| 1. |
- Nilsson, Björn, et al.
(författare)
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Threshold-free high-power methods for the ontological analysis of genome-wide gene expression studies
- 2007
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 8:5, s. R74-
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Tidskriftsartikel (refereegranskat)abstract
- Ontological analysis facilitates microarray data interpretation. We describe new ontological analysis methods which, unlike existing approaches, are threshold-free and statistically powerful. We perform extensive evaluations and introduce a new concept, detection spectra, to characterize methods. We show that different ontological analysis methods exhibit distinct detection spectra, and that it is critical to account for this diversity. Our results argue strongly against the continued use of existing methods, and provide directions towards an enhanced approach.
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| 2. |
- Boström, Petra, 1972, et al.
(författare)
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Self-reported psychological wellbeing in adolescents: the role of intellectual/developmental disability and gender.
- 2018
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Ingår i: Journal of intellectual disability research : JIDR. - : Wiley. - 1365-2788 .- 0964-2633. ; 62:2, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- The Wellbeing in Special Education Questionnaire was developed to assess subjective wellbeing in young persons with intellectual and developmental disabilities (ID/DD) as this perspective is rarely included in research. The present study explored how ID/DD and gender are related to self-reported wellbeing among adolescents.Students with (n=110) or without (n=110) ID/DD, aged 12-16years, completed the Wellbeing in Special Education Questionnaire. Analyses of the effects of gender and disability status on peer relations and conflict, mental health, mental ill-health, school environment and family relations were carried out.The experiences of the school environment and of positive mental health aspects did not differ between students with and without ID/DD, but those with ID/DD reported more mental health problems and less positive experiences of peer relations and family. Generally, boys reported more positive experiences of school and less mental health problems than girls.Including the subjective perspective of young persons with ID/DD through self-reports can provide essential information about wellbeing that cannot be gained from proxy ratings. The results suggest both differences and similarities in self-reported wellbeing between boys and girls with and without ID/DD and potentially also in how they perceived the concepts measured.
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| 3. |
- Boström, Petra, 1972, et al.
(författare)
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Subjective Mental Health, Peer Relations, Family, and School Environment in Adolescents with Intellectual Developmental Disorder: A First Report of a New Questionnaire Administered on Tablet PCs
- 2016
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Ingår i: Journal of Mental Health Research in Intellectual Disabilities. - : Informa UK Limited. - 1931-5864 .- 1931-5872. ; 9:4, s. 207-231
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have explored the subjective mental health of adolescents with intellectual disabilities, while proxy ratings indicate an overrepresentation of mental health problems. The present study reports on the design and an initial empirical evaluation of the Well-being in Special Education Questionnaire (WellSEQ). Questions, response scales, and an application for tablet PCs were developed in cooperation with students and teachers in special education schools. One hundred and thirteen students (age 12-16) and their parents and teachers participated. Positive results in terms of test-retest reliability, internal consistency of scales, and response rates were obtained. Level of reading appeared to affect the students' understanding of items. Teachers' and parents' ratings on the WellSEQ correlated well with established measures. Correlations between proxy ratings and students' reports varied. The questionnaire and technology of WellSEQ may enable students with IDD to participate independently in research with good completion rates and reliable responding.
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| 4. |
- Eldblom, Julia, et al.
(författare)
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Word reading, vocabulary, and mental health problems in adolescent girls and boys with intellectual and developmental disabilities
- 2021
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Ingår i: International Journal of Developmental Disabilities. - : Informa UK Limited. - 2047-3869 .- 2047-3877. ; 67:2, s. 131-139
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Tidskriftsartikel (refereegranskat)abstract
- Reading difficulties are linked to several disadvantages in the general population. Less is known about correlates of reading difficulties in individuals with intellectual and severe developmental disabilities (IDD). Vocabulary and word reading were assessed in 112 adolescents with IDD, recruited from Special needs comprehensive schools in Sweden (grundsarskolor in Swedish). Proxy-ratings of mental health were collected from teachers and parents for a subset of the participants. Relationships between all measures were investigated. Reading and vocabulary were poorly developed in both groups and significantly associated. While mental health problems were common, there were no significant associations with word reading or with vocabulary knowledge. Thus, the study did not confirm an association between reading difficulties and mental health problems in adolescents with IDD. Still, the frequency of mental health problems and the low reading abilities point to the need for further intervention for adolescents with IDD.
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| 5. |
- Hakansson, P., et al.
(författare)
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Establishment and phenotypic characterization of human U937 cells with inducible P210 BCR/ABL expression reveals upregulation of CEACAM1 (CD66a)
- 2004
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 18:3, s. 538-47
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Tidskriftsartikel (refereegranskat)abstract
- Chronic myeloid leukemia (CML) is characterized by the expression of the P210 BCR/ABL fusion protein. The molecular mechanisms behind this oncogene-mediated hematological disease are, however, not fully understood. Here, we describe the establishment and phenotypic characterization of U937 cells in which P210 BCR/ABL can be conditionally expressed using tetracycline. The induction of BCR/ABL in the obtained clones resulted in a rapid phosphorylation of the STAT1, STAT3 and STAT5 molecules, consistent with the findings in other model systems. Phenotypic characterization of the clones revealed that BCR/ABL induces a slight decrease in the proliferation and viability, without a marked effect on cell cycle distribution, the rate of apoptosis or on cellular differentiation, as judged by several cell surface markers and capacity to reduce nitro blue tetrazolium. Interestingly, BCR/ABL was found to upregulate the expression of carcinoembryonic-related antigen (CEA)CAM1 (CD66a), which is a plasma membrane-linked glycoprotein belonging to the CEAs and involved in signal transduction and cellular adhesion. The expression of CEACAM1 was reversible upon imatinib treatment in BCR/ABL-expressing U937 cells as well as in BCR/ABL-positive K562 cells. The established cell lines may prove useful in further modeling and dissection of BCR/ABL-induced leukemogenesis.
