bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of cytokine generation and mediator release by human basophils treated with desloratadine
Authors: Schroeder J. T. , Schleimer R. P. , Lichtenstein L. M. , Kreutner W. 
Published: March 2003

Background Desloratadine is a non‐sedating, clinically effective, anti‐allergic therapy that has been shown to exhibit anti‐inflammatory properties that extend beyond its ability to antagonize histamine at H1‐receptor sites. This latter effect has been shown in vitro to be both IgE‐dependent and ‐independent.Objective In this study, we addressed the ability of desloratadine to inhibit the in vitro generation of interleukin (IL)‐4 and IL‐13 from human basophils while concurrently comparing its efficacy in preventing mediator release by these cells.Methods Basophil‐enriched suspensions were treated with various concentrations of desloratadine for 15 min before stimulating with either anti‐IgE antibody, calcium ionophore, IL‐3 or phorbol ester. Histamine (fluorimetry), LTC4 (RIA) and IL‐4 (ELISA) were all assayed using the same 4‐h culture supernatants. IL‐13 (ELISA) was measured in supernatants harvested after 20 h incubation. IL‐4 mRNA expression (dilutional RT‐PCR) was also examined.Results Desloratadine was found to be nearly six–seven times more potent in preventing the secretion of IL‐4 and IL‐13 induced by anti‐IgE than it was at inhibiting the release of histamine and LTC4. These cytokines were equally inhibited by desloratadine following activation with ionomycin despite the lack of an effect on the histamine induced with ionomycin. Desloratadine had a lesser effect regarding inhibition of the IL‐13 secreted in response to IL‐3 and PMA. There was no evidence that desloratadine mediated its inhibitory effects by causing decreased cell viability. Finally, IL‐4 mRNA accumulation was remarkably inhibited, by as much as 80%, following pretreatment with desloratadine.Conclusion While capable of inhibiting histamine and LTC4 release by human basophils, desloratadine is more effective at targeting the signals regulating IL‐4 and IL‐13 generation in these cells. This inhibitory effect on cytokine generation provides additional evidence that this antihistamine exerts anti‐inflammatory properties.
Difference in exposure to airborne major rat allergen (Rat n 1) and to endotoxin in rat quarters according to tasks
Authors: Lieutier‐Colas F. , Meyer P. , Larsson P. , Malmberg P. , Frossard N. , Pauli G. , De Blay F. 
Published: March 2003

Endotoxins found in occupational settings constitute a risk factor in the severity of respiratory allergic symptoms.Objectives To assess the airborne concentrations of major rat allergen (Rat n 1) and endotoxin under various circumstances.Methods We took 483 airborne samples from 12 sites: 114 individual samples for endotoxin measurements and 113 for Rat n 1, from 38 workers (nine animal technicians, nine laboratory technicians, nine scientists and 11 students); and 256 static samples in rat rooms and experimental rooms, with or without disturbance, for simultaneous endotoxin and Rat n 1 measurements. Rat n 1 was measured with a two‐site monoclonal ELISA and endotoxins with the Limulus method.Results Airborne Rat n 1 and endotoxin were significantly higher in rat rooms than in experimental rooms. Animal technicians had the greatest exposure to both Rat n 1 and endotoxin. Cage cleaning and rat feeding induced the highest exposure to Rat n 1 and endotoxin. Furthermore, we observed no significant difference in endotoxin exposure between researchers with or without rat contact during the sample period. There was no correlation between the number of rats present and airborne endotoxin concentrations.Conclusions Exposure to airborne Rat n 1 and endotoxin is higher during cleaning and feeding tasks than during any other task, we feel that a major source of both is contaminated bedding that becomes airborne during disturbance.
DNA sequence variants of the platelet‐derived growth factor A‐chain gene
Authors: Baron R. , Silverman E. S. , Grasemann H. , Collins T. , Drazen J. M. 
Published: March 2003

