bluuebunny/crossref_metadata_2025_split huggingface dataset:
The proteolytic activity of the major dust mite allergen Der p 1 enhances the IgE antibody response to a bystander antigen
Authors: Gough L. , Sewell H. F. , Shakib F. 
Published: March 2003

Background We have recently demonstrated that immunization of mice with proteolytically active Der p 1, the major dust mite allergen, results in a significant enhancement in total and Der p 1‐specific IgE synthesis compared to mice immunized with Der p 1 that has been irreversibly blocked with the cysteine protease inhibitors E‐64 and iodoacetamide. Thus, the demonstration that the proteolytic activity of Der p 1 enhances total IgE production, apart from increasing Der p 1‐specific IgE, suggests that this allergen may have an IgE‐specific adjuvant effect.Objective To determine if the proteolytic activity of Der p 1 has an IgE‐specific adjuvant effect.Methods We have examined this concept in experiments whereby ovalbumin, used as a bystander antigen, was injected alone or coinjected with either proteolytically active or inactive Der p 1 into groups of mice and IgE and IgG antibody responses were measured.Results Here we demonstrate for the first time that the proteolytic activity of Der p 1, when given at 10‐fold higher concentration, enhances the IgE antibody response to ovalbumin.Conclusions These findings show that the proteolytic activity of Der p 1 leads to the augmentation of IgE antibody responses to itself and to other allergens present in the microenvironment.
Increased carbon monoxide levels in the nasal airways of subjects with a history of seasonal allergic rhinitis and in patients with upper respiratory tract infection
Authors: Andersson J. A. , Uddman R. , Cardell L. O. 
Published: March 2003

BackgroundCarbon monoxide (CO) has emerged as an endogenously produced gaseous mediator known to be involved in bronchial smooth muscle regulation. Increased amounts of CO have been found in exhaled air during asthma and lower airway inflammation. Recently CO has been shown to be produced in the nasal airways, but there are no reports of altered CO levels in nasal airways during inflammation.ObjectiveThis study was designed to investigate if CO levels increase in the human nasal airways during inflammatory conditions, such as allergy and upper airway respiratory tract infection (URTI).MethodsCO was sampled separately from the upper and lower airways of 13 healthy control subjects, six patients with a history of allergic rhinitis and six patients with URTI.ResultsNasal CO levels were increased in subjects with allergic rhinitis, compared to healthy controls (2.07 ± 0.15 ppm, n = 6 and 1.62 ± 0.08 ppm, n = 13, respectively, P < 0.01). CO levels were also increased in patients with URTI, compared to the same controls (1.92 ± 0.09 ppm, n = 6, P < 0.05). Normal levels of CO were found in air from the lower airways among subjects with allergic rhinitis, whereas corresponding levels in the URTI patients were increased.ConclusionThe present data demonstrates that upper airway CO levels increase in parallel with different inflammatory stimuli, such as allergy and infection, suggesting a role for CO as marker or mediator of nasal inflammation.
Transforming growth factor‐bβ1 suppresses atopic dermatitis‐like skin lesions in NC/Nga mice
Authors: Sumiyoshi K. , Nakao A. , Ushio H. , Mitsuishi K. , Okumura K. , Tsuboi R. , Ra C. , Ogawa H. 
Published: March 2003

BackgroundAtopic dermatitis is a chronic, relapsing inflammatory disorder characterized by pruritic and eczematous skin lesions. Transforming growth factor (TGF)‐β1 has been implicated in the suppression of inflammatory responses.ObjectiveThe purpose of this study is to determine whether TGF‐β1 suppresses skin lesions in a mouse model of atopic dermatitis.MethodsWe used the NC/Nga strain of mice as an in vivo model of atopic dermatitis. The effects of exogenous TGF‐β1 on atopic dermatitis‐like skin lesions in NC/Nga mice were evaluated clinically, histologically and immunologically.ResultsSubcutaneous injection of recombinant TGF‐β1 macroscopically suppressed eczematous skin lesions in NC/Nga mice associated with reduced serum immunoglobulin E (IgE) levels. Histological analysis showed that TGF‐β1 significantly inhibited the infiltration of inflammatory cells such as mast cells and eosinophils into the skin of NC/Nga mice. Spontaneous interferon (IFN)‐γ production from splenocytes of NC/Nga mice was down‐regulated by the treatment with TGF‐β1 and neutralizing antibody against IFN‐γ inhibited skin lesions in NC/Nga mice. The inhibitory effect of TGF‐β1 on the skin lesions lasted at least 1 week after cessation of the treatment.ConclusionThese findings indicate that TGF‐β1 suppressed atopic dermatitis‐like skin lesions in NC/Nga mice at least in part through down‐regulation of IFN‐γ. These results suggest that TGF‐β1 may have a therapeutic potential for atopic dermatitis.
Controlled administration of penicillin to patients with a positive history but negative skin and specific serum IgE tests
Authors: Torres M. J. , Mayorga C. , Leyva L. , Guzman A. E. , Cornejo‐García J. A. , Juarez C. , Blanca M. 
Published: March 2003

