bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of costimulatory CD80/CD86‐CD28/CD152 molecules in nasal mucosa of patients with perennial allergic rhinitis
Authors: Hattori H. , Okano M. , Yoshino T. , Akagi T. , Nakayama E. , Saito C. , Satoskar A. R. , Ogawa T. , Azuma M. , Nishizaki K. 
Published: March 2003

Background B7 molecules (CD80, CD86) and their counter‐receptors, CD28 and CD152 (CTLA‐4), play an important role in T cell‐mediated immune responses. We previously demonstrated that B7 molecules are selectively up‐regulated not only on B cells but also on T cells from the peripheral blood mononuclear cells of patients with perennial rhinitis cultured with allergen. However, the expression of CD80/CD86 molecules and their counter‐receptors in nasal mucosa, the actual inflammatory site of allergic rhinitis, has not yet been clarified.Patients and methods Inferior turbinates from patients with either allergy to house dust or non‐allergic rhinitis were excised and immunohistologically stained. In addition, the inferior turbinates were challenged with paper discs containing extracts of house dust and subsequently excised. Samples were double stained with immunofluorescent‐labelled antibody to identify cells bearing CD86.Results Without the nasal provocation, only the expression of CD86 was increased in nasal mucosa of patients with allergic rhinitis compared with those with non‐allergic rhinitis. However, following the nasal provocation with house dust, not only CD86, but also CD80, CD28, and CD152 were significantly expressed in allergic patients. Immunofluorescent double staining revealed CD86 expression in CD19, CD1a, CD14 and CD3 lymphocytes.Conclusion These results indicate that the expression of CD80/CD86 molecules and their counter‐receptors is induced in allergic patients following nasal provocation with allergen, suggesting a local amplification of allergen‐specific immune responses in perennial rhinitis.
Benefits of high altitude allergen avoidance in atopic adolescents with moderate to severe asthma, over and above treatment with high dose inhaled steroids
Authors: Grootendorst D. C. , Dahlén S‐E. , Van Den Bos J. W. , Duiverman E. J. , Veselic‐Charvat M. , Vrijlandt E. J. L. E. , O'Sullivan S. , Kumlin M. , Sterk P. J. , Roldaan A. C. 
Published: March 2003

Some patients with severe asthma cannot be controlled with high doses of inhaled steroids (ICS), which may be related to ongoing environmental allergen exposure.We investigated whether 10 weeks of high altitude allergen avoidance leads to sustained benefits regarding clinical and inflammatory markers of disease control in adolescents with persistent asthma despite treatment with high dose ICS.Eighteen atopic asthmatic adolescents (12–18 yr, 500–2000 µg ICS daily) with established house dust mite allergy, participated in a parallel‐group study. Quality of life (PAQL), lung function, bronchial hyperresponsiveness (BHR) to adenosine and histamine, induced sputum and urine samples were collected repeatedly from 10 patients during a 10‐week admission period to the Swiss Alps (alt. 1560 m) and at 6 weeks after return to sea level. Results were compared with those in eight patients, studied in their home environment at sea level for a similar time period. Throughout the study, asthma medication remained unchanged in both groups.During admission to high altitude, PAQL, lung function, BHR to adenosine and histamine, and urinary levels of eosinophil protein X (U‐EPX), leukotriene E4 (U‐LTE4) and 9α11β prostaglandin F2 (U‐9α11β PGF2) improved significantly (P < 0.05), with a similar tendency for sputum eosinophils (P < 0.07). Furthermore, the changes in PAQL and BHR to adenosine and histamine were greater in the altitude than in the control group (P < 0.05). At 6 weeks after renewed allergen exposure at sea level, the improvements in PAQL (P < 0.05), BHR to adenosine (P < 0.07) and histamine (P < 0.05), as well as U‐EPX (P < 0.05) and U‐LTE4 (P < 0.05) were maintained.A short period of high altitude allergen avoidance, on top of regular treatment with ICS and long‐acting β2‐agonists, results in improvement of asthma, as assessed by clinical and inflammatory markers of disease severity. These findings indicate that short‐term, rigorous allergen avoidance can improve the long‐term control of severe asthma over and above what can be achieved even by high doses of inhaled steroids.
Assessment of oxidant stress in allergic asthma by measurement of the major urinary metabolite of F2‐isoprostane, 15‐F2t‐IsoP (8‐iso‐PGF2α)
Authors: Dworski R. , Jackson Roberts Ii L. , Murray J. J. , Morrow J. D. , Hartert T. V. , Sheller J. R. 
Published: March 2003