Background Platelet‐derived growth factor A‐chain (PDGF‐A) is a potent connective tissue mitogen implicated in lung growth and development. PDGF‐A may have a role in asthma through effects on fibroblasts and bronchial smooth muscle cells.Objective To test the hypothesis that there exist variations in the PDGF‐A gene associated with the asthma phenotype.Methods We screened genomic DNA from normal and asthmatic subjects using single‐stranded conformational polymorphism (SSCP) for mutations in the promoter and all seven exons of the gene.Results Four transition polymorphisms (three novel) were identified: one each in exons 3 and 4 (overall population allele frequencies 0.18 and 0.02, respectively) which did not alter the protein sequence, one in exon 4 (frequency 0.005) which resulted in a valine to isoleucine substitution, and one in intron 5 (frequency 0.5). The intron 5‐sequence variant is close to the 3′ end of exon 5 but does not appear to affect alternative splicing of PDGF‐A exon 6 RNA. The frequencies of the polymorphisms in exons 3 and intron 5 did not differ between the asthmatic and non‐asthmatic subjects, but there was a significant frequency difference between Caucasian and African‐American subjects for each of these polymorphisms (P = 0.03 and 0.003, respectively).Conclusion No association was found between the sequence variants in the PDGF‐A gene and the development of asthma. However, the allele frequency of some of the sequence variants differed between the Caucasian and African‐American subjects.
In vivo kinetics of the immunoglobulin E response to allergen: bystander effect of coimmunization and relationship with anaphylaxis
Authors: Von Garnier C. , Astori M. , Kettner A. , Dufour N. , Corradin G. , Spertini F. 
Published: March 2003

Background Murine models of hypersensitivity to allergens are useful tools for the evaluation of preclinical strategies to down‐regulate the IgE response.Objective To monitor the long‐term kinetics of T and B cell responses to allergen as a function of allergen dosage and to investigate the effect of parallel immunization with a second antigen; to correlate B cell response with anaphylaxis.Methods CBA/J mice were sensitized every other week by subcutaneous injections of phospholipase A2 (PLA2) and/or ovalbumin (OVA) adsorbed to alum. Specific antibody isotype responses, T cell proliferation, T cell cytokine production and anaphylaxis were assessed throughout the sensitization phase.Results Low‐dose immunization with PLA2 (0.1 µg) favoured a long‐term, specific T helper (Th)2 response with high IgE and IL‐4 production in contrast to high‐dose PLA2 (10 µg) immunization, which biased the immune response towards a Th1 response with high IgG2a and low IL‐4 production. Parallel immunization with an unrelated antigen (ovalbumin) had a significant bystander effect on the immunization with PLA2, which was also dose‐dependent. Finally, although anaphylaxis as measured by rectal temperature drop was allergen‐specific, it could be induced in the high‐ and low‐dose immunization groups, and was not solely dependent on IgE levels.Conclusion Though low‐dose allergen immunization appears to induce an efficient IgE response, the intensity and quality of this response may be modulated by bystander effects of parallel immunization and does not correlate strictly with anaphylaxis. This observation has relevance to the design of clinical immunotherapy protocols using murine model‐based data.
What is the role of the hevein‐like domain of fruit class I chitinases in their allergenic capacity?
Authors: Dìaz‐Perales A. , Sánchez‐Monge R. , Blanco C. , Lombardero M. , Carillo T. , Salcedo G. 
Published: March 2003

Background Class I chitinases are the major panallergens in fruits associated with the latex–fruit syndrome. These enzymes contain an N‐terminal hevein‐like domain homologous to latex hevein, and a larger catalytic domain. The role of these domains in their allergenic capacity is still controversial.Objective We sought to evaluate the role of both domains of class I chitinases in their IgE‐binding properties, using Cas s 5, the major allergen from chestnut, as a model.Methods Recombinant Cas s 5 and its deleted form, lacking the hevein‐like domain, designated rCat, were expressed in Pichia pastoris using the pPIC 9 vector. Both recombinant products were purified from the supernatants of transformed yeast cultures by gel‐filtration and cation‐exchange chromatography. The isolated proteins were characterized by N‐terminal sequencing, enzymatic activity and N‐glycosylation tests, anti‐chitinase and specific IgE immunodetection. Immunoblot, RAST and CAP inhibition assays were also performed.Results Both purified rCas s 5 and rCat showed the expected N‐terminal amino acid sequences and an enzymatic activity similar to that of their natural counterparts isolated from chestnut seeds, and were strongly recognized by anti‐chitinase antibodies. In contrast, only rCas s 5, but not rCat, bound specific IgE from sera of patients suffering from the latex–fruit syndrome, and fully inhibited IgE‐binding to natural Cas s 5 in immunoblot inhibition assays. Latex hevein also exerted a strong immunoblot inhibition of IgE‐binding to chestnut Cas s 5. RAST and CAP inhibition using whole chestnut extract on the solid phase, rendered inhibition levels around 70–90% for rCas s 5 and 60% for rCat, in contrast to the immunoblotting results.Conclusions Recombinant Cas s 5 behaves like natural Cas s 5 in IgE‐binding assays in vitro. The hevein‐like domain of allergenic class I chitinases seems to include all their main IgE‐binding epitopes when tested by immunodetection and immunoblot inhibition experiments. RAST and CAP inhibition assays, on the contrary, suggest that relevant epitopes are also harboured in the catalytic domain of these allergens.
Increase of allergen‐specific immunoglobulin E antibodies from 1973 to 1994 in a Finnish population and a possible relationship to Helicobacter pylori infections1
Authors: Kosunen T. U. , Höök‐Nikanne J. , Salomaa A. , Sarna S. , Aromaa A. , Haahtela T. 
Published: March 2003

