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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 41 (1994), S. C256 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract T lymphocytes present in allergically inflamed tissue synthesize and secrete the cytokines IL-3, IL-4, IL-5 and GM-CSF which may act as chemotaxins on eosinophils. In contrast to the former cytokines, IL-4 is chemotactic only for eosinophils from peripheral blood of patients with atopic dermatitis and not for eosinophils from normal individuals. IL-4 has the same chemotactic potency as the other cytokines. The optimal chemotactic potency is reached at a concentration of 10 nM. In contrast, neutrophils do not respond chemotactically to IL-4. Checkerboard analysis, inhibition studies with monoclonal anti-IL-4. Abs and desensitization experiments indicated specific interaction of IL-4 with eosinophils. In eosinophils from normal individuals, IL-4 responsiveness could be induced by pretreatment of the cells with IL-5 and GM-CSF. In addition to the fact that IL-4 may be responsible for selective eosinophil transendothelial migration, IL-4 may exert an important modulatory mode of action on eosinophil migration and function within allergically inflamed tissue. Our findings suggest the presence of a functional IL-4R on eosinophils from atopic dermatitis patients.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 20 (1990), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Langerhans cells (LC) are very potent antigen-presenting cells. In atopic disorders such as allergic rhinitis and atopic dermatitis LC are known to bear IgE surface molecules. IgE-positive LC can bind allergen and present it to T lymphocytes to induce an allergen-specific T-cell response and IgE synthesis. Therefore, IgE-bearing LC might play an important role in the triggering of the immune system to maintain ongoing IgE synthesis. The importance of the IgE-bearing LC in atopy has not been assessed but deserves further investigation to find out more about the part played by these cells, not only in the atopic disorders described here but also in others such as gastrointestinal allergy and allergic asthma.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Allergic rhinitis, asthma and atopic dermatitis are closely associated. Although population-based studies report a high prevalence of rhinitis among asthma patients, less is known of the association between rhinitis and atopic dermatitis and the severity of concomitant rhinitis.Objectives We aimed to determine the prevalence and severity of allergic rhinitis among asthmatics and patients with atopic dermatitis and assessed whether age and comorbidity influence the severity of rhinitis signs and symptoms.Methods Three hundred and twenty-five patients recruited for a multicentre trial to study the effect of encasings of mattresses, pillows and duvets on signs and symptoms of allergic rhinitis and/or asthma and/or atopic dermatitis recorded visual analogue scores (VAS) and daily symptom scores and underwent nasal challenge tests with house dust mite (HDM).Results Based on history and clinical symptoms 92% of the 164 asthmatic patients and 85% of the 86 patients with atopic dermatitis could be diagnosed as having rhinitis. Inclusion of a positive provocation to HDM did not result in a substantial lower prevalence of rhinitis. Subjects reported moderate symptoms, with mean rhinitis VAS scores ranging from 40.0 to 55.0. Presence of atopic dermatitis was associated with lower rhinitis VAS and symptoms scores, whereas in multivariate analysis the presence of asthma was positively associated with nasal responsiveness to HDM.Conclusion The prevalence of nasal symptoms in patients with bronchial asthma or atopic dermatitis and sensitized to house dust mites is high. Although the majority of patients experience mild to moderate symptoms, the presence of nasal disease needs to be examined in all patients with atopic disorders.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Atopic dermatitis (AD) is often associated with allergic asthma (AA). Inhalation of allergens influences the activity of AA but the effect on the skin in AD is unclear.Objectives We evaluated the degree of bronchial hyperresponsiveness to methacholine in eight AD patients with AA (AD+) and eight AD patients without AA (AD–) and studied bronchial and cutaneous responses after allergen inhalation challenge.Methods All patients were treated in hospital for their eczema with tar ointment (pix liquida) and orally administered antihistamines (mean hospital stay 37 days). After clearing of the skin lesions allergen inhalation challenge was performed. Cutaneous responses were studied by measuring the‘Costa’ score before and 24 h after allergen inhalation challenge.Results The median value of the provocative concentration of methacholine causing a 20% fall (PC20 Mch) in forced expiratory volume in 1 second (FEV1) was significantly higher in the AD– group compared to the AD+ group with median values of 10.70 and 0.60mg/mL, respectively. These values did not change significantly in both groups during hospital stay. After challenge all AD+ patients showed early and late asthmatic responses whereas only four AD– patients showed early asthmatic responses (mean values of the maximal fall in FEVl during the EAR 37%/16% and in PEF during the LAR 27%/4% for AD+ and AD–patients, respectively). The‘Costa’ score increased in both groups (mean score before 19.1/ 24.4 and after challenge 26.8/26.9 for AD+ and AD+ patients, respectively). The increase in the AD– group was significantly higher compared with the AD– group (P= 0.016).Conclusion We conclude that allergen inhalation challenge causes a flare up of the skin lesions in atopic dermatitis patients. This was more prominent in atopic dermatitis patients who already suffered from an IgE-mediated allergic inflammation in the lung.