bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum eosinophil cationic protein levels measured during exacerbation of asthma: characteristics of patients with low titres
Authors: Matsumoto H. , Niimi A. , Minakuchi M. , Izumi T. 
Published: March 2003

Background Serum eosinophil cationic protein (ECP) levels reflect ongoing eosinophilic airway inflammation and are used as a marker for asthma activity. ECP levels, however, may not be elevated in some asthmatic patients, even when they are symptomatic.Objective To clarify the characteristics of patients with ‘low’ ECP titres despite asthma exacerbation.Methods Serum ECP levels were measured in 113 asthmatic patients during exacerbation. Patients were divided into two groups according to ECP titre: a high ECP group (H; ECP ≥ 16.0 µg/L) and a low ECP group (L; ECP <16.0 µg/L). Twenty‐two patients who had recently received systemic steroids were excluded and the clinical features of the remaining patients in H (n = 54) and L (n = 37 were compared.Results Gender, atopic or smoking status, disease severity, inhaled steroid or theophylline usage, peak expiratory flow (% personal best) and forced expiratory volume in 1 s (FEV1) (% predicted) did not significantly differ between the two groups. Patients in L were significantly older and had longer disease duration and lower serum IgE levels than those in H. Multivariate analysis combining age, disease duration and IgE levels showed that age and disease duration were independently associated with ECP level. Airway wall thickness, assessed in a subset of patients using computed tomography, was significantly larger in L.Conclusion Serum ECP levels in asthmatic patients may not be elevated during exacerbation and thus may not be a useful marker in patients who are older, have longer disease duration or possibly have thicker airway walls. Mechanisms other than eosinophilic inflammation, such as airway remodelling, may be involved in asthma exacerbation in these patients.
Cloning and expression of Aspergillus fumigatus allergen Asp f 16 mediating both humoral and cell‐mediated immunity in allergic bronchopulmonary aspergillosis (ABPA)
Authors: Banerjee B. , Kurup V. P. , Greenberger P. A. , Johnson B. D. , Fink J. N. 
Published: March 2003

Background Aspergillus fumigatus, a ubiquitous fungus, is responsible for a number of lung disorders in atopic and non‐atopic individuals. Standardized, pure, and relevant allergens are desirable for reliable immunodiagnosis of the disease and to understand the structural and functional properties of these allergens and the role they play in causing ABPA.Objective Molecular cloning and characterization of a relevant allergen from A. fumigatus cDNA library.Materials and methods A cDNA library was constructed from 96 h old mycelium of A. fumigatus using λ ZAP expression vector. A novel gene encoding an A. fumigatus allergen was identified by screening the library with sera from ABPA patients. The gene was cloned and the allergen over‐expressed in Escherichia coli. This recombinant allergen, Asp f 16, was evaluated in ELISA and Western blots using sera from patients and normal subjects and peripheral blood mononuclear cells (PBMC) for antigen‐induced stimulation.Results Seventy percent of the patients with ABPA demonstrated high levels of serum IgE antibodies to Asp f 16, a 43‐kDa protein, whereas patients with allergic asthma, Aspergillus skin test‐positive asthmatics without clinical evidence of ABPA, and normal controls failed to show Asp f 16‐specific IgE binding by ELISA. The deduced amino acid sequences of Asp f 16 showed extensive sequence homology to 30.6‐kDa Asp f 9 at the N‐terminal region of the protein. PBMC from the majority of patients with ABPA exhibited significant proliferation with the recombinant Asp f 16 allergen.Conclusion Specific humoral and cell‐mediated immune responses of Af‐sensitized patients against Asp f 16 suggest its usefulness in the immunodiagnosis of hypersensitivity diseases due to Af and understanding the pathophysiology of ABPA.
Influenza virus A stimulates expression of eotaxin by nasal epithelial cells
Authors: Kawaguchi M. , Kokubu F. , Kuga H. , Tomita T. , Matsukura S. , Suzaki H. , Huang S.‐K. , Adachi M. 
Published: March 2003

