| 1. |
- Bengnér, Malin, et al.
(author)
-
Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity.
- 2014
-
In: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 36:2, s. 571-582
-
Journal article (peer-reviewed)abstract
- Cytomegalovirus (CMV) infection induces profound changes in different subsets of the cellular immune system. We have previously identified an immune risk profile (IRP) where CMV-associated changes in the T cell compartment, defined as a CD4/CD8 ratio < 1, are associated with increased mortality in elderly people. Since natural killer (NK) cells have an important role in the defense against viral infections, we examined whether the expansion of CD8 + T cells seen in individuals with CD4/CD8 ratio < 1 is coupled to a parallel skewing of the NK cell compartment. A number of 151 subjects were examined with CMV serology and a flow cytometry panel for assessment of T cell and NK cell subsets. CMV-seropositive individuals had higher frequencies of CD57 + and NKG2C + NK cells and lower frequencies of NKG2A + NK cells, in line with a more differentiated NK cell compartment. Intriguingly, however, there was no correlation between CD4/CD8 ratio and NK cell repertoires among CMV-seropositive donors, despite the profound skewing of the T cell compartment in the group with CD4/CD8 ratio < 1. Conversely, donors with profound expansion of NK cells, defined as NKG2C + NK cells with high expression of CD57 and ILT-2, did not display more common changes in their T cell repertoire, suggesting that NK cell expansion is independent of the T cell-defined IRP. Altogether, these results indicate that the effect of CMV on CD8 T cells and NK cells is largely nonoverlapping and independent.
|
|
| 2. |
|
|
| 3. |
- Garmy, Pernilla, et al.
(author)
-
Sömnstörningar hos barn : kunskapsdokument
- 2015
-
Reports (other academic/artistic)abstract
- Ett möte med experter på barns sömnproblem genomfördes i februari 2014 varvid detta kunskapsdokument togs fram. Kunskapssammanställningen och rekommendationerna har tagits fram gemensamt av experterna och bygger på konsensus bland deltagarna. Läkemedelsverkets ansvar var att facilitera mötet samt att tillsammans med experterna sammanställa kunskapsdokumentet. Som stöd för kunskapsdokumentet finns bakgrundsdokument som respektive författare ansvarar för. I bakgrundsdokumenten finns, förutom detaljerad information om varje ämnesområde, även referenser. Socialstyrelsen medverkade vid expertmötet, liksom i framtagandet av kunskapsdokumentet. Inför mötet har SBU (2013) identifierat kunskapsluckor inom området, vilka publicerats i SBU:s databas över vetenskapliga kunskapsluckor, se www.sbu.se. En vetenskaplig kunskapslucka innebär att systematiska litteraturöversikter saknas eller att de visar på osäker effekt. Man fann att detta gäller "Melatonin till barn som har flera funktionsnedsättningar och sömnproblem", "Melatonin som behandling av sömnproblem hos barn med adhd" och " Melatonin för i övrigt friska barn med sömnproblem". SBU konstaterade tidigare (2010) att "Effekten av alimemazin vid behandling av sömnbesvär" också är envetenskaplig kunskapslucka.
|
|
| 4. |
- Garmy, Pernilla, et al.
(author)
-
Sömnstörningar hos barn : kunskapsdokument
- 2015
-
Book (other academic/artistic)abstract
- Ett möte med experter på barns sömnproblem genomfördes i februari 2014 varvid detta kunskapsdokument togs fram. Kunskapssammanställningen och rekommendationerna har tagits fram gemensamt av experterna och bygger på konsensus bland deltagarna. Läkemedelsverkets ansvar var att facilitera mötet samt att tillsammans med experterna sammanställa kunskapsdokumentet. Som stöd för kunskapsdokumentet finns bakgrundsdokument som respektive författare ansvarar för. I bakgrundsdokumenten finns, förutom detaljerad information om varje ämnesområde, även referenser. Socialstyrelsen medverkade vid expertmötet, liksom i framtagandet av kunskapsdokumentet. Inför mötet har SBU (2013) identifierat kunskapsluckor inom området, vilka publicerats i SBU:s databas över vetenskapliga kunskapsluckor, se www.sbu.se. En vetenskaplig kunskapslucka innebär att systematiska litteraturöversikter saknas eller att de visar på osäker effekt. Man fann att detta gäller "Melatonin till barn som har flera funktionsnedsättningar och sömnproblem", "Melatonin som behandling av sömnproblem hos barn med adhd" och " Melatonin för i övrigt friska barn med sömnproblem". SBU konstaterade tidigare (2010) att "Effekten av alimemazin vid behandling av sömnbesvär" också är envetenskaplig kunskapslucka.
|
|
| 5. |
- Hanson, Mikael G. V., et al.
