in Moree (aOR 0.97, 95% CI 0.62–1.53). Children from Wagga were more likely to have lived on a livestock farm than children from Moree (26.1% vs. 9.1%, 95% CI for the difference 8.9–25.4).Conclusion Having lived on a farm in Australia can confer protection against atopy in children. Further studies are needed to identify possible protective mechanisms associated with farm animals or to establish whether the protective effect is explained by other related exposures.
Release of cysteinyl leukotrienes with aspirin stimulation and the effect of prostaglandin E2 on this release from peripheral blood leucocytes in aspirin‐induced asthmatic patients
Authors: Çelik G. , Bavbek S. , Misirligil Z. , Melli M. 
Published: March 2003

Background The decrease in prostaglandin E2 (PGE2) release due to aspirin (ASA)‐induced cyclooxygenase inhibition and the increment in cysteinyl leukotriene (Cys‐LT) release secondary to the removal of the inhibitory effect of PGE2 on Cys‐LT release have been suggested in the pathogenesis of aspirin‐induced asthma (AIA).Objective In this study, we aimed to investigate the in vitro release of Cys‐LT and to determine the effect of PGE2 on Cys‐LT release from peripheral blood leucocytes of patients with AIA after stimulation by ASA.Patients and methods Patients with AIA (n = 13), patients with ASA‐tolerant asthma (ATA) (n = 12) and healthy volunteers as controls (n = 13) were included to the study. ASA and PGE2 at three different concentrations were applied to the peripheral blood leucocytes of the study group, and Cys‐LT levels following stimulants were assessed by enzyme immunoassay method.Results There was no difference in baseline Cys‐LT levels between groups (AIA 353.4 ± 55.5 pg/mL, ATA 354.7 ± 40.3 pg/mL, and control group 368.5 ± 30.2 pg/mL; P > 0.05). Though not present in other groups, the Cys‐LT level of 453.6 ± 70.0 pg/mL following ASA stimulation was higher than baseline in patients with AIA (P = 0.04). When PGE2 was added to the ASA‐stimulated samples of patients with AIA, Cys‐LT levels were measured as 298.7 ± 78.6 pg/mL, 279.8 ± 79.9 pg/mL, and 243.4 ± 51.3 pg/mL at PGE2 10−7 m, 10−6 m and 10−5 m concentrations, respectively. These levels were lower than the ASA‐stimulated Cys‐LT values (P = 0.03, P = 0.01 and P = 0.01, respectively). The inhibitory effect of different PGE2 concentrations on Cys‐LT release was also present in patients with ATA and in controls.Conclusion The increase in Cys‐LT levels following ASA stimulation seems to be unique to AIA, which was not present in patients with ATA and in healthy controls. The inhibitory effect of PGE2 on stimulated Cys‐LT levels is another important finding to elucidate the role of PGE2 in the pathogenesis of AIA.
IL‐5 deficiency abolishes aspects of airway remodelling in a murine model of lung inflammation
Authors: Trifilieff A. , Fujitani Y. , Coyle A. J. , Kopf M. , Bertrand C. 
Published: March 2003

Background and objectives Lung remodelling is a recognized feature of chronic asthma. In the present study, we have used IL‐5‐deficient mice to evaluate the role of this cytokine and eosinophilic inflammation in the initial stages of the structural changes occurring in the lung after antigen challenge.Methods Ovalbumin‐sensitized wild type and IL‐5‐deficient mice were daily challenged for 5 consecutive days and killed 3 or 7 days after the last challenge to study the inflammatory and remodelling events, respectively.Results Wild type mice challenged with ovalbumin exhibited an accumulation of eosinophils in the bronchoalveolar lavage (BAL) fluid, associated with a production of BAL cellular fibronectin. Histological analysis also revealed an antigen‐specific increase in epithelial and alveolar cell proliferation together with an increase in mucus producing epithelial cells. Eosinophilic infiltration and the associated lung remodelling were totally abrogated in IL‐5‐deficient mice. In wild type mice, treated intranasally with 1 µg of murine IL‐5 for 5 consecutive days, no BAL eosinophilia and structural changes of the lungs could be observed.Conclusion Our results demonstrate that eosinophil accumulation, but not IL‐5 alone, plays a central role in the initial stages of the lung remodelling process and suggests that therapies directed at inhibiting eosinophilic inflammation may be beneficial in treating chronic asthma.
IFN‐γ but not IL‐4 T cells of the asthmatic bronchial wall show increased incidence of apoptosis
Authors: Cormican L. , O'Sullivan S. , Burke C. M. , Poulter L. W. 
Published: March 2003

Background Previous observations have established that IFN‐γ production is depressed in CD4+ T cells from atopic asthmatics compared with non‐asthmatics.Objective The aim of this study was to determine if decreased IFN‐γ production could be due to a dissociation between levels of apoptosis within the T cell subsets of the asthmatic bronchial wall.Methods Twenty asthmatics (10 atopic and 10 non‐atopic) and eight non‐atopic non‐asthmatics underwent bronchoscopy. Cryostat sections of these biopsies were investigated using immunohistological techniques to determine the relative number of CD4/FAS+ and CD4/Bcl‐2+ cells. Detection of IFN‐γ+ and IL‐4+ was combined with TUNEL staining to determine the proportions of the Th1 and Th2 cells undergoing apoptosis.Results Experiments revealed raised proportions of activated CD4+ T cells as assessed by expression of HLA‐DR and CD25+ expression in the asthmatic samples. Expression of Bcl‐2 by the CD4+ cell population was significantly reduced in the asthmatic compared with the control group (P = 0.002). There was no significant difference in the expression of CD4+ Fas‐ligand or the number of CD4+ undergoing apoptosis in the asthmatic and non‐asthmatic groups. However, the IFN‐γ+ (P = 0.04) but not IL‐4+ T cells in the asthmatic biopsies had significantly higher proportions of apoptotic cells compared with the control group.Conclusion The evidence supports the hypothesis that Th1/Th2 imbalance in asthmatic inflammation may be a result of premature apoptosis within the Th1 subset.