bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary nucleic acids promote a shift in Th1/Th2 balance toward Th1‐dominant immunity
Authors: Sudo  , Aiba  , Takaki  , Tanaka  , Yu  , Oyama  , Koga  , Kubo  
Published: March 2003

BackgroundDietary sources of nucleic acids and their relative components are known to affect host immune function; however, it has not yet been clarified whether such dietary nucleic acids influence the pathogenesis of allergic reaction.ObjectiveThe purpose of this study is to elucidate the effect of dietary nucleic acids on Th1/Th2 balance.MethodsBoth human flora‐associated and specific pathogen‐free BALB/c mice were maintained on either nucleic acid‐free, or ‐supplemented diets. The effects of nucleic acids on both in vivo antibody levels and in vitro splenocyte cytokine production were compared using these mice.ResultsSupplementation of nucleic acids caused a reduction in the serum antibody levels of total IgM, IgG, IgG1, and IgE in the human flora‐associated mice without affecting the composition of intestinal flora. In contrast, there was no significant difference of the serum IgG2a levels between nucleic acid‐free and ‐supplemented mice. Such a phenomenon as that, the supplementation of dietary nucleic acids reduces the serum IgE or IgG1 levels, but not the IgG2a level, was also seen in the specific pathogen free mice. Moreover, when the mice were systematically challenged with ovalbumin, the supplementation of nucleic acids also suppressed the serum ovalbumin‐specific IgE and IgG1 antibody levels as well as in vitro IL‐4 and IL‐10 secretion, while enhancing both the serum ovalbumin‐specific IgG2a antibody levels and in vitro IFN γ secretion.ConclusionThese results suggested that dietary nucleic acids may play an important role in promoting a shift in Th1/Th2 balance toward Th1‐dominant immunity.
Defective tumour necrosis factor‐alpha production in mother's milk is related to cow's milk allergy in suckling infants
Authors: Järvinen  , Laine  , Suomalainen  
Published: March 2003

BackgroundThe precise role of leucocytes in human milk is still unresolved.ObjectiveTo assist in clarifying the immune mechanisms involved in the development of CMA in suckling infants, we studied the role of immunoregulatory leucocytes and their mediators in human breast milk.MethodsThe study population consisted of 43 lactating mothers and their infants, aged 0.25–8.0 months, followed‐up prospectively from birth. Of these mothers, 27 had an infant with challenge‐proven cow's milk allergy manifested with either skin (n = 23), gastrointestinal (n = 2) or skin and gastrointestinal symptoms (n = 3). Sixteen mothers with a healthy infant served as controls. We evaluated the spontaneous and mitogen‐induced tumour necrosis factor‐alpha (TNFα) and interferon‐gamma (IFNγ) production of human milk leucocytes and isolated peripheral blood lymphocytes in vitro with a commercial ELISA kit.ResultsTNFα production of breast milk leucocytes was significantly lower in the mothers with a cow's milk‐allergic infant, whereas IFNγ production of these cells was comparable in the two groups.ConclusionOur results suggest that in the breast milk of mothers having an infant with cow's milk allergy, the number and function of TNFα‐producing cells is defective. This might lead to a disturbance in the development of oral tolerance and thereby to the development of CMA in suckling infants. These novel results may help in clarifying the etiopathogenesis of CMA.
Late onset reactions to oral food challenge are linked to low serum interleukin‐10 concentrations in patients with atopic dermatitis and food allergy
Authors: Sütas  , Kekki  , Isolauri  
Published: March 2003