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| 6. |
- Hansen, Nils, et al.
(författare)
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SOCS2 is dispensable for BCR/ABL1-induced chronic myeloid leukemia-like disease and for normal hematopoietic stem cell function.
- 2013
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 27, s. 130-135
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Tidskriftsartikel (refereegranskat)abstract
- Suppressor of cytokine signaling 2 (SOCS2) is known as a feedback inhibitor of cytokine signaling and is highly expressed in primary bone marrow (BM) cells from patients with chronic myeloid leukemia (CML). However, it has not been established whether SOCS2 is involved in CML, caused by the BCR/ABL1 fusion gene, or important for normal hematopoietic stem cell (HSC) function. In this study, we demonstrate that although Socs2 was found to be preferentially expressed in long-term HSCs, Socs2-deficient HSCs were indistinguishable from wild-type HSCs when challenged in competitive BM transplantation experiments. Furthermore, by using a retroviral BCR/ABL1-induced mouse model of CML, we demonstrate that SOCS2 is dispensable for the induction and propagation of the disease, suggesting that the SOCS2-mediated feedback regulation of the JAK/STAT pathway is deficient in BCR/ABL1-induced CML.Leukemia advance online publication, 24 July 2012; doi:10.1038/leu.2012.169.
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| 7. |
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| 8. |
- Johnels, Petra
(författare)
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Molecular and functional studies of the BCR/ABL1 fusion gene
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The BCR/ABL1 fusion gene is associated with chronic myeloid leukemia and a subgroup of acute lymphoblastic leukemia. The general aim of this thesis was to increase the understanding of BCR/ABL1-induced leukemogenesis by molecular and functional studies of this fusion gene. In Article I, an experimental U937 cell line model with inducible expression of BCR/ABL1 was established and characterized. Expression of BCR/ABL1 activated the JAK/STAT pathway, but showed no marked effects on proliferation, differentiation, and apoptosis. In addition, a reversible upregulation of the cell-surface marker CEACAM1, implicated in cell adhesion and signal transduction, was identified upon expression of BCR/ABL1. In Article II, the BCR/ABL1-inducible U937 cells were used to investigate the transcriptional effects of BCR/ABL1. Approximately 60 genes were induced by BCR/ABL1, including genes encoding transcription factors, kinases, and signal transduction molecules. About one third of the genes were IFN-responsive, which may indicate an overlap with IFN-induced signal transduction or activation of cellular defense and/or negative feedback mechanisms. In Article III, the tyrosine kinase activity of BCR/ABL1 was blocked with imatinib in five Ph-positive cell lines. Approximately 140 genes, mainly involved in signal transduction and metabolic pathways, were identified as affected by BCR/ABL1. Several genes implicated in negative feedback-regulation of well-known signaling pathways were positively regulated by BCR/ABL1, which may act to suppress tumor-promoting effects elicited by the fusion gene. In Article IV, the P190 or the P210 BCR/ABL1 fusion variant was retrovirally expressed in primitive human cord blood cells. In these cells, expression of both P190 and P210 BCR/ABL1 resulted in increased proliferation and differentiation towards the erythroid lineage. Approximately 220 genes were identified as targets of P190/P210 BCR/ABL1-mediated signaling. The similar biological and transcriptional effects induced by these two variants indirectly support the hypothesis of a separate cellular origin for these fusion genes to explain their association with different leukemias. A recurrent finding between the three experimental models was a deregulated expression of different SOCS family members, which regulate signaling mediated particularly via the JAK/STAT pathway. Apart from providing important pathogenetic insights into BCR/ABL1-induced leukemogenesis, the present study identified a number of pathways/individual genes that may provide attractive targets for the development of novel therapies against Ph-positive leukemias.
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| 9. |
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| 10. |
- Järås, Marcus, et al.
(författare)
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Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage
- 2009
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Ingår i: Experimental Hematology. - : Elsevier BV. - 1873-2399 .- 0301-472X. ; 37:3, s. 367-375
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The P190 and P210 BCR/ABL1 fusion genes are mainly associated with different types of hematologic malignancies, but it is presently unclear whether they are functionally different following expression in primitive human hematopoietic cells. Materials and Methods. We investigated and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. Results. Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under in vitro conditions favoring B-cell differentiation, neither P190 nor P210 BCR/ABL1-expressing cells formed detectable levels of CD19-positive cells. Gene expression profiling revealed that P190 BCR/ABL1 and P210 BCR/ABL1 induced almost identical gene expression profiles. Conclusions. Our data suggest that the early cellular and transcriptional effects of P190 BCR/ABL1 and P210 BCR/ABL1 expression are very similar when they are expressed in the same human progenitor cell population, and that STAT5 is an important regulator of BCR/ABL1-induced erythroid cell expansion. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
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