bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDE4 inhibition and a corticosteroid in chronically antigen exposed conscious guinea‐pigs
Authors: Danahay  , Broadley  
Published: March 2003

BackgroundThe physiological and pharmacological consequences of repeated aero‐allergen challenge have not been previously characterized in conscious, sensitized guinea‐pigs.ObjectivesThis study was undertaken to compare the effects of two anti‐inflammatory compounds, dexamethasone and Ro 20–1724, on an acute and chronic airway inflammation, in terms of airway function, reactivity and leucocyte infiltration.MethodsSensitized guinea‐pigs received eight saline or ovalbumin (OvA) inhalation exposures over 4 weeks and either vehicle, the type 4 PDE inhibitor, Ro 20–1724 (3 mgkg−1), or dexamethasone (1.5 mg/kg−1), 30 min before and 6 h after each challenge. Airway function of the conscious animal (sGaw) was monitored over the duration of the first and final OvA challenge. Airway reactivity to the thromboxane mimetic, U46619, was also determined following the final OvA exposure as was the leucocyte infiltration.ResultsThe first antigen challenge induced a large early (0–3 h) and smaller late (17–24 h) bronchoconstrictor response. Neither phase was affected by the drug treatments. The final OvA challenge induced early and late phase bronchoconstrictor responses but of similar magnitude. The late phase was also significantly prolonged. Ro 20–1724 and dexamethasone significantly attenuated both phases. Airway reactivity to the inhaled thromboxane‐mimetic, U46619, was also significantly enhanced at 120 h after the final OvA exposure in contrast to the saline challenged group. This hyperreactivity was attenuated by Ro 20–1724 and dexamethasone. Bronchoalveolar lavage after repeated OvA exposures revealed eosinophilia which was attenuated by Ro 20–1724 and dexamethasone.ConclusionsThis model demonstrates differential airway responses to acute and chronic antigen challenge. Repeated administration of dexamethasone and Ro 20–1724 with each OvA exposure attenuted all of the chronic inflammatory responses: early and late phase responses, hyperreactivity and eosinophilia.
Inhibition of substance P‐induced histamine release from rat peritoneal mast cells by low doses of protoporphyrin plus long‐wave ultraviolet light irradiation: decreased intracellular calcium as a possible mechanism
Authors: Amano  , Kurosawa  , Miyachi  
Published: March 2003

BackgroundA considerable amount of recent interest has been devoted to the down‐regulatory effects of photosensitizers plus long‐wave ultraviolet light (UVA) irradiation on multiple biologic systems. However, these effects on mast cells are controversial.ObjectiveWe have investigated the effect of low doses of protoporphyrin (PP) plus UVA irradiation (PP/UVA) on substance P (SP)‐induced histamine release from rat mast cells.MethodsRat peritoneal mast cells purified on a Percoll gradient were treated with 3 ng/mL PP and/or UVA, and challenged with SP. In some experiments, IgE‐sensitized mast cells were stimulated by antirat IgE in the presence of phosphatidylserine. Histamine released from mast cells and intracellular calcium concentrations ([Ca2+]i) were measured, respectively.ResultsSP at a concentration of 10−5 mol/L caused a significant histamine release with the increase in [Ca2+]i. PP or UVA irradiation alone at doses used in the present study induced no histamine release from mast cells and had no significant effects on SP‐induced histamine release from the cells. On the other hand, PP/UVA inhibited SP‐induced histamine release in a dose‐dependent manner of UVA with the reduction of SP‐induced maximal increases in [Ca2+]i. Comparing with the inhibitory effects of PP/UVA on anti‐IgE‐induced histamine release from IgE‐sensitized mast cells and maximal increases in [Ca2+]i in the cells, the inhibitory effects of PP/UVA on the findings in SP‐stimulated mast cells were less.ConclusionThese data suggest that low doses of PP/UVA inhibits histamine release from SP‐activated rat peritoneal mast cells through the suppression of [Ca2+]i.
Impaired NK1.1+ T cells do not prevent the development of an IgE‐dependent allergic phenotype
Authors: Daser  , Gerstner  , Hansen  , Bulfone‐Paus  , Renz  
Published: March 2003