(author)
-
A short-term dietary supplementation with high doses of vitamin E increases NK cell cytolytic activity in advanced colorectal cancer patients
- 2007
-
In: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 56:7, s. 973-984
-
Journal article (peer-reviewed)abstract
- Cancer patients with advanced disease display signs of immune suppression, which constitute a major obstacle for effective immunotherapy. Both T cells and NK cells are affected by a multitude of mechanisms of which the generation of reactive oxygen species is of major importance. Therefore, we hypothesized that two weeks of high-dose treatment with the anti-oxidant vitamin E may enhance NK cell function in cancer patients by protecting from oxidative stress. Seven patients with colorectal cancer (Dukes stage C and D) received a daily dose of 750 mg of vitamin E during a period of two weeks and the function, phenotype and receptor expression of NK cells were analyzed. The short-term vitamin E treatment significantly improved NK cell cytolytic activity in six out of the seven patients analyzed. The increased NK cell activity in patients' PBMC was not due to increased numbers of NK cells or an increase in the proportion of the CD56(dim) NK cell subpopulation. Furthermore, neither an increased perforin expression nor an enhanced ability of NK cells to produce IFN-gamma was observed as a result of vitamin E treatment. Finally, vitamin E treatment was associated with a minor, but consistent, induction of NKG2D expression in all patients analyzed. In conclusion, this pilot study demonstrates that vitamin E may boost NK cell function in patients with colorectal cancer. Further studies are warranted to explore the potential of vitamin E as an adjuvant for immunotherapy against cancer and to determine the underlying mechanism(s) behind vitamin E induced NK cell activation.
|
|
| 6. |
- Lindgren, Peter, et al.
(author)
-
The long-term cost-effectiveness of clopidogrel plus aspirin in patients undergoing percutaneous coronary intervention in Sweden
- 2005
-
In: Clinical Therapeutics. - : Elsevier BV. - 0149-2918 .- 1879-114X. ; 27:1, s. 100-110
-
Journal article (peer-reviewed)abstract
- Background: The Percutaneous CoronaryIntervention-Clopidogrel in Unstable Angina to Prevent Recurrent Events (PCI-CURE) study, which examined the effect of adding clopidogrel to aspirin versus aspirin alone in patients with unstable coronary artery disease (CAD) undergoing PCI, found a relative risk reduction in cardiovascular deaths and myocardial infarction among those treated with clopidogrel. In addition, a within-trial cost-effectiveness analysis showed favorable costs per event avoided. However, to estimate the long-term effects, a modeling approach is necessary. Objectives: The purpose of this study was to estimatethe long-term cost-effectiveness of treating patients undergoing PCI with clopidogrel plus aspirin in Sweden. Methods: A Markov model was developed. Transitionprobabilities were estimated based on a register of patients treated in the coronary care units at 74 (out of 78) hospitals throughout Sweden. Patients were assumed to be treated for 1 year with an effect based on data from the PCI-CURE study. Costs were collected from published sources and recalculated to year-2004 euros (1.00 = US $1.24). Life-years gained were used as the measure of effectiveness. The perspective was that of the Swedish society, with a separate analysis using a health care cost perspective. Results: After inclusion and exclusion criteria were applied, 3474 patients were included in the model analysis. The model predicted a net gain in survival of 0.04 year per patient when adding clopidogrel. This yielded a net increase of 449 if only direct costs were included, with indirect costs, the net increase was 332. The resulting cost-effectiveness ratios were €10,993 and 8127 per life-year gained. Conclusions: The predicted cost-effectiveness ratios were well below the threshold values generally considered cost-effective. Adding clopidogrel to aspirin appeared to be cost-effective in this model analysis of patients with unstable CAD undergoing PCI in Sweden. Copyright © 2005 Excerpta Medica, Inc.
|
|
| 7. |
- Lovric, Jelena, 1980, et al.
(author)
-
Multimodal Imaging of Chemically Fixed Cells in Preparation for NanoSIMS
- 2016
-
In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 88:17, s. 8841-8848
-
Journal article (peer-reviewed)abstract
- In this work, we have employed time-of-flight secondary ion mass spectrometry (ToF-SIMS) to image chemically fixed adrenal cells prepared for transmission electron microscopy (TEM) and subsequent high-spatial-resolution NanoSIMS imaging. The sample fixation methodology preserves cell morphology, allows analysis in the ultrahigh vacuum environment, and reduces topographic artifacts, thus making these samples particularly favorable for ToF-SIMS analysis. ToF-SIMS imaging enables us to determine the chemistry and preservation capabilities of the chemical fixation as well as to locate specific ion species from OsO4. The OsO4 species have been localized in lysosomes of cortical cells, a type of adrenal cell present in the culture. NanoSIMS imaging of the 190Os16O– ion species in cortical cells reveals the same localization as a wide range of OsO4 ions shown with ToF-SIMS. Even though we did not use during NanoSIMS imaging the exact OsxOy– ion species discovered with ToF-SIMS, ToF-SIMS allowed us to define the specific subcellular features in a high spatial resolution imaging mode. This study demonstrates the possibility for application of ToF-SIMS as a screening tool to optimize high-resolution imaging with NanoSIMS, which could replace TEM for localization in ultrahigh resolution imaging analyses.
