| 1. |
- Stattin, Eva-Lena, et al.
(author)
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A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans
- 2010
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 86:2, s. 126-137
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Journal article (peer-reviewed)abstract
- Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN revealed heterozygosity for a missense mutation (c.6907G > A) in affected individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3 domain C-type lectin, which mediates interactions with other proteins in the cartilage extracellular matrix. Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein. Mass spectrometric analyses of aggrecan purified from patient cartilage verified that V2303M aggrecan is produced and present in the tissue. Our results provide a molecular mechanism for the etiology of familial osteochondritis dissecans and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo.
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| 2. |
- Ponsot, Elodie, 1973-, et al.
(author)
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Skeletal muscle telomere length is not impaired in healthy physically active old women and men
- 2008
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In: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 37:4, s. 467-472
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Journal article (peer-reviewed)abstract
- We have previously shown that the number of satellite cells is lower in old than young men and women. The aim of this study was to further explore the effects of aging on the regenerative potential of skeletal muscle in 16 young and 26 old men and women with comparable physical activity level (young, 25 +/- 4 years; old, 75 +/- 4 years). Mean and minimum telomere lengths were determined using Southern blot analyses on biopsies obtained from the tibialis anterior muscle. There were no significant age or gender effects on mean and minimal telomeric lengths, suggesting that the replicative potential in the remaining satellite cells in the tibialis anterior muscle is not impaired with increasing age and the existence of in vivo regulatory mechanisms allowing the maintenance of telomere length. These results imply that moderate physical activity regularly performed by old subjects is not associated with accelerated telomere loss.
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| 3. |
- Shahim, Pashtun, 1984, et al.
(author)
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Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury
- 2016
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 73:11, s. 1308-1315
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Journal article (peer-reviewed)abstract
- Importance:Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury.Objective:To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury.Design, Settings, and Participants:A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging.Main Outcomes and Measures:Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid β, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid.Results:A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (ρ = 0.58, P = .02 and ρ = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05).Conclusions and Relevance:Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy.
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| 4. |
- Rönmark, Eva, et al.
(author)
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High incidence and persistence of airborne allergen sensitization up to age 19 years
- 2017
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995. ; 72:5, s. 723-730
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Journal article (peer-reviewed)abstract
- BACKGROUND: Longitudinal population-based studies about the natural history of allergic sensitization are rare. The aim was to study incidence and persistence of airborne allergen sensitization up to young adulthood and risk factors for early and late onset of sensitization.METHODS: All children aged 7-8 years in two municipalities in Northern Sweden were invited to a parental questionnaire and skin prick tests (SPTs) to ten airborne allergens, and 2148 (88%) participated. The protocol was repeated at age 11-12 and 19 years, and 1516 participated in all three examinations.RESULTS: Prevalence of any positive SPT increased from 20.6% at age 7-8 years to 30.6% at 11-12 years, and 42.1% at 19 years. Animals were the primary sensitizers at age 7-8 years, 16.3%, followed by pollen, 12.4%. Mite and mold sensitization was low. Mean annual incidence of any positive SPT varied between 2.8 and 3.4/100 per year, decreased by age for animal, and was stable for pollen. Sensitization before age 7-8 years was independently associated with family history of allergy, OR 2.1 (95% CI 1.6-2.8), urban living, OR 1.9 (95% CI 1.2-2.9), and male sex, OR 1.3 (95% CI 1.0-1.7), and negatively associated with birth order, OR 0.8 (95% CI 0.7-1.0), and furry animals at home, OR 0.7 (95% CI 0.7-0.9). Incidence after age 11-12 years was associated only with family history of allergy. Multisensitization at age 19 years was significantly associated with early age at sensitization. Remission of sensitization was uncommon.CONCLUSION: The increasing prevalence of allergic sensitization by age was explained by high incidence and persistence. After age 11-12 years, the factors urban living, number of siblings, and male sex lost their importance.
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| 5. |
- Shahim, Pashtun, 1984, et al.
(author)
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Astroglial activation and altered amyloid metabolism in human repetitive concussion
- 2017
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In: Neurology. - : American Academy of Neurology. - 0028-3878 .- 1526-632X. ; 88:15, s. 1400-1407
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Journal article (peer-reviewed)abstract
- Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood–brain barrier (BBB) impairment.Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25–12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Aβ38, Aβ40, Aβ42, sAPPα, and sAPPβ), and BBB function (CSF:serum albumin ratio).Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS >1 year. Athletes with PCS >1 year had higher RPQ scores and number of concussions than athletes with PCS <1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS >1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of Aβ40 and Aβ42 than controls. The CSF:serum albumin ratio was unaltered.Conclusions: This study suggests that PCS may be associated with biomarker evidence of astroglial activation and β-amyloid (Aβ) dysmetabolism in the brain. There was no clear evidence of Aβ deposition as Aβ40 and Aβ42 were reduced in parallel. The CSF:serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS.
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| 6. |
- Kadi, Fawzi, et al.
