bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human T cells that have been conditioned by the proteolytic activity of the major dust mite allergen Der p 1 trigger enhanced immunoglobulin E synthesis by B cells
Authors: Ghaemmaghami A. M. , Shakib F. 
Published: March 2003

SummaryBackground We have previously demonstrated that the proteolytic activity of Der p 1 selectively cleaves human CD25, the 55 kDa α subunit of the IL‐2 receptor. As a result of cleavage of surface CD25, peripheral blood T cells produce less IFN‐γ and more IL‐4, thereby leading to progressive polarization of the T cells towards a Th2 cytokine profile. Therefore, these observations underline the potential role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis.Objective To study the effect of T cells that have been conditioned by the proteolytic activity of Der p 1 on IgE synthesis by B cells.Methods We have examined this concept in experiments whereby T cells that have been exposed to either proteolytically active or inactive Der p 1 were cocultured with autologous B cells and IgE antibody synthesis was monitored.Results Here we demonstrate for the first time that coculturing T cells that have been in contact with proteolytically active Der p 1 with autologous B cells leads to augmentation of IgE antibody responses.Conclusions The proteolytic activity of Der p 1 conditions human T cells, which then become empowered to trigger enhanced IgE synthesis by B cells.
Determination of interleukin‐5 secretion from drug‐specific activated ex vivo peripheral blood mononuclear cells as a test system for the in vitro detection of drug sensitization
Authors: Sachs B. , Erdmann S. , Malte Baron J. , Neis M. , Al Masaoudi T. , Merk H. F. 
Published: March 2003

SummaryBackground In vitro detection of drug sensitization is still limited. The lymphocyte transformation test, which determines drug‐specific proliferation, is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction's clinical phenotype. Accumulation of eosinophils following IL‐5 secretion from drug‐specific stimulated T cells is a characteristic histological feature of drug‐induced skin eruptions.Objective We determined whether in vitro drug‐specific activation of ex vivo peripheral blood mononuclear cells from 10 patients with drug‐induced maculopapular exanthems and three patients with severe skin reactions results in secretion of IL‐5, IL‐10 or IFN‐γ and assessed the sensitivity and specificity of drug‐specific IL‐5 secretion as a test system compared with the lymphocyte transformation test and patch tests. Furthermore, the subsets of CD4+ and CD8+ T cells involved in drug‐specific proliferation, IL‐5 secretion and mRNA expression were examined in three patients.Methods Drug‐specific proliferation of peripheral blood mononuclear cells in the lymphocyte transformation test was investigated by 3H‐thymidine uptake, and culture supernatants taken after 5 days were analysed for IL‐5, IL‐10 and IFN‐γ concentrations by ELISA technique. IL‐5 mRNA expression was determined by RT‐PCR.Results Drug‐specific activation of peripheral blood mononuclear cells consistently resulted in IL‐5 and to a lesser extent in IL‐10 and IFN‐γ secretion. The sensitivities of the patch test, lymphocyte transformation test and assessment of drug‐specific IL‐5 secretion for the detection of drug sensitization were 55%, 75% and 92%, respectively.Conclusion These data suggest a role for the determination of drug‐specific IL‐5 secretion by ex vivo peripheral blood mononuclear cells for the in vitro detection of drug‐sensitization in drug‐induced maculopapular exanthems.
Increased Th1 and Th2 allergen‐induced cytokine responses in children with atopic disease
Authors: Smart J. M. , Kemp A. S. 
Published: March 2003

