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Sökning: WFRF:(Rosen Anders)

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  • Bergh, Ann-Charlotte, et al. (författare)
  • Silenced B-cell receptor response to autoantigen in a poor-prognostic subset of chronic lymphocytic leukemia
  • 2014
  • Ingår i: Haematologica. - Ferrata Storti Foundation. - 0390-6078. ; 99:11, s. 1722-1730
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic lymphocytic leukemia B-cells express auto/xeno-antigen-reactive antibodies that bind to self-epitopes and resemble natural IgM antibodies in their repertoire. One of the antigenic structures recognized is oxidation-induced malonedialdehyde present on low-density lipoprotein, apoptotic blebs, and on certain microbes. The poor-prognostic stereotyped subset #1 (Clan I IGHV genes-IGKV1(D)-39) express IgM B-cell receptors that bind oxidized low-density lipoprotein. In this study, we have used for the first time this authentic cognate antigen, since it is more faithful to B-cell physiology than anti-IgM, for analysis of downstream B-cell receptor-signal transduction events. Multivalent oxidized low-density lipoprotein showed specific binding to subset #1 IgM/IgD B-cell receptors, whereas native low-density lipoprotein did not. The antigen-binding induced prompt receptor-clustering, followed by internalization. However, the receptor-signal transduction was silenced, revealing no Ca2+ mobilization or cell-cycle entry, while phosphorylated extracellular-regulated kinase1/2 basal levels were high and could not be elevated further by oxidized low-density lipoprotein. Interestingly, B-cell receptor responsiveness was recovered after 48 hours culture in the absence of antigen in half of the cases. Toll-like receptor 9-ligand was found to breach the B-cell receptor-signaling incompetence in 5 of 12 cases pointing to intra-subset heterogeneity. Altogether, this study supports B-cell receptor-unresponsiveness to cognate self-antigen on its own in poor-prognostic subset #1 chronic lymphocytic leukemia indicating that these cells proliferate by other mechanisms that may override B-cell receptor-silencing brought about in a context of self-tolerance/anergy. These novel findings have implications for the understanding of chronic lymphocytic leukemia pathobiology and therapy.
  • Fridberg, Marie, et al. (författare)
  • Protein expression and cellular localization in two prognostic subgroups of diffuse large B-cell lymphoma: Higher expression of ZAP70 and PKC-beta II in the non-germinal center group and poor survival in patients deficient in nuclear PTEN
  • 2007
  • Ingår i: Leukemia Lymphoma. - InformaWorld. - 1042-8194. ; 48:11, s. 2221-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) show varying responses to conventional therapy, and this might be contributed to the differentiation stage of the tumor B-cells. The aim of the current study was to evaluate a panel of kinases (ZAP70, PKC-beta I and II and phosphorylated PKB/Akt) and phosphatases (PTEN, SHP1 and SHP2) known to be frequently deregulated in lymphoid malignancies. De novo DLBCL cases were divided into two subgroups, the germinal center (GC) group (14/28) and the non-germinal center (non-GC) or activated B-cell (ABC) group (14/28). ZAP70 and PKC-beta II were expressed in a significantly higher percentage of tumor cells in the clinically more aggressive non-GC group compared with the prognostically favourable GC group. Also, the subcellular localization of PKC-beta I and II differed in DLBCL cells, with the PKC-beta I isoform being expressed in both the cytoplasm and nucleus, while PKC-beta II was found exclusively in the cytoplasm. Loss of nuclear PTEN correlated with poor survival in cases from both subgroups. In addition, five cell lines of DLBCL origin were analyzed for protein expression and for mRNA levels of PTEN and SHP1. For the first time, we show that ZAP70 is expressed in a higher percentage of tumor cells in the aggressive non-GC subgroup of DLBCL and that PKC-beta I and II are differently distributed in the two prognostic subgroups of de novo DLBCL.
  • Myhrinder, Anna Lanemo, et al. (författare)
  • Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia
  • 2013
  • Ingår i: Leukemia and Lymphoma. - 1042-8194 .- 1029-2403. ; 54:8, s. 1769-1779
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface membrane receptors determines whether the cells will be proliferating, anergic or apoptotic. To better understand the role of antigen in leukemogenesis, CLL cell lines producing monoclonal antibodies (mAbs) will facilitate structural analysis of antigens and supply DNA for genetic studies. We present here a comprehensive genotypic and phenotypic characterization of available CLL and normal B-cell-derived lymphoblastoid cell lines (LCLs) from the same individuals (n = 17). Authenticity and verification studies of CLL-patient origin were done by IGHV sequencing, fluorescence in situ hybridization (FISH) and DNA/short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA.
