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Sökning: LAR1:gu > Högskolan i Skövde

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  • Abdul-Hussein, Saba, et al. (författare)
  • Expression profiles of muscle disease-associated genes and their isoforms during differentiation of cultured human skeletal muscle cells.
  • 2012
  • Ingår i: BMC musculoskeletal disorders. - 1471-2474. ; 13
  • 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.
  • Abdul-Hussein, Saba, et al. (författare)
  • Phenotypes of Myopathy-Related Beta-Tropomyosin Mutants in Human and Mouse Tissue Cultures
  • 2013
  • Ingår i: Plos One. - 1932-6203. ; 8:9
  • 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 β-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-β-TM(EGFP) mutant showed perinuclear aggregates. The G53ins-β-TM(EGFP) mutant tended to accumulate in myoblasts but was incorporated into filamentous structures of myotubes. The K49del-β-TM(EGFP) and E122K-β-TM(EGFP) mutants induced the formation of rod-like structures in human cells. The N202K-β-TM(EGFP) mutant failed to integrate into thin filaments and formed accumulations in myotubes. The accumulation of mutant β-TM(EGFP) 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 β-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.
  • Adamovic, Tatjana, et al. (författare)
  • Nonrandom pattern of chromosome aberrations in 17beta-estradiol-induced rat mammary tumors: indications of distinct pathways for tumor development.
  • 2007
  • Ingår i: Genes, chromosomes & cancer. - 1045-2257. ; 46:5, s. 459-69
  • 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 17b-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.
  • Adamovic, Tatjana, et al. (författare)
  • 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
  • Ingår i: Genes, chromosomes & cancer. - 1045-2257. ; 44:2, s. 139-53
  • 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.
  • Adamovic, Tatjana, et al. (författare)
  • Rearrangement and allelic imbalance on chromosome 5 leads to homozygous deletions in the CDKN2A/2B tumor suppressor gene region in rat endometrial cancer
  • 2008
  • Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 184:1, s. 9-21
  • Tidskriftsartikel (refereegranskat)abstract
    • The inbred BDII rat is a valuable experimental model for the genetic analysis of hormone-dependent endometrial adenocarcinoma (EAC). One common aberration detected previously by comparative genomic hybridization in rat EAC is loss affecting mostly the middle part of rat chromosome 5 (RNO5). First, we applied an RNO5-specific painting probe and four region-specific gene probes onto tumor cell metaphases from 21 EACs, and found that rearrangements involving RNO5 were common. The copy numbers of loci situated on RNO5 were found to be reduced, particularly for the CDKN2A/2B locus. Second, polymerase chain reaction analysis was performed with 22 genes and markers and homozygous deletions of the CDKN2A exon 1? and CDKN2B genes were detected in 13 EACs (62%) and of CDKN2A exon 1? in 12 EACs (57%) Third, the occurrence of allelic imbalance in RNO5 was analyzed using 39 microsatellite markers covering the entire chromosome and frequent loss of heterozygosity was detected. Even more intriguing was the repeated finding of allele switching in a narrow region of 7 Mb across the CDKN2A/2B locus. We conclude that genetic events affecting the middle part of RNO5 (including bands 5q31<img src="http://www.sciencedirect.com/scidirimg/entities/223c.gif" />q33 and the CDKN2A locus) contribute to the development of EAC in rat, with the CDKN2A locus having a primary role.
  • Adebayo Awe, Julius, et al. (författare)
  • Three-Dimensional Telomeric Analysis of Isolated Circulating Tumor Cells (CTCs) Defines CTC Subpopulations
  • 2013
  • Ingår i: Translational Oncology. - Neoplasia Press. - 1936-5233. ; 6:1, s. 51-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating tumor cells (CTCs) have been identified with the potential to serve as suitable biomarkers for tumor stage and progression, but the availability of effective isolation technique(s) coupled with detailed molecular characterization have been the challenges encountered in making CTCs clinically relevant. For the first time, we combined isolation of CTCs using the ScreenCell filtration technique with quantitative analysis of CTC telomeres by TeloView. This resulted in the identification and molecular characterization of different subpopulations of CTCs in the same patient. Three-dimensional (3D) telomeric analysis was carried out on isolated CTCs of 19 patients that consisted of four different tumor types, namely, prostate, colon, breast, melanoma, and one lung cancer cell line. With telomeric analysis of the filter-isolated CTCs, the level of chromosomal instability (CIN) of the CTCs can be determined. Our study shows that subpopulations of CTCs can be identified on the basis of their 3D telomeric properties.
