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- Agaton, C., et al.
(author)
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Affinity proteomics for systematic protein profiling of chromosome 21 gene products in human tissues
- 2003
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 2, s. 405-
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Journal article (peer-reviewed)abstract
- Here we show that an affinity proteomics strategy using affinity-purified antibodies raised against recombinant human protein fragments can be used for chromosome-wide protein profiling. The approach is based on affinity reagents raised toward bioinformatics-designed protein epitope signature tags corresponding to unique regions of individual gene loci. The genes of human chromosome 21 identified by the genome efforts were investigated, and the success rates for de novo cloning, protein production, and antibody generation were 85, 76, and 56%, respectively. Using human tissue arrays, a systematic profiling of protein expression and subcellular localization was undertaken for the putative gene products. The results suggest that this affinity proteomics strategy can be used to produce a proteome atlas, describing distribution and expression of proteins in normal tissues as well as in common cancers and other forms of diseased tissues.
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| 4. |
- Engström, G, et al.
(author)
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Geographic distribution of stroke incidence within an urban population : relations to socioeconomic circumstances and prevalence of cardiovascular risk factors
- 2001
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In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 32:5, s. 1098-1103
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Geographic differences in stroke incidence indicate a potential for prevention. The present study from the city of Malmö, Sweden, sought to investigate whether incidence of stroke in residential areas is related to prevalence of cardiovascular risk factors and socioeconomic circumstances.METHODS: The Stroke Register in Malmö, Sweden, was used for retrieval of the 3540 patients who suffered a first stroke between 1989 and 1998. The Malmö Diet and Cancer cohort (n=28 466) was used to assess area specific prevalence of hypertension, diabetes, smoking, and being overweight and for computation of a cardiovascular risk score. Socioeconomic circumstances for the 17 administrative areas were expressed in terms of a composite score.RESULTS: Standardized stroke incidence ranged among areas from 437 to 743 per 100 000 for men and from 223 to 518 per 100 000 for women. Socioeconomic score correlated significantly with area-specific stroke rates among men (r=-0.62, P=0.008) and women (r=-0.67, P=0.004). Incidence of stroke was significantly associated with cardiovascular risk score for each area (men, r=0.53, P<0.05; women, r=0.76, P<0.001). The cardiovascular score and the socioeconomic score together accounted for 44% of the geographic variance among men and 63% among women.CONCLUSIONS: Marked differences occurred in stroke incidence among residential areas within this urban population. High-rate areas were characterized by a higher prevalence of smoking, hypertension, diabetes, and being overweight and by inferior socioeconomic circumstances. These risk factors accounted for a substantial proportion of the geographic variance in incidence of stroke.
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| 5. |
- Engström, Gunnar, et al.
(author)
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Long-term effects of inflammation-sensitive plasma proteins and systolic blood pressure on incidence of stroke.
- 2002
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In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 33:12, s. 2744-2749
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Journal article (peer-reviewed)abstract
- Background and Purpose— The present study investigated the relationships between inflammation-sensitive plasma proteins (ISPs) and systolic blood pressure (SBP), as well as the joint long-term effects of ISP and SBP on incidence of stroke. Methods— BP and 5 ISPs (fibrinogen, {alpha}1-antitrypsin, haptoglobin, ceruloplasmin, orosomucoid) were assessed in 6071 healthy men 28 to 61 years of age. All-cause mortality and incidence of stroke were monitored over a mean follow-up of 18.7 years in men defined by SBP (<120, 120 to 139, >=140 mm Hg) and ISP (0 to 1 or 2 to 5 ISPs in the top quartile). Results— SBP and diastolic BP were significantly and positively associated with the number of ISPs in the top quartile. As expected, elevated SBP was associated with an increased incidence of stroke. Among men with SBP >=140 mm Hg, there were, however, significant differences between those with high and low ISP levels. After risk factor adjustment, men with SBP >=140 mm Hg and high ISP levels had a relative risk of stroke of 4.3 (95% CI, 2.3 to 7.8) compared with men with SBP <120 mm Hg and low ISP levels. In the absence of high ISP levels, the risk associated with SBP >=140 was 2.5 (95% CI,1.4 to 4.6). Men with high ISP levels had a significantly increased risk of stroke also after exclusion of the events from the first 10 years of follow-up. Conclusions— High ISP levels are associated with elevated BP. These proteins are associated with an increased risk of stroke among men with high BP and provide information on stroke risk even after many years of follow-up.
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| 6. |
- Engström, Gunnar, et al.
(author)
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Lung function and cardiovascular risk: relationship with inflammation-sensitive plasma proteins.