BackgroundAberrant cytokine production in vitro has been associated with atopic disease. No study has as yet been made of the circulating cytokine profiles in atopic patients with food allergy in response to oral allergen challenge.ObjectiveTo assess the effect of oral allergen challenge on the serum cytokine concentrations in patients with atopic dermatitis and food allergy.MethodsSerum concentrations of interleukin (IL)‐10, transforming growth factor beta 1, IL‐1ra, IL‐6, IL‐5, IL‐4 and interferon (IFN)‐γ were measured before and after double‐blind, placebo‐controlled food challenges (DBPCFC) (n = 73). Before DBPCFC, combined skin prick and patch testing was performed for cow milk, egg, soybean and cereals, and production of IFNγ, IL‐4, IL‐10 and tumour necrosis factor alpha (TNFα) was determined in supernatants of cultures of peripheral blood mononuclear cells (PBMCs) stimulated by cow milk.ResultsThe oral food challenge triggered immediate onset exanthematous reactions in 22 cases and late onset eczematous reactions in 29. The late‐reacting cases had more positive skin patch test and negative skin prick test reactivities with allergenic food, and they had lower serum IL10 concentrations than immediate‐reacting cases. In challenge‐positive cases, IL‐10 concentrations increased from 2.9 (0.1–5.04) pg/mL to 3.9 (1.2–8.3) pg/mL in response to DBPCFC, P = 0.05, median (interquartile ranges), but not in those tolerant to cow milk. PBMCs of patients with cow milk allergy but not of those tolerant to cow milk generated TNFα in response to cow milk in vitro.ConclusionThese results indicate that oral allergen challenge in atopic patients with food allergy triggers systemic release of IL‐10. Patients with late onset reactions were found to have lower serum IL‐10 concentrations than their immediate‐reacting counterparts. Considering that IL‐10 is an inhibitory cytokine of delayed‐type hypersensitivity, low IL‐10 in late‐reacting patients may explain the high frequency of their positive skin patch tests combined with negative skin prick tests.
Lung epithelial H292 cells induce differentiation of immature human HMC‐1 mast cells by interleukin‐6 and stem cell factor
Authors: Pompen  , Smids  , Dingemans  , Jansen  , Out  , Lutter  
Published: March 2003

BackgroundImmature mast cells migrate into tissues where they differentiate into mature mast cells under the influence of local factors. In the airways of asthmatics increased numbers of chronically activated mast cells are located nearby the airway epithelium.ObjectiveThe aim of this study was to evaluate whether and, if so, which products released by epithelial cells may affect mast cell proliferation and differentiation.MethodsWe performed in vitro studies using the human lung mucoepidermoid carcinoma‐derived H292 cell line and the immature human mast cell line, HMC‐1. Proliferation was assessed by 3H‐thymidine incorporation. Differentiation of HMC‐1 cells was inferred from tryptase production.ResultsExposure of HMC‐1 cells to medium conditioned for 48 h by H292 cells resulted in a reduction of proliferation with 65 ± 4.9% (mean ± sem, n = 9) at day 5. Culturing HMC‐1 cells for 8 days in the presence of H292‐conditioned medium resulted in morphological changes indicative of differentiation, and in a 3.0 ± 0.4‐fold increase of tryptase production (P = 0.0039, n = 9). Conditioned medium from H292 cells that were stimulated by LPS also inhibited HMC‐1 proliferation. Inhibitory antibodies against two mediators from H292 cells, interleukin‐6 (IL‐6) and stem cell factor (SCF), abolished the increase in HMC‐1 tryptase production induced by H292‐conditioned medium. Recombinant human (rh) IL‐6, but not rhSCF, reduced HMC‐1 proliferation with 44% and 13% at day 3 and 5, respectively. Surprisingly, rhIL‐6 did not increase HMC‐1 tryptase production significantly whereas incubation with rhSCF did (1.5 ± 0.1‐fold, P = 0.002, n = 10) although the increase was less than observed for conditioned medium.ConclusionEpithelial‐derived IL‐6 and SCF are implicated in differentiation of HMC‐1 cells but additional factors are not excluded. As activated primary bronchial epithelial cells also express IL‐6 and SCF, it should be considered that these cells are involved in mast cell differentiation within the airways, particularly in diseases where epithelial cells are activated, such as asthma.
Endogenous glucocorticoids and antigen‐induced acute and late phase pulmonary responses
Authors: Stokes Peebles  , Togias  , Bickel  , Diemer  , Hubbard  , Schleimer  
Published: March 2003

BackgroundSeveral studies suggest that endogenous glucocorticoids can dampen the severity of experimental allergic reactions in animals.ObjectiveTo investigate the influence that endogenous glucocorticoids have on the course of IgE‐mediated pulmonary early and late phase reactions.MethodsTwenty‐one allergic asthmatic and six healthy control subjects underwent inhaled antigen challenge with measurements of plasma cortisol and cortisone by gas chromatography‐mass spectrometry.ResultsThere were no differences between the asthmatic and control groups in the baseline levels of cortisol or cortisone. However, the asthmatic subjects had significantly higher cortisol levels (67.2 ± 8.6 vs 35.1 ± 4.5 ng/mL; P = 0.04) and had higher cortisol/cortisone ratios (4.8 ± 0.6 vs 3.0 ± 0.2; P = 0.01) 8 h after challenge compared to the control subjects. Among the asthmatic subjects, those whose FEV1 recovered rapidly had higher baseline levels of cortisol and those who displayed a late phase reaction had lower levels of cortisol during the late phase period.ConclusionThe results suggest that endogenous glucocorticoids may play a significant role in the modulation of airway responses to antigen challenge, and that antigen challenge may induce cortisol production in allergic subjects.
Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects
Authors: Cederbrant K. , Marcusson‐StÅhl M. , Hultman P. 
Published: March 2003

