| 841. |
- Hollander, Peter, et al.
(författare)
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Autoimmune and Atopic Disorders and Risk of Classical Hodgkin Lymphoma
- 2015
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 182:7, s. 624-632
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Tidskriftsartikel (refereegranskat)abstract
- Results from previous investigations have shown associations between the risk of Hodgkin lymphoma (HL) and a history of autoimmune and atopic diseases, but it remains unknown whether these associations apply to all types of HL or only to specific subtypes. We investigated immune diseases and the risk of classical HL in a population-based case-control study that included 585 patients and 3,187 controls recruited from October 1999 through August 2002. We collected information on immune diseases through telephone interviews and performed serological analyses of specific immunoglobulin E reactivity. Tumor Epstein-Barr virus (EBV) status was determined for 498 patients. Odds ratios with 95% confidence intervals were calculated using logistic regression analysis. Rheumatoid arthritis was associated with a higher risk of HL (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.47, 4.70), especially EBV-positive HL (OR = 3.18; 95% CI: 1.23, 8.17), and with mixed-cellularity HL (OR = 4.25; 95% CI: 1.66, 10.90). HL risk was higher when we used proxies of severe rheumatoid arthritis, such as ever having received daily rheumatoid arthritis medication (OR = 3.98; 95% CI: 2.08, 7.62), rheumatoid arthritis duration of 6-20 years (OR = 3.80; 95% CI: 1.72, 8.41), or ever having been hospitalized for rheumatoid arthritis (OR = 7.36; 95% CI: 2.95, 18.38). Atopic diseases were not associated with the risk of HL. EBV replication induced by chronic inflammation in patients with autoimmune diseases might explain the higher risk of EBV-positive HL.
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| 842. |
- Holm, Angelika
(författare)
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Aquaporins in Infection and Inflammation
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ability of eukaryotic cells to change their shape and to migrate directionally is highly dependent on active volume regulation in cells building up tissues as well as in individual cells. Transmembrane fluxes of water via specialized water channels, called aquaporins (AQPs), facilitate the changes of volume and shape, which additionally require a complex interplay between the plasma membrane and the cytoskeleton. AQPs have been shown to be involved in the development of inflammatory processes and diseases. The aims of the studies underlying this thesis were to further elucidate the expression and function of AQPs in both bacterial and viral infections as well as in the inflammatory disease, microscopic colitis. For this, molecular techniques qPCR, immunoblotting and live, holographic, confocal and super-resolution imaging were used.When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI- mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3OC12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages.Viruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections.Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC.Taken together, this thesis provides new evidence on the importance of water homeostasis regulation through AQPs during infections and inflammation and opens up a door for further investigations of roles for AQPs in inflammatory processes.
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| 843. |
- Horne, B D, et al.
(författare)
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Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 107:2, s. 232-240
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Tidskriftsartikel (refereegranskat)abstract
- By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6-11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6-11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that "effective" dose constituted a treatment response index . Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R2 was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1-1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R2= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
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| 844. |
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| 845. |
- Hultberg, Björn, et al.
(författare)
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Concentrations of plasma methylmalonic acid in 80-year-olds show only weak relation to psychological performance
- 1999
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621. ; 37:10, s. 963-967
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Tidskriftsartikel (refereegranskat)abstract
- Most studies of the relation between psychological performance in the elderly and deficiencies of cobalamin and folate have used methods that determine the blood concentrations of these vitamins, which might not reflect the vitamin status in the tissues. Recently, two new markers, plasma homocysteine and methylmalonic acid, have attracted growing interest since they are considered to reflect the status of cobalamins and folates in the tissues. In a previous study, we noted a strong association between five parameters of well-being and lower concentrations of plasma homocysteine. In the present study, we have extended these observations by determination of plasma methylmalonic acid in the same healthy elderly population. In the present study, 18 out of 100 subjects had increased plasma methylmalonic acid and in 7 of these subjects, the concentrations of serum cobalamin, blood folate, plasma homocysteine and serum creatinine were within normal limits. The relation between plasma methylmalonic acid concentrations and concentrations of serum cobalamin and blood folates and five parameters of well-being were investigated. Concentrations of plasma methylmalonic acid were only weakly associated with the concentrations of serum cobalamin and lower scores on the logical reasoning test. The present study clearly shows that the levels of plasma methylmalonic acid show a much lesser association with the parameters of well-being than did plasma homocysteine.
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| 846. |
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| 847. |
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| 848. |
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| 849. |
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| 850. |
- Hultberg, Björn, et al.
(författare)
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The association between plasma beta-hexosaminidase and its isoenzyme patterns and retinopathy in type 1 diabetes mellitus
- 1991
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Ingår i: Clinica Chimica Acta. - 0009-8981. ; 196:2-3, s. 177-183
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Tidskriftsartikel (refereegranskat)abstract
- beta-Hexosaminidase and its isoenzyme patterns were investigated in plasma from patients with Type 1 diabetes mellitus. The patients were divided into three main groups matched for duration of diabetes: (a) proliferative retinopathy (b), progress of retinopathy within a two-year period (c) and with no background retinopathy. When all patients were compared to a reference group, a significant increase of plasma beta-hexosaminidase activity was found. Patients with proliferative retinopathy had significantly increased activity of plasma beta-hexosaminidase compared to the reference group but not compared to the other diabetic patients. The isoenzyme distribution was not different in any of the diabetic subgroups compared to the reference group. It was also shown that various degrees of diabetic nephropathy did not influence total plasma Hex or the isoenzyme pattern.
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