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Sökning: WFRF:(Lindgren Elisabet)

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1.
  • Manti, M., et al. (författare)
  • Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice
  • 2020
  • Ingår i: FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 34:11, s. 14440-14457
  • Tidskriftsartikel (refereegranskat)abstract
    • Nerve growth factor (NGF) is critical for the development and maintenance of the peripheral sympathetic neurons. NGF is also involved in the ovarian sympathetic innervation and in the development and maintenance of folliculogenesis. Women with the endocrine disorder, polycystic ovary syndrome (PCOS), have an increased sympathetic nerve activity and increased ovarian NGF levels. The role of ovarian NGF excess in the PCOS pathophysiology and in the PCOS-related features is unclear. Here, using transgenic mice overexpressesing NGF in the ovarian theca cells (17NF mice), we assessed the female embryonic development, and the reproductive and metabolic profile in adult females. Ovarian NGF excess caused growth restriction in the female fetuses, and a delayed gonocyte and primary oocyte maturation. In adulthood, the 17NF mice displayed irregular estrous cycles and altered ovarian expression of steroidogenic and epigenetic markers. They also exhibited an increased sympathetic output with increased circulating dopamine, and metabolic dysfunction reflected by aberrant adipose tissue morphology and function, impaired glucose metabolism, decreased energy expenditure, and hepatic steatosis. These findings indicate that ovarian NGF excess leads to adverse fetal development and to reproductive and metabolic complications in adulthood, mirroring common features of PCOS. This work provides evidence that NGF excess may be implicated in the PCOS pathophysiology.
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2.
  • Engström, Elisabet, et al. (författare)
  • Auditory event-related potentials and mismatch negativity in children with hearing loss using hearing aids or cochlear implants – A three-year follow-up study
  • 2021
  • Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier. - 0165-5876 .- 1872-8464. ; 140
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The primary aim was to examine how event-related potentials (ERPs) and mismatch negativity (MMN) change and develop over time among children with hearing loss (HL) using hearing aids (HAs) or cochlear implants (CIs). Children with normal hearing (NH) were tested as a reference group. Methods: This three-year follow-up study included 13 children with sensorineural HL (SNHL); 7 children using bilateral HAs and 6 children using CIs; and 10 children with NH as a reference group. ERPs were recorded at baseline and after three years. At time for the original study the children were approximately 5–8 years old and at the follow-up study 8–11 years old. ERP recordings and data processing were identical in both sessions. A standard stimulus alternated with five different deviants (gap, intensity, pitch, location and duration), presented in a pseudorandom sequence, thus following the multi-feature paradigm, Optimum-1. MMN was calculated from the average ERP of each deviant minus the standard stimuli. Repeated measures ANOVA was used for the statistical analyses and the results were based on samples within a specific time interval; 80–224 ms. Results: There was a statistically significant difference in the obligatory responses between the NH and HA groups at baseline, but this difference disappeared after three years in our follow-up study. The children with HA also showed a significant difference in mean ERP at baseline compared to follow-up, and significant differences between the deviants at follow-up but not at baseline. This suggests an improvement over time among the children with HAs. On the other hand, the children with CIs did not differ from the NH children at baseline, but after three years their mean ERP was significantly lower compared to both the children with HA and NH, indicating a reduced development of the central auditory system in this age span among the children with CIs. Regarding MMN, there was an interaction between the duration deviant and time for the children with HA, also indicating a possible improvement over time among the HA children. Conclusions: This three-year follow-up study shows neurophysiological differences between children with HL and children with NH. The results suggest a delay in the central auditory processing among the HA children compared to children with NH, but a possible catch-up, over time, and this potential may be worth to be utilized. Regarding the CI children, similar improvement in this age span is missing, meaning there are differences between the subgroups of children with HL, i.e. the children with HAs vs. CIs. The results highlight the importance of distinguishing between subgroups of children with HL in further research.
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3.
