bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociation of T helper type 2 cytokine‐dependent airway lesions from signal transducer and activator of transcription 6 signalling in experimental chronic asthma
Authors: Foster P. S. , Webb D. C. , Yang M. , Herbert C. , Kumar R. K. 
Published: May 2003

SummaryBackground Type 2 T helper lymphocytes (Th2 cells) and their cytokine products are important in the pathogenesis of asthma.Objective To examine the contribution of the signal transducer and activator of transcription (STAT) 6 pathway, involved in Th2 cytokine signalling, to the development of lesions of chronic asthma.Methods BALB/c mice sensitized to ovalbumin were chronically challenged by inhalational of low mass concentrations of antigen for 6 weeks. Airway lesions in wild‐type mice were compared with those in STAT6‐deficient mice and in IL‐4/13 double‐deficient mice by histomorphometry and immunohistochemistry. Airway responses to methacholine were evaluated by whole‐body plethysmography. Cytokine production by peribronchial lymph node cells was quantified by enzyme immunoassay.Results STAT6–/– mice developed a variety of airway lesions that were at least equivalent to those in wild‐type mice, including accumulation of intraepithelial eosinophils and of chronic inflammatory cells in the lamina propria, subepithelial fibrosis and epithelial thickening. In addition, STAT6–/– mice exhibited exaggerated airway hyper‐reactivity (AHR) compared to wild‐type animals. This was despite a shift from a Th2 to a Th1 pattern of immunoglobulin production by plasma cells in the inflammatory infiltrate and diminished mucous cell hyperplasia/metaplasia, together with increased production of IFN‐γ by peribronchial lymph node cells, consistent with absence of signalling via the STAT6 pathway. In contrast, gene‐targeted IL‐4/13–/– mice exhibited markedly diminished eosinophil recruitment and airway remodelling, as well as absence of AHR.Conclusions In this model, the effects of STAT6 deficiency were in marked contrast to the suppression of inflammation and AHR described in models of allergic bronchopulmonary inflammation. These results, which provide evidence of STAT6‐independent AHR in an inhalational challenge model of chronic asthma, emphasize the critical effector roles of IL‐4 and IL‐13, as well as the need to use appropriate models to understand cytokine signalling pathways that may be potential therapeutic targets in asthma.
Generation of monoclonal antibodies against Blo t 3 using DNA immunization with in vivo electroporation
Authors: Yang L. , Cheong N. , Wang D. Y. , Lee B. W. , Kuo I. C. , Huang C. H. , Chua K. Y. 
Published: May 2003

SummaryBackground House dust mite allergy is closely associated with allergic diseases. Blomia tropicalis mite species is an important clinical species in the tropics. The cDNA clone encoding Blo t 3, a group 3 allergen from B. tropicalis, has been isolated in our laboratory.Objective This study was designed to generate Blo t 3‐specific monoclonal antibodies (mAbs) for the detection, characterization and purification of this allergen.Methods Mice were immunized intramuscularly with naked plasmid DNA encoding Blo t 3 gene with in vivo electroporation. Hybridomas were generated by the fusion of the splenocytes to X63‐Ag8.653 myeloma cells. Purified native Blo t 3 was obtained by mAb immuno‐affinity purification and the allergenicity of native Blo t 3 was determined by human IgE enzyme‐linked immunosorbent assay (ELISA).Results A panel of class‐switched and high‐affinity mAb recognizing a wide spectrum of Blo t 3 epitopes have been generated. These mAbs are useful for western immunoblot assay, sandwich ELISA and affinity purification of native Blo t 3. Allergenicity of native Blo t 3 protein was examined with 44 mite‐allergic sera and approximately 57% of the tested sera had positive serum IgE reactivity to the native Blo t 3.Conclusions These results demonstrated that intramuscular injection of naked DNA encoding Blo t 3 gene combined with in vivo electroporation is an effective and simple method to raise monoclonal antibodies that can be used for characterization and purification of Blo t 3.
Differences in circulating dendritic cell subtypes in cord blood and peripheral blood of healthy and allergic children
Authors: Hagendorens M. M. , Ebo D. G. , Schuerwegh A. J. , Huybrechs A. , Van Bever H. P. , Bridts C. H. , De Clerck L. S. , Stevens W. J. 
Published: May 2003

