| 1. |
- Jakobsson, Trille, et al.
(författare)
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Physical Activity objectively assessed over a Year in Children and Adolescents with Cerebral Palsy who are Non-Ambulant using ActiGraph GT3X Accelerometer
- 2024
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Konferensbidrag (refereegranskat)abstract
- Introduction: Children gain increased health and wellbeing by participating in physical activity (PA). In children and adolescents with cerebral palsy who are non-ambulant (children with CP-NA), levels of PA have been indicated to be lower compared to children and adolescents without physical disabilities. However, research on PA in children with CP-NA is limited. Therefore, this study aims to evaluate objectively assessed PA over the course of one year when using ActiGraph GT3X accelerometer in children with CP-NA. Participants and methods: Accelerometer data were retrieved from 32 children with CP-NA (4 - 17 years) in Region Skane, Sweden. Participants wore the ActiGraph GT3X accelerometer all waking hours for up to four periods of seven consecutive days over a year. Statistically sensitivity analyses were run to explore differences in PA between subtypes of cerebral palsy and GMFCS level IV and V. Results: In total 481 days and 85 periods of valid accelerometer data were obtained. Light PA was statically significantly higher for children with dyskinetic CP-NA compared to spastic CP-NA (median (IQR) 57 (37.42-88.1) vs. 34.42 (20.42-55.96), p = <0.001). Light PA (median (IQR) 57 (36.67-88.5) vs. 25.42 (17-38.75), p = <0.001) and moderate to vigorous PA (median (IQR) 1.83 (1-4.17) vs. 1.67 (0.67-2), p = <0.001) were statically significantly higher for children with CP-NA GMFCS level IV compared to level V. Conclusion: Preliminary results indicate differences in PA levels between subtype of cerebral palsy and GMFCS level. Further analyses to explore potential differences in PA over the year will be run.
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| 2. |
- Varga, Tibor V, et al.
(författare)
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Acute and Long-Term Changes in Blood-Borne Biomarkers in Response to Dynamic Standing in Nonambulant Children With Cerebral Palsy
- 2024
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Ingår i: Pediatric Exercise Science. - Champaign, IL : Human Kinetics. - 0899-8493 .- 1543-2920. ; 36:1, s. 15-22
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate acute and long-term changes in hormonal and inflammatory biomarkers in nonambulant children with cerebral palsy in response to dynamic standing exercise.Methods: Fourteen children with severe cerebral palsy were recruited. Anthropometrics and body composition measures were obtained. Physical activity levels before the study were assessed using hip-worn accelerometry. All children underwent a 30-minute dynamic standing exercise using the Innowalk standing aid. Respiratory data during exercise were collected using indirect calorimetry. Blood samples were collected before and after exercise. Blood samples were also obtained after two 16-week exercise protocols, in a resting state. Hormonal and inflammatory metabolites were measured from blood serum/plasma, and acute and long-term changes in biomarker levels were assessed using Wilcoxon signed-rank tests.Results: Of the 14 children at baseline, all had slightly/moderately/severely elevated C-reactive protein and cortisol levels. C-reactive protein levels were decreased following a 30-minute bout of dynamic standing (before exercise: 53 mg/L [interquartile range: 40-201]; after exercise: 39 mg/L [interquartile range: 20-107]; P = .04).Conclusions: We show that several hormonal and inflammatory biomarkers are dysregulated in children with cerebral palsy. Our preliminary results from a small, but deep-phenotyped prospective cohort indicate acute and long-term alterations of several biomarkers in response to exercise. ©2023 The Authors.
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| 3. |
- Aksel Jacobsen, Freja, et al.