  • Engström, Elisabet, et al. (författare)
  • Computer-assisted reading intervention for children with hearing impairment using cochlear implants : Effects on auditory event-related potentials and mismatch negativity
  • 2020
  • Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier. - 0165-5876 .- 1872-8464. ; 137
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The primary aim was to find out whether a computer-assisted reading intervention program with a phonic approach can affect event-related (ERPs) and mismatch negativity (MMN) in hearing impaired (HI) children using cochlear implants (CIs).METHODS: This study involved a test group of 15 HI children with CIs and a control group of 14 normal hearing (NH) children. The children were 4 years and 10 months to 8 years and 1 month old. ERPs were recorded immediately before and after 4 weeks of training with a computer-assisted reading intervention, GraphoGame. A multi-feature paradigm, Optimum-1, was used, i.e. a standard stimulus alternated with five different deviants: gap intensity, pitch, location and duration. MMN was calculated from the mean amplitude ERP of each deviant minus the standard stimulus response in a specific time interval, 80 - 224 ms. Repeated measures ANOVA was used for the statistical analysis.RESULTS: The results did not show any significant changes with the computerassisted training in the ERPs and MMNs among the HI children with CIs. The presence of both MMN and a positive mismatch response (pMMR), which might reflect an immaturity, complicates interpreting the results in this age group. Individually, there was a mix of MMNs and pMMRs among all participants, pre and post training, and the change of each deviant after intervention was not predictable.CONCLUSIONS: There are no significant changes in ERP or MMN after intervention, however lack of significances must be interpreted with caution. Besides the presence of both MMNs and pMMRs, only modest changes are to be expected on an individual basis and small samples hinder making statistical conclusions regarding the training's effects. The study contributes to some more descriptive pieces of ERPs and MMNs among the HI children with CIs. The issues of MMN and pMMR are highlighted.
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4.
  • Engström, Elisabet, et al. (författare)
  • Computer-assisted reading intervention for children with sensorineural hearing loss using hearing aids : Effects on auditory event-related potentials and mismatch negativity
  • 2019
  • Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier. - 0165-5876 .- 1872-8464. ; 117, s. 17-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The primary aim was to investigate whether computer-assisted reading intervention somehow can affect event-related potentials (ERP) and mismatch negativity (MMN) in hearing impaired (HI) children with hearing aids (HAs) and normal hearing (NH) children. Methods: The study included 15 HI children with sensorineural hearing loss (SNHL) using bilateral HAs and 14 NH children as a reference group; all children between the ages of 5 and 8. A multi-feature MMN-paradigm, Optimum-1, with a standard stimulus alternating with 5 different deviants was used. ERPs were recorded pre and post intervention, i.e. one month of repeatedly computer-assisted training (GraphoGame). MMN was calculated from the average ERP of each deviant minus standard. Data were based on samples within a specific time interval, 80–224 ms, and repeated measures ANOVA was used to analyze possible interactions. Results: There was a significant difference between groups before training, though, the mean obligatory responses or MMN was not statistically significantly different before versus after training, neither among the NH nor the HI children. Further, the HI children did generally achieve lower levels in GraphoGame compared to the NH children. Altogether, our findings indicate differences between the groups and that training may affect the neurophysiological processing in the brain, gaining the HI children. Both MMN and positive mismatch response (pMMR) were seen among both the HA and NH children, irrespective to deviant type. Individually, changes of the MMN and pMMR after training seem unpredictable. Conclusion: There are statistically significant differences in both the obligatory responses in ERP and the MMNs between the NH and HI groups before the computer-assisted training. Though, these differences disappear after the intervention. This suggests possible training effects regarding the central auditory processing among the HI children.
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5.
  • Nilsson, E., et al. (författare)
  • Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome
  • 2018
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 103:12, s. 4465-4477
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown. Objective: To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate them to phenotypic variations. Design/Participants: In a case-control study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-, and body mass index. matched controls (n = 14) were analyzed by array-based DNA methylation and mRNA expression profiling. Results: Eighty-five unique transcripts were differentially expressed in muscle from women with PCOS vs controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS had reduced expression of genes involved in immune system pathways. Two CpG sites showed differential DNA methylation after correction for multiple testing. However, an mRNA expression of similar to 30% of the differentially expressed genes correlated with DNA methylation levels of CpG sites in or near the gene. Functional follow-up studies demonstrated that KLF10 is under transcriptional control of insulin, where insulin promotes glycogen accumulation in myotubes of human muscle cells. Testosterone downregulates the expression levels of COL1A1 and MAP2K6. Conclusion: PCOS is associated with aberrant skeletal muscle gene expression with dysregulated pathways. Furthermore, we identified specific changes in muscle DNA methylation that may affect gene expression. This study showed that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, can explain the metabolic abnormalities seen in these women.
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6.
  • Ohlin, Elisabet, et al. (författare)
  • Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia.