Asthma is a chronic inflammatory disease of the airways which may involve an oxidant injury to the lung. Assessment of oxidant stress is difficult in vivo, but measurement of F2‐isoprostanes (F2‐IsoPs), free radical‐catalysed products of arachidonic acid, appears to offer a reliable approach for quantitative measurement of oxidative stress status in vivo. We have recently developed a mass spectrometric assay for 2,3‐dinor‐5,6‐dihydro‐15‐F2t‐IsoP (15‐F2t‐IsoP‐M), the major urinary metabolite of the F2‐IsoP, 15‐F2t‐IsoP (8‐iso‐PGF2a). Measurement of the urinary excretion of this metabolite offers a reliable index of oxidative stress status in vivo that has advantages over measuring unmetabolized F2‐IsoPs in urine and plasma.To assess the occurrence of oxidative stress in patients with atopic asthma following allergen exposure in vivo by measuring the urinary excretion of 15‐F2t‐IsoP‐M.Analysis of 15‐F2t‐IsoP‐M by GC‐NICI‐MS in nine mild atopic asthmatics following inhaled allergen provocation and four asthmatic subjects after inhaled challenge with methacholine.Urinary excretion of 15‐F2t‐IsoP‐M increased at 2 h after allergen challenge and remained significantly elevated in all urine collections during the subsequent 8‐h period of the study compared to the baseline value (anova, and Student–Newman–Keuls multiple comparisons test). No increase in the urinary excretion of 15‐F2t‐IsoP‐M occurred after inhalation of methacholine.Allergen challenge causes an oxidant injury in human atopic asthmatics. 15‐F2t‐IsoP‐M is a valuable marker of oxidant stress in vivo.
Cytokine mRNA expression in patients with mild allergic asthma following low dose or cumulative dose allergen provocation
Authors: Prieto J. , Van Der Ploeg I. , Roquet A. , Gigliotti D. , Dahlén B. , Eklund A. , Grunewald J. 
Published: March 2003

Background Allergen provocation is a very useful way to study the inflammatory response in asthmatic patients. Although cumulative dose regimens are most often applied, another provocation model with repeated inhalations of low doses of allergens has recently come into use.Objective We were interested to compare these two allergen provocation models. To evaluate the inflammation induced by either model, we examined the mRNA expression of several cytokines that are implicated in the orchestration of the inflammatory response observed in asthma.Methods Interleukin (IL)‐4, IL‐5, IL‐13 and interferon (IFN)‐γ mRNA expression was analysed in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) CD4+ and PB CD8+ T cells following any of the two provocation regimens. IL‐4 and IFN‐γ mRNA expression was analysed by a competitive reverse transcriptase‐polymerase chain reaction (RT‐PCR) method, while IL‐5 and IL‐13 were analysed semiquantitatively, before and after allergen provocation with either model.Results After low dose provocations none of the cell populations studied showed a clear change in the pattern of IL‐4 or IFN‐γ gene expression. In contrast, after cumulative dose provocation there was a clear tendency towards an increased IL‐4 mRNA expression in BAL cells, correlating with a significant increase in IL‐4 mRNA in PB CD4+ as well as in CD8+ T cells (P = 0.005 and P = 0.04, respectively). Regardless of the allergen provocation method used, in PB IL‐4 mRNA was preferentially expressed by CD4+ cells while IFN‐γ was expressed more by CD8+ cells. IL‐5 transcripts increased after low dose provocations in PB CD4+ T cells in six of eight patients, while after cumulative dose provocation IL‐5 mRNA increased in BAL cells in six out of nine patients but decreased especially in PB CD8+ T cells in six out of eleven patients, suggesting an accumulation of IL‐5 expressing cells to the lungs.Conclusion Thus, the cumulative dose provocation regimen can induce a more pronounced Th2‐like immune response in asthmatic patients than the low dose provocation model.
The interaction of the polymorphisms in transporter of antigen peptides (TAP) and lymphotoxin α (LT‐α) genes and atopic diseases in the Czech population
Authors: Izakovičová Hollá L. , Vašků A. , Izakovič V. , Znojil V. 
Published: March 2003