  • Vikstrom, Pernilla, et al. (författare)
  • Atypical sensory processing pattern following median or ulnar nerve injury - A case-control study
  • 2018
  • Ingår i: BMC Neurology. - BioMed Central. - 1471-2377. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Due to brain plasticity a transection of a median or ulnar nerve results in profound changes in the somatosensory areas in the brain. The permanent sensory deprivation after a peripheral nerve injury might influence the interaction between all senses. The aim of the study was to investigate if a median and/or ulnar nerve injury gives rise to a changed sensory processing pattern. In addition we examined if age at injury, injured nerve or time since injury influence the sensory processing pattern. Methods: Fifty patients (40 men and 10 women, median age 43) operated due to a median and/or ulnar nerve injury were included. The patients completed the Adolescent/Adult Sensory Profile questionnaire, which includes a comprehensive characterization on how sensory information is processed and how an individual responds to multiple sensory modalities. AASP categorizes the results into four possible Quadrants of behavioral profiles (Q1-low registration, Q2-sensory seeking, Q3-sensory sensitivity and Q4-sensory avoiding). The results were compared to 209 healthy age and gender matched controls. Anova Matched Design was used for evaluation of differences between the patient group and the control group. Atypical sensory processing behavior was determined in relation to the normative distribution of the control group. Results: Significant difference was seen in Q1, low registration. 40% in the patient group scored atypically in this Quadrant compared to 16% of the controls. No correlation between atypical sensory processing pattern and age or time since injury was seen. Conclusion: A peripheral nerve injury entails altered sensory processing pattern with increased proportion of patients with low registration to sensory stimulus overall. Our results can guide us into more client centered rehabilitation strategies.
  • Abdiu, A, et al. (författare)
  • Thioredoxin blood level increases after severe burn injury
  • 2000
  • Ingår i: Antioxidants and Redox Signaling. - 1523-0864. ; 2:4, s. 707-716
  • Tidskriftsartikel (refereegranskat)abstract
    • We have investigated the thioredoxin (TRX) levels in severely burned patients and the possible origin of TRX, based on the recent understanding that TRX is a potent antioxidant with cytoprotective functions. Serum and plasma samples from burns patients and healthy blood donors were collected during the first 10 post-bum days and analyzed in a sandwich TRX enzyme-linked immunosorbent assay (ELISA). The TRX levels found were correlated to a panel of blood tests. The presence of TRX in platelets was investigated by immunoelectron microscopy and Western blotting. TRX serum levels of the severely burned patients showed a significant increase, with a mean serum TRX concentration on the day of injury of 76.5 ▒ 19.5 ng/ml (mean ▒ SD) and on post-burn day one 122.6 ▒ 66.9 ng/ml, compared to control blood donor levels of 22.7 ▒ 12.2 ng/ml (p = 0.0041 and 0.0117, respectively). A second peak of increase was found on post-burn days 7 to 9 with a four- to five-fold rise in concentration compared to controls. TRX elevation correlated well with increased platelet (p = 0.007) and leukocyte counts (p = 0.002). We also demonstrated by immunoelectron microscopy and Western blotting the presence of TRX in platelets. In conclusion, our demonstration of TRX release in burn injuries indicates that the TRX system is involved in a rapid antioxidant defense, coagulation processes, cell growth, and control of the extracellular peroxide tone intimately linked to cytoprotection and wound healing in burns. One of the cell types that delivers TRX promptly and efficiently into the blood may be the platelet.
  • Alehagen, U, et al. (författare)
  • Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens
  • 2013
  • Ingår i: International Journal of Cardiology. - 0167-5273. ; 167:5, s. 1860-1866
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSelenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking.MethodsA 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention.The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan–Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied.ResultsDuring a follow up time of 5.2 years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P = 0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months; P = 0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P = 0.03).ConclusionLong-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography.
  • Alehagen, Urban, et al. (författare)
  • Relatively high mortality risk in elderly Swedish subjects with low selenium status
  • 2016
  • Ingår i: European Journal of Clinical Nutrition. - Nature Publishing Group. - 0954-3007. ; 70:1, s. 91-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Objectives: The daily dietary intake of selenium (Se), an essential trace element, is still low in Sweden in spite of decades of nutritional information campaigns and the effect of this on the public health is presently not well known. The objective of this study was to determine the serum Se levels in an elderly Swedish population and to analyze whether a low Se status had any influence on mortality.Subjects/Methods: Six-hundred sixty-eight (n=668) elderly participants were invited from a municipality and evaluated in an observational study. Individuals were followed for 6.8 years and Se levels were re-evaluated in 98 individuals after 48 months. Clinical examination of all individuals included functional classification, echocardiography, electrocardiogram and serum Se measurement. All mortality was registered and endpoints of mortality were assessed by Kaplan–Meier plots, and Cox proportional hazard ratios adjusted for potential confounding factors were calculated.Results: The mean serum Se level of the study population (n=668) was 67.1 μg/l, corresponding to relatively low Se intake. After adjustment for male gender, smoking, ischemic heart disease, diabetes, chronic obstructive pulmonary disease and impaired heart function, persons with serum Se in the lowest quartile had 43% (95% confidence interval (CI): 1.02–2.00) and 56% (95% CI: 1.03–2.36) increased risk for all-cause and cardiovascular mortality, respectively. The result was not driven by inflammatory effects on Se concentration in serum.Conclusion: The mean serum Se concentration in an elderly Swedish population was 67.1 μg/l, which is below the physiological saturation level for several selenoprotein enzymes. This result may suggest the value of modest Se supplementation in order to improve the health of the Swedish population.
