bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies of differential gene expression in clinically derived eosinophil populations
Authors: Kilty I. C. , Vickers P. J. 
Published: March 2003

BackgroundInflux of eosinophils into the post‐capillary bronchial epithelium and the subsequent release of inflammatory mediators is characteristic of the late phase of asthmatic attacks. The genes that serve to predispose the peripheral blood eosinophils of asthmatics to undergo this process are poorly defined. The aim of this report is to describe the differential gene expression of both the known pro‐inflammatory genes 5‐lipoxygenase and 5‐lipoxygenase‐activating protein (FLAP) and novel cDNA sequences in eosinophils derived from clinical samples.MethodsNovel cDNA sequences representing genes upregulated in peripheral blood eosinophils of asthmatic as compared with nonasthmatic patients were identified by differential display polymerase chain reaction (DDPCR). The differential expression of these sequences, in addition to known pro‐inflammatory genes, were then studied by reverse dot blotting of amplified RNA generated from the eosinophils of nonasthmatic donors, asthmatic donors, asthmatic donors taking steroids, interleukin (IL) ‐3, IL‐5, granulocyte‐macrophage colony stimulating factor‐ (GM‐CSF) treated eosinophils from asthmatic donors and the eosinophilic cell line AML14.ResultsFour unique DDPCR‐generated 3′UTR DNA fragments were identified that showed differing patterns of expression between the eosinophil populations of interest. Expression of each of the novel clones was increased in the peripheral blood eosinophils of asthmatics and downregulated in those donors taking steroids. Expression of 5‐lipoxygenase was not found to vary between the different eosinophil populations, whereas FLAP was induced by treatment with the cytokine cocktail in both primary eosinophils and the eosinophilic cell line AML14.ConclusionThe differential regulation of the novel cDNA sequences and FLAP in the range of eosinophil populations studied suggest that they may provide clinically relevant therapeutic targets. Moreover, the procedures used in these studies may provide a general approach to the study of differential gene expression in small numbers of cells such as those obtained from clinical samples.
The prevalence of immunoglobulin E antibodies to the proteins of rubber (Hevea brasiliensis) latex and grass (Phleumpratense) pollen in sera of British blood donors
Authors: Merrett  , Merrett  , Kekwick  
Published: March 2003

BackgroundAlthough there have been many studies of the prevalence of latex allergy in populations deemed to be at risk, little is known of the potential allergic susceptibility to latex products prevailing in the general population.ObjectiveTo assess the possible prevalence of allergy to latex goods in a population of blood donors by measurement of specific antilatex immunoglobulin (Ig) E in blood, to relate this to prevalence of antigrass IgE in the blood donations, and to assess the prevalence of antibodies to grass, house dust mite and cat allergens in those donors having antilatex IgE antibodies.MethodsSera from two groups of donations obtained in the English West Midlands were assayed. A group of 2000 donations obtained in midwinter was assayed for antilatex and antigrass pollen IgE. A group of 5000 midsummer donations was assayed for total IgE, and antilatex IgE and the sera giving a positive reaction, assayed for antigrass pollen, antihouse dust mite and anticat IgE. The nature of the principal latex and grass pollen polypeptides reacting with IgE in the sera was assessed by immunoblotting.ResultsAnti‐latex IgE was detected in approximately 4% of the winter and 7% of the summer donations. The prevalence of antigrass IgE in the winter donations was approximately 20% and amongst the latex‐positive sera approximately 84% contained antigrass IgE. Of the summer donations of latex‐positive sera, 96% contained antigrass, 48.6% antimite IgE and 34% anticat IgE. The prevalence of both antilatex and antigrass IgE was age and sex related. Inhibition studies indicated cross‐reactivity of IgE with latex and grass pollen proteins.ConclusionsWhilst 4–7% of the population may have serum IgE reacting with latex, the levels are low compared with those reacting with the aeroallergens studied. The apparent cross‐reactivity of some serum IgE with both latex and grass pollen taken with other evidence suggests that, in some individuals, allergy to latex may arise from an initial sensitization by grass pollen.
p38 MAP kinase regulates TNFα‐, IL‐1α‐ and PAF‐induced RANTES and GM‐CSF production by human bronchial epithelial cells
Authors: Hashimoto  , Matsumoto  , Gon  , Maruoka  , Kujime  , Hayashi  , Takeshita  , Horie  
Published: March 2003