Background The prevalence of atopic diseases – hayfever, asthma and eczema – has increased over the past decades. The increase may be associated with decreased rates of infections such as measles, hepatitis A, tuberculosis, toxoplasmosis, and, as recently suggested, Helicobacter pylori gastritis.Objective Since the increase of atopy has been mainly based on clinical studies, we wanted to study the prevalence of allergen‐specific Immunoglobulin (Ig)E antibodies in two cross‐sectional, adult population‐based serum samples two decades apart. Since the sera had been tested for H. pylori antibodies, we also had a chance to look for a possible relationship between these two findings.Methods We determined the prevalence rate of allergen‐specific serum IgE antibodies against birch and timothy pollen, and cat and dog epithelium allergens by the radioallergosorbent test in a 15–54‐years‐old Finnish population using 326 sera collected in 1973 and 319 sera collected in 1994 from randomly selected subjects.Results From 1973 to 1994 allergen‐specific IgE prevalence rates and IgE antibody levels rose. In 1994, the prevalence rate of positive findings in 15–24‐year‐old population had increased from 11 to 38% (3.5‐fold increase, P = 0.0001, OR 5.12, CI 95% 2.32–11.3). In older 10‐year age groups similar trends did not reach significance, but the overall change was significant with all three cut‐off levels of allergen‐specific IgE analysed.The percentage of IgE‐positive persons rose mainly in the subgroup with no H. pylori antibodies. In 1994 21% of the H. pylori‐negative subjects had IgE antibodies compared with 5% of the H. pylori‐positive subjects (in 1973 11% in both subgroups).Conclusions IgE‐based evidence for an increase in IgE‐mediated allergy was uncovered. The increase occurred mainly in the subgroup with no antibodies to H. pylori, which support the hypothesis that H. pylori could be one of the microbes counteracting atopy.
Pulmonary function changes and immunomodulation of cytokine expression by zafirlukast after sensitization and allergen challenge in brown Norway rats
Authors: Lin C.‐C. , Lin C.‐Y. , Liaw S.‐F. , Chen A. 
Published: March 2003

SummaryBackground The cysteinyl leukotrienes are known important mediators in bronchial asthma.Objective Our purpose was to evaluate the effect of zafirlukast on the late‐phase reaction, bronchial hyper‐responsiveness (BHR) and T cell‐related cytokine mRNA expression in ovalbumin (OA)‐sensitized brown Norway rats (BNRs).Methods Thirty BNRs were equally divided into three groups. Group I and II animals were sensitized and then provoked with OA. Zafirlukast was given intraperitoneally (i.p.) to group I animals prior to provocation. Group II animals received i.p. normal saline. Group III animals (controls) were not sensitized and breathed aerosolized saline. After OA provocation, the animals were anaesthetized. Pulmonary function tests (PFT) were performed at baseline and after varying doses of acetylcholine. Thereafter, bronchoalveolar lavage (BAL) was performed and the lungs were examined histologically. Total RNA was extracted from lung tissue and reverse transcriptase‐polymerase chain reaction (RT‐PCR) was performed using primers for IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, TNF‐α, IFN‐γ, iNOS and β‐actin.Results Group II OA‐treated BNRs had worse PFT results, more severe bronchoconstriction in response to acetylcholine, and more severe inflammation in lung tissue than the other two groups. Group II had higher IL‐2, IL‐4, IL‐10 and IFN‐γ cytokine levels in BAL fluid and higher IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IFN‐γ, TNF‐α and iNOS mRNA levels when compared with group I.Conclusion Zafirlukast is effective in preventing late‐phase bronchoconstriction and BHR, reducing inflammatory response, and decreasing IL‐2, IL‐4, IL‐5, IL‐6, IL‐10 and IFN‐γ and iNOS mRNA expression.
Cysteinyl leukotrienes induce human eosinophil locomotion and adhesion molecule expression via a CysLT1 receptor‐mediated mechanism
Authors: Fregonese L. , Silvestri M. , Sabatini F. , Rossi G. A. 
Published: March 2003