(författare)
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A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation
- 2018
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Ingår i: Journal of Neuroimmune Pharmacology. - New York, NY : Springer-Verlag New York. - 1557-1890 .- 1557-1904. ; 13:2, s. 265-276
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a neuroinflammatory degenerative disease, caused by activated immune cells infiltrating the CNS. The disease etiology involves both genetic and environmental factors. The mouse genetic locus, Eae27, linked to disease development in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis, was studied in order to identify contributing disease susceptibility factors and potential drug targets for multiple sclerosis. Studies of an Eae27 congenic mouse strain, revealed that genetic variation within Eae27 influences EAE development. The Abl2 gene, encoding the non-receptor tyrosine kinase Arg, is located in the 4,1 megabase pair long Eae27 region. The Arg protein plays an important role in cellular regulation and is, in addition, involved in signaling through the B- and T-cell receptors, important for the autoimmune response. The presence of a single nucleotide polymorphism causing an amino acid change in a near actin-interacting domain of Arg, in addition to altered lymphocyte activation in the congenic mice upon immunization with myelin antigen, makes Abl2/Arg a candidate gene for EAE. Here we demonstrate that the non-synonymous SNP does not change Arg’s binding affinity for F-actin but suggest a role for Abl kinases in CNS inflammation pathogenesis by showing that pharmacological inhibition of Abl kinases ameliorates EAE, but not experimental arthritis. © 2018 The Author(s)
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| 4. |
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| 5. |
- Andersson, Alva, et al.
(författare)
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Functional muscle power in the lower extremity in adults with congenital heart disease
- 2023
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Ingår i: International Journal of Cardiology Congenital Heart Disease. - : Elsevier BV. - 2666-6685. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to investigate functional muscular power in the lower extremity in adults with congenital heart disease (ACHD) and compare results with those of healthy persons. Secondarily, we set out to assess muscle power in relation to age, sex, and complexity of ACHD.Methods: Between 2013 and 2019, 1126 patients attended the ACHD Unit of Sahlgrenska University Hospital/Ostra and performed a test battery to determine physical fitness. Of these patients, 559 who performed the Timed-Stands Test (TST)-which requires 10 stands from a chair at the maximal possible speed-were included in the study.Results: Patients with ACHD performed the TST slower than reference (14.6 s [12.0-18.0] vs. 11.7 s [9.8-14.3], p < 0.001). Men with ACHD performed the TST more rapidly or according to reference in 8% of patients aged 18-39 years, 21% of patients aged 40-65 years, and 55% of patients aged >65 years. Women with ACHD performed the TST more rapidly or according to reference in 21% of patients aged 18-39 years, 56% of patients aged 40-65 years, and 32% of patients aged >65 years. Men with ACHD performed the TST significantly faster than women with ACHD (p < 0.001).Conclusions: Decreased functional muscle power was observed in patients with ACHD and was most pronounced in patients aged 18-39 years. Decreased muscle power is important to detect and requires further assessment because it may contribute to an increased risk of falling and developing lifestyle related diseases.
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| 6. |
- Andersson, Linda, 1973, et al.
(författare)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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| 7. |
- Andersson, Åsa, 1960-, et al.
(författare)
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A transcriptional regulator controlling severity in experimental arthritis
- 2019
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Ingår i: Annals of the Rheumatic Diseases. - London, UK : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 78:Suppl. 2, s. 667-667
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Tidskriftsartikel (refereegranskat)abstract
- Background: Susceptibility to Rheumatoid Arthritis (RA) is dependent on complex interactions among genetic and environmental factors. Protein candidates and their role in pathways leading to chronic inflammation of the joints, in addition to their potential as drug targets, can be revealed with the help of experimental models for disease (1). From the results of functional genetic studies, we have recently shown that the T-box gene, TBX3, is a candidate gene in Collagen Induced Arthritis (CIA), an experimental model for RA (2). TBX3 encodes a transcriptional regulator involved in differentiation of several organs, including bone, during embryonic development. It has, in addition, been demonstrated important in oncogenesis (3). Our studies suggest that TBX3 has a role in B-cell activation and is important for the severity of disease in the CIA model (2). Objectives: The objective of this project is to understand the role for the transcriptional regulator TBX3 in development of RA. Methods: Bioinformatics based comparative studies of mouse and human alleles in the regulatory region of TBX3. CRISPR/Cas9-introduced deletions and base modifications in human B-cell lines. Activation of genetically modified B-cells in vitro, followed by analyses of proliferative response and antibody production. Results: Studies of CIA development in mice with single nucleotide polymorphisms (SNPs) in the regulatory region of Tbx3 revealed a significant difference in severity of arthritis. In line with this, the anti-collagen type II antibody titers were shown substantially higher in mice with more severe arthritis, even before onset of disease. In addition, preliminary data shows that the proliferative response to Type II collagen upon re-challenge of lymph node cells in vitro is higher in these mice, suggesting a more active response to the disease-inducing antigen. Because the TBX3 gene is conserved between mouse and human, we are investigating whether similar genetic variations are found in the regulatory region of the human TBX3 gene and whether the putative genetic variation would lead to a distinct B-cell phenotype upon activation in vitro. Conclusion: We suggest that the oncoprotein TBX3 is a novel candidate contributing to disease severity in experimental arthritis. Investigations of genetic variation in the TBX3 gene and its role in the activation of human B-cells will reveal whether this protein is a candidate for influencing also development of RA.