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Atopic dermatitis (AD) is considered a T-cell mediated disease. Activated T-cells, mainly of the CD4-subtype. are abundantly present in lesional AD skin. Although not many intact eosinophils are present, deposits of eosinophil derived major-basic-protein (MBP) and eosinophil-cationic-protein (ECP) suggest eosinophil involvement. After patch testing AD patients with aeroallergens, an eczematous reaction develops after 24 48 hr at the site of application. This patch test reaction shows macroscopic resemblance to lesional AD skin and does not take place in normal individuals, asthma and allergic rhinitis patients. Lymphocytes together with eosinophils infiltrate into the dennis 26 hr after allergen application. Twenty-four to forty-eight hours after patch testing, eosinophils are in an activated state since they release ECP (being EG2-positive). At this point in time eosinophils have also infiltrated the epidermis. Here they are EG2-negative. Forty-eight to seventy-two hours after patch testing the eczematous reaction decreases. This coincides with disappearance of eosinophils from both the dermis and the epidermis; then, a dendritic staining pattern can be observed in the epidermis with anti-eosinophil peroxidase. Thus, eosinophils infiltrate the dermis and epidermis after patch testing AD patients with aeroallergens and release part of their granular constituents. Recent in vitro investigations revealed that eosinophils from the circulation of AD patients react more powerfully in in vitro test systems such as chemi luminescence, chemotaxis and endolhelial adherence and transmigration. 11 is very likely that this activated (= primed) state is caused by the influence of lymphocyte-derived cytokines like IL-3, IL-5 and GM-CSF, since activated lymphocytes in the circulation (and tissue) may release these cytokines. The primed state of the eosinophils may facilitate tissue inlillration. The subsequent activation of eosinophils within the tissue leading to mediator release and the function of these mediators need to be further elucidated. The close similarity between the cellular events after a patch test reaction to aeroallergens in AD patients and those present in lesional AD skin suggests that the patch test reaction may be a helpful in rim model to study the pathogenesis of AD. The prominent involvement of lymphocytes and eosinophils in this reaction also suggests some similarity with late phase reactions (LPR) observed in the skin after intracutaneous allergen challenge.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the first part of this study peripheral blood lymphocyte subpopulations. Iheir activation slate and various serum parameters were measured in extrinsic and intrinsic atopic dermatitis (AD) patients compared to normal individuals. Beside the characteristic eosinophilia, significantly increased numbers of CD4+ T cells with increased expression of IL-2 receptors (IL-2R) and HLA-DR were noted in the AD patients. In addition, extrinsic AD patients showed increased numbers of CD23+ B cells and decreased numbers of CD16+ natural killer cells. Moreover, increased serum levels of eosinophil canonic protein (ECP) and soluble 1L-2R as well as soluble factors lhat prolong survival of eosinophils in vitro could be demonstrated. In the second section of this study we determine how these blood immunological parameters relate to the clinical severity of the skin lesions of AD, by weekly analysis of 12 AD patients attending a high altitude clinic for 3 to 6 weeks. The patients were divided into two groups on the basis of treatment with topical steroids, but during the observation period a significant improvement in clinical status was observed in all AD patients independent of topical steroid therapy. A progressive decrease in eosinophil and activated T cell numbers. soluble IL-2R levels and serum eosinophil survival prolonging activity could be demonstrated, which closely correlated with the clinical severity of the AD.