SummaryBackground Different types of circulating dendritic cells have been described. Dendritic cells influence differentiation of naive T lymphocytes into T helper type 1 (Th1) and Th2 effector cells.Objective The purpose of this study was to evaluate the number of circulating DC subtypes in peripheral blood of allergic and healthy children and in cord blood of neonates from allergic and non‐allergic parents.Methods Circulating dendritic cells were flow cytometrically identified in whole blood samples as lineage (CD3, CD14, CD16, CD19, CD20, CD56) negative, CD34 negative and HLA‐DR‐positive cells. According to the expression of CD123 and CD11c, different DC subtypes were identified.Results Apart from DC1 (CD11c+ CD123dim+) and DC2 (CD11c– CD123high+), a third DC population was described with less differentiated phenotypic characteristics, namely CD11c– CD123dim+, and therefore defined here as less differentiated DC (ldDC). These ldDC represented the major DC population in cord blood and showed an age‐depended decrease. The highest level of ldDC was detected in children with atopic dermatitis, whereas asthmatic children showed the lowest ldDC counts. Furthermore, high‐dose inhaled corticosteroid treatment in asthmatic children was related to a decreased ldDC number. The number of circulating DC2 was significantly lower in allergic children, especially in asthmatics, compared to healthy children. In cord blood, no differences in DC subtypes were detectable between neonates at low and high risk for allergic disorders.Conclusion These results indicate that, apart from DC1 and DC2, a third population of dendritic cells, identified as CD11c– CD123dim+ cells and defined as less differentiated DC, must be considered in the evaluation of circulating DC. Furthermore, DC2 counts were decreased in allergic children, especially in asthmatics, which might be the consequence of an increased recruitment to the target organs.
Mucosal and systemic inflammatory changes in allergic rhinitis and asthma: a comparison between upper and lower airways
Authors: Braunstahl G.‐J. , Fokkens W. J. , Overbeek S. E. , KleinJan A. , Hoogsteden H. C. , Prins J.‐B. 
Published: May 2003

SummaryBackground Local airway inflammation and airway remodelling are considered important in the clinical expression of allergic asthma.Objective The aim of this study was to compare airway inflammation and remodelling in nasal and bronchial mucosa of subjects with allergic rhinitis with or without asthma.Methods Four experimental groups were formed: allergic asthma and rhinitis (n = 19); allergic rhinitis, no asthma (n = 18); atopic subjects, no asthma, no rhinitis (n = 8) and non‐allergic healthy control subjects (n = 16). Blood samples, nasal and bronchial biopsy specimens were collected during stable disease. Immunohistochemistry was performed for eosinophils (MBP), mast cells (CD117) and vascular endothelium (CD31). Epithelial loss, reticular basement membrane (RBM) thickness and subepithelial vascularity was assessed with a computer‐assisted image analysis system.Results In nasal and bronchial mucosa, numbers of eosinophils were significantly higher in rhinitis patients with and without asthma than in asymptomatic atopics (P < 0.05) and controls (P ≤ 0.01). In bronchial mucosa, the RBM was significantly thickened in rhinitis patients with and without asthma compared to asymptomatic atopics (P < 0.05) and controls (P < 0.01), while in nasal mucosa no differences were seen. Patients with asthma and rhinitis had increased numbers of blood eosinophils (P = 0.05) and skin test reactivity (P = 0.01) compared to patients with rhinitis only. No significant differences could be found between the investigated groups with respect to serum IL‐5 and eotaxin levels, the number of mucosal mast cells and the degree of epithelial loss and subepithelial vascularity. Epithelial desquamation was significantly increased in the bronchial mucosa compared to nasal mucosa, not only in asthmatics (P < 0.001), but also in atopics without asthma and rhinitis (P = 0.02).Conclusions This study shows that allergic inflammation, increased basement membrane thickness and epithelial desquamation are present in the lower airways of atopic subjects, even before the onset of clinical symptoms. Despite the presence of inflammatory cells, no structural changes could be assessed in nasal mucosa of allergic patients.
Monomeric immunoglobulin E stabilizes FcεRIα from the human basophil cell line KU812 by protecting it from natural turnover
Authors: Jensen B. M. , Hansen J. B. , Dissing S. , Gerwien J. , Skov P. S. , Poulsen L. K. 
Published: May 2003

