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1.
  • Ahlström-Emanuelsson, Cecilia, et al. (author)
  • Effects of topical formoterol alone and in combination with budesonide in a pollen season model of allergic rhinitis.
  • 2007
  • In: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 101:6, s. 1106-1112
  • Journal article (peer-reviewed)abstract
    • Background: beta(2)-Agonists may exert mast cell stabilizing and anti-plasma exudation effects. White available data suggest no or only marginal effects of beta(2)-agonists on symptoms of allergic rhinitis, little is known about whether these drugs may add to the efficacy of anti-rhinitis drugs. Objective: To examine effects of a beta(2)-agonist, alone and in combination with an intranasal glucocorticosteroid, on symptoms and signs of allergic rhinitis. Methods: Patients were examined in a pollen season model. Budesonide 64 mu g, alone and in combination with formoterot 9 mu g, as well as formoterot 9 mu g alone was given in a placebo-controlled and crossover design. After 7 days of treatment, the patients received allergen challenges for 7 days. Symptoms and nasal peak inspiratory flow (PIF) were recorded. Nasal lavages with and without histamine were carried out at the end of each challenge series. These lavages were analysed for tryptase, eosinophil cationic protein (ECP), and alpha(2)-macroglobutin as indices of mast cell activity, eosinophil activity, and plasma exudation, respectively. Results: Budesonide reduced symptoms of allergic rhinitis and improved nasal PIF in the morning, in the evening as well as post allergen challenge. Formoterol alone did not affect symptoms or nasal PIF and did not affect the efficacy of budesonide. Tryptase, ECP, and alpha(2)-macroglobutin were significantly reduced by budesonide. Formoterol alone did not affect these indices and did not affect the anti-inflammatory effect of budesonide. Conclusion: The present dose of formoterot does not affect symptoms and inflammatory signs of allergic rhinitis and does not add to the efficacy of topical budesonide.
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3.
  • Dencker, Magnus, et al. (author)
  • Aerobic fitness related to cardiovascular risk factors in young children.
  • 2012
  • In: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 1432-1076 .- 0340-6199. ; 171:4, s. 705-710
  • Journal article (peer-reviewed)abstract
    • Low aerobic fitness (maximum oxygen uptake (VO(2PEAK))) is predictive for poor health in adults. In a cross-sectional study, we assessed if VO(2PEAK) is related to a composite risk factor score for cardiovascular disease (CVD) in 243 children (136 boys and 107 girls) aged 8 to 11 years. VO(2PEAK) was assessed by indirect calorimetry during a maximal exercise test and scaled by body mass (milliliters per minute per kilogram). Total body fat mass (TBF) and abdominal fat mass (AFM) were measured by Dual-energy X-ray absorptiometry. Total body fat was expressed as a percentage of total body mass (BF%) and body fat distribution as AFM/TBF. Systolic and diastolic blood pressure (SDP and DBP) and resting heart rate (RHR) were measured. The mean artery pressure (MAP) and pulse pressure (PP) were calculated. Echocardiography, 2D-guided M-mode, was performed. Left atrial diameter (LA) was measured and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z scores (value for the individual - mean value for group)/SD were calculated by sex. The sum of z scores for DBP, SDP, PP, MAP, RHR, LVM, LA, RWT, BF%, AFM and AFM/TBF were calculated in boys and girls, separately, and used as composite risk factor score for CVD. Pearson correlation revealed significant associations between VO(2PEAK) and composite risk factor score in both boys (r = -0.48 P < 0.05) and in girls (r = -0.42, P < 0.05). One-way ANOVA analysis indicated significant differences in composite risk factor score between the different quartiles of VO(2PEAK) (P < 0.001); thus, higher VO(2PEAK) was associated with lower composite risk factor score for CVD. In conclusion, low VO(2PEAK) is associated with an elevated composite risk factor score for CVD in both young boys and girls.
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4.
  • Dencker, Magnus, et al. (author)
  • BMI and objectively measured body fat and body fat distribution in prepubertal children.
  • 2007
  • In: Clinical Physiology and Functional Imaging. - 1475-0961. ; 27:1, s. 12-16
  • Journal article (peer-reviewed)abstract
    • Background Body Mass Index (BMI) is often used as a surrogate estimate of body fat in epidemiological studies. This study explores the association between BMI, body fat and body fat distribution assessed by Dual-Energy X-Ray Absorptiometry (DXA) in younger children. Methods Cross-sectional study of 246 children (138 boys and 108 girls) aged 8-11 years. DXA was used to quantify abdominal fat mass (AFM), total body fat (TBF) and also total body fat as percentage of total body mass (BF%). Body fat distribution was calculated as AFM/TBF. Results We found close correlations between BMI vs. TBF, BF% and AFM (r = 0.94, r = 0.92 and r = 0.93) for boys and (r = 0.95, r = 0.92 and r = 0.95) for girls, respectively (P < 0.05 for all r-values). However, significantly lower correlation (P < 0.001 for difference between the r-values) existed for body fat distribution (r = 0.64 for boys and 0.73 for girls). Conclusion Percentage body fat, TBF and AFM were all closely associated with BMI, suggesting that BMI serves as a good surrogate marker for obesity in population studies. However, a significantly lower correlation existed for BMI vs. body fat distribution, which may be a limitation when BMI is used to study cardiovascular risk factors in epidemiological studies.
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5.
  • Dencker, Magnus, et al. (author)
  • Body Fat, Abdominal Fat, and Body Fat Distribution Is Related to Left Atrial Diameter in Young Children.
  • 2012
  • In: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 20, s. 1104-1108
  • Journal article (peer-reviewed)abstract
    • In adults, the size of the left atria (LA) has important prognostic information. In obese adults, adolescents and children enlargement of LA have been observed. This has not been investigated on a population-based level in young children. We therefore assessed if total body fat mass (TBF), abdominal fat, and body fat distribution were related to LA diameter. Cross-sectional study of 244 children (boys = 137 and girls n = 107) aged 8-11 years, recruited from an urban population-based cohort. Dual-energy X-ray absorptiometry (DXA) measured total lean body mass, TBF, and abdominal fat mass (AFM). Body fat was also calculated as a percentage of body mass (BF%). Body fat distribution (AFM/TBF) was calculated. Echocardiography was performed with two-dimensional guided M-mode. LA diameter was measured and left ventricular mass (LVM) was calculated. Systolic blood pressure and diastolic blood pressure were measured and maturity assessed according to Tanner. There were significant (P < 0.05) univariate correlations for all children between TBF (r = 0.40), BF% (r = 0.32), AFM (r = 0.41), and AFM/TBF (r = 0.41) vs. LA diameter. Multiple regression analyses with the inclusion of possible confounders such as lean body mass, blood pressure, gender, age, and Tanner stage revealed that TBF, AFM, and AFM/TBF were all independently related to LA diameter. Differences in the different body fat measurements explained 6-9% of the variance in LA size. These results demonstrated that both total body fat, AFM, and body fat distribution are already at a young age negatively and independently associated to LA diameter.
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6.
  • Dencker, Magnus, et al. (author)
  • Body fat, abdominal fat and body fat distribution related to cardiovascular risk factors in pre-pubertal children.
  • 2012
  • In: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 101:8
  • Journal article (peer-reviewed)abstract
    • Aim We analysed whether total body fat, abdominal fat and body fat distribution are associated with higher composite risk factor scores for cardiovascular disease (CVD) in young children. Methods Cross-sectional study of 238 children aged 8-11 years. Total body fat (TBF) and abdominal fat mass (AFM) were measured by DXA. TBF was expressed as a percentage of body weight (BF%). Body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO(2PEAK) ), systolic and diastolic blood pressure (SBP, DBP), and resting heart rate (RHR) were measured. Mean artery pressure (MAP) and pulse pressure (PP) were calculated. Left atrial diameter (LA) was measured, and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z-scores were calculated. Sum of z-scores for SBP, DBP, MAP, PP, RHR, LVM, LA, RWT, and -VO(2PEAK) were calculated in boys and girls, separately, and used as composite risk factor score. Results Pearson correlations between ln BF%, ln AFM and AFM/TBF versus composite risk factor score for boys were r=0.56, r=0.59, and r=0.48, all P<0.001, and for girls r=0.45, r=0.50, and r=0.48, all P<0.001. Conclusion Total body fat, abdominal fat and body fat distribution were all associated with higher composite risk factor scores for CVD in young children. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.
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7.
  • Dencker, Magnus, et al. (author)
  • Body fat, abdominal fat and body fat distribution related to VO(2PEAK) in young children.