SummaryBackground Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen‐induced T cell responses can provide information on cytokine production by allergen‐reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non‐specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN‐γ responses to allergens in atopic subjects.Objective To examine childhood polyclonal and allergen‐induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease.Methods PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non‐atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic).Results Atopic children had significantly reduced IFN‐γ and increased IL‐4 and IL‐5 but not IL13 production to SEB superantigen stimulation when compared with non‐atopic children. HDM and RYE allergens stimulated significantly increased IFN‐γ, IL‐5 and IL‐13, while OVA stimulated significantly increased IFN‐γ production in atopic children.Conclusion We show that a polyclonal stimulus induces a reduced Th1 (IFN‐γ) and increased Th2 (IL‐4 and IL‐5) cytokine pattern. In contrast, the allergen‐induced cytokine responses in atopic children were associated with both increased Th1 (INF‐γ) and Th2 (IL‐5 and IL‐13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to allergens exists concomitantly with a decreased Th1 response to a polyclonal stimulus in atopic children.
The importance of maximal airway response to methacholine in the prediction of asthma development in patients with allergic rhinitis
Authors: Koh Y. Y. , Kang E. K. , Min Y‐G. , Kim C. K. 
Published: March 2003

SummaryBackground Allergic rhinitis is a known predictor and correlate of asthma incidence. However, it is not clear which patients with allergic rhinitis are at greater risk of the development of asthma.Objective The aim of this study was to investigate whether airway hypersensitivity and/or increased maximal response on the dose–response curve to methacholine would predict the development of asthma in subjects with allergic rhinitis.Methods One hundred and forty‐one children with allergic rhinitis were prospectively studied for 7 years. At the initiation of the study, bronchial provocation test with methacholine using a stepwise increasing concentration technique was performed to measure PC20 (provocative concentration causing a 20% fall in FEV1) and maximal response. Each subject was evaluated at least every 6 months and details of asthmatic symptoms or signs experienced during the intervening period were taken.Results Twenty of 122 subjects available for the follow‐up developed asthma. Nine (19.6%) of 46 hypersensitive (PC20 < 18 mg/mL) subjects developed asthma, compared with 11 (14.5%) of 76 normosensitive subjects (P = 0.462). Eight (32%) of 25 subjects without maximal response plateau developed asthma, compared with 12 (12.4%) of 97 subjects with maximal response plateau (P = 0.018). Score test for trend revealed a significant association between the level of maximal response (P = 0.007), but not the degree of methacholine PC20 (P = 0.123), and the future development of asthma.Conclusion An increased maximal airway response to methacholine is shown to be a better predictor for the future development of asthma in patients with allergic rhinitis, than airway hypersensitivity to methacholine.
An association study between the Clara cell secretory protein CC16 A38G polymorphism and asthma phenotypes
Authors: Mansur A. H. , Fryer A. A. , Hepple M. , Strange R. C. , Spiteri M. A. 
Published: March 2003

SummaryBackgroundPreviously, an association has been reported between an increased risk of asthma and a polymorphism in the Clara cell secretory protein (CC16) gene [namely, an adenine to guanine substitution in the CC16 gene at position 38 (A38G) downstream from the transcription initiation site within the noncoding region of exon 1]. Homozygous individuals for the polymorphic sequence (AA genotype) were reported to have a significant (6.9 fold) increased risk of developing asthma. This finding has not been confirmed independently.ObjectiveTo validate the association of CC16 A38G polymorphism to asthma in a separate well‐characterized population through a case–control study.MethodsWe conducted an association study using a sample of 217 unrelated Northern European Caucasians. Individuals were clinically characterized by a validated respiratory questionnaire, spirometry and bronchial reactivity measurement, and genotyped for the A38G polymorphism using PCR and restriction digestion. Association analysis was performed using the nonparametric Chi‐squared tests.ResultsIn the unselected population, 43.3% participants were homozygous for the CC16*G allele and 45.4% were heterozygous (AG). We observed no significant difference in the distribution of positive bronchial reactivity to methacholine (at FEV1PC20of ≤ 8 mg/mL) across the three genotypes. Homozygous individuals for the CC16*A allele did not demonstrate an increased risk of asthma when compared to heterozygous or GG homozygotes. In addition, no significant difference was observed in the distribution of the CC16*A or *G alleles in the asthmatics vs. non‐asthmatics.ConclusionCC16 polymorphism A38G does not influence the predisposition to asthma in this sample.
High‐level expression of recombinant house dust mite allergen Der p 1 in Pichia pastoris
Authors: Jacquet A. , Magi M. , Petry H. , Bollen A. 
Published: March 2003