Background Although subjects with a positive history of immediate allergy to penicillin and negative skin test are traditionally considered to tolerate penicillin, current evidence indicates that they may develop an immediate reaction despite negative skin and serum specific IgE tests. It is thought that these patients require additional tests to confirm the diagnosis.Objective To assess in a large group of patients with a history of immediate allergy to penicillins but with both skin test and CAP‐FEIA‐negative to classical and side chain penicillin determinants, the role of controlled administration of betalactams as a diagnostic test.Methods A group of 330 patients with a history of immediate allergic reactions to penicillins was studied by two evaluators from the same allergy unit using the following protocol: skin tests with major and minor determinants of benzylpenicillin (benzylpenicilloyl‐poly l‐lysine and minor determinant mixture), amoxicillin and ampicillin, and determination of specific IgE antibodies to penicillins, by CAP‐FEIA, in serum. If both tests proved negative, a controlled administration of the drug was then carried out.Results A total of 89 (27%) patients were skin test and CAP‐FEIA‐negative and therefore required controlled administration of the drug. Of these, 49 developed an immediate response and were therefore considered allergic, and the remainder had good tolerance after administration of both benzylpenicillin and amoxicillin. The clinical characteristics of this group were similar to the other allergic patients who were skin test or CAP‐FEIA‐positive, except that they were younger (P < 0.01). Twenty‐two (45%) developed a response to benzylpenicillin and 27 (55%) had a selective response to amoxicillin. Although all reactions appeared within 1 h, a positive correlation was found between the dose inducing the response and the time elapsed from drug administration, for both benzylpenicillin and amoxicillin (P < 0.001).Conclusion These data indicate that an important number of subjects are not correctly identified if only skin tests and/or CAP‐FEIA are used and that this is particularly relevant for side chain‐specific reactions and younger subjects. This suggests that new diagnostic tests are required so as to limit the use of controlled administration.
Effect of formaldehyde on the expression of adhesion molecules in nasal microvascular endothelial cells: the role of formaldehyde in the pathogenesis of sick building syndrome
Authors: Kim W. J. , Terada N. , Nomura T. , Takahashi R. , Lee S. D. , Park J. H. , Konno A. 
Published: March 2003

Background Formaldehyde is associated with sick building syndrome (SBS), a set of diffuse and irritative symptoms predominantly involving the eyes and the respiratory tract. However, its pathophysiological mechanism in SBS has not yet been clarified.Objective In this study we investigated the effect of formaldehyde on the expression of adhesion molecules on human mucosal microvascular endothelial cells (HMMECs). Furthermore, we investigated the effect of formaldehyde on adhesiveness of HMMECs to eosinophils.Materials and methods HMMECs were incubated with various concentrations of formaldehyde (1 ng/mL−1 µg/mL) for 24 h, and the expressions of intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule (VCAM‐1) on HMMECs were evaluated by flow cytometry. The change in the expression of ICAM‐1 and VCAM‐1 mRNA was then evaluated by reverse transcriptase polymerase chain reaction. To understand the role of formaldehyde in eosinophilic inflammation of the nasal mucosa, we examined the effects of formaldehyde on the adhesiveness between HMMECs and eosinophils by eosinophil adhesion assay.Results Formaldehyde increased the surface expressions of ICAM‐1 and VCAM‐1 on HMMECs. Formaldehyde also induced ICAM‐1 and VCAM‐1 mRNA. In addition, the adhesiveness between HMMECs and eosinophils was also increased by formaldehyde.Conclusion These in vitro studies suggest that formaldehyde may play a role as the irritant of the nasal mucosa by increasing the expressions of adhesion molecules on HMMECs and by enhancing the adhesiveness between HMMECs and eosinophils.
Associations of FceεR1‐bβ polymorphisms with immunoglobin E antibody responses to common inhalant allergens in a rural population
Authors: Van Hage‐Hamsten M. , Johansson E. , Kronqvist M. , Loughry A. , Cookson W. O. C. M. , Moffatt M. F. 
Published: March 2003

