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| 2. |
- Landin-Olsson, Mona, et al.
(författare)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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| 3. |
- Page, Brent D. G., et al.
(författare)
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Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADPribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5 substrates and underscore the biological requirement for NUDT5 in gene regulation and proliferation of breast cancer cells. We confirm the involvement of NUDT5 in ADP-ribose metabolism and dissociate a relationship to oxidized nucleotide sanitation. Furthermore, we identify potent NUDT5 inhibitors, which are optimized to promote maximal NUDT5 cellular target engagement by CETSA. Lead compound, TH5427, blocks progestin-dependent, PAR-derived nuclear ATP synthesis and subsequent chromatin remodeling, gene regulation and proliferation in breast cancer cells. We herein present TH5427 as a promising, targeted inhibitor that can be used to further study NUDT5 activity and ADP-ribose metabolism.
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| 4. |
- Sanjeevi, Carani B., et al.
(författare)
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The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
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Tidskriftsartikel (refereegranskat)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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| 6. |
- Hallgren, C G, et al.
(författare)
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Markers of high fish intake are associated with decreased risk of a first myocardial infarction
- 2001
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 86:3, s. 397-404
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Tidskriftsartikel (refereegranskat)abstract
- High intake of fish has been associated with reduced risk of CHD. The high content of n-3 polyunsaturated fatty acids (PUFA) in fish has been suggested to be a protective factor. In addition, fish is the entirely dominating source of methylmercury for the general population, and the concentration of Hg in erythrocytes (Ery-Hg) is often used as an index of fish consumption. Our aim was to study the relationships between a first-ever myocardial infarction, Ery-Hg, activity of gluthathione peroxidase in erythrocytes (Ery-GSH-Px) and plasma concentration of the n-3 PUFA eicosapentaenoic and docosahexaenoic acids (P-PUFA). In a population-based prospective nested case-control study within Northern Sweden seventy-eight cases of a first-ever myocardial infarction were compared with 156 controls with respect to Ery-Hg, P-PUFA and Ery-GSH-Px. Both Ery-Hg and P-PUFA, but not Ery-GSH-Px, were significantly higher in subjects reporting high fish intake (at least one meal per week) than in those with lower intake. This finding suggests that Ery-Hg and P-PUFA reflect previous long-term fish intake. Low risk of myocardial infarction was associated with high Ery-Hg or high P-PUFA. In a multivariate model the risk of myocardial infarction was further reduced in subjects with both high Ery-Hg and high P-PUFA (odds ratio 0.16, 95 % CI 0.04, 0.65). In conclusion, there is a strong inverse association between the risk of a first myocardial infarction and the biomarkers of fish intake, Ery-Hg and P-PUFA, and this association is independent of traditional risk factors.
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| 7. |
- Häggblad, Erik, 1972-
(författare)
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In Vivo Diffuse Reflectance Spectroscopy of Human Tissue : From Point Measurements to Imaging
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents the non-invasive use of diffuse reflectance spectroscopy (DRS) to provide information about the biochemical composition of living tissue. During DRS measurements, the incident, visible light is partially absorbed by chromophores but also scattered in the tissue before being remitted.Human skin and heart, the main tissue objects in this thesis, are dependent on a sufficient inflow of oxygenized blood, and outflow of metabolic byproducts. This process could be monitored by DRS using the spectral fingerprints of the most important tissue chromophores, oxyhemoglobin and deoxyhemoglobin.The Beer-Lambert law was used to produce models for the DRS and has thus been a foundation for the analyses throughout this work. Decomposition into the different chromophores was performed using least square fitting and tabulated data for chromophore absorptivity.These techniques were used to study skin tissue erythema induced by a provocation of an applied heat load on EMLA-treated skin. The absorbance differences, attributed to changes in the hemoglobin concentrations, were examined and found to be related to, foremost, an increase in oxyhemoglobin.To estimate UV-induced border zones between provoked and nonprovoked tissue a modified Beer-Lambert model, approximating the scattering effects, was used. An increase of chromophore content of more than two standard deviations above mean indicated responsive tissue. The analysis revealed an edge with a rather diffuse border, contradictory to the irradiation pattern.Measuring in the operating theater, on the heart, it was necessary to calculate absolute chromophore values in order to assess the state of the myocardium. Therefore, a light transport model accounting for the optical properties, and a calibrated probe, was adopted and used. The absolute values and fractions of the chromophores could then be compared between sites and individuals, despite any difference of the optical properties in the tissue.A hyperspectral imaging system was developed to visualize the spatial distribution of chromophores related to UV-provocations. A modified Beer-Lambert approximation was used including the chromophores and a baseline as an approximate scattering effect. The increase in chromophore content was estimated and evaluated over 336 hours.In conclusion, advancing from a restricted Beer-Lambert model, into a model estimating the tissue optical properties, chromophore estimation algorithms have been refined progressively. This has allowed advancement from relative chromophore analysis to absolute values, enabling precise comparisons and good prediction of physiological conditions.
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| 8. |
- Kirsebom, O. S., et al.
(författare)
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Measurement of the 2+→0+ ground-state transition in the β decay of F 20
- 2019
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Ingår i: Physical Review C. - 2469-9985. ; 100:6
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Tidskriftsartikel (refereegranskat)abstract
- We report the first detection of the second-forbidden, nonunique, 2+→0+, ground-state transition in the β decay of F20. A low-energy, mass-separated F+20 beam produced at the IGISOL facility in Jyväskylä, Finland, was implanted in a thin carbon foil and the β spectrum measured using a magnetic transporter and a plastic-scintillator detector. The β-decay branching ratio inferred from the measurement is bβ=[0.41±0.08(stat)±0.07(sys)]×10-5 corresponding to logft=10.89(11), making this one of the strongest second-forbidden, nonunique β transitions ever measured. The experimental result is supported by shell-model calculations and has significant implications for the final evolution of stars that develop degenerate oxygen-neon cores. Using the new experimental data, we argue that the astrophysical electron-capture rate on Ne20 is now known to within better than 25% at the relevant temperatures and densities.
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| 9. |
- Pearce, Mark, et al.
(författare)
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Balloon-borne hard X-ray polarimetry with PoGOLite
- 2012
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Ingår i: 2012 IEEE Nuclear Science Symposium and Medical Imaging Conference Record (NSS/MIC). - : IEEE. - 9781467320306 ; , s. 1885-1892
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Konferensbidrag (refereegranskat)abstract
- PoGOLite is a hard X-ray polarimeter operating in the 25-100 keV energy band. The instrument design is optimised for the observation of compact astrophysical sources. Observations are conducted from a stabilised stratospheric balloon platform at an altitude of approximately 40 km. The primary targets for first balloon flights of a reduced effective area instrument are the Crab and Cygnus-X1. The polarisation of incoming photons is determined using coincident Compton scattering and photo-absorption events reconstructed in an array of plastic scintillator detector cells surrounded by a bismuth germanate oxide (BGO) side anticoincidence shield and a polyethylene neutron shield. A custom attitude control system keeps the polarimeter field-of-view aligned to targets of interest, compensating for sidereal motion and perturbations such as torsional forces in the balloon rigging. An overview of the PoGOLite project is presented and the outcome of the ill-fated maiden balloon flight is discussed.
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| 10. |
- Sun, Chengjun, et al.
(författare)
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CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
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Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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