bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure to endotoxin or other bacterial components might protect against the development of atopy
Authors: Von Mutius  , Braun‐Fahrländer  , Schierl  , Riedler  , Ehlermann  , Maisch  , Waser  , Nowak  
Published: March 2003

BackgroundSeveral recent studies have shown that growing up on a farm confers significant protection against the development of atopy. These findings point particularly towards the importance of exposure to stable dust and farm animals. It has furthermore been reported that endotoxin, an intrinsic part of the outer membrane of gram negative bacteria, is abundant in environments where livestock and poultry is kept.The aim of this study was therefore to measure the level of environmental endotoxin exposure in homes of farmers' children, children with regular contact to livestock and control children with no contact to farm animals.MethodsEighty‐four farming and nonfarming families were identified in rural areas in Southern Germany and Switzerland. Samples of settled and airborne dust were collected in stables, and of settled dust indoors from kitchen floors and the children's mattresses. Endotoxin concentrations were determined by a kinetic Limulus assay.ResultsEndotoxin concentrations were highest in stables of farming families, but were also significantly higher indoors in dust from kitchen floors (143 EU/mg vs 39 EU/mg, P < 0.001) and children's mattresses (49479 EU/m2 vs 9383 EU/m2, P < 0.001) as compared to control children from nonfarming families. In addition, endotoxin levels were also significantly higher in mattresses and dust from kitchen floors in households where children had regular contact to farm animals (38.6 EU/mg and 23340 EU/m2, respectively) as compared to control subjects.ConclusionWe propose that the level of environmental exposure to endotoxin and other bacterial wall components is an important protective determinant for the development of atopic diseases in childhood.
Personal exposure to allergenic pollen and mould spores in inland New South Wales, Australia
Authors: Mitakakis T. Z. , Tovey E. R. , Xuan W. , Marks G. B. 
Published: March 2003

BackgroundIn inland NSW, Australia, allergic sensitization to the fungi Alternaria and Cladosporium and to pollen is common and an important risk factor for asthma.ObjectiveWe report the results of a series of experiments designed to assess the nature of personal exposure to these airborne allergenic particles. We have tested the effect of exposure conditions and level of activity on measurements of the personal exposure.MethodPersonal Air Samplers (PAS) and Nasal Air Samplers (NAS) were employed. NAS are fitted just inside the nose and collect inhaled particles by impaction, while the PAS use a pump‐operated filter with constant air flow (2 L/min). Thirty‐three subjects (adults and children) used both NAS and PAS simultaneously for four one hour periods during which they performed activities or rested, both inside and outside their homes. Samples were analysed by light microscopy. Alternaria spores, Cladosporium spores, grass pollen and nongrass pollen were counted.ResultsBoth samplers detected substantial variation in exposure between subjects. Between members of the same household, the intrahouse correlation coefficient ranged from < 0 − 0.38. Levels of pollen grains and fungal spores inhaled were higher during periods of activity than during rest, and higher while subjects were outdoors than indoors. During the active outdoor period, the number of Alternaria spores inhaled ranged from 4 to 794 (median 11) spores/hr, Cladosporium from 0 to 396 (median 4) spores/hr, grass pollen from 0 to 81 (median 1) grains/hr and nongrass pollen from 0 to 72 (median 5) grains/hr.ConclusionThis is the first study to quantify individual inhaled levels of allergenic fungal spores and pollen under normal domestic circumstances. Exposure can be substantial and highly variable between individuals. The amount of particles inhaled relates both to location of the individual and activity being performed, independent of age group.
Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged ≥ 6 years
Authors: Storms W. , Michele T. M. , Knorr B. , Noonan G. , Shapiro G. , Zhang J. , Shingo S. , Reiss T. F. 
Published: March 2003