SummaryBackground Polymorphisms within the β subunit of the high‐affinity receptor for IgE (FcεR1‐β) on chromosome 11q13 have been related to atopy and asthma and the lymphotoxin α (LTα) gene on chromosome 6 is implicated in asthma.Objective To elucidate the association of polymorphisms in the FcεR1‐β and LTα genes to IgE responses and asthma in a family‐orientated rural population.Methods A total of 461 adult farmers, who participated in an epidemiological follow‐up study on respiratory symptoms among farmers on the Swedish island of Gotland, were examined. The traits assessed included serum total IgE, IgE antibody responses to 21 common inhalant allergens and asthma.Results The 237G mutation was only detected in seven persons. Atopy was found to be associated with the RsaI‐ex7 AB‐genotype (OR = 1.9; P = 0.04). The RsaI‐ex7 B allele had a significant influence on IgE responses to pollens and dust mites (OR = 5.5; P = 0.03 and OR = 5.2; P = 0.049, respectively). The influence of this allele was stronger when the association towards single dust mite species (Lepidoglyphus destructor) was estimated (OR = 7.1, P = 0.03) and the association increased even more when the major allergen of L. destructor (rLep d 2) was analysed (OR = 11.2, P = 0.02). These associations were independent of sex, age and smoking, and the estimates of RsaI‐in2 independent of RsaI‐ex7. RsaI‐in2, RsaI‐ex7 and LTα genotypes were unassociated with total serum IgE. No significant difference in the distribution of RsaI‐in2, RsaI‐ex7 and LTα genotypes was found among subjects with atopy or asthma compared to healthy controls.Conclusion This study supports the notion that polymorphisms in the FcεR1‐β gene have significant effects on IgE responsiveness. Secondly, dust mites in rural populations influence the expression of genes on chromosome 11q13.
Genetic deficiency of human mast cell a‐tryptase
Authors: Soto D. , Malmsten C. , Blount J. L. , Muilenburg D. J. , Caughey G. H. 
Published: March 2003

SummaryBackground Human α‐ and β‐tryptases are proteases secreted by mast cells. Beta (but not α) tryptases are implicated in asthma. Genes encoding both types of tryptases cluster on chromosome 16p13.3.Objective This study examines the hypothesis, generated from mapping data, that α‐alleles compete with some β‐alleles at one locus and that an adjacent locus contains β‐alleles exclusively. This hypothesis predicts that β‐alleles outnumber α and that some genomes lack α genes altogether.Methods To test this hypothesis, we developed PCR‐based techniques to distinguish α from β genes. We then genotyped genomic DNA from individuals and tryptase‐expressing cell lines.Results In support of our hypothesis, we find that α‐tryptase deficiency affects 80/274 (29%) of individuals surveyed. The genotype of the α‐deficient individuals is ββββ, due to inheritance of four β genes. The percentage of the population with the mixed genotypes ααββ and αβββ is 21% and 50%, respectively. Accounting for all α‐ and β‐alleles at the tandem loci on 16p13.3, overall α‐allele frequency is only 0.23, with β‐alleles considerably outnumbering α as hypothesized. In samples of defined ethnicity, α deficiency affects 45% of Caucasians, but a much lower percentage of other backgrounds, including African‐Americans and Asians. Examination of cell lines reveals that HMC‐1 and U‐937 lack α‐genes; thus, lack of α transcripts in these cells is due to absence of α‐genes rather than β‐selective transcription. By contrast, α‐transcribing Mono Mac 6 and KU812 cells contain α‐ and β‐genes.Conclusions Genetic α‐tryptase deficiency is common and varies strikingly between ethnic groups. Because β‐tryptases are implicated in allergic disorders, inherited differences in α/β‐genotype may affect disease susceptibility, severity and response to tryptase inhibitor therapy.
Expression and activation of 15‐lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition
Authors: Chu H. W. , Balzar S. , Westcott J. Y. , Trudeau J. B. , Sun Y. , Conrad D. J. , Wenzel S. E. 
Published: March 2003

