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- Benson, Mikael, 1954, et al.
(författare)
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DNA microarray analysis of chromosomal susceptibility regions to identify candidate genes for allergic disease: A pilot study
- 2004
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 124:7, s. 813-819
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Tidskriftsartikel (refereegranskat)abstract
- Objective-To examine whether DNA microarray analysis of chromosomal susceptibility regions for allergy can help to identify candidate genes. Material and Methods-Nasal biopsies were obtained from 23 patients with allergic rhinitis and 12 healthy controls. RNA was extracted from the biopsies and pooled into three patient and three control pools. These were then analysed in duplicate with DNA microarrays containing 12626 genes. Candidate genes were further examined in nasal biopsies (real-time polymerase chain reaction) and blood samples (single nucleotide polymorphisms) from other patients with allergic rhinitis and from controls. Results-A total of 37 differentially expressed genes were identified according to criteria involving both the size and consistency of the gene expression levels. The chromosomal location of these genes was compared with the chromosomal susceptibility regions for allergic disease. Using a statistical method, five genes were identified in these regions, including serine protease inhibitor, Kazal type, 5 (SPINK5) and HLA-DRB2. The relevance of these genes was examined in other patients with allergic rhinitis and in controls; none of the genes were differentially expressed in nasal biopsies. Moreover, no association between allergic rhinitis and SPINK5 polymorphisms was found, at either the genotype or haplotype level. Conclusions-DNA microarray analysis of chromosomal susceptibility regions did not lead to identification of candidate genes that could be validated in a new material. However, because gene polymorphisms may cause differential gene expression, further studies, including validation data, are needed to examine this approach.
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- Benson, Mikael, 1954, et al.
(författare)
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DNA microarray analysis of transforming growth factor-β and related transcripts in nasal biopsies from patients with allergic rhinitis
- 2002
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Ingår i: Cytokine. ; 18:1, s. 20-25
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Tidskriftsartikel (refereegranskat)abstract
- Decreased activity of anti-inflammatory cytokines like transforming growth factor (TGF)-β may contribute to allergic inflammation. In vivo effects of TGF-β-effects are difficult to infer from local concentrations, since TGF-β-effects depend on a complex system of regulatory proteins and receptors. Instead the effects of TGF-β might be inferred by examining TGF-β-inducible transcripts. In this study DNA microarrays were used to examine local expression of TGF-β, TGF-β-regulatory and -inducible transcripts in nasal biopsies from patients with symptomatic allergic rhinitis and healthy controls. In addition, nasal fluids were analysed with cytological and immunological methods. Nasal fluid eosinophils, albumin, eosinophil granulae proteins and IgE, but not TGF-β, were higher in patients than in controls. DNA microarray analysis of nasal mucosa showed expression of transcripts encoding TGF-β, TGF-β-regulatory proteins and -receptors at variable levels in patients and controls. By comparison, analysis of 28 TGF-β-inducible transcripts indicated that 23 of these had lower measurement values in patients than in controls, while one was higher, and the remaining four were absent in both patients and controls. In summary, TGF-β and a complex system of regulatory genes and receptors are expressed in the nasal mucosa. Low expression of TGF-β-inducible transcripts may indicate decreased TGF-β activity in allergic rhinitis. DNA microarray analysis may be a way to study cytokine effects in vivo.
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- Benson, Mikael, 1954, et al.
(författare)
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DNA microarrays to study gene expression in allergic airways.
- 2002
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Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 0954-7894 .- 1365-2222. ; 32:2, s. 301-8
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Tidskriftsartikel (refereegranskat)abstract
- Allergic rhinitis results from interactions between a large number of cells and mediators in different compartments of the body. DNA microarrays allow simultaneous measurement of expression of thousands of genes in the same tissue sample.
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- Benson, Mikael, 1954, et al.
(författare)
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Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps.
- 2004
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 113:6, s. 1137-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.
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- Benson, Mikael, 1954, et al.
(författare)
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Increased expression of Vascular Endothelial Growth Factor-A in seasonal allergic rhinitis.
- 2002
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 20:6, s. 268-73
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Tidskriftsartikel (refereegranskat)abstract
- Increased vascular dilatation and permeability characterize allergic rhinitis. In this study oligonucleotide microarrays (Affymetrix HuGe95A) were used to identify differentially expressed vasoactive genes in nasal biopsies from 23 patients with symptomatic seasonal allergic rhinitis (SAR) and 12 healthy controls. RNA was extracted from the biopsies and pooled in three patient and three control pools. Out of 12,626 analysed transcripts, 39 were higher and 81 lower in the patients. Of these transcripts two have vasoactive effects: Vascular Endothelial Growth Factor-A (VEGF-A) and the Beta-1-Adrenergic Receptor. Both were higher in patients than in controls. The mean +/- SEM expression levels in arbitrary units of VEGF-A were 130 +/- 123 in the patients and 59 +/- 53 in the controls. The fold ratio in expression levels between patients/controls was 2.2. The corresponding values for the beta-1-adrenergic receptor were 129 +/- 123 in the patients and 40 +/- 31 in the controls. The fold ratio between patient/controls was 3.2. The role of VEGF-A was assessed by determining VEGF-A concentrations in nasal fluids from another 30 patients with SAR before and after allergen provocation. VEGF-A increased from 124.3 +/- 30.2 to 163.2 +/- 37.8 pg/ml after challenge, P < 0.05. In summary, oligonucleotide microarray analysis of nasal biopsies and protein analyses of nasal fluids indicate that VEGF-A may be an important mediator in SAR.
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- Peredo, A. M., et al.
(författare)
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Towards a theory of indigenous entrepreneurship
- 2004
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Ingår i: International Journal of Entrepreneurship and Small Business. - : InderScience Publishers. - 1476-1297 .- 1741-8054. ; 1:1-2, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- Indigenous populations throughout the world suffer from chronic poverty, lower education levels, and poor health. The 'second wave' of indigenous development, after direct economic assistance from outside, lies in indigenous efforts to rebuild their 'nations' and improve their lot through entrepreneurial enterprise. This paper suggests that there is a distinguishable kind of activity appropriately called 'indigenous entrepreneurship'. We begin by defining the indigenous population and noting some general facts about their numbers and distribution. In an effort to discern the potential for development on indigenous peoples' own terms, we then explore three frameworks for understanding efforts at development, including indigenous development: modernisation theory, dependency theory and (at somewhat greater length) regulation theory. After distinguishing 'indigenous' from 'ethnic' entrepreneurship, we conclude by identifying a number of lead questions that present themselves at the outset of an enquiry into the nature of indigenous entrepreneurship.
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