BackgroundRANTES and granulocyte macrophage‐colony stimulating factor (GM‐CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen‐activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM‐CSF production in human bronchial epithelial cells (BECs) has not yet been determined.ObjectiveIn the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)‐α, interleukin (IL)‐1α and platelet‐activating factor (PAF)‐stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM‐CSF expression in order to clarify the intracellular signal regulating RANTES and GM‐CSF production by human BECs.ResultsThe results showed that TNFα, IL‐1α and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM‐CSF production by TNFα‐, IL‐1α‐ or PAF‐stimulated human BECs.ConclusionsThese results indicate that p38 MAP kinase plays an important role in TNFα‐, IL‐1α‐ or PAF‐activated signalling pathway which regulates RANTES and GM‐CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway.
Interleukin‐13 and tumour necrosis factor‐α synergistically induce eotaxin production in human nasal fibroblasts
Authors: Terada  , Hamano  , Nomura  , Numata  , Hirai  , Nakajima  , Yamada  , Yoshie  , Ikeda‐Ito  , Konno  
Published: March 2003

BackgroundThere is increasing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. However, the mechanism involved in the production of eotaxin has yet to be clarified. Most recently, it has been shown that interleukin (IL) ‐4 induces eotaxin in dermal fibroblasts. A novel cytokine termed IL‐13, which binds to the α‐chain of the IL‐4 receptor, shares many biological activities with IL‐4. It is known that fibroblasts express the IL‐4 receptor and produce collagen type I upon stimulation with IL‐4.ObjectiveWe investigated whether IL‐13, as well as IL‐4, are able to induce eotaxin production in human nasal mucosal fibroblasts (HNMFs). Furthermore, we investigated the effect of costimulation of IL‐13 and TNFα on eotaxin production.MethodsHNMFs, isolated from inferior nasal mucosa samples, were stimulated by various kind of cytokines for 1–36 h at 37 °C in 5% CO2. The change in the expression of eotaxin mRNA was then evaluated by reverse transcriptase‐polymerase chain reaction and the Southern blot analysis. The amount of eotaxin in the culture media was measured by ELISA.ResultsIL‐13 as well as IL‐4 dose‐dependently induced eotaxin expression in HNMFs. Furthermore, IL‐13 and TNFα synergistically induced eotaxin expression in HNMFs, while they hardly induced eotaxin expression in endothelial cells, epithelial cells or eosinophils. The synergy was observed when pre‐incubation of HNMFs with IL‐13 was followed by a stimulation with TNFα, or HNMFs were simultaneously stimulated with IL‐13 and TNFα.ConclusionThese results strongly indicate that IL‐13, as well as IL‐4, may be important in eotaxin‐mediated eosinophilic inflammation in nasal mucosa. In addition, in nasal mucosa, fibroblasts are the major cell source for eotaxin.
Effect of aerosolized administration of KF19514, a phosphodiesterase 4 inhibitor, on bronchial hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea‐pigs
Authors: Myou  , Fujimura  , Kurashima  , Tachibana  , Hirose  , Nakao  
Published: March 2003