SummaryBackground The major house dust mite Der p 1 allergen is associated with allergic disease. Heterologous over‐expression of biologically active Der p 1 was previously attempted but with limited success.Objective The aim of this study was to establish an efficient system for the production of recombinant Der p 1.Methods The proform of Der p 1 was expressed in Pichia pastoris as a fusion with the α mating factor signal sequence. The recombinant product was purified from culture medium and compared to Der p 1 isolated from mite culture, in terms of enzymatic activity as well as IgE binding capacity.Results ProDer p 1 was efficiently secreted into culture medium as a hyperglycosylated protein of 40–60 kDa. Postpurification dialysis in acidic buffer was required for the autocatalytic processing of Der p 1. During this treatment, the prosequence was efficiently removed to give highly glycosylated recombinant mature Der p 1. Competition ELISA experiments as well as cysteine proteinase activity assays indicated that recombinant processed Der p 1 was similar to natural Der p 1 isolated from mite cultures in terms of IgE binding and enzymatic activities. However, the histamine releasing activity of recombinant Der p 1 was slightly weaker than that of natural Der p 1.Conclusion This efficient system for recombinant Der p 1 expression leads the way for the design of new diagnostics for house dust mite allergy, epitope mapping, allergen engineering, structural and immunological studies and new immunotherapeutic treatments.
The use of a neural network to forecast daily grass pollen concentration in a Mediterranean region: the southern part of the Iberian Peninsula
Authors: Sánchez‐Mesa J. A. , Galan C. , Martínez‐Heras J. A. , Hervás‐Martínez C. 
Published: March 2003

SummaryBackgroundPollen allergy is a common disease causing hayfever in 15% of the population in Europe. Medical studies report that a prior knowledge of pollen content in the air can be useful in the management of pollen‐related diseases.ObjectivesThe aim of this work was to forecast daily Poaceae pollen concentrations in the air by using meteorological data and pollen counts from previous days as independent variables.MethodsLinear regression models and co‐evolutive neural network models were used for this study. Pollen was monitored by a Hirst‐type spore trap using standard techniques. The data were obtained from the Spanish Aerobiology Network database, University of Cordoba Monitoring Unit. The set of data includes a series of 20 years, from 1982 to 2001. A classification of the years according to their allergenic potential was made using a K‐mean cluster analysis with pollen and meteorological parameters. Statistical analysis was applied to all the years of each class with the exception of the most recent year, which was used for model validation.ResultsIt was observed that cumulative variables and pollen values from previous days are the most important factors in the models. In general, neural network equations produce better results than linear regression equations.ConclusionCo‐evolutive neural network models, which obtain the best forecasts (an almost 90%“good” classification), make it possible to predict daily airborne Poaceae pollen concentrations. This new system based on neural network models is a step toward the automation of the pollen forecast process.
Allergy development after bone marrow transplantation from a non‐atopic donor
Authors: Shalit M. , Amar A. , Or R. 
Published: March 2003

SummaryBackground Transfer of allergy from atopic bone marrow donors to recipients is known to occur. Development of allergy in a non‐atopic patient transplanted from a non‐atopic donor is an unfamiliar phenomenon in clinical practice.Objectives To clarify the course of events causing a bone marrow recipient to acquire an allergic disease in such non‐conducive circumstances.Methods Full medical history, prick and intradermal skin tests, and serum IgE levels were obtained from both donor and recipient patients. DNA and red blood cell phenotype analyses were used to detect the degree of chimerism.Results Only the recipient patient showed positive specific IgE antibodies and skin tests to house dust mite. The recipient patient displayed 100% donor chimera, based on all engraftment markers sought.Conclusion Full engraftment after allogeneic bone marrow transplantation may be associated with modulation ofT and B cell function, which in turn could cause the onset of allergic disease after bone marrow transplantation.
Polyclonal and allergen‐induced cytokine responses in children with elevated immunoglobulin E but no atopic disease
Authors: Smart J. M. , Tang M. L. K. , Kemp A. S. 
Published: March 2003