Objective Montelukast is a leukotriene receptor antagonist administered orally once daily for treatment of chronic asthma in adults and children. A comprehensive analysis of safety data from double‐blind, randomized, placebo‐controlled trials with montelukast has not been previously reported.Patients and methods A pooled analysis of safety data from 11 multicentre, randomized, controlled montelukast Phase IIb and III trials and five long‐term extension studies was performed. A total of 3386 adult patients (aged 15–85 years) and 336 paediatric patients (aged 6–14 years) were enrolled in the trials; 2031 adults received montelukast for up to 4.1 years, and 257 children received montelukast for up to 1.8 years. Summary statistics comparing incidences of adverse events among treatment groups were calculated.Results The overall incidence of clinical and laboratory adverse events among montelukast‐treated patients, both adult and paediatric, was similar to that among patients receiving placebo. There were no clinically relevant differences in individual adverse events, including infectious upper respiratory conditions and transaminase elevations, between montelukast and placebo groups. Discontinuations due to adverse events occurred with similar frequencies during placebo, montelukast and inhaled beclomethasone therapy. No dose‐related adverse effects of montelukast were observed in adults treated with dosages as high as 200 mg per day (20 times the recommended dose) for 5 months. This tolerability profile montelukast observed in clinical trials has been generally reflected in the post‐marketing safety experience seen to date.Conclusion These data indicate a tolerability profile for montelukast similar to placebo during both short‐term and long‐term administration, even at doses substantially higher than the recommended clinical dose of 10 mg once daily for adults and 5 mg once daily for children aged 6–14 years.
IL‐5 priming of the PMA‐induced oxidative metabolism of human eosinophils from allergic and normal subjects during a pollen season
Authors: Woschnagg C. , Garcia R. , Rak S. , Venge P. 
Published: March 2003

AimTo study the effect of IL‐5 priming on the PMA‐induced oxidative metabolism of blood eosinophils from allergic patients and healthy controls, during pollen exposure.MethodsTwenty birch pollen allergic patients with seasonal symptoms of rhinitis or rhinitis plus asthma were studied during the birch pollen season of Sweden. Eosinophils were purified to > 95% by Percoll gradients followed by the MACS system. Oxidative metabolism was measured by a lucigenin enhanced chemiluminescence (CL) assay. Eosinophils were primed with IL‐5 and subsequently stimulated with PMA. The signal transduction mechanisms of IL‐5 priming were studied using the MEK inhibitor PD 98059, the PkC inhibitors Staurosporine, Ro 318220, Gö 6983 and the PI3kinase inhibitor Wortmannin.ResultsDuring the season, the eosinophils from the allergic patients showed a reduced t½rise compared to the non‐allergic controls (P = 0.019) after stimulation. IL‐5 reduced the total PMA CL response both in control and patients’ cells (P = 0.012 and 0.0054 resp.), whereas it primed it in terms of the t½rise of the curves, in both groups (P = 0.012 and 0.0015 resp.). The PMA‐induced CL reactions were inhibited by PD 98059, all PkC‐inhibitors and Wortmannin. IL‐5 priming counteracted only the MEK inhibition significantly.ConclusionsBlood eosinophils from allergic patients are primedin vivo,as compared to eosinophils from non‐allergic controls, during a pollen season. Interleukin‐5 primes equally the PMA‐induced oxidative metabolism of human eosinophils from healthy or allergic subjects.The mechanism of IL‐5 priming after PMA stimulation of oxygen radical production is MEK independent.
A3 receptors mediate rapid inflammatory cell influx into the lungs of sensitized guinea‐pigs
Authors: Spruntulis L. M. , Broadley K. J. 
Published: March 2003

Background Inhaled adenosine causes bronchoconstriction in asthmatics and may modulate inflammatory cell activity. Elevated adenosine levels occur in the lungs after antigen challenge of asthmatics.Objectives The aim of this study was to investigate whether the bronchoconstrictor effects of the adenosine derivative, 5′‐AMP, were associated with altered migration of inflammatory cells into the airways using a sensitized atopic guinea‐pig model previously shown to display a bronchoconstrictor response. Comparisons were made with the effects of inhaled antigen.Methods Airway responses of conscious sensitized guinea‐pigs to inhalation exposures of 5′‐AMP were determined by whole body plethysmography as the change in specific airway conductance (sGaw). Influx of leucocytes into the airways was determined by bronchoalveolar lavage (BAL).Results 5′‐AMP caused bronchoconstrictor airway responses in sensitized animals. Dose‐dependent infiltration of inflammatory cells into the lungs occurred 1 h after 5′‐AMP exposure. No bronchoconstriction or cell influx was seen in unsensitized guinea‐pigs. Exposure to ovalbumin (OA) also caused influx of inflammatory cells. Twenty‐four hours after an OA exposure, 5′‐AMP produced no bronchoconstriction. The P1‐receptor antagonists, 8‐PT and 8‐SPT, inhibited the 5′‐AMP‐induced bronchoconstriction, indicating that the bronchoconstriction seen in sensitized animals is mediated by A1 or A2 receptors. They had no effect on the cell influx, whereas the A3 antagonist, MRS‐1220, significantly inhibited cellular infiltration, suggesting mediation through A3 receptors. At 24 h after an OA challenge and accompanying the cellular influx, there was airway hyper‐responsiveness to the bronchoconstriction by histamine. In contrast, no hyper‐responsiveness to histamine was seen 1 h after 3 mm or 24 h after 300 mm 5′‐AMP.Conclusions 5′‐AMP caused a rapid migration of eosinophils and macrophages into the airways only in sensitized guinea‐pigs, and this was blocked by the A3 antagonist MRS‐1220. This was not associated with bronchial hyper‐reactivity to histamine.
Allergenic proteins are fragmented in low concentrations of sodium hypochlorite
Authors: Chen P. , Eggleston P. A. 
Published: March 2003