BackgroundAlthough phosphodiesterase (PDE) 3 and 4 inhibitors have received much attention for the treatment of bronchial asthma, systemic adverse effects have also been reported.ObjectiveThe purpose of this study was to investigate the effect of inhaled olprinone, a newly developed PDE3 inhibitor, and KF19514, a PDE1 and 4 inhibitor, on antigen‐induced airway reactions in guinea‐pigs.MethodsFifteen minutes after inhalation of olprinone (0.1 or 1.0 mg/mL) and KF19514 (0.1 or 0.01 mg/mL), animals were given an antigen challenge. Bronchial hyper‐responsiveness and bronchoalveolar lavage fluid cell analysis were performed 24 h after the antigen challenge.ResultsInhalation of olprinone and KF19514 caused a dose‐related inhibition of antigen‐induced bronchoconstriction. Antigen inhalation significantly increased bronchoconstrictor responses to methacholine, and airway accumulation of neutrophils and eosinophils, 24 h after the antigen challenge. These responses were dose‐dependently prevented by KF19514, but not by olprinone.ConclusionThe results indicate that inhaled PDE inhibitors might be useful for treatment of bronchial asthma.
Why do some dietary migraine patients claim they get headaches from placebos?
Authors: Strong  
Published: March 2003

BackgroundIn six double‐blind studies involving 182 tests of dietary migraine patients sensitive to tyramine and β‐phenylethylamine, 18% reported headaches from placebos which were all concealed in gelatin capsules.ObjectiveThe purpose of this research was to test a hypothesis: gelatin is partially hydrolysed animal protein; (partially) hydrolysed vegetable protein (PHVP) is known to cause migraine; perhaps the gelatin caused some of the headaches.MethodThe author tested this hypothesis on himself because he suffers from dietary migraine. He proved this in a double‐blind test with tyramine hydrochloride (TYH). The amount required for the test was so small (1 mg) that it was tasteless and capsules were unnecessary. The author then undertook tests with a capsule, PHVP, monosodium glutamate (MSG) aspartame (a dipeptide) and TYH, adjusting quantities to give a moderate headache. Samples were mixed with foods to simulate normal eating: the capsule with potato chips, aspartame with orange juice and the rest with cottage cheese or ricotta cheese. Times were measured from ingestion (1) to start of the headache and (2) to maximum headache intensity. Each experiment was repeated three times. The headaches were relieved with caffeine.ResultsOf eight double‐blind test samples, the author identified correctly the two placebos and five of the six samples containing tyramine. Quantities giving moderate headaches were: 1 gelatin capsule, 400 mg MSG, 118 mg PHVP, 4.0 mg aspartame and 1.0 mg TYH. Typical times for the three repetitions of the two time periods were 8, 9 and 11 and 17, 19 and 22 min.ConclusionsCapsules may give headaches to dietary migraine patients that are similar to those from foods. This would explain some of the headaches of patients from placebos. The double‐blind test and the repeatability of the time measurements demonstrated the validity of the experiments.
Preventive treatment of intranasal fluticasone propionate reduces cytokine mRNA expressing cells before and during a single nasal allergen provocation
Authors: Kleinjan A. , Holm A. F. , Dijkstra M. D. , Boks S. S. , Severijnen L.‐A. F. , Mulder P. G. , Fokkens W. J. 
Published: March 2003

BackgroundThe local production and release of a number of cytokines regulate allergic upper airway inflammation. Medication is usually used at the presentation of the first symptoms. There are, however, clues that it is advisable to start taking the corticosteroid before the grass pollen season begins.MethodsThis single allergen provocation study was conducted in autumn, out of the hay fever season. Nasal mucosa biopsies were taken twice before provocation (before and after 4 weeks of preventive treatment) and three times after allergen provocation (1 h, 24 h and 1 week). The preventive treatment used was fluticasone propionate aqueous nasal spray (FPANS) (n = 10) or a placebo (n = 9). Eosinophils and mRNA positive cells (in situ hybridization for IL‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐13, IFNγ, RANTES and TNFα) were counted in the biopsies.ResultsPreventive treatment with FPANS out of season resulted in a decrease in eosinophils and mRNA positive cells for IL‐5 and IL‐6. After allergen provocation, levels of most of the measured cytokines (IL‐3, IL‐5, IL‐6, IL‐13, IFNγ, RANTES and TNFα) and eosinophils were reduced using corticosteroids. The numbers of cells (eosinophils, IL‐3, IL‐6 and IL‐8) correlated with nasal symptoms. Significant correlations in the early and late allergic phase were found between eosinophils and cytokines (IL‐3, IL‐10 and IL‐13).ConclusionThese results indicate that preventive treatment with FPANS prior to contact with grass pollen is effective in reducing the increase of cytokine mRNA positive cells in reaction to grass pollen contact.
The relationship of eosinophil granule proteins to ions in the sputum of patients with cystic fibrosis
Authors: Halmerbauer G. , Arri S. , Schierl M. , Strauch E. , Koller D. Y. 
Published: March 2003