BackgroundAntigen‐specific cell lines or clones are often used as models of drug‐specific allergy. However, cloning procedures are time consuming, and the repeated antigen stimulation cycles as well as the addition of various growth enhancers may affect the in vivo relevance of these systems.ObjectiveUsing bacampicillin‐allergic subjects, we wanted to investigate the applicability of primary recall in vitro lymphocyte responses to characterize type I and type IV allergy. The sensitivity and specificity of LTT (Lymphocyte transformation test), when used as an in vitro diagnostic tool, were also assessed.MethodsA total of 39 patients with symptoms of type I (rhinitis) or type IV (allergic contact dermatitis, ACD) allergy following occupational exposure to bacampicillin, were included. Ten individuals without penicillin allergy or occupational exposure to bacampicillin served as controls. All subjects were LTT tested. Four patients with rhinitis and two patients with ACD were available for studying the immunophenotype and the TCR‐Vβ repertoire of bacampicillin induced lymphoblasts as well as the cytokine profiles and expression of the activation markers CD23 and CD134 in primary PBMC cultures.ResultsLTT was positive in 87% and at least one of the skin tests was positive in 85% of the patients with allergic symptoms. 69% of the patients with type I allergies were patch test‐positive. Results from LTT and skin test correlated in 87% of the cases. The combined sensitivity of LTT and skin tests was 92%. The specificity of LTT was 90% in healthy controls. Bacampicillin induced lymphoblasts were mainly CD4 + in both ACD and rhinitis patients. The TCR‐Vβ profiles of the predominant CD4 + lymphoblasts were heterogeneous with individual skewing towards Vβ2, Vβ3, Vβ5.1 and/or Vβ14. An increased expression of IFNγ was detected in bacampicillin treated PBMC cultures from the ACD but not from rhinitis patients. IL‐5 was detected in bacampicillin exposed PBMC cultures from all patients but not from healthy controls. This Th2 environment could also be verified by CD23 and CD134 expression.ConclusionLTT and skin tests are equally sensitive in identifying bacampicillin allergic subjects. When the two tests are combined, the sensitivity increases. The patch test is useful not only for detection of type IV but also for the identification of type I allergies. When using primary PBMC cultures, IFNγ is the most suitable cytokine to discriminate between type I and type IV allergy. IL‐5 can possibly be used as a general marker for bacampicillin induced allergy. Thus, primary cell cultures may be considered as an alternative to T‐cell lines or clones for the study of drug induced allergy.
Assessment of latex allergy in a healthcare population: are the available tests valid?
Authors: Pridgeon C. , Wild G. , Ashworth F. , Egner W. , Ward A. M. 
Published: March 2003