SummaryBackground Reduced Th1 and elevated Th2 cytokine responses are considered to be a principal mechanism in the generation of the inflammation leading to the manifestations of atopic disease in the skin of atopic dermatitis and in the airways of asthma. If reduced Th1 and elevated Th2 responses are principal determinants of the manifestation of atopic disease it might be expected that subjects with established disease would exhibit differences in their cytokine profiles as compared with atopic patients without clinical disease.Objective To determine whether asymptomatic atopic children exhibit a cytokine imbalance similar to that seen in patients with established atopic disease or if they behave like non‐atopic controls. Cytokine responses in a group of children with elevated IgE but no clinical manifestations of disease, atopic children with established disease and non‐atopic controls were compared.Methods We examined allergen‐induced (house dust mite, HDM, rye grass pollen and RYE) cytokine responses in parallel with polyclonal (staphylococcal enterotoxin B, SEB) cytokine responses in a group of children with elevated serum IgE levels without current or past evidence of atopic disease (median age 6.6 years) and compared these with a non‐atopic control group (median age 6.5 years) and a group of children with atopic disease (median age 6.7 years).Results Symptomatic atopic children had reduced SEB‐induced IFN‐γ and increased SEB‐induced IL‐4 and IL‐5 as compared with non‐atopic controls. In contrast, SEB‐induced IFN‐γ, IL‐4 and IL‐5 production in asymptomatic atopics was not significantly different from the non‐atopic control subjects. Allergen‐induced Th1 (IFN‐γ) and Th2 (IL‐5 and IL‐13) cytokine production was increased in both symptomatic atopics and asymptomatic atopics when compared with non‐atopic controls.Conclusion The defect in polyclonally induced IFN‐γ production was associated with the clinical manifestation of atopic disease but not the atopic state per se. This suggests that the global reduction in IFN‐γ is the key determinant of the development of overt atopic disease. In contrast, elevated allergen‐induced Th2 cytokine responses in children related to the atopic state per se irrespective of the presence of clinical atopic disease.
Specific sensitization to common allergens and pulmonary function in the European Community Respiratory Health Survey
Authors: Jaén A. , Sunyer J. , Basagaña X. , Chinn S. , Zock J. P. , Antó J. M. , Burney P. ,   the European Community Respiratory Health Survey (ECRHS)
Published: March 2003

SummaryBackground The role of atopy in the evolution to chronic obstructive disease remains controversial.Aim We aimed to assess the association between individual sensitization to common allergens and lung function.Method We analysed data from 12 687 subjects aged 20 to 44 years, from 34 centres in 15 countries participating in the European Community Respiratory Health Survey (ECRHS). Participants performed a blood test, lung function test, methacholine challenge, and answered an administered questionnaire. The relationships between specific IgE, FEV1 and FEV1/FVC ratio were assessed for each study centre stratified by sex, followed by random effects meta‐analysis.Results Asthmatics sensitized to house dust mite had a lower FEV1 (− 119 mL in women and − 112 mL in men) and FEV1/FVC ratio (− 1.95%, and − 2.48%) than asthmatics without sensitization. Asthmatics sensitized to cat had a lower FEV1 (statistically significant for women only) and a lower FEV1/FVC ratio. Asthmatic women sensitized to grass had a lower FEV1 and a lower ratio, and those sensitized to Cladosporium had a lower FEV1. A weak association was found with sensitization to cat and to Cladosporium among non‐asthmatic women, which disappeared after adjusting for BHR.Conclusion We conclude that atopy was related to a lower lung function, which was only apparent among asthmatics. This relationship was explained by specific sensitization to cat and to house dust mite, the latter being homogeneous across areas.
Evaluation of the CD14 C‐159 T polymorphism in the German Multicenter Allergy Study cohort
Authors: Sengler C. , Haider A. , Sommerfeld C. , Lau S. , Baldini M. , Martinez F. , Wahn U. , Nickel R. ,   the German Multicenter Allergy Study Group
Published: March 2003

