| 1. |
- Abdul-Hussein, Saba, et al.
(författare)
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Expression profiles of muscle disease-associated genes and their isoforms during differentiation of cultured human skeletal muscle cells
- 2012
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The formation of contractile myofibrils requires the stepwise onset of expression of muscle specific proteins. It is likely that elucidation of the expression patterns of muscle-specific sarcomeric proteins is important to understand muscle disorders originating from defects in contractile sarcomeric proteins.METHODS: We investigated the expression profile of a panel of sarcomeric components with a focus on proteins associated with a group of congenital disorders. The analyses were performed in cultured human skeletal muscle cells during myoblast proliferation and myotube development.RESULTS: Our culture technique resulted in the development of striated myotubes and the expression of adult isoforms of the sarcomeric proteins, such as fast TnI, fast TnT, adult fast and slow MyHC isoforms and predominantly skeletal muscle rather than cardiac actin. Many proteins involved in muscle diseases, such as beta tropomyosin, slow TnI, slow MyBPC and cardiac TnI were readily detected in the initial stages of muscle cell differentiation, suggesting the possibility of an early role for these proteins as constituent of the developing contractile apparatus during myofibrillogenesis. This suggests that in disease conditions the mechanisms of pathogenesis for each of the mutated sarcomeric proteins might be reflected by altered expression patterns, and disturbed assembly of cytoskeletal, myofibrillar structures and muscle development.CONCLUSIONS: In conclusion, we here confirm that cell cultures of human skeletal muscle are an appropriate tool to study developmental stages of myofibrillogenesis. The expression of several disease-associated proteins indicates that they might be a useful model system for studying the pathogenesis of muscle diseases caused by defects in specific sarcomeric constituents.
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| 2. |
- Abdul-Hussein, Saba, et al.
(författare)
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Phenotypes of Myopathy-Related Beta-Tropomyosin Mutants in Human and Mouse Tissue Cultures
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in TPM2 result in a variety of myopathies characterised by variable clinical and morphological features. We used human and mouse cultured cells to study the effects of beta-TM mutants. The mutants induced a range of phenotypes in human myoblasts, which generally changed upon differentiation to myotubes. Human myotubes transfected with the E41K-beta-TMEGFP mutant showed perinuclear aggregates. The G53ins-beta-TMEGFP mutant tended to accumulate in myoblasts but was incorporated into filamentous structures of myotubes. The K49del-beta-TMEGFP and E122K-beta-TMEGFP mutants induced the formation of rod-like structures in human cells. The N202K-beta-TMEGFP mutant failed to integrate into thin filaments and formed accumulations in myotubes. The accumulation of mutant beta-TMEGFP in the perinuclear and peripheral areas of the cells was the striking feature in C2C12. We demonstrated that human tissue culture is a suitable system for studying the early stages of altered myofibrilogenesis and morphological changes linked to myopathy-related beta-TM mutants. In addition, the histopathological phenotype associated with expression of the various mutant proteins depends on the cell type and varies with the maturation of the muscle cell. Further, the phenotype is a combinatorial effect of the specific amino acid change and the temporal expression of the mutant protein.
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| 3. |
- Abulafia, C., et al.
(författare)
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Relationship between Cognitive and Sleep-wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer's Disease
- 2017
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Early neuropathological changes characteristic of late-onset Alzheimer's disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 +/- 0.4 vs. 8.6 +/- 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler's vocabulary 51.4 +/- 1.3 vs. 44.3 +/- 1.5, t = 2.49, df = 49, p < 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 +/- 0.47 h vs. 3.8 +/- 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep-wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.
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| 4. |
- Adamovic, Tatjana, 1974, et al.
(författare)
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Nonrandom pattern of chromosome aberrations in 17beta-estradiol-induced rat mammary tumors: indications of distinct pathways for tumor development.