Background To facilitate allergen removal from indoor environments, it would be helpful to have household cleaning products that modified allergenic activity. Because NaOCl dissolves proteins in high concentrations and is both capable of killing bacteria and viruses and inactivating viral antigens at somewhat lower concentrations, we explored its effects on Mus m 1 and other indoor allergens.Objective To examine the ability of NaOCl to reduce the allergenicity of Mus m 1 and other indoor allergens.Methods Using purified mouse urinary allergen, we examined the effect on protein measured by Coomassie protein assay and on Mus m 1 measured by ELISA. We also examined the effects using SDS/PAGE and Western blots probed with sheep anti‐Mus m 1 and with allergic human serum.Results When NaOCl and Mus m 1 were combined in a molar ratio of 100 : 1, IgE binding to Mus m 1 on Western blot was significantly reduced. At higher NaOCl concentrations the protein appeared to fragment and eventually became undetectable. Fragmentation appeared to be random in that peptides of a wide range of apparent molecular weight were produced. The reaction was complete within 1–2 min at OCl : pr ratios of greater than 200 : 1 and was optimal at pH 7.4. Immunological activity of other allergens (Fel d 1, Bla g 1, Der p 1) was decreased in vitro and dried allergen extracts were removed from surfaces. Adding an extraneous protein, BSA, to NaOCl:Mus m 1 solutions decreased the effect of NaOCl on the allergen.Conclusions We concluded that NaOCl at concentrations commonly used in household products is capable of dramatically affecting allergenic protein.
IFN‐γ production in response to IL‐18 or IL‐12 stimulation by peripheral blood mononuclear cells of atopic patients
Authors: Shikano H. , Kato Z. , Kaneko H. , Watanabe M. , Inoue R. , Kasahara K. , Takemura M. , Kondo N. 
Published: March 2003

Background Several studies have shown that interleukin (IL)‐4 and interferon‐gamma (IFN‐γ) are important for the regulation of immunoglobulin E (IgE) production and that IL‐18 and IL‐12 induce IFN‐γ.Objective IFN‐γ production in response to IL‐18 or IL‐12 stimulation was investigated in peripheral blood mononuclear cells (PBMCs) of atopic patients with various levels of serum IgE.Methods Cytokine production from PBMCs was measured following stimulation with a non‐specific stimulator (phytohemagglutinin: PHA), IL‐18 or IL‐12 in 12 healthy controls and 26 atopic patients with various serum IgE levels.Results IFN‐γ production by IL‐18‐stimulated PBMCs was positively correlated with IFN‐γ production by IL‐12‐stimulated PBMCs (P < 0.05). However some atopic patients showed discrepancy between the levels of IFN‐γ production stimulated by IL‐12 and by IL‐18.Conclusions The results shown here suggest the presence of abnormalities in the IL‐12 and/or IL‐18 signalling pathways, such as genetic defects in the atopic patients.
T cell involvement in cutaneous drug eruptions
Authors: Hari Y. , Frutig‐Schnyder K. , Hurni M. , Yawalkar N. , Zanni M. P. , Schnyder B. , Kappeler A. , Von Greyerz S. , Braathen L. R. , Pichler W. J. 
Published: March 2003

