| 1. |
- Ge, Changrong P, et al.
(författare)
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Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage
- 2017
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Ingår i: JCI INSIGHT. - : AMER SOC CLINICAL INVESTIGATION INC. - 2379-3708. ; 2:13
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Tidskriftsartikel (refereegranskat)abstract
- Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.
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| 2. |
- Kaprio, J, et al.
(författare)
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The Older Finnish Twin Cohort - 45 Years of Follow-up
- 2019
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 22:4, s. 240-254
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Tidskriftsartikel (refereegranskat)abstract
- The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.
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| 3. |
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| 4. |
- Virtanen, KA, et al.
(författare)
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Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects
- 2003
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:2, s. 283-290
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the effects of rosiglitazone (4 mg b.i.d.) and metformin (1 g b.i.d.) monotherapy for 26 weeks on adipose tissue insulin-stimulated glucose uptake in patients (n = 41) with type 2 diabetes. Before and after the treatment, glucose uptake was measured using 2-[18F]fluoro-2-deoxyglucose and positron emission tomography and adipose tissue masses were quantified using magnetic resonance imaging. Rosiglitazone improved insulin-stimulated whole-body glucose uptake by 44% (P < 0.01 vs. placebo). Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2.0 kg in the metformin group (P < 0.05 vs. placebo). In visceral adipose tissue, glucose uptake increased by 29% (from 17.8 ± 2.0 to 23.0 ± 2.6 μmol · kg−1 · min−1, P < 0.05 vs. placebo) in the rosiglitazone group but to a lesser extent (17%) in the metformin group (from 16.2 ± 1.5 to 18.9 ± 1.7 μmol · kg−1 · min−1, P < 0.05 vs. baseline). Because the visceral adipose tissue mass simultaneously decreased with both treatments (P < 0.05), no change was observed in total visceral glucose uptake per depot. Rosiglitazone significantly enhanced glucose uptake in the femoral subcutaneous area, either when expressed per tissue mass (from 10.8 ± 1.2 to 17.1 ± 1.7 μmol · kg−1 · min−1, P < 0.01 vs. placebo) or per whole-fat depot (P < 0.05 vs. placebo). In conclusion, metformin treatment resulted in improvement of glycemic control without enhancement of peripheral insulin sensitivity. The improved insulin sensitivity of the nonabdominal subcutaneous adipose tissue during treatment with rosiglitazone partly explains the enhanced whole-body insulin sensitivity and underlies the central role of adipose tissue for action of peroxisome proliferator-activated receptor γ agonist in vivo.
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| 5. |
- Hagg, S, et al.
(författare)
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Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
- 2017
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:4, s. e1100-
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Tidskriftsartikel (refereegranskat)abstract
- The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=−0.053; 95% CI: −0.087, −0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10−5), whereas carriers performed better in STROOP (β=−0.074; 95% CI: −0.140, −0.009; P=0.03). Causal associations were found for STROOP only (β=−0.598 per s.d.-increase of TL; 95% CI: −1.125, −0.072; P=0.026), with a larger effect in ɛ4-carriers (β=−0.699; 95% CI: −1.330, −0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.
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| 6. |
- Hallsten, K, et al.
(författare)
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Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:12, s. 3479-3485
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Tidskriftsartikel (refereegranskat)abstract
- Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone (P < 0.05) and metformin (P < 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% (P < 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% (P < 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1) improves insulin responsiveness in resting skeletal muscle and 2) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise.
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| 7. |
- Hannukainen, J, et al.
(författare)
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In Vivo Measurements of Glucose Uptake in Human Achilles Tendon During Different Exercise Intensities
- 2005
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Ingår i: International Journal of Sports Medicine. - : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 26, s. 727-731
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Tidskriftsartikel (refereegranskat)abstract
- Muscular contraction and loading of adjacent tendons has been demonstrated to cause increased blood flow and metabolic activity in the peritendinous region. However, it is poorly known to what extent the human tendon itself takes up glucose during exercise. Thus, the purpose of this study was to measure tendon glucose uptake with increasing exercise intensity and to compare it to muscle glucose uptake at the same intensities. Eight young men were examined on three separate days during which they performed 35 min of cycling at 30, 55 and 75 % of VO2max, respectively. Glucose uptake was measured directly by positron emission tomography (PET) with 2-[ (18)F]fluoro-2-deoxyglucose ([18F]FDG). [18F]FDG was injected after 10 min of exercise that was continued for a further 25 min after the injection. PET scanning of the thigh and Achilles region was performed after the exercise. Glucose uptake of the Achilles tendon (AT) remained unchanged (7.1 +/- 1.5, 6.6 +/- 1.1, and 6.0 +/- 1.1 micromol.kg(-1).min(-1)) with the increasing workload, although the glucose uptake in m. quadriceps femoris simultaneously clearly increased (48 +/- 35, 120 +/- 35, and 152 +/- 74 micromol.kg(-1).min(-1), p < 0.05). In conclusion, the AT takes up glucose during exercise but in significantly smaller amounts than the skeletal muscle does. Furthermore, glucose uptake in the AT is not increased with the increasing exercise intensity. This may be partly explained by the cycle ergometry exercise used in the present study, which probably causes only a little increase in strain to the AT with increasing exercise intensity.
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| 8. |
- Nygård, K., et al.
(författare)
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ForMAX – a beamline for multiscale and multimodal structural characterization of hierarchical materials
- 2024
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Ingår i: Journal of Synchrotron Radiation. - : International Union of Crystallography (IUCr). - 0909-0495 .- 1600-5775. ; 31:Pt 2, s. 363-377
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Tidskriftsartikel (refereegranskat)abstract
- The ForMAX beamline at the MAX IV Laboratory provides multiscale and multimodal structural characterization of hierarchical materials in the nanometre to millimetre range by combining small- and wide-angle X-ray scattering with full-field microtomography. The modular design of the beamline is optimized for easy switching between different experimental modalities. The beamline has a special focus on the development of novel fibrous materials from forest resources, but it is also well suited for studies within, for example, food science and biomedical research.
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| 9. |
- Orava, J., et al.
(författare)
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Blunted Metabolic Responses to Cold and Insulin Stimulation in Brown Adipose Tissue of Obese Humans
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 21:11, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. Design and Methods: Using positron emission tomography (PET), cold-and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans were quantified. Further, cold-induced glucose uptake was measured in obese subjects before and after a 5-month conventional weight loss. Results: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. Conclusions: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.
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| 10. |
- Amm, O., Janhunen, P., Kauristie, K., Opgenoorth, H.J., Pulkkinen, T.I. and Viljanen, A.
(författare)
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Mesoscale ionospheric electrodynamics observed with the MIRACLE network: 1. Analysis of a pseudobreakup spiral.
- 2001
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Ingår i: Journal of Geophysical Research. ; 106:111, s. 24675-24690
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Tidskriftsartikel (refereegranskat)abstract
- A short-lived auroral spiral is observed on February 3, 1999, around 2204 UT, using the Multi-Instrument Array for Ionosphere-Magnetosphere Coupling Studies (MIRACLE) network of ground-based instruments in Fennoscandia, which consists of magnetometers, co
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