(author)
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The behaviour of satellite cells in response to exercise : what have we learned from human studies?
- 2005
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In: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 451:2, s. 319-327
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Journal article (other academic/artistic)abstract
- Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards the understanding of satellite cell behaviour in exercised human muscles. It is hypothesised currently that exercise in humans can induce (1) the activation of satellite cells without proliferation, (2) proliferation and withdrawal from differentiation, (3) proliferation and differentiation to provide myonuclei and (4) proliferation and differentiation to generate new muscle fibres or to repair segmental fibre injuries. In humans, the satellite cell pool can increase as early as 4 days following a single bout of exercise and is maintained at higher level following several weeks of training. Cessation of training is associated with a gradual reduction of the previously enhanced satellite cell pool. In the elderly, training counteracts the normal decline in satellite cell number seen with ageing. When the transcriptional activity of existing myonuclei reaches its maximum, daughter cells generated by satellite cell proliferation are involved in protein synthesis by enhancing the number of nuclear domains. Clearly, delineating the events and the mechanisms behind the activation of satellite cells both under physiological and pathological conditions in human skeletal muscles remains an important challenge.
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| 7. |
- Ambrosio, Fabrisia, et al.
(author)
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The effect of muscle loading on skeletal muscle regenerative potential : an update of current research findings relating to aging and neuromuscular pathology
- 2009
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In: American Journal of Physical Medicine & Rehabilitation. - Baltimore : Lippincott Williams & Wilkins. - 0894-9115 .- 1537-7385. ; 88:2, s. 145-155
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Research review (peer-reviewed)abstract
- Skeletal muscle is a dynamic tissue with a remarkable ability to continuously respond to environmental stimuli. Among its adaptive responses is the widely investigated ability of skeletal muscle to regenerate after loading or injury or both. Although significant basic science efforts have been dedicated to better understand the underlying mechanism controlling skeletal muscle regeneration, there has been relatively little impact in the clinical approaches used to treat skeletal muscle injuries and wasting. The purpose of this review article is to provide an overview of the basic biology of satellite cell function in response to muscle loading and to relate these findings in the context of aging and neuromuscular pathology for the rehabilitation medicine specialist.
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| 8. |
- Gard, Anna, et al.
(author)
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Widespread White Matter Abnormalities in Concussed Athletes Detected by 7T Diffusion Magnetic Resonance Imaging
- 2024
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In: Journal of Neurotrauma. - : Mary Ann Liebert Inc.. - 0897-7151 .- 1557-9042.
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Journal article (peer-reviewed)abstract
- Sports-related concussions may cause white matter injuries and persistent post-concussive symptoms (PPCS). We hypothesized that athletes with PPCS would have neurocognitive impairments and white matter abnormalities that could be revealed by advanced neuroimaging using ultra-high field strength diffusion tensor (DTI) and diffusion kurtosis (DKI) imaging metrics and cerebrospinal fluid (CSF) biomarkers. A cohort of athletes with PPCS severity limiting the ability to work/study and participate in sport school and/or social activities for ≥6 months completed 7T magnetic resonance imaging (MRI) (morphological T1-weighed volumetry, DTI and DKI), extensive neuropsychological testing, symptom rating, and CSF biomarker sampling. Twenty-two athletes with PPCS and 22 controls were included. Concussed athletes performed below norms and significantly lower than controls on all but one of the psychometric neuropsychology tests. Supratentorial white and gray matter, as well as hippocampal volumes did not differ between concussed athletes and controls. However, of the 72 examined white matter tracts, 16% of DTI and 35% of DKI metrics (in total 28%) were significantly different between concussed athletes and controls. DKI fractional anisotropy and axial kurtosis were increased, and DKI radial diffusivity and radial kurtosis decreased in concussed athletes when compared with controls. CSF neurofilament light (NfL; an axonal injury marker), although not glial fibrillary acidic protein, correlated with several diffusion metrics. In this first 7T DTI and DKI study investigating PPCS, widespread microstructural alterations were observed in the white matter, correlating with CSF markers of axonal injury. More white matter changes were observed using DKI than using DTI. These white matter alterations may indicate persistent pathophysiological processes following concussion in sport.
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| 9. |
- Alrifaiy, Ahmed, et al.
(author)
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A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy : first investigations of single biological cells
- 2015
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In: Biomedical engineering online. - : Springer Science and Business Media LLC. - 1475-925X. ; 14
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Journal article (peer-reviewed)abstract
- The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O 2 to an anoxic value of 0.0-0.5% O 2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 ± 1 s and a fully developed deoxygenated spectrum was observed after 298 ± 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 ± 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 ± 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 ± 0.412 M Ω and 889.7 ± 1.74 M Ω respectively.
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| 10. |
- Kadi, Fawzi, et al.
(author)
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Satellite cells and myonuclei in young and elderly women and men
- 2004
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In: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 29:1, s. 120-127
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Journal article (peer-reviewed)abstract
- The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.
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