| 1. |
- Eneslätt, Kjell, et al.
(författare)
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Persistence of cell-mediated immunity three decades after vaccination with the live vaccine strain of Francisella tularensis
- 2011
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Ingår i: European Journal of Immunology. - Weinheim : Wiley-VCH Verlagsgesellschaft. - 0014-2980 .- 1521-4141. ; 41:4, s. 974-980
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy of many vaccines against intracellular bacteria depends on the generation of cell-mediated immunity, but studies to determine the duration of immunity are usually confounded by re-exposure. The causative agent of tularemia, Francisella tularensis, is rare in most areas and, therefore, tularemia vaccination is an interesting model for studies of the longevity of vaccine-induced cell-mediated immunity. Here, lymphocyte proliferation and cytokine production in response to F. tularensis were assayed in two groups of 16 individuals, vaccinated 1-3 or 27-34 years previously. As compared to naïve individuals, vaccinees of both groups showed higher proliferative responses and, out of 17 cytokines assayed, higher levels of MIP-1β, IFN-γ, IL-10, and IL-5 in response to recall stimulation. The responses were very similar in the two groups of vaccinees. A statistical model was developed to predict the immune status of the individuals and by use of two parameters, proliferative responses and levels of IFN-γ, 91.1% of the individuals were correctly classified. Using flow cytometry analysis, we demonstrated that during recall stimulation, expression of IFN-γ by CD4(+) CCR7(+) , CD4(+) CD62L(+) , CD8(+) CCR7(+) , and CD8(+) CD62L(+) cells significantly increased in samples from vaccinated donors. In conclusion, cell-mediated immunity was found to persist three decades after tularemia vaccination without evidence of decline.
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| 2. |
- Holm, Karolina, et al.
(författare)
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Global H3K27 trimethylation and EZH2 abundance in breast tumor subtypes
- 2012
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Ingår i: Molecular Oncology. - : Elsevier. - 1574-7891 .- 1878-0261. ; 6:5, s. 494-506
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Tidskriftsartikel (refereegranskat)abstract
- Polycomb repressive complex 2 (PRC2) and its core member enhancer of zeste homolog 2 (EZH2) mediate the epigenetic gene silencing mark: trimethylation of lysine 27 on histone 3 (H3K27me3). H3K27me3 is characteristic of the chromatin at genes involved in developmental regulation in undifferentiated cells. Overexpression of EZH2 has been found in several cancer types such as breast, prostate, melanoma and bladder cancer. Moreover, overexpression is associated with highly proliferative and aggressive types of breast and prostate tumors. We have analyzed the abundance of EZH2 and H3K27me3 using immunohistochemistry in two large and Well-characterized breast tumor data sets encompassing more than 400 tumors. The results have been analyzed in relation to the molecular subtypes of breast tumors (basal-like, luminal A, luminal B, HER2-enriched and normal-like), as well as in subtypes defined by clinical markers (triple negative, ER+/HER2-/Ki67low, ER+/HER2-/Ki67high and HER2+), and were validated in representative breast cancer cell lines by western blot. We found significantly different expression of both EZH2 and H3K27me3 across all subtypes with high abundance of EZH2 in basal-like, triple negative and HER2-enriched tumors, and high H3K27me3 in luminal A, HER2-enriched and normal-like tumors. Intriguingly, the two markers show an inverse correlation, particularly for the basal-like and triple negative tumors. Consequently, high expression of EZH2 was associated with poor distant disease-free survival whereas high expression of H3K27me3 was associated with better survival. Additionally, none of 182 breast tumors was found to carry a previously described EZH2 mutation affecting Tyr641. Our observation that increased expression of EZH2 does not necessarily correlate with increased abundance of H3K27me3 supports the idea that EZH2 can have effects beyond epigenetic silencing of target genes in breast cancer.
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| 3. |
- Kautto, Ethel, et al.