Background Transporter antigen peptide gene (TAP) products are involved in antigen processing. These genes, inducible by interferon γ, as well as lymphotoxin α (LT‐α), are located in the HLA region. Their involvement in immune response regulation makes them candidate atopy susceptibility genes.Objective This study investigates a possible association between previously identified polymorphisms within the TAP‐1 and LT‐α genes and clinically manifested atopic diseases in the Czech population.Methods Caucasian subjects of Czech nationality (n = 427) were included in our study. We examined 184 healthy controls and 243 patients with histories of atopic asthma, allergic rhinitis and atopic dermatitis or their combinations. We used the amplification refractory mutation system polymerase chain reaction to determine TAP‐1 gene polymorphisms. LT‐α genotypes were determined by PCR and restriction analysis by NcoI.Results No significant differences were found in allele or genotype frequencies of the LT‐α gene, as well as in polymorphisms for Val→Ile at codon 333 and Gly→Asp at codon 637 in the TAP‐1 gene between controls and patients. However, analysis of the concurrence of the double genotypes of the TAP‐1 polymorphism at codon 333 and the LT‐α genes showed differences between controls and atopic patients (P < 0.02).Conclusion Several reports have indicated that different HLA products and genes may be risk factors for or protective factors against the development of atopy. We report no association between polymorphisms in the LT‐α and TAP‐1 genes alone and atopic diseases in the central Europe Caucasian (Czech) population, but there was an interesting interaction between the TAP333 and LT‐α polymorphisms.
T cell responses to recombinant isoforms, synthetic peptides and a mutant variant of Lep d 2, a major allergen from the dust mite Lepidoglyphus destructor
Authors: Eriksson T. L. J. , Gafvelin G. , Elfman L. H. M. , Johansson C. , Van Hage‐Hamsten M. , Olsson S. 
Published: March 2003

Background The dust mite Lepidoglyphus destructor is an important cause of allergic reactions to dust, especially in farming environments. Two isoforms, recombinant (r)Lep d 2.01 and rLep d 2.02, of the major allergen Lep d 2, have previously been expressed as recombinant proteins. These isoforms differ 10.4% at the amino acid level. Furthermore, a mutant form of Lep d 2.01 (rLep d 2.6Cys) with a highly reduced IgE reactivity, has also been produced.Objective To investigate the T cell responses to the recombinant isoforms of Lep d 2, the Lep d 2.6Cys mutant and peptides of Lep d 2, in allergic and non‐allergic individuals.Methods Peripheral blood mononuclear cells from 18 allergic and 16 non‐allergic individuals were stimulated with the different antigens and the proliferative responses were measured. The cytokine production (interleukin (IL)‐4, IL‐5 and interferon (IFN)‐γ) were measured by ELISA.Results Higher T cell proliferation was measured to isoform 01 than to 02 in 28/34 subjects. The responses to rLep d 2.6Cys were lower than to isoform 01 in most subjects, but higher than to Lep d 2.02. Two immuno‐dominant peptides, corresponding to amino acid residue 11–25 and 61–75 were identified. The atopic subjects produced significantly lower IFN‐γ in response to Lep d 2.01 as compared to the non‐atopics.Conclusions There was a significant difference in T cell response between the two isoforms of rLep d 2. The hypoallergenic mutant rLep d 2.6Cys was able to evoke a T cell response with a magnitude which is between the two isoforms. Amino acid residue 11–25 and 61–75 are the most frequently recognized parts of Lep d 2 and are likely to contain the immuno‐dominant T cell epitopes.
Inhalation of a harmless antigen (ovalbumin) elicits immune activation but divergent immunoglobulin and cytokine activities in mice
Authors: Swirski F. K. , Gajewska B. U. , Alvarez D. , Ritz S. A. , Cundall M. J. , Cates E. C. , Coyle A. J. , Gutierrez‐Ramos J.‐C. , Inman M. D. , Jordana M. , Stämpfli M. R. 
Published: March 2003