  • 2011
  • Ingår i: Brain. - : Oxford University Press. - 1460-2156 .- 0006-8950. ; 134, s. 2339-2357
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiogenesis and increased permeability of the blood-brain barrier have been reported to occur in animal models of Parkinson's disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood-brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson's disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson's disease.
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7.
  • Benrick, Anna, 1979-, et al. (författare)
  • Electroacupuncture mimics exercise-induced changes in skeletal muscle gene expression in women with polycystic ovary syndrome
  • 2020
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:6, s. 2027-2041
  • Tidskriftsartikel (refereegranskat)abstract
    • ContextAutonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture but the mechanisms are largely unknown.ObjectiveTo identify the molecular mechanisms underlying electroacupuncture-induced glucose uptake in skeletal muscle in insulin-resistant overweight/obese women with and without polycystic ovary syndrome (PCOS).Design/ParticipantsIn a case-control study, skeletal muscle biopsies were collected from 15 women with PCOS and 14 controls before and after electroacupuncture. Gene expression and methylation was analyzed using Illumina BeadChips arrays.ResultsA single bout of electroacupuncture restores metabolic and transcriptional alterations and induces epigenetic changes in skeletal muscle. Transcriptomic analysis revealed 180 unique genes (q < 0.05) whose expression was changed by electroacupuncture, with 95% of the changes towards a healthier phenotype. We identified DNA methylation changes at 304 unique sites (q < 0.20), and these changes correlated with altered expression of 101 genes (P < 0.05). Among the 50 most upregulated genes in response to electroacupuncture, 38% were also upregulated in response to exercise. We identified a subset of genes that were selectively altered by electroacupuncture in women with PCOS. For example, MSX1 and SRNX1 were decreased in muscle tissue of women with PCOS and were increased by electroacupuncture and exercise. siRNA-mediated silencing of these 2 genes in cultured myotubes decreased glycogen synthesis, supporting a role for these genes in glucose homeostasis.ConclusionOur findings provide evidence that electroacupuncture normalizes gene expression in skeletal muscle in a manner similar to acute exercise. Electroacupuncture might therefore be a useful way of assisting those who have difficulties performing exercise.
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8.
  • Engström, Elisabet, et al. (författare)
  • Computer-assisted reading intervention for children with sensorineural hearing loss using hearing aids : Effects on auditory event-related potentials and mismatch negativity
  • 2019
  • Ingår i: International Journal of Pediatric Otorhinolaryngology. - 0165-5876 .- 1872-8464. ; 117, s. 17-25
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:The primary aim was to investigate whether computer-assisted reading intervention somehow can affect event-related potentials (ERP) and mismatch negativity (MMN) in hearing impaired (HI) children with hearing aids (HAs) and normal hearing (NH) children.METHODS:The study included 15 HI children with sensorineural hearing loss (SNHL) using bilateral HAs and 14 NH children as a reference group; all children between the ages of 5 and 8. A multi-feature MMN-paradigm, Optimum-1, with a standard stimulus alternating with 5 different deviants was used. ERPs were recorded pre and post intervention, i.e. one month of repeatedly computer-assisted training (GraphoGame). MMN was calculated from the average ERP of each deviant minus standard. Data were based on samples within a specific time interval, 80-224 ms, and repeated measures ANOVA was used to analyze possible interactions.RESULTS:There was a significant difference between groups before training, though, the mean obligatory responses or MMN was not statistically significantly different before versus after training, neither among the NH nor the HI children. Further, the HI children did generally achieve lower levels in GraphoGame compared to the NH children. Altogether, our findings indicate differences between the groups and that training may affect the neurophysiological processing in the brain, gaining the HI children. Both MMN and positive mismatch response (pMMR) were seen among both the HA and NH children, irrespective to deviant type. Individually, changes of the MMN and pMMR after training seem unpredictable.CONCLUSION:There are statistically significant differences in both the obligatory responses in ERP and the MMNs between the NH and HI groups before the computer-assisted training. Though, these differences disappear after the intervention. This suggests possible training effects regarding the central auditory processing among the HI children.
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9.
  • Huttner, Hagen B, et al. (författare)
  • The age and genomic integrity of neurons after cortical stroke in humans
  • 2014
  • Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 17:6, s. 801-803
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived (14)C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.
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10.
  • Ilinca, A., et al. (författare)
  • MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor
  • 2021
  • Ingår i: Neurology-Genetics. - : Lippincott Williams & Wilkins. - 2376-7839. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke. Methods We studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses. Results Fifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease. Conclusions Our data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.
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