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  • 1
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 56 (2001), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Our aim was to study the risk of laboratory animal all_ergy (LAA) among research staff working in laboratories separate from the animal confinement area. The roles of atopy and exposure intensity in LAA were studied with special regard to exposure to male rodents, who excrete higher levels of urinary all_ergens than female rodents. Methods: Eighty rodent-exposed subjects gave blood samples for the analysis of total IgE, Phadiatop, and specific IgE against rat (RUA) and mouse urinary all_ergens (MUA), and answered questionnaires. Air samples were collected for RUA and MUA aeroall_ergen measurement in both laboratories and animal confinement facilities. Results: Twenty percent of the subjects had IgE 〉0.35 kU/l to RUA and/or MUA, and 32% had experienced animal work-related symptoms, although 90% of aeroall_ergen samples from the research department laboratories were below the detection limit (〈0.26 ng RUA per m3 and 〈0.8 ng MUA per m3). Atopy (positive Phadiatop), total IgE 〉100 kU/l, other all_ergies (especiall_y to other animals), or more than 4 years of exposure significantly increased laboratory animal sensitization and symptoms. Working with mainly male rodents gave odds ratios (95% CI) of 3.8 (0.97–15) for sensitization and 4.4 (1.4–14) for symptoms. Subjects with both exposure to mainly male rodents and atopy or elevated total IgE had a 10-fold higher frequency of sensitization than exposed subjects with neither risk factor. Conclusions: A majority of subjects with a combination of exposure to mainly male rodents and atopy or elevated total IgE developed sensitization to and symptoms from laboratory animals. Current low exposure seems to maintain the presence of specific IgE. Further measures must be undertaken to provide a safe workplace for laboratory animal workers.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 55 (2000), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: xxBackground: Measurement of airborne allergens has hitherto been done with the use of fixed-location pumps or personal air samplers. Our objective was to find out whether ionizers could be good tools for collecting airborne allergens. As a model we have used cat allergen (Fel d 1). We have compared Fel d 1 levels collected by the ionizer at different time periods, as well as comparing Fel d 1 levels obtained with the ionizer with those of low- and high-volume pumps. Methods: Dust samples from floors and air samples collected with ionizers and pumps, obtained in 31 homes with cat, 23 homes without cats, and 28 day-care centres, were analysed for cat allergen content (Fel d 1) by ELISA. Results: Fel d 1 was present in the reservoir in all homes with cats, ranging from 660 to 375000 ng/g (GM 75000) and in the air collected by the ionizer from 2.0 to 204 ng/24 h (GM 19.3). The allergen in homes without cat varied from 〈55 to 1800 ng/g (GM 166). Corresponding levels in air were found in two of these homes (2.3 and 7.3 ng/24 h). There was a correlation between the number of cats and the amount of airborne cat allergen (r: 0.47; P〈0.05). The levels in day-care centres were 〈55 to 3070 ng/g in dust (GM 360) and 〈1.1 to 7.9 ng/24 h in the air (GM 1.6). We obtained a moderately strong correlation between air and dust samples in homes with cats (rs: 0.64; P〈0.001) and in day-care centres (rs: 0.49; P〈0.05). We found that a collection period of 24 h is preferable for the ionizer. The intrahome reliability coefficient was nearly two times higher for the ionizer (r: 0.69) than the pump (r: 0.39). Conclusions: The ionizer seems to be a good tool for monitoring the environment. It is easy to use and silent and does not disturb the airflow in the room.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Copenhagen : Blackwell Publishing Ltd
    Allergy 54 (1999), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Earlier studies have shown that farmers are to a low degree sensitized to animal allergens. We have measured the amount of cat (Fel d 1) and dog (Can f 1) in farm households and examined the relationship between exposure and sensitization to cat and dog allergens. Methods: Dust samples from the homes of 403 farmers who had participated in an epidemiologic follow-up study on respiratory symptoms were analyzed for allergen content by two-site ELISA methods. Results: Fel d 1 was detected in 99.5% of the farmers' households ranging from 0.055 to 1455 μg/g dust in mattresses (GM 13.2) and to 3775 μg/g dust in living-room carpets (GM 17.1). Can f 1 was detected in 90.6% of the households from 0.2 to 116 μg/g dust in mattresses (GM 2.0) and to 504 μg/g dust in carpets (GM 4.3). Homes with pets present had the highest levels of the allergens (P〈0.001). A total of 8.4% and 7.4% of the farmers were sensitized to cat and dog, respectively. A significant correlation was noted between exposure to the allergens and specific IgE to cat and dog, respectively (P〈0.001). Sensitization to cat (OR=4.9) and dog (OR=17.8) was significantly associated with asthma. Conclusions: In spite of the abundance of Fel d 1 and Can f 1, farmers are only to a low degree sensitized to cats and dogs.