| 1. |
- Dand, Nick, et al.
(författare)
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Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling
- 2017
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Ingår i: Human Molecular Genetics. - : OXFORD UNIV PRESS. - 0964-6906 .- 1460-2083. ; 26:21, s. 4301-4313
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.
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| 2. |
- Franke-Stenport, Victoria, et al.
(författare)
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Titanium implants and BMP-7 in bone : an experimental model in the rabbit
- 2003
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Ingår i: Journal of materials science. Materials in medicine. - 0957-4530 .- 1573-4838. ; 14:3, s. 247-254
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluates the effect of rhBMP-7/OP-1 on the osseointegration of commercially pure titanium implants in an experimental implant model in rabbits. Threaded titanium implants with two transverse parallel canals were inserted in the femur and tibia of rabbits. The canals were filled with, 10 microg of BMP-7/collagen carrier, pure collagen carrier or were left empty as a control. The stiffness of the implant fixation was evaluated by Resonance Frequency Analysis (RFA) at baseline and four weeks postoperatively. Percentage of bone ingrowth in the canals was measured on microradiographs. Histomorphometry along the threaded part of the implants was performed on 15 microm thin sections. The results from the RFA demonstrated a higher mean value for the BMP-7 treated implants in the tibia than the carrier treated implants but not compared to the control implants. The control implants in the tibia demonstrated more bone ingrowth in the upper canal than to the carrier or the BMP-7 treated implants. Apart from these differences there were no significant effects of BMP. In this study BMP-7 did not contribute to any substantially improved bone anchorage of titanium implants.
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| 3. |
- Hammar, Mats, et al.
(författare)
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Tibolone and low-dose continuous combined hormone treatment : Vaginal bleeding pattern, efficacy and tolerability
- 2007
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Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 114:12, s. 1522-1529
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy. Design: A randomised, double-blind, double-dummy, group comparative intervention trial. Setting: Multicentre study executed in 32 centres in 7 European countries. Sample: Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years. Methods: Participants were randomised to receive 2.5 mg tibolone or 1 mg 17ß estradiol plus 0.5 mg norethisterone acetate (E 2/NETA) daily for 48 weeks. Main outcome measures: Prevalence of vaginal bleeding, hot flushes and adverse events. Results: The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%, P < 0.001) when compared with the E 2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%, P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%, P < 0.001). Conclusion: Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy. © 2007 The Authors.
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| 4. |
- Henstrom, M., et al.
(författare)
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Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome
- 2018
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucraseisomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p. Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.
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| 5. |
- Kassapidou, Maria, et al.
(författare)
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Inflammatory Response to Cobalt-Chromium Alloys Fabricated With Different Techniques
- 2021
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Ingår i: Journal of Oral & Maxillofacial Research. - : UAB Stilus Optimus. - 2029-283X. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explore the in vitro cytokine expression of human peripheral blood mononuclear cells exposed to cobalt-chromium alloys, manufactured with different techniques, in comparison with commercially pure titanium grade 4 and titanium alloy grade 23.Material and Methods: Peripheral blood mononuclear cells (PBMC) were collected from 10 healthy blood donors and exposed to machine-ground coin-shaped: (a) cobalt-chromium (Co-Cr) specimens (n = 5) manufactured by four techniques, i.e. cast, milled, laser melted and presintered milled; (b) commercially pure titanium grade 4; and (c) titanium alloy grade 23. The cells were cultured for 4, 24 and 72 hours followed by investigations of pro- and anti-inflammatory cytokine release using Bio-Plex Pro (TM).Results: In general, the PBMC produced significantly more cytokines when exposed to the cast and presintered milled Co-Cr materials compared to laser melted, milled Co-Cr and titanium materials.Conclusions: Within the limitation of the present study, it may be suggested that cast and presintered milled cobalt-chromium alloys provoke a stronger inflammatory response compared to milled and laser melted cobalt-chromium alloys and titanium materials.
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