| 1. |
- Andersson, Niklas, 1970, et al.
(författare)
-
A variant near the interleukin-6 gene is associated with fat mass in Caucasian men
- 2010
-
Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 34:6, s. 1011-9
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.
|
|
| 2. |
- Annerbrink, Kristina, 1974, et al.
(författare)
-
Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid
- 2010
-
Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 179:2, s. 231-234
-
Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin 1 to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
|
|
| 3. |
- Barregård, Lars, 1948, et al.
(författare)
-
Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources.
- 2010
-
Ingår i: Environmental research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 110:1, s. 47-54
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves. OBJECTIVES: To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors. METHODS: Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and cold vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam, fish consumption, and iron stores were evaluated. RESULTS: The median kidney concentrations were 12.9microg/g (wet weight) for cadmium, 0.21microg/g for mercury, and 0.08microg/g for lead. Kidney Cd increased by 3.9microg/g for a 10 year increase in age, and by 3.7microg/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5microg/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed. CONCLUSIONS: In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure.
|
|
| 4. |
- Daborg, Jonny, et al.
(författare)
-
Association of the RAGE G82S polymorphism with Alzheimer's disease
- 2010
-
Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 117:7, s. 861-867
-
Tidskriftsartikel (refereegranskat)abstract
- The receptor for advanced glycation end-products (RAGE) has been implicated in several pathophysiological processes relevant to Alzheimer's disease (AD), including transport and synaptotoxicity of AD-associated amyloid beta (A beta) peptides. A recent Chinese study (Li et al. in J Neural Transm 117:97-104, 2010) suggested an association between the 82S allele of the functional single nucleotide polymorphism (SNP) G82S (rs2070600) in the RAGE-encoding gene AGER and risk of AD. The present study aimed to investigate associations between AGER, AD diagnosis, cognitive scores and cerebrospinal fluid AD biomarkers in a European cohort of 316 neurochemically verified AD cases and 579 controls. Aside from G82S, three additional tag SNPs were analyzed to cover the common genetic variation in AGER. The 82S allele was associated with increased risk of AD (P (c) = 0.04, OR = 2.0, 95% CI 1.2-3.4). There was no genetic interaction between AGER 82S and APOE epsilon 4 in producing increased risk of AD (P = 0.4), and none of the AGER SNPs showed association with A beta(42), T-tau, P-tau(181) or mini-mental state examination scores. The data speak for a weak, but significant effect of AGER on risk of AD.
|
|
| 5. |
- Edén, Arvid, 1975, et al.
(författare)
-
Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.
- 2010
-
Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 26:5, s. 533-40
-
Tidskriftsartikel (refereegranskat)abstract
- Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.
|
|
| 6. |
- Johnson, Mats, 1956, et al.
(författare)
-
Open-label trial of atomoxetine hydrochloride in adults with ADHD.
- 2010
-
Ingår i: Journal of Attention Disorders. - : SAGE Publications. - 1087-0547 .- 1557-1246. ; 13:5, s. 539-545
-
Tidskriftsartikel (refereegranskat)abstract
- Background: While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Methods: Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Results: Ten patients met primary efficacy criteria at 10 weeks. Only one patient completed the whole study. Six patients discontinued before 10 weeks and thirteen at 10 weeks or later, mainly because of side-effects (aggression, depressed mood, raised liver enzymes, thyroid hormones, diastolic blood pressure), decreasing efficacy or non-compliance. Conclusion: Fifty percent responded to treatment, but only one patient (5%) felt sufficient improvement to continue for one year. Dosage may have been too low, and baseline impairment too high, for atomoxetine to have sufficient effect on ADHD symptoms in our group of adults. The majority had few side-effects, but several terminated treatment because of adverse effects.
|
|
| 7. |
- Lindgren, Georg, et al.
(författare)
-
Non-traditional stochastic models for ocean waves
- 2010
-
Ingår i: The European Physical Journal. Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 185, s. 209-224
-
Forskningsöversikt (refereegranskat)abstract
- We present two flexible stochastic models for 2D and 3D ocean waves with potential to reproduce severe and non-homogeneous sea conditions. The first family consists of generalized Lagrange models for the movements of individual water particles. These models can generate crest-trough and front-back statistically asymmetric waves, with the same degree of asymmetry as measured ocean waves. They are still in the Gaussian family and it is possible to calculate different slope distributions exactly from a wave energy spectrum. The second model is a random field model that is generated by a nested stochastic partial differential equation. This model can be adapted to spatially non-homogeneous sea conditions and it can approximate standard wave spectra. One advantage with this model is that Hilbert space approximations can be used to obtain computationally efficient representations with Markov-type properties that facilitate the use of sparse matrix techniques in simulation and estimation.
|
|
| 8. |
- Mossberg, Ann-Kristin, et al.
