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  • 251.
    Nilsen, Tom
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Influence of 8 parameters when coating avian calprotectin antibodies to latex particlesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Aim: To find the parameters affecting sensitivity and security zone in the preparation process of immunoparticles with avian antibodies for use in particle enhanced turbidimetric immunoassays. Method: 12 combinations of 8 parameters were tested in the preparation process of the immunoparticles. The study was designed according to Taguchi L12 screening method and analysed using DOE KISS PRO XL. Results/Conclusion: The parameters affecting the sensitivity and security zone the most were conductivity of the conjugate buffer, coating grade and pH of the conjugate buffer.

  • 252.
    Nilsen, Tom
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Gentian AS, Moss, Norway.
    Sunde, Kathrin
    Gentian AS, Moss, Norway.
    Hansson, Lars-Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Mandic Havelka, Aleksandra
    Karolinska Univ Hosp, Karolinska Inst & Clin Chem, Dept Mol Med & Surg, Stockholm, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    A novel turbidimetric immunoassay for fecal calprotectin optimized for routine chemistry analyzers2017Inngår i: Journal of clinical laboratory analysis (Print), ISSN 0887-8013, E-ISSN 1098-2825, Vol. 31, nr 4, artikkel-id e22061Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Fecal calprotectin assays are widely used to exclude inflammatory bowel disease (IBD) in patients with suspected IBD. A problem with the fecal calprotectin assays is the rather long test-turnaround times. A particle enhanced turbidimetric immunoassays (PETIA) for fecal calprotectin would reduce test-turnaround times and would permit more laboratories to perform the measurements. The aim of this study was to evaluate a new feces calprotectin PETIA.

    METHOD: Using routine fecal samples the feces calprotectin PETIA was validated on two chemistry analyzers, Mindray BS-380 and Cobas 501.

    RESULTS: The assay is linear in the range 11-2000 μg/g, with a limit of quantitation of approximately 10 μg/g. No antigen excess hook effect was observed up to 10 000-15 000 μg/g depending on the instrument used. The turbidimetric method showed a good agreement with the Bühlmann ELISA. The total coefficient of variation was 3%-8% in the 50-100 μg/g range.

    CONCLUSION: The fecal calprotectin PETIA, fCal Turbo, is well suited for rapid analysis of fecal calprotectin on Mindray BS-380 or Cobas 501 clinical chemistry analyzers. The test results are commutable with Bühlmann fecal MRP8/14 ELISA.

  • 253.
    Nilsen, Tom
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Serum calprotectin levels in elderly males and females without bacterial or viral infections2014Inngår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, nr 12, s. 1065-1068Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Calprotectin is released from activated leukocytes and calprotectin can thus be used as a marker for leukocyte activation. Faeces calprotectin is not only used as a marker for inflammatory bowel disease but can also be used to detect leukocyte activation in other body fluids. The aim of the present study was to study serum calprotectin levels in non-infected elderly individuals to establish reference intervals for the marker.

    METHODS: Serum calprotectin was analyzed by immunoturbidimetry in 75year old females and males without known infections. Individuals with CRP>20mg/L were excluded as this could indicate a subclinical infection. The calprotectin levels in the remaining 713 individuals were used to calculate reference values for this population. The Spearman rank correlations between calprotectin and 27 other laboratory biomarkers were also investigated.

    RESULTS: There was a strong positive Spearman rank correlation between calprotectin and CRP (p<0.000001) and alkaline phosphatase (p<0.000001). There were also significant negative correlations between calprotectin and ApoA1 and direct HDL-cholesterol.

    CONCLUSIONS: The reference interval for serum-calprotectin for all study subjects was 0.3-2.6mg/L. Leukocyte alkaline phosphatase contributes to serum alkaline phosphatase levels.

  • 254.
    Nilsson, Kenneth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Elfving, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Påhlson, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Rickettsia helvetica in patient with meningitis, Sweden, 20062010Inngår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 16, nr 3, s. 490-492Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pathogenicity of Rickettsia helvetica is relatively unknown. We isolated a spotted fever group rickettsial organism from a patient with subacute meningitis. Nucleotide sequences of the 16S rRNA, ompB, and 17kDa genes identified the isolate as R. helvetica. This organism may be associated with serious infections such as central nervous system disorders.

  • 255.
    Nilsson, Kenneth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Wallménius, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Rundlöf-Nygren, Pernilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Strömdahl, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Påhlson, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    African tick bite fever in returning Swedish travellers: Report of two cases and aspects of diagnostics2017Inngår i: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 7, nr 1, artikkel-id 1343081Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: African tick-bite fever, caused by Rickettsia africae, is endemic in rural areas of sub-Saharan Africa and a possible cause of fever in returning Swedish travellers. Two patients are presented, and the advantages and disadvantages of different diagnostic methods are discussed.

    Patients and methods: Two middle-aged men fell ill with fever after returning home from South Africa. Both had single eschars and one also presented with a lymph node swelling. Samples were taken for serology, general bacterial culture from the wound (Patient 1) using a swab and additionally for Patient 2 PCR of a skin biopsy from the eschar.

    Results and discussion: Both patients seroconverted one month after onset. Real-time PCR of the biopsy was positive, where sequencing of the gltA gene was 99–100% consistent with R. africae. A drop of fluid from the biopsy contained a sufficient number of bacteria to also allow for isolation of rickettsiae in Vero cell culture. Direct molecular detection by PCR from a swab used for bacteria culture from the eschar from Patient 1 also yielded a positive result. In conclusion, the findings highlight the usefulness of swabs for early non-invasive diagnosis of African tick-bite fever in febrile travellers.

  • 256. Norberg, Maria
    et al.
    Lindhagen, Elin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Kanduri, Meena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Hematologi och immunologi.
    Rickardson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Stamatopoulos, Kostas
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Hematologi och immunologi.
    Aleskog, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Screening for Cytotoxic Compounds in Poor-prognostic Chronic Lymphocytic Leukemia2012Inngår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, nr 8, s. 3125-3136Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/Aim: For chronic lymphocytic leukemia (CLL) patients with poor-prognostic genomic aberrations the therapeutic options are limited. We used the Spectrum Collection library to identify compounds with anti-leukemia activity in high-risk CLL.

    Materials and Methods: We identified substances with equal high cytotoxic activity in vitro in samples from poor-prognostic CLL (11q-/17p-, n=3) as compared to those from favourable-prognostic CLL (13q-, n=3). Cell survival was measured by fluorometric microculture cytotoxicity assay.

    Results: Out of 2,000 compounds, 65 had a similar effect in both prognostic groups. Fifteen compounds were selected for dose-response experiments in 16 additional CLL samples. Of these compounds, 12 continued to have similar cytotoxicity between prognostic subgroups. Additional experiments demonstrated that in CLL cells with 11q or 17p deletion, 5-azacytidine induced apoptosis in a dose-dependent manner and lipoprotein lipase expression was reduced following orlistat treatment.

    Conclusion: Using primary cultures of cells from high-risk CLL patients for compound screening is a feasible approach and that 5-azacytidine and orlistat exemplify substances that exhibit cytotoxicity in poor-risk CLL.

  • 257.
    Nordberg, Marika
    et al.
    Linköping universitet, Kliinisk och experimentell medicin.
    Forsberg, Pia
    Linköping universitet, Klinisk och experimentell medicin.
    Berglund, Johan
    Bjöersdorff, Anneli
    Djursjukhusgruppen, Danderyd.
    Ernerudh, Jan
    Linköping universitet, Klinisk immunologi.
    Garpmo, Ulf
    Kalmar länslasarett, Klinisk Mikrobiologi.
    Haglund, Mats
    Kalmar länslasarett, Infektionssjukdomar.
    Nilsson, Kenneth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eliasson, Ingvar
    Norra Älvsborgs sjukhus, .
    Aetiology of tick-borne infections in an adult swedish population-are co-infections with multiple agents common2014Inngår i: Open Journal of Clinical Diagnostics, ISSN 2162-5816, E-ISSN 2162-5824, Vol. 4, nr 1, s. 31-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In Scandinavia, tick-borne infections affecting humans include Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA). Each of these infections can present with unspecific symptoms. In this prospective clinical study, we recruited patients based on two independent inclusion criteria; 1) patients with unspecific symptoms, i.e. fever (≥38.0˚C) or a history of feverishness and/or any combination of headache, myalgia or arthralgia and 2) patients with erythema migrans (EM), following an observed tick bite or tick exposure within one month  prior to onset of symptoms. A total of 206 patients fulfilled the study. Among these, we could identify 186 cases of LB (174 with EM), 18 confirmed and two probable cases of HGA and two cases of TBE. Thirteen of the HGA cases presented without fever. Furthermore, 22 of the EM patients had a sub-clinical co-infection with Anaplasma phagocytophilum, based on serology. Both TBE cases had co-infections, one with Borrelia burgdorferi and one with Anaplasma phagocytophilum. We conclude that it is important to consider several causative agents and possible co-infections in the clinical management of infectious diseases where ticks may be suspected as vectors.

