bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the release of eosinophil cationic protein by eosinophil adhesion
Authors: Xu  , HÅkansson  
Published: March 2003

BackgroundVarying release of eosinophil granule proteins depending on the stimulus and environmental factors has previously been reported.ObjectiveTo investigate the degranulation from adherent eosinophils by using mixed granulocytes.MethodsGranulocytes isolated by Percoll gradient centrifugation were incubated on plates coated with plasma and tissue fibronectin, fibrinogen or human serum albumin (HSA) and stimulated with Mn2+, phorbol‐myristate‐acetate (PMA), formyl‐methionyl‐leucyl‐phenylalanine (f‐MLP) and combinations thereof, respectively. The release of eosinophil cationic protein (ECP) was measured by radioimmunoassay.ResultsUnstimulated eosinophils incubated in wells coated with plasma and tissue fibronectin, fibrinogen or HSA did not release any ECP. Furthermore, Mn2+ (5 mmol/L) did not induce release of ECP despite the fact that adhesion of eosinophils to these four proteins was induced. PMA stimulated a dose‐dependent release of ECP. Contemporaneous stimulation of eosinophils with PMA and Mn2+ induced a dramatically increased release of ECP regardless of which protein the eosinophils were adhering to. A small but significant release of ECP was found when eosinophils incubated on plates coated with fibrinogen and HSA were stimulated by f‐MLP. Contemporaneous stimulation of eosinophils with f‐MLP and Mn2+ did not induce any synergistic effect on the release of ECP. On the contrary, Mn2+ inhibited the release of ECP induced by f‐MLP from eosinophils. Serum‐opsonized Sephadex particles stimulated a potent increase of the release of ECP up to 12%–14% in the presence of plasma fibronectin and, in particular, fibrinogen. The kinetics of eosinophil adhesion and degranulation showed that the cellular adhesion preceded the degranulation response and that the degranulation patterns depend on the stimuli and environment.ConclusionThe present study indicated that cellular adhesion plays an important role in the regulation of eosinophil degranulation, but that adhesion and degranulation can be induced separately.
In vivo expression of signal transducer and activator of transcription factor 6 (STAT6) in nasal mucosa from atopic allergic rhinitis: effect of topical corticosteroids
Authors: Ghaffar  , Christodoulopoulos  , Lamkhioued  , Wright  , Ihaku  , Nakamura  , Frenkiel  , Hamid  
Published: March 2003

BackgroundThe allergen‐induced late nasal response is associated with a high local expression of interleukin (IL) ‐4, a TH2‐type cytokine implicated in immunoglobulin (Ig) E production, tissue eosinophilia and other events considered to be relevant to allergic inflammation. Interaction of IL‐4 with its receptor activates at least two distinct signalling pathways that culminate in the transcription of specific target genes. One pathway involves the activation of a transcription factor termed signal transducer and activator of transcription factor 6 (STAT6).ObjectiveTo investigate the expression of STAT6 in the allergen‐induced late nasal response and to examine the effect of local steroid treatment on STAT6 expression.MethodsInferior turbinate biopsies were obtained from subjects with allergic rhinitis out of the allergen season. Subjects were then randomized into topical steroid‐ (n = 6) and placebo‐treated (n = 6) groups in a double‐blind fashion. After a 6‐week treatment period, a second nasal biopsy was performed 24 h after local challenge with allergen. STAT6 immunoreactivity was examined in biopsy specimens by immunocytochemistry using a specific monoclonal antibody. Numbers of inflammatory cells (CD3+ T cells and MBP+ eosinophils) and IL‐4 mRNA+ cells were investigated by immunocytochemistry and in situ hybridization, respectively.ResultsSTAT6 immunoreactivity was detected in all biopsies studied and localized predominantly to inflammatory tissue of the nasal mucosa. After allergen challenge, expression of STAT6 was markedly increased in placebo‐treated patients (P < 0.01). By confocal microscopy, STAT6 was localized to the cytoplasm and the nucleus of positively‐staining cells. The allergen‐induced increase in STAT6 immunoreactive cells was not observed in the steroid‐treated patients. The change in STAT6 immunoreactivity after allergen challenge correlated significantly with the change in numbers IL‐4 mRNA+ cells (r = 0.74, P = 0.006) and CD3+ T cells (r = 0.76, P = 0.004), but not MBP+ eosinophils.ConclusionThis study provides the first evidence of increased STAT6 expression in vivo in human allergic inflammation. The results support a role for STAT6 and IL‐4 in the pathogenesis of late nasal response and show that decreases in STAT6 expression parallel the reduction in IL‐4 expression that occurs with topical steroid treatment.
Prevalence of sensitization to Tetranychus urticae in greenhouse workers
Authors: Navarro  , Delgado  , Sanchez  , Orta  , Martínez  , Palacios  , Martínez  , Conde  
Published: March 2003