BackgroundThe induction of TH2 immune responses is critically dependent on initial IL‐4. Although crucial, the source of this early IL‐4 has not been identified. One candidate is a CD1 restricted NK1.1+ T cell subpopulation which is known to produce such early IL‐4.Objectives and methodsThe necessity of NK1.1+ T cells for the expression of an IgE‐dependent phenotype was investigated in a NK1.1+ T cell deficient mouse model. The allergic phenotype was defined as immediate cutaneous hypersensitivity. It was induced by immunization of mice with ovalbumin. Mouse strains used were C57BL/6 mice and C57BL/6 mice homozygous for a targeted mutation of the β2 microglobulin gene with consecutive loss of CD1 expression, which leads to a drastic reduction of NK1.1+ T cells. Manifestation of an allergic sensitization was assessed by intradermal allergen challenge after i.v. injection of Evans blue solution. The blue stained weal formations were quantified with the Bonitur method. In addition, the Th2 response was confirmed by the measurement of cytokines and serum immunoglobulins. The capability to produce early IL‐4 was tested through the assessment of IL‐4 mRNA shortly after a single challenge.ResultsWild type and mutated mice did not differ in any of the immunological parameters measured.ConclusionA single exposure to antigen with or without adjuvant induces early IL‐4 production in C57BL/6 β2 m−/− mice. This early IL‐4 is therefore independent of the presence of NK1.1+ T cells and functional MHC class I molecules and leads to IgE production and immediate cutaneous hypersensitivity.
Analysis of induced sputum for studying allergen‐specific IgE antibodies in airway secretion from asthmatic patients
Authors: Nahm  , Park  
Published: March 2003

BackgroundAllergen‐specific IgE antibodies have been considered to play an important role in the pathogenesis of atopic asthma. However, studies on allergen‐specific IgE antibodies in airway secretion from asthmatic patients are very rare compared with those in serum.ObjectivesThe present study was undertaken to determine whether induced sputum might provide a useful method for analysing allergen‐specific IgE antibodies in airway secretions from asthmatic patients.MethodsSpecific IgE antibodies to house dust mite (HDM) antigen were measured in induced sputum from 10 HDM‐sensitive asthmatic patients and 12 non‐allergic controls by enzyme‐linked immunosorbent assay. HDM‐specific IgE was regarded as positive when the absorbance value was higher than mean + 2 SD of controls. Their antigen‐binding characteristics were determined by immunoblot analysis.ResultsHDM‐specific IgE was positive in induced sputum from seven of 10 HDM‐sensitive asthmatics. The IgE binding to HDM antigen could be inhibited by fluid phase HDM antigen in a dose‐dependent manner, not by mugwort antigen. Treatment of induced sputum with dithiothreitol decreased the antigen‐specific bindings, and increased the non‐specific bindings on the measurement of HDM‐specific IgE. These effects were significant in a concentration of dithiothreitol greater than 0.05%. Immunoblot analysis revealed that HDM‐specific IgE antibodies in induced sputum recognized the HDM antigens with molecular weights of 42, 34, 32, 25 and 14 kDa. These antigen binding characteristics were similar to those in serum.ConclusionWe conclude that analysis of induced sputum is a useful non‐invasive method for studying allergen‐specific IgE antibodies in airway secretion from asthmatic patients.
Enzymatic activity of soluble phospholipase A2 does not affect the specific IgE, IgG4 and cytokine responses in bee sting allergy
Authors: Wymann  , Akdis  , Blesken  , Akdis  , Crameri  , Blaser  
Published: March 2003

BackgroundThe soluble bee venom phospholipase A2 (PLA) represents the major allergen/antigen for allergic and hyperimmune individuals following bee sting. A number of studies implicate enzymes, and PLA in particular, as potent allergens. We have studied specific activation of T cells by enzymatically active and inactive mutants of PLA, and secretion of cytokines regulating IgE and IgG4 antibody formation.MethodsRecombinant (r) wild type PLA (rPLA‐WT) and an enzymatically inactive rPLA (rPLA‐H34Q) were produced in Escherichia coli. Eleven bee venom allergic patients and three hyperimmune, healthy individuals were included in the study. After specific stimulation of PBMC with the rPLA variants, proliferative response, IFNγ, IL‐2, IL‐4, IL‐5, and IL‐13 production, as well as total and PLA‐specific IgE and IgG4 production, were analysed.ResultsSimilar levels of specific B cell recognition, proliferative and cytokine responses were observed after stimulation with either enzymatically active or inactive rPLA. In addition, equal amounts of antigen‐specific and total IgE and IgG4 antibodies were produced by stimulation with both forms of rPLA.ConclusionsThe enzymatic activity of PLA does not influence the specific activation and cytokine production by T cells from bee venom‐sensitized or hyperimmune individuals, or the IgE/IgG4 antibodies synthesis by B cells in vitro.
Direct measurements of temperature and humidity in dust mite microhabitats
Authors: Cunningham  
Published: March 2003