  • 258.
    Nordeman, Patrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Johansson, Leif B. G.
    Linkoping Univ, Dept Chem, IFM, S-58183 Linkoping, Sweden..
    Back, Marcus
    Linkoping Univ, Dept Chem, IFM, S-58183 Linkoping, Sweden..
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI.
    Hall, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI.
    Sjölander, Daniel
    Linkoping Univ, Dept Chem, IFM, S-58183 Linkoping, Sweden..
    Westermark, Gunilla T.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Nilsson, Lars
    Univ Oslo, Dept Pharmacol, N-0316 Oslo, Norway..
    Hammarström, Per
    Linkoping Univ, Dept Chem, IFM, S-58183 Linkoping, Sweden..
    Nilsson, K. Peter R.
    Linkoping Univ, Dept Chem, IFM, S-58183 Linkoping, Sweden..
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    C-11 and F-18 Radiolabeling of Tetra- and Pentathiophenes as PET-Ligands for Amyloid Protein Aggregates2016Inngår i: ACS Medicinal Chemistry Letters, ISSN 1948-5875, E-ISSN 1948-5875, Vol. 7, nr 4, s. 368-373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Three oligothiophenes were evaluated as PET ligands for the study of local and systemic amyloidosis ex vivo using tissue from patients with amyloid deposits and in vivo using healthy animals and PET-CT. The ex vivo binding studies revealed that all three labeled compounds bound specifically to human amyloid deposits. Specific binding was found in the heart, kidney, liver, and spleen. To verify the specificity of the oligothiophenes toward amyloid deposits, tissue sections with amyloid pathology were stained using the fluorescence exhibited by the compounds and evaluated with multiphoton microscopy. Furthermore, a in vivo monkey PET-CT study showed very low uptake in the brain, pancreas, and heart of the healthy animal indicating low nonspecific binding to healthy tissue. The biological evaluations indicated that this is a promising group of compounds for the visualization of systemic and localized amyloidosis.

  • 259.
    Nordin, Gunnar
    et al.
    Equalis, Uppsala, Sweden.
    Ekvall, Sara
    Equalis, Uppsala, Sweden.
    Kristoffersson, Carolina
    Equalis, Uppsala, Sweden.
    Jonsson, Ann-Sofie
    Landstinget Varmland, Dept Clin Chem, Karlstad, Sweden.
    Bäck, Sten-Erik
    Lund Univ Hosp, Dept Clin Chem, Lund, Sweden.
    Rollborn, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Accuracy of determination of the glomerular filtration marker iohexol by European laboratories as monitored by external quality assessment2019Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 57, nr 7, s. 1006-1011Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Glomerular filtration is the most important kidney function. The most accurate glomerular filtration rate (GFR) estimates are based on the clearance of exogenous filtration markers. Of these, iohexol is the only exogenous marker that is included in an external quality assessment (EQA) scheme. The aim of the present study was to evaluate the performance of the European laboratories participating in Equalis' EQA scheme for iohexol. Methods Weighed amounts of iohexol (Omnipaque) were added to plasma samples and distributed to laboratories participating in the EQA scheme for iohexol. All laboratories performed the assays in a blinded fashion. Results The number of participating laboratories varied between 27 and 34 during the study period. Iohexol was determined by HPLC in 77% of the laboratories and by UPLC/MS/MS methods in 15% of the laboratories. The mean interlaboratory coefficient of variation was 4.7% for the HPLC methods and 6.4% for the UPLC/MS/MS methods. The mean bias between calculated and measured iohexol values was -1.3 mg/L (95% confidence interval ±0.3) during the first part of the study period and 0.1 mg/L (±0.3) during the later part. Conclusions The low interlaboratory variation demonstrates that iohexol can be measured reliably by many laboratories and supports the use of iohexol as a GFR marker when there is a need for high quality GFR measurements.

  • 260. Nordström, Lena
    et al.
    Sernbo, Sandra
    Eden, Patrik
    Grønbaek, Kirsten
    Kolstad, Arne
    Räty, Riikka
    Karjalainen, Marja-Liisa
    Geisler, Christian
    Ralfkiaer, Elisabeth
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Laurell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Delabie, Jan
    Ehinger, Mats
    Jerkeman, Mats
    Ek, Sara
    SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma: a Nordic Lymphoma Group study2014Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 166, nr 1, s. 98-108Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.

  • 261.
    Norman, Holly
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Zahrisson, Håkan
    Hedström, Yvette
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Andersson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Nordquist, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Eriksson, Lars I
    Libelius, Rolf
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Myofibrillar protein and gene expression in acute quadriplegic myopathy2009Inngår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 285, nr 1-2, s. 28-38Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dramatic muscle wasting, preferential loss of myosin and impaired muscle function in intensive care unit (ICU) patients with acute quadriplegic myopathy (AQM) have traditionally been suggested to be the result of proteolysis via specific proteolytic pathways. In this study we aim to investigate the mechanisms underlying the preferential loss of thick vs. thin filament proteins and the reassembly of the sarcomere during the recovery process in muscle samples from ICU patients with AQM. Quantitative and qualitative analyses of myofibrillar protein and mRNA expression were analyzed using SDS-PAGE, confocal microscopy, histochemistry and real-time PCR. The present results demonstrate that the transcriptional regulation of myofibrillar protein synthesis plays an important role in the loss of contractile proteins, as well as the recovery of protein levels during clinical improvement, myosin in particular, presumably in concert with proteolytic pathways, but the mechanisms are specific to the different thick and thin filament proteins studied.

  • 262. Nylander, Martina
    et al.
    Osman, Abdimajid
    Ramström, Sofia
    Aklint, Emma
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lindahl, Tomas L
    The role of thrombin receptors PAR1 and PAR4 for PAI-1 storage, synthesis and secretion by human platelets2012Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 129, nr 4, s. e51-e58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION:

    Arterial thrombi contain more platelets than venous thrombi and are more resistant to fibrinolysis. This resistance could partly be due to plasminogen activator inhibitor 1 (PAI-1) secreted by platelets. The aim of this study was to elucidate differences between thrombin receptors protease-activated receptor (PAR) 1 and 4 and platelet storage, secretion and synthesis of platelet PAI-1, as compared to other platelet α-granule proteins such as VEGF and endostatin.

    MATERIALS AND METHODS:

    Human isolated platelets were incubated with thrombin (0.5U/ml), PAR1-activating peptide (AP) (0.4-30μM) or PAR4-AP (1.5-300μM) for up to 24hours. ELISA, western blot and fluorescence microscopy were used to measure secretion, contents and localization of PAI-1, VEGF and endostatin.

    RESULTS:

    Our results show that PAI-1 and VEGF might be co-localized and that endostatin does not co-localize with either PAI-1 or VEGF. PAI-1 and VEGF show a similar secretion pattern, being more sensitive to low grade PAR1 activation, but secretion was also observed with higher concentrations of PAR4-APs. PAI-1 is secreted in an active form. PAI-1 mRNA was found in platelets, and elevated levels of PAI-1 were detected after 24hours incubation of platelets.

    CONCLUSIONS:

    PAI-1 and VEGF, but not endostatin, might be stored in the same α-granule in human platelets. PAI-1 and VEGF also show a similar secretion pattern, being more sensitive to PAR1 than to PAR4 activation, but the secretion is not exclusively selective. Our results also show that platelet PAI-1 is increased if incubated for 24hours, both with addition of PAR1-activating peptide and without activation, which could indicate de novo synthesis.

