| 1. |
- Jönsson, Maria, 1977-, et al.
(författare)
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FLT3 ligand regulates apoptosis through AKT-dependent inactivation of transcription factor Fox03
- 2004
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 318:4, s. 899-903
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Tidskriftsartikel (refereegranskat)abstract
- Proliferation, differentiation, and survival of hematopoietic cells are regulated by cytokines, acting through specific receptors. FLT3 ligand (FL) is one of the most important cytokines for regulation of the hematopoietic system, and its receptor FLT3 is expressed on both stem cells and progenitors. Regulation of Forkhead transcription factors has been described as an important mechanism to control apoptosis and cell cycle progression in hematopoietic progenitors. Here we report that FL induces AKT/PKB activation, which in turn phosphorylates and thereby inactivates the Forkhead protein FoxO3 in the progenitor cell line FDC-P1 stably expressing murine FLT3 receptor. Phosphorylation of AKT and FoxO3 was blocked by the PI-3 kinase inhibitor LY294002 but not by the MAP kinase inhibitor PD98059. Expression of a mutated FoxO3, in which all three inhibitory phosphorylation sites were mutated to alanine, led to rapid increase of apoptotic cells in the presence of FL. These results suggest that FL-induced regulation of apoptosis is executed by FoxO3. (C) 2004 Elsevier Inc. All rights reserved.
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| 2. |
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| 3. |
- Ahrén, Maria, et al.
(författare)
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Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5753-5762
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Tidskriftsartikel (refereegranskat)abstract
- Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study. We report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in NI RI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy. X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is. an extremely high MR signal at the cellular and molecular level.
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| 4. |
- Dam, Veerle, et al.
(författare)
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Association of menopausal characteristics and risk of coronary heart disease : A pan-European case-cohort analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:4, s. 1275-1285
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Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
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| 5. |
- 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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| 6. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 7. |
- Gustafsson, Håkan, et al.
(författare)
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Magnetic and Electron Spin Relaxation Properties of (GdxY1-x)(2)O-3 (0 <= x <= 1) Nanoparticles Synthesized by the Combustion Method. Increased Electron Spin Relaxation Times with Increasing Yttrium Content
- 2011
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:13, s. 5469-5477
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Tidskriftsartikel (refereegranskat)abstract
- The performance of a magnetic resonance imaging contrast agent (CA) depends on several factors, including the relaxation times of the unpaired electrons in the CA. The electron spin relaxation time may be a key factor for the performance of new CAs, such as nanosized Gd2O3 particles. The aim of this work is, therefore, to study changes in the magnetic susceptibility and the electron spin relaxation time of paramagnetic Gd2O3 nanoparticles diluted with increasing amounts of diamagnetic Y2O3. Nanoparticles of (GdxY1-x)(2)O-3 (0 <= x <= 1) were prepared by the combustion method and thoroughly characterized (by X-ray diffraction, transmission electron microscopy, thermogravimetry coupled with mass spectroscopy, photoelectron spectroscopy, Fourier transform infrared spectroscopy, and magnetic susceptibility measurements). Changes in the electron spin relaxation time were estimated by observations of the signal line width in electron paramagnetic resonance spectroscopy, and it was found that the line width was dependent on the concentration of yttrium, indicating that diamagnetic Y2O3 may increase the electron spin relaxation time of Gd2O3 nanoparticles.
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| 8. |
- Gustafsson, Håkan, 1976-, et al.
(författare)
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Magnetic and Electron Spin Relaxation Properties of (GdxY1-x)2O3 (0 ≤ x ≤ 1) Nanoparticles Synthesized by the Combustion Method. Increased Electron Spin Relaxation Times with Increasing Yttrium Content
- 2011
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Ingår i: The Journal of Physical Chemistry C. - United States : American Chemical Society. - 1932-7447 .- 1932-7455. ; 115:13, s. 5469-5477
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Tidskriftsartikel (refereegranskat)abstract
- The performance of a magnetic resonance imaging contrast agent (CA) depends on several factors, including the relaxation times of the unpaired electrons in the CA. The electron spin relaxation time may be a key factor for the performance of new CAs, such as nanosized Gd2O3 particles. The aim of this work is, therefore, to study changes in the magnetic susceptibility and the electron spin relaxation time of paramagnetic Gd2O3 nanoparticles diluted with increasing amounts of diamagnetic Y2O3. Nanoparticles of (GdxY1-x)2O3 (0 e x e 1) were prepared by the combustion method and thoroughly characterized (by X-ray di.raction, transmission electron microscopy, thermogravimetry coupled with mass spectroscopy, photoelectron spectroscopy, Fourier transform infrared spectroscopy, and magnetic susceptibility measurements). Changes in the electron spin relaxation time were estimated by observations of the signal line width in electron paramagnetic resonance spectroscopy, and it was found that the line width was dependent on the concentration of yttrium, indicating that diamagnetic Y2O3 may increase the electron spin relaxation time of Gd2O3 nanoparticles.
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| 9. |
- Gustafsson, Håkan, et al.
(författare)
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Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging
- 2015
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 73:4, s. 1682-1691
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.
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| 10. |
- Hedlund, Anna, 1973-, et al.
(författare)
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Detection of Gd2O3 Nanoparticles in Hematopoietic Cells for MRI Contrast Enhancement
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3 ) nanoparticles generate higher relaxivity than currently available Gd chelates. The Gd2O3 nanoparticles are also promising for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles and to improve techniques for monitoring hematopoietic stem cell migration by MRI. We studied particle uptake in two cell lines; the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles as well as superparamagnetic iron oxide particles (SPIOs) for comparison. In addition, it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by microscopic techniques, MRI and analyzed for particle content. Results showed that particles were intracellular, however in Ba/F3 only sparsely. The relaxation times were shortened with increasing particle concentration. Overall relaxivities, r1 and r2 for Gd2O3 nanoparticles in all cell samples measured were 5.1 ± 0.3 and 14.9 ± 0.7 (s-1mM-1) respectively. Goodness of fit was 0.97 in both cases. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. Viability of treated cells was not significantly decreased and thus, we conclude that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells.
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