SummaryBackground The mechanisms involved in eosinophil recruitment by cysteinyl‐leukotrienes (CysLTs) remain to be defined.Objective We investigated whether CysLTs LTC4, LTD4 and LTE4 could directly stimulate in vitro adhesion molecule expression and cell locomotion of blood eosinophils from atopic asthmatic donors.
Methods Mab staining and FACS analysis were used to evaluate Mac‐1 and LFA‐1 expression on eosinophils before and after CysLTs stimulation. Eosinophil locomotion was tested using a 48‐well Boyden microchamber.
Results CysLTs, at the concentrations of 1 and 10 nM, were able to significantly up‐regulate Mac‐1 expression (P < 0.05, each comparison) but not LFA‐1 expression (P > 0.05, each comparison). A dose‐dependent, eosinophil chemotaxis was also induced by LTC4, LTD4 and LTE4 (0.1–10 nM) (P < 0.01, each comparison). Montelukast (0.01 nM to 10 nM), a specific CysLT1 receptor antagonist, significantly down‐regulated LTC4, LTD4 and LTE4‐induced Mac‐1 expression (P < 0.01, each comparison) and the CysLT‐induced eosinophil migration (P < 0.01, each comparison). In contrast, montelukast did not affect Mac‐1 expression or cell migration when eosinophils were stimulated by the ‘non‐specific activators’, such as fMLP or C5a (P > 0.05, each comparison).Conclusion These data demonstrate that CysLTs are active in vitro in directly up‐regulating human eosinophil functions involved in eosinophil recruitment. The down‐regulation of Mac‐1 expression and eosinophil chemotaxis by the potent and selective CysLT1 receptor antagonist montelukast indicated the specificity of the LTC4‐, LTD4‐ and LTE4‐induced response.
Outcome of a latex avoidance program in a high‐risk population for latex allergy – a five‐year follow‐up study
Authors: Reider N. , Kretz B. , Menardi G. , Ulmer H. , Fritsch P. 
Published: March 2003

SummaryBackground Children with a shunted hydrocephalus are at highest risk for developing an immediate type allergy to latex. Limited data are available for preventive or therapeutical approaches.Objective To evaluate the effectiveness of latex avoidance, with special regard to status of sensitization and compliance.Methods In 1995, 131 children with a shunted hydrocephalus were screened for sensitization to latex by skin prick test and determination of specific IgE. Patients and parents were instructed on latex‐avoiding strategies. Hospital physicians, family doctors and dentists were advised to perform further surgical and other medical interventions under latex‐free conditions.In 2000, 100 of these 131 patients were re‐evaluated according to the same testing procedures. Special attention was directed at the extent prophylaxis had been performed.Results In 1995, 30/100 patients re‐evaluable in 2000 proved sensitized to latex, 70 had negative testing results. In 2000, 64/70 patients were still negative, six had meanwhile developed latex‐specific IgE. Seven out of thirty subjects with former positive testing had changes within the same RAST‐class, 20 showed a decline of at least one RAST‐class, whereas in three cases an increase of latex‐specific IgE was found. However, only 34 patients, mainly those being already sensitized, had thoroughly followed both medical and private prophylaxis. Within this group, 16 subjects (47.1%) had improved and another nine (26.5%) were still negative. Only three (8.8%) already previously sensitized patients presented with a further increase of latex‐specific IgE. Medical prevention contributed more to the outcome than home prevention. No statistically significant correlation with latex‐avoidance was observed, however, in previously unsensitized subjects. Underlying disease, atopy, number of operations, and age did not prove as significant variables.Conclusion Secondary prevention results in a decrease of specific IgE in latex‐sensitized patients with hydrocephalus. This is due to medical more than home prophylaxis. Sensitization obviously occurs mainly in early childhood, thus primary prevention remains to be the main target.
Fluticasone inhibits the progression of allergen‐induced structural airway changes
Authors: Vanacker N. J. , Palmans E. , Pauwels R. A. , Kips J. C. 
Published: March 2003