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Exposure to furred pets in early life has been considered to increase the risk of allergic sensitization and consequent development of asthma later in children. However, recently, it has been suggested that early exposure to pets prevents sensitization. The aim of this study was to evaluate the importance of early exposure to pets and other environmental risk factors in asthmatic children. Methods: This is a follow-up study after 2 years of a previously investigated group of 193 asthmatic children, aged 1–4 years. The study was completed by 181 children, who were clinically examined; serum IgE antibodies were also measured and a questionnaire was answered. Results: Children with reported exposure to cats during the first 2 years of life were more likely to have developed sensitization to cat by 4 years of age than unexposed children. High levels of cat allergen (Fel d 1≥8 µg/g dust) were associated with an increased risk of sensitization to cat and, in combination with tobacco smoke, also with the development of more severe asthma. Conclusions: In young asthmatic children, early exposure to cat and tobacco smoke increased the risk of allergic sensitization and further development of more severe asthma later in childhood.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Allergen-specific immunotherapy (SIT) is commonly conducted with allergen extracts adsorbed to aluminium hydroxide (alum). Drawbacks linked to the use of alum, such as the formation of granuloma at the site of injection, have led to suggestions of novel allergen carriers. An alternative carrier is 2 μm carbohydrate-based particles (CBPs). In mouse, allergen-coupled CBPs have been demonstrated to skew the allergen-specific immune response towards a Th1-like activity (Grönlund et al. Immunology, 2002). We here coupled the recombinant major cat allergen Fel d 1 to CBPs (CBP-Fel d 1) by cyanogen-bromide activation, resulting in covalent binding. The effect of CBP-Fel d 1 on monocyte-derived dendritic cells (MDDCs) from healthy human blood donors was studied. We found that the majority of the CD1a+ MDDCs were capable of taking up FITC-labelled CBP-Fel d 1, as demonstrated by flow cytometry and confocal laser scanning microscopy. Furthermore, incubation with CBP-Fel d 1 resulted in an upregulation of the costimulatory molecule CD86 on the MDDCs, which was not observed with Fel d 1 or CBPs alone. Finally, CBP-Fel d 1 induced a fivefold increase in the release of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α and a fourfold increase in the release of the chemokine interleukin-8 from MDDCs. Taken together, the effects CBPs possess make them interesting as novel allergen carriers for SIT.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The cause of the chronic inflammation in atopic keratoconjunctivitis (AKC), the ocular manifestation of atopic eczema/dermatitis syndrome, is largely unknown.Objective To investigate the possibility that microorganisms may be important in the inflammatory activity in AKC.Methods Fifteen patients with AKC participated in the study. The presence of aerobic bacteria and fungi was related to the severity of clinical signs, the numbers of inflammatory cells in tears and conjunctival biopsies, and the concentration of various cytokines in tears. In addition, serological evidence for IgE sensitization to Staphylococcus aureus B antigen and Malassezia sympodialis antigen was investigated. Twelve healthy subjects were included for control purposes.Results The patients exhibited moderate clinical signs of AKC. No relation was found between the severity of AKC and the presence of microorganisms, despite the fact that S. aureus was frequently isolated. AKC patients showed significantly higher levels of IFN-γ, TNF-α (tumour necrosis factor-α), IL-2, IL-4, IL-5 and IL-10 than controls. An association was found between conjunctival signs and the levels of all cytokines except IL-5.Conclusion We found no evidence to suggest that periocular and ocular microcolonization are related to inflammatory parameters in AKC. However, confirmation of the present results in a longitudinal study with repeated clinical examinations and samplings in the same individual is required before the contribution of S. aureus to on-going inflammation in AKC can be dismissed.