| 11. |
- Benson, Mikael, 1954
(författare)
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Pathophysiological effects of glucocorticoids on nasal polyps: an update.
- 2005
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Ingår i: Current opinion in allergy and clinical immunology. - : Lippincott Williams & Wilkins. - 1528-4050 .- 1473-6322. ; 5:1, s. 31-5
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: The exact mechanisms by which glucocorticoids exert their beneficial effects on nasal polyps are not clearly defined. Nasal polyps, asthma and allergic rhinitis share common features such as mucosal infiltration with eosinophils and mast cells as well as local IgE production. The present review is an update on the pathophysiological mechanisms of glucocorticoids on nasal polyps described during the last 2 years. RECENT FINDINGS: The reduction of leukocyte numbers in nasal polyps following glucocorticoid treatment depends on several mechanisms, for example altered balance between the two isoforms of the human glucocorticoid receptors, GRalpha and GRbeta. Another explanation may be inhibition of CD4+ T by CD8+ T cells. Increased expression of the antiinflammatory cytokine transforming growth factor beta may contribute to this. A DNA microarray study which examined the expression of some 22 000 genes showed increased expression of several antiinflammatory genes in nasal polyps after treatment with glucocorticoids. The antiinflammatory gene that increased most was uteroglobin (also known as Clara cell protein 16) which is abundantly expressed in airway secretions and thought to have an important role in regulating inflammation. SUMMARY: Glucocorticoids affect both pro and antiinflammatory pathways in nasal polyps. Upregulation of antiinflammatory genes such as transforming growth factor beta and uteroglobin may play an important role. Elucidation of these mechanisms may help us to understand not only the effects of glucocorticoids on nasal polyps, but also on related disorders such as allergic rhinitis and asthma.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Clermont, Gilles, et al.
(författare)
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Bridging the gap between systems biology and medicine
- 2009
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 1:9
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT : Systems biology has matured considerably as a discipline over the last decade, yet some of the key challenges separating current research efforts in systems biology and clinically useful results are only now becoming apparent. As these gaps are better defined, the new discipline of systems medicine is emerging as a translational extension of systems biology. How is systems medicine defined? What are relevant ontologies for systems medicine? What are the key theoretic and methodologic challenges facing computational disease modeling? How are inaccurate and incomplete data, and uncertain biologic knowledge best synthesized in useful computational models? Does network analysis provide clinically useful insight? We discuss the outstanding difficulties in translating a rapidly growing body of data into knowledge usable at the bedside. Although core-specific challenges are best met by specialized groups, it appears fundamental that such efforts should be guided by a roadmap for systems medicine drafted by a coalition of scientists from the clinical, experimental, computational, and theoretic domains.
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| 16. |
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| 17. |
- Johansson, S., et al.
(författare)
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Low levels of CC16 in nasal fluid of children with birch pollen-induced rhinitis
- 2005
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 60:5, s. 638-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clara cell protein 16 (CC16; secretoglobin 1A1) is an anti-inflammatory protein mainly expressed in the epithelial cells in the airways. OBJECTIVE: To compare the levels of CC16 in nasal lavage (NAL) from children with intermittent allergic rhinitis and healthy controls and to study the effect of a local steroid. METHODS: Thirty schoolchildren with birch pollen allergy and 30 healthy controls from the same schools were included in the study. The NAL fluid was collected before the season, during the birch pollen season and, for the patients, after 1 week of treatment with a local steroid. Symptom scores were obtained on every occasion. CC16 and eosinophil cationic protein (ECP) were analyzed with enzyme-linked immunosorbent assay. RESULTS: The nasal fluid levels of CC16 were significantly lower in patients than in controls, before and during pollen season. Before the season, the median CC16 concentrations were 9.1 (range 1.1-117) microg/l in patients and 25.7 (6.1-110.2) microg/l in controls. During the season, the median CC16 concentrations in nasal fluid were 12.9 (2.3-89.7) microg/l in the allergic children and 22.0 (9.5-90.1) microg/l in the healthy controls (P = 0.0005). Symptom scores, nasal fluid eosinophils and ECP were higher in patients during the season. Treatment with a local steroid did not change the CC16 levels. CONCLUSIONS: Nasal fluid CC16 levels were lower in children with birch pollen-induced allergic rhinitis than in healthy controls both before and during the pollen season. We speculate that reduction in anti-inflammatory activity by CC16 may contribute to the pathogenesis of allergic rhinitis.