  • 2011
  • In: International Journal of Pediatric Obesity. - : Informa UK Limited. - 1747-7174 .- 1747-7166. ; 6:2-2, s. 597-602
  • Journal article (peer-reviewed)abstract
    • Abstract Objective. Aerobic fitness, defined as maximum oxygen uptake (VO(2PEAK)), and body fat measurements represent two known risk factors for disease. The purpose of this study was to investigate the relationship between VO(2PEAK) and body fat measurements in young children at a population-based level. Methods. Cross-sectional study of 225 children (128 boys and 97 girls) aged 8-11 years, recruited from a population-based cohort. Total lean body mass (LBM), total fat mass (TBF), and abdominal fat mass (AFM) were measured by dual-energy x-ray absorptiometry. Body fat was also calculated as a percentage of body mass (BF%) and body fat distribution as AFM/TBF. VO(2PEAK) was assessed by indirect calorimetry during maximal exercise test. Results. Significant relationships existed between body fat measurements and VO(2PEAK) in both boys and girls, with Pearson correlation coefficients for absolute values of VO(2PEAK) (0.22-0.36, P< 0.05), and for VO(2PEAK) scaled by body mass (-0.38 - -0.70, P<0.05). No relationships were detected for VO(2PEAK) scaled to LBM (-0.17-0.04, all not significant). Boys and girls in the lowest quartile according to body fat measurements had higher absolute values of VO(2PEAK) and lower values of VO(2PEAK) scaled by body mass, compared with those in the highest quartile. No differences were found for VO(2PEAK) scaled to LBM. Conclusions. Our findings document the coexistence of two known risk factors for disease at a young age and confirms that VO(2PEAK) was scaled to LBM may be a better, body fat independent way of expressing fitness.
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8.
  • Dencker, Magnus, et al. (author)
  • Body fat related to daily physical activity and insulin concentrations in non-diabetic children.
  • 2008
  • In: Clinical Physiology and Functional Imaging. - 1475-0961. ; 28, s. 211-215
  • Journal article (peer-reviewed)abstract
    • This study explored the associations between body fat versus daily physical activity and insulin concentrations in non-diabetic young children in a cross-sectional study of 172 children (93 boys and 79 girls) aged 8-11 years. Blood samples were analysed for serum insulin and daily physical activity was measured by accelerometers. Time spent performing vigorous activity was estimated from accelerometer data by using established cut-off points. Dual-energy x-ray absorptiometry (DXA) was used to quantify abdominal fat mass (AFM) and total body fat (TBF), also calculated as percentage of body weight (BF%). Body fat distribution was calculated as AFM/TBF. Body fat distribution was independently linked to both insulin concentrations and physical activity. In contrast, TBF, AFM, and BF% were linked to physical activity only and not to insulin concentrations. In conclusion in this population of non-diabetic children, body fat distribution was independently associated with increased concentrations of insulin and deceased amount of vigorous activity per day. Also, AFM, TBF, and BF% were independently related to minutes of vigorous activity per day.
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9.
  • Dencker, Magnus, et al. (author)
  • Cystatin B, cathepsin L and D related to surrogate markers for cardiovascular disease in children
  • 2017
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:11
  • Journal article (peer-reviewed)abstract
    • Objective: This study investigated potential associations between novel biomarkers for cardiovascular disease and other surrogate markers for health. Methods: Community sample of 170 (92 boys and 78 girls) children aged 8–11 years. Total fat mass (TBF) and abdominal fat (AFM) were measured by Dual-energy x-ray absorptiometry (DXA). Total body fat was also expressed as percentage of total body mass (BF%), and body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO2PEAK), systolic and diastolic blood pressure (SBP and DBP) and pulse pressure (PP) were measured. Echocardiography was performed. Left atrial size (LA) and left ventricular mass (LVM) were measured. A follow-up DXA scan was available in 152 children (84 boys and 68 girls). Frozen serum samples were analyzed for cystatin B, cathepsin L and cathepsin D. Results: Partial correlations between cystatin B versus lnTBF, lnBF%, lnAFM, AFM/TBF, VO2PEAK and PP were; r = 0.38, 0.36, 0.38, 0.29, -0.25 and 0.25, P = 0.001 or less for all. Weaker predominantly non-significant correlations were found for cathepsin L, whereas cathepsin D was not related to any surrogate markers for health. No significant correlations were found between biomarkers and change in body fat over 2 years. Conclusion: Findings from this community-based cohort of young children show that surrogate markers for cardiovascular disease such as total fat mass, percent body fat, abdominal fat, body fat distribution, maximal oxygen uptake and pulse pressure were all associated with cystatin B. This was not found for cathepsin L or cathepsin D.
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10.
  • Dencker, Magnus, et al. (author)
  • Daily physical activity and its relation to aerobic fitness in children aged 8-11 years.
  • 2006
  • In: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 96:5, s. 587-592
  • Journal article (peer-reviewed)abstract
    • A positive relationship between daily physical activity and aerobic fitness exists in adults. Studies in children have given conflicting results, possibly because of differences in methods used to assess daily physical activity and fitness. No study regarding daily physical activity and fitness in children has been published, where fitness has been assessed by direct measurement of maximum oxygen uptake and related to daily physical activity intensities by accelerometers. We examined 248 children (140 boys and 108 girls), aged 7.9-11.1 years. Maximum workload and maximal oxygen uptake (VO2PEAK) by indirect calorimetry were measured during a maximum bicycle ergometer exercise test. Exercise capacity was adjusted for body mass and (body mass)(2/3). Daily physical activity was evaluated by accelerometers, worn around the waist for 4 days. Mean accelerometer counts and time spent in vigorous physical activity were calculated. VO2PEAK was correlated with mean accelerometer counts (r=0.23 for boys and r=0.23 for girls, both P < 0.05), but somewhat better with time spent in vigorous activity (r=0.32 for boys, r=0.30 for girls, both P < 0.05). All results remained virtually the same regardless of the method used to adjust for differences in body size.
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11.
  • Dencker, Magnus, et al. (author)
  • Galectin-3 levels relate in children to total body fat, abdominal fat, body fat distribution, and cardiac size
  • 2018
  • In: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 0340-6199 .- 1432-1076. ; 177:3, s. 461-467
  • Journal article (peer-reviewed)abstract
    • Galectin-3 has recently been proposed as a novel biomarker for cardiovascular disease in adults. The purpose of this investigation was to assess relationships between galectin-3 levels and total body fat, abdominal fat, body fat distribution, aerobic fitness, blood pressure, left ventricular mass, left atrial size, and increase in body fat over a 2-year period in a population-based sample of children. Our study included 170 children aged 8–11 years. Total fat mass and abdominal fat were measured by dual-energy x-ray absorptiometry (DXA). Body fat distribution was expressed as abdominal fat/total fat mass. Maximal oxygen uptake was assessed by indirect calorimetry during a maximal exercise test and scaled to body mass. Systolic and diastolic blood pressure and pulse pressure were measured. Left atrial size, left ventricular mass, and relative wall thickness were measured by echocardiography. Frozen serum samples were analyzed for galectin-3 by the Proximity Extension Assay technique. A follow-up DXA scan was performed in 152 children 2 years after the baseline exam. Partial correlations, with adjustment for sex and age, between galectin-3 versus body fat measurements indicated weak to moderate relationships. Moreover, left atrial size, left ventricular mass, and relative wall thickness and pulse pressure were also correlated with galectin-3. Neither systolic blood pressure nor maximal oxygen uptake was correlated with galectin-3. There was also a correlation between galectin-3 and increase in total body fat over 2 years, while no such correlations were found for the other fat measurements. Conclusion: More body fat and abdominal fat, more abdominal body fat distribution, more left ventricular mass, and increased left atrial size were all associated with higher levels of galectin-3. Increase in total body fat over 2 years was also associated with higher levels of galectin-3.(Table presented.)
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12.
  • Dencker, Magnus, et al. (author)
  • Gender differences and determinants of aerobic fitness in children aged 8-11 years.
  • 2007
  • In: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 99, s. 19-26
  • Journal article (peer-reviewed)abstract
    • Previous studies of gender differences in maximum oxygen uptake have come to different conclusions. Limited data exists where the determinants of maximum oxygen uptake have been evaluated in a comprehensive manner. Thus, we examined 248 children (140 boys and 108 girls), aged 7.9-11.1 years. Body composition was determined by dual-energy X-ray absorptiometry, measured variables were total body fat (TBF) and lean body mass (LBM). Maximal oxygen uptake (VO2peak) was measured by indirect calorimetry during a maximal cycle exercise test. Daily physical activity was assessed by accelerometers and duration of vigorous activity per day (VPA) was calculated. Left ventricular inner diastolic diameter (LVDD) was measured by echocardiography. Lung function was evaluated with spirometric testing and whole body plethysmography. Boys had between 8 and 18% higher values than girls for VO2peak, dependent upon whether VO2peak was expressed in absolute values or scaled to body mass, LBM or if allometric scaling was used. In multiple regression analysis absolute values of aerobic fitness were independently related to LBM, maximal heart rate (Max HR), gender, LVDD, and VPA. Furthermore, when VO2peak was scaled to body mass it was independently related to In TBF, Max HR, gender, VPA, and LVDD. Lung function had no relation to VO2peak. Our study concludes that body composition is the main predictor for VO2peak, in children aged 8-11 years, whereas VPA or LVDD has only a modest impact. Existing gender differences in VO2peak cannot be explained only by differences in body composition, physical activity, or heart size.
