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Sökning: WFRF:(Höglund Caroline O.)

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1.
  • Tuisku, Jouni, et al. (författare)
  • Effects of age, BMI and sex on the glial cell marker TSPO : a multicentre [11C]PBR28 HRRT PET study
  • 2019
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 46:11, s. 2329-2338
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C-11]PBR28. Methods [C-11]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V-T) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results There were significant positive correlations between age and V-T in the frontal and temporal cortex. BMI showed a significant negative correlation with V-T in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V-T. A subgroup analysis revealed a positive correlation between V-T and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.
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2.
  • Harper, Lorraine, et al. (författare)
  • Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up
  • 2012
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 1468-2060. ; 71:6, s. 955-960
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study. Methods Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised. Results Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs. Discussion Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.
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3.
  • Axelsson, J., et al. (författare)
  • Effects of Sustained Sleep Restriction on Mitogen-Stimulated Cytokines, Chemokines and T Helper 1/T Helper 2 Balance in Humans
  • 2013
  • Ingår i: Plos One. - 1932-6203. ; 8:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. Methods: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00 - 07.00 h) followed by 5 days with restricted sleep (03.00 - 07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-alpha), interleukin (IL) -1 beta, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed. Results: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-alpha and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day. Conclusions: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences. BAS AK, 1991, IMMUNOLOGICAL REVIEWS, V123, P5
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4.
  • Gad, Helge, et al. (författare)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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5.
  • Heijl, Caroline, et al. (författare)
  • Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials.
  • 2011
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 1468-2060. ; 70, s. 1415-1421
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: /st> Because standard immunosuppressive treatment for antineutrophil cytoplasm antibody-associated vasculitis (AAV) (granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA)) has been associated with a significant risk of developing cancer, the cancer incidence of treated AAV patients was assessed. METHODS: /st> This analysis concerned 535 patients with newly diagnosed AAV from 15 countries who had been enrolled between 1995 and 2002 in four European clinical trials. Over the period 2004-7, study participants' follow-up events were updated, including cancers diagnosed. Age, sex and area-standardised incidence ratios (SIR) and their 95% CI were calculated by linkage to five national cancer databases. RESULTS: /st> During the 2650 person-years' observation period, 50 cancers were diagnosed in 46 patients. SIR (95% CI) were 1.58 (1.17 to 2.08) for cancers at all sites, 1.30 (0.90 to 1.80) for cancers at all sites excluding non-melanoma skin cancer (NMSC), 2.41 (0.66 to 6.17) for bladder cancer, 3.23 (0.39 to 11.65) for leukaemia, 1.11 (0.03 to 6.19) for lymphoma and 2.78 (1.56 to 4.59) for NMSC. Subgroup SIR for cancers at all sites were 1.92 (1.31 to 2.71) for GPA and 1.20 (0.71 to 1.89) for MPA. CONCLUSIONS: /st> Cancer rates for AAV patients treated with conventional immunosuppressive therapy exceeded those expected for the general population. This cancer excess was largely driven by an increased incidence of NMSC. The smaller cancer risk magnitude in this cohort, compared with previous studies, might reflect less extensive use of cyclophosphamide in current treatment protocols. Longer follow-up data are warranted to appraise the risk of developing cancers later during the course of AAV.
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