  • Ahluwalia, Bani, et al. (författare)
  • Effects of Aloe barbadensis Mill. extract (AVH200 (R)) on human blood T cell activity in vitro
  • 2016
  • Ingår i: Journal of Ethnopharmacology. - 0378-8741. ; 179, s. 301-309
  • 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® 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® 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® Multi-Spot Assay system and ELISA.RESULTS: The presence of AVH200® resulted in a reduced expression of CD25 among CD3(+) T cells and suppression of T cell proliferation in a dose dependent manner. Furthermore, AVH200® reduced the expression of CD28 on CD3(+) T cells. AVH200® also reduced the secretion of IL-2, IFN-γ and IL-17A in PBMC cultures. The AVH200® dose dependent reduction in T cell activation and proliferation recorded in the cell cultures was not due to apoptosis or cell death. Additionally, AVH200® was found to be more effective as compared to AVE200 in reducing T cell activation and proliferation.CONCLUSION: AVH200® has the potential to reduce the activation, proliferation and cytokine secretion of healthy human blood T cells. Our study suggests that AVH200® has a suppressive effect on human blood T cells in vitro.
  • Ahmadi, Nasser S., et al. (författare)
  • 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
  • Ingår i: Esc Heart Failure. - 2055-5822. ; 3:3, s. 205-211
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsLeft 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 resultsThe 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.ConclusionsSRH, 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.
  • Akhavan, Sharareh, et al. (författare)
  • Midwives' experiences of doula support for immigrant women in Sweden : A qualitative study
  • 2012
  • Ingår i: Midwifery. - Elsevier. - 0266-6138. ; 28:1, s. 80-85
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: to describe and analyse midwives’ experiences of doula support for immigrant women in Sweden. Design: qualitative study, analysed using content analysis. Data were collected via interviews. Setting: interviews were conducted at the midwives’ workplaces. One midwife was interviewed at a cafe. Participants: ten midwives, who participated voluntarily and worked in maternity health care in western Sweden. Findings: the interview data generated three main categories. (1) ‘A doula is a facilitator for the midwife’ has two subcategories, ‘In relation to the midwife’ and ‘In comparison with an interpreter’, (2) ‘Confident women giving support, ’has two subcategories, ‘Personal characteristics and attitudes’ and ‘Good support,’ (3) ‘Doulas cover shortcomings’ has two subcategories, ‘In relation to maternity care’ and ‘In relation to ethnicity’. Key conclusion and implications for practice: The findings of this study show that midwives experience that doulas are a facilitator for them. Doulas provide support by enhancing the degree of peace and security and improving communication with the women in childbirth. Doulas provide increased opportunities for transcultural care. They may increase childbearing women’s confidence and satisfaction, help meet the diverse needs of childbearing women and improve care quality.
  • Altersved, Ewa, et al. (författare)
  • Advanced practice nurses : A new resource for Swedish primary health-care teams
  • 2011
  • Ingår i: International Journal of Nursing Practice. - John Wiley & Sons. - 1322-7114. ; 17:2, s. 174-180
  • Tidskriftsartikel (refereegranskat)abstract
    • Advanced practice nurses: A new resource for Swedish primary health-care teams This study is associated with the first evaluation of the four first advanced practice nurses (APNs), part of a primary health-care team in Sweden. The aim is to describe health-care teams' experiences of the new APN role and investigate what opportunities and barriers to the role exist. Eighty-one respondents answered a 14-question questionnaire with a Likert scale and one open-ended question. The Kruskal-Wallis test was used to investigate differences between professional groups' answers. The qualitative material was analysed using deductive content analysis. Though mostly positive experiences of the role were found, differences did exist between the professional groups. APNs are considered a resource in that access to care, cooperation and patient flow increased. Barriers include APNs' limited autonomy and inability to prescribe medication. To further develop the role, the right to prescribe medication and strategic leadership within the Swedish health-care system, policy and legislation are needed.
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