SummaryBackground Inhaled corticosteroids are widely used as first‐line therapy in patients with asthma. The concept of early introduction is more and more accepted.Objective In our rat model of airway remodelling, we investigated whether treatment with inhaled fluticasone propionate can inhibit further progression of established structural airway changes.Methods Sensitized Brown Norway rats were exposed to aerosolized ovalbumin (1%) from day 14 to 42. From day 28 to 42, animals were treated with inhaled fluticasone or placebo 30 min before each allergen challenge. One control group was exposed to PBS from day 28 to 42, a second control group throughout the whole experiment.Results Exposure to ovalbumin during 2 weeks induced structural airway changes, including epithelial cell proliferation, increase in airway wall area and fibronectin deposition. Goblet cell number was increased, although not significantly compared with PBS. Continuing allergen exposure for 2 weeks further enhanced each of these features. In addition, the amount of collagen in the airway wall was enhanced by 4 weeks allergen exposure compared with PBS‐exposed animals. These additional increases were inhibited by treatment with fluticasone during the last 2 weeks.Conclusion The progression of established allergen‐induced structural airway changes in sensitized rats can be inhibited by treatment with fluticasone.
A double‐blind, placebo‐controlled study on the diagnostic accuracy of an electrodermal test in allergic subjects
Authors: Semizzi M. , Senna G. , Crivellaro M. , Rapacioli G. , Passalacqua G. , Canonica W. G. , Bellavite P. 
Published: March 2003

SummaryBackground Many unconventional diagnostic procedures based on bioelectrical skin responses are presently widely used for allergic diseases, but rigorous experimental evaluations of their accuracy are still lacking.Aim We assessed whether an electrodermal device can correctly diagnose respiratory allergy.Methods The diagnostic accuracy of the electrodermal device was assessed in double‐blind fashion in 72 allergic patients and 28 healthy volunteers. A random sequence of substances in sealed vials, including histamine, allergens, immunoglobulins at various dilutions and physiological saline, were tested in duplicate in each subject.Results A wide variability of the measurements was found in most patients irrespective of their allergy status and of the substance tested. Allergic patients showed more negative skin electrical response at the second trial, compared to normal controls, independent of the tested substance. No significant difference in skin electrical response between allergens and negative controls could be detected.Conclusion We conclude that the studied bioelectrical method, under blind testing, cannot correctly detect respiratory allergy.
Der p 2 isoallergens have different allergenicity, and quantification with 2‐site ELISA using monoclonal antibodies is influenced by the isoallergens
Authors: Park J. W. , Kim K. S. , Jin H. S. , Kim C. W. , Kang D. B. , Choi S. Y. , Yong T.‐S. , Oh S. H. , Hong C.‐S. 
Published: March 2003

SummaryBackground Der p 2 isoallergens have been reported and the possibility of different allergenicity has also been suggested. In addition, the quantification with 2‐site ELISA may be affected by the isoallergens.Objectives Two different recombinant Der p 2 (rDer p 2) isoallergens were compared in terms of human IgE responses and the reliability of quantification of them with two‐site ELISA kits which use monoclonal antibodies (mAbs) as capture and detection of Der p 2.Methods Seven different Der p 2 cDNA from the cultured Dermatophagoides pteronyssinus (DP) were cloned and polymorphism in nine amino acid residues was found. Two different recombinant isoallergens (rDer p 2A and rDer p 2B) were expressed and compared to their human IgE immune responses by ELISA and the ELISA inhibition test with 23 sera of DP‐allergic patients. The reliability of quantification of two different available 2‐site ELISA kits, which used mAbs for capture and detection of Der p 2, was evaluated.Results The ELISA optical density of rDer p 2B‐specific IgE (sIgE) was higher than that of rDer p 2A (P < 0.001). The ELISA inhibition curve of rDer p 2B sIgE in pool I sera (n = 5; high sIgE both to rDer p 2A and rDer p 2B) did not show any differences in the 50% inhibition concentration and maximum inhibitory percentage of rDer p 2A and rDer p 2B sIgE. However, with pool II sera (n = 5; markedly higher sIgE to rDer p 2B than rDer p 2A), the 50% inhibitory concentrations (10 µg/mL vs. 40 ng/mL) and maximum inhibitory percentage (61% vs. 99%) of rDer p 2B sIgE with the two recombinant isoallergens were quite different. rDer p 2B could be quantified with two different 2‐site ELISA kits, but rDer p 2A was detected by only one kit.Conclusion We conclude that isoallergens of Der p 2 may have different IgE immune responses. Quantification of Der p 2 with 2‐site ELISA kits that adopted mAbs, might be affected by the prevalent form of the isoallergens in reservoir dust.