  • 263.
    Nyström, Sofie
    et al.
    Linköping Univ.
    Panahi, Aida Vahdat Shariat
    Linköping Univ.
    Nilsson, K. Peter R.
    Linkoping Univ.
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Westermark, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hammarstrom, Per
    Linköping Univ.
    Lundmark, Katarzyna
    Linköping Univ.
    Seed-dependent templating of murine AA amyloidosis2017Inngår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, s. 140-141Artikkel i tidsskrift (Annet vitenskapelig)
  • 264.
    Olausson, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Peterson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Bergström, Mats
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Evaluation of the Meritas® BNP Test for Point-of-Care Testing2015Inngår i: Clinical Laboratory, ISSN 1433-6510, Vol. 61, nr 7, s. 727-730Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: BNP and NT-proBNP are widely used as rule-out tests for heart failure (HF) and they are frequently requested by primary care doctors. A point-of-care (POC) test would reduce the time to diagnosis for patients with suspected HF. The aim of the study was to evaluate a POC BNP test.

    METHODS: Plasma BNP results obtained with the Meritas® POC instrument (n = 82) were compared with the corresponding plasma BNP results analyzed on an Advia Centaur analyzer (Siemens Healthcare, Erlangen, Germany).

    RESULTS: The two methods showed concordant results with a Passing-Bablok correlation between the two methods: BNP(Meritas) = 1.00 x BNP(Siemens) + 1.09; r = 0.9773.

    CONCLUSIONS: The study show that the Meritas® BNP assay could be used in primary care permitting rapid BNP testing to rule out heart failure.

  • 265.
    Olausson, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Petterson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Bergström, Mats
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Evaluation of the Meritas® BNP Test for Point-of-Care Testing2015Inngår i: Clinical Laboratory, ISSN 1433-6510, Vol. 61, nr 7, s. 727-730Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: BNP and NT-proBNP are widely used as rule-out tests for heart failure (HF) and they are frequently requested by primary care doctors. A point-of-care (POC) test would reduce the time to diagnosis for patients with suspected HF. The aim of the study was to evaluate a POC BNP test.

    Methods: Plasma BNP results obtained with the Meritas® POC instrument (n = 82) were compared with the corresponding plasma BNP results analyzed on an Advia Centaur analyzer (Siemens Healthcare, Erlangen, Germany).

    Results: The two methods showed concordant results with a Passing-Bablok correlation between the two methods: BNPMeritas = 1.00 x BNPSiemens + 1.09; r = 0.9773.

    Conclusions: The study show that the Meritas® BNP assay could be used in primary care permitting rapid BNP testing to rule out heart failure.

  • 266.
    Ouchterlony, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Evaluation of different methods for analysis of specific gravity of canine and feline urine2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Urine specific gravity is used for evaluation of kidney function in dogs and cats. The most commonly used method to determine urine specific gravity is the refractometer. There are refractometers specifically calibrated for feline urine.The aim of this study was to evaluate how five different types of refractometers, of which two were calibrated for feline urine, report urine specific gravity. The evaluation also included comparison of the results with two other methods; determination of dry weight and chemical analysis of urine.Patient urine samples from 31 dogs and 27 cats were used. For analysis, methods included five refractometers, drying and determination of dry weight, and chemical analysis of concentration of eight solutes in urine. A urine dipstick specific gravity method was also included in the evaluation.The refractometers reported persistently different results but comparable results to the chemical analysis. The two refractometers designed for feline urine reported similar and consistently false low values. Results from the drying were interpreted to be false high and urine dipstick analysis of specific gravity reported false low results and was considered inaccurate.The conclusion is that none of the methods included reported correct results compared to the chemical analysis; the results were either false low or false high.

  • 267. Parkkinen, L
    et al.
    Hartikainen, P
    Alafuzoff, Irina
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Abundant glial alpha-synuclein pathology in a case without overt clinical symptoms.2007Inngår i: Clinical Neuropathology, ISSN 0722-5091, Vol. 26, nr 6, s. 276-83Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Screening of 1,800 brains with alpha-synuclein (alphaS) immunohistochemistry revealed five cases with abundant glial cytoplasmic inclusions (GCIs) within the white matter of the brainstem. Surprisingly, retrospective clinical assessment showed that one of these subjects did not fulfil the currently recommended clinical consensus criteria for the multiple system atrophy (MSA). One of the hallmark lesions of MSA, alphaS-positive GCIs, were widespread and abundant in this atypical case that nonetheless lacked any significant neuronal loss. If the patient had met the clinical criteria for MSA, the neuropathological phenotype would have undeniably confirmed the clinically suggested diagnosis. However, lacking overt clinical signs of MSA, the neuropathological phenotype in this subject is prone to be variably denoted or overlooked. We would therefore like to advise neuropathologists to acknowledge these cases with "occult" alpha-synucleinopathy and to inform the clinicians of such a finding. Whether these cases represent a preclinical stage of MSA or simply a biological coincidence, is yet unknown. The observation of abundant GCIs in an asymptomatic subject is, however, important, because even if these cases are rare in number, their occurrence challenge the current presumption, whereby simply the number of alphaS-positive GCIs mediates the neuronal dysfunction responsible for the clinical symptoms of MSA.

  • 268. Parkkinen, Laura
    et al.
    Pirttilä, Tuula
    Alafuzoff, Irina
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Applicability of current staging/categorization of alpha-synuclein pathology and their clinical relevance.2008Inngår i: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 115, nr 4, s. 399-407Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In Parkinson's disease (PD) and dementia with Lewy bodies (DLB) alpha-synuclein (alphaS) pathology is seen that displays a predictable topographic distribution. There are two staging/categorization systems, i.e. Braak's and McKeith's, currently in use for the assessment of alphaS pathology. The aim of these diagnostic strategies in pathology is, in addition to assess the stage/severity of pathology, to assess the probabilities of the related clinical symptomatology i.e. dementia and extrapyramidal symptoms (EPS). Herein, we assessed the applicability of these two staging/categorization systems and the frequency of dementia and EPS in a cohort of 226 alphaS-positive-subjects. These subject were selected from a large autopsy sample (n = 1,720), irrespective of the clinical presentation, based on the detection of alphaS-immunoreactivity (IR) in one of the most vulnerable nuclei; in the dorsal motor nucleus of vagus, substantia nigra and basal forebrain. The frequency of alphaS-IR lesions in this large cohort was 14% (248 out of 1,720). If applicable, each of the 226 subjects with all required material available was assigned a neuropathological stage/category of PD/DLB and finally the neuropathological data was analyzed in relation to dementia and EPS. 83% of subjects showed a distribution pattern of alphaS-IR that was compatible with the current staging/categorization systems. Around 55% of subjects with widespread alphaS pathology (Braak's PD stages 5-6) lacked clinical signs of dementia or EPS. Similarly, in respect to those subjects that fulfilled the McKeith criteria for diffuse neocortical category and displaying only mild concomitant Alzheimer's disease-related pathology, only 48% were demented and 54% displayed EPS. It is noteworthy that some subjects (17%) deviated from the suggested caudo-rostral propagation suggesting alternative routes of progression, perhaps due to concomitant diseases and genetic predisposition. In conclusion, our results do indeed confirm that current staging/categorization systems can readily be applied to most of the subjects with alphaS pathology. However, finding that around half of the subjects with abundant alphaS pathology remain neurologically intact is intriguing and raises the question whether we do assess the actual disease process.