Increased sputum levels of eosinophil granule proteins have been reported despite normal eosinophil numbers in peripheral blood and in the lung in cystic fibrosis (CF). Mechanisms of eosinophil priming and activation are still unclear in CF.In the present study we investigated whether ion concentrations in the sputa of CF patients are related to eosinophil activity.We assessed concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX), major basic protein (MBP) and ions (Na+, Cl−, Ca2+, Mg2+) in sputum samples of 29 children with CF as well as in 10 controls with bronchial asthma.Patients with CF demonstrated significantly higher levels of ECP, Na+, Cl− and Ca2+ levels than asthmatics (P < 0.04, P < 0.0001, P < 0.0001, P < 0.02). No differences were seen between concentrations of EPX and Mg2+ in the two groups. In CF, eosinophil granule proteins correlated significantly with Ca2+ and Mg2+ concentrations (ECP, P < 0.0001, r = 0.65, P < 0.0001, r = 0.66; MBP, P < 0.03, r = 0.41, P < 0.03, r = 0.42), furthermore inversely with Cl− concentrations (ECP, P < 0.0003, r = − 0.63; EPX, P < 0.02, r = − 0.45; MBP, P < 0.03, r = − 0.41) but not with Na+ levels. ECP, Na+ and Cl− were also correlated with lung function variables (FVC, P < 0.04, r = − 0.38, P < 0.02, r = 0.44, P < 0.03, r = 0.41; FEV1, P < 0.007, r = − 0.49, P < 0.006, r = 0.5, P < 0.008, r = 0.48; MEF50, P < 0.003, r = − 0.54, NS, P < 0.03, r = 0.42; MEF25, P < 0.039, r = − 0.4, P < 0.005, r = 0.51, P < 0.05, r = 0.37).Our results demonstrated a significant relationship of eosinophil degranulation and ions in CF, indicating that ion composition in CF sputa may be at least partly be responsible for high levels of eosinophil products despite low eosinophil numbers.
Nasal endoscopy in asthmatic children: assessment of rhinosinusitis and adenoiditis incidence, correlations with cytology and microbiology
Authors: Tosca M. A. , Riccio A. M. , Marseglia G. L. , Caligo G. , Pallestrini E. , Ameli F. , Mira E. , Castelnuovo P. , Pagella F. , Ricci A. , Ciprandi G. , Canonica G. W. 
Published: March 2003

Background Upper respiratory airway diseases may induce a worsening of asthma. Sinusitis represents one of the most common chronic diseases. The association of asthma and sinusitis varies greatly in different studies, depending on diagnostic procedures.Objective The aims were: (i) to demonstrate that nasal endoscopy may be easily feasible in asthma at paediatric age; (ii) to evaluate the incidence of rhinosinusitis and adenoiditis in children with asthma by nasal endoscopy; (iii) to correlate inflammatory parameters such as cytology and microbiological cultures with nasal endoscopy findings.Subjects and methods One hundred and forty‐five asthmatic children were evaluated, 48 males and 97 females, with an average age of 7.27 years. Evaluated parameters were the incidence of rhinosinusal infections in asthmatic children, and the role of: (i) nasal endoscopy, (ii) nasal cytology, and (iii) nasal microbiology in their diagnoses.Results Nasal endoscopy was successfully performed on 128 patients. Twenty‐six children had endoscopic rhinosinusitis alone, 10 had adenoiditis alone, and 35 showed endoscopic rhinosinusitis associated with adenoiditis. There were significant correlations between endoscopic rhinosinusitis and adenoiditis (P < 0.001), between clinical and endoscopic rhinosinusitis (P < 0.001), between endoscopic rhinosinusitis and adenoiditis and microbiology (P < 0.05 and P < 0.0001, respectively), and between microbiology and cytology (P < 0.05).Conclusion This study shows that rhinosinusal infections are common in asthmatic children. Moreover, nasal endoscopy might represent a fruitful tool in the management of asthmatic children.
Long‐term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older
Authors: Williams B. , Noonan G. , Reiss T. F. , Knorr B. , Guerra J. , White R. , Matz J. 
Published: March 2003