Background The most frequent side‐effects of drug therapy are skin eruptions. Their pathomechanism is rather unclear.Objective In this prospective study we investigated the T cell activation and drug specificity in different forms of drug‐induced exanthemas from 22 patients.Methods During acute drug allergy, liver parameters and T cell subset activation in the circulation (up‐regulation of CD25 and HLA‐DR) were evaluated and skin biopsies of the acute lesion performed. After recovery, the causative drug was identified by lymphocyte transformation (LTT) and scratch‐patch tests.Results Seventeen of 22 (17/22) patients had maculo‐papular exanthema, 4/22 bullous exanthema and 1/22 urticaria. The causative drugs were mainly antibiotics, anti‐epileptics and anti‐hypertensives. Up‐regulation of HLA‐DR on circulating CD4+ and/or CD8+ T cells was detected in 17 patients, being most marked in patients with bullous reactions or hepatic involvement. The LTT was positive in 14/21 analysed and the patch test in 7/15. All patients showed lymphocytic infiltration in the skin biopsy of the acute lesion. Generally CD4+ T cells dominated; a higher percentage of circulating CD8+ T cells was found in patients with bullous skin reactions or hepatic involvement.Conclusion Our data demonstrate activation and drug specificity of T cells in drug‐induced skin eruptions. A predominant CD8+ T cell activation leads to more severe (bullous) skin symptoms or liver involvement, while predominant activation of CD4+ cells elicits mainly maculo‐papular reactions.
The relationship between low level nitrogen dioxide exposure and child lung function after cold air challenge
Authors: Ponsonby A.‐L. , Glasgow N. , Gatenby P. , Mullins R. , Mcdonald T. , Hurwitz M. , Pradith B. , Attewell R. 
Published: March 2003

Background Nitrogen dioxide (NO2) or home gas appliance use has been inconsistently associated with adverse respiratory outcomes in childhood.Objectives (i) To examine the contribution of home gas appliance type and personal NO2 exposure. (ii) To examine the relationship between NO2 exposure and child lung function and respiratory history. (iii) To assess whether these relationships vary by house dust mite sensitization status.Methods A cross‐sectional survey of 344 children (71% of the eligible group) with a mean age of 9.1 years from four randomly selected schools in the Australian Capital Territory from July to September 1999. Study measurements included a parental questionnaire, NO2 exposure by passive gas samplers, skin prick testing for 10 aeroallergens and lung function at rest and after cold air challenge.Results Total NO2 exposure was low with a mean concentration of 10.1 ppb. No associations were found between NO2 exposure or gas appliance use and asthma, wheeze or baseline lung function. Personal NO2 exposure was associated with a reduction in forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) after cold air challenge (adjusted difference − 0.12% (− 0.23% to − 0.01%) per 1 ppb increase). After exclusion of children who had home heating changed because of asthma, gas heater use was also significantly associated with a reduction in this measure (adjusted difference − 2.0% (− 3.7% to − 0.2%)). There was some evidence that these reductions were greater among the non‐mite‐sensitized children.Conclusions The effect of low‐level NO2 exposure on these respiratory outcomes was not marked. The possible effect of low‐level NO2 exposure on non‐specific bronchial reactivity requires confirmation. Future studies on NO2 and respiratory health should include measures of house dust mite sensitization and bronchial hyper‐responsiveness.
Molecular cloning, expression and modelling of cat allergen, cystatin (Fel d 3), a cysteine protease inhibitor
Authors: Ichikawa K. , Vailes L. D. , Pomés A. , Chapman M. D. 
Published: March 2003

Background Cats are an important source of indoor allergens. However, only two cat allergens, Fel d 1 and albumin, have been cloned and sequenced. IgE antibodies to Fel d 1 and albumin do not fully account for IgE responses to cat and there is good immunochemical evidence that cats produce other allergens.Objective To identify and define the molecular structure of the other potential cat allergens.Methods A cat skin cDNA library was screened using pooled serum obtained from five asthmatic patients which contained high levels of IgE antibody to cat dander. Selected cDNA clones were screened by plaque immunoassay and one cDNA clone, encoding cystatin, was expressed in E. coli. The three dimensional structure of cat cystatin was modelled using the SWISS‐MODEL computer program.Results Three positive cDNA clones (A, B and C) were identified, two of which were fully sequenced. Clones A and C encoded the same 98 amino acid residue sequence which showed 79% and 75% homology with bovine and human cystatin A, respectively. The cat cystatin sequence contained the conserved cysteine protease inhibitor signature and two of three lipocalin motifs. By plaque immunoassay, 60–90% of cat allergic sera had IgE ab to the expressed cystatin clones. The cysteine protease inhibitor motif was also partially conserved in dog allergen sequences, Can f 1 and Can f 2, which are lipocalins. The recombinant protein was expressed in E. coli as an 11‐kDa protein, corresponding to the predicted MW of cat cystatin. The three‐dimensional structure of cat cystatin was modelled on human cystatin structures.Conclusion A newly identified allergen, cystatin (Fel d 3), has been cloned from cat skin and is a member of the cysteine protease inhibitor family.
Selective development of a strong Th2 cytokine profile in high‐risk children who develop atopy: risk factors and regulatory role of IFN‐γ, IL‐4 and IL‐10
Authors: Van Der Velden V. H. J. , Laan M. P. , Baert M. R. M. , De Waal Malefyt R. , Neijens H. J. , Savelkoul H. F. J. 
Published: March 2003