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13.
  • Dencker, Magnus, et al. (author)
  • Total body fat, abdominal fat, body fat distribution and surrogate markers for health related to adipocyte fatty acid-binding protein (FABP4) in children
  • 2017
  • In: Journal of Pediatric Endocrinology and Metabolism. - : Walter de Gruyter GmbH. - 0334-018X .- 2191-0251. ; 30:4, s. 375-382
  • Journal article (peer-reviewed)abstract
    • The aim of the study was to assess possible relationships between adipocyte fatty acid-binding protein (FABP4) and total body fat (TBF), abdominal fat, body fat distribution, aerobic fitness, blood pressure, cardiac dimensions and the increase in body fat over 2 years in a community sample of children. A cross-sectional study was used in a community sample of 170 (92 boys and 78 girls) children aged 8-11 years. TBF and abdominal fat (AFM) were measured by dual-energy X-ray absorptiometry (DXA). TBF was also expressed as percentage of total body mass (BF%), and body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO2PEAK) was assessed by indirect calorimetry during a maximal exercise test and scaled to body mass. Systolic and diastolic blood pressure (SBP and DBP) and pulse pressure (PP) were measured. Echocardiography was performed. Left atrial (LA) size was measured, and left ventricular mass (LVM) was calculated. A follow-up DXA scan was available in 152 children (84 boys and 68 girls). Frozen serum samples were analyzed for FABP4. Partial correlations, with adjustment for sex, between FABP4 vs. ln TBF, ln BF%, ln AFM, AFM/TBF and VO2PEAK were (r=0.69, 0.68, 0.69, 0.49 and -0.39, p<0.05 for all). Moreover, SBP, PP, LVM and LA were also weakly correlated with FABP4 (r=0.23, 0.22, 0.28 and 0.21, p<0.05 for all). Correlations between FABP4 vs. increase in TBF and AFM over 2 years were 0.29 and 0.26, p<0.05, for both. (Increase in percent body fat or change in fat distribution were not correlated.) Findings from this community-based cohort of young children show that increased body fat and abdominal fat, more abdominal body fat distribution, low fitness, more LVM and increased LA, increased SBP and PP were all associated with increased levels of FABP4. Increase in TBF and abdominal fat over 2 years were also associated with increased levels of FABP4.
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14.
  • Dencker, Magnus, et al. (author)
  • Tracking of Physical Activity with Accelerometers Over a Two-year Time Period.
  • 2013
  • In: Journal of Physical Activity & Health. - 1543-5474. ; 10:2, s. 241-248
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Limited data exists of tracking and changes in accelerometer measured physical activity in children. METHODS: Physical activity was assessed by accelerometers for four days in 167 children (boys n=90, girls n=77), aged 9.8±0.6 years. Follow-up measurement was made 2.0±0.1 yrs later (range 1.9-2.1 yrs). General physical activity (GPA) was defined as mean count/minute. Minutes of inactivity, light- moderate- and vigorous physical activity (LMVPA), moderate and vigorous physical activity (MVPA) and vigorous physical activity (VPA) per day were calculated both as absolute values and as percentage of total registration time. RESULTS: Spearman rank order correlation indicated low tracking of MVPA and VPA in girls (r=0.25-0.33, P<0.05), and low-moderate tracking of GPA, inactivity, LMVPA, MVPA and VPA in boys (r=0.23-0.40, P<0.05). Time in inactivity increased at follow-up by 5-14%. Most of the assessed physical activity variables were decreased at follow-up by 6-30%. CONCLUSIONS: Physical activity tracks at a low-moderate degree from age 10 to age 12 years, which confirm previous investigations that have used self-report assessments. The low-moderate tracking of physical activity variables indicate that those who were most active initially remained most active. Increasing inactive behaviour was observed and that several other physical activity variables were decreased at follow-up.
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15.
  • Emerging Risk Factors, Collaboration, et al. (author)
  • The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases
  • 2007
  • In: Eur J Epidemiol. - 0393-2990. ; 22:12, s. 839-69
  • Journal article (peer-reviewed)abstract
    • Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
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16.
  • Falt, Anette, et al. (author)
  • Exposure of infants to budesonide through breast milk of asthmatic mothers
  • 2007
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 120:4, s. 798-802
  • Journal article (peer-reviewed)abstract
    • Background: Maintenance treatment with inhaled corticosteroids is often required for asthmatic nursing women. Data on the transfer of inhaled corticosteroids from plasma to breast milk and the subsequent exposure of the breast-feeding infant has been unavailable. Objective: We sought to assess budesonide concentrations in milk and plasma of asthmatic nursing women receiving maintenance treatment with the Pulmicort Turbuhaler and estimate the exposure of their breast-fed infants. Methods: Milk and plasma samples were collected up to 8 hours after dosing from 8 mothers receiving budesonide maintenance treatment (200 or 400 mu g twice daily). Pharmacokinetic parameters were calculated from budesonide milk and plasma concentrations. Infant exposure was estimated based on average milk budesonide concentrations. A single blood sample was obtained from 5 infants close to expected infant maximum concentration. Results: Budesonide concentrations in milk reflected those in maternal plasma, supporting passive diffusion of budesonide between plasma and milk, and was always lower than that in plasma. The mean milk/plasma ratio was 0.46. The estimated daily infant dose was 0.3% of the daily maternal dose for both dose levels, and the average plasma concentration in infants was estimated to be 1/600th of the concentrations observed in maternal plasma, assuming complete infant oral bioavailability. Budesonide concentrations in infant plasma samples were all less than the limit of quantification. Conclusion: Maintenance treatment with inhaled budesonide (200 or 400 mu g twice daily) in asthmatic nursing women results in negligible systemic exposure to budesonide in breast-fed infants. Clinical implications: These data support continued use of inhaled budesonide during breast-feeding.
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17.
  • Fridolfsson, Jonatan, 1992, et al. (author)
  • Physical activity spectrum discriminant analysis—A method to compare detailed patterns between groups
  • 2021
  • In: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 31:12, s. 2333-2342
  • Journal article (peer-reviewed)abstract
    • Investigating physical activity (PA) patterns as a detailed intensity spectrum instead of crude intensity categories have improved the ability to analyze the relationship between measured PA and health variables. The aim of this methodological study was to introduce and investigate the utility of using detailed PA intensity spectrum compared to crude PA intensity categories for comparison of PA between groups and between repeated measures. The study sample consisted of two groups of children, where one group was scheduled for extended physical education (PE) by daily classes while the other group followed usual PE schedule. Accelerometer data was processed into traditional crude PA intensity categories and into detailed PA intensity spectrum. Multivariate partial least squares regression for discriminant analysis (PLS-DA) was applied for PA intensity spectrum group comparison and compared to traditional univariate statistical analysis. Repeated measures were investigated using independent PLS-DA as well as multilevel PLS-DA for paired analysis. While traditional analysis of crude PA intensity categories was unable to find any group differences, multivariate analysis of the PA intensity spectrum identified statistically significant differences. By the extension of multilevel PLS-DA for paired comparison, a clear difference in the PA intensity spectrum was demonstrated between repeated measures. In conclusion, analysis of detailed PA intensity spectrum demonstrates utility for comparing detailed PA data between groups and between repeated measures in interventional and observational research.
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19.
  • Gunnarsson, Mikael, et al. (author)
  • Long-term biokinetics and radiation exposure of patients undergoing 14C-glycocholic acid and 14C-xylose breath tests.