SummaryBackground The high affinity IgE receptor (FcεRI) on mast cells and basophils is up‐regulated by its own ligand IgE; however, the mechanism is unknown.Objective To study the IgE‐mediated effect on FcεRI on basophils by using the human basophilic cell line KU812.Methods Expression of cell surface FcεRI was assessed by flow cytometry. Western blot technique was used to illustrate tyrosine‐phosphorylation and the Ca2+ level in KU812 was measured by fluorescence of Fura‐2. Soluble specimens of the α‐chain from FcεRI (FcεRIα) were obtained by lysing 107 KU812 pr. mL. FcεRIα was detected by a sandwich immunoradiometric assay employing the IgE‐binding capacity of FcεRIα in conjunction with a monoclonal antibody. Polyclonal rabbit anti‐FcεRIα was used for detection of FcεRIα by Western blotting.Results We found that monomeric IgE did not induce tyrosine‐phosphorylation in KU812, which was the case when stimulating with IgE cross‐linked by anti‐IgE binding. Further, only cross‐linking of IgE, but not monomeric IgE, increased the Ca2+ level. Using the immunoradiometric assay, we found a temperature dependent reduction in the amount of FcεRIα. Samples incubated at 37 °C for 5 h displayed a 16‐fold decrease in the FcεRIα level compared with samples incubated at 4 °C. In the presence of IgE the reduction at 37°C was only threefold.Conclusion These results indicate that IgE does not induce intracellular signals in KU812, i.e., tyrosine‐phosphorylation or Ca2+ release. Instead it appears that FcεRIα is an unstable protein that IgE stabilizes and thereby protects from a temperature dependent turnover.
Effect of lysed Enterococcus faecalis FK‐23 (LFK) on allergen‐induced peritoneal accumulation of eosinophils in mice
Authors: Shimada T. , Cheng L. , Ide M. , Fukuda S. , Enomoto T. , Shirakawa T. 
Published: May 2003

SummaryBackground The interest in anti‐allergy immunoregulation by lactic acid bacteria has been growing for the last few decades. There is some evidence to suggest that lysed Enterococcus faecalis FK‐23 (LFK) could relieve the clinical symptoms of pollinosis. However, the mechanism responsible for this phenomenon remains unknown.Objective To identify the effect of LFK, a lysozyme treated and heat‐killed preparation from the lactic acid bacteria Enterococcus faecalis FK‐23 strain, on allergen‐induced eosinophil accumulation.Methods BALB/c mice were sensitized with ragweed pollen extract, and peritoneal accumulation of eosinophils was induced. A total of 60 mg (0.5 mL) LFK was orally administered to the experimental mouse every day during 21 days of the sensitization period. In addition, LFK 4 mg, 25 mg and 60 mg (each 0.5 mL) were also orally administered to a mouse of each group every day for 21 days. Saline was fed in a dose of 0.5 mL/mouse per day for the same duration as a control.Results Compared with control mice, LFK‐treated mice exhibited decreased ragweed pollen allergen‐induced peritoneal accumulation of eosinophils (P = 0.013), which showed a tendency to be in a dose‐dependent fashion (P = 0.14).Conclusion The results provide laboratory evidence of the role for LFK, a lactic acid bacteria preparation, in combating eosinophil accumulation.
Characterization of wheezing phenotypes in the first 10 years of life
Authors: Kurukulaaratchy R. J. , Fenn M. H. , Waterhouse L. M. , Matthews S. M. , Holgate S. T. , Arshad S. H. 
Published: May 2003

SummaryBackground Childhood wheezing illnesses are characterized into different phenotypes. However, severity of the disease associated with these phenotypes has not been extensively studied.Objectives To determine characteristics of childhood wheezing phenotypes in the first decade of life using health outcomes plus measurements of atopy, lung function and bronchial hyper‐responsiveness.Methods A whole population birth cohort (n = 1456) was prospectively studied to examine the natural history of childhood wheezing. Children were seen at 1, 2, 4 and 10 years for questionnaire completion and prospectively collected data used to define wheezing phenotypes. Assessment was made of adverse health outcomes plus spirometry, bronchial hyper‐responsiveness, serum IgE measurement at 10 years and skin test sensitization at both 4 and 10 years for wheezing phenotypes.Results Phenotypic analysis identified that 37% early life wheezers (symptom onset by age 4 years) still wheezed at 10 years. These persistent wheezers showed significantly more physician‐diagnosed asthma in early life (P < 0.005 at 2 years) than early transient wheezers (wheezing transiently with onset by age 4 years). Overall they experienced greater multiple hospital admissions (P = 0.024), specialist referral (P = 0.009) and use of inhaled (P < 0.001) and oral steroids (P < 0.001) than early transient wheezers. They also demonstrated enhanced bronchial hyper‐responsiveness compared with early transient wheezers (P < 0.001). However, both groups of early life wheezers showed impairment of baseline lung function at 10 years in comparison with non‐wheezers: FEV1 (P < 0.029) and FEV1/FVC ratio (P < 0.001) with persistent wheeze and PEF (P = 0.036) with early transient wheeze. Late‐onset wheezers (onset from 5 years onwards) had similar BHR to persistent wheezers but maintained normal lung function at age 10 and had lower cumulative prevalence of adverse health outcomes than persistent wheezers.Conclusions Persistent wheezing with early childhood onset is associated with substantial morbidity in the first decade of life in association with high levels of atopy, bronchial hyper‐responsiveness and impaired lung function at 10 years of age. Late‐onset wheezing in the first decade of life could harbour potential for similarly significant disease subsequently.
Longitudinal decline in pulmonary function in atopic cough and cough variant asthma
Authors: Fujimura M. , Nishizawa Y. , Nishitsuji M. , Abo M. , Kita T. , Nomura S. 
Published: May 2003