  • 269. Paulsson, Janna
    et al.
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Prognostic relevance of cancer-associated fibroblasts in human cancer2014Inngår i: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 25, s. 61-68Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Prognostication is an integral part of cancer diagnostic and helps oncologists to guide treatment decisions and therapy intensity. Accumulating evidence suggest that the stroma compartment also contains independent prognostic information, best exemplified by the impact of immune cells and cells of the vasculature on cancer progression. Similarly, strong experimental evidence exist that stromal fibroblasts, often designated cancer associated fibroblasts (CAFs), are actively involved in tumorigenesis. Thus, it can be anticipated that the molecular repertoire of CAFs is likewise important for the clinical behavior of the tumor. In this review we present recent studies addressing the prognostic impact of CAFs, with the focus on human lung and breast cancer. Several single markers have been suggested, either CAF specific or CAF derived, that in immunohistochemical studies have demonstrated independent association with survival. This includes members of the platelet derived growth factor receptor (PDGFR) family, CAF-markers like podoplanin and fibroblast activation protein (FAP) as well as transcription factors (FoxF1) and secreted factors (matrix metalloproteinases (MMPs), SPARC). However, most studies are based on explorative evaluations on single patient cohorts and require further validation. Using a more comprehensive approach, microarray studies have been employed to create gene expression signatures that detect an activated fibroblast state. These "stroma signatures" have been applied to identify specific CAF features associated with prognosis in several independent data sets of breast and lung cancer patients. Early studies in breast cancer have also demonstrated that fibroblast features influence therapy response. Thus, many strategies have been used to present encouraging proof-of-concept findings that CAFs could be exploited for prognostication. However, these studies also highlight the difficulties to conclusively define an "activated stroma" and to identify the individual factors involved in clinically relevant tumor-stroma interactions.

  • 270. Peuchant, Olivia
    et al.
    Le Roy, Chloé
    Herrmann, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    Clerc, Maithé
    Bébéar, Cécile
    de Barbeyrac, Bertille
    MLVA Subtyping of Genovar E Chlamydia trachomatis Individualizes the Swedish Variant and Anorectal Isolates from Men who Have Sex with Men2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 2, s. e31538-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study describes a new multilocus variable number tandem-repeat (VNTR) analysis (MLVA) typing system for the discrimination of Chlamydia trachomatis genovar D to K isolates or specimens. We focused our MLVA scheme on genovar E which predominates in most populations worldwide. This system does not require culture and therefore can be performed directly on DNA extracted from positive clinical specimens. Our method was based on GeneScan analysis of five VNTR loci labelled with fluorescent dyes by multiplex PCR and capillary electrophoresis. This MLVA, called MLVA-5, was applied to a collection of 220 genovar E and 94 non-E genovar C. trachomatis isolates and specimens obtained from 251 patients and resulted in 38 MLVA-5 types. The genetic stability of the MLVA-5 scheme was assessed for results obtained both in vitro by serial passage culturing and in vivo using concomitant and sequential isolates and specimens. All anorectal genovar E isolates from men who have sex with men exhibited the same MLVA-5 type, suggesting clonal spread. In the same way, we confirmed the clonal origin of the Swedish new variant of C. trachomatis. The MLVA-5 assay was compared to three other molecular typing methods, ompA gene sequencing, multilocus sequence typing (MLST) and a previous MLVA method called MLVA-3, on 43 genovar E isolates. The discriminatory index was 0.913 for MLVA-5, 0.860 for MLST and 0.622 for MLVA-3. Among all of these genotyping methods, MLVA-5 displayed the highest discriminatory power and does not require a time-consuming sequencing step. The results indicate that MLVA-5 enables high-resolution molecular epidemiological characterisation of C. trachomatis genovars D to K infections directly from specimens.

  • 271.
    Peura, Sari
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, Sci Life Labs, Almas Alle 5, S-75007 Uppsala, Sweden.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Unit Paediat Allergy & Pulmonol, Stockholm, Sweden.
    Andolf, Ellika
    Karolinska Inst, Danderyd Hosp, Div Obstet & Gynaecol, Dept Clin Sci, Stockholm, Sweden.
    Hedman, Anna
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Pershagen, Göran
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Normal values for calprotectin in stool samples of infants from the population-based longitudinal born into life study2018Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 78, nr 1-2, s. 120-124Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Faecal calprotectin is a protein used as a diagnostic marker for inflammatory bowel diseases. We determined upper limits for normal calprotectin values for neonatal, 6, 12 and 24 months old children using a turbidimetric immunoassay in a cohort of Swedish children. The advantage of the method is that opposite to previously used enzyme-linked immunosorbent assay (ELISA) method, it enables measuring single samples, and thus, shortens the analysis time significantly. There were 72 samples (41.7% female) collected neonatally, 63 samples (34.9% female) at 6 months, 60 samples (40.0% female) at 12 months and 51 samples (43.1% female) at 24 months. The upper limits for normal values were 233, 615, 136 and 57 µg mg-1 for infants aged 0, 6, 12 and 24 months, respectively.

  • 272. Picken, M M
    et al.
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Amyloid detection and typing: summary of current practice and recommendations of the consensus group2011Inngår i: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, ISSN 1744-2818, Vol. 18, nr Suppl 1, s. 48-50Artikkel i tidsskrift (Fagfellevurdert)
  • 273. Pikkarainen, Maria
    et al.
    Hartikainen, Päivi
    Alafuzoff, Irina
    Department of Neuroscience and Neurology, University of Kuopio Finland .
    Neuropathologic features of frontotemporal lobar degeneration with ubiquitin-positive inclusions visualized with ubiquitin-binding protein p62 immunohistochemistry.2008Inngår i: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 67, nr 4, s. 280-98Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genetic, clinical, and neuropathologic heterogeneity have been observed in frontotemporal lobar degeneration with ubiquitin (Ubq)-positive inclusions (FTLD-U) and FTLD-U with motor neuron disease. Here, the distribution and morphologic features of neuronal and glial inclusions in the brains of 20 FTLD-U and 2 FTLD-U/motor neuron disease cases were assessed using immunohistochemistry for Ubq-binding protein p62. Eighteen cases displayed TAR DNA-binding protein 43-immunoreactive lesions and were classified as Types 3 (neuronal cytoplasmic inclusions and neurites; 72%), 2 (primarily neuronal cytoplasmic inclusions; 17%), or 1 (primarily neurites; 11%) FTLD-U. The distribution of p62-immunoreactivity varied considerably in each type. Of 4 unclassifiable cases, 2 displayed p62-immunoreactive lesions suggestive of FTLD-U with a mutation in the charged multivesicular body protein 2B gene; 1 suggested basophilic inclusion body disease, and 1 was of a type not previously described. By immunohistochemistry for Ubq-binding protein p62, the distribution of abnormalities was wider than expected; in approximately half of the cases, there were p62-positive but TAR DNA-binding protein 43-negative inclusions in the cerebellum, a region not previously considered to be affected. In other regions, TAR DNA-binding protein 43-, Ubq-, and Ubq-binding protein p62 labeling of inclusions was variable. Whether variations in inclusion morphologies, immunoreactivity, and topographic distribution are due to methodologic factors, different stages of inclusion and disease evolution, different disease entities or biologic modifications of the same disease are presently unclear.

  • 274. Pikkarainen, Maria
    et al.
    Martikainen, Paula
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    The effect of prolonged fixation time on immunohistochemical staining of common neurodegenerative disease markers2010Inngår i: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 69, nr 1, s. 40-52Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The goals of this study were to determine the effects of prolonged fixation time and to optimize antigen retrieval (AR) methods on immunohistochemical (IHC) staining of common neurodegenerative disease markers. A panel of commercial antibodies (Abs) to amyloid-beta, ubiquitin, p62/sequestosome, tau, and alpha-synuclein was applied to a 2-mm tissue microarray using several AR methods. The IHC outcomes were assessed in sections that included 2 types of specimens taken from 20 postmortem brains: short-term fixation of up to 70 days before paraffin embedment and long-term fixation of up to 14 years in formalin. Good amyloid-beta IHC staining was obtained with all amyloid-beta Abs applied when a formic acid AR method was used, even after 14 years of fixation. Ubiquitin immunoreactivity was also optimally labeled with this method. The p62/sequestosome IHC outcome was optimal for tissue fixed up to 10 years, but only when the p62-lck-ligand-Ab with heat AR method was used. All hyperphosphorylated tau Abs tested worked with fixation up to 10 years, in particular with the heat AR method, whereas Abs against tau isoforms RD3 and RD4 were applicable only when the fixation time was 6 months or shorter. alpha-Synuclein-immunoreactive structures were visualized up to 14 years but only by the use of Syn42-Ab after formic acid AR or after a combination of heat and formic acid methods.

  • 275. Pilebro, Björn
    et al.
    Arvidsson, Sandra
    Lindqvist, Per
    Sundström, Torbjörn
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Suhr, Ole
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Positron emission tomography (PET) utilizing Pittsburgh compound B (PIB) for detection of amyloid heart deposits in hereditary transthyretin amyloidosis (ATTR)2018Inngår i: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 25, nr 1, s. 240-248Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing (11)C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer's disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis.