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Exposure to house dust mite (HDM) allergens can lead to the development of allergic complaints. Mattress covers seem to be an obvious option for lowering allergen exposure in sensitized individuals. Previous studies have shown that Dermatophagoides pteronissinus was the most prevalent HDM species in the Netherlands.Objective In the present study, we investigated the effect of mattress covers on Der p 1 and Der f 1 concentrations in dust samples in three areas in the Netherlands; Groningen, Utrecht and Rotterdam.Methods Dust was obtained from mattresses of 277 patients at the beginning of the study and after 12 months of the placebo-controlled intervention. It was analysed for allergen content by immunoassay. The differential effect of the intervention on Der p 1 vs. Der f 1 was analysed in a subgroup with Der p 1+Der f 1〉1 μg/g dust (N=161). It was tested whether the intervention caused a significant change in the Der f 1/Der p 1 ratio.Results At t=0 we found very similar levels of the group 1 allergens of both species. The relatively high prevalence of D. farinae in our study was geographically restricted: the median Der f 1/Der p 1 ratio was 11.1 in the Rotterdam area compared with 1.32 in the Utrecht area and 0.33 in the Groningen area. Analysis of our data showed that the favourable intervention effect found for the combined allergen data (reduction factor=2.9, P〈0.001) is essentially due to a favourable effect of the intervention on the Der f 1 levels only (reduction factor=3.6, P〈0.001). The effect on the Der p 1 level was remarkably small (reduction factor: 1.2, P=0.48). In the intervention group, the Der f 1/Der p 1 ratio decreased after 12 months by a factor 2.0, whereas in the placebo group it increased (probability of the intervention effect: P〈0.005).Conclusion Mite-impermeable covers are more effective in reducing the level of Der f 1 than that of Der p 1.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 33 (2003), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The risk for allergic reactions depends on the sensitivity of individuals and the quantities of offending food ingested. The sensitivity varies among allergic individuals, as does the threshold dose of a food allergen capable of inducing an allergic reaction.Objective This study aimed at determining the distribution of minimum provoking doses of hazelnut in a hazelnut-allergic population.Methods Thirty-one patients with a history of hazelnut-related allergic symptoms, a positive skin prick test to hazelnut and/or an elevated specific IgE level, were included. Double-blind, placebo-controlled food challenges (DBPCFC) were performed with seven increasing doses of dried hazelnut (1 mg to 1 g hazelnut protein) randomly interspersed with seven placebo doses.Results Twenty-nine patients had a positive challenge. Itching of the oral cavity and/or lips was the first symptom in all cases. Additional gastrointestinal symptoms were reported in five patients and difficulty in swallowing in one patient. Lip swelling was observed in two patients, followed by generalized urticaria in one of these. Threshold doses for eliciting subjective reactions varied from a dose of 1 mg up to 100 mg hazelnut protein (equivalent to 6.4–640 mg hazelnut meal). Extrapolation of the dose–response curve showed that 50% of our hazelnut-allergic population will suffer from an allergic reaction after ingestion of 6 mg (95% CI, 2–11 mg) of hazelnut protein. Objective symptoms were observed in two patients after 1 and 1000 mg, respectively.Conclusion DBPCFCs demonstrated threshold doses in half of the hazelnut-allergic patients similar to doses previously described to be hidden in consumer products. This stresses the need for careful labelling and strategies to prevent and detect contamination of food products with hazelnut residues.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Allergen-specific immunotherapy for food allergy has been hindered by severe side-effects in the past. Well-characterized hypo-allergenic recombinant food allergens potentially offer a safe solution.Objective To demonstrate hypo-allergenicity of a mutated major food allergen from apple, Mal d 1, in vitro and in vivo.Methods A mutant of the major apple allergen, Mal d 1, was obtained by site-directed mutagenesis exchanging five amino acid residues. Fourteen patients with combined birch pollen-related apple allergy were included in the study. Hypo-allergenicity of the mutant rMal d 1 (rMal d 1mut) compared with rMal d 1 was assessed by in vitro methods, i.e. RAST (inhibition), immunoblotting and basophil histamine release (BHR) and in vivo by skin prick test and double-blind placebo-controlled food challenge (DBPCFC).Results RAST analysis (n=14) revealed that IgE reactivity to rMal d 1mut was twofold lower than that of the wild-type molecule (95% confidence interval (CI): 1.7–2.4). RAST inhibition (n=6) showed a 7.8-fold decrease in IgE-binding potency (95% CI: 3.0–12.6). In contrast to this moderate decrease in IgE-binding potency, the biological activity of rMal d 1mut assessed by SPT and BHR decreased 10–200-fold. Hypo-allergenicity was confirmed by DBPCFC (n=2) with both recombinant molecules.Conclusion A moderate decrease in IgE-binding potency translates into a potent inhibition of biological activity. This is the first study that confirms by DBPCFC that a mutated recombinant major food allergen is clinically hypo-allergenic. This paves the way towards safer immunotherapy for the treatment of food-allergic patients.
    Type of Medium: Electronic Resource
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