Background Tetranychus urticae (TU) is a macroscopic mite which infests a large number of plants of economic interest worldwide. It has recently been described as a cause of occupational allergic disease in greenhouse workers. However, there are no epidemiological data concerning the prevalence of TU allergy in an unselected exposed population.ObjectiveThe aims were to study the prevalence of TU sensitization among greenhouse workers and its relationship to the working environment and to personal factors.MethodsWe studied 246 consecutive greenhouse workers, recruited directly from the field. A clinical and epidemiological questionnaire, a skin‐prick test (SPT) to TU and common allergens and TU‐specific IgE (RAST) determinations were performed. Seventy‐five healthy volunteers and 152 atopic patients were used as a control group.ResultsThe prevalence of a positive SPT to TU was of 25%. Forty‐five workers (19%) were TU‐allergic, occurring more often in atopic greenhouse workers (P < 0.0001). Seven per cent showed asymptomatic sensitization. The time of exposure to TU was significantly greater in the TU‐allergic patients (P < 0.05). The probability of sensitization to TU was 3.7 times greater in exposed than in non‐exposed subjects (P < 0.0001).ConclusionsIn this study, the prevalence of TU sensitization was 25%. There were significant associations with TU allergy and atopy and the time of exposure to TU.
Diagnostic accuracy of sputum outcomes in chronic stable asthma
Authors: Rosi  , Ronchi  , Grazzini  , Duranti  , Scano  
Published: March 2003

BackgroundAsthma with non‐remitting airflow obstruction may not always be differentiated from COPD with airway hyperreactivity. Many attempts have been made to find useful markers for the distinction between these two disorders.Objective and methodsIn order to help the finding of a useful marker for the diagnosis of asthma in the population of patients with airway obstruction we analysed the diagnostic accuracy of sputum eosinophils and sputum ECP in 91 patients with asthma, 15 patients with chronic bronchitis, 32 patients with chronic obstructive pulmonary disease (COPD) and 20 controls subjects, by performing ROC analysis.ResultsSputum eosinophils were above the normal range of our laboratory (0–3.7%) in 48 asthma patients and in six COPD patients, while sputum ECP (normal range < 85 μg/L) was high in 65 asthma patients, in 24 COPD patients and in nine chronic bronchitis patients. The ROC analysis revealed that sputum eosinophils count (AUC = 0.82) was more accurate than both sputum ECP levels (AUC = 0.56) (P < 0.0001) and β2‐reversibility (AUC = 0.53) (P = 0.0001) in differentiating asthmatic from non‐asthmatic subjects (COPD, chronic bronchitis patients and normal subjects). The diagnostic accuracy of ECP was similar to that of bronchial reversibility (P = 0.76). When ROC analysis was performed by including only patients with airway obstruction (36 asthmatics with airway obstruction and COPD patients), both eosinophil count (AUC = 0.77) and β2‐reversibility (AUC = 0.66) were more accurate than ECP measurement (AUC = 0.39) in discriminating asthmatics from COPD patients (P < 0.00001 and P = 0.04, respectively).ConclusionSputum eosinophils seem to be valid markers for detecting asthma in a population of patients with airway obstruction. Moreover, the higher diagnostic accuracy of eosinophils in the sputum compared to sputum ECP and bronchial reversibility reinforces the role of cytological analysis of sputum in the diagnosis of chronic stable bronchial asthma.
Airway inflammation and hyperresponsiveness to adenosine 5′‐monophosphate in chronic obstructive pulmonary disease
Authors: Rutgers  , Timens  , Tzanakis  , Kauffman  , Van Der Mark  , Koëter  , Postma  
Published: March 2003

BackgroundChronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation.ObjectiveTo investigate the role of airway inflammation in hyperresponsiveness to adenosine 5′‐monophosphate (AMP) in COPD.MethodsWe investigated inflammatory indices in induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies in subjects with COPD with and without hyperresponsiveness to AMP. Twelve nonatopic subjects with COPD with hyperresponsiveness to AMP (mean ± SD, age 63 ± 8 years, FEV1% predicted 56 ± 13%), six without BHR (age 60 ± 6 years, FEV1% predicted 65 ± 11%) and 11 healthy nonatopic controls without BHR (age 58 ± 8 years, FEV1% predicted 104 ± 11%) participated in the study.ResultsSubjects with COPD with BHR had significantly higher numbers of mucosal CD8 + and higher percentages of sputum eosinophils than those without BHR (median, 550 cells/mm2; range, 30–1340 vs 280 cells/mm2; range, 110–450, P = 0.045; and median, 2.7%; range, 0.5–8.5 vs 0.6%; range, 0–0.8 %, P = 0.0036, respectively). No differences were observed in BAL fluid.ConclusionWe conclude that hyperresponsiveness to AMP in COPD is associated with airway inflammation that is characterized by increased numbers of mucosal CD8 + cells and percentages of sputum eosinophils. Hyperresponsiveness to AMP may be used as a marker of airway inflammation in COPD, but its significance in the clinical course remains to be determined.
Lack of linkage between chromosome 5q23–33 markers and IgE/bronchial hyperreactivity in 67 Scottish families
Authors: Mansur  , Christie  , Turner  , Bishop  , Markham  , Helms  , Morrison  
Published: March 2003

BackgroundRaised serum immunoglobulin E (IgE) and bronchial hyperreactivity (BHR) are risk factors for the expression of the asthma phenotype. Previous studies have reported evidence for linkage between these traits and markers on the 5q23–33 cytokine gene cluster.ObjectiveTo test for linkage between total serum IgE/BHR and microsatellite markers which map to the 5q23–33 region in an ethnically distinct cohort of families from Aberdeen, Scotland.MethodsWe performed a linkage study between five polymorphic markers (spanning the chromosome 5q23–33 region) and total serum IgE and BHR traits. A cohort of 67 families, who were recruited originally to study the natural history of wheeze, were clinically characterized and genotyped for D5S404, IL4, IRF‐1, IL9, D5S436 markers. Linkage analyses were performed using the nonparametric Haseman‐Elston algorithm for the quantitative trait log IgE, and the nonparametric LOD score (NPL‐score) of the GENEHUNTER package for the qualitative traits serum IgE and BHR.ResultsThe results of the nonparametric linkage analysis using either the Haseman‐Elston algorithm or NPL‐score were consistent and showed no evidence for linkage with IgE. There was also no evidence for linkage between the BHR traits (at cut‐off values of PD20FEV1 < 8 mmol and 16 mmol) and any of the tested five microsatellite markers.ConclusionsThis study presents evidence against the presence of a gene with a major effect on total serum IgE or BHR in the 5q23–33 region, in this ethnic group.
Effect of a 4‐week treatment with theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid‐naive asthmatics
Authors: Louis  , Bettiol  , Cataldo  , Sele  , Henquet  , Radermecker  
Published: March 2003