Background Respiratory virus is one of the most common causes of airway inflammation, but its pathogenic mechanisms are not well understood. Eotaxin is a potent eosinophil chemoattractant and is a selective agonist for C‐C chemokine receptor 3 (CCR3). Although it has recently been demonstrated that epithelial cells express eotaxin, both in vivo and in vitro, there are few data concerning the expression in viral infection.Objects We hypothesized that eotaxin may play an important role in attracting inflammatory cells into the airway after viral infection and analysed whether viral infection induces eotaxin in nasal epithelial cells in vitro.Methods Nasal epithelial cells obtained from polypectomy for nasal polyp were infected with influenza virus A (subtype H3N2). The cells and supernatants were collected 8, 24 and 48 h after infection. Eotaxin mRNA was analysed by RT‐PCR. Eotaxin concentration in the supernatants was analysed by enzyme‐linked immunosorbent assay. We also examined a blocking assay to analyse the intervention of pro‐inflammatory cytokines, TNF‐α and IL‐1β in eotaxin production induced by influenza virus.Results The results showed that eotaxin was expressed constitutively in uninfected cells, but was up‐regulated for both mRNA and protein levels in infected cells. Blocking experiments using anti‐TNF‐α and anti‐IL‐1β antibodies showed no effects of these agents on the level of eotaxin. In addition, UV‐inactivated virus did not enhance the expression of eotaxin.Conclusions These results suggest that influenza virus A infection in nasal epithelial cells stimulates the expression of eotaxin, and may play an important role in the pathogenesis of airway inflammation by inducing eotaxin.
Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six‐year follow‐up study.
Authors: Pajno G. B. , Barberio G. , De Luca FR. , Morabito L. , Parmiani S. 
Published: March 2003

Background Specific immunotherapy (SIT) is a recognized way of treating IgE‐mediated respiratory diseases. The clinical outcome is usually better in allergic children than in adults.Objective To increase our knowledge of the ability of SIT to prevent the onset of new sensitizations in monosensitized subjects, so far poorly documented.Methods 134 children (age range 5–8 years), who had intermittent asthma with or without rhinitis, with single sensitization to mite allergen (skin prick test and serum‐specific IgE), were enrolled. SIT was proposed to all the children's parents, but was accepted by only 75 of them (SIT Group). The remaining 63 children were treated with medication only, and were considered the Control Group. Injective SIT with mite mix was administered to the SIT Group during the first three years and all patients were followed for a total of 6 years. All patients were checked for allergic sensitization(s) by skin prick test and serum‐specific IgE every year until the end of the follow‐up period.Results Both groups were comparable in terms of age, sex and disease characteristics. 123 children completed the follow‐up study. At the end of the study, 52 out of 69 children (75.4%) in the SIT Group showed no new sensitization, compared to 18 out of 54 children (33.3%) in the Control Group (P < 0.0002). Parietaria, Gramineae and Olea were the most common allergens responsible for the new sensitization(s).Conclusions According to our data, SIT may prevent the onset of new sensitizations in children with respiratory symptoms monosensitized to house dust mite (HDM).
Efficacy of leukotriene receptor antagonist in chronic urticaria. A double‐blind, placebo‐controlled comparison of treatment with montelukast and cetirizine in patients with chronic urticaria with intolerance to food additive and/or acetylsalicylic acid
Authors: Pacor M. L. , Di Lorenzo G. , Corrocher R. 
Published: March 2003

Background The cause and pathogenesis of chronic urticaria are still poorly understood. IgE‐independent reactions, are common in adult patients with chronic urticaria, who have daily spontaneous occurrence of weals. H1‐receptor antagonists (antihistamines) are the major class of therapeutic agents used in the management of urticaria and angioedema. Nevertheless, chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone. It has been postulated that mediators other than histamine, such as kinins, prostaglandin and leukotrienes, may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines. In this study, which was randomized double‐blind, placebo‐controlled, we compare the clinical efficacy and safety of montelukast (MT) 10 mg given once a day and cetirizine (CET) 10 mg given once a day with placebo (PLA), in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid (ASA) and/or food additives.Patients and methods A group of 51 patients, ranging in age from 15 to 71 years, with chronic urticaria and positive challenge to food additives and/or ASA, participated in this study for a period of 4 weeks, starting from a 3‐day run‐in. The assessment of the efficacy was based on scores of daily urticaria symptoms.Results MT significantly increased the percentage of symptom‐free days for hive and itch. Analysis of frequency distribution of urticaria scores for each symptom gave similar results (MT vs. CET and MT vs. PLA, P < 0.001). The interference with sleep due to their skin condition was also lower in the group treated with MT (P < 0.001). In addition, the median number of days without the rescue medication was significantly higher in the MT group (24 days) than both the CET and the PLA groups (18 days, P < 0.001, and 20 days, P < 0.001, respectively). Finally, a low incidence of adverse events was observed in this study.Conclusion The results of this comparative study demonstrate that montelukast orally administered once a day is very effective for the treatment of cutaneous symptoms in patients with chronic urticaria due to food additives and/or ASA.
Heterogeneity of IgE epitopes of vinyl sulphone reactive dye: human serum albumin that react with IgE
Authors: Park J. W. , Kang D. B. , Choi S. Y. , Kim C. W. , Kim K. S. , Hong C.‐S. 
Published: March 2003