    METHODS: Ten patients with biopsy-proven V30M ATTR amyloidosis and discrete or no signs of cardiac involvement were included. Patients were grouped according to TTR-fragmentation. All underwent DPD scintigraphy, echocardiography, and PIB-PET. A left ventricular PIB-retention index (PIB-RI) was established and compared to five normal volunteers.

    RESULTS: PIB-RI was increased in all patients (P < 0.001), but was significantly higher in type B than in type A (0.129 ± 0.041 vs 0.040 ± 0.006 min(-1), P = 0.009). Cardiac DPD uptake was elevated in group A and absent in group B.

    CONCLUSION: PIB-PET, in contrast to DPD scintigraphy, has the potential to specifically identify cardiac amyloid depositions irrespective of amyloid fibril composition. The heart appears to be a target organ for amyloid deposition in ATTR amyloidosis.

  • 276.
    Pincikova, Terezia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning. Karolinska Univ Hosp Huddinge, Stockholm CF Ctr, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Pediat, Stockholm, Sweden;Karolinska Univ Hosp Huddinge, Karolinska Inst, Ctr Infect Med, Dept Med, F59, S-14186 Stockholm, Sweden.
    Paquin-Proulx, Dominic
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Ctr Infect Med, Dept Med, F59, S-14186 Stockholm, Sweden;George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA.
    Moll, Markus
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Ctr Infect Med, Dept Med, F59, S-14186 Stockholm, Sweden.
    Flodström-Tullberg, Malin
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Ctr Infect Med, Dept Med, F59, S-14186 Stockholm, Sweden.
    Hjelte, Lena
    Karolinska Univ Hosp Huddinge, Stockholm CF Ctr, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Pediat, Stockholm, Sweden.
    Sandberg, Johan K.
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Ctr Infect Med, Dept Med, F59, S-14186 Stockholm, Sweden.
    Severely Impaired Control of Bacterial Infections in a Patient With Cystic Fibrosis Defective in Mucosal-Associated Invariant T Cells2018Inngår i: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 153, nr 5, s. E93-E96Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here we report a unique case of a patient with cystic fibrosis characterized by severely impaired control of bacterial respiratory infections. This patient's susceptibility to such infections was much worse than expected from a cystic fibrosis clinical perspective, and he died at age 22 years despite extensive efforts and massive use of antibiotics. We found that this severe condition was associated with a near-complete deficiency in circulating mucosal-associated invariant T (MAIT) cells as measured at several time points. MAIT cells are a large, recently described subset of T cells that recognize microbial riboflavin metabolites presented by the highly evolutionarily conserved MR1 molecules. The MAIT cell deficiency was specific; other T-cell subsets were intact. Even though this is only one unique case, the findings lend significant support to the emerging role of MAIT cells in mucosal immune defense and suggest that MAIT cells may significantly modify the clinical phenotype of respiratory diseases.

  • 277.
    Pommerenke, C.
    et al.
    Leibniz Inst DSMZ German Collect Microorganisms &, Braunschweig, Germany..
    Hauer, V.
    Leibniz Inst DSMZ German Collect Microorganisms &, Braunschweig, Germany..
    Zaborski, M.
    Leibniz Inst DSMZ German Collect Microorganisms &, Braunschweig, Germany..
    MacLeod, R. A. F.
    Leibniz Inst DSMZ German Collect Microorganisms &, Braunschweig, Germany..
    Nagel, S.
    Leibniz Inst DSMZ German Collect Microorganisms &, Braunschweig, Germany..
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Geffers, R.
    Helmholtz Ctr Infect Res, Genome Analyt Res Grp, Braunschweig, Germany..
    Drexler, H. G.
    Leibniz Inst DSMZ German Collect Microorganisms &, Braunschweig, Germany..
    Quentmeier, H.
    Leibniz Inst DSMZ German Collect Microorganisms &, Braunschweig, Germany..
    Chromosome 11q23 aberrations activating FOXR1 in B-cell lymphoma2016Inngår i: Blood Cancer Journal, ISSN 2044-5385, E-ISSN 2044-5385, Vol. 6, artikkel-id e433Artikkel i tidsskrift (Fagfellevurdert)
  • 278.
    Popova, Svetlana N
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Tarvainen, I
    Capellari, S
    Parchi, P
    Hannikainen, P
    Pirinen, E
    Haapasalo, H
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Divergent clinical and neuropathological phenotype in a Gerstmann-Sträussler-Scheinker P102L family2012Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, nr 5, s. 315-323Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:

    Gerstmann-Sträussler-Scheinker syndrome belongs to the genetic prion diseases being associated with mutations in the prion protein gene (PRNP). The most common is the point mutation at codon 102, leading to the substitution of proline to leucine (P102L). Previous reports have indicated a phenotypic heterogeneity among individuals with this mutation. Here, we describe the clinical and pathological phenotype in members of the first Finnish kindred with the P102L mutation in the PNRP gene.

    MATERIALS AND METHODS:

    Genetic and clinical information was available in five members of a family, while a systematic histologic and immunohistochemical assessment of the post-mortem brain was carried out in three.

    RESULTS:

    Clinical presentation, disease duration and the clinical phenotype (ataxia vs dementia) varied between patients. There was a significant correlation between clinical symptoms and the neuroanatomical distribution of prion protein-immunoreactive aggregates, i.e. subtentorial predominance in ataxia vs cortical predominance in dementia. A significant concomitant Alzheimer is disease-related pathology was observed in the brain of one patient with dementia as onset symptom.

    CONCLUSIONS:

    This is the first Scandinavian family carrying the P102L mutation in the PRNP gene. Gerstmann-Sträussler-Scheinker syndrome should be considered in the differential diagnosis when handling with patients with ataxia and/or dementia of unclear aetiology.

  • 279.
    Posautz, Annika
    et al.
    Univ Vet Med, Austria..
    Kuebber-Heiss, Anna
    Univ Vet Med, Austria..
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Different population - different prevalence or, what is going on in the European brown hare (Lepus europaeus)2017Inngår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, s. 142-143Artikkel i tidsskrift (Annet vitenskapelig)
  • 280.
    Pouliou, Evi
    et al.
    Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece.;Univ Athens, Sch Med, Dept Pathol, Athens, Greece..
    Xochelli, Aliki
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Ctr Res & Technol Hellas CERTH, Inst Appl Biosci, Thessaloniki, Greece.
    Kanellis, George
    Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece..
    Stalika, Evangelia
    Ctr Res & Technol Hellas CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Sutton, Lesley-Ann
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Navarro, Alba
    Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain.;Univ Barcelona, Inst Biomed Res August Pi i Sunyer, Barcelona, Spain..
    Agathangelidis, Andreas
    Ist Sci San Raffaele, IRCCS, Div Mol Oncol, Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, Milan, Italy.;Univ Vita Salutte San Raffaele, Milan, Italy..
    Dimosthenous, Kypros
    Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, Hematopoiet Cell Transplantat Unit, Thessaloniki, Greece..
    Patsouris, Efstratios
    Univ Athens, Sch Med, Dept Pathol, Athens, Greece..
    Korkolopoulou, Penelope
    Univ Athens, Sch Med, Dept Pathol, Athens, Greece..
    Sundström, Christer
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Ghia, Paolo
    Ist Sci San Raffaele, IRCCS, Div Mol Oncol, Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, Milan, Italy.;Univ Vita Salutte San Raffaele, Milan, Italy..
    Ponzoni, Maurilio
    Ist Sci San Raffaele, Milan, Italy..
    Sander, Birgitta
    Karolinska Inst, Dept Lab Med, Div Pathol, Huddinge, Sweden.;Karolinska Univ Hosp, Huddinge, Sweden..
    Campo, Elias
    Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain.;Univ Barcelona, Inst Biomed Res August Pi i Sunyer, Barcelona, Spain..
    Rosenquist, Richard
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Hadzidimitriou, Anastasia
    Ctr Res & Technol Hellas CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Ctr Res & Technol Hellas CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, Hematopoiet Cell Transplantat Unit, Thessaloniki, Greece..
    Papadaki, Theodora
    Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece..
    Numerous Ontogenetic Roads to Mantle Cell Lymphoma: Immunogenetic and Immunohistochemical Evidence2017Inngår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 187, nr 7, s. 1454-1458Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To obtain insight into the ontogeny of mantle cell lymphoma (MCL), we assessed 206 patients from a morphological, immunohistochemical, and immunogenetic perspective. Our series included nodal (n = 151), extranodal. (n = 28), and primary splenic (n = 27) MCL cases. Skewing of the immunoglobulin heavy variable (IGHV) gene repertoire was noted, with only four IGHV genes accounting for 46% of cases and approximately 70% of cases (107/154) bearing an imprint of somatic hypermutation (SHM) ranging from minimalto pronounced. Interestingly, a distinctive immunophenotypic and immunogenetic profile was identified for primary splenic MCL, which was enriched for DBA.44-positive cases (P < 0.001) and used the IGHV1-8 gene more frequently (P = 0.02) compared to nodal or extranodal cases, alluding to distinct immunopathogenetic and antigen selection processes. Expression of CD27 (considered a marker of activated B cells) was generally dissociated from SHM and was more prevalent in cases with no or minimal/borderline SHM. These findings support the idea that antigen drive is relevant for most MCL cases, although the specific antigens and the precise location of affinity maturation remain to be elucidated. Moreover, they raise the intriguing hypothesis of multiple cellular origins for MCL.