Background Exposure to aerosolized harmless antigen such as ovalbumin (OVA) has previously been shown to induce inhalation tolerance, a state characterized by inhibition of IgE synthesis and airway inflammation, upon secondary immunogenic antigen encounter. Immune events associated with this phenomenon are still poorly understood.Objective The aim of this study was to investigate cellular and molecular mechanisms underlying this state of ‘unresponsiveness’.Methods; After initial repeated OVA exposure, mice were subjected to a protocol of antigen‐induced airway inflammation, encompassing two intraperitoneal injections of OVA adsorbed to aluminium hydroxide followed by airway challenge. We assessed immune events in the draining lymph nodes after sensitization, and in the lungs after challenge.Results In animals initially exposed to OVA, we observed, at the time of sensitization, considerable expansion of T cells, many of which expressed the activation markers CD69 and CD25, as well as increased numbers of antigen‐presenting cells, particularly B cells. While these animals produced low levels of IgE, the observed elevated levels of IgG1 signified isotype switching. Splenocytes and lymph node cells from OVA‐exposed mice produced low levels of IL‐4, IL‐5, IL‐13 and IFN‐γ, indicating aborted effector function of both T helper (Th)2‐ and Th1‐associated cytokines. Real time quantitative polymerase chain reaction (PCR) (TaqMan) analysis of costimulatory molecules in the lungs after in vivo challenge showed that B7.1, B7.2, CD28 and CTLA‐4 mRNA expression was low in animals initially exposed to OVA. Ultimately, these events were associated with abrogated airway inflammation and attenuated airway hyper‐responsiveness. The decreased inflammation was antigen‐specific and independent of IL‐10 or IFN‐γ.Conclusion Initial exposure to OVA establishes a programme that prevents the generation of intact, fully functional inflammatory responses upon secondary antigen encounter. The absence of inflammation, however, is not associated with categorical immune unresponsiveness.
Type I allergy to natural rubber latex and type IV allergy to rubber chemicals in health care workers with glove‐related skin symptoms
Authors: Nettis E. , Assennato G. , Ferrannini A. , Tursi A. 
Published: March 2003

Background It has been established that there are type I and type IV allergens in latex gloves.Objective The purpose of the study was to establish the prevalence of rubber glove‐induced skin symptoms among health care workers in one Italian hospital.Methods Health care workers (n = 1584) were evaluated using a written questionnaire and 295 respondents with glove‐induced skin symptoms were tested. We performed: skin prick test with latex glove extract and commercial latex, and environmental and food allergens; glove use test; patch tests with a rubber additive series; and RASTs.Results Hospital employees who used or had used latex gloves at work were 1294. Three hundred and sixteen (24.4%) reported glove‐induced symptoms, namely, cutaneous symptoms in all the cases and non‐cutaneous symptoms in 105 subjects (8.1%). Twenty‐seven of the 295 symptomatic employees tested (9.1%) were latex sensitive. Thirty‐one patients (10.5%) exhibited positive patch test to rubber‐related allergens. The most positive readings were obtained from the Thiuram mix and the Carba mix, with 12 and 9 positivities, respectively. The risk factors for latex skin sensitization were: a previous history of atopy and asthma; history of surgery; pre‐existing hand dermatitis; work‐related symptoms; and positive skin tests to common inhalant and certain foods (P < 0.05). Subjects who exhibited positive patch test were significantly more likely to have a prior hand dermatitis (P < 0.001). Of the 295 cases, 275 (93.2%) were contact dermatitis (CD), 13 (4.4%) contact urticaria (CU) (including protein CD) and 7 (2.4%) CD associated with CU.Conclusions Our results show a high prevalence of rubber glove‐induced dermatoses among the employees in one Italian hospital. The majority of skin complaints of latex gloves are related to skin irritation rather than to allergy. The immediate allergy to latex and the delayed allergy to rubber chemicals suggest that all the health care workers with glove‐related dermatitis should undergo both skin prick test and glove use test to detect type I hypersensitivity to latex, and patch test to detect type IV hypersensitivity to rubber chemicals.
Repeated ozone exposures enhance bronchial allergen responses in subjects with rhinitis or asthma
Authors: Holz O. , Mücke M. , Paasch K. , Böhme S. , Timm P. , Richter K. , Magnussen H. , Jörres R. A. 
Published: March 2003

SummaryBackground Single exposures to > 200 p.p.b. of ozone are capable of enhancing the early‐phase lung function response to allergen.Objective The aim of the present study was to compare the effect of single vs. repeated exposures to ozone on early and late‐phase allergen responses.Methods Eleven subjects with allergic asthma and 22 subjects with allergic rhinitis underwent single exposures to filtered air, 125 p.p.b. and 250 p.p.b. ozone, as well as repeated exposures to 125 p.p.b. ozone on four consecutive days. Twenty hours after the (final) exposure, subjects inhaled a single dose of allergen and a sputum induction was performed 6–7 h later.Results In the subjects with rhinitis, the mean early‐phase response of FEV1 and the number of ≥ 20% reductions were significantly greater after exposure to 250 or 4 × 125 p.p.b. ozone compared with filtered air. In addition, most of the ≥ 15% late‐phase responses in FEV1 occurred after exposure to 4 × 125 p.p.b., as well as the strongest effects on sputum parameters. The rise in the number of eosinophils was statistically significant in both groups. Regarding the number of lymphocytes and the concentrations of mast cell tryptase, histamine or LDH, significance was, however, only reached in the asthma group.Conclusion Our data suggest that repeated exposure to ozone, at a peak ambient air level, can enhance both functional and inflammatory responses to inhaled allergen in subjects with pre‐existing allergic airway diseases, and that these effects might reach a clinically relevant magnitude.
Sputum processing: a new method to improve cytospin quality
Authors: Ronchi M. C. , Galli G. , Zonefrati R. , Tanini A. , Scano G. , Duranti R. 
Published: March 2003