Background Vinyl sulphone reactive dye (vRD), which consists of vinyl sulphone reactive groups and a chromogen, can elicit IgE‐mediated occupational asthma (OA) by haptenation. Human serum albumin (HSA) is known as the most reliable carrier protein for the vRD, the IgE epitopes of vRD‐HSA are not well characterized. In this study we evaluated the epitope of vRD‐HAS‐specific IgE.Methods Two vRD (Remazole Black‐GR and Remazole Orange‐3R), Procion Red‐MX‐5B, which has a dichlorotriazine reactive group, and vinyl sulphone (VS), were haptenated to HSA, respectively. vRD‐HSA was denatured by heat or mercaptoethanol treatment and the allergenicities of denatured and non‐denatured vRD‐HSA were compared by ELISA and IgE immunoblotting using the sera of six vRD‐OA patients. vRD‐HSA‐specific, Procion Red‐MX‐5B (pRD)‐HSA‐specific and VS‐HAS‐specific IgE were also measured with ELISA and the cross‐reactivity between them was evaluated with ELISA inhibition.Results Denaturation of vRD‐HSA by heat affected its allergenicity markedly in five of six sera of RD‐OA. When vRD was conjugated to the pre‐heated HSA, its allergenicity also disappeared or was markedly attenuated compared with the vRD‐HSA in five of six sera. Mercaptoethanol treatment markedly affected the allergenicity of the RD‐HSA in all six RD‐OA sera. Immunoblotting from non‐denatured PAGE showed strong IgE affinity to vRD‐HSA but immunoblotting from denatured SDS PAGE did not show IgE affinity. Among six RD‐OA patients, five and four patients had pRD‐HSA‐specific and VS‐HSA‐specific IgE, respectively. However, the vRD‐HSA‐specific IgE was neither inhibited by pRD‐HSA nor VS‐HSAConclusion We considered that the conformational structure of HSA would be critical for the IgE epitopes during the haptenation process and both of the chromogen and reactive groups of the vRD would contribute to the formation of IgE epitope. Our results also confirmed the heterogeneity of IgE epitopes in the RD‐HSA complex.
PHA‐induced IL‐12Rβ2 mRNA expression in atopic and non‐atopic children
Authors: Janefjord C. K. , Jenmalm M. C. 
Published: March 2003