- 2007
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:5, s. 459-69
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens play an important role in breast cancer etiology and the ACI rat provides a novel animal model for defining the mechanisms through which estrogens contribute to mammary cancer development. In crossing experiments between the susceptible ACI strain and two resistant strains, COP (Copenhagen) and BN (Brown Norway), several quantitative trait loci (QTL) that affect development of 17beta-estradiol (E2)-induced mammary tumors have been defined. Using comparative genomic hybridization (CGH), we have analyzed cytogenetic aberrations in E2-induced mammary cancers and have found clear patterns of nonrandom chromosomal involvement. Approximately two thirds of the tumors exhibited copy number changes. Losses of rat chromosome 5 (RNO5) and RNO20 were particularly common, and it was found that these two aberrations often occurred together. A third recurrent aberration involving proximal gain and distal loss in RNO6 probably defined a distinct subgroup of tumors, since it never occurred in combination with RNO5 loss. Interestingly, QTL with powerful effects on mammary cancer development have been mapped to RNO5 and RNO6. These findings suggest that there were at least two genetic pathways to tumor formation in this rat model of E2-induced mammary cancer. By performing CGH on mammary tumors from ACI rats, F1 rats from crosses between the ACI and COP or BN strains and ACI.BN-Emca8 congenic rats, which carry the BN allele of the Emca8 QTL on RNO5 on the ACI genetic background, we were able to determine that the constitution of the germ line influences the pattern of chromosomal aberrations.
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| 5. |
- Adamovic, Tatjana, 1974, et al.
(författare)
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Oncogene amplification in the proximal part of chromosome 6 in rat endometrial adenocarcinoma as revealed by combined BAC/PAC FISH, chromosome painting, zoo-FISH, and allelotyping.
- 2005
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 44:2, s. 139-53
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Tidskriftsartikel (refereegranskat)abstract
- The inbred BDII rat is a valuable experimental model for the genetic analysis of endometrial adenocarcinoma (EAC). One common aberration detected by comparative genomic hybridization in rat EAC was gain/amplification affecting the proximal part of rat chromosome 6 (RNO6). We applied rat and mouse chromosome painting probes onto tumor cell metaphase preparations in order to detect and characterize gross RNO6 aberrations. In addition, the RNO6q11-q16 segment was analyzed by fluorescence in situ hybridization with probes representing 12 cancer-related genes in the region. The analysis revealed that seven tumors contained large RNO6-derived homogeneously staining regions (HSRs) in addition to several normal or near-normal RNO6 chromosomes. Five tumors (two of which also had HSRs) exhibited a selective increase of the RNO6q11-q16 segment, sometimes in conjunction with moderate amplification of one or a few genes. Most commonly, the amplification affected the region centered around band 6q16 and included the Mycn, Ddx1, and Rrm2 genes. A second region, centering around Slc8a1 and Xdh, also was affected by gene amplification but to a lesser extent. The aberrations in the proximal part of RNO6 were further analyzed using allelotyping of microsatellite markers in all tumors from animals that were heterozygous in the proximal RNO6 region. We could detect allelic imbalance (AI) in 12 of 20 informative tumors, 6 of which were in addition to those already analyzed by molecular cytogenetic methods as described. Our findings suggest that increase/amplification of genes in this chromosome region contribute to the development of this hormone-dependent tumor.
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| 6. |
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| 7. |
- Ahlstrand, Inger, et al.
(författare)
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Health-promoting factors among students in higher education within health care and social work : a cross-sectional analysis of baseline data in a multicentre longitudinal study
- 2022
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Ingår i: BMC Public Health. - London : BioMed Central. - 1471-2458. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Educational environments are considered important in strengthening students’ health status and knowledge, which are associated with good educational outcomes. It has been suggested to establish healthy universities based on a salutogenic approach – namely, health promotion. The aim of this study was to describe health-promoting resources and factors among first-semester students in higher education in healthcare and social work.Methods: This cross-sectional study is based on a survey distributed among all students in seven healthcare and social work programmes at six universities in southern Sweden. The survey was carried out in 2018 using a self-reported, web-based questionnaire focussing on general health and well-being, lifestyle factors together with three validated instruments measuring health-promoting factors and processes: the Sense of Coherence (SOC) scale, Salutogenic Health Indicator Scale (SHIS) and Occupational Balance Questionnaire (OBQ).Results: Of 2283 students, 851 (37.3%) completed the survey, of whom 742 (87.1%) were women; 722 (84.8%) were enrolled on healthcare programmes, and 129 (15.2%) were enrolled on social work programmes. Most reported good general health and well-being (88.1% and 83.7%, respectively). The total mean scores for the SOC scale, SHIS and OBQ were, respectively, 59.09 (SD = 11.78), 44.04 (SD = 9.38) and 26.40 (SD = 7.07). Well-being and several healthy lifestyles were related to better general health and higher SOC, SHIS and OBQ scores. Multiple linear and logistic regressions showed that perceived well-being and no sleeping problems significantly predicted higher general health and higher SOC, SHIS and OBQ scores. Being less sedentary and non-smoking habits were significant predictors of higher SOC.Conclusions: Swedish students in higher education within the healthcare and social work sector report good general health and well-being in the first semester, as well as health-promoting resources (i.e. SOC, SHIS and OBQ), and in some aspects, a healthy lifestyle. High-intensity exercise, no sleeping problems and non-smoking seem to be of importance to both general health and health-promotive resources. This study contributes to knowledge about the health promotive characteristics of students in the healthcare and social work fields, which is of importance for planning universities with a salutogenic approach.