  • 2007
  • In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 22:6, s. 762-771
  • Journal article (peer-reviewed)abstract
    • The (14)C-glycocholic acid and (14)C-xylose breath tests are clinically used for the diagnosis of intestinal diseases, such as bacterial overgrowth in the small intestine. The two tests have in earlier studies been thoroughly evaluated regarding their clinical value, but due to the long physical half-life of (14)C and the limited biokinetic and dosimetric data, which are available for humans, several hospitals have been restrictive in their use. The aim of this study was to investigate the long-term biokinetics and dosimetry of the two (14)C compounds in patients and volunteers, using the highly sensitive accelerator mass spectrometry (AMS) technique. Eighteen (18) subjects were included, 9 for each compound. The (14)C content in samples from exhaled air, urine, and, for some subjects, also feces were analyzed with both liquid scintillation counting (LSC) and AMS. The results from the glycocholic acid study showed that, up to 1 year after the administration, 67%+/-6% (mean+/-standard deviation) of the administered activity was recovered in exhaled air, 2.4%+/-0.4% was found in urine, and 7.6% (1 subject) in feces. In the xylose study, the major part was found in the urine (66%+/-2%). A significant part was exhaled (28%+/-5%), and the result from an initial 72-hour stool collection from 2 of the subjects showed that the excretion by feces was insignificant. The absorbed dose to various organs and tissues and the effective dose were calculated by using biokinetic models, based on a combination of experimental data from the present study and from earlier reports. In the glycocholic acid study, the highest absorbed dose was received by the colon (1.2 mGy/MBq). In the xylose study, the adipose tissue received 0.8 mGy/MBq. The effective dose was estimated to 0.5 (glycocholic acid) and 0.07 mSv/MBq (xylose). Thus, from a radiation protection point of view, we see no need for restrictions in using the two (14)C-labeled radiopharmaceuticals on adults with the activities normally administered (0.07-0.4 MBq).
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21.
  • Hallgren, Oskar, et al. (author)
  • Splicosomal and serine and arginine-rich splicing factors as targets for TGF-β
  • 2012
  • In: Fibrogenesis & tissue repair. - : Springer Science and Business Media LLC. - 1755-1536. ; 5:1, s. 6-6
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Transforming growth factor-β1 (TGF-β1) is a potent regulator of cell growth and differentiation. TGF-β1 has been shown to be a key player in tissue remodeling processes in a number of disease states by inducing expression of extracellular matrix proteins. In this study a quantitative proteomic analysis was undertaken to investigate if TGF-β1 contributes to tissue remodeling by mediating mRNA splicing and production of alternative isoforms of proteins.METHODOLOGY/PRINCIPAL FINDINGS: The expression of proteins involved in mRNA splicing from TGF-β1-stimulated lung fibroblasts was compared to non-stimulated cells by employing isotope coded affinity tag (ICATTM) reagent labeling and tandem mass spectrometry. A total of 1733 proteins were identified and quantified with a relative standard deviation of 11% +/- 8 from enriched nuclear fractions. Seventy-six of these proteins were associated with mRNA splicing, including 22 proteins involved in splice site selection. In addition, TGF-β1 was observed to alter the relative expression of splicing proteins that may be important for alternative splicing of fibronectin. Specifically, TGF-β1 significantly induced expression of SRp20, and reduced the expression of SRp30C, which has been suggested to be a prerequisite for generation of alternatively spliced fibronectin. The induction of SRp20 was further confirmed by western blot and immunofluorescence.CONCLUSIONS: The results show that TGF-β1 induces the expression of proteins involved in mRNA splicing and RNA processing in human lung fibroblasts. This may have an impact on the production of alternative isoforms of matrix proteins and can therefore be an important factor in tissue remodeling and disease progression.
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22.
  • Hasan, Mahmudul, et al. (author)
  • The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5-epimerization of glucuronic acid in higher organisms
  • 2021
  • In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 12:5, s. 1869-1885
  • Journal article (peer-reviewed)abstract
    • Dermatan sulfate epimerase 1 (DS-epi1, EC 5.1.3.19) catalyzes the conversion of d-glucuronic acid to l-iduronic acid on the polymer level, a key step in the biosynthesis of the glycosaminoglycan dermatan sulfate. Here, we present the first crystal structure of the catalytic domains of DS-epi1, solved at 2.4 Å resolution, as well as a model of the full-length luminal protein obtained by a combination of macromolecular crystallography and targeted cross-linking mass spectrometry. Based on docking studies and molecular dynamics simulations of the protein structure and a chondroitin substrate, we suggest a novel mechanism of DS-epi1, involving a His/double-Tyr motif. Our work uncovers detailed information about the domain architecture, active site, metal-coordinating center and pattern of N-glycosylation of the protein. Additionally, the structure of DS-epi1 reveals a high structural similarity to proteins from several families of bacterial polysaccharide lyases. DS-epi1 is of great importance in a range of diseases, and the structure provides a necessary starting point for design of active site inhibitors.
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23.
  • Johansson, Lars, 1972, et al. (author)
  • Statistical modelling of pedestrian wind speed using high‐resolution digital surface models
  • 2012
  • In: The Eight International Conference on Urban Climates. ; :abstract 183
  • Conference paper (other academic/artistic)abstract
    • Spatial variations of near ground wind speed (2magl) within urban areas are simulated by using a statistical model. The model is built upon the statistical relationship between derivatives extracted from digital surface models characterizing urban geometries (sky view factor, fetch, frontal area index) and wind speed, using statistical regression techniques. The geometric parameters are calculated for a number of urban settings in Gothenburg, Sweden. Wind speed patterns are derived using the three-dimensional microclimate model, ENVI-met. The model closely estimate the wind speed within-the major parts of the model domains such as in squares, and narrow streets as well as canyons perpendicular to the incoming wind direction. However, the output wind speed patterns are largely different from the wind speed simulated by ENVI-met in wide streets and around buildings where wind speed is high. Statistical models, as presented here, would be useful for not only climatologist/ meteorologist but also urban designers to consider wind modes depending on urban geometries and also to estimate thermal comfort influenced by wind.
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24.
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25.
  • Lindberg, Fredrik, 1974, et al. (author)
  • Infrastrukturnära vegetation i Göteborg
  • 2013
  • Reports (other academic/artistic)abstract
    • Ett flertal ekosystemtjänster kan identifieras utifrån vegetation inom urbana områden, så som biologisk mångfald, klimatreglering, luft- och vattenrening, markhantering, ljuddämpning samt rekreation och välbefinnande. Den här studien fokuserar på grönska i områden i anslutning av infrastruktur. Studien använder sig av Laserscannat flygdata (LiDAR) som är en relativt ny metod där man har möjlighet av kartera utbredning och diverse egenskaper av högre vegetation (träd och buskar) med mycket stor noggrannhet. Resultat från studien visar att andelen högre vegetation nära infrastruktur är betydligt mindre (halverad) än den totala referensytan (Göteborgs kommun). Försök att uppskatta den årliga ackumuleringen av kol i biomassa med hjälp av LiDAR-data, som ett exempel på en ekosystemtjänst, har också enomförts. Resultat från dessa försök visar på stora osäkerheter och vid tolkning av resultaten av sådana beräkningar är det viktigt att tänka på att de specifika värdena endast är grova approximationer; modellen antar ett uniformt förhållande mellan biomassa och vegetationstäcke, medan det i verkligheten finns stora variationer mellan olika platser, främst beroende på varierande ålder- och artsammansättning. Dessa genskaper kan inte tas fram med hjälp av LiDAR.
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26.
  • Lindberg, Fredrik, 1974, et al. (author)
  • Träden i staden – Användningen av LiDAR-data för att identifiera urban vegetation
  • 2013
  • Reports (other academic/artistic)abstract
    • Detaljerad kartläggning av urban vegetation är en viktig förutsättning för att värdera ekosystemtjänster i städer. Dock saknas som regel detaljerad information om vegetationsom faller utanför stadens detaljplanering och markanvändningskartor, speciellt gäller detta vegetationens tredimensionella egenskaper. I denna studie har två olika LiDARdatasetanvänts för att kartlägga den urbana vegetationen med avseende på dessutbredning och tredimensionella egenskaper (vegetationshöjd, stamzonhöjd och krönhöjd): (1) nationella Lantmäteriet (LM) och (2) från Göteborg stads stadsbyggnadskontor (SBK). Dataseten skiljer sig åt, främst i fråga om punkttäthet, klassificering och årstid för insamling, vilket innebär olika förutsättningar för vegetationskartering. I rapporten redovisas skillnader mellan dataseten och hur dessa skillnader påverkar kartläggningen av vegetation i urban miljö. Resultaten jämfördes medfältobservationer. Fyra områden (1x1 km) i Göteborg användes som fallstudie. Resultaten visar att vegetationens utbredning och höjd kan uppskattas bra med LiDARdata i urbana miljöer om punkttätheten är hög och klassificeringen medger bra separeringav returer. SBK-data uppfyller båda dessa kriterier. Den lägre punkttätheten och den grövre klassificeringen av LM-data medför att mycket vegetation utelämnas samt attoönskade objekt i större grad inkluderas i analysen. Beräknad vegetationshöjd korrelerar väl med fältobservationer, vilket gäller båda dataseten. Kronhöjd visar något sämrekorrelation på grund av stor osäkerhet i beräkning av stamzonhöjd. Filtrering av preliminära vegetationsraster har genomförts vilket löser en del problem med oönskade objekt och artefakter som härrör från rumsliga variationer i punktmolnets täthet. Filtreringinnebär dock manipulation av data och är därför också en osäkerhetsfaktor. LM-data kräver mer filtrering, framför allt måste celler med låga värden (
  •  
27.