SummaryObjective Cough variant asthma and atopic cough are different clinical manifestations of eosinophilic airway inflammation presenting with isolated chronic non‐productive cough. The aim of this study was to examine the longitudinal change in pulmonary function in cough variant asthma and atopic cough.Methods Longitudinal change in FEV1 was prospectively examined in 20 patients with cough variant asthma, 14 patients with atopic cough and 271 asymptomatic healthy subjects. All were lifetime non‐smokers. Of the 20 cough variant asthma patients, 13 were taking long‐term inhaled corticosteroid therapy (ICS) (beclomethasone dipropionate 615 ± 58 µg/day) and the other seven were not. Spirometry was taken at first visit, after cough was almost completely relieved on therapy, and at least once every year for 5 or more years afterwards.Results The slope of longitudinal change in FEV1 was not significantly different among cough variant asthma patients (− 0.029 ± 0.007/year), atopic cough patients (− 0.021 ± 0.022/year) and asymptomatic subjects (− 0.028 ± 0.002 L/year). In patients with cough variant asthma, the slope in patients not taking inhaled corticosteroids (ICS) was 0.032 ± 0.007 L/year, which was not significantly different from that in patients taking ICS (− 0.027 ± 0.010 L/year).Conclusion Pulmonary function decline is not greater in cough variant asthma than atopic cough and the normal population, and long‐term ICS has no effect on the decline in cough variant asthma.
Neonatal interleukin‐12 capacity is associated with variations in allergen‐specific immune responses in the neonatal and postnatal periods
Authors: Prescott S. L. , Taylor A. , King B. , Dunstan J. , Upham J. W. , Thornton C. A. , Holt P. G. 
Published: May 2003

SummaryBackground and objectives A reduced capacity of antigen presenting cells (APC) to provide pro‐T helper 1 (Th1) signals, such as IL‐12, to T cells during early life may be implicated in the development of T helper 2 (Th2)‐mediated allergic disease. In this study we examined the relationships between the capacity for IL‐12 responses in the neonatal period and atopic risk (family allergy), in vitro T cell responses to allergens, and the subsequent development of allergic disease at 6 yearsMethods The capacity of circulating neonatal (and maternal) APC to produce IL‐12 p70 in response to LPS (and IFN‐γ) stimulation was assessed in a group of 60 children with previously well‐characterized immune responses to allergens and atopic outcomes. The IL‐12 responses were compared with allergen‐induced lymphoproliferation (to house dust mite (HDM) ovalbumin (OVA), cat and β‐lactoglobulin (BLG)) and IL‐13 and IFN‐γ cytokine responses (to OVA, HDM and phytohaemaglutinin (PHA)) in the neonatal and postnatal periods. IL‐12 responses were also compared according to atopic risk and atopic outcomes (doctor‐diagnosed asthma, eczema, food allergies and sensitization as evidenced by skin prick testing) at 6 years clinical follow‐up.Results Maternal peripheral blood mononuclear cells (PBMC) synthesized significantly greater amounts of IL‐12 than neonatal PBMC, though within maternal‐infant pairs IL‐12 responses were significantly correlated (r = 0.4, P = 0.019). Moreover, neonatal IL‐12 responses were positively correlated with neonatal allergen proliferation for HDM (r = 0.6, P < 0.0001), OVA (r = 0.55, P < 0.0001), cat (r = 0.5, P = 0.003) and BLG (r = 0.55, P = 0.001), but negatively correlated with neonatal IL‐13 responses to both allergens tested (HDM: r = − 0.4, P = 0.03 and OVA: r = − 0.5, P = 0.001). Both neonatal and maternal IL‐12 responses were positively correlated with postnatal IFN‐γ responses to HDM at 12, 18 and 24 months of age (responses after age of 2 years were not assessed). There was no relationship between atopic risk and IL‐12 capacity in the neonatal period, but there was a (non‐significant) trend for neonatal IL‐12 responses to be lower in the high‐risk children who developed clinical allergy at 6 years (compared with the low risk group) although the number in this analysis was small.Conclusions Reduced APC IL‐12 production in the perinatal period was associated with reduced T cell activation (lymphoproliferation), stronger neonatal Th2 responses, and weaker Th1 responses to allergen in the postnatal period. This supports the notion that variations in APC function in early life may contribute to altered allergen‐specific cytokine responses associated with later allergy.
CD63 expression on basophils as a tool for the diagnosis of pollen‐associated food allergy: sensitivity and specificity
Authors: Erdmann S. M. , Heussen N. , Moll‐Slodowy S. , Merk H. F. , Sachs B. 
Published: May 2003