  • 281.
    Pyykko, Okko T.
    et al.
    Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland.
    Nerg, Ossi
    Kuopio Univ Hosp, Neurol NeuroCtr, Kuopio, Finland;Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.
    Niskasaari, Hanna-Mari
    Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland.
    Niskasaari, Timo
    Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland.
    Koivisto, Anne M.
    Kuopio Univ Hosp, Neurol NeuroCtr, Kuopio, Finland;Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.
    Hiltunen, Mikko
    Univ Eastern Finland, Inst Biomed, Dept Neurol, Kuopio Univ Hosp, Kuopio, Finland.
    Pihlajamaki, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Dept Clin Nutr, Kuopio, Finland;Kuopio Univ Hosp, Clin Nutr & Obes Ctr, Kuopio, Finland.
    Rauramaa, Tuomas
    Kuopio Univ Hosp, Dept Pathol, Kuopio, Finland;Univ Eastern Finland, Inst Clin Med Pathol, Kuopio, Finland.
    Kojoukhova, Maria
    Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Soininen, Hilkka
    Kuopio Univ Hosp, Neurol NeuroCtr, Kuopio, Finland;Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.
    Jaaskelainen, Juha E.
    Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland.
    Leinonen, Ville
    Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland.
    Incidence, Comorbidities, and Mortality in Idiopathic Normal Pressure Hydrocephalus2018Inngår i: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 112, s. E624-E631Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECT: To investigate the incidence, comorbidities, mortality, and causes of death in idiopathic normal pressure hydrocephalus (iNPH). METHODS: A cohort of 536 patients with possible NPH from a defined population with a median follow-up time of 5.1 years, (range 0.04-19.9 years) was included in the study. Patients were evaluated by brain imaging and intraventricular pressure monitoring, with a brain biopsy specimen immunostained against amyloid-beta and hyper-phosphorylated tau. Hospital records were reviewed for vascular diseases and type 2 diabetes mellitus (T2DM). Death certificates and yearly population of the catchment area were obtained from national registries. RESULTS: A total of 283 patients had a clinical diagnosis of iNPH, leading to a median annual incidence of 1.58 iNPH patients per 100,000 inhabitants (range, 0.8-4.5). Alzeimer disease-related brain biopsy findings were less frequent in iNPH patients than in non-iNPH patients (P < 0.05). An overrepresentation of hypertension (52% vs. 33%, P < 0.001) and T2DM (23% vs. 13%, P = 0.002) was noted in iNPH patients. Age (hazard ratio [HR] 1.04/year, 95% confidence interval [CI] 1.03-1.06, P< 0.001) and T2DM (HR 1.63, 95% CI 1.23-2.16, P < 0.001) increased the risk of death in the iNPH patients and in the total population. iNPH was associated with decreased risk of death (HR 0.63, 95% CI 0.50-0.78, P < 0.001). The most frequent causes of death were cardiovascular and cerebrovascular disease. Dementia as a cause of death was more common in non-iNPH patients (27% vs. 10%, P < 0.001). CONCLUSIONS: Hypertension and T2DM are common in iNPH and the latter causes excess mortality in the affected patients.

  • 282. Pyykkö, Okko T
    et al.
    Lumela, Miikka
    Rummukainen, Jaana
    Nerg, Ossi
    Seppälä, Toni T
    Herukka, Sanna-Kaisa
    Koivisto, Anne M
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Puli, Lakshman
    Savolainen, Sakari
    Soininen, Hilkka
    Jääskeläinen, Juha E
    Hiltunen, Mikko
    Zetterberg, Henrik
    Leinonen, Ville
    Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 3, s. e91974-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPP alpha were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the brain biopsy. Quantified Ab load in the brain biopsy showed a negative correlation with CSF levels of Ab42 in ventricular (r = 20.295, p = 0.003) and lumbar (r = 20.356, p = 0.01) samples, while the levels of Ab38 and Ab40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions: The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.

  • 283.
    Quentmeier, Hilmar
    et al.
    Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
    Drexler, Hans G.
    Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
    Hauer, Vivien
    Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
    MacLeod, Roderick A. F.
    Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
    Pommerenke, Claudia
    Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
    Uphoff, Cord C.
    Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
    Zaborski, Margarete
    Leibniz Inst DSMZ German Collect Microorganisms &, Dept Human & Anim Cell Lines, Braunschweig, Germany..
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Univ Uppsala Hosp, Uppsala, Sweden..
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Univ Uppsala Hosp, Uppsala, Sweden..
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Diffuse Large B Cell Lymphoma Cell Line U2946: Model for MCL1 Inhibitor Testing2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 12, artikkel-id e0167599Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma worldwide. We describe the establishment and molecular characteristics of the DLBCL cell line U-2946. This cell line was derived from a 52-year-old male with DLBCL. U-2946 cells carried the chromosomal translocation t(8; 14) and strongly expressed MYC, but not the mature B-cell lymphoma associated oncogenes BCL2 and BCL6. Instead, U-2946 cells expressed the antiapoptotic BCL2 family member MCL1 which was highly amplified genomically (14n). MCL1 amplification is recurrent in DLBCL, especially in the activated B cell (ABC) variant. Results of microarray expression cluster analysis placed U-2946 together with ABC-, but apart from germinal center (GC)-type DLBCL cell lines. The 1q21.3 region including MCL1 was focally coamplified with a short region of 17p11.2 (also present at 14n). The MCL1 inhibitor A-1210477 triggered apoptosis in U-2946 (MCL1(pos)/BCL2(neg)) cells. In contrast to BCL2(pos) DLBCL cell lines, U-2946 did not respond to the BCL2 inhibitor ABT-263. In conclusion, the novel characteristics of cell line U-2946 renders it a unique model system to test the function of small molecule inhibitors, especially when constructing a panel of DLBCL cell lines expressing broad combinations of antiapoptotic BCL2-family members.

  • 284. Rafiefard, Farideh
    et al.
    ÖRVELL, CLAES
    Bondeson, Kåre
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Genotyping of respiratory syncytial virus (RSV) group A in Stockholm, Sweden, using PCR and two-dimensional melting curve analysis2008Inngår i: Apmis, Vol. 116, nr 4, s. 317-22Artikkel i tidsskrift (Fagfellevurdert)
  • 285.
    Raja, Erna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Tzavlaki, Kalliopi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Molekylär cellbiologi.
    Vuilleumier, Robin
    Edlund, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Kahata, Kaoru
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Zieba, Agata
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Morén, Anita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Watanabe, Yukihide
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Voytyuk, Iryna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Söderberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Pyrowolakis, George
    Heldin, Carl-Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Moustakas, Aristidis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    The protein kinase LKB1 negatively regulates bone morphogenetic protein receptor signaling2016Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, nr 2, s. 1120-1143Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The protein kinase LKB1 regulates cell metabolism and growth and is implicated in intestinal and lung cancer. Bone morphogenetic protein (BMP) signaling regulates cell differentiation during development and tissue homeostasis. We demonstrate that LKB1 physically interacts with BMP type I receptors and requires Smad7 to promote downregulation of the receptor. Accordingly, LKB1 suppresses BMP-induced osteoblast differentiation and affects BMP signaling in Drosophila wing longitudinal vein morphogenesis. LKB1 protein expression and Smad1 phosphorylation analysis in a cohort of non-small cell lung cancer patients demonstrated a negative correlation predominantly in a subset enriched in adenocarcinomas. Lung cancer patient data analysis indicated strong correlation between LKB1 loss-of-function mutations and high BMP2 expression, and these two events further correlated with expression of a gene subset functionally linked to apoptosis and migration. This new mechanism of BMP receptor regulation by LKB1 has ramifications in physiological organogenesis and disease.

