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- Bergenfelz, Caroline
(författare)
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Immunosuppressive Myeloid Cells in Breast Cancer and Sepsis
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Immune cells play paradoxical roles in cancer progression. On one hand, the immune system protects us against tumor development by recognizing and eliminating cancerous cells. On the other hand, tumor-associated immune cells can contribute to tumor progression by secreting growth factors as well as immunosuppressive, pro-angiogenic and/or pro-metastatic mediators. In this thesis we identified a factor (Wnt5a) that may be involved in skewing immune responses towards immunosuppressive, tumor promoting immune cell populations. In a pro-inflammatory setting (i.e. in the presence of exogenous pathogen-associated molecular patterns; PAMPs, or endogenous damage-associated molecular patterns; DAMPs), Wnt5a promoted the generation of immunosuppressive monocytes (CD14+HLA-DRlow/-Co-receptorlow/-). This was at the expense of generation of pro-inflammatory macrophages (M1). In addition, Wnt5a inhibited monocyte to dendritic cell differentiation (Mo-mDC). When co-injecting monocytes from healthy blood donors with MCF-7 or MDA-MB-231 breast cancer cells (luminal A and basal-like, respectively) into immunodeficient mice, monocytes promoted the generation of an activated tumor stroma and were preferentially recruited to basal-like tumors. Furthermore, monocytes from breast cancer patients were affected early during the disease, gradually becoming reprogrammed towards a novel population of monocytic myeloid-derived suppressor cells (Mo-MDSCs). The gene-expression profile of cancer-derived monocytes was remarkably similar to that of reprogrammed immunosuppressive monocytes from patients with gram-negative sepsis. This suggests that Mo-MDSCs may be generated in a similar manner in cancer and sepsis (by reprogramming of monocytes towards an immunosuppressive phenotype). We finally propose that Mo-MDSCs and granulocytic MDSCs are preferentially induced by different PAMPs. Altogether, we conclude that myeloid cells are skewed towards an immunosuppressive and tissue remodeling phenotype early during breast cancer. This resembles the situation during severe infections such as sepsis and most likely has a positive impact on tumor progression.
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- de Bruijn, Robert
(författare)
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Cardiovascular and hematological responses to voluntary apnea in humans
- 2007
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with cardiovascular and hematological responses to voluntary apnea in humans, with a special focus on O2 usage and storage. Humans, and many other air‐breathing animals, respond to apnea (breath holding) with a collection of interacting cardiovascular reflexes, which are collectively called the diving response. In humans, the main characteristics of the diving response are a reduction in heart rate (bradycardia), decreased cardiac output, peripheral vasoconstriction and increased arterial blood pressure. Another response during apnea in mammals, more recently also observed in man, is a transient increase in hemoglobin concentration across a series of apneas, probably due a reduction in spleen size. There may also be long‐term effects on erythropoiesis in the apneic diver, as suggested by high hemoglobin levels observed in divers. The focus of the included studies are the short transient diving response (I), the more slowly occurring transient hematological changes to apnea, most likely related to a reduction in spleen size (II), and the possible effects of repeated apnea on serum erythropoietin concentration (III). I) The aim was to study the effects of body immersion on the O2‐conserving effect of the human diving response. The results showed that, regardless of body immersion, apnea with face immersion causes a stronger cardiovascular diving response compared to during apnea alone, leading to a smaller reduction in arterial oxygen saturation levels. Thus the diving response is triggered and conserves O2 even during whole‐body immersion, which has previously only been observed during apnea without whole‐body immersion. II) The aim was to study hematological responses to voluntary repeated maximal‐duration apneas in divers and non‐divers. Increases in hemoglobin concentration were found across a series of 3 apneas in elite breath‐hold divers, elite cross‐country skiers and untrained subjects. However a larger increase in hemoglobin was found in divers compared to non‐divers, which suggests a possible training effect of their extensive apnea‐specific training. In contrast, physical endurance training does not appear to affect the hematological response to apnea. III) The aim was to study the effects of serial voluntary apnea on the serum erythropoietin concentration. In a comparison between elite breath‐hold divers and subjects untrained in apnea, divers were found to have a 5% higher resting hemoglobin concentration. An average maximum increase in erythropoietin of 24 % was found in untrained subjects after 15 maximal duration apneas, preceded by 1 min of hyperventilation. This suggests a possible erythropoietic effect of apnea‐induced hypoxia, which may connect the increased resting hemoglobin found in divers to their apnea‐specific training. It was concluded from these studies that man responds to apnea with a series of different adjustments in order to limit O2 usage and increase O2 storage: The classical diving response is effectively restricting O2‐consumption also during full immersion, the spleen related hemoglobin increase occurs in both divers and non‐divers with different levels of physiological training, but is more prominent in divers, and finally, the observed high levels of hemoglobin concentration in divers may be related to enhanced erythropoiesis during dive training.