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| 8. |
- Ahluwalia, Bani, et al.
(författare)
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Effects of Aloe barbadensis Mill. extract (AVH200 (R)) on human blood T cell activity in vitro
- 2016
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Ingår i: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 179, s. 301-309
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Tidskriftsartikel (refereegranskat)abstract
- Ethnopharmacological relevance: Aloe barbadensis Mill. (Aloe vera) is a widely used medicinal plant well reputed for its diverse therapeutic applications. It has been used for thousands of years in folk medicine to treat various conditions and the Aloe vera gel has been reported to possess anti-inflammatory as well as immunostimulatory and immunomodulatory properties. However, the mode of action is still unclear. Aim of the study: The aim of this study was determine the effects of two well-defined A. barbadensis Mill. extracts AVH200 (R) and AVE200 on human blood T cells in vitro. Materials and methods: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated polyclonally in the presence or absence of AVH200 (R) and AVE200. The T cell phenotype was investigated by flow cytometry, cell proliferation was determined by CFSE dye and thymidine assay, respectively and cytokine secretion was determined by MSD (R) Multi-Spot Assay system and ELISA. Results: The presence of AVH200 (R) resulted in a reduced expression of CD25 among CD3(+) T cells and suppression of T cell proliferation in a dose dependent manner. Furthermore, AVH200 (R) reduced the expression of CD28 on CD3(+) T cells. AVH200 (R) also reduced the secretion of IL-2, IFN-gamma and IL-17A in PBMC cultures. The AVH200 (R) dose dependent reduction in T cell activation and proliferation recorded in the cell cultures was not due to apoptosis or cell death. Additionally, AVH200 (R) was found to be more effective as compared to AVE200 in reducing T cell activation and proliferation. Conclusion: AVH200 (R) has the potential to reduce the activation, proliferation and cytokine secretion of healthy human blood T cells. Our study suggests that AVH200 (R) has a suppressive effect on human blood T cells in vitro.
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| 9. |
- Ahmadi, Nasser, 1958, et al.
(författare)
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Clinical characteristics of asymptomatic left ventricular diastolic dysfunction and its association with self-rated health and N-terminal B-type natriuretic peptide: a cross-sectional study
- 2016
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 3:3, s. 205-211
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Tidskriftsartikel (refereegranskat)abstract
- Aims Left ventricular hypertrophy, obesity, hypertension, and N-terminal B-type natriuretic peptide (Nt-proBNP) predict left ventricular diastolic dysfunction with preserved systolic function (DD-PSF). Self-rated health (SRH) is shown to be associated with chronic diseases, but the association of SRH with DD-PSF is unclear. In light of the clinical implications of DD-PSF, the following goals are of considerable importance: (1) to determine the role of SRH in patients with DD-PSF in the general population and (2) to study the association between Nt-proBNP and DD-PSF. Methods and results The current study is a cross-sectional study conducted on a random sampling of a rural population. Individuals 30-75 years of age were consecutively subjected to conventional echocardiography and tissue velocity imaging. Data were collected on 500 (48%) men and 538 (52%) women (n = 1038). DD-PSF was the main outcome, and SRH and Nt-proBNP were the primary indicators. Diabetes mellitus, hypertension, and obesity were accounted for as major confounders of the association with SRH. DD-PSF was identified in 137 individuals, namely, 79 men (15.8%) and 58 women (10.8%). In a multivariate regression model, SRH (OR 2.95; 95% CI 1.02-8.57) and Nt-proBNP (quartile 4 vs. quartile 1 OR 4.23; 95% CI 1.74-10.26) were both independently associated with DD-PSF. Conclusions SRH, evaluated based on a descriptive question on general health, should be included in the diagnostic process of DD-PSF. In agreement with previous studies, our study confirms that Nt-proBNP is a major indicator of DD-PSF.
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| 10. |
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