| 1. |
- Hellquist, Anna, et al.
(författare)
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Variation in STAT4 is associated with systemic lupus erythematosus in a Finnish family cohort
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:5, s. 883-886
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:To investigate if 10 single nucleotide polymorphisms (SNPs) and haplotypes in the STAT4 gene, previously associated with SLE in a Swedish case-control cohort, also are associated with SLE risk in a Finnish SLE family cohort.METHOD: Genotyping was performed in 192 Finnish families, with 237 affected individuals and their healthy relatives, using the SNPstream genotyping system.RESULTS:TDT analysis provided the strongest signal of association for two linked SNPs; rs7582694 (P-value = 0.002, OR = 2.57) and rs10181656 (P-value = 0.001, OR = 2.53). We further performed haplotype association analysis using a sliding window approach which showed that the strongest association signal originates from SNPs in intron 3 of STAT4.CONCLUSION:Our results provide evidence that the main association signal for STAT4 with SLE previously reported in Caucasians is the same in the Finnish population. This is the first study that confirms the association of STAT4 with SLE in a family cohort.
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| 2. |
- Hjältén, Joakim, et al.
(författare)
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Variable responses of natural enemies to Salix triandra phenotypes with different secondary chemistry
- 2007
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Ingår i: Oikos. - : Wiley-Blackwell. - 0030-1299 .- 1600-0706. ; 116:5, s. 751-758
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Tidskriftsartikel (refereegranskat)abstract
- Plant phenotypes often differ in their resistance to natural enemies, but the mechanism for this has seldom been identified. The aim of this study was to determine if the spatial patterns of phenotype use of a highly specialized insect herbivore (the galling sawfly Pontania triandrae) in a natural willow population can be related to phenotypic variation in plant secondary chemistry. Furthermore, we tested if traits that confer resistance to one type of natural enemy, i.e. the galling sawfly, also confer resistance to others, in our case a leaf beetle Gonioctena linnaeana and the rust fungus Melampsora amygdalinae. We identified 18 phenotypes with high and 18 phenotypes with low gall density in our field population and determined gall densities, the degree of leaf damage and rust infection on each phenotype and collected leaves for chemical analyses. The concentration of phenolics was higher in phenotypes with high density of galls suggesting that this galling sawfly may use phenolics as oviposition cues. Rust infection showed the opposite pattern, with lower levels on clones with high concentration of phenolics, while leaf damage by G. linnaeana did not differ between clone types. This indicates that these important natural enemies may assert divergent selection on willow phenotypes and that this might provide a mechanism for maintaining phenotypic variation within willow populations.
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| 3. |
- Julkunen, Petro, et al.
(författare)
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Biomechanical, biochemical and structural correlations in immature and mature rabbit articular cartilage.
- 2009
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Ingår i: Osteoarthritis and Cartilage. - : Saunders Elsevier. - 1063-4584 .- 1522-9653. ; 17:12, s. 1628-1638
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The structure and composition of articular cartilage change during development and growth. These changes lead to alterations in the mechanical properties of cartilage. In the present study, biomechanical, biochemical and structural relationships of articular cartilage during growth and maturation of rabbits are investigated.DESIGN: Articular cartilage specimens from the tibial medial plateaus and femoral medial condyles of female New Zealand white rabbits were collected from seven age-groups; 0 days (n=29), 11 days (n=30), 4 weeks (n=30), 6 weeks (n=30), 3 months (n=24), 6 months (n=24) and 18 months (n=19). The samples underwent mechanical testing under creep indentation. From the mechanical response, instantaneous and equilibrium moduli were determined. Biochemical analyses of tissue collagen, hydroxylysylpyridinoline (HP) and pentosidine (PEN) cross-links in full thickness cartilage samples were conducted. Proteoglycans were investigated depth-wise from the tissue sections by measuring the optical density of Safranin-O-stained samples. Furthermore, depth-wise collagen architecture of articular cartilage was analyzed with polarized light microscopy. Finite element analyses of the samples from different age-groups were conducted to reveal tensile and compressive properties of the fibril network and the matrix of articular cartilage, respectively.RESULTS: Tissue thickness decreased from approximately 3 to approximately 0.5mm until the age of 3 months, while the instantaneous modulus increased with age prior to peak at 4-6 weeks. A lower equilibrium modulus was observed before 3-month-age, after which the equilibrium modulus continued to increase. Collagen fibril orientation angle and parallelism index were inversely related to the instantaneous modulus, tensile fibril modulus and tissue thickness. Collagen content and cross-linking were positively related to the equilibrium compressive properties of the tissue.CONCLUSIONS: During maturation, significant modulation of tissue structure, composition and mechanical properties takes place. Importantly, the present study provides insight into the mechanical, chemical and structural interactions that lead to functional properties of mature articular cartilage.