SummaryBackground Although 15(S)‐hydroxyeicosatetraenoic acid (15(S)‐HETE), a product of 15‐lipoxygenase (15‐LO), may be involved in mild to moderate asthma, little is known about its potential roles in severe asthma.Objectives This study was performed to evaluate 15(S)‐HETE levels in bronchoalveolar lavage fluid (BALF) from severe asthmatics with and without airway eosinophils and from the control groups. In addition, 15‐LO protein expression was examined in endobronchial biopsy, while its expression and activation were evaluated in BAL cells.Results While 15(S)‐HETE levels in BALF were significantly higher in all severe asthmatics than normal subjects, severe asthmatics with airway eosinophils had the highest levels compared with mild, moderate asthmatics and normal subjects. 15(S)‐HETE levels were associated with tissue eosinophil numbers, sub‐basement membrane thickness and BALF tissue inhibitor of metalloproteinase‐1 levels, and were accompanied by increased 15‐LO expression in bronchial epithelium. In addition, activation of 15‐LO was suggested by the increased proportion of 15‐LO in the cytoplasmic membrane of alveolar macrophages from severe asthmatics.Conclusion The data suggest that severe asthmatics with persistent airway eosinophils manifest high levels of 15(S)‐HETE in BALF, which may be associated with airway fibrosis. It is likely that 15‐LO expression and activation by airway cells explain the increased 15(S)‐HETE levels.
Non‐covalent presentation of sulfamethoxazole to human CD4+ T cells is independent of distinct human leucocyte antigen‐bound peptides
Authors: Burkhart C. , Britschgi M. , Strasser I. , Depta J. P. H. , Von Greyerz S. , Barnaba V. , Pichler W. J. 
Published: March 2003

SummaryBackground It has been shown that drugs comprise a group of non‐peptide antigens that can be recognized by human T cells in the context of HLA class II and that this recognition is involved in allergic reactions. Recent studies have demonstrated a MHC‐restricted but processing‐ and metabolism‐independent pathway for the presentation of allergenic drugs such as lidocaine and sulfamethoxazole (SMX) to drug‐specific T cells. However, there is little information so far on the precise molecular mechanisms of this non‐covalent drug presentation.Objective The aim of this study was to evaluate the requirements for a specific peptide occupying the groove of the MHC class II molecule for the efficient presentation of non‐covalently bound drugs to CD4+ T cells.Methods We analysed the effect of coincubation or prepulse of antigen presenting cells (APC) with different peptides on the proliferative responses of SMX‐specific CD4+ T cell clones. In a second series of experiments, we eluted HLA‐bound peptides from the surface of antigen presenting cells by mild acid treatment. Successful removal of peptides was tested directly using labelled peptides and functionally by monitoring activation and proliferation of peptide‐specific T cell clones. Finally, the presentation of SMX to SMX‐specific T cell clones before and after elution of MHC class II bound peptides was tested.Results We found that neither peptide coincubation nor peptide prepulse of APC altered the proliferative response of SMX‐specific T cells. APC treated with the acid for a short time retained cell viability, MHC class II expression and antigen presenting cell function. However, defined peptides could be eluted from surface MHC class II molecules nearly quantitatively. Nevertheless, the chemically non‐reactive drug SMX could still be presented to specific T cells independent of the presence of distinct self‐peptides.Conclusion Our data suggest that small molecules like drugs can bind to a multitude of HLA‐bound peptides or that, similar to superantigens, they might bind directly to HLA.
Intranasal application of chitin microparticles down‐regulates symptoms of allergic hypersensitivity to Dermatophagoides pteronyssinus and Aspergillus fumigatus in murine models of allergy
Authors: Strong P. , Clark H. , Reid K. 
Published: March 2003