BackgroundLatex allergy can cause serious, preventable work‐related health problems in healthcare workers who are a high risk group for this form of allergy. Type I hypersensitivity can produce life‐threatening systemic effects, and involves an allergen‐specific immunoglobulin (IgE) response to proteins found in latex. The estimated prevalence of latex ‘allergy’ in healthcare workers varies widely (2.8% − 18%), and studies do not always distinguish between those who are positive in an assay for latex‐specific IgE and those with clinical allergy.ObjectiveTo assess the performance of four in‐vitro methods and three skin testing methods for detecting latex‐specific IgE in a group of UK healthcare workers. Test results were compared with reported clinical symptoms defined by questionnaire.MethodsSkin prick testing was carried out on volunteers using three reagents: (a) stallergenes commercial latex extract (Cedex, France); (b) an in‐house latex glove extract; and (c) a fresh glove piece. Specific IgE levels were determined using Pharmacia AutocapTM (Uppsala, Sweden), Pharmacia UnicapTM (Uppsala, Sweden), DPC Immulite® (Los Angeles, USA) and Hycor HytecTM (Irvine, California, USA) methods. Each volunteer completed a questionnaire detailing latex exposure and allergic history.Results In vitro methods for detecting specific IgE to natural rubber latex were positive in 3.6%, to 43.6% of the same population. Skin prick tests positivity varied between 2.9% and 14.3% with different extracts. From the subjects tested 9.1% reported symptoms which could be consistent with type I allergy, although none had been given a pre‐existing diagnosis of latex allergy, and 43.6% of volunteers reported symptoms consistent with type IV hypersensitivity or irritant dermatitis. Contingency tables and chi‐squared analysis revealed no correlation between most methods. No correlation was shown between symptoms consistent with type I allergy and any in vitro or skin testing method for latex‐specific IgE.ConclusionsA wide variation between testing procedures was found, and no method could be correlated with reported symptoms of type I allergy. At least one in vitro specific IgE assay produced a high percentage of positive results at variance with the clinical symptoms in volunteers. A clinical history is essential in establishing type I hypersensitivity to latex and test results should not be used in isolation. The incidence of clinical sensitization may be seriously over‐estimated if only laboratory parameters are used.
Safety of allergen‐specific immunotherapy. Relation between dosage regimen, allergen extract, disease and systemic side‐effects during induction treatment
Authors: Mellerup M. T. , Hahn G. W. , Poulsen L. K. , Malling H.‐J. 
Published: March 2003

BackgroundAllergen‐specific immunotherapy is a well‐documented treatment for allergic rhinitis, asthma, and allergy to Hymenoptera venoms. The drawbacks of injection immunotherapy are related to the risk of inducing systemic side‐effects (especially during the induction phase), the time used to reach the maintenance dose, and the percentage of patients completing the induction phase).ObjectiveTo investigate the practicability and safety of three different patient‐friendly induction regimens of clustered immunotherapy (several injections administered during each visit).MethodsSince 1990, three different clustered induction regimens (regimen 1 = exclusively aqueous extracts; regimen 2 = a combination of aqueous and alum depot extracts; and regimen 3 = induction using exclusively alum depot extracts) have been investigated in 657 patients (10 369 injections).ResultsA total of 454 systemic (immediate and late) reactions were observed in 257 patients corresponding to 4.4% of the injections and 39.1% of the patients. Most of the systemic reactions were of little or no clinical importance (93% grade 1 and grade 2) and < 1% anaphylactic reactions. The 8‐week induction regimen using exclusively alum depot extracts showed a statistical significant lower frequency and severity of systemic side‐effects. Immunotherapy with cat and mite allergen extracts showed the highest frequency of severe side‐effects, which may be related to these extracts being used predominantly in asthmatic patients. The lowest frequency of systemic side‐effects was observed in patients allergic to Hymenoptera venoms and these patients furthermore showed the highest number of patients (97%) completing the induction phase.ConclusionAn 8‐week clustered induction regimen using alum depot extract seems an acceptable compromise in relation to a reduction in the time used to reach maintenance dose and the risk of inducing clinically relevant systemic side‐effects, and consequently imply a reduction in the costs of the treatment.
Mutation screening of interferon regulatory factor 1 gene (IRF‐1) as a candidate gene for atopy/asthma
Authors: Noguchi E. , Shibasaki M. , Arinami T. , Yamakawa‐Kobayashi K. , Yokouchi Y. , Takeda K. , Matsui A. , Hamaguchi H. 
Published: March 2003

BackgroundIL‐4 gene cluster on chromosome 5 contains several candidate genes for atopy and asthma. Several independent studies have shown evidence for linkage between the markers flanking IL‐4 gene cluster and asthma and/or asthma‐related traits. Interferon regulatory factor 1 (IRF‐1) is located approximately 300 kb telomeric to IL‐4 and recent study reveals that IRF‐1 deficiency results in an elevated production of Th2‐related cytokines and a compensatory decrease in the expression of native cell‐ and Th1‐related cytokines.ObjectiveTo determine if there are any mutations associated with the development of atopy and asthma present in the coding exons and 5′ flanking region of the IRF‐1 gene.Methods and resultsWe have screened the promoter and coding regions of the IRF‐1 gene in atopic asthmatics and controls by SSCP method. We found three novel nuclear variants (the −300G/T and 4396 A/G polymorphisms and the 6355G > A rare variant) in the IRF‐1 gene. No variants causing amino acid alterations of IRF‐1 were detected. The −300G/T polymorphism was in nearly complete linkage disequilibrium with the 4396 A/G polymorphism. An association between the 4396 A > G polymorphism and atopy/asthma was examined by transmission disequilibrium test in 81 asthmatic families. Either of 4396 A or 4396G alleles was not significantly preferentially transmitted to atopy‐ or asthma‐affected children.ConclusionThe IRF‐1 gene is less likely to play a substantial role in the development of atopy and asthma in the Japanese population.
Natural rubber latex allergy in children: a follow‐up study
Authors: Ylitalo L. , Alenius H. , Turjanmaa K. , Palosuo T. , Reunala T. 
Published: March 2003