  • Lindberg, Fredrik, 1974, et al. (author)
  • Träden i staden – Användningen av LiDAR-data för att identifiera urban vegetation
  • 2013
  • Reports (other academic/artistic)abstract
    • Detaljerad kartläggning av urban vegetation är en viktig förutsättning för att värdera ekosystemtjänster i städer. Dock saknas som regel detaljerad information om vegetation som faller utanför stadens detaljplanering och markanvändningskartor, speciellt gäller detta vegetationens tredimensionella egenskaper. I denna studie har två olika LiDARdataset använts för att kartlägga den urbana vegetationen med avseende på dess utbredning och tredimensionella egenskaper (vegetationshöjd, stamzonhöjd och krönhöjd): (1) nationella Lantmäteriet (LM) och (2) från Göteborg stads stadsbyggnadskontor (SBK). Dataseten skiljer sig åt, främst i fråga om punkttäthet, klassificering och årstid för insamling, vilket innebär olika förutsättningar för vegetationskartering. I rapporten redovisas skillnader mellan dataseten och hur dessa skillnader påverkar kartläggningen av vegetation i urban miljö. Resultaten jämfördes med fältobservationer. Fyra områden (1x1 km) i Göteborg användes som fallstudie. Resultaten visar att vegetationens utbredning och höjd kan uppskattas bra med LiDARdata i urbana miljöer om punkttätheten är hög och klassificeringen medger bra separering av returer. SBK-data uppfyller båda dessa kriterier. Den lägre punkttätheten och den grövre klassificeringen av LM-data medför att mycket vegetation utelämnas samt att oönskade objekt i större grad inkluderas i analysen. Beräknad vegetationshöjd korrelerar väl med fältobservationer, vilket gäller båda dataseten. Kronhöjd visar något sämre korrelation på grund av stor osäkerhet i beräkning av stamzonhöjd. Filtrering av preliminära vegetationsraster har genomförts vilket löser en del problem med oönskade objekt och artefakter som härrör från rumsliga variationer i punktmolnets täthet. Filtrering innebär dock manipulation av data och är därför också en osäkerhetsfaktor. LM-data kräver mer filtrering, framför allt måste celler med låga värden (< 2m) avlägsnas för att ta bort oönskade objekt, till exempel bilar. Den lägre upplösningen i LM-data gör också att filtreringen blir mer oprecis.
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28.
  • Malmström, Erik, et al. (author)
  • The importance of fibroblasts in remodelling of the human uterine cervix during pregnancy and parturition.
  • 2007
  • In: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407. ; 13, s. 333-341
  • Journal article (peer-reviewed)abstract
    • It is well established that fibroblasts play a crucial role in pathophysiological extracellular matrix remodelling. The aim of this project is to elucidate their role in normal physiological remodelling. Specifically, the remodelling of the human cervix during pregnancy, resulting in an enabled passage of the child, is used as the model system. Fibroblast cultures were established from cervices of non-pregnant women, women after 36 weeks of pregnancy and women directly after partus. The cells were immunostained and quantified by western blots for differentiation markers. The cultures were screened for cytokine and metalloproteinase production and characterized by global proteome analysis. The cell cultures established from partal donors differ significantly from those from non-pregnant donors, which is in accordance with in vivo findings. A decrease in alpha-smooth actin and prolyl-4hydroxylase and an increase in interleukin (IL)-6, IL-8 and matrix metalloproteinases (MMP)-1 and MMP-3 were observed in cultures from partal donors. 2D-gel electrophoresis followed by mass spectrometry showed that the expression of 59 proteins was changed significantly in cultures of partal donors. The regulated proteins are involved in protein kinase C signalling, Ca2+ binding, cytoskeletal organization, angiogenesis and degradation. Our data suggest that remodelling of the human cervix is orchestrated by fibroblasts, which are activated or recruited by the inflammatory processes occurring during the ripening cascade.
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29.
  • Malmström, Johan, et al. (author)
  • Nanocapillary liquid chromatography interfaced to tandem matrix-assisted laser desorption/ionization and electrospray ionization-mass spectrometry: Mapping the nuclear proteome of human fibroblasts.
  • 2003
  • In: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 24:21, s. 3806-3814
  • Journal article (peer-reviewed)abstract
    • Miniaturized liquid chromatography nanoseparation in combination with minigel fractionation of human primary cell nuclei is presented. We obtained high-sensitivity and high-throughput identification of expressed proteins by subcellular fractionation and nanocapillary liquid chromatography interfaced to both electrospray ionization (ESI)- and matrix-assisted laser desorption/ionisation (MALDI) tandem mass spectrometry. The reversed-phase nanocapillary eluents were applied directly onto the MALDI target plate as discrete crystal spots using in-line matrix infusion. When working with primary cells, only a limited amount of sample is available. To maximize the number of identified proteins from a restricted amount of sample, miniaturized sample preparation protocols and nanoflow separation is a necessity, especially when working with low-abundant proteins. From the same isolated nuclear sample, complementary separation of intact proteins by two-dimensional (2-D) gel electrophoresis was made. In total 594 gene products from the nuclear preparations were identified out of which 261 were unique. Several proteins involved in transcriptional events were identified such as TATA-binding protein, EBNA-co-activator, and interleukin enhancer binding proteins, indicating that sufficient proteomic depth is obtained to study transcriptional controlling events. Our results suggest that by sample prefractionation and downscaled nanoflow separation along with a combined mass spectrometry strategy, it is possible to identify a large number of nuclear proteins from human primary cells. These findings are of particular importance due to the disease link of these targets cells.
  •  
30.
  • Malmström, Johan, et al. (author)
  • Proteome annotations and identifications of the human pulmonary fibroblast.
  • 2004
  • In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 3:3, s. 525-537
  • Journal article (peer-reviewed)abstract
    • We hereby report on a three year project initiative undertaken by our research team encompassing large-scale protein expression profiling and annotations of human primary lung fibroblast cells. An overview is given of proteomic studies of the fibroblast target cell involved in several diseases such as asthma, idiopatic pulmonary disease, and COPD. It has been the objective within our research team to map and identify the protein expressions occurring in both activated-, as well as resting cell states. The JGGL database www.2DDB.org has been built around these data, allowing advanced hypothesis building using the interactive query bioinformatic tools developed. Gene ontology has been applied to these annotations, classifying and correlating protein expressions to function. The localization as well as the biological processes involved for the annotations are being presented including an annotation-, and sequence-identification strategy, resulting in close to 2000 protein identities. Both gel based, high resolution 2D-gels, and liquid-phase separation (three-dimensional HPLC), as well as the combination of gel- and LC-based approaches (1D-gels and nano-capillary LC, reversed-phase) were utilized. Protein sequencing and structure identities were acquired by a combination of MALDI-, and electrospray-mass spectrometry techniques. Phenotypical and morphological characterizations were also made for this human disease target cell in both stimulated- and resting-cell states. The use of functional assays that demonstrate the key regulating role of growth factors and cytokine stimuli such as PDGF, TGF-, and EGF and the effect of ECM molecules such as Biglycan, are also presented and discussed.
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31.
  • Malmström, Lars, et al. (author)
  • 2DDB – a bioinformatics solution for analysis of quantitative proteomics data
  • 2006
  • In: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 7:158
  • Journal article (peer-reviewed)abstract
    • Background We present 2DDB, a bioinformatics solution for storage, integration and analysis of quantitative proteomics data. As the data complexity and the rate with which it is produced increases in the proteomics field, the need for flexible analysis software increases. Results 2DDB is based on a core data model describing fundamentals such as experiment description and identified proteins. The extended data models are built on top of the core data model to capture more specific aspects of the data. A number of public databases and bioinformatical tools have been integrated giving the user access to large amounts of relevant data. A statistical and graphical package, R, is used for statistical and graphical analysis. The current implementation handles quantitative data from 2D gel electrophoresis and multidimensional liquid chromatography/mass spectrometry experiments. Conclusion The software has successfully been employed in a number of projects ranging from quantitative liquid-chromatography-mass spectrometry based analysis of transforming growth factor-beta stimulated fi-broblasts to 2D gel electrophoresis/mass spectrometry analysis of biopsies from human cervix. The software is available for download at SourceForge.
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32.