  • 286.
    Rao, Shuan
    et al.
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Sigl, Verena
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Wimmer, Reiner Alois
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Novatchkova, Maria
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Jais, Alexander
    Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria.;Max Planck Inst Metab Res, Dept Neuronal Control Metab, D-50931 Cologne, Germany..
    Wagner, Gabriel
    Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria..
    Handschuh, Stephan
    Univ Vet Med, VetCore Facil Res, A-1220 Vienna, Austria..
    Uribesalgo, Iris
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Hagelkruys, Astrid
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Kozieradzki, Ivona
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Tortola, Luigi
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Nitsch, Roberto
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Cronin, Shane J.
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Orthofer, Michael
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    Branstetter, Daniel
    Amgen Inc, Dept Pathol, Seattle, WA 98119 USA..
    Canon, Jude
    Amgen Inc, Dept Oncol Res, Seattle, WA 98119 USA..
    Rossi, John
    Amgen Inc, Dept Mol Sci, Seattle, WA 98119 USA..
    D'Arcangelo, Manolo
    Univ Colorado, Ctr Canc, Aurora, CO 80045 USA..
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    La Fleur, Linnea
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Edlund, Karolina
    Leibniz Res Ctr Working Environm & Human Factors, D-44139 Dortmund, Germany..
    Bergqvist, Michael
    Gavle Cent Hosp, Dept Oncol, S-80187 Gavle, Sweden..
    Ekman, Simon
    Karolinska Inst, Dept Oncol Pathol, S-17177 Stockholm, Sweden..
    Lendl, Thomas
    Gregor Mendel Inst Mol Plant Biol GMI, A-1030 Vienna, Austria..
    Popper, Helmut
    Med Univ Graz, Inst Pathol, Res Unit Mol Lung & Pleura Pathol, A-8036 Graz, Austria..
    Takayanagi, Hiroshi
    Univ Tokyo, Dept Immunol, Tokyo 1088639, Japan..
    Kenner, Lukas
    Med Univ Vienna, Dept Clin Pathol, A-1090 Vienna, Austria.;Ludwig Boltzmann Inst Canc Res, A-1090 Vienna, Austria.;Univ Vet Med Vienna, Unit Pathol Lab Anim, A-1220 Vienna, Austria..
    Hirsch, Fred R.
    Univ Colorado, Ctr Canc, Aurora, CO 80045 USA..
    Dougall, William
    Amgen Inc, Dept Oncol Res, Seattle, WA 98119 USA.;QIMR, Berghofer Med Res Inst, Dept Immunol Canc & Infect, Brisbane, Qld 4006, Australia..
    Penninger, Josef
    Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
    RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer2017Inngår i: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 31, nr 20, s. 2099-2112Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas(G12D) in mouse lung epithelial cells markedly impairs the progression of KRas(G12D)-driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas(G12D)-driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer.

  • 287.
    Rauramaa, Tuomas
    et al.
    Univ Eastern Finland, Inst Clin Med, Unit Pathol, Kuopio, Finland;Kuopio Univ Hosp, Dept Pathol, POB 1777, FIN-70211 Kuopio, Finland.
    Saxlin, Anna
    Tampere Univ Hosp, Dept Pathol, Fimlab Labs, Tampere, Finland.
    Lohvansuu, Kaisa
    Univ Jyvaskyla, Ctr Interdisciplinary Brain Res, Jyvaskyla, Finland;Univ Jyvaskyla, Dept Psychol, Jyvaskyla, Finland.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Pitkanen, Asla
    Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland.
    Soininen, Hilkka
    Univ Eastern Finland, Sch Med, Dept Neurol, Kuopio, Finland.
    Epilepsy in neuropathologically verified Alzheimer's disease2018Inngår i: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 58, s. 9-12Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Subjects with Alzheimer's disease (AD) have been shown to be at a higher risk for epilepsy. The vast majority of the previous studies have not included a full neuropathological examination. Methods: The objective of this study was to assess the prevalence of epilepsy and clinicopathological characteristics in a well-defined study group of 64 subjects with AD. We evaluated the clinicopathological findings in 64 subjects (mean age at death 85 +/- 8.6 years) from a longitudi-nal study cohort of patients with dementia. Results: Eleven out of the 64 subjects (17%) had a history of epilepsy, which is comparable to previous studies. The subjects with AD and epilepsy were significantly younger at the time of AD diagnosis and at the time of hospitalisation. In addition, their duration of AD was longer. Concomitant neuropathology in addition to AD was common in both groups and the ApoE genotypes did not differ significantly between the groups. Conclusion: The strength of this study is a thorough neuropathological examination of all study subjects. Our findings support the previous literature regarding the prevalence of epilepsy in subjects with AD. We have shown that the subjects with AD and epilepsy differ significantly from the subjects without epilepsy.

  • 288.
    Rawstron, Andy C.
    et al.
    St Jamess Inst Oncol, Leeds.
    Kreuzer, Karl-Anton
    Universitätsklinikum Köln, Köln.
    Soosapilla, Asha
    Laverty Pathol, Sydney.
    Spacek, Martin
    Univ Hosp, Prague.
    Stehlikova, Olga
    Masaryk Univ, CEITEC, Brno; Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno.
    Gambell, Peter
    Peter MacCallum Canc Ctr, Melbourne.
    McIver-Brown, Neil
    Royal Bournemouth Hosp, Bournemouth.
    Villamor, Neus
    Hosp Clin Barcelona, Hematopathol Unit, Barcelona.
    Psarra, Katherina
    Evangelismos Med Ctr, Athens.
    Arroz, Maria
    CHLO Hosp S Francisco Xavier, Dept Clin Pathol, Flow Cytometry Lab, Lisbon.
    Milani, Raffaella
    Osped San Raffaele, Milan.
    de la Serna, Javier
    Hosp Univ 12 Octubre, Madrid.
    Teresa Cedena, M.
    Hosp Univ 12 Octubre, Madrid.
    Jaksic, Ozren
    Dubrava Univ Hosp, Zagreb.
    Nomdedeu, Josep
    Hosp Santa Creu & Sant Pau, Barcelona.
    Moreno, Carol
    Hosp Santa Creu & Sant Pau, Barcelona.
    Rigolin, Gian Matteo
    St Anna Univ Hosp, Ferrara.
    Cuneo, Antonio
    St Anna Univ Hosp, Ferrara.
    Johansen, Preben
    Aalborg Univ Hosp, Dept Haematol, Clin Canc Res Ctr, Aalborg; Aalborg Univ, Dept Clin Med, Aalborg.
    Johnsen, Hans E.
    Aalborg Univ Hosp, Dept Haematol, Clin Canc Res Ctr, Aalborg; Aalborg Univ, Dept Clin Med, Aalborg.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Niemann, Carsten Utoft
    Copenhagen Univ Hosp, Rigshosp, Copenhagen.
    Kern, Wolfgang
    MLL Munich Leukemia Lab, Munich.
    Westerman, David
    Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno.
    Trneny, Marek
    Univ Hosp, Prague.
    Mulligan, Stephen
    Laverty Pathol, Sydney.
    Doubek, Michael
    Masaryk Univ, CEITEC, Brno.
    Pospisilova, Sarka
    Masaryk Univ, CEITEC, Brno.
    Hillmen, Peter
    St Jamess Inst Oncol, Leeds.
    Oscier, David
    Royal Bournemouth Hosp, Bournemouth.
    Hallek, Michael
    Univ Klinikum Köln, Köln.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Milan; IRCCS Ist Sci San Raffaele, Milan.
    Montserrat, Emili
    Univ Barcelona, Hosp Clin, Dept Hematol, Barcelona.
    Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project2018Inngår i: Cytometry. Part B, Clinical cytometry., ISSN 1552-4949, E-ISSN 1552-4957, Vol. 94, nr 1, s. 121-128Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the diagnosis of CLL. ERIC/ESCCA members classified 14 of 35 potential markers as “required” or “recommended” for CLL diagnosis, consensus being defined as >75% and >50% agreement, respectively. An approach to validate “required” markers using normal peripheral blood was developed. Responses were received from 150 participants with a diagnostic workload >20 CLL cases per week in 23/150 (15%), 5–20 in 82/150 (55%), and <5 cases per week in 45/150 (30%). The consensus for “required” diagnostic markers included: CD19, CD5, CD20, CD23, Kappa, and Lambda. “Recommended” markers potentially useful for differential diagnosis were: CD43, CD79b, CD81, CD200, CD10, and ROR1. Reproducible criteria for component reagents were assessed retrospectively in 14,643 cases from 13 different centers and showed >97% concordance with current approaches. A pilot study to validate staining quality was completed in 11 centers. Markers considered as “required” for the diagnosis of CLL by the participants in this study (CD19, CD5, CD20, CD23, Kappa, and Lambda) are consistent with current diagnostic criteria and practice. Importantly, a reproducible approach to validate and apply these markers in individual laboratories has been identified. Finally, a consensus “recommended” panel of markers to refine diagnosis in borderline cases (CD43, CD79b, CD81, CD200, CD10, and ROR1) has been defined and will be prospectively evaluated.

