| 1. |
- Buus, Terkild Brink, et al.
(författare)
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Single-cell heterogeneity in Sézary syndrome
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:16, s. 2115-2126
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Tidskriftsartikel (refereegranskat)abstract
- Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
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| 2. |
- Feith, Marek, et al.
(författare)
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Circulating tumor cell models mimicking metastasizing cells in vitro : discrimination of colorectal cancer cells and white blood cells using digital holographic cytometry
- 2022
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Ingår i: Photonics. - Basel : MDPI. - 2304-6732. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is the second most metastatic disease with the majority of cases detected in Western countries. Metastases are formed by circulating altered phenotype tumor cells causing 20% of CRC related deaths. Metastatic cells may show higher expression of surface molecules such as CD44, and changes in morphological properties are associated with increased invasiveness and poor prognosis. In this study, we intended to mimic the environment for metastasizing cells. Here, we used digital holographic cytometry (DHC) analysis to determine cellular morphological properties of three metastatic and two non-metastatic colorectal cancer cell lines to show differences in morphology between the CRC cells and peripheral blood mononuclear cells (PBMCs). By establishing differences in cell area, cell thickness, cell volume, and cell irregularity even when the CRC cells were in minority (5% out of PBMCs), DHC does discriminate between CRC cells and the PBMCs in vitro. We also analyzed the epithelial marker EpCAM and migration marker CD44 using flow cytometry and demonstrate that the CRC cell lines and PBMC cells differ in EpCAM and CD44 expression. Here, we present DHC as a new powerful tool in discriminating cells of different sizes in suspension together with a combination of biomarkers.
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| 3. |
- Gaines, Hans, et al.
(författare)
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Six-week follow-up after HIV-1 exposure: a position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
- 2016
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 48:2, s. 93-98
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Forskningsöversikt (refereegranskat)abstract
- In 2014 the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy (RAV) conducted a review and analysis of the state of knowledge on the duration of follow-up after exposure to human immunodeficiency virus (HIV). Up until then a follow-up of 12 weeks after exposure had been recommended, but improved tests and new information on early diagnosis motivated a re-evaluation of the national recommendations by experts representing infectious diseases and microbiology, county medical officers, the RAV, the Public Health Agency, and other national authorities. Based on the current state of knowledge the Public Health Agency of Sweden and the RAV recommend, starting in April 2015, a follow-up period of 6 weeks after possible HIV-1 exposure, if HIV testing is performed using laboratory-based combination tests detecting both HIV antibody and antigen. If point-of-care rapid HIV tests are used, a follow-up period of 8 weeks is recommended, because currently available rapid tests have insufficient sensitivity for detection of HIV-1 antigen. A follow-up period of 12 weeks is recommended after a possible exposure for HIV-2, since presently used assays do not include HIV-2 antigens and only limited information is available on the development of HIV antibodies during early HIV-2 infection. If pre- or post-exposure prophylaxis is administered, the follow-up period is recommended to begin after completion of prophylaxis. Even if infection cannot be reliably excluded before the end of the recommended follow-up period, HIV testing should be performed at first contact for persons who seek such testing.
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| 4. |
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| 5. |
- Gulliksen, Jan, 1965-, et al.
(författare)
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Making a difference : a survey of the usability profession in Sweden
- 2004
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Ingår i: Proceedings of the third Nordic conference on Human-computer interaction. - New York : ACM Press. - 1581138571 ; , s. 207-215
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Konferensbidrag (refereegranskat)abstract
- Poor usability in interactive systems/products is still a major problem for users and buyers, despite efforts made by an increasing number of usability professionals. How come this is so and what are the main obstacles to usability work? In this paper we report the results of a survey of usability professionals in Sweden, conducted in 2003. The survey identified, e.g. their background and experiences, the type of employment, organization, and products/systems, the software development process being used and some key success factors for usability work. The results indicate, among other things, that management support and project management support are essential for the usability worker. Moreover, they face problems such as, usability and user involvement having low priority in the projects.
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| 6. |
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| 7. |
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| 8. |
- Karlsson, Jan, 1969-, et al.
(författare)
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High emission of carbon dioxide and methane during ice thaw in high latitude lakes
- 2013
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Ingår i: Geophysical Research Letters. - : John Wiley & Sons. - 0094-8276 .- 1944-8007. ; 40:6, s. 1123-1127
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Tidskriftsartikel (refereegranskat)abstract
- The winter period is seldom included in the estimates of aquatic-atmospheric carbon exchange. In this study we quantified the flux of carbon dioxide (CO2) and methane (CH4) over 3 years from 12 small subarctic lakes. The lakes accumulated consistent and high amounts of CO2 and CH4 (56–97% as CO2) over the winter, resulting in a high flux during ice thaw. The CO2 flux during ice thaw increased with increasing mean depth of the lakes, while the CH4 flux was high in lakes surrounded by mires. The ice thaw period was quantitatively important to the annual gas balances of the lakes. For nine of the lakes, 11 to 55% of the annual flux occurred during thaw. For three of the lakes with an apparent net annual CO2 uptake, including the thaw period reversed the balance from sink to source. Our results suggest that the ice thaw period is critically important for the emissions of CO2 and CH4 in small lakes.
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| 9. |
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| 10. |
- Persson, Jenny, et al.
(författare)
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Cytokine response to lipoprotein lipid loading in human monocyte-derived macrophages
- 2006
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 5:17
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Macrophage foam cell formation is a prominent feature of human atherosclerotic plaques, usually considered to be correlated to uptake of and inflammatory response to oxidized low density lipoproteins (OxLDL). However, there are alternative pathways for formation of macrophage foam cells and the effect of such lipid loading on macrophage function remains to be fully characterized. In the present study we investigated basal and inducible cytokine expression in primary human macrophages either loaded with triglycerides through incubation with very low density lipoproteins (VLDL) or with cholesterol through incubation with aggregated LDL (AgLDL). We then analyzed how foam cell lipid content affected secretion of three pro-inflammatory cytokines: interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and of one chemokine: interleukin-8 (IL-8), all of which are considered pro-inflammatory, pro-atherosclerotic, and are expressed by cells in atherosclerotic tissue. RESULTS: Formation of triglyceride-loaded foam cells resulted in a four-fold increase in basal IL-1beta secretion, whereas cholesterol loading lacked significant effect on IL-1beta secretion. In contrast, secretion of TNF-alpha and IL-6 decreased significantly following both cholesterol and triglyceride loading, with a similar trend for secretion of IL-8. Lipid loading did not affect cell viability or expression of caspase-3, and did not significantly affect macrophage ability to respond to stimulation with exogenous TNF-alpha. CONCLUSION: Lipid loading of primary human macrophages resulted in altered cytokine secretion from cells, where effects were similar regardless of neutral lipid composition of cells. The exception was IL-1beta, where triglyceride, but not cholesterol, lipid loading resulted in a stimulation of basal secretion of the cytokine. It is apparent that macrophage cytokine secretion is affected by lipid loading by lipoproteins other than OxLDL. As both VLDL and AgLDL have been found in the vessel wall, macrophage cytokine response to uptake of these lipoproteins may have a direct effect on atherosclerotic development in vivo. However, macrophage neutral lipid amount and composition did not affect cellular activation by exogenous TNF-alpha, making it likely that lipoprotein lipid loading can affect foam cell cytokine secretion during basal conditions but that the effects can be overruled by TNF-alpha during acute inflammation.
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