  • Martinsson, Anders, et al. (author)
  • Elfiske i Västra Götalands län 2005
  • 2006
  • Reports (other academic/artistic)abstract
    • I Länsstyrelsens effektuppföljningsprogram för kalkningsverksamheten ingår provtagning av både kemi och biologi. För kalkningsplanering används i först hand de vattenkemiska resultaten men den biologiska effektuppföljningen är ett mycket viktigt komplement för bedömningen av hur kalkningen har lyckats och omkalkningsstrategin fungerar. De är också viktiga för att få en indikation om hur väl ekosystemen i våra försurningspåverkade vattendrag fungerar och att de utpekade målarterna förekommer i livskraftiga bestånd. Elfiske och bottenfauna är de mest betydelsefulla undersökningarna för de biologiska bedömningarna men inom kalkeffektuppföljningen ingår även nätprovfiske och kräftprovfiske. Melica har tillsammans med Thorsson & Åberg Miljö och vattenvård AB och Sportfiskarna genomfört årets elfisken.
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33.
  • Nielsen, Magnus, et al. (author)
  • Interpretation of captopril renography using artificial neural networks
  • 2005
  • In: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 25:5, s. 293-296
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to develop a method based on artificial neural networks for interpretation of captopril renography tests for the detection of renovascular hypertension caused by renal artery stenosis and to assess the value of different measurements from the test. A total of 250 99mTc-MAG3 captopril renography tests were used in the study. The material was collected from two different patient groups. One group consisted of 101 patients who also had undergone a renal angiography. The angiographies, which were used as gold standard, showed a significant renal artery stenosis in 53 of the 101 cases. The second group consisted of 149 patients, who's captopril renography tests all were interpreted as not compatible with significant renal artery stenosis by an experienced nuclear medicine physician. Artificial neural networks were trained for the diagnosis of renal artery stenosis using eight measures from each renogram. The neural network was then evaluated in separate test groups using an eightfold cross validation procedure. The performance of the neural networks, measured as the area under the receiver operating characteristic curve, was 0.93. The sensitivity was 91% at a specificity of 90%. The lowest performance was found for the network trained without use of a parenchymal transit measure, indicating the importance of this feature. Artificial neural networks can be trained to interpret captopril renography tests for detection of renovascular hypertension caused by renal artery stenosis. The result almost equals that of human experts shown in previous studies. © 2005 Blackwell Publishing Ltd.
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34.
  • Nielsen, Magnus, et al. (author)
  • Interpretation of captopril renography using artificial neural networks.
  • 2005
  • In: Clinical Physiology and Functional Imaging. - 1475-0961. ; 25:5, s. 293-296
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to develop a method based on artificial neural networks for interpretation of captopril renography tests for the detection of renovascular hypertension caused by renal artery stenosis and to assess the value of different measurements from the test. A total of 250 99mTc-MAG3 captopril renography tests were used in the study. The material was collected from two different patient groups. One group consisted of 101 patients who also had undergone a renal angiography. The angiographies, which were used as gold standard, showed a significant renal artery stenosis in 53 of the 101 cases. The second group consisted of 149 patients, who's captopril renography tests all were interpreted as not compatible with significant renal artery stenosis by an experienced nuclear medicine physician. Artificial neural networks were trained for the diagnosis of renal artery stenosis using eight measures from each renogram. The neural network was then evaluated in separate test groups using an eightfold cross validation procedure. The performance of the neural networks, measured as the area under the receiver operating characteristic curve, was 0.93. The sensitivity was 91% at a specificity of 90%. The lowest performance was found for the network trained without use of a parenchymal transit measure, indicating the importance of this feature. Artificial neural networks can be trained to interpret captopril renography tests for detection of renovascular hypertension caused by renal artery stenosis. The result almost equals that of human experts shown in previous studies.
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35.
  • Persson, Gunnar, et al. (author)
  • Relative systemic availability of budesonide in patients with asthma after inhalation from two dry powder inhalers
  • 2008
  • In: Current Medical Research and Opinion. - 1473-4877. ; 24:5, s. 1511-1517
  • Journal article (peer-reviewed)abstract
    • Background: To improve dosing consistency and product features, budesonide inhalation powder delivered via a dry powder inhaler (DPI) (DPI-A* 200 mu g) was redesigned to include lactose, a newly shaped mouthpiece, and a new dose indicator (DPI-B dagger). Budesonide CPI-B is available in two strengths (90 mu g, 180 mu g). Objective: To compare the relative rate and extent of the systemic availability of budesonide inhaled via DPI-A and DPI-B and test for systemic absorption bioequivalence. Methods: Adults (n = 37) with asthma as defined by the American Thoracic Society were randomized in an open-label, crossover, single-center, single-dose study to budesonide DPI-A 200 mu g x 4 inhalations, budesonide DPI-B 180 mu g x 4 inhalations, or budesonide DPI-B 90 mu g x 8 inhalations, on 3 days, each separated by a washout period of >= 5 days. Plasma samples were collected immediately before and up to 12 h after dosing. Primary pharmacokinetic variables were area under the drug plasma concentration-time curve from 0 to infinity (AUC(0-infinity)) and maximum plasma concentration (C-max); plasma concentration at 12 h (C-12h) and time to maximum plasma concentration (T-max) were secondary variables. Treatments were considered bioequivalent if the 90% confidence intervals (Cls) for their AUC(0-infinity) and C-max ratios fell between 80 and 125%. Adverse events were collected. Results: The 90% Cls for the ratios of AUC(0-infinity) and C-max for budesonide DPI-A 200 mu g and DPI-B 180 mu g and for both budesonide DPI-B strengths fell between 80% and 125% (AUC(0-infinity): budesonide DPI-B 180 mu g x 4/DPI-A 200 mu g x 4: 96.3% [90% Cl: 90.9,102,1]; budesonide DPI-B 180 mu g x 4/DPI-B 90 mu g x 8: 92.2% [90% Cl: 87.0, 97.7]; C-max: (budesonide DPI-B 180 mu g x 4/DPI-A 200 mu g x 4:100.4% [95% Cl: 92.1, 109.4]; budesonide DPI-B 180 mu g x 4/DPI-B 90 mu g x 8: 94.4% [90% Cl: 86.6,102.9]). No differences in C-12h and T-max were found between treatments. All treatments were well tolerated. Conclusions: Budesonide DPI-A 200 mu g and CPI-B 180 mu g have systemic absorption bioequivalence, and DPI-B 90 mu g and 180 mu g are dose-strength equivalent when administered at the same dose. These results may not be generalized to all patients with asthma, as this analysis included only patients with mild-to-moderate asthma aged >= 19 years.
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36.
  • Reza, Mariana, et al. (author)
  • Automated Bone Scan Index as an Imaging Biomarker to Predict Overall Survival in the Zometa European Study/SPCG11
  • 2021
  • In: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 4:1, s. 49-55
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Owing to the large variation in treatment response among patients with high-risk prostate cancer, it would be of value to use objective tools to monitor the status of bone metastases during clinical trials. Automated Bone Scan Index (aBSI) based on artificial intelligence has been proposed as an imaging biomarker for the quantification of skeletal metastases from bone scintigraphy.OBJECTIVE: To investigate how an increase in aBSI during treatment may predict clinical outcome in a randomised controlled clinical trial including patients with high-risk prostate cancer.DESIGN, SETTING, AND PARTICIPANTS: We retrospectively selected all patients from the Zometa European Study (ZEUS)/SPCG11 study with image data of sufficient quality to allow for aBSI assessment at baseline and at 48-mo follow-up. Data on aBSI were obtained using EXINIboneBSI software, blinded for clinical data and randomisation of zoledronic acid treatment. Data on age, overall survival (OS), and prostate-specific antigen (PSA) at baseline and upon follow-up were available from the study database.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association between clinical parameters and aBSI increase during treatment was evaluated using Cox proportional-hazards regression models, Kaplan-Meier estimates, and log-rank test. Discrimination between prognostic variables was assessed using the concordance index (C-index).RESULTS AND LIMITATIONS: In this cohort, 176 patients with bone metastases and a change in aBSI from baseline to follow-up of ≤0.3 had a significantly longer median survival time than patients with an aBSI change of >0.3 (p<0.0001). The increase in aBSI was significantly associated with OS (p<0.01 and C-index=0.65), while age and PSA change were not.CONCLUSIONS: The aBSI used as an objective imaging biomarker predicted outcome in prostate cancer patients in the ZEUS/SPCG11 study. An analysis of the change in aBSI from baseline to 48-mo follow-up represents a valuable tool for prognostication and monitoring of prostate cancer patients with bone metastases.PATIENT SUMMARY: The increase in the burden of skeletal metastases, as measured by the automated Bone Scan Index (aBSI), during treatment was associated with overall survival in patients from the Zometa European Study/SPCG11 study. The aBSI may be a useful tool also in monitoring prostate cancer patients with newly developed bone metastases.
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37.