Background IL‐12 is a strong inducer of Th1 responses. Stimulation via the CD2 receptor increases IFN‐γ production and enhances the responsiveness of activated T‐cells to IL‐12, possibly due to an up‐regulation of the signal transducing β2 chain of the IL‐12 receptor (IL‐12Rβ2). Atopic children have a reduced Th1‐like immunity and a reduced CD2 expression. Our hypothesis is that atopic individuals have a reduced function of the CD2 pathway, causing reduced responsiveness to IL‐12 and decreased IFN‐γ production.Objective The aim was to study the mRNA expression of the IL‐12Rβ2 chain, after stimulation via the CD2 pathway in peripheral blood mononuclear cells (PBMC), of atopic and non‐atopic children, and to investigate correlations to the production of Th1 and Th2 cytokines.Materials and methods The study included 23 skin prick test positive, and 9 non‐sensitized, 12‐year‐old children. PBMC were stimulated for 24 h with phytohemagglutinin (PHA) (2 µg/mL), which stimulates T cells through the CD2 pathway. Expression of IL‐12Rβ2 mRNA was analysed by quantitative real time PCR and the cytokine production was detected with ELISA.Results Atopic and non‐atopic children had similar baseline expression of IL‐12Rβ2 mRNA, whereas PHA‐induced IL‐12Rβ2 mRNA expression was lower in atopic than in non‐atopic children. The PHA‐induced IL‐12Rβ2 mRNA expression correlated well with the PHA‐induced IFN‐γ production and with the IFN‐γ/IL‐4 ratio.Conclusion PBMC from atopic children expressed less IL‐12Rβ2 mRNA than non‐atopic children after stimulation via the CD2 pathway (PHA). This may indicate a reduced capacity to respond to Th1‐inducing stimuli in atopic children.
Long‐term absence of sensitization to mepivacaine as assessed by a diagnostic protocol including patch testing
Authors: Astarita C. , Gargano D. , Romano C. , Cutajar M. , Manguso F. , Montanaro D. , Napolitano A. , Pezzuto F. , Lo Schiavo M. , Altucci P. , Abbate G. 
Published: March 2003

BackgroundProspective assessment of non‐reactivity to local anaesthetics is a frequent reason for allergy consultation.ObjectivesTo investigate the clinical profiles of subjects referred for allergy evaluation; to prospectively reduce the frequency of evaluation by assessing the persistence, during clinical use, of non‐reactivity to contaminant/additive‐free mepivacaine; and to determine the usefulness of a diagnostic protocol involving patch testing.MethodsIn a prospective study, 198 consecutive patients underwent collection of clinical data, skin prick tests and patch tests using allergens/antigens relevant for the investigation, and an intradermal/subcutaneous challenge procedure using contaminant/additive‐free mepivacaine, as appropriate. Patients were followed up for 3 years for assessment of non‐reactivity persistence using the same diagnostic protocol.ResultsOnly one‐third of the patients had a history of previous adverse local anaesthetic reactions. Absence of sensitization to contaminant/additive‐free mepivacaine persisted in all subjects completing the follow‐up. Controlled challenge with mepivacaine was negative in 196 patients with both negative specific skin prick tests and patch tests but it was eventful in two subjects with positive specific patch tests. A few subjects displayed positive skin prick tests and/or patch tests for latex and/or additives.ConclusionsA few patients had a relevant history for potential local anaesthetic‐induced adverse reactions. Upon assessment of absence of sensitization and reactivity, contaminant/additive‐free mepivacaine could safely be given for as long as 3 years. The patch testing was shown to be useful and safe for prediction of challenge outcomes. True allergic reactions to contaminant/additive‐free mepivacaine were not observed in our patient series.
Increased HLA‐DR expression after exposure of human monocytic cells to air particulates
Authors: Don Porto Carero A. , Hoet P. H. M. , Nemery B. , Schoeters G. 
Published: March 2003

Background The expression of HLA‐DR on the cell membrane of antigen‐presenting cells is of major importance for the induction of an allergic response in the airways. Environmental particulates are thought to play an important role in inducing or enhancing allergic sensitization, possibly by increasing the expression of HLA‐DR on the cell membrane of antigen‐presenting cells. In addition, these particulates may synergize with common sensitizing agents in inducing or enhancing HLA‐DR and thus antigen presentation.Objective In this study, we investigated the potential of three particle types, namely carbon black, diesel exhaust particles and urban air particulates (0.1–1000 ng/cm2), to induce the expression of HLA‐DR on differentiated THP‐1 cells, taken as a model for alveolar macrophages. We also assessed the ‘adjuvant’ potential of the particles on interferon (IFN)‐γ, a known enhancer of HLA‐DR.Results By themselves, the particles (0.1–1000 ng/cm2) were not able to induce HLA‐DR on the THP‐1 cells after an incubation of 48 h. However, even at very low concentrations, carbon black (from 1 ng/cm2 on) and diesel exhaust particles (from 0.1 ng/cm2 on), interacted with IFN‐γ (100 U/mL) to enhance HLA‐DR expression (up to 2.5‐fold increase).Conclusion This finding may reflect in vitro one of the mechanisms by which pollutant particles exert an ‘adjuvant’ activity and may partially explain how exposure to particles can be related to the enhancement of allergic sensitization.
Elevated expression of interleukin‐9 mRNA in the bronchial mucosa of atopic asthmatics and allergen‐induced cutaneous late‐phase reaction: relationships to eosinophils, mast cells and T lymphocytes
Authors: Ying S. , Meng Q. , Kay A. B. , Robinson D. S. 
Published: March 2003

