| 1601. |
- Kemmer, D., et al.
(författare)
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Exploring the foundation of genomics : a Northern blot reference set for the comparative analysis of transcript profiling technologies
- 2004
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Ingår i: Comparative and functional genomics. - : Hindawi Limited. - 1531-6912 .- 1532-6268. ; 5:8, s. 584-595
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we aim to create a reference data collection of Northern blot results and demonstrate how such a collection can enable a quantitative comparison of modern expression profiling techniques, a central component of functional genomics studies. Historic ally, Northern blots were the de facto standard for determining RNA transcript levels. However, driven by the demand for analysis of large sets of genes in parallel, high-throughput methods, such as microarrays, dominate modern profiling efforts. To facilitate assessment of these methods, in comparison to Northern blots, we created a database of published Northern results obtained with a standardized commercial multiple tissue blot (dbMTN). In order to demonstrate the utility of the dbMTN collection for technology comparison, we also generated expression profiles for genes across a set of human tissues, using multiple profiling techniques. No method produced profiles that were strongly correlated with the Northern blot data. The highest correlations to the Northern blot data were determined with microarrays for the subset of genes observed to be specifically expressed in a single tissue in the Northern analyses. The database and expression profiling data are available via the project website (http://www.cisreg.ca). We believe that emphasis on multitechnique validation of expression profiles is justified, as the correlation results between platforms are not encouraging on the whole. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat
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| 1602. |
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| 1603. |
- Keskin, Isil, et al.
(författare)
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Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in ALS patients and their relatives
- 2017
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : TAYLOR & FRANCIS LTD. - 2167-8421 .- 2167-9223. ; 18:5-6, s. 457-463
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To characterise stabilities in erythrocytes of mutant SOD1 proteins, compare SOD1 enzymatic activities between patients with different genetic causes of ALS and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations.Methods: Blood samples from 4072 individuals, ALS patients with or without a SOD1 mutation, family members and controls were studied. Erythrocyte SOD1 enzymatic activities normalised to haemoglobin content were determined, and effects of haemoglobin disorders on dismutation assessed. Coding SOD1 sequences were analysed by Sanger sequencing, exon copy number variations by fragment length analysis and by TaqMan Assay.Results: Of the 44 SOD1 mutations found, 75% caused severe destabilisation of the mutant protein but in 25% it was physically stable. Mutations producing structural changes caused halved erythrocyte SOD1 activities. There were no differences in SOD1 activities between patients without a SOD1 mutation and control individuals or carriers of TBK1 mutations and C9orf72(HRE). In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Thalassemias and iron deficiency were associated with increased SOD1 activity/haemoglobin ratios.Conclusion: Adjunct erythrocyte SOD1 activity analysis reliably signals destabilising SOD1 mutations including intronic mutations that are missed by exon sequencing.
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| 1604. |
- Keskin, Isil, 1987-, et al.
(författare)
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Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in erythrocytes in ALS patients and their relatives
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Our objective was to in blood samples from 3723 individuals including ALS patients without a coding SOD1 mutation and 372 control individuals characterize stabilities of mutant SOD1s, compare SOD1 enzymatic activities between patients with different genetic causes of ALS, and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations. Erythrocyte SOD1 enzymatic activities normalized to hemoglobin content were determined. Coding SOD1 sequences were analyzed by Sanger sequencing, copy number variations by fragment length analysis and by TaqMan Assay. Hemoglobin disorders were searched for. Of the 46 SOD1 mutations found, ¾ caused severe destabilization of the mutant protein but in ¼ SOD1 was essentially physically stable. Mutations producing structural changes all caused halved SOD activities. There were no differences in SOD1 activities between controls and patients without any detected SOD1 mutations or patients with C9ORF72HRE or TBK1 mutations. In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Also, no uncommon variants in exon-flanking sequences were detected. Thalassemias and iron deficiency anemia were associated with increased SOD1 activity/hemoglobin ratios. In conclusion, adjunct erythrocyte SOD activity analysis is of value to signal the presence of exon and splice-site-intron mutations that influence the SOD1 structure.