SummaryBackground Previous studies have demonstrated that chitin in the form of microparticles that can be phagocytosed is a potent macrophage stimulator and promotes a Th1 cytokine response and it has been shown that oral administration of chitin microparticles is effective in down‐regulating serum IgE and lung eosinophilia in a mouse model of ragweed allergy. To date there have been no studies on the effectivness of directly applying chitin microparticles to the respiratory tract as a treatment for allergic symptoms.Objective To test the effectivness of chitin microparticles when given intranasally as a treatment for the symptoms of respiratory allergy and allergic asthma and to compare its effectivness in two different mouse models of allergy, namely to Dermatophagoides pteronyssinus and Aspergillus fumigatus.Results The intranasal application of microgram doses of chitin microparticles is an effective treatment for reducing serum IgE and peripheral blood eosinophilia, airway hyper‐responsiveness and lung inflammation in both allergy models results in elevation in Th1 cytokines IL‐12, IFN‐γ and TNF‐α and reduction in IL‐4 production during allergen challenge.Conclusion Chitin microparticle suspensions have Th1 immunostimulatory properties and are effective when administered intranasally in mice. The stimulation of the nasal associated lymphoid tissue with chitin microparticles could offer a novel and natural approach to treating allergic disease in humans.
Increased airway inflammatory cells in endurance athletes: what do they mean?
Authors: Bonsignore M. R. , Morici G. , Vignola A. M. , Riccobono L. , Bonanno A. , Profita M. , Abate P. , Scichilone N. , Amato G. , Bellia V. , Bonsignore G. 
Published: March 2003

SummaryBackground Inflammatory cells are increased in the airways of endurance athletes, but their role in causing exercise‐induced respiratory symptoms and bronchoconstriction, or their possible long‐term consequences, are uncertain.Aim To put the results of athlete studies in perspective, by analysing the pathogenesis of airway cell changes and their impact on respiratory function.Results Athletes of different endurance sports at rest showed increased airway neutrophils. Elite swimmers and skiers also showed large increases in airway eosinophils and lymphocytes, possibly related to chronic, exercise‐related exposure to irritants or cold and dry air, respectively. Post‐exercise studies reported variable responses of airway cells to exercise, but found no evidence of inflammatory cell activation in the airways, at variance with exercise‐induced neutrophil activation in peripheral blood. The increase in airway inflammatory cells in athletes can result from hyperventilation‐induced increase in airway osmolarity stimulating bronchial epithelial cells to release chemotactic factors. Hyperosmolarity may also inhibit activation of inflammatory cells by causing shedding of adhesion molecules, possibly explaining why airway inflammation appears ‘frustrated’ in athletes. Data on exhaled nitric oxide are few and variable, not allowing conclusions about its usefulness as a marker of airway inflammation in athletes, or its role in modulating bronchial responsiveness.Conclusions The acute and long‐term effects of exercise on airway cells need further study. Airway inflammatory cells are increased but not activated in athletes, both at rest and after exercise, and airway inflammation appears to regress in athletes quitting competitions. Altogether, these findings do not clearly indicate that habitual intense exercise may be detrimental for respiratory health. Rather, airway changes may represent chronic adaptive responses to exercise hyperventilation. An improved understanding of the effects of exercise on the airways will likely have a clinical impact on sports medicine, and on the current approach to exercise‐based rehabilitation in respiratory disease.
Endotoxin levels in Estonian and Swedish house dust and atopy in infancy
Authors: Böttcher M. F. , Björkstén B. , Gustafson S. , Voor T. , Jenmalm M. C. 
Published: March 2003

SummaryBackground Immune responses, including those to allergens, may be T helper (Th)2 skewed in newborns. In order to redress the fetal Th1/Th2 imbalance, Th1‐stimulating factors, such as bacterial endotoxin, may be required. The increasing prevalence and severity of atopic diseases in industrialized countries, which are in marked contrast with the low prevalence of allergy among children in the formerly socialist countries of Europe, have been suggested to be caused by a reduced microbial stimulation.Aim To relate the endotoxin levels in house dust from two countries with a low (Estonia) and a high (Sweden) prevalence of allergy to the development of atopic disease and sensitization in the children during the first 2 years of life.Methods The study included 108 children from Tartu, Estonia and 111 children from Linköping, Sweden. Skin prick tests were performed at 3, 6, 12 and 24 months of age, and questionnaires were distributed to the families. At 24 months, a paediatrician examined the children. Dust samples were collected from mattresses and carpets and the endotoxin concentration was determined by a chromogenic Limulus assay.Results The endotoxin levels were higher in Estonian than in Swedish house dust (median levels 29 (range 0.25–280) and 14 (range 0.25–99) EU/mg dust, respectively, P < 0.001). Furthermore, the levels were inversely related to the development of atopic disease and sensitization in the Swedish, but not in the Estonian, children.Conclusions The low prevalence of atopic disease in Estonia may, at least in part, be related to the high endotoxin levels in this country. The findings support that high levels of endotoxin, or other bacterial products with Th1‐stimulating properties, might protect children from developing atopic disease.