| 1. |
- Lourenço Dos Santos, Sofia, et al.
(författare)
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Oxidative proteome alterations during skeletal muscle ageing
- 2015
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Ingår i: Redox Biology. - : Elsevier BV. - 2213-2317. ; 5, s. 267-274
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Tidskriftsartikel (refereegranskat)abstract
- Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated) proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the 'oxi-proteome' or 'carbonylome', have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.
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| 2. |
- Norén, Bengt, et al.
(författare)
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Visual assessment of biliary excretion of Gd-EOB-DTPA in patients with suspected diffuse liver disease–A biopsy-verified prospective study
- 2015
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Ingår i: European Journal of Radiology Open. - : Elsevier BV. - 2352-0477. ; 2, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To qualitatively evaluate late dynamic contrast phases, 10, 20 and 30. min, after administration of Gd-EOB-DTPA with regard to biliary excretion in patients presenting with elevated liver enzymes without clinical signs of cirrhosis or hepatic decompensation and to compare the visual assessment of contrast agent excretion with histo-pathological fibrosis stage, contrast uptake parameters and blood tests. Methods: 29 patients were prospectively examined using 1.5T MRI. The visually assessed presence or absence of contrast agent for each of five anatomical regions in randomly reviewed time-series was summarized on a four grade scale for each patient. The scores, including a total visual score, were related to the histo-pathological findings, the quantitative contrast agent uptake parameters, expressed as KHep or LSC_N, and blood tests. Results: No relationship between the fibrosis grade or contrast uptake parameters could be established. A negative correlation between the visual assessment and alkaline phosphatase (ALP) was found. Comparing a sub-group of cholestatic patients with fibrosis score and Gd-EOB-DTPA dynamic parameters did not add any additional significant correlation. Conclusions: No correlation between visually assessed biliary excretion of Gd-EOB-DTPA and histo-pathological or contrast uptake parameters was found. A negative correlation between the visual assessment and alkaline phosphatase (ALP) was found.
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| 3. |
- Pedersen, Annie, 1981, et al.
(författare)
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Haemostatic biomarkers are associated with long-term recurrent vascular events after ischaemic stroke
- 2016
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 116:3, s. 537-543
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Tidskriftsartikel (refereegranskat)abstract
- Ischaemic stroke patients continue to be at risk for recurrent vascular events for many years. Predictors of long-term prognosis are needed. It was the objective of this study to investigate levels of four haemostatic proteins as long-term predictors of recurrent vascular events after ischaemic stroke. We prospectively followed 548 ischaemic stroke patients, 18-69 years, and registered recurrent vascular events. Plasma levels of tissue-type plasminogen activator (t-PA), von Willebrand factor (VWF), fibrinogen and thrombin activatable fibrinolysis inhibitor activation peptide (TAFI-AP) were measured three months after index stroke. Cox regression models were used to assess associations to outcomes for single biomarkers and for a combined biomarker measure. For single biomarkers significantly associated with any of the outcomes, we performed subanalyses stratified for age, sex, diabetes and atherosclerosis. During 5,637 person-years of follow-up, we registered 74 vascular deaths, 90 recurrent strokes and 62 coronary events. Levels of t-PA, VWF and fibrinogen were significantly associated with vascular death and coronary events. After adjustment, the association between t-PA and vascular death remained (HR per 1 SD increase in plasma level 1.27, 95 % CI 1.00-1.61, p=0.047). The combined effect of t-PA, VWF and fibrinogen was associated with coronary events (adjusted HR 1.35, 1.02-1.80, p=0.04). In non-diabetic patients, an association with coronary events was seen for VWF levels (adjusted HR 2.23,1.45-3.43, p
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| 4. |
- Stattin, Eva-Lena, et al.
(författare)
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A novel ECEL1 mutation expands the phenotype of distal arthrogryposis multiplex congenita type 5D to include pretibial vertical skin crease
- 2018
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Ingår i: American Journal of Medical Genetics. Part A. - : WILEY. - 1552-4825 .- 1552-4833. ; 176:6, s. 1405-1410
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Tidskriftsartikel (refereegranskat)abstract
- Arthrogryposis multiplex congenita (AMC) is a heterogeneous disorder characterized by multiple joint contractures often in association with other congenital abnormalities. Pretibial linear vertical creases are a rare finding associated with arthrogryposis, and the etiology of the specific condition is unknown. We aimed to genetically and clinically characterize a boy from a consanguineous family, presenting with AMC and pretibial vertical linear creases on the shins. Whole exome sequencing and variant analysis revealed homozygous novel missense variants of ECEL1 (c.1163T > C, p.Leu388Pro, NM_004826) and MUSK (c.2572C > T, p.Arg858Cys, NM_005592). Both variants are predicted to have deleterious effects on the protein function, with amino acid positions highly conserved among species. The variants segregated in the family, with healthy mother, father, and sister being heterozygous carriers and the index patient being homozygous for both mutations. We report on a unique patient with a novel ECEL1 homozygous mutation, expanding the phenotypic spectrum of Distal AMC Type 5D to include vertical linear skin creases. The homozygous mutation in MUSK is of unknown clinical significance. MUSK mutations have previously shown to cause congenital myasthenic syndrome, a neuromuscular disorder with defects in the neuromuscular junction.
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