BackgroundThe precise mechanism of action of theophylline in asthma is not fully understood but recent data have drawn attention to its potential anti‐inflammatory effect.ObjectiveThe purpose of this study was to assess the effect of theophylline on sputum eosinophilia and sputum eosinophil chemotactic activity in steroid‐naive asthmatics.MethodWe performed a 4‐week randomized double‐blind, placebo‐controlled, parallel group study in 21 mild to moderate steroid‐naive asthmatics whose sputum eosinophilia was found twice > 5% during the run in period. Eleven subjects received 600 mg/24 h theophylline for the first 2 weeks and 900 mg/24 h for the last 2 weeks while 10 subjects took a placebo for 4 weeks. Sputum was induced after 2 and 4 weeks of treatment and 1 week after stopping the treatment. The sputum samples were compared for their cell counts, eosinophil cationic protein (ECP) levels and eosinophil chemotactic activity using micro‐Boyden chambers.ResultsSerum theophylline concentrations reached 7 and 11 μg/mL at V3 and V4, respectively. Intragroup comparisons showed that theophylline, but not placebo, caused a significant reduction in sputum eosinophil counts at V3 (62 ± 10% from baseline, P < 0.01) and a strong trend at V4 (67 ± 16% from baseline, P = 0.07) when compared to baseline. The intergroup difference obtained after comparing the area under the curve over the 4 week treatment period only approached the statistical significance (P = 0.08). At baseline the fluid phase of the sputum contained a significant eosinophil chemotactic activity which was inhibited after a 4‐week treatment by theophylline (P < 0.01) but not by placebo. The mean sputum theophylline levels after 4 weeks of treament (1.7 μg/mL) was lower than that required to cause significant inhibition of eosinophil chemotaxis in vitro.ConclusionTheophylline decreases the natural sputum eosinophil chemotactic activity present in asthmatics. However, when using a small sample size, the 35% reduction in sputum eosinophilia achieved by theophylline failed to reach statistical significance when compared to that seen after placebo.
Preliminary criteria for the definition of allergic rhinitis: a systematic evaluation of clinical parameters in a disease cohort (II)
Authors: Ng M. L. S. , Warlow R. S. , Chrishanthan N. , Ellis C. , Walls R. S. 
Published: March 2003

BackgroundThis study is a development of the work done in ‘Preliminary criteria for the definition of allergic rhinitis: a systematic evaluation of clinical parameters in a disease cohort (I)’.ObjectiveWe sought to develop criteria which could be routinely used to define allergic rhinitis.MethodsA total of  47 allergic rhinitis and 23 normal subjects were evaluated with a detailed questionnaire and history, physical examination, serum total immunoglobulin (Ig) E, skin prick tests and serum EAST's.ResultsBased on this data, we developed a preliminary scoring system by which a reliable diagnosis of allergic rhinitis can be made, which is based on the prevalence adjusted strength of association delta (∂) rank values described in this report. Cumulative frequency histograms were constructed for allergic rhinitis and normal subjects in a variety of configurations.ConclusionA simple scoring system which can be used to diagnose allergic rhinitis on a routine basis was developed in this study.
Interleukin‐10 generation in atopic children following oral Lactobacillus rhamnosus GG
Authors: Pessi T. , Sütas Y. , Hurme M. , Isolauri E. 
Published: March 2003

Oral Lactobacillus rhamnosus GG ingestion for 5 days to 4 weeks has been shown to alleviate clinical symptoms of gastrointestinal inflammation and atopic dermatitis.To determine whether oral Lactobacillus rhamnosus GG may act by generating immunosuppressive mediator in atopic children. Lactobacillus rhamnosus GG (ATCC 53103) at a daily dose of 2 × 1010 cfu was added for 4 weeks to the diets of nine children (mean age, 21 months) with atopic dermatitis. Blood and faecal samples were collected before supplementation and at early (2 weeks) and late stage (4 and 8 weeks from the beginning). The concentrations of interleukin‐6 (IL‐6), IL‐10, IL‐12, tumour necrosis factor‐α (TNFα) and interferon‐γ (IFNγ) in sera, as well as the production of IL‐2, IL‐4, IL‐10 and IFNγ in mitogen‐induced peripheral blood mononuclear cells, were assessed. Secretory IgA and TNFα were also determined in faeces.The serum IL‐10 concentration differed significantly between before, early and late samples (P < 0.001) due to the elevation of serum IL‐10 in the later phase of oral Lactobacillus rhamnosus GG ingestion. The enhancement of IL‐10 production in mitogen‐induced cultures preceded the rise in serum IL‐10.The enhanced IL‐10 generation in vivo substantiates the anti‐inflammatory properties of specific probiotic bacteria strains, and provides an additional reason for considering such treatments for patients with intestinal inflammation.
Studies on linkage and association of atopy with the chromosomal region 12q13–24
Authors: Heinzmann A. , Grotherr P. , Jerkic S.‐P. , Lichtenberg A. , Braun S. , Kruse S. , Forster J. , Kuehr J. , Deichmann K. A. 
Published: March 2003