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| 1605. |
- Khalili, Payam, 1977-, et al.
(författare)
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Combined effects of brachial pulse pressure and sialic acid for risk of cardiovascular events during 40 years of follow-up in 37 843 individuals
- 2012
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Ingår i: Journal of Hypertension. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 30:9, s. 1718-1724
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Pulse pressure (PP) is a risk marker for cardiovascular disease (CVD) in individuals 50 years and older. Inflammation is suggested to influence atherosclerosis, but could also increase PP. We aimed to examine the combined effects of PP and the inflammatory marker sialic acid, and their independent roles on CVD risk. Methods: From a population-based study in Sweden between 1962 and 1965, 18 429 men and 19 414 women at the age of 50 or older were selected and followed for first CVD event until 2005. We investigated the biological interactions between sialic acid and PP. The associations of PP and sialic acid with risk of CVD were calculated by using Cox proportional hazards model. Adjustments were made for conventional risk factors, mean arterial pressure (MAP) and socioeconomic status. Results: The mean age was 59.5 (SD 6.5) years and the number of incident CVD events in men and women were 3641 and 3227, respectively. No biological interaction was seen between PP and sialic acid. In men, the adjusted hazard ratio for PP was 0.92 [95% confidence interval (CI) 0.88-0.96, P < 0.0001) for 1 SD of PP, and 1.09 (95% CI 1.05-1.13, P < 0.0001) for 1 SD of sialic acid. In women, the corresponding figures were 1.02 (95% CI 0.97-1.07, P = 0.48) and 1.09 (95% CI 1.05-1.13, P < 0.0001). Conclusions: Sialic acid but not PP was an independent risk factor for CVD. The risk induced by PP is highly affected by MAP. This suggests that both estimated arterial stiffness and inflammation contribute through different pathways to risk of CVD.
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| 1606. |
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| 1607. |
- Khalili, Payam, 1977-
(författare)
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Risk factors for cardiovascular events and incident hospital-treated diabetes in the population
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Well-established risk factors for CVD include increasing age, male sex, sedentary lifestyle, obesity, smoking, diabetes, hypertension, dyslipidaemia and low socio-economic status. Traditional risk factors do, however, not fully explain cardiovascular risk in general. In this thesis we focused on two conventional risk factors (smoking, blood pressure), and two unconventional risk markers (adiponectin, an adipocyte derived protein; and sialic acid (SA), a marker of systemic inflammation) for prediction of CVD events.Aims: In Paper I we examined to what degree smoking habits modify the risk of CVD in relation to systolic blood pressure levels in middle-aged men. In Paper II we investigated the predictive role of adiponectin for risk of CVD as well as the cross-sectional associations between adiponectin and markers of glucose metabolism, also in men. In Paper III we examined if increasing pulse pressure (PP) and increasing levels of SA both increase the risk of CVD and whether their effects act in synergism. In Paper IV the association of SA with risk of incident diabetes mellitus and related complications, resulting in hospitalization, was studied.Subjects and Methods: Two large-scale, population-based, screening studies with long follow-up periods have been used. The Malmö Preventive Project (MPP) was used with 22,444 individuals in Paper I and a sub cohort of 3,885 individuals in Paper II. The Värmland Health Survey (VHS) was used in Papers III and IV with 37,843 and 87,035 individuals, respectively.Results: CVD risk increases with increasing systolic blood pressure levels and this risk is almost doubled in smokers. Total adiponectin level is not associated with increased risk of future CVD but it is inversely associated with markers of glucose metabolism. PP and SA both contribute to risk of future CVD. Adjustment for mean arterial pressure reduces the risk induced by PP. Elevated SA contributes to increased risk of incident diabetes and related complications leading to hospitalization.
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| 1608. |
- Khalili, Payam, 1977-, et al.