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| 18. |
- Keen, Christina, et al.
(författare)
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Bet v 1-specific IgA increases during the pollen season but not after a single allergen challenge in children with birch pollen-induced intermittent allergic rhinitis
- 2005
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Ingår i: Pediatr Allergy Immunol. - : Wiley-Blackwell. - 0905-6157 .- 1399-3038. ; 16:3, s. 209-16
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Tidskriftsartikel (refereegranskat)abstract
- Allergen-specific immunoglobulins of the Immunoglobulin A (IgA) type have been found in the nasal fluid of patients with allergic rhinitis. IgA may play a protective role, but there are also data which show that allergen-specific IgA can induce eosinophil degranulation. The aim of this study was to quantitate Bet v 1-specific IgA in relation to total IgA in the nasal fluid of children with birch pollen-induced intermittent allergic rhinitis and healthy controls, after allergen challenge and during the natural pollen season. Eosinophil cationic protein (ECP), Bet v 1-specific IgA and total IgA were analyzed in nasal fluids from 30 children with birch pollen-induced intermittent allergic rhinitis and 30 healthy controls. Samples were taken before the pollen season, after challenge with birch pollen and during the pollen season, before and after treatment with nasal steroids. During the pollen season, but not after nasal allergen challenge, Bet v 1-specific IgA increased in relation to total IgA in children with allergic rhinitis. No change was found in the healthy controls. The ratio of Bet v 1-specific IgA to total IgA increased from 0.1 x 10(-3) (median) to 0.5 x 10(-3) in the allergic children, p < 0.001. No change was seen after treatment with nasal steroids, although symptoms, ECP and eosinophils were reduced. In conclusion, allergen-specific IgA in relation to total IgA increases in nasal fluids during the pollen season in allergic children but not in healthy controls. These findings are compatible with the hypothesis that allergen-specific IgA plays a role in the allergic inflammation and further studies are needed to clarify the functional role of these allergen-specific antibodies.
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| 19. |
- Mobini, Reza, 1965, et al.
(författare)
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A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation.
- 2009
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Ingår i: BMC systems biology. - : Springer Science and Business Media LLC. - 1752-0509. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes. RESULTS: To test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4+ cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, IL7R, was selected for further validation. The expression levels of IL7R in allergen challenged CD4+ cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies. CONCLUSION: We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.
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| 20. |
- Olsson, Maja, 1975, et al.
(författare)
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Increased expression of aquaporin 3 in atopic eczema.
- 2006
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 61:9, s. 1132-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dry skin in atopic eczema depends on increased water loss. The mechanisms behind this are poorly understood. The aim of this work was to identify genes that may contribute to water loss in eczema. METHODS: Affymetrix DNA microarrays U133A were used to analyse gene expression in skin biopsies from 10 patients with atopic eczema and 10 healthy controls. RESULTS: DNA microarray analysis showed up-regulation of 262 genes and down-regulation of 129 genes in atopic eczema. The known functions of these genes were analysed using Gene Ontology to identify genes that could contribute to increased water loss. This led to identification of aquaporin 3 (AQP3), which has a key role in hydrating healthy epidermis. Increased expression of AQP3 was found in eczema compared with healthy skin. This was confirmed with real-time polymerase chain reaction (P<0.001). In healthy skin, epidermal AQP3 immunoreactivity was weak and mainly found in the stratum basale. A gradient was formed with decreasing AQP3 staining in the lower layers of the stratum spinosum. By contrast, in acute and chronic atopic eczema strong AQP3 staining was found in both the stratum basale and the stratum spinosum. CONCLUSIONS: Aquaporin 3 is the predominant aquaporin in human skin. Increased expression and altered cellular distribution of AQP3 is found in eczema and this may contribute to water loss.
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