  • Samuelsson, Ulf, et al. (author)
  • Geographical variation in the incidence of type 1 diabetes in the Nordic countries : A study within NordicDiabKids
  • 2020
  • In: Pediatric Diabetes. - : Blackwell Publishing. - 1399-543X .- 1399-5448. ; 21:2, s. 259-265
  • Journal article (peer-reviewed)abstract
    • Background: The incidence of type 1 diabetes (T1D) is high in the Nordic countries with geographic differences between as well as within countries. Objective: To describe the geographical distribution of the incidence of T1D among children in four Nordic countries, an area where the population is considered genetically similar.Methods: Data on children 0 to 14 years of age and diagnosed with T1D 2006 to 2011 was collected from four Nordic national pediatric quality diabetes registries. Data included year of diagnosis (2006-2011), sex, and age at diagnosis. Figures for number of children at risk during 2006 to 2011—as well as total population, proportion with foreign background and size of populated areas of geographic regions—were collected from official statistics.Results: The total incidence during the study period for all four countries was 35.7/100 000 person years but differed between the countries (range 18.2-44.1; P <.001). The incidence difference between the countries was most obvious in the highest age group, 10 to 14 years of age, whereas there was no difference in the youngest age group 0 to 5 years of age. Iceland had similar incidence in the entire country, whereas the other countries had areas with different incidence. Densely populated areas, such as major cities, had the lowest incidence.Conclusion: The incidence of T1D differed between the Nordic countries and also between the neighboring countries and generally decreased with population density. This indicates that environmental factors may contribute to the level of incidence of T1D.
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38.
  • Tanha, Tina, et al. (author)
  • Lack of physical activity in young children is related to higher composite risk factor score for cardiovascular disease.
  • 2011
  • In: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 100, s. 717-721
  • Journal article (peer-reviewed)abstract
    • Aim: This study evaluates if accelerometer measured physical activity is related to higher composite risk factor scores for cardiovascular disease (CVD) in children. Methods: Cross-sectional study that included 223 children aged 7.9-11.1 years (boys n=123, girls n=100). Daily physical activity was assessed by accelerometers for four days. Body fat was quantified by dual x-ray absorptiometry. Maximal oxygen uptake was measured during a maximal exercise test. Resting heart rate and blood pressure were measured. Z-scores [(value for the individual-mean value for group)/SD] were calculated for each variable and the sum of different risk factor z-scores used as an index of composite risk factors score for CVD. Results: Partial correlations, from General Linear Model, between moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA) and general physical activity (GPA) versus index of composite risk factor score were in boys -0.29, -0.33 and -0.30 (all p<0.05). The corresponding correlations in girls were -0.28, -0.32 (both p<0.05), and -0.18, (NS). Conclusion: Low amounts of MVPA and VPA were related to higher composite risk factor scores for CVD in children aged 8-11 years.
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39.
  • Thorsson, Lars, et al. (author)
  • Pharmacokinetics and systemic activity of fluticasone via Diskus and pMDI, and of budesonide via Turbuhaler
  • 2001
  • In: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 52:5, s. 529-538
  • Journal article (peer-reviewed)abstract
    • AIMS: To determine the basal pharmacokinetics, lung uptake and plasma cortisol suppression for two commonly prescribed inhaled corticosteroids. METHODS: Twenty-one subjects (13 healthy and 8 mild asthmatic patients) received fluticasone propionate via a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) (healthy subjects only) and Diskus and budesonide via Turbuhaler, 1000 microg twice daily for 7 days. Intravenous doses (200 microg) of both compounds were used as references. Plasma concentrations of fluticasone and budesonide were determined during 48 h by liquid chromatography plus tandem mass spectrometry (LC-MS-MS). Plasma concentrations of cortisol were determined by LC-MS every second hour for 24 h at baseline, and following each treatment. RESULTS: The volume of distribution was found to be larger and the elimination half-life and mean absorption time longer for fluticasone than for budesonide. The systemic availability of budesonide via Turbuhaler (39%) was significantly higher than that of fluticasone via Diskus (13%) (ratio 3.0 [2.5, 3.6] with 95% confidence interval [CI]), and via pMDI (21%) (ratio 1.8 [1.3, 2.3]). In addition, at steady state the systemic availability of fluticasone via pMDI was significantly higher than via Diskus (ratio 1.6 [1.1, 2.2]). The lung deposition of budesonide via Turbuhaler was 2.2-fold [1.7, 2.9] higher than that of fluticasone pMDI and 3.4-fold [2.8, 4.0] higher than that of fluticasone Diskus. In addition, the lung deposition of fluticasone via pMDI was 1.5-fold [1.1, 2.9] higher than that via the Diskus inhaler. Plasma cortisol (24 h) was significantly reduced vs baseline for all three treatments. The cortisol concentration vs baseline was 12% for fluticasone pMDI, which was significantly lower (ratio 0.32 [0.24, 0.42]) than that for fluticasone Diskus (39%), and for budesonide Turbuhaler (46%) (ratio 0.27 [0.21, 0.37]). The plasma cortisol concentration did not differ significantly between treatments with fluticasone Diskus and budesonide Turbuhaler (ratio 0.87 [0.65; 1.15]). CONCLUSIONS: Budesonide and fluticasone differ in their pharmacokinetic properties in that although clearance is the same, the rate of uptake and elimination is slower for fluticasone. Despite a significantly higher pulmonary availability of budesonide via Turbuhaler, the plasma cortisol suppression is less than that of fluticasone via pMDI and similar to that of fluticasone via Diskus. There is no indication of any difference between healthy subjects and mild asthmatic patients in the pharmacokinetics and plasma cortisol suppression of fluticasone and budesonide.
  •  
40.
  • Thorsson, Lars (author)
  • Studies on the deposition, bioavailability and systemic activity of glucocorticoids in man
  • 1998
  • Doctoral thesis (other academic/artistic)abstract
    • The local deposition, pharmacokinetics, and systemic activity of inhaled and intranasal glucocorticosteroids in different formulations and devices(ICSs) has been investigated. After nasal administration of the ICS budesonide (Bud), the systemic availability (F) was found to be significantly higher from an aqueous pump spray and from the powder inhaler Turbuhaler, than from a pressurized metered dose inhaler (pMDI), and the uptake process was slower and less complete with the pMDI formulation. Lung deposition of Bud from a pMDI plus Nebuhaler, and from Turbuhaler, was found to be twice as high as with a pMDI alone, whereas Ftotal was only about 50% higher. Thus, a larger proportion of Ftotal was derived from lung deposited Bud when using a pMDI plus Nebuhaler, spacer and Turbuhaler, than when using a pMDI. It was also found that the pMDI resulted in a significantly larger variability in lung deposition than Turbuhaler. In addition, a marked reduction in F was found when the pMDI canisters were not shaken properly before administration which confirms that the pMDI is very dependent on proper handling. Fluticasone propionate (FP), was found to accumulate in plasma during repeated dosing due to a slow systemic elimination. The accumulation is a probable explanation for the marked plasma cortisol suppression observed with repeated dosing within the clinical dose range. In conclusion, the present study has shown differences in local deposition, pharmacokinetics and systemic activity of inhaled glucocorticoid formulations, features which may contribute to differences in therapeutic properties.
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41.
  • Thorsson, Sofia, 1972, et al. (author)
  • Carbon monoxide concentrations in outdoor wood-fired kitchens in Ouagadougou, Burkina Faso-implications for women's and children's health
  • 2014
  • In: Environmental Monitoring & Assessment. - : Springer Science and Business Media LLC. - 0167-6369 .- 1573-2959. ; 186:7, s. 4479-4492
  • Journal article (peer-reviewed)abstract
    • A majority of households in developing countries rely on biomass fuel for cooking, typically burned in open fires or simple stoves. The incomplete combustion of these fuels causes adverse health effects such as respiratory diseases, especially among women and children. However, quantitative data on pollution levels and on associated diseases are limited. We examined cooking habits and self-reported health in 31 households with outdoor open wood fires in Ouagadougou, Burkina Faso, using structured interviews. In eight households, carbon monoxide (CO) was measured using passive sampling. In addition, meteorology and ambient CO concentrations were assessed. The average CO concentration during cooking was 4.3 ppm, with a maximum of 65.3 ppm and minimum of 0.3 ppm (1-min values). A clear daily pattern was observed, with relatively low concentrations during the day and high during the evening, occasionally exceeding the World Health Organization 1- and 8-h guidelines when the air stabilised. On average, CO concentrations were 43 % higher in kitchens located in closed yards than in those located in open yards, showing that fireplace location affected the levels. Eye irritation and coughing among women and children were reported by 30 % of the households. Based on previously reported relations between CO concentrations and fine particles (< 2.5 mu m), the exposure to biomass smoke appears to be high enough to pose a considerable health risk among women and children in households with outdoor open wood fires. The results suggest that burning should be limited between sunset and dawn and in areas with limited ventilation to reduce pollutions levels.