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| 4. |
- Järvinen, Tiina M., et al.
(författare)
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Polymorphisms of the ITGAM Gene Confer Higher Risk of Discoid Cutaneous Than of Systemic Lupus Erythematosus
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:11, s. e14212-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lupus erythematosus (LE) is a heterogeneous disease ranging from mainly skin-restricted manifestations (discoid LE [DLE] and subacute cutaneous LE) to a progressive multisystem disease (systemic LE [SLE]). Genetic association studies have recently identified several strong susceptibility genes for SLE, including integrin alpha M (ITGAM), also known as CD11b, whereas the genetic background of DLE is less clear. Principal Findings: To specifically investigate whether ITGAM is a susceptibility gene not only for SLE, but also for cutaneous DLE, we genotyped 177 patients with DLE, 85 patients with sporadic SLE, 190 index cases from SLE families and 395 population control individuals from Finland for nine genetic markers at the ITGAM locus. SLE patients were further subdivided by the presence or absence of discoid rash and renal involvement. In addition, 235 Finnish and Swedish patients positive for Ro/SSA-autoantibodies were included in a subphenotype analysis. Analysis of the ITGAM coding variant rs1143679 showed highly significant association to DLE in patients without signs of systemic disease (P-value = 4.73x10(-11), OR = 3.20, 95% CI = 2.23-4.57). Significant association was also detected to SLE patients (P-value = 8.29x10(-6), OR = 2.14, 95% CI = 1.52-3.00), and even stronger association was found when stratifying SLE patients by presence of discoid rash (P-value = 3.59x10(-8), OR = 3.76, 95% CI = 2.29-6.18). Significance: We propose ITGAM as a novel susceptibility gene for cutaneous DLE. The risk effect is independent of systemic involvement and has an even stronger genetic influence on the risk of DLE than of SLE.
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| 5. |
- Kekkonen, Riina-A., et al.
(författare)
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Effect of probiotic Lactobacillus rhamnosus GG intervention on global serum lipidomic profiles in healthy adults
- 2008
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 14:20, s. 3188-3194
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate the effect of three weeks' intervention with a probiotic Lactobacillus rhamnosus GG (LGG) bacteria on global serum lipidomic profiles and evaluate whether the changes in inflammatory variables (CRP, TNF-alpha and IL-6) are reflected in the global lipidomic profiles of healthy adults.METHODS: We performed UPLC/MS-based global lipidomic platform analysis of serum samples (n = 26) in a substudy of a randomised, double-blind, placebo-controlled 3-wk clinical intervention trial investigating the immunomodulatory effects of probiotics in healthy adults.RESULTS: A total of 407 lipids were identified, corresponding to 13 different lipid classes. Serum samples showed decreases in the levels of lysophosphatidylcholines (LysoGPCho), sphingomyelins (SM) and several glycerophosphatidylcholines (GPCho), while triacylglycerols (TAG) were mainly increased in the probiotic LGG group during the intervention. Among the inflammatory variables, IL-6 was moderately associated by changes in global lipidomic profiles, with the top-ranked lipid associated with IL-6 being the proinflammatory LysoGPCho (20:4). There was a weak association between the lipidomic profiles and the two other inflammatory markers, TNF-alpha and CRP.CONCLUSION: This was the first study to investigate the effects of probiotic intervention on global lipidomic profiles in humans. There are indications that probiotic LGG intervention may lead to changes in serum global lipid profiles, as reflected in decreased GPCho, LysoGPCho and SM as well as mainly increased TAG.