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| 4. |
- de Bruijn, Robert, et al.
(författare)
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Erythropoietin production as a result of repeated apneas
- 2004
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Konferensbidrag (refereegranskat)abstract
- Background: It has been known for decades that high altitude hypoxia will lead to increased erythropoiesis. Hypoxia in mainly the kidney results in an increased production of erythropoietin (EPO) stimulating erythropoiesis. High altitude natives display a higher haemoglobin concentration than sea level residents, which in turn increase their haemoglobin concentration as part of the adaptation to altitude. Another group of humans exposed to hypoxia is apneic divers, which may endure transient acute hypoxia, spaced by periods of normal breathing. We recently found higher haemoglobin levels in elite apneic divers, compared to groups of elite skiers and untrained subjects, suggesting that apnea training may induce erythropoiesis in humans. It is well known that diving mammals display high haemoglobin concentrations, and the beneficial effects are obvious: A larger oxygen store before diving prolongs the aerobic dive limit, and a higher haemoglobin concentration may speed up recovery after apneas and act as a buffer against acidosis during the dive. Although our group comparisons reveal a higher haemoglobin concentration in divers, it cannot be determined whether this is a training effect or genetically determined i.e. if individuals with higher concentrations of haemoglobin are more prone to take up apneic diving. Methods: To investigate if apnea training can induce EPO production, 5 previously untrained volunteers (3 men and 2 women, mean ageSD 28 5.5 years) performed 15 maximal apneas in a horizontal position in air. The apneas were grouped in 3 series of 5 apneas and spaced by 2 minutes of which 1 minute was spent slightly hyperventilating, to produce apneas sufficiently long to induce hypoxia. Series were spaced by 10 minutes resting periods. To determine EPO levels, venous blood samples were taken before apneas and directly after the last apnea series, followed by samples 1, 2, 3 and 5 hours after the apneas. Results: Mean baseline EPO before the apneas was 10.2 U/L. In all subjects EPO levels increased during the 5 hours period after the apneas. The time for EPO-peak values were different among individuals. The mean peak value occurred after 3 h, where the mean increase was 12 % of the pre apnea reference value. Conclusion: The results suggest that apnea induced intermittent hypoxia could lead to increased erythropoiesis. The evaluation of these findings in a larger group of subjects, including measurements of the individual circadian variations in EPO production, is in progress.
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| 8. |
- Jalali-Roudsar, Amir Abbas, et al.
(författare)
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Critical angles effect : Vanishing of cubic magnetocrystalline anisotropy in ferromagnetic resonance spectra
- 2002
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 66:10, s. 104419-1-104419-5
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Tidskriftsartikel (refereegranskat)abstract
- The shapes of ferromagnetic resonance (FMR) spectra of laser deposited epitaxial Y3Fe5O12 (YIG) films strongly depend on the orientation of the magnetic field with respect to the crystalline axes of the film. Strain and compositional inhomogeneties in the films define local magnetic anisotropies and could be responsible for the complexity of FMR spectra. We show that, in accordance with the Smit-Suhl formula, the contribution from a spatial distribution of the cubic magnetocrystalline anisotropy to the FMR spectra vanishes at certain orientations ("critical angles") of the magnetic field. We prove experimentally that it is a necessary condition to orient the magnetic field at the critical angles in order to measure single-line FMR spectra in an inhomogenous laser deposited YIG film.
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| 9. |
- Jalalian, Abolfazl, et al.
(författare)
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Piezoelectricity and electrostriction in biocompatible (Na,K)NbO3 nanofiber scaffolds
- 2014
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 104:24, s. 243701-
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Tidskriftsartikel (refereegranskat)abstract
- Single phase and highly crystalline biocompatible ferroelectric (Na,K)NbO3 (NKN) nanofibers were synthesized by sol-gel assisted electrospinning technique. Low amplitude piezoelectric response as well as electrostriction effect in NKN fibers were examined using piezoelectric force microscopy technique. Piezoelectric coefficient d(33) is strongly anisotropic varying from 75.8 to 18.3 pm/V for, respectively, out-of-axis and on-axis oriented ferroelectric domains in NKN fibers. Hysteresis P-E loop for individual nanofiber reconstructed from the bipolar E-field-induced butterfly strain curve yields: coercive field E-c = 31 kV/cm, remnant P-r = 6.2 mu C/cm(2), and the maximum achieved polarization P-max = 21.2 mu C/cm(2). Enhanced piezoelectric effect and strong electrostriction promise NKN fibers as electrically polarizable scaffolds for tissue engineering and for energy harvesting biocompatible nanogenerators.
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