BackgroundNatural rubber latex (NRL) allergy occurs frequently in children with spina bifida and other children with disorders requiring multiple operations. Also atopic children who have not undergone surgery can be sensitized to NRL, but the outcome of these children has not been studied.ObjectiveTo study how NRL‐allergic children manage at home and whether their skin prick test (SPT) reactivity, latex RAST or IgE antibody levels to NRL allergens change during the follow‐up.MethodsTwenty‐four NRL‐allergic children who had not undergone surgery and eight children with histories of multiple operations were followed up for a mean of 2.8 years. Clinical symptoms were recorded and all children were re‐examined with SPT, latex RAST and ELISA for IgE antibodies to prohevein (Hev b 6.01), hevein (Hev b 6.02) and rubber elongation factor (REF, Hev b 1).ResultsNineteen of the 24 NRL‐allergic children (79%) who had not undergone surgery had occasionally contacts to balloons and other NRL products at home, and 10 of them experienced symptoms ranging from contact urticaria to systemic reactions. Three of the eight NRL‐allergic children with a history of multiple operations had contacts to rubber balloons without any symptoms, and five children underwent 1–8 uneventful operations in a latex‐free environment. SPT reactivity to NRL allergens, latex‐RAST or IgE antibody levels to prohevein or hevein did not change in either group of NRL‐allergic children during the follow‐up.ConclusionsOccurrence of clinical symptoms and no decrease in SPT reactivity or IgE levels to NRL allergens in the course of the present follow‐up study imply that more attention should be paid to the protection of NRL‐allergic children from rubber contacts in the home environment.
Combined effects of aerobiological pollutants, chemical pollutants and meteorological conditions on asthma admissions and A & E attendances in Derbyshire UK, 1993–96.
Authors: Lewis S. A. , Corden J. M. , Forster G. E. , Newlands M. 
Published: March 2003

BackgroundThe effect of outdoor aeroallergen exposure in asthma may be enhanced by air pollutants, including ozone, nitrogen dioxide and particulates, and by certain weather conditions. It is not yet established whether these interactions are important in determining asthma morbidity at the population level.ObjectiveWe have investigated the joint effects of aeroallergens, rainfall, thunderstorms and outdoor air pollutants on daily asthma admissions and Accident and Emergency (A & E) attendance using routinely collected data between 1993 and 1996 from Derby in central England.MethodsDaily counts during the aeroallergen season of grass and birch pollen, basidiospores, Didymella, Alternaria and Cladosporium, maximum 1 hour ozone and nitrogen dioxide and daily average black smoke measurements, all made in the vicinity of the city centre, were categorized in tertiles. Rainfall was classified as dry, light (≤ 2 mm) or heavy (> 2 mm). The modifying effect of outdoor pollutant levels, and rainfall or the occurrence of a thunderstorm, upon the effects of individual aeroallergens on asthma admissions and A & E attendance were investigated by fitting appropriate interactions in log linear autoregression models with adjustment for potential confounders.ResultsWe found a significant interaction between the effects of grass pollen and weather conditions upon A & E attendance, such that the increase with grass pollen count was most marked on days of light rainfall (adjusted rate ratio for ≥ 50 vs < 10 grains/m3 at lag 2 days = 2.1, 95% CI 1.4, 3.3). Asthma admissions increased with Cladosporium count. We found no statistically significant interactions between effects of any individual aeroallergen and outdoor air pollutant upon either measure of asthma morbidity.ConclusionsRainfall and thunderstorms are important effect modifiers in the relation between grass pollen and measures of acute asthma morbidity. Interactions between ambient levels of aeroallergens and chemical pollutants in the Derby area do not play a major role in determining asthma admissions and A & E attendance.