BackgroundUp to 70% of atopic asthmatics have a positive skin test to the dust mite allergen Der p 1. Reduction of dust mite numbers by lowering room humidity control is one suggested technique for reducing dust mite allergen levels to clinically acceptable levels. Trials of this technique in temperate climates have reported mixed results. It has been speculated that one reason for this is that humidity changes in room ambient air are not tightly linked to humidity changes in the dust mite microenvironment (in the base of carpets, bedding, furniture etc.).ObjectiveTo directly measure humidities and temperatures in dust mite microenvironments and compare these to ambient conditions, and so gather data on how the microclimates are influenced by room conditions and moisture and heat sources, such as an occupant in a bed.MethodsA special small humidity device has been developed which can discriminate humidity changes over distances of millimetres. With these devices microclimates have been measured in the base of carpets, in layers through bedding, and in furniture.ResultsMeasured base‐of‐carpet humidities were significantly higher than room humidities. Bedding relative humidities show complex behaviour according to the distance separation between the measuring point and the occupant. Immediately below the occupant, bed relative humidities fall when the person enters the bed. Similar behaviour is observed in a sofa.ConclusionSome dust mite microclimates have been shown to be very different from room conditions. Consequently, reduction of dust mite numbers and allergen levels cannot be guaranteed by the controlling of room humidities.
Unreliability of IgE/IgG4 antibody testing as a diagnostic tool in food intolerance
Authors: Jenkins  , Vickers  
Published: March 2003

BackgroundSome clinicians link chronic disease in certain patients to ‘food intolerance’. This is currently diagnosed by exclusion dieting, a time‐consuming and tedious technique. It has been claimed that IgE/IgG4 antibody testing is a rapid and valid method of determining food intolerance.ObjectiveTo determine the test/retest reliability of IgE/IgG4 antibody testing as a diagnostic tool.MethodsBlinded testing of duplicate blood samples from nine patients with suspected food intolerance was undertaken by tertiary referral centre using the services of a commercial laboratory. The proportions of consistent and inconsistent results for tests of 95 different foods were analysed.ResultsTest/retest reliability was low. Even though the study method systematically over‐estimated kappa, this value never exceeded 0.51, regardless of the statistical model used. All but one patient had a greater number of inconsistent results than had been prespecified as an unacceptable level of disagreement. In one case, 50 out of 95 test results were inconsistent on retest.ConclusionsWe found no evidence that IgE/IgG4 antibody testing as performed by this laboratory is a reliable diagnostic tool.
Urinary excretion of inflammatory mediators during allergen‐induced early and late phase asthmatic reactions
Authors: O'sullivan  , Roquet  , DahlÉN  , DahlÉN  , Kumlin  
Published: March 2003

BackgroundIt is generally accepted that the early asthmatic response to inhaled allergen is a result of IgE‐mediated mast cell activation. In contrast, the underlying mechanism of the late asthmatic response is much less clear.ObjectiveIn order to investigate the pattern of mediator release during the early and late asthmatic responses to allergen, measurements of the urinary excretion of the mast cell markers 9α,11β‐PGF2 and Nτ‐methylhistamine were made. In addition, urinary levels of eosinophil protein X (EPX) and leukotriene E4 (LTE4) were measured.MethodsTwelve mild atopic asthmatics participated in the study. On the study day, pulmonary function was recorded at baseline and for 12 h after inhalation of allergen. Urine was collected prior to challenge and thereafter at 1 h intervals. Measurements of 9α,11β‐PGF2 and LTE4 were made with enzyme‐immunoassay, and levels of Nτ‐methylhistamine and EPX were analysed with radioimmunoassay.ResultsAll subjects developed both an early and late phase airway response. Within 1 h of the early peak airway response, there was a significant increase in the urinary concentrations (AUC/h) of 9α,11β‐PGF2 (49.3 ± 9.2 to 142.5 ± 49.2; P < 0.001) Nτ‐methylhistamine (10.4 ± 1.4 to 19.5 ± 1.4; P < 0.001) and LTE4 (43.7 ± 5.9 to 105.9 ± 21.3; P < 0.001). Levels of all three mediators were also significantly increased above baseline during the LAR to 79.4 ± 9.5 (P < 0.01), 19.8 ± 1.9 (P < 0.001) and 85.6 ± 10.4 (P < 0.001), respectively. Levels of EPX remained unchanged during the early and late responses (39.2 ± 10.2 to 37.5 ± 18.5, 33.9 ± 6.8).ConclusionsThese results indicate that mast cell activation is a feature not only of the early but also the late asthmatic response. Finally, increased LTE4 supports the contribution of the leukotrienes to airway obstruction during both phases of the asthmatic response to allergen.
The long‐term effects of capsaicin aqueous spray on the nasal mucosa
Authors: Blom  , Severijnen  , Van Rijswijk  , Mulder  , Gerth Van Wijk  , Fokkens  
Published: March 2003