(författare)
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What happens to food choices when a gluten-free diet is required? : A prospective longitudinal population-based study among Swedish adolescent with coeliac disease and their peers
- 2014
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Ingår i: Journal of Nutritional Science. - : Cambridge University Press. - 2048-6790. ; 3:e2
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Tidskriftsartikel (refereegranskat)abstract
- A dietary survey was performed during a large screening study in Sweden among 13-year-old adolescents. The aim was to study how the intake of food groups was affected by a screening-detected diagnosis of celiac disease (CD) and its gluten-free (GF) treatment. Food intake, was reported using a food frequency questionnaires (FFQ) and intake reported by the adolescents who was screened to CD was compared with the intake of two same-aged referent groups: i) adolescents diagnosed to CD prior screening and ii) adolescents without CD.. The food intake groups were measured at baseline before the screening-detected cases were aware of their CD, and 12-18 months later.The result showed that the food intakes are affected by a screen detected CD and its dietary treatment. Many flour-based foods were reduced such as pizza, fish fingers, and pastries. The result also indicated that the bread intake was lower before the screened diagnosis compared to the other studied groups, but increased afterwards. Specially manufactured GF-products (e.g. pasta and bread) were frequently used in the screened CDgroup after changing to a GF-diet. Our results suggest that changing to a GF-diet reduces the intake of some popular foods, and the ingredients on the plate are altered, but this do not necessarily include a change of food groups. The availability of manufactured GF-replacement products makes it possible for adolescents to keep many of their old food habits when diagnosed with CD in Sweden.
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| 4. |
- Rennstam, Karin, et al.
(författare)
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Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer.
- 2010
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 122, s. 315-324
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Tidskriftsartikel (refereegranskat)abstract
- Decreased expression of Numb, resulting in activation of the proto-oncogene Notch1 and reduction in the tumor suppressor p53, has been demonstrated in mammary carcinomas. The aim of this study was to investigate the relationship between Numb protein expression and clinicopathological characteristics, tumor biological subtypes and putative cancer stem cell markers in a well-characterized cohort of primary human breast cancers. Immunohistochemistry was performed on tissue microarrays of primary invasive breast tumors using a polyclonal anti-Numb primary antibody. Of the 241 tumors evaluated, 50 (21%) displayed deficient or reduced Numb immunoreactivity. Retained Numb expression was significantly correlated to estrogen (ER) and progesterone receptor (PR) positivity (P < 0.001 and P = 0.004, respectively). Interestingly, we found that a higher percentage of the tumors with deficient or reduced Numb expression belonged to the triple-negative (ER-/PR-/HER2-) subgroup compared to tumors with retained Numb expression (P = 0.004). Transcriptional profiling of a subset of these tumors linked NOTCH1 and BIRC5, both downstream targets of Numb, to the triple-negative subgroup in an inverse manner. Typically, subgroups characterized by the low expression of Numb expressed higher levels of NOTCH1 and BIRC5 (encoding survivin). We also found deficient expression of Numb in a significantly higher proportion of BRCA1 dependent tumors, which are usually triple-negative, compared to sporadic tumors. The expression of Numb in 14 breast cancer cell lines correlated similarly to their respective molecular subtypes. We further established an inverse correlation between the Numb expression levels and the CD44+/CD24- cancer stem cell phenotype (P = 0.05) in primary tumors. Finally, decreased Numb expression was associated with poorer distant disease-free survival (P = 0.01). Taken together, our results indicate that loss of Numb expression is a marker of tumor aggressiveness, potentially linked to BRCA1 status and a cancer stem cell phenotype in primary breast cancer.
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| 5. |
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| 6. |
- Sahlin, Ullrika, et al.
(författare)
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A benefit analysis of screening for invasive species - base-rate uncertainty and the value of information
- 2011
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Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 2:5, s. 500-508
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Tidskriftsartikel (refereegranskat)abstract
- 1.. Implementation of the full spectra of screening tools to prevent the introduction of invasive species results in a need to evaluate the cost-efficiency of gathering the information needed to screen for these species. 2. We show how the Bayesian value of information approach can be used to derive the benefit of a screening model based on species traits, which in combination with the base rate of invasiveness, i.e. the proportion of invasive species among those introduced and established, predicts species-specific invasiveness. 3. A pre-posterior Bayesian analysis demonstrated that the benefit of the screening model of invasiveness depends on both the accuracy in predictions and the uncertainty in the base rate of invasiveness. However, even though increasing model accuracy always generates higher model benefit, acknowledging or neglecting the uncertainty in the base rate of invasiveness does not. This means that uncertainty in the base rate is important to consider in the cost-benefit analysis of the screening model. 4. As an example, we derived the benefit of basing decisions on a screening model trained for a data set on species traits of invasive and non-invasive marine macroalgae introduced into Europe. The benefit ranged from 0.6% to 19% of the loss of introducing an invasive species, where the actual value can be estimated if we know the monetary values of impacts from introducing invasive and not introducing non-invasive species. 5. Cost-benefit analyses of screening models for invasive species is one means to reach efficient management of the risks of non-indigenous species. Value of information is a useful tool for benefit analysis of predictive models with respect to decision-making, which goes beyond the investigations of model accuracy. Here, we use value of information analysis to evaluate which sources of uncertainty that is most worth while to reduce and how to set the cost of gathering further species-specific information which will improve the accuracy of a screening.
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