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- Lindehammer, Sabina, et al.
(författare)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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- Siegbahn, Anna, et al.
(författare)
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Exploration of the active site of beta 4GalT7 : modifications of the aglycon of aromatic xylosides
- 2015
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Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 13:11, s. 3351-3362
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Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans (PGs) are macromolecules that consist of long linear polysaccharides, glycosaminoglycan (GAG) chains, covalently attached to a core protein by the carbohydrate xylose. The biosynthesis of GAG chains is initiated by xylosylation of the core protein followed by galactosylation by the galactosyltransferase beta 4GalT7. Some beta-D-xylosides, such as 2-naphthyl beta-D-xylopyranoside, can induce GAG synthesis by serving as acceptor substrates for beta 4GalT7 and by that also compete with the GAG synthesis on core proteins. Here we present structure-activity relationships for beta 4GalT7 and xylosides with modifications of the aromatic aglycon, using enzymatic assays, cell studies, and molecular docking simulations. The results show that the aglycons reside on the outside of the active site of the enzyme and that quite bulky aglycons are accepted. By separating the aromatic aglycon from the xylose moiety by linkers, a trend towards increased galactosylation with increased linker length is observed. The galactosylation is influenced by the identity and position of substituents in the aromatic framework, and generally, only xylosides with beta-glycosidic linkages function as good substrates for beta 4GalT7. We also show that the galactosylation ability of a xyloside is increased by replacing the anomeric oxygen with sulfur, but decreased by replacing it with carbon. Finally, we propose that reaction kinetics of galactosylation by beta 4GalT7 is dependent on subtle differences in orientation of the xylose moiety.
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- Siegbahn, Anna, et al.
(författare)
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Exploration of the active site of β4GalT7: modifications of the aglycon of aromatic xylosides.
- 2015
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Ingår i: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0539 .- 1477-0520. ; 13:11, s. 3351-3362
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Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans (PGs) are macromolecules that consist of long linear polysaccharides, glycosaminoglycan (GAG) chains, covalently attached to a core protein by the carbohydrate xylose. The biosynthesis of GAG chains is initiated by xylosylation of the core protein followed by galactosylation by the galactosyltransferase β4GalT7. Some β-d-xylosides, such as 2-naphthyl β-d-xylopyranoside, can induce GAG synthesis by serving as acceptor substrates for β4GalT7 and by that also compete with the GAG synthesis on core proteins. Here we present structure-activity relationships for β4GalT7 and xylosides with modifications of the aromatic aglycon, using enzymatic assays, cell studies, and molecular docking simulations. The results show that the aglycons reside on the outside of the active site of the enzyme and that quite bulky aglycons are accepted. By separating the aromatic aglycon from the xylose moiety by linkers, a trend towards increased galactosylation with increased linker length is observed. The galactosylation is influenced by the identity and position of substituents in the aromatic framework, and generally, only xylosides with β-glycosidic linkages function as good substrates for β4GalT7. We also show that the galactosylation ability of a xyloside is increased by replacing the anomeric oxygen with sulfur, but decreased by replacing it with carbon. Finally, we propose that reaction kinetics of galactosylation by β4GalT7 is dependent on subtle differences in orientation of the xylose moiety.
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- Sigurdardottir, Gunnthorunn, et al.
(författare)
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Systemic treatment and narrowband ultraviolet B differentially affect cardiovascular risk markers in psoriasis.
- 2014
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Ingår i: The Journal of American Academy of Dermatology. - : Elsevier. - 0190-9622 .- 1097-6787. ; 70:6, s. 1067-1075
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psoriasis is associated with a systemic inflammation and an increased frequency of the metabolic syndrome, both of which are believed to link psoriasis to an increased risk of cardiovascular disease.OBJECTIVE: The study aimed to investigate the systemic expression of markers of cardiovascular risk and determine their response to ultraviolet B therapy and treatment with the tumor necrosis factor-alfa inhibitor, etanercept.METHODS: Six markers of cardiovascular risk were measured in 28 patients with psoriasis and 28 control subjects.RESULTS: Five of the 6 investigated markers were elevated in patients with psoriasis. Four of these correlated to the body mass index and waist-hip ratio, suggesting a link to the metabolic syndrome. Total plasminogen activator inhibitor-1 remained elevated independently of these factors. The levels of the investigated risk markers decreased considerably after tumor necrosis factor-alfa inhibitor treatment but remained unaffected by ultraviolet therapy.LIMITATIONS: A relatively limited study population and nonrandomization are limitations.CONCLUSION: These findings suggest that the choice of treatment in psoriasis may influence the cardiovascular risk in patients with psoriasis and the metabolic syndrome.
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