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| 2. |
- Ekoff, Maria, et al.
(författare)
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The BH3-only protein Puma plays an essential role in cytokine deprivation-induced apoptosis of mast cells
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:9, s. 3209-3217
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells play critical roles in the regulation of inflammation. One characteristic feature of mast cells is their relatively long lifespan in vivo. Members of the Bcl-2 protein family are regulators of cell survival and apoptosis, where the BH3-only proteins are critical proapoptotic proteins. In this study we investigated the role of the BH3-only proteins Noxa, Bad, Bim, Bmf, Bid, and Puma in apoptosis of mucosal-like mast cells (MLMCs) and connective tissue-like mast cells (CTLMCs). We demonstrate that Puma is critical for the induction of mast-cell death following cytokine deprivation and treatment with the DNA-damaging agent etoposide in MLMCs and CTLMCs. Using p53-/- mast cells, we found that cytokine deprivation-induced apoptosis, in contrast to that elicited by etoposide, is p53-independent. Interestingly, mast cells deficient in FOXO3a, previously proposed as a transcription factor for Puma induction in response to growth factor deprivation, were markedly resistant to cytokine withdrawal compared with wildtype cells. Moreover, overexpression of phosphorylation-deficient, constitutively active FOXO3a caused an up-regulation of Puma. In conclusion, our data demonstrate a pivotal role for Puma in the regulation of cytokine deprivation-induced mast-cell apoptosis and suggest a plausible role for Puma in the regulation of mast cell numbers in vivo. © 2007 by The American Society of Hematology.
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| 3. |
- Klasson, Anna, et al.
(författare)
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Positive MRI Enhancement in THP-1 Cells with Gd2O3 Nanoparticles
- 2008
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Ingår i: Contrast Media and Molecular Imaging. - : Wiley. - 1555-4309 .- 1555-4317. ; 3:3, s. 106-111
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Tidskriftsartikel (refereegranskat)abstract
- There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd2O3) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd2O3-labeled cells have shorter T1 and T2 relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd2O3 nanoparticles can be used as a positive contrast agent for cell labeling. The r1 for cell samples was 4.1 and 3.6 s-1 mm-1 for cell culture medium. The r2 was 17.4 and 12.9 s-1 mm-1, respectively. For r1, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (pr1 = 0.36), but r2 was significantly different for the two different series (pr2 = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd2O3 nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells.
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| 4. |
- Möller, Christine, et al.
(författare)
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Stem cell factor promotes mast cell survival via inactivation of FOXO3a-mediated transcriptional induction and MEK-regulated phosphorylation of the proapoptotic protein Bim
- 2005
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 106:4, s. 1330-1336
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells are found in tissues throughout the body where they play important roles in the regulation of inflammatory responses. One characteristic feature of mast cells is their longevity. Although it is well established that mast cell survival is dependent on stem cell factor (SCF), it has not been described how this process is regulated. Herein, we report that SCF promotes mast cell survival through inactivation of the Forkhead transcription factor FOXO3a (forkhead box, class O3A) and down-regulation and phosphorylation of its target Bim (Bcl-2 [B-cell lymphoma-2] interacting modulator of cell death), a Bcl-2 homology 3 (BH3)-only proapoptotic protein. SCF induced a rapid and transient phosphorylation of Akt (protein kinase B) and FOXO3a. SCF treatment prevented up-regulation of Bim protein expression and led to increased Bim phosphorylation. Bim phosphorylation was inhibited by PD98059 and LY294002 treatment, suggesting the involvement of mitogen-activated protein kinase kinase/mitogen-activated protein kinase (MEKJMAPK) and phosphatidylinositol 3 (PI3)-kinase pathways in this process. Overexpression of phosphorylation-deficient FOXO3a caused an up-regulation of Bim and induced mast cell apoptosis even in the presence of SCF. Mast cell apoptosis induced by the phosphorylation-deficient FOXO3a was attenuated in bim(-/-) mast cells. Because apoptosis is abnormally reduced in bim(-/-) mast cells, these data provide evidence that Akt-mediated inhibition of FOXO3a and its transcription target Bim provides an important mechanism by which SCF acts to prevent apoptosis in mast cells.
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| 6. |
- Scandurra, Isabella, et al.
(författare)
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Heuristic evaluation performed by usability-educated clinicians : education and attitudes
- 2007
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Ingår i: INFORMATION TECHNOLOGY IN HEALTH CARE 2007. - : IOS Press. - 9781586037772 - 9781607502685 ; , s. 205-216
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Konferensbidrag (refereegranskat)abstract
- Heuristic evaluation is a usability testing method aiming to improve the user interface design. Traditionally, a panel of experts in usability and human factor issues evaluate and judge the compliance of computer software according to recognized usability principles, the heuristics. In this paper, we investigate clinicians' attitudes towards learning and performing a heuristic evaluation and present the procedure of educating the healthcare staff and their accomplishment of the evaluation. 18 clinicians were recruited for a 2-hours education and filled in a post-education questionnaire regarding their opinions of the evaluation method when applied by clinicians. Six of the clinicians participated later in a heuristic evaluation of a web-based virtual health record,Their time spent for evaluation and analysis of results was approximately four hours each. Opinions from the six "clinical evaluators" were gathered in an post-evaluation form and compared to the post-education questionnaire. The results of 18 clinicians indicate that there is an interest in learning and participating in such evaluations. Our interpretation is that it is feasible to educate healthcare staff to perform rapid usability inspections to locate usability defects and additionally emphasize the domain specific problems residing in health information systems.
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| 10. |
- André-Petersson, Lena, et al.
(författare)
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Social support at work and the risk of myocardial infarction and stroke in women and men.
- 2007
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 1873-5347 .- 0277-9536. ; 64:4, s. 830-841
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that lack of social support in a work place characterized by high levels of stress, may increase the likelihood of future cardiovascular disease. The aim of this study was to analyze the prospective impact of social support at work in combination with self-reported work stress on incidence of myocardial infarction (MI) and stroke in a cohort of 4707 women (mean age: 54.2 years) and 3063 men (mean age: 55.5 years) in Malmo, Sweden. The results are based oil self-reports of work-related stress and social support collected at baseline examinations between the years 1992 and 1996. Work-stress was operationalized according to the Karasek job strain model. Data on incidence of NIL and stroke were obtained from national and regional registers. At the end of follow-up, December 31, 2001, 38 women had experienced an MI and 53 had had a stroke. Corresponding figures for men were 114 MIs and 81 strokes. The first finding was that social support at work was an independent predictor of an M I and stroke among women. The second finding was that there was no evidence to support the iso-strain model. The third finding was that low levels of social support at work together with a passive work situation indicated an increased risk of a future cardiovascular outcome (NI I or stroke) during follow-up in the female group. In men, no association was found between any psychosocial work conditions and incidence of MI or stroke during the same follow-up period. (c) 2006 Elsevier Ltd. All rights reserved.
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