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| 8. |
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| 9. |
- Andersson, Åsa, 1960-
(författare)
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B cell repertoire development in normal physiology and autoimmune disease
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The B cell repertoire in the neonatal immune system (IS) is characterised by reactivity towards self-components, including other immunoglobulin (Ig) V-regions. These properties have been suggested to be a requirement for the development of a normal immune system. DNA sequencing of two interacting Ig idiotypes, derived from neonatal, preimmune mice, demonstrated that such idiotypic connectivity is germ- line encoded and devoid of VDJ junctional diversity. The serum levels of the same Ig idiotypes were studied in normal mice and demonstrated that the expression in serum fluctuated over time in a pattern compatible with a complex dynamic system. In contrast, similar analyses in autoimmune mice or humans demonstrated fluctuations in Ig titers that differed significantly from the healthy individuals. These findings suggested that pathological autoimmunity may be associated with fundamental alterations in the dynamics of natural antibody (ab) expression. This was further investigated in the nonobese diabetic (NOD) mouse, an animal model for human Type I diabetes. Suppression of the early B cell development in the NOD mouse prevented the development of diabetes, suggesting a role for B cells/Igs in the development of diabetes in these mice. Furthermore, neonatal injections of polyclonal Ig preparations or single, monoclonal natural abs inhibited disease induction. The prevention of diabetes development by one such natural ab was demonstrated to be dependent on both the dose injected and the timing of administration. Studies of the B cell repertoire development in NOD mice, compared to normal mice, by DNA-sequence analyses of IgVH rearrangements utilising genes from the most D-proximal Vh family, Vh7183, supported the idea of an aberrant B cell repertoire in this mouse model. Thus, the adult NOD mouse retained a neonatal pattern of Vh7183 rearrangements. This pattern could, however, be "normalised" by neonatal injection of a natural antibody, previously demonstrated to prevent the development of T cell dependent autoimmunity in the NOD mouse.
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| 10. |
- Andersson, Åsa, 1960-, et al.
(författare)
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B-cells and Inflammation in the Absence of the Abelson Related Gene (Arg)
- 2016
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Ingår i: Journal of Clinical & Cellular Immunology. - Los Angeles, CA : Omics Publishing Group. - 2155-9899. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- The Abelson non-receptor tyrosine kinases, c-Abl and Arg, are important regulators of cellular processes in cancer, inflammation, infection, and neuronal dynamics. Recent research on the role for these kinases in processes involving interactions with the cytoskeleton or signaling molecules, may lead to further insight into the pathogenesis of a variety of disorders, including chronic inflammatory diseases. In a mouse model for multiple sclerosis, we recently reported that Arg deficient mice develop T-cell mediated autoimmune neuro-inflammation with the same severity as littermate controls, but display a different B-cell phenotype upon immunization. Here we comment on these results and discuss the role for Arg in B-cell activation and homeostasis.
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