BackgroundCapsaicin has been shown previously to reduce nasal complaints in patients with a non‐allergic non‐infectious perennial rhinitis. Proposed pathophysiological mechanisms for non‐allergic non‐infectious perennial rhinitis include a chronic inflammatory disorder of an antigenic or neurogenic nature as well as the possibility of a functional neuronal disorder. We hypothesized that the beneficial effect of capsaicin might be the result of a down‐regulation of inflammation (by a reduction of inflammatory cells) or through modulation of neural tissue density.MethodsPatients were treated with either a placebo or capsaicin spray solution delivering 0.15 mg of capsaicin per nostril once every second or third day for a total of seven treatments. Both sides were treated each visit. Biopsies were taken before and 2 weeks, 3 months and 9 months after the treatment period. Immunohistochemical staining of the biopsy specimen was performed to ascertain the effect of treatment on immunocompetent cell densities (quantitative) and neural tissue densities (semi‐quantitative) in the nasal mucosa.ResultsNasal complaints were significantly reduced in the capsaicin‐treated group. The number of CD1+, CD25+, CD3+, CD68+, BMK13+, IgE+, tryptase+, and chymase+ cells did not significantly differ between capsaicin and placebo group. No significant differences between both groups were found in pan‐neurogenic staining of nasal mucosa using neurofilament and synaptophysine.ConclusionCapsaicin aqueous nasal spray has previously been shown to reduce nasal complaints without affecting cellular homeostasis or overall neurogenic staining up to 9 months after treatment. Immunocompetent cells are not involved in non‐allergic non‐infectious perennial rhinitis.
Vascular adhesion molecules in nocturnal asthma: a possible role for VCAM‐1 in ongoing airway wall inflammation
Authors: Ten Hacken  , Postma  , Bosma  , Drok  , Rutgers  , Kraan  , Timens  
Published: March 2003

BackgroundIncreased airway inflammation at night is thought to be one of the underlying mechanisms in nocturnal asthma. Vascular adhesion molecules may be important for the recruitment of inflammatory cells in the process of asthmatic airway inflammation.ObjectiveTo determine the possible role of vascular adhesion molecules in increased airway inflammation at night in subjects with nocturnal asthma.MethodsBronchial biopsies were obtained at 16.00 h and 04.00 h from 13 healthy controls, 15 asthmatic patients with PEF variation ≤ 15% and 10 asthmatic patients with PEF variation > 15%. Biopsies were snap‐frozen and double‐immunostained for CD31 in combination with P‐selectin, E‐selectin, ICAM‐1 or VCAM‐1.ResultsNo significant day–night differences in expression of adhesion molecules were found in any of the three groups. The percentage of VCAM‐1 positive vessels in biopsies of asthmatic patients was higher than in biopsies of healthy controls: 5.8 vs 2.5% (P < 0.05) at 16.00 h and 11 vs 0% (P < 0.05) at 04.00 h. In asthma, VCAM‐1 expression was correlated with the number of EG2 positive cells: at 16.00 h (rho = 0.57, P < 0.01) as well as at 04.00 h (rho = 0.64, P < 0.01). Moreover, VCAM‐1 expression was correlated with the number of CD25 positive cells at 16.00 h (rho = 0.43, P < 0.05) and at 04.00 h (rho = 0.41, P < 0.05).ConclusionIncreased nocturnal airway obstruction in asthma is not associated with an increased nocturnal expression of vascular E‐selectin, P‐selectin, ICAM‐1 or VCAM‐1. The relationship between vascular VCAM‐1 expression and sub‐mucosal EG2 and CD25 positive cells, both at 16.00 h and 04.00 h, suggests a role for VCAM‐1 in the ongoing airway wall inflammation of asthma.
Prediction of sensitization to inhalant allergens in childhood: evaluating family history, atopic dermatitis and sensitization to food allergens
Authors: Kulig  , Bergmann  , Niggemann  , Burow  , Wahn  ,   THE MAS STUDY GROUP
Published: March 2003