|
|
| 8. |
|
|
| 9. |
- Mukherjee, Sourav P., et al.
(author)
-
Graphene Oxide Elicits Membrane Lipid Changes and Neutrophil Extracellular Trap Formation
- 2018
-
In: Chem. - : Elsevier BV. - 2451-9294 .- 2451-9308. ; 4:2, s. 334-358
-
Journal article (peer-reviewed)abstract
- Understanding the biological interactions of graphene-based materials is important for the safe use of these materials. Previous studies have explored the interaction between graphene oxide (GO) and macrophages but not the impact of GO on neutrophils, key cells of the immune system. Here, we synthesized GO sheets with differing lateral dimensions and showed by using an array of analytical and imaging techniques, including transmission and scanning electron microscopy, confocal microscopy, and time-of-flight secondary ion mass spectroscopy (ToF-SIMS), that GO elicited the formation of neutrophil extracellular traps (NETs). ToF-SIMS revealed pronounced perturbations of plasma membrane lipids, including a decrease in cholesterol and increased levels of oxidized cholesterol species. The induction of NETs was size dependent and associated with the production of mitochondrial reactive oxygen species and calcium influx. Importantly, antioxidant treatment reduced the production of NETs. These studies provide evidence that a previously undescribed biological effect of GO manifests through direct effects on membrane lipids. Graphene oxide (GO) is being investigated for various biomedical applications. Understanding the interactions between GO and living cells is of critical importance for the safe use of these materials in patients. In the present study, we identified effects of GO on neutrophils, the most common type of white blood cell. We first synthesized GO sheets of different sizes and carefully characterized the materials. Then, using various analytical and imaging techniques, we found that GO triggered so-called neutrophil extracellular traps or NETs. NETs are normally deployed by neutrophils to capture and destroy pathogens. We were able to show that GO caused significant changes in the lipid composition of the neutrophil cell membrane, whereby the oxidation of cholesterol set into motion a cascade of intracellular events leading to the formation of NETs. These studies show that GO acts directly on the neutrophil cell membrane and leads to the activation of a conserved anti-pathogen response. Graphene oxide (GO) is a promising material for a variety of biomedical and other applications. The increasing use of GO necessitates careful assessment of potential health hazards. Using primary neutrophils as a model, Mukherjee et al. show that GO elicits neutrophil extracellular traps. Furthermore, by using ToF-SIMS, the authors noted pronounced perturbations of plasma membrane lipids in cells exposed to GO.
|
|
| 10. |
- Nygren, Håkan, 1952, et al.
(author)
-
Bioimaging TOF-SIMS of tissues by gold ion bombardment of a silver-coated thin section.
- 2004
-
In: Microscopy research and technique. - : Wiley. - 1059-910X .- 1097-0029. ; 65:6, s. 282-6
-
Journal article (peer-reviewed)abstract
- The imaging time-of-flight secondary-ion-mass-spectrometry (TOF-SIMS) method was utilized to address the problem of cholesterol localization in rat tissues. Rat kidneys were fixed, cryoprotected by sucrose, frozen, sectioned by cryoultramicrotomy, and dried at room temperature. The samples were either covered with a thin silver layer or analyzed uncovered in an imaging TOF-SIMS instrument equipped with an Au1-3(+)-source. The yield of desorbed secondary ions for some species was up to 600-fold higher after silver coating of the samples. Reference samples of cholesterol were silver-coated and analyzed by TOF-SIMS to define significant peaks, specific for cholesterol. Such peaks were found at m/z = 386 (C27H46O+), m/z = 493 (C27H46O107Ag+), m/z = 495 (C27H46O109Ag+), m/z = 879 (C54H92O2 107Ag+), and m/z = 881 (C54H92O2 109Ag+). The silver-cationized cholesterol (493 < or = m/z < or = 495) signal was localized by imaging TOF-SIMS in the kidney sections and showed a high cholesterol content in the kidney glomeruli. A more diffuse distribution of cholesterol was also found over areas representing the cytoplasm or plasma membrane of the epithelial cells in the proximal tubules of rat kidney.
|
|
