| 11. |
- Jäghult, Susanna, et al.
(author)
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Identifying predictors of low health-related quality of life among patients with inflammatory bowel disease : comparison between Crohn's disease and ulcerative colitis with disease duration
- 2011
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In: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 20:11-12, s. 1578-1587
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Journal article (peer-reviewed)abstract
- Aim. To identify predictors of low health-related quality of life among patients with inflammatory bowel disease and make a comparison between Crohn's disease and ulcerative colitis with disease duration. Background. Studies have shown that patients with inflammatory bowel disease rate their health-related quality of life lower, as compared with a general population. Design. Survey. Methods. In this study, 197 patients in remission were included and divided into a Crohn's disease group and an ulcerative colitis group. Each group was also divided into separate groups whether the patients had short disease duration or long disease duration. Generic instruments, combined with disease-specific questionnaires, were used for measuring health-related quality of life. Results. The analysis showed a non-significant effect for diagnosis, but a significant effect for disease duration showing that the patients with short disease duration had lower scores of health-related quality of life compared with patients with long disease duration. A significant interaction between diagnosis and disease duration was also revealed. Conclusion. Patients with longer disease duration experienced a better health-related quality of life than patients with short disease duration. Patients with Crohn's disease and short disease duration have the lowest health-related quality of life and are in greatest need of education and support. Relevance to clinical practice. It is important to identify which patients' are in the greatest need of education and support.
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| 12. |
- Loth, Daan W, et al.
(author)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Journal article (peer-reviewed)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 13. |
- Myrtennäs, Kerstin, et al.
(author)
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Genome sequence of Francisella Tularensis subspecies holarctica Strain FSC200, isolated from a child with Tularemia
- 2012
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In: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 194:24, s. 6965-6966
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Journal article (peer-reviewed)abstract
- Here we report the complete, accurate 1.89-Mb genome sequence of Francisella tularensis subsp. holarctica strain FSC200, isolated in 1998 in the Swedish municipality Ljusdal, which is in an area where tularemia is highly endemic. This genome is important because strain FSC200 has been extensively used for functional and genetic studies of Francisella and is well-characterized.
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| 14. |
- Semenas, Julius, et al.
(author)
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The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer
- 2014
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:35, s. E3689-E3698
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Journal article (peer-reviewed)abstract
- Nitrogen-containing heterocyclic compounds are an important class of molecules that are commonly used for the synthesis of candidate drugs. Phosphatidylinositol-4-phosphate 5-kinase-α (PIP5Kα) is a lipid kinase, similar to PI3K. However, the role of PIP5K1α in oncogenic processes and the development of inhibitors that selectively target PIP5K1α have not been reported. In the present study we report that overexpression of PIP5K1α is associated with poor prognosis in prostate cancer and correlates with an elevated level of the androgen receptor. Overexpression of PIP5K1α in PNT1A nonmalignant cells results in an increased AKT activity and an increased survival, as well as invasive malignant phenotype, whereas siRNA-mediated knockdown of PIP5K1α in aggressive PC-3 cells leads to a reduced AKT activity and an inhibition in tumor growth in xenograft mice. We further report a previously unidentified role for PIP5K1α as a druggable target for our newly developed compound ISA-2011B using a high-throughput KINOMEscan platform. ISA-2011B was discovered during our synthetic studies of C-1 indol-3-yl substituted 1,2,3,4-tetrahydroisoquinolines via a Pictet-Spengler approach. ISA-2011B significantly inhibits growth of tumor cells in xenograft mice, and we show that this is mediated by targeting PIP5K1α-associated PI3K/AKT and the downstream survival, proliferation, and invasion pathways. Further, siRNA-mediated knockdown of PIP5K1α exerts similar effects on PC3 cells as ISA-2011B treatment, significantly inhibiting AKT activity, increasing apoptosis and reducing invasion. Thus, PIP5K1α has high potential as a drug target, and compound ISA-2011B is interesting for further development of targeted cancer therapy.
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| 15. |
- Tsilidis, Konstantinos K., et al.
(author)
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Insulin-like growth factor pathway genes and blood concentrations, dietary protein and risk of prostate cancer in the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)
- 2013
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In: International Journal of Cancer. - Hoboken, NJ, USA : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 133:2, s. 495-504
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Journal article (peer-reviewed)abstract
- It has been hypothesized that a high intake of dairy protein may increase prostate cancer risk by increasing the production of insulin-like growth factor 1 (IGF-1). Several single nucleotide polymorphisms (SNPs) have been weakly associated with circulating concentrations of IGF-1 and IGF binding protein 3 (IGFBP-3), but none of these SNPs was associated with risk of prostate cancer. We examined whether an association between 16 SNPs associated with circulating IGF-1 or IGFBP-3 concentrations and prostate cancer exists within subgroups defined by dietary protein intake in 5,253 cases and 4,963 controls of European ancestry within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). The BPC3 includes nested casecontrol studies within large North-American and European cohorts. Per-allele odds ratios for prostate cancer for the SNPs were compared across tertiles of protein intake, which was expressed as the percentage of energy derived from total, animal, dairy or plant protein sources, using conditional logistic regression models. Total, animal, dairy and plant protein intakes were significantly positively associated with blood IGF-1 (p<0.01), but not with IGFBP-3 concentrations (p>0.10) or with risk of prostate cancer (p>0.20). After adjusting for multiple testing, the SNP-prostate cancer associations did not differ by intakes of protein, although two interactions by intake of plant protein were of marginal statistical significance [SSTR5 (somatostatin receptor 5)-rs197056 (uncorrected p for interaction, 0.001); SSTR5-rs197057 (uncorrected p for interaction, 0.002)]. We found no strong evidence that the associations between 16 IGF pathway SNPs and prostate cancer differed by intakes of dietary protein.
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| 16. |
- Xiao, Fang, et al.
(author)
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Slc26a3 deficiency is associated with loss of colonic HCO3 (-) secretion, absence of a firm mucus layer, and barrier impairment in mice.
- 2014
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In: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 211:1, s. 161-175
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Journal article (peer-reviewed)abstract
- DRA (downregulated in adenoma, Slc26a3) is a member of the SLC26 family of anion transporters, which is mutated in congenital chloride diarrhoea (CLD). Besides Cl(-) -rich diarrhoea, CLD patients also have a higher than average incidence of intestinal inflammation. In a search for potential explanations for this clinical finding, we investigated colonic electrolyte transport, the mucus layer, and susceptibility against dextran sodium sulphate (DSS)-induced colitis in Slc26a3(-/-) mice.
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