| 1. |
- 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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| 2. |
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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- Bjarnason, Ragnar, 1959, et al.
(författare)
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Cartilage oligomeric matrix protein increases in serum after the start of growth hormone treatment in prepubertal children
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:10, s. 5156-60
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Tidskriftsartikel (refereegranskat)abstract
- Both GH and IGF-I stimulate bone growth, but the molecular mechanisms mediating their effects on the growth plate are not fully understood. We measured gene expression by microarray analysis in primary cultured human chondrocytes treated with either GH or IGF-I. One of the genes found to be up-regulated by both GH and IGF-I was that encoding cartilage oligomeric matrix protein (COMP). This protein is predominantly found in the extracellular matrix of cartilage. Mutations in the COMP gene have been associated with syndromes of short stature. To verify that COMP is regulated by GH in vivo, we measured COMP levels in serum in short children treated with GH. The study included 113 short prepubertal children (14 girls and 99 boys) with a mean (+/- sd) age of 8.84 +/- 2.76 yr, height sd score of -2.74 +/- 0.67, and IGF-I sd score of -1.21 +/- 1.07 at the start of GH administration. Serum levels of COMP were 1.58 +/- 0.28, 1.83 +/- 0.28 (P < 0.0001), 1.91 +/- 0.28 (P < 0.0001), 1.78 +/- 0.28 (P < 0.001), and 1.70 +/- 0.24 (P < 0.05) microg/ml at baseline and after 1 wk and 1, 3, and 12 months, respectively.In conclusion, we have demonstrated that COMP expression is up-regulated by both GH and IGF-I in primary cultured human chondrocytes. Furthermore, serum levels of COMP increase after the start of GH treatment in short children.
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| 7. |
- Carlsson, Björn, 1958, et al.
(författare)
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Total RNA and array-based expression monitoring.
- 2000
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 18:6
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Chen, Yun, 1966, et al.
(författare)
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Neonatal losartan treatment suppresses renal expression of molecules involved in cell-cell and cell-matrix interactions
- 2004
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Ingår i: Journal of the American Society of Nephrology. - : Lippincott Williams & Wilkins. - 1046-6673 .- 1533-3450. ; 15:5, s. 1232-43
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Tidskriftsartikel (refereegranskat)abstract
- Lack of neonatal angiotensin II type 1 receptor (AT(1)) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT(1) receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, approximately 30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, alpha-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin alpha6 and caused relocalization of integrins alpha6 and alpha3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT(1) receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and alpha-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.
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| 9. |
- Gabrielsson, Britt, 1957, et al.
(författare)
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Depot-specific expression of fibroblast growth factors in human adipose tissue.
- 2002
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Ingår i: Obesity research. - : Wiley. - 1071-7323 .- 1550-8528. ; 10:7, s. 608-16
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the expression of several fibroblast growth factors (FGFs) and FGF-receptors (FGFRs) in human adipose tissue and adipose-tissue cell fractions obtained from both subcutaneous (sc) and omental (om) depots.
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| 10. |
- Gabrielsson, Britt, 1957, et al.
(författare)
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High expression of complement components in omental adipose tissue in obese men.
- 2003
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Ingår i: Obesity research. - : Wiley. - 1071-7323 .- 1550-8528. ; 11:6, s. 699-708
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Accumulation of visceral fat is recognized as a predictor of obesity-related metabolic disturbances. Factors that are predominantly expressed in this depot could mediate the link between visceral obesity and associated diseases. RESEARCH METHODS AND PROCEDURES: Paired subcutaneous and omental adipose tissue biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA microarrays in triplicate and by real-time polymerase chain reaction. Serum C3 and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing a cross section of the general population. Body composition was measured by computerized tomography. RESULTS: Complement components C2, C3, C4, C7, and Factor B had higher expression in omental compared with subcutaneous adipose tissue ( approximately 2-, 4-, 17-, 10-, and 7-fold, respectively). In addition, adipsin, which belongs to the alternative pathway, and the classical pathway components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue distribution showed high expression of C2, C3, and C4 in omental adipose tissue, and only liver had higher expression of these genes. Serum C3 levels correlated with both visceral and subcutaneous adipose tissue in both men (r = 0.65 and p < 0.001 and r = 0.52 and p < 0.001, respectively) and women (r = 0.34 and p = 0.023 and r = 0.49 and p < 0.001, respectively), whereas C4 levels correlated with only visceral fat in men (r = 0.36, p = 0.015) and with both depots in women (visceral: r = 0.58, p < 0.001; and subcutaneous: r = 0.51, p < 0.001). DISCUSSION: Recent studies show that the metabolic syndrome is associated with chronically elevated levels of several immune markers, some of which may have metabolic effects. The high expression of complement genes in intra-abdominal adipose tissue might suggest that the complement system is involved in the development of visceral adiposity and/or contributes to the metabolic complications associated with increased visceral fat mass.
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