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| 6. |
- Lötjönen, Pauno, et al.
(författare)
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Strain-dependent modulation of ultrasound speed in articular cartilage under dynamic compression.
- 2009
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier. - 1879-291X .- 0301-5629. ; 35:7, s. 1177-1184
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical properties of articular cartilage may be determined by means of mechano-acoustic indentation, a clinically feasible technique for cartilage diagnostics. Unfortunately, ultrasound speed varies in articular cartilage during mechanical compression. This can cause significant errors to the measured mechanical parameters. In this study, the strain-dependent variation in ultrasound speed was investigated during dynamic compression. In addition, we estimated errors that were induced by the variation in ultrasound speed on the mechano-acoustically measured elastic properties of the tissue. Further, we validated a computational method to correct these errors. Bovine patellar cartilage samples (n = 7) were tested under unconfined compression. Strain-dependence of ultrasound speed was determined under different compressive strains using an identical strain-rate. In addition, the modulation of ultrasound speed was simulated using the transient compositional and structural changes derived from fibril-reinforced poroviscoelastic (FRPVE) model. Experimentally, instantaneous compressive strain modulated the ultrasound speed (p < 0.05) significantly. The decrease of ultrasound speed was found to change nonlinearly as a function of strain. Immediately after the ramp loading ultrasound speed was found to be changed -0.94%, -1.49%, -1.84%, -1.87%, -1.89% and -2.15% at the strains of 2.4%, 4.9%, 7.3%, 9.7%, 12.1% and 14.4%, respectively. The numerical simulation revealed that the compression-related decrease in ultrasound speed induces significant errors in the mechano-acoustically determined strain (39.7%) and dynamic modulus (72.1%) at small strains, e.g., at 2.4%. However, at higher strains, e.g., at 14.4%, the errors were smaller, i.e., 12.6% for strain and 14.5% for modulus. After the proposed computational correction, errors related to ultrasound speed were decreased. By using the correction, with e.g., 2.4% strain, errors in strain and modulus were decreased from 39.7% to 7.2% and from 72.1% to 35.3%, respectively. The FRPVE model, addressing the changes in fibril orientation and void ratio during compression, showed discrepancy of less than 1% between the predicted and measured ultrasound speed during the ramp compression.
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| 7. |
- Wang, Chuan, et al.
(författare)
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Genes identified in Asian SLE GWASs are also associated with SLE in Caucasian populations
- 2013
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Ingår i: European Journal of Human Genetics. - : Nature Publishing Group: Open Access Hybrid Model Option B. - 1018-4813 .- 1476-5438. ; 21:9, s. 994-999
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies (GWASs) conducted in Asian populations have identified novel risk loci for systemic lupus erythematosus (SLE). Here, we genotyped 10 single-nucleotide polymorphisms (SNPs) in eight such loci and investigated their disease associations in three independent Caucasian SLE case–control cohorts recruited from Sweden, Finland and the United States. The disease associations of the SNPs in ETS1, IKZF1, LRRC18-WDFY4, RASGRP3, SLC15A4, TNIP1 and 16p11.2 were replicated, whereas no solid evidence of association was observed for the 7q11.23 locus in the Caucasian cohorts. SLC15A4 was significantly associated with renal involvement in SLE. The association of TNIP1 was more pronounced in SLE patients with renal and immunological disorder, which is corroborated by two previous studies in Asian cohorts. The effects of all the associated SNPs, either conferring risk for or being protective against SLE, were in the same direction in Caucasians and Asians. The magnitudes of the allelic effects for most of the SNPs were also comparable across different ethnic groups. On the contrary, remarkable differences in allele frequencies between Caucasian and Asian populations were observed for all associated SNPs. In conclusion, most of the novel SLE risk loci identified by GWASs in Asian populations were also associated with SLE in Caucasian populations. We observed both similarities and differences with respect to the effect sizes and risk allele frequencies across ethnicities.
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