  • Anders, Andre, et al. (författare)
  • High quality ZnO:Al transparent conducting oxide films synthesized by pulsed filtered cathodic arc deposition
  • 2010
  • Ingår i: Thin Solid Films. - 0040-6090 .- 1879-2731. ; 518:12, s. 3313-3319
  • Tidskriftsartikel (refereegranskat)abstract
    • Aluminum-doped zinc oxide, ZnO:Al or AZO, is a well-known n-type transparent conducting oxide with great potential in a number of applications currently dominated by indium tin oxide. In this study, the optical and electrical properties of AZO thin films deposited on glass and silicon by pulsed filtered cathodic arc deposition are systematically studied. In contrast to magnetron sputtering, this technique does not produce energetic negative ions, and therefore ion damage can be minimized. The quality of the AZO films strongly depends on growth temperature while only marginal improvements are obtained with post-deposition annealing. The best films, grown at a temperature of about 200 degrees C, have resistivities in the low to mid 10(-4) Omega cm range with a transmittance better than 85% in the visible part of the spectrum. It is remarkable that relatively good films of small thickness (60 nm) can be fabricated using this method.
  • Barral, AM, et al. (författare)
  • Thioredoxin, thioredoxin reductase and tumour necrosis factor-alpha expression in melanoma cells : correlation to resistance against cytotoxic attack
  • 2000
  • Ingår i: Melanoma research. - 0960-8931. ; 10:4, s. 331-343
  • Tidskriftsartikel (refereegranskat)abstract
    • Although malignant melanomas are often associated with cytotoxic lymphocyte infiltration, these cells are largely ineffective in inducing tumour cell kill, indicating that the melanoma cells have protective mechanisms. These mechanisms are not fully understood, but cytokines and redox-active antioxidant proteins such as catalase, superoxide dismutase, thioredoxin (Trx) and Trx reductase (TrxR) present in the tumour cells constitute part of this protection. In this study firstly we investigated the constitutive intracellular expression of Trx, TrxR, the cytokines interleukin (IL)-1alpha, IL1beta, IL2, IL4, IL6, IL8, IL10, tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) in normal melanocytes and ten primary and metastatic malignant melanoma cell lines. Secondly, we analysed whether redox stimulation by Trx alone or in combination with the phorbol ester PMA affected the expression and release of TNFalpha. Thirdly, we explored the possible correlation between Trx/TrxR expression and resistance to exogenous TNFalpha. All the cultured cells showed intracellular overexpression of Trx and TrxR, which was not always the case for melanoma cells in vivo (tissue sections). The predominant intracellular cytokines found were TNFalpha, IL1alpha and IL1beta. In spite of its presence in the Golgi apparatus, none of the cell lines secreted TNFalpha constitutively, and only one melanoma, FM3, released detectable amounts after stimulation. In contrast, U-937 monocyte control cells released high amounts of TNFalpha on identical stimulation. All the melanoma cell lines were relatively resistant against exogenous TNFalpha, and there was a significant correlation (P < 0.01) between intracellular Trx/TrxR expression and TNFalpha resistance (IC50). In conclusion, Trx and TrxR, as well as TNFalpha, IL1alpha and IL1beta, were highly expressed in cultured normal skin melanocytes and malignant melanoma cell lines. In contrast to U-937 monocytic cells, TNFalpha showed a secretory block in these cells, suggesting a cytoprotective and possible autocrine role for TNFalpha. The intracellular expression of Trx and TrxR together with endogenous TNFalpha was correlated with the resistance to TNFalpha-induced cytotoxicity.
  • Bjorkman, A, et al. (författare)
  • Phantom digit somatotopy: a functional magnetic resonance imaging study in forearm amputees.
  • 2012
  • Ingår i: European Journal of Neuroscience. - Wiley-Blackwell. - 1460-9568. ; 36:1, s. 2098-2106
  • Tidskriftsartikel (refereegranskat)abstract
    • Forearm amputees often experience non-painful sensations in their phantom when the amputation stump is touched. Cutaneous stimulation of specific stump areas may be perceived as stimulation of specific phantom fingers (stump hand map). The neuronal basis of referred phantom limb sensations is unknown. We used functional magnetic resonance imaging to demonstrate a somatotopic map of the phantom fingers in the hand region of the primary somatosensory cortex after tactile stump stimulation. The location and extent of phantom finger activation in the primary somatosensory cortex corresponded well to the location of normal fingers in a reference population. Stimulation of the stump hand map resulted in an increased bilateral activation of the primary somatosensory cortex compared with stimulation of forearm regions outside the stump hand map. Increased activation was also seen in contralateral posterior parietal cortex and premotor cortex. Ipsilateral primary somatosensory cortex activation might represent a compensatory mechanism and activation of the non-primary fronto-parietal areas might correspond to awareness of the phantom limb, which is enhanced when experiencing the referred sensations. It is concluded that phantom sensation elicited by stimulation of stump hand map areas is associated with activation of finger-specific somatotopical representations in the primary somatosensory cortex. This suggests that the primary somatosensory cortex could be a neural substrate of non-painful phantom sensations. The stump hand map phenomenon might be useful in the development of prosthetic hand devices.
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