Background Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration. The effects of these agents over extended periods of time have not been reported.Objective To describe the long‐term effect of oral montelukast, a potent and specific cysteinyl leukotriene receptor antagonist, compared with inhaled corticosteroids in both adult and paediatric patients with chronic asthma.Methods Male and female patients with chronic, stable asthma (adults aged 15–85 years, children aged 6–14 years), who had completed double‐blind, placebo‐controlled clinical studies, participated in three extension studies with oral montelukast taken once daily (10 mg tablet for adults, 5 mg chewable tablet for paediatric patients) or inhaled corticosteroids (beclomethasone 200 μg twice daily for adults, beclomethasone 100 μg or equivalent three times daily for children). A double‐blind adult extension study was 37 weeks in duration; open‐label adult extension studies were 156 (adults) and 112 (paediatric) weeks in duration. A total of 436, 374, and 245 patients entered these extension studies, respectively.Results Treatment with both montelukast and inhaled corticosteroids resulted in improvement in multiple parameters of asthma control. Improvements in daytime symptom scores were generally comparable among treatment groups. No tachyphylaxis to the effects of montelukast was evident. In the adult open‐label study, however, the effect of beclomethasone on mean forced expiratory volume in 1 second (FEV1) gradually decreased from start of the study to the end of the follow‐up treatment period.Conclusion Both montelukast and inhaled corticosteroids were effective in controlling mild to moderate chronic asthma; the relative effectiveness of montelukast and beclomethasone were similar in open‐label conditions. The hypothesis, that clinical practice conditions (e.g., adherence) may have a significant impact on the effectiveness of these therapies, should be tested in future clinical trials.
Rhinovirus infection up‐regulates eotaxin and eotaxin‐2 expression in bronchial epithelial cells
Authors: Papadopoulos N. G. , Papi A. , Meyer J. , Stanciu L. A. , Salvi S. , Holgate S. T. , Johnston S. L. 
Published: March 2003

Background Human rhinoviruses (RVs) are the most common precipitants of asthma exacerbations. RV infection of bronchial epithelium results in local airway inflammation inducing eosinophil recruitment and activation. Induction of eosinophil chemoattractants could represent a central mechanism, as well as a prime target for intervention.Objective To assess the effect of RV infection on mRNA expression and production of eosinophil chemoattractants by bronchial epithelial cells in‐vitro.Methods BEAS‐2B cells were infected with major and minor RVs and the mRNA expression of IL‐8, RANTES, MIP‐1α, eotaxin, eotaxin‐2, MCP‐2, MCP‐3 and MCP‐4 was assessed by reverse transcription PCR. In cases where mRNA induction was observed, a fluoroimmunoassay was used to confirm protein production. To assess the virus‐specificity of the observed reactions, cells were also exposed to inactivated RVs.Results RV infection was able to up‐regulate mRNA expression of IL‐8, RANTES, MIP‐1α, eotaxin and eotaxin‐2, did not affect MCP‐4, while MCP‐2 and MCP‐3 were not expressed either at baseline or after virus infection. Protein production was confirmed for IL‐8, RANTES and eotaxin, but not for MIP‐1α. When RVs were inactivated cytokine up‐regulation was almost completely lost.Conclusion Infection of bronchial epithelial cells with RVs results in the production of a wide array of mediators that are able to chemoattract eosinophils. These include the eosinophil‐specific molecules eotaxin and eotaxin‐2, in addition to IL‐8 and RANTES, which are the most abundant. Eosinophil recruitment after RV infection of bronchial epithelium could represent a central event in the pathogenesis of virus‐induced asthma exacerbations.