(författare)
-
HAMLET Interacts with Lipid Membranes and Perturbs Their Structure and Integrity.
- 2010
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:2
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cell membrane interactions rely on lipid bilayer constituents and molecules inserted within the membrane, including specific receptors. HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded alpha-lactalbumin (HLA) and oleic acid that is internalized by tumor cells, suggesting that interactions with the phospholipid bilayer and/or specific receptors may be essential for the tumoricidal effect. This study examined whether HAMLET interacts with artificial membranes and alters membrane structure. METHODOLOGY/PRINCIPAL FINDINGS: We show by surface plasmon resonance that HAMLET binds with high affinity to surface adherent, unilamellar vesicles of lipids with varying acyl chain composition and net charge. Fluorescence imaging revealed that HAMLET accumulates in membranes of vesicles and perturbs their structure, resulting in increased membrane fluidity. Furthermore, HAMLET disrupted membrane integrity at neutral pH and physiological conditions, as shown by fluorophore leakage experiments. These effects did not occur with either native HLA or a constitutively unfolded Cys-Ala HLA mutant (rHLA(all-Ala)). HAMLET also bound to plasma membrane vesicles formed from intact tumor cells, with accumulation in certain membrane areas, but the complex was not internalized by these vesicles or by the synthetic membrane vesicles. CONCLUSIONS/SIGNIFICANCE: The results illustrate the difference in membrane affinity between the fatty acid bound and fatty acid free forms of partially unfolded HLA and suggest that HAMLET engages membranes by a mechanism requiring both the protein and the fatty acid. Furthermore, HAMLET binding alters the morphology of the membrane and compromises its integrity, suggesting that membrane perturbation could be an initial step in inducing cell death.
|
|
| 9. |
- Orlandi, Ivan, et al.
(författare)
-
Sir2-dependent asymmetric segregation of damaged proteins in ubp10 null mutants is independent of genomic silencing.
- 2010
-
Ingår i: Biochimica et Biophysica Acta - Molecular Cell Research. - : Elsevier BV. - 0167-4889. ; 1803:5, s. 630-638
-
Tidskriftsartikel (refereegranskat)abstract
- Carbonylation of proteins is an irreversible oxidative damage that increases during both chronological and replicative yeast aging. In the latter, a spatial protein quality control system that relies on Sir2 is responsible for the asymmetrical damage segregation in the mother cells. Proper localization of Sir2 on chromatin depends on the deubiquitinating enzyme Ubp10, whose loss of function deeply affects the recombination and gene-silencing activities specific to Sir2. Here, we have analyzed the effects of SIR2 and UBP10 inactivations on carbonylated protein patterns obtained in two aging models such as stationary phase cells and size-selected old mother ones. In line with the endogenous situation of higher oxidative stress resulting from UBP10 inactivation, an increase of protein carbonylation has been found in the ubp10Δ stationary phase cells compared with sir2Δ ones. Moreover, Calorie Restriction had a salutary effect for both mutants by reducing carbonylated proteins accumulation. Remarkably, in the replicative aging model, whereas SIR2 inactivation resulted in a failure to establish damage asymmetry, the Sir2-dependent damage inheritance is maintained in the ubp10Δ mutant which copes with the increased oxidative damage by retaining it in the mother cells. This indicates that both Ubp10 and a correct association of Sir2 with the silenced chromatin are not necessary in such a process but also suggests that additional Sir2 activities on non-chromatin substrates are involved in the establishment of damage asymmetry.
|
|
| 10. |
- Sundström, Karin, et al.
(författare)
-
Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix.
- 2010
-
Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755 .- 1055-9965. ; 19:10, s. 2469-78
-
Tidskriftsartikel (refereegranskat)abstract
- The link between squamous cell cervical carcinoma and human papillomavirus (HPV) 16/18 is well established, but the magnitude of the risk association is uncertain and the importance of other high-risk HPV (HRHPV) types is unclear.
|
|