  •  
42.
  • Tykesson, Emil, et al. (author)
  • Deciphering the mode of action of the processive polysaccharide modifying enzyme dermatan sulfate epimerase 1 by hydrogen-deuterium exchange mass spectrometry
  • 2016
  • In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6539 .- 2041-6520. ; 7:2, s. 1447-1456
  • Journal article (peer-reviewed)abstract
    • Distinct from template-directed biosynthesis of nucleic acids and proteins, the enzymatic synthesis of heterogeneous polysaccharides is a complex process that is difficult to study using common analytical tools. Therefore, the mode of action and processivity of those enzymes are largely unknown. Dermatan sulfate epimerase 1 ( DS-epi1) is the predominant enzyme during the formation of iduronic acid residues in the glycosaminoglycan dermatan sulfate. Using recombinant DS-epi1 as a model enzyme, we describe a tandem mass spectrometry-based method to study the mode of action of polysaccharide processing enzymes. The enzyme action on the substrate was monitored by hydrogen-deuterium exchange mass spectrometry and the sequence information was then fed into mathematical models with two different assumptions of the mode of action for the enzyme: processive reducing end to non-reducing end, and processive non-reducing end to reducing end. Model data was scored by correlation to experimental data and it was found that DS-epi1 attacks its substrate on a random position, followed by a processive mode of modification towards the non-reducing end and that the substrate affinity of the enzyme is negatively affected by each additional epimerization event. It could also be shown that the smallest active substrate was the reducing end uronic acid in a tetrasaccharide and that octasaccharides and longer oligosaccharides were optimal substrates. The method of using tandem mass spectrometry to generate sequence information of the complex enzymatic products in combination with in silico modeling can be potentially applied to study the mode of action of other enzymes involved in polysaccharide biosynthesis.
  •  
43.
  • Westergren-Thorsson, G, et al. (author)
  • Altered dermatan sulfate proteoglycan synthesis in fibroblast cultures established from skin of patients with systemic sclerosis
  • 1996
  • In: Journal of Rheumatology. - 0315-162X. ; 23:8, s. 406-1398
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To study whether changes in the properties of skin from patients with systemic sclerosis (SSc) are the result of altered metabolism of dermatan sulfate proteoglycans.METHODS: Fibroblast cultures were established from skin of healthy controls, and from affected and unaffected skin of patients with SSc. Synthesized proteoglycans were labeled with 3H glucosamine and 35S sulfate. The amount of mRNA of the different dermatan sulfate proteoglycans was determined by hybridization with the corresponding cDNA probes.RESULTS: A 2-fold increase in secretion of total proteoglycans was found in cell cultures from affected and normal appearing skin from patients with SSc. The production of 2 different dermatan sulfate proteoglycans was increased. Aggrecan/versican increased 4-fold and decorin 2-fold in cultures of affected skin from patients with SSc. The mRNA for decorin increased 3-fold, while the mRNA level for versican increased only slightly. Similar but less marked changes were noted in cultures from normal appearing skin. In contrast, the biglycan mRNA level decreased and the product could only be found in very small amounts in SSc cultures.CONCLUSION: This marked alteration of dermatan sulfate proteoglycan metabolism distinguishes not only affected skin but also normal appearing SSc skin from that of controls. The altered proteoglycan production may affect organization of matrix fibers and thereby the fibrotic process observed in patients with SSc.
  •  
44.
  • Westergren-Thorsson, Gunilla, et al. (author)
  • Transforming growth factor-beta induces selective increase of proteoglycan production and changes in the copolymeric structure of dermatan sulphate in human skin fibroblasts
  • 1992
  • In: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 205:1, s. 277-286
  • Journal article (peer-reviewed)abstract
    • Human embryonic skin fibroblasts were pretreated with transforming growth factor-beta (TGF-beta) for 6 h and then labeled with [35S]sulphate and [3H]leucine for 24 h. Radiolabeled proteoglycans from the culture medium and the cell layer were isolated and separated by isopycnic density-gradient centrifugation, followed by gel, ion-exchange and hydrophobic-interaction chromatography. The major proteoglycan species were examined by polyacrylamide gel electrophoresis in sodium dodecyl sulphate before and after enzymatic degradation of the polysaccharide chains. The results showed that TGF-beta increased the production of several different 35S-labelled proteoglycans. A large chondroitin/dermatan sulphate proteoglycan (with core proteins of approximately 400-500 kDa) increased 5-7-fold and a small dermatan sulphate proteoglycan (PG-S1, also termed biglycan, with a core protein of 43 kDa) increased 3-4-fold both in the medium and in the cell layer. Only a small effect was observed on another dermatan sulphate proteoglycan, PG-S2 (also named decorin). These observations are generally in agreement with results of other studies using similar cell types. In addition, we have found that the major heparan sulphate proteoglycan of the cell layer (protein core approximately 350 kDa) was increased by TGF-beta treatment, whereas all the other smaller heparan sulphate proteoglycans with protein cores from 250 kDa to 30 kDa appeared unaffected. To investigate whether TGF-beta also influences the glycosaminoglycan (GAG) chain-synthesizing machinery, we also characterized GAGs derived from proteoglycans synthesized by TGF-beta-treated cells. There was generally no increase in the size of the GAG chains. However, the dermatan sulphate chains on biglycan and decorin from TGF-beta treated cultures contained a larger proportion of D-glucuronosyl residues than those derived from untreated cultures. No effect was noted on the 4- and 6-sulphation of the GAG chains. By the use of p-nitrophenyl beta-D-xyloside (an initiator of GAG synthesis) it could be demonstrated that chain synthesis was also enhanced in TGF-beta-treated cells (approximately twofold). Furthermore, the dermatan sulphate chains synthesized on the xyloside in TGF-beta-treated fibroblasts contained a larger proportion of D-glucuronosyl residues than those of the control. These novel findings indicate that TGF-beta affects proteoglycan synthesis both quantitatively and qualitatively and that it can also change the copolymeric structure of the GAG by affecting the GAG-synthesizing machinery. Altered proteoglycan structure and production may have profound effects on the properties of extracellular matrices, which can affect cell growth and migration as well as organisation of matrix fibres.
  •  
45.
  • Zimmerman, Malin, et al. (author)
  • Temporal trend of autonomic nerve function and HSP27, MIF and PAI-1 in type 1 diabetes
  • 2017
  • In: Journal of Clinical and Translational Endocrinology. - : Elsevier BV. - 2214-6237. ; 8, s. 15-21
  • Journal article (peer-reviewed)abstract
    • Aim Diabetes mellitus type 1 (T1D) has numerous complications including autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their possible roles in effects of diabetes on the autonomic nervous system. Methods Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were analyzed. Results Autonomic nerve function deteriorated over time during the 20-year-period, but levels of HSP27, MIF, and PAI-1 were not associated with cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I-ratio. Conclusions Neither the neuroprotective substance HSP27 nor the inflammatory substances, MIF and PAI-1 were associated with measures of cardiovascular autonomic nerve function, but a deterioration of such function was observed in relation to increasing HbA1c in T1D during a 20-year follow-up period. Improved glucose control might be associated with protection against autonomic neuropathy in T1D.
  •  
46.
  • Åhrman, Emma, et al. (author)
  • Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis
  • 2018
  • In: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 189, s. 23-33
  • Journal article (peer-reviewed)abstract
    • Remodeling of the extracellular matrix (ECM) is a common feature in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Here, we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease, using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the disease proteomes, with specific focus on the matrisome, using data-independent acquisition and targeted data analysis (SWATH-MS). Our work provides an in-depth proteomic characterization of human lung tissue during impaired tissue remodeling. In addition, we show important quantitative and qualitative effects of the solubility of matrisome proteins. COPD was characterized by a disease-specific increase in ECM regulators, metalloproteinase inhibitor 3 (TIMP3) and matrix metalloproteinase 28 (MMP-28), whereas for IPF, impairment in cell adhesion proteins, such as collagen VI and laminins, was most prominent. For both diseases, we identified increased levels of proteins involved in the regulation of endopeptidase activity, with several proteins belonging to the serpin family. The established human lung quantitative proteome inventory and the construction of a tissue-specific protein assay library provides a resource for future quantitative proteomic analyses of human lung tissues. Significance: We present a sequential tissue extraction strategy to determine changes in extractability of matrisome proteins in end-stage COPD and IPF compared to healthy control tissue. Extensive quantitative analysis of the proteome changes of the disease states revealed altered solubility of matrisome proteins involved in ECM regulators and cell-ECM communication. The results highlight disease-specific remodeling mechanisms associated with COPD and IPF.
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