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 35 (2005), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy.Objective The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen.Methods The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay.Results Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400–900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1.Conclusion By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Exposure to indoor allergens, such as dust mites, has been recognized as a risk factor for sensitization and symptoms.Objective To develop a two-site ELISA for the determination of Lep d 2 in the reservoir, to measure dust mite allergen exposure (Lep d 2, Der p 1, Der f 1 and Der 2) in farm households, and to investigate whether exposure to these allergens is associated with sensitization, asthma and rhinoconjunctivitis.Methods Monoclonal antibodies to recombinant (r)Lep d 2 were produced with standard hybridoma technique. Dust samples from 393 households were analysed for allergen content by two-site ELISA methods.Results A two-site Lep d 2 ELISA was developed with a detection limit of 0.09 µg/g. The assay was highly reproducible and levels of Lep d 2 showed a strong correlation with the number of Lepidoglyphus mites (rs: 0.7; P = 0.0002). Lep d 2 was detected in 20% of the homes; levels ranged from 0.09 to 1.7 µg/g of dust. Der p 1 was recorded in 59% of the samples, ranging from 0.055 to 139 µg/g, and Der f 1 and Der 2 in 40% and 50% of the samples, ranging from 0.055 to 24.5 µg/g and 24.3 µg/g, respectively. Dermatophagoides allergens were significantly higher in mattresses than in carpets (P 〈 0.0001), but this difference was not observed with Lep d 2. A strong relationship between immunoglobulin (Ig)E to rLep d 2 and asthma (OR = 10.4) and rhinoconjunctivitis (OR = 7.5) was seen. Furthermore, sensitization to D. pteronyssinus was significantly associated with asthma (OR: 13.7) and rhinoconjunctivitis (OR: 5.7).Conclusion When assessing mite allergen exposure in rural homes, not only the Der p 1, Der f 1 and Der 2 allergens, but also the Lep d 2 allergen should be taken into consideration.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability.Objective To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction.Methods Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively.Results All 10 patients tolerated the highest accumulated dose, 8.124 µg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined.Conclusion The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Polymorphisms within the β subunit of the high-affinity receptor for IgE (FcεR1-β) on chromosome 11q13 have been related to atopy and asthma and the lymphotoxin α (LTα) gene on chromosome 6 is implicated in asthma.Objective To elucidate the association of polymorphisms in the FcεR1-β and LTα genes to IgE responses and asthma in a family-orientated rural population.Methods A total of 461 adult farmers, who participated in an epidemiological follow-up study on respiratory symptoms among farmers on the Swedish island of Gotland, were examined. The traits assessed included serum total IgE, IgE antibody responses to 21 common inhalant allergens and asthma.Results The 237G mutation was only detected in seven persons. Atopy was found to be associated with the RsaI-ex7 AB-genotype (OR = 1.9; P = 0.04). The RsaI-ex7 B allele had a significant influence on IgE responses to pollens and dust mites (OR = 5.5; P = 0.03 and OR = 5.2; P = 0.049, respectively). The influence of this allele was stronger when the association towards single dust mite species (Lepidoglyphus destructor) was estimated (OR = 7.1, P = 0.03) and the association increased even more when the major allergen of L. destructor (rLep d 2) was analysed (OR = 11.2, P = 0.02). These associations were independent of sex, age and smoking, and the estimates of RsaI-in2 independent of RsaI-ex7. RsaI-in2, RsaI-ex7 and LTα genotypes were unassociated with total serum IgE. No significant difference in the distribution of RsaI-in2, RsaI-ex7 and LTα genotypes was found among subjects with atopy or asthma compared to healthy controls.Conclusion This study supports the notion that polymorphisms in the FcεR1-β gene have significant effects on IgE responsiveness. Secondly, dust mites in rural populations influence the expression of genes on chromosome 11q13.
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