Background The immunological processes in early life and their relation to allergic sensitization leading to a Th2 cytokine profile are still not well understood.Objective To analyse the environmental and genetic risk factors and immunological responses at birth in relation to the development of atopic disease at 12 months of age in a longitudinal study of high‐risk children.Methods High‐risk children were followed from birth till 12 months of age. Mononuclear cells obtained at birth and 6 and 12 months thereafter were analysed for their proliferative and cytokine responses after polyclonal and allergen‐specific stimulation.Results At 12 months of age 25% children had developed an atopic disease. Two atopic parents, parental smoking and atopic dermatitis of at least one of the parents were significant risk factors. In cord blood of newborns who developed atopy, an increased percentage of CD4+CD45RO+ cells and an increased polyclonal‐stimulated proliferation were observed. Furthermore, an impaired allergen‐induced, but not polyclonal‐stimulated IFN‐γ production was found, suggesting a regulatory defect. At 6 and 12 months of age, a strong Th2 profile (characterized by increased levels of IL‐4, IL‐5, and IL‐13) after both polyclonal and, to a lesser extent, allergen‐specific stimulation was found in the children developing atopy. Allergen‐induced IL‐10 production at 12 months of age was only observed in the non‐atopic children.Conclusion Our data indicate that the first 6 months of life represent a critical time window for the initiation of immunological changes resulting in the development of atopy. The selective development of a Th2 cytokine profile in high‐risk children who develop atopy is due to increased production of Th2 cytokines, possibly caused by impaired allergen‐induced IFN‐γ production in the neonatal period. Furthermore, the decreased allergen‐induced IL‐10 levels observed in the atopic children at 12 months of age may result in a lack of down‐regulation of the inflammatory process.
Human mast cell progenitors in peripheral blood from atopic subjects with high IgE levels.
Authors: Nomura I. , Katsunuma T. , Matsumoto K. , Iida M. , Tomita H. , Tomikawa M. , Kawahara H. , Akasawa A. , Pawankar R. , Saito H. 
Published: March 2003

Background It remains unclear whether the number of circulating mast cell progenitors is increased in patients with atopic diseases. Distinct genotypes are reported to affect mast cell/basophil activation.Objective We compared the number and function of mast cell progenitors present in the peripheral blood from donors with normal IgE (IgE < 400 U/mL) and those with atopic dermatitis accompanied by high serum IgE (IgE > 5000 U/mL).Methods Purified peripheral blood cells were cultured in serum‐free methylcellulose containing stem cell factor (SCF), IL‐6 plus IL‐3. Fresh methylcellulose containing the cytokines was layered over every 2 weeks. The cultured mast cells were retrieved from the methylcellulose and were functionally analysed.Results Mast cell colonies were distinguished at 6 weeks of culture as other colony types had been degenerated. The number of mast cell colony‐forming cells varied depending on donors and was not significantly increased in peripheral blood from the hyper‐IgE atopic patients. A significant inversed correlation was found between the number of mast cells per one colony and the ages of donors. The cultured mast cells derived from atopic patients and those from normal IgE donors equally expressed FcεRI and released histamine through FcεRI, although IL‐4 priming in vitro markedly enhanced the function of mast cells regardless of donors.Conclusions These results indicate that the number of circulating mast cell progenitors may be regulated by unknown individual factors unrelated to IgE levels. Mast cell function may be regulated largely by environmental factors, such as IL‐4, but not determined by their progenitors' genotypes.