SummaryBackground Interleukin‐9 is a T cell‐derived Th2‐type cytokine that has been linked to airway hyper‐responsiveness, mucus hypersecretion and mast cell infiltration in animal models. We recently demonstrated the potential for IL‐9 to act in human eosinophil development and survival.Objectives The aims of this study were: (i) to compare IL‐9 mRNA expression in bronchial biopsies between atopic asthmatics and normal controls, (ii) to investigate kinetic expression of IL‐9 mRNA in skin biopsies after allergen challenge; and (iii) to relate IL‐9 expression to infiltration of eosinophils, mast cell and T lymphocytes in local tissue.Methods Bronchial biopsies were obtained from atopic asthmatics (n = 12) and normal non‐asthmatics (n = 12) at baseline. Skin biopsies were obtained from atopic subjects (n = 11) at 1, 3, 6, 24, 48 and 72 h after allergen challenge. Diluent challenge sites at 24 h were used as controls. IL‐9 mRNA was identified using the technique of in situ hybridization. The numbers of eosinophils, mast cells and T cells were evaluated by immunohistochemistry.Results The numbers of IL‐9 mRNA+ cells present in the bronchial mucosa were significantly greater in atopic asthmatics than those in normal controls (P = 0.003). The numbers of eosinophils, but not mast cells, were also significantly higher in asthmatics (P < 0.005). The numbers of IL‐9 mRNA+ cells present in the airway of asthmatics significantly correlated with the numbers of eosinophils (r = 0.623, P = 0.03), but not mast cells or T cells. Compared with diluent challenge, the numbers of IL‐9 mRNA+ cells were significantly elevated at all allergen‐challenged sites in the skin, with maximal signals at 48 h (P < 0.005). At 72 h, the numbers of IL‐9 mRNA+ cells significantly correlated with the numbers of eosinophils (r = 0.707, P = 0.015).Conclusion Elevated expression of IL‐9 in allergic inflammation may contribute to local eosinophil infiltration and survival in asthma and other allergic atopic diseases.
An interaction between the IL‐4Rα gene and infection is associated with atopic eczema in young children
Authors: Callard R. E. , Hamvas R. , Chatterton C. , Blanco C. , Pembrey M. , Jones R. , Sherriff A. , Henderson J. ,   the ALSPAC Study Team
Published: March 2003

SummaryBackground A gain of function mutation (Q551‐ > R) in the IL‐4 receptor α‐chain (IL‐4Rα) has been found to be associated with atopy in some studies but not others. The different results may be explained by interactions between the IL‐4Rα polymorphism and environmental factors.Objectives To identify interactions between the R551 mutation and environmental factors that are associated with atopy.Methods DNA from the Children in Focus (CiF) cohort of the Avon Longitudinal Study of Parents and Children (ALSPAC) was genotyped by heteroduplex formation for the presence of the R551 polymorphism. The data were then analysed for associations with flexural eczema as an indicator of atopic eczema, skin prick tests to allergens and serum IgE levels, and for interactions with environmental factors.Results A significant (P = 0.02) positive association was seen between the R551 polymorphism and flexural eczema in children up to 6 months of age who had not been given antibiotics, but not in children who had been given antibiotics. This association was maintained as a trend until 30 to 42 months of age but was no longer statistically significant. There was no significant association between the R551 polymorphism and positive skin prick tests or levels of serum IgE at 61 months of age, consistent with the effect of the R551 polymorphism being restricted to early life.Conclusion There is an association between the R551 polymorphism and flexural eczema in children at 6 months of age who have not had infection requiring treatment with antibiotics. Restriction of the R551 association with eczema to children who have not had antibiotics lends support to the ‘hygiene hypothesis’, which states that exposure to infection in childhood can protect against allergic disease.