SummaryBackground Multiple genetic studies have shown linkage of atopy‐related phenotypes to chromosome 5q31. In this region several candidate genes for atopy are localized such as the Th2 cytokines IL‐4, IL‐5 and IL‐13, but also CD14, a receptor for LPS. Recently, a functional CD14 promoter polymorphism was related to total and specific IgE responsiveness.Objective The aim of our study was to evaluate the role of this single nucleotide polymorphism (SNP) in a large German birth cohort.Methods Atopy‐related phenotypes were longitudinally carefully evaluated in over 800 children from birth to the age of 10 years. Yearly visits included standardized interviews, physical examinations and determination of total and specific IgE antibodies. Pulmonary function tests and histamine provocations were performed at the age of seven. Eight‐hundred and seventy‐two children of the Multicenter Allergy Study (MAS) cohort were genotyped using melting curve and restriction digest analyses.Results CD14‐159 allele frequencies were consistent with previous reports, however, no association of the SNP with asthma, atopic dermatitis, allergic rhinitis, total or specific IgE levels could be observed.Conclusion The CD14‐159 SNP might not play a major role in the development of atopy in German children.
Metalloproteinase‐9 is increased after toluene diisocyanate exposure in the induced sputum from patients with toluene diisocyanate‐induced asthma
Authors: Park H.‐S. , Kim H.‐A. , Jung J.‐W. , Kim Y.‐K. , Lee S.‐K. , Kim S.‐S. , Nahm D.‐H. 
Published: March 2003

SummaryBackground and objective Persistent asthma symptoms are associated with airway inflammation and remodeling, which may be mediated through metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP). The aim of this study was to evaluate MMPs and TIMP involvement in toluene diisocyanate (TDI)‐induced asthma.Materials and method Induced sputum was collected in eight newly diagnosed TDI‐induced asthma subjects (group I) before and 7 h after the TDI and placebo challenges and in 12 subjects with TDI‐induced occupational asthma diagnosed 5 years previously with persistent asthma symptoms (group II). Sera was collected in group I at diagnosis, and in group II, they were collected at the time of the study. 12 nonasthmatic healthy subjects were enrolled as controls. MMP‐9, MMP‐2 and TIMP‐1 levels in both sputum and serum were measured by enzyme‐linked immunosorbent assay (ELISA). Gelatinase activity in the sputum was confirmed by zymographic analysis.Results The serum TIMP‐1 level was significantly higher in asthma patients than in healthy controls (P = 0.01), while MMP‐9 level was significantly lower in asthmatic patients (P = 0.03). There was no significant difference in MMP‐2 level (P = 0.27). MMP‐9 level in the sputum was significantly increased after the TDI challenges (P = 0.01). TIMP‐1 level in sputum tended to increase after TDI challenges, but no statistical significance was noted (P = 0.09). MMP‐9 and MMP‐9/TIMP‐1 levels in the sputum were significantly higher in group II than in group I (P = 0.04, P = 0.02) with no significant difference in TIMP‐1 level. Minimal amount of MMP‐2 was found in sputum. Zymography demonstrated that MMP‐9 level increased and active form of MMP‐9 was generated after the TDI bronchoprovocation test.Conclusion TDI exposure leads to overproduction of MMP‐9, which may induce airway inflammation and remodeling, and then contribute to persistent asthmatic symptoms in TDI‐induced asthma.