- 2002
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In: Circulation. - 1524-4539. ; 106:20, s. 2555-2560
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Journal article (peer-reviewed)abstract
- Background— The inverse relationship between pulmonary function and incidence of cardiovascular disease remains largely unexplained. This prospective study explored the hypothesis of a relationship with inflammation-sensitive plasma proteins. Methods and Results— Forced vital capacity (FVC) and plasma levels of fibrinogen, {alpha} 1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 5064 healthy men aged 28 to 61 years. All-cause mortality, cardiovascular mortality, and incidence of myocardial infarction were monitored over a mean follow-up period of 18.4 years. Low FVC (fourth quartile) was associated with higher protein levels and with increased incidences of myocardial infarction and cardiovascular death. Adjustments for protein levels reduced the age-adjusted relative risks (RRs) for myocardial infarction (from 1.99, 95% CI 1.5 to 2.6, to 1.70, 95% CI 1.3 to 2.2) and cardiovascular death (from 2.71, 95% CI 1.9 to 3.9, to 2.28, 95% CI 1.6 to 3.3) among men with low FVC, corresponding to {approx}25% of the excess risk. The risk factor–adjusted RRs were reduced from 1.45 (95% CI 1.1 to 1.9) to 1.38 (95% CI 1.1 to 1.8) and from 1.96 (95% CI 1.4 to 2.8) to 1.85 (95% CI 1.3 to 2.7) for myocardial infarction and cardiovascular death, respectively, corresponding to {approx}10% to 15% of the excess risk. Among men with low FVC, the risk factor–adjusted RR for myocardial infarction was 2.5 (95% CI 1.7 to 3.6) for those with high protein levels (>=2 proteins in top quartile) and 1.7 (95% CI 1.1 to 2.4) for those with low protein levels (<=1 protein in top quartile; reference, top quartile of FVC and low protein levels). Conclusions— FVC is significantly and inversely associated with plasma levels of inflammation-sensitive plasma proteins. This relationship contributes to but cannot fully explain the increased cardiovascular risk among men with low FVC.
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| 7. |
- Engström, Gunnar, et al.
(author)
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Respiratory decline in smokers and ex-smokers--an independent risk factor for cardiovascular disease and death
- 2000
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In: Journal of Cardiovascular Risk. - 1350-6277. ; 7:4, s. 267-272
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVE: Although smoking is associated with an increased incidence of cardiovascular disease and death, many smokers remain healthy after many years of smoking. Our objective was to assess whether this variation is related to rate of decline of respiratory function. DESIGN: This was a population-based cohort study, its subjects being men born in 1914 from Malmo, Sweden. METHODS: All 291 smokers who since the baseline examination in 1969 had remained in Malmo were invited to a follow-up examination in 1982. Of the 242 participants, 199 men without history of myocardial infarction or stroke were included in the study. Eighty-four of them had quit smoking. The incidence of cardiovascular disease and death during 14 years was studied in relation to the decline in lung function [forced expiratory volume during 1 second (FEV1.0) and vital capacity] between 55 and 68 years of age. RESULTS: Fifty-nine (51%) smokers and 43 (51%) ex-smokers died. Forty-four (38%) smokers and 29 (35%) ex-smokers suffered a cardiovascular event. The mortality rate among smokers in the high, middle and low thirds with regard to the decline in FEV1.0 was 66.5, 44.0, and 37.6, respectively, per 1000 person-years (P for trend = 0.04). The corresponding figures in ex-smokers were 88.7, 42.0, and 35.1 (P for trend = 0.002). The cardiovascular event rate among smokers in these three groups was 56.0, 41.0, and 22.7 events, respectively, per 1000 person-years (P for trend = 0.01). The association remained significant after adjustments for potential confounders. A change in vital capacity was associated with a similar pattern of disease and death. CONCLUSION: Although smoking is associated with an accelerated respiratory decline, there are marked differences between smokers. The increased cardiovascular event and death rates among those whose lung function declined the most suggests that the change in respiratory function can be used as a measure of individual susceptibility.
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| 8. |
- Lind, P., et al.
(author)
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Risk of Myocardial Infarction and Stroke in Smokers Is Related to Plasma Levels of Inflammation-Sensitive Proteins.
- 2004
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 24:3, s. 577-582
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Journal article (peer-reviewed)abstract
- Background— The extent to which differences in cardiovascular risk between smokers with similar daily tobacco consumption may be related to plasma levels of inflammation-sensitive proteins (ISP) and whether these proteins are associated with levels of carboxyhemoglobin (COHb%) have not been clarified. Methods and Results— In a population-based cohort of 1489 never smokers, 1685 former smokers, and 2901 current smokers, aged 28 to 61 years, plasma levels of orosomucoid ({alpha}1-acid glycoprotein), {alpha}1-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. COHb% levels were available for 2098 of them. Incidence of myocardial infarction, stroke, and death were monitored over 18.7±4.7 years. The proportion with high ISP levels (ie, >=2 ISP in the top quartile) increased progressively with daily tobacco consumption (P<0.01) and COHb% (P<0.01). In all smoking categories, the incidence of stroke, cardiac events, and death was related to ISP. In heavy smokers, high ISP levels were associated with adjusted relative risks of 1.57 (1.05 to 2.35) and 1.50 (1.11 to 2.03) for cardiac events and death, respectively. Corresponding figures for moderate and light smokers were 1.59 (1.13 to 2.24) and 1.14 (0.87 to 1.49), respectively, and 1.32 (0.95 to 1.85) and 1.48 (1.10 to 1.98), respectively. Conclusion— ISP levels are related to COHb% in smokers. High levels are associated with an increased cardiovascular risk.
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