SummaryBackground  Sputum examination is being increasingly used as a non‐invasive method for studying airway inflammation. However, the application of sputum still presents some methodological problems and the results of sputum analysis may be substantially flawed by salivary contamination, cell and mucus debris. In addition, much work is needed to deepen the possibility of extensive application of cell and molecular biology techniques to sputum analysis.Objective  In an attempt to improve the technique of sputum processing, we investigated the effect of: (i) 20 and 11 µm filtration in addition to 40 µm on salivary contamination; (ii) Percoll density gradient centrifugation on sputum slides quality; (iii) a culture medium (Minimum Essential Medium containing HEPES 22 mm, pH 7.4: MEM) as washing and suspension solution compared to PBS on cell viability.Methods  Induced sputum samples were obtained in 37 asthmatics. 21 samples were processed as selected sputum and 16 samples as entire expectorates. After dithiotreitol (DTT) homogenization, each specimen was aliquoted in two parts of equal volume. One portion was processed with the usual method, the other using a modified method: cell pellet was suspended in sterile MEM, filtered through 40, 20 and 11 µm net filters and separated from the residual debris by Percoll gradient centrifugation.Results  As compared to the current sputum processing this method resulted in: (i) no selective bronchial cellular loss; (ii) a significant decrease of salivary contamination, particularly in entire expectorates in which squamous cells were reduced from 47 (36) to 15.5% (20) as median values and interquartile range; (iii) a higher proportion of good quality cytospins; (iv) maintenance of cell viability over the time (88% vs. 81% in MEM and PBS, respectively) 1 h after sample collection.Conclusion  In the present study we demonstrated that the proposed method is feasible and makes it possible to overcome most of the technical limits met with the commonly used method, pointing to a potential extension of induced sputum application for more sophisticated techniques.
Are cysteinyl leukotrienes involved in allergic responses in human skin?
Authors: Church M. K. , Griffiths T. J. , Jeffery S. , Ravell L C. , Cowburn A. S. , Sampson A. P. , Clough G. F. 
Published: March 2003

SummaryBackground Cysteinyl leukotrienes have been suggested to be involved in producing the symptoms of both the early and late phases of the allergic response in the lung and other tissues.Objective To use scanning laser Doppler imaging, microdialysis and immunocytochemistry to explore the mediator and cellular mechanisms of the dermal allergic response.Methods Thirteen atopic volunteers received intradermal injections into the forearm of grass pollen or D. pteronyssinus extract. Changes in dermal blood flow up to 8 h were monitored by scanning laser Doppler imaging. The release of histamine, PGD2 and LTC4/D4/E4 was assessed by dermal microdialysis. Skin biopsies were taken at 6 h to determine numbers of mast cells, eosinophils, basophils, Langerhans' cells, and monocytes/macrophages, and the expression of COX‐1, COX‐2, 5‐LO and FLAP.Results Allergen provocation produced an immediate weal and flare response followed by an erythematous induration peaking at 6 h. During the first hour, c. 84 pmoles of histamine and c. 0.3 pmoles of PGD2 were recovered by microdialysis (both P < 0.001) but LTC4/D4/E4 was undetectable. No histamine, PGD2 or LTC4/D4/E4 was detectable at later times. Immunocytochemical examination of biopsies taken at 8 h showed increased numbers of eosinophils and basophils and in COX‐2, 5‐LO and FLAP, but not COX‐1. Expression of 5‐LO and FLAP was associated primarily with eosinophils.Conclusions These findings suggest that inflammatory cells recruited to the site of allergen injection are not activated to release detectable amounts of cysteinyl leukotrienes. Hence, it is unlikely that the late‐phase erythematous induration is mediated by this autocoid.