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- Konradsen, Jon R., et al.
(författare)
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Severe childhood asthma and allergy to furry animals : Refined assessment using molecular-based allergy diagnostics
- 2014
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 25:2, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- Background Infants born prematurely are often treated with supplemental oxygen, which can increase their risk for airway hyper-responsiveness (AHR), asthma, reduced lung function, and altered responses to respiratory viral infections later in childhood. Likewise, exposure of newborn mice to hyperoxia alters baseline pulmonary mechanics and the host response to influenza A virus infection in adult mice. Here, we use this mouse model to test the hypothesis that neonatal hyperoxia also promotes AHR and exacerbated allergen-induced symptoms in adult mice. Methods Baseline lung mechanics and AHR measured by methacholine provocation were assessed in adult male and female mice exposed to room air or 100% oxygen (hyperoxia) between post-natal days 0-4. AHR and lung inflammation were evaluated after adult female mice were sensitized with ovalbumin (OVA) plus alum and challenged with aerosolized OVA. Results Baseline lung compliance increased and resistance decreased in adult female, but not male, mice exposed to neonatal hyperoxia compared with siblings exposed to room air. Neonatal hyperoxia significantly enhanced methacholine-induced AHR in female mice, but did not affect allergen-induced AHR to methacholine or lung inflammation. Conclusion Increased incidence of AHR and asthma is reported in children born prematurely and exposed to supplemental oxygen. Our findings in adult female mice exposed to hyperoxia as neonates suggest that this AHR reported in children born prematurely may reflect non-atopic wheezing due to intrinsic structural changes in airway development.
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| 2. |
- Onell, Annica, et al.
(författare)
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Kinetic determinations of molecular interactions using Biacore : minimum data requirements for efficient experimental design
- 2005
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Ingår i: Journal of Molecular Recognition. - : Wiley. - 0952-3499 .- 1099-1352. ; 18:4, s. 307-17
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Tidskriftsartikel (refereegranskat)abstract
- Reliable kinetic estimates can be obtained from significantly less data than is commonly used today, particularly in the characterization of 1:1 interactions involving low molecular weight compounds and proteins. We have designed a rational and cost-effective strategy to determine kinetic constants using Biacore's surface plasmon resonance-based biosensors and show that the number of measurements necessary for accurate kinetic determinations can be greatly reduced, increasing sample throughput and saving sample material. Simulated and measured data for a range of possible 1:1 interactants were studied to find the minimum requirements of a data set for kinetic analysis. The results showed that kinetic constants in the region 10(4) < k(a) < 10(7) M(-1) s(-1) (association) and 10(-4) < k(d) < 10(-1) s(-1) (dissociation) could easily be determined in a 1:1 interaction model. Owing to the information-dense nature of Biacore data, only two sample concentrations were necessary to reliably determine the kinetics. A standard sample concentration series consisting of 10-fold dilutions between approximately 10 microM and approximately 1 nM consistently provided at least two concentrations with sufficient information about the interaction in this region. Determinations of the constants became increasingly unreliable outside this region. If the rate constants prove to be outside the specified region or the data fits poorly to the 1:1-MTL model, more experiments are required. General recommendations for the design of a cost-effective assay to deliver reliable kinetic measurements are provided.
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| 3. |
- Soeria-Atmadja, Daniel, et al.
(författare)
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IgE sensitization to fungi mirrors fungal phylogenetic systematics
- 2010
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 125:6, s. 1379-1386
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fungal allergy is an elusive disease, and little progress has been made in this field during recent years. Moreover, because of the complexity of the organisms, it is difficult to categorize fungi systematically on the basis of morphologic characterization. However, recent molecular phylogenetics studies have substantially improved fungal categorization. In parallel, new approaches to analyze large IgE antibody datasets enable identification and visualization of IgE sensitization patterns. Objective: To study whether molecular phylogenetic relationships of fungal species, commonly used in allergy diagnosis, also are reflected in IgE sensitization profiles of individuals sensitized to fungi. Methods: A dataset was compiled of recorded serum IgE antibody levels to 17 different fungal species from 668 individuals sensitized to at least I of the 17 species. By applying a clustering method to this dataset, the fungal species were grouped into a hierarchical organization. Finally, the resulting organization was compared with recently published fungal systematics. Results: The hierarchical structure of fungi, based on the presence of IgE antibodies in sensitized individuals, very well reflected phylogenetic relationships. Examples include the distinct separation of basal fungi from the subkingdom Dikarya as well as individual cluster formations of fungi belonging to the subphylum Saccharomycotina and order Pleosporales. Conclusion: To our knowledge, this is the first in-depth study that demonstrates a close relationship between molecular fungal systematics and IgE sensitization to fungal species. Because close evolutionary organisms typically have a higher degree of protein similarity, IgE cross-reactivity is likely the main reason for obtained organization. (J Allergy Clin Immunol 2010;125:1379-86.)
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