BackgroundA family history of atopy is a poor predictor of sensitization to inhalant allergens and allergic disease during childhood. We recently identified early sensitization to food allergens, especially hen's egg, as a valuable predictor of subsequent sensitization to inhalant allergens.Objective(1) Whether prediction will be improved by in vitro allergy tests at 1 year of age in combination with family history and medical history data. (2) Comparison with the capacities of in vitro tests to predict sensitization to aeroallergens.MethodsOf an observational birth cohort study (MAS) 49 children who were sensitized to inhalant allergens at 5 years of age and 116 non‐sensitized controls were included in the present study. For the prediction of sensitization to inhalant allergens the following prognostic factors were evaluated: atopic family history (FH), atopic dermatitis (AD) during the first year of life, two in vitro allergy tests for specific IgE to common food allergens at 1 year of age (fx5 [Pharmacia] and single allergen specific tests (sIgE) for four allergens) and ‘high’ total serum IgE, defined by three different cut off points.ResultsThe combination of medical history data and laboratory tests resulted in the best predictive discrimination. The positive predictive values (PPV) were higher if sensitization to food was detected by single allergen specific tests (PPV: 66%/75%/100% corresponding to the three evaluated risk groups) than by the qualitative fx5 (PPV: 46%/65%/100%). The negative predictive values were equal for both tests (69 and 92% for the two low risk groups). High total serum IgE had low predictive capacity.ConclusionDuring infancy the prediction of sensitization to inhalant allergens should be based on medical history data and allergy tests determining sensitization to food allergens. The in vitro tests improve the predictive discrimination, but the individual risk profile of the child must be considered for a reliable and valid prediction.
Rapid symptom relief in rhinitis
Authors: Bousquet J. 
Published: March 2003

In some patients, symptoms of allergic rhinitis can be severe and therefore rapid relief is required. There are many treatment options for allergic rhinitis but histamine H1 blockers and topical corticosteroids represent the first‐line treatment. Although the latter drugs are usually very effective on nasal symptoms, their onset of action is around 24 h. Thus drugs that are more rapidly effective are of interest. Recently 400 French specialists (in Allergy, ENT and Pneumology) met together to define the criteria for selecting a drug for the treatment of rhinitis. Twelve criteria were proposed and rapid onset of action (less than 24 h) was among the foremost designated criteria. In the first trial, a comparison of mizolastine (10 mg once daily [od]) with cetirizine (10 mg od) and placebo was carried out in the management of seasonal allergic rhino‐conjunctivitis (SAR) with special focus on onset of action. A total of 375 patients were included in this European multicentric, randomized, parallel group and placebo‐controlled study. By comparison to placebo, both cetirizine and mizolastine reduced significantly nasal and ocular symptoms during the 28‐day follow‐up trial. The percentage of responders ranged from 40% in the placebo group to 55% in the mizolastine group and 53% in the cetirizine group. Both active drugs were effective from the first intake with a rapid onset within 2 h. However, mizolastine was more rapidly and more profoundly effective than cetirizine during the first 12 h. A second trial included 257 patients suffering from perennial allergic rhino‐conjunctivitis (PAR) in a 4‐week double‐blind placebo‐controlled multicentric study. During the study, patients recorded, using a diary card, ocular and nasal symptoms, including nasal blockage. The mean values of nasal score between day 1, 14 and 28 in the mizolastine group were statistically significantly lower than those in the placebo group. The mean values of ocular score showed a statistical difference in recordings between day 1 and day 14 in favour of the mizolastine group. Mizolastine was an effective drug both in SAR and PAR with a rapid onset of action. Mizolastine relieved symptoms more effectively than cetirizine (SAR) and placebo (SAR and PAR) at the beginning of treatment.
Association between mast cell chymase genotype and atopic eczema: comparison between patients with atopic eczema alone and those with atopic eczema and atopic respiratory disease
Authors: TANAKA  , SUGIURA  , UEHARA  , SATO  , HASHIMOTO‐TAMAOKI  , FURUYAMA  
Published: March 2003

BackgroundIt has remained unclear whether genetic background of patients with atopic eczema (AE) alone is identical to that of patients with both AE and atopic respiratory disease.ObjectiveWe aimed to assess whether there is a genetic difference between these two groups of AE patients.MethodWe determined the genotype with regard to an allelic polymorphism in the gene for mast cell chymase (MCC; a serine protease secreted from mast cells) in 169 AE patients.ResultsMCC genotype was significantly associated with pure AE patients who did not have a predisposition to atopic respiratory disease and whose serum IgE concentration was < 500 IU/mL. The distribution of MCC genotypes also differed significantly between the latter patients and those AE patients with bronchial asthma and a serum IgE concentration of > 2000 IU/mL.ConclusionThese results suggest that pure AE is associated with genetic variants of MCC, and that the genetic basis of pure AE differs from that of AE associated with atopic asthma.