SummaryBackground Basophil activation is associated with the expression of CD63. Because allergens can induce basophil activation by cross‐linking specific IgE, increased CD63 expression has been proposed as a novel in vitro test for immediate type allergy.Objective We compared the CD63‐based basophil activation test (BAT) in the diagnosis of allergy to carrot, celery and hazelnut with skin prick tests (SPT) and measurement of allergen‐specific IgE.Methods Twenty‐nine patients with a history of an oral allergy syndrome induced by carrot, celery or hazelnut (n = 20 for each allergen) and 20 controls were studied. SPT were performed with standardized and native carrot, celery and hazelnut extracts. Allergen‐specific IgE was determined by the CAP FEIA method and basophil activation was determined by flow cytometry upon double staining with anti‐IgE/anti‐CD63 mAb.Results SPT with native carrot, celery and hazelnut showed sensitivities of 100%, 100% and 90%, and specificities of 80%, 80% and 90%. SPT with commercial extracts of the same allergens gave sensitivities of 85%, 80% and 85%, and specificities of 80%, 80% and 90%. Sensitivity of allergen‐specific IgE and the BAT for carrot, celery and hazelnut was 80% vs. 85%, 70% vs. 85%, and 80% vs. 90%, with corresponding specificities of 80% vs. 85%, 80% vs. 80%, and 95% vs. 90%. The cut‐off for a positive BAT was 10% CD63+ basophils. Moreover, there was a positive correlation between IgE reactivity and the number of CD63+ basophils for all food allergens (carrot: r = 0.69, celery: r = 0.67, hazelnut: r = 0.66).Conclusions Quantification of basophil activation by CD63 expression is a valuable new in vitro method for diagnosis of immediate type food sensitization. Although double‐blind placebo‐controlled food challenges remain the gold standard, the CD63‐based BAT may supplement routine diagnostic tests such as SPT or allergen‐specific IgE in the future.
Food hypersensitivity among Finnish university students: association with atopic diseases
Authors: Mattila L. , Kilpeläinen M. , Terho E. O. , Koskenvuo M. , Helenius H. , Kalimo K. 
Published: May 2003

SummaryBackground Food hypersensitivity (FH) is commonly suspected, especially among adults with atopic diseases. Symptoms of FH vary from oral allergy syndrome (OAS) to gastrointestinal, respiratory and systemic reactions. More data are needed regarding patient groups at risk for FH, and symptoms and foods responsible for the reactions.Methods FH was studied in 286 Finnish university students. Four study groups were selected: subjects (i) with current atopic dermatitis (AD) with or without allergic rhinoconjunctivits (ARC) or asthma (n = 41); (ii) with past AD with or without ARC or asthma (n = 89); (iii) with ARC or asthma (n = 69); (iv) without clinically confirmed atopic disease (n = 87). A thorough clinical examination was performed with a questionnaire specifying adverse events to foods. In addition, IgE specific to five foods, and skin prick tests to four foods were determined.Results FH was reported by 172 subjects (60.1%), more often by females (66.3%) than by males (47.9%) (P = 0.003). FH was most frequent among subjects with AD, among those with current AD in 73.2%, with past AD in 66.3%, and with ARC or asthma in 63.8%; 44.8% of subjects without any atopic disease reported FH. Kiwi fruit caused symptoms most frequently (38.4%), followed by milk (32.6%), apple (29.1%), tomato (27.9%), citrus fruits (25.0%), tree nuts (23.3%), and peanut (17.4%). A total of 720 separate symptoms to 25 food items were reported. OAS was most common (51.2%), followed by gastrointestinal symptoms (23.5%), worsening of AD (11.4%), urticaria (4.2%), rhinitis or conjunctivitis (5.7%) and asthma (4.0%). Severe reactions occurred in 3.5% (25/720). Negative IgE and skin prick test to foods predicted well negative history, but the value of positive test results was limited.Conclusions FH was reported most often by students with current AD and multiple atopic diseases. Severe reactions occurred especially in patients with ARC and asthma. After excluding lactose intolerance, milk hypersensitivity was frequently reported.