BackgroundSeveral studies have shown linkage of bronchial asthma, allergic rhinitis and total serum IgE concentration to the chromosomal region 12q13–24 in ethnical diverse populations. This region harbours a number of candidate genes for asthma and atopy, including stem cell factor (SCF), leukotriene A4 hydrolase (LTA4H), thyroid receptor 2 (TR2), and signal transducer and activator of transcription 6 (STAT6). However, the same region was shown as well to be linked to other diseases with inflammatory character. So far no variants in any of these genes have been published which would allow association studies and confirm the pathogenicity of any of these genes.ObjectiveWe wanted to test for linkage of the chromosomal region 12q13–24 with the atopic phenotype without regard to clinical manifestations. Furthermore we screened for common nucleotide polymorphisms in candidate genes to enable association studies.MethodsWe employed sib‐pair linkage analysis and transmission disequilibrium testing with regard to four highly polymorphic microsatellite markers in 12q13–24 in atopic nuclear families. In addition, we looked for polymorphisms in the genes coding for SCF, LTA4H, TR2 and STAT6 performing SSCP‐analysis and direct genomic sequencing.ResultsWe found no evidence for linkage of the genomic region 12q13–24 to elevated total serum IgE levels, specific sensitization to common inhalant allergens or atopy. Furthermore we identified three nucleotide polymorphisms including one common variant in the gene coding for SCF. No association of this polymorphism and any of the atopic phenotypes was seen.ConclusionWe conclude from our data that genes in the chromosomal region 12q13–24 and in particular SCF are unlikely to exert a major effect on the induction of the atopic phenotype in our Caucasian population. However, we did not focus on the asthmatic and thereby inflammatory aspect of atopy which might explain these results in contradiction to previous studies.
Mast cells and their secretory granules are angiogenic in the chick embryo chorioallantoic membrane
Authors: Ribatti D. , Crivellato E. , Candussio L. , Nico B. , Vacca A. , Roncali L. , Dammacco F. 
Published: March 2003

Background Many data suggest that the density of mast cells is highly correlated with the extent of both normal and pathological angiogenesis.Objective In this study we have compared in an in vivo assay, the chick embryo chorioallantoic membrane, the angiogenic potential of mast cell suspensions isolated from rats, degranulated mast cells and their secretory granules.Methods Gelatin sponges adsorbed with cell suspensions of rat mast cells, degranulated mast cells and their secretory granules were implanted on the top of the chorioallantoic membrane at day 8 of incubation. At day 12 the angiogenic response was evaluated macroscopically, microscopically and by a morphometric method of ‘point counting’.Results Isolated mast cells and their secretory granules, but not degranulated mast cells, induced an angiogenic response in the chorioallantoic membrane. The addition of antifibroblast growth factor‐2 or antivascular endothelial growth factor antibodies reduced the angiogenic response of both mast cells and their secretory granules by 50% and 30%, respectively.Conclusion These data support the evidence that the angiogenic properties of mast cells depend on the angiogenic molecules contained in their secretory granules and indicate that fibroblast growth factor‐2 and vascular endothelial growth factor are the angiogenic cytokines primarily and perhaps synergistically responsible for this vasoproliferative activity.
The development of an antibody to trimellitic anhydride
Authors: Griffin P. , Allan L. , Beckett P. , Elms J. , Curran A. D. 
Published: March 2003

Acid anhydrides are a group of highly reactive chemicals used widely in the formulation of paints and plastics. Exposure to acid anhydrides causes several occupational lung diseases such as pneumonititis and asthma. Whilst anhydrides, specifically trimellitic anhydride (TMA), have been shown to bind to lung tissue in an animal model, further investigation has been hampered by the lack of a reagent which would enable the identification of primary target proteins for the binding of TMA.Our objective was to develop an antibody to TMA which would enable in vitro studies of TMA interactions with lung epithelial proteins.We developed a monoclonal antibody which binds soley to TMA. We have demonstrated that the antibody can be used to detect TMA bound to different human proteins with little non‐specific binding to unconjugated proteins. We then exposed cells of the A549 lung epithelial cell line to TMA in vitro and have shown by western blotting that binding occurs in the 20‐35 Kd weight range.We have developed a specific and sensitive reagent to detect TMA bound to proteins. We have used this to show that when TMA is incubated with a lung epithelial cell line, that the TMA binds to proteins with a restricted molecular weight range. These results suggest that the current paradigm for the detection of IgE to small molecular weight reactive chemicals, which presupposes that the chemical binds to serum albumin, may need further investigation.