| 31. |
- 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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| 32. |
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| 33. |
- Benson, Mikael, 1954, et al.
(författare)
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Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis
- 2005
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Ingår i: Clin Exp Allergy. - : Wiley. ; 35:4, s. 473-478
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample. OBJECTIVE: To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls. METHODS: Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44,927 genes and variants. RESULTS: Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively (P<0.05). CONCLUSION: IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes.
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| 34. |
- 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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| 35. |
- 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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| 36. |
- Benson, Mikael, 1954, et al.
(författare)
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Inverse relation between nasal fluid Clara Cell Protein 16 levels and symptoms and signs of rhinitis in allergen-challenged patients with intermittent allergic rhinitis.
- 2007
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 62:2, s. 178-83
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Decreased levels of the anti-inflammatory Clara Cell Protein 16 (CC16) are found in intermittent allergic rhinitis (IAR) and asthma. In asthma this decrease has been associated with hyperreactivity and the A38G single nucleotide polymorphism (SNP). The aim of this study was to examine if IAR is associated with signs and symptoms of rhinitis and the A38G SNP. METHODS: Nasal fluid CC16 was analyzed in 20 patients with IAR before allergen challenge and 1 and 6 h after challenge, and from 28 healthy controls. The A38G SNP was analyzed in 80 patients with IAR and 106 controls. Nasal biopsies were obtained from three subjects in each group for immunohistochemical analysis of CC16. RESULTS: In the allergen-challenged patients symptoms and rhinoscopic signs of rhinitis increased after 1 h and normalized after 6 h. In contrast, nasal fluid CC16 decreased 1 h after allergen challenge and returned to baseline after 6 h. Nasal fluid CC16 levels did not differ from controls before and 6 h after challenge. Immunohistochemical investigation showed intense CC16 staining in the nasal epithelium of both patients before season and healthy controls, but weak staining in symptomatic patients during season. No significant association between the A38G SNP and IAR was found. CONCLUSION: There was an inverse relation between nasal fluid CC16 levels and symptoms and signs of rhinitis in allergen-challenged patients with IAR. However, there was no association between IAR and the A38G SNP.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Benson, Mikael, et al.
(författare)
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Systembiologin kan förändra sjukvården radikalt. Ger underlag för individualiserad prediktion, prevention och behandling : [Systems biology can radically change health care. Basis for individualized prediction, prevention and treatment]
- 2007
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Ingår i: Läkartidningen. - : Läkartidningen. - 0023-7205 .- 1652-7518. ; 104:42, s. 3037-3041
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Tidskriftsartikel (refereegranskat)abstract
- Vanliga sjukdomar som allergi, diabetes och cancer är komplexa, dvs de beror på obalans mellan ett stort antal gener och miljöfaktorer, snarare än på enskilda »felande« gener. Det finns teknik för att samtidigt analysera mRNA- och proteinuttryck för alla människans gener. Detta har resulterat i väldiga datamängder, som kan bidra till att öka förståelsen av komplexa sjukdomar. Problemet är att strukturera och tolka informationen.Systembiologi syftar till att konstruera ett teoretiskt ramverk för att beskriva hur molekylära signalvägar och nätverk, snarare än enskilda molekyler, orsakar sjukdom. Detta har börjat ge kliniska resultat, tex individualiserad medicinering vid behandling av cancer.Inom de närmsta decennierna förutspås systembiologisk forskning få klinisk betydelse, inte bara för att individualisera behandling, utan även för att förutsäga eller förebygga sjukdomar. Läkemedelsindustrin gör också stora systembiologiska satsningar för att utveckla nya mediciner.Det är därför angeläget att svenska kliniker, forskare och beslutsfattare snarast tar ställning till hur klinisk systembiologisk forskning ska bedrivas i Sverige.I denna artikel ges en introduktion till nya tekniker för att samtidigt studera människans alla gener. Dessutom beskrivs systembiologiska principer för att tolka resultaten och vilka kliniska konsekvenser detta kan få.
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