(författare)
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Sialic acid and incidence of hospitalization for diabetes and its complications during 40-years of follow-up in a large cohort : The Värmland survey
- 2014
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Ingår i: Primary Care Diabetes. - : Elsevier BV. - 1751-9918 .- 1878-0210. ; 8:4, s. 352-357
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine the association of sialic acid (SA) with first recorded diabetes mellitus-related hospitalization.Methods: From a population-based study in Varmland, Sweden, between 1962 and 1965, 87,035 men and women were selected and followed for first recorded diabetes-related hospitalization until 2005. The association of SA was calculated and stratified for gender by Cox's proportional hazards models. Adjustments were made for conventional risk factors and socioeconomic status. Association analyses were made for comparisons between SA-levels above and below median.Results: The mean age was 47.2 (SD 13.0) years and the total numbers of incident diabetes-related hospitalizations in men and women were 3445 and 3273, respectively. Hazard ratios per one standard deviation of SA were 1.12 (95% CI: 1.08-1.17, p < 0.0001) in men and 1.17 (95% CI: 1.13-1.22, p < 0.0001) in women. Interaction analyses indicated a relatively higher SA-associated risk in women than in men with above median SA levels.Conclusions: In this large population-based cohort followed for more than 40 years, elevated SA, as a marker of systemic inflammation, was independently associated with risk of diabetes and diabetes-related hospitalizations. (C) 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
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| 1609. |
- Khalili, Payam, et al.
(författare)
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Siliac-acid and incidence of hospitalization for diabetes and its complications during 40-years of follow-up in a large cohort : the Värmland survey
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aim To examine the association of sialic acid (SA) with first recorded diabetes mellitus-related hospitalization.Methods From a population-based study in Värmland, Sweden, between 1962 and 1965, 87,035 men and women were selected and followed for first recorded diabetesrelated hospitalization until 2005. The association of SA was calculated and stratified for gender by Cox´s proportional hazards models. Adjustments were made for conventional risk factors and socioeconomic status. Association analyses were made for comparisons between SA-levels above and below median.Results The mean age was 47.2 (SD 13.0) years and the total numbers of incident diabetes-related hospitalizations in men and women were 3445 and 3273, respectively. Hazard ratios per one standard deviation of SA were 1.12 (95% CI: 1.08 to 1.17, p<0.0001) in men and 1.17 (95% CI: 1.13 to 1.22, p<0.0001) in women. Interaction analyses indicated a relatively higher SA-associated risk in women than in men with above median SA levels.Conclusions In this large population-based cohort followed for more than 40 years, elevated SA, as a marker of systemic inflammation, was independently associated with risk of diabetes and diabetes-related hospitalizations.
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| 1610. |
- Khalili, Payam, et al.
(författare)
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Total adiponectin does not predict cardiovascular events in middle-aged men in a prospective, long-term follow-up study
- 2010
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Ingår i: Diabetes & Metabolism. - : Elsevier BV. - 1262-3636 .- 1878-1780. ; 36:2, s. 137-143
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Tidskriftsartikel (refereegranskat)abstract
- Aim. Plasma total adiponectin is a marker of insulin resistance, but its role in predicting cardiovascular events is unclear. We aimed to investigate the role of adiponectin as a predictor of cardiovascular risk in middle-aged men, and to describe the association between adiponectin and glucose metabolism. Methods. In this population-based prospective study of middle-aged men (n=3885), total adiponectin was analyzed. All individuals had undergone an oral glucose tolerance test (OGTTs), and the mean follow-up duration was 27 years. Regression analyses were carried out for indices of glucose metabolism in relation to quintiles (Q1-Q5) of total aliponectin levels. After stratification for smoking or not, the association between total adiponectin and the first incidence of fatal or non-fatal cardiovascular disease (CVD) was analyzed, using Cox's proportional-hazards regression model.Results. In a separate multiple-regression analysis and after adjusting for possible confounders, the relationship between adiponectin levels and markers of glucose metabolism were found to be significant (P<0.05). However, adiponectin did not independently predict the risk of stroke, coronary events, or a combination of these two outcomes.Conclusion. Levels of total plasma adiponectin are not useful for predicting long-term cardiovascular events in middle-aged men, but are strongly associated with glucose metabolism and markers of insulin resistance. (c) 2010 Elsevier Masson SAS. All rights reserved.
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