  • 289.
    Renaud, Guillaume
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Llano-Diez, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Ravar, Barbara
    Gorza, Luisa
    Feng, Han-Zhong
    Jin, Jian-Ping
    Cacciani, Nicola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Gustafson, Ann-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Ochala, Julien
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Corpeno, Rebeca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Li, Meishan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Hedström, Yvette
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Ford, G Charles
    Nair, K Sreekumaran
    Larsson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Sparing of muscle mass and function by passive loading in an experimental intensive care unit model2013Inngår i: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 591, nr 5, s. 1385-1402Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The response to mechanical stimuli, i.e., tensegrity, plays an important role in regulating cell physiological and pathophysiological function and the mechanical silencing observed in intensive care unit (ICU) patients leads to a severe and specific muscle wasting condition. This study aims at unravelling the underlying mechanisms and the effects of passive mechanical loading on skeletal muscle mass and function at the gene, protein and cellular levels. A unique experimental rat ICU model has been used allowing long-term (weeks) time-resolved analyses of the effects of standardized unilateral passive mechanical loading on skeletal muscle size and function and underlying mechanisms. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. the unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle mass and function is likely a consequence of a reduced oxidative stress revealed by lower levels of carbonylated proteins, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle size and function associated with the mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients.

  • 290. Renoux, VM
    et al.
    Zriwil, A
    Peitzsch, C
    Michaëlsson, J
    Friberg, Danielle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Soneji, S
    Sitnicka, J
    Identification of a Human Natural Killer Cell Lineage-Restricted Progenitor in Fetal and Adult Tissues2015Inngår i: ImmunityArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Natural killer (NK) cells are cytotoxic lymphocytes and play a vital role in controlling viral infections and cancer. In contrast to B and T lymphopoiesis where cellular and regulatory pathways have been extensively characterized, the cellular stages of early human NK cell commitment remain poorly understood. Here we demonstrate that a LinCD34+CD38+CD123CD45RA+CD7+CD10+CD127 population represents a NK lineage-restricted progenitor (NKP) in fetal development, umbilical cord blood, and adult tissues. The newly identified NKP has robust NK cell potential both in vitro and in vivo, generates functionally cytotoxic NK cells, and lacks the ability to produce T cells, B cells, myeloid cells, and innate lymphoid-like cells (ILCs). Our findings identify an early step to human NK cell commitment and provide new insights into the human hematopoietic hierarchy.

  • 291.
    Ridefelt, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Axelsson, John
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Diurnal variability of total calcium during normal sleep and after an acute shift of sleep2012Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 50, nr 1, s. 147-151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Serum total calcium is becoming a widely used test when screening for hyperparathyroidism (HPT) and other causes of hypercalcemia, even if serum calcium is tightly regulated in the body it is unclear whether the reference values are correct for tests taken at different times of the day or for individuals with altered sleep patterns. Thus, the aim was to investigate how timing of testing and sleep affects serum calcium.

    Methods: The diurnal variation of total calcium in serum during night-time and day-time conditions was studied in seven healthy volunteers. Serum samples for calcium measurements were collected every hour (48 samples per individual) to evaluate the effect of sampling times, sleep and food intake on the test results.

    Results: The median intra-individual coefficients of variations for calcium were 3.3% during night-time sleep and 2.8% during day-time sleep conditions. There was a clear diurnal variation in serum calcium, with a trough at 08.00 h in the morning after night-time sleep and a difference of approximately 0.07 mmol/L between trough and peak. Calcium was lower around the end of the sleep periods, for both night-time and day-time sleep. Food intake did not affect calcium concentrations.

    Conclusions: Evaluation of serum calcium results should take diurnal variation into account and allow slightly higher calcium values in the afternoon in comparison with samples collected in the morning.

  • 292.
    Ridefelt, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Gustafsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Aldrimer, Mattias
    Hellberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Alkaline phosphatase in healthy children: reference intervals and prevalence of elevated levels.2014Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, nr 6, s. 399-404Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Transient hyperphosphatasemia (TH) is an often unnoticed benign entity, primarily affecting children below 5 years of age. However, the prevalence among healthy children is unknown. We used data from a Swedish pediatric reference interval project to estimate the prevalence of high alkaline phosphatase (ALP) among healthy children and to calculate pediatric reference intervals.

    METHODS: Blood was collected from 699 subjectively healthy children aged 6 months to 18 years. After exclusion of subjects with high ALP, age- and gender-specific reference intervals were calculated.

    RESULTS: Six children had ALP levels >16.7 µkat/l (>1,000 U/l), including 4 females and 2 males aged 7-22 months. The prevalence in the age group from 6 months to 2 years was 6.2% (6/97). None of the older children had levels of ALP >16.7 µkat/l. The study did not include the follow-up of these apparently healthy children. Consequently, conditions others than TH explaining the elevated ALP could not be excluded. However, general chemistry analyses, such as liver enzymes, calcium, intact PTH and vitamin D, were essentially normal in these children.

    CONCLUSIONS: The prevalence of high ALP among subjectively healthy children was approximately 2.4% below 5 years of age and 6.2% below 2 years. Reference intervals vary with age and gender.  

  • 293.
    Ridefelt, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Albumin adjustment of total calcium does not improve the estimation of calcium status2017Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, nr 6, s. 442-447Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is a longstanding controversy as to whether plasma measurements of total calcium should be adjusted for albumin concentration, and if so which formulas are the most appropriate.Methods: Ionised calcium, total calcium and albumin results, analysed at the same time at Uppsala University Hospital Laboratory between February 2005 and June 2013, were retrieved from a laboratory information system. The dataset included results from 20,003 patients. Total calcium was albumin-modified by a locally derived formula, based on 3106 patients from the dataset, and formulas from the literature. The agreement between the reference method ionised calcium and unadjusted total calcium and the seven different albumin-modifying calcium formulas, respectively, were compared with intra-class correlation coefficients (ICC).Results: Total calcium showed substantial agreement to ionised calcium, ICC 0.85 (95% CI 0.84-0.86) for the whole validation cohort. Albumin-modified calcium by different formulas showed significantly less or equal agreement, however the locally determined formula performed better than formulas taken from the literature. Also, total calcium classified the patient as hypo-normo- or hypercalcemic right in 82% of the patients. The albumin-modified calcium did not classify patients significantly better except in the subgroup hypoalbuminemia (<30g/L) where the local formula classified the patients slightly better than total calcium.Conclusions: Albumin modification of total calcium determinations is unlikely to add valuable information, and this practice should be abandoned. Ionised calcium should be used more frequently when aberrant results for total calcium are followed up, or in patients with known hypoalbuminemia.

  • 294.
    Rinne, Juha O.
    et al.
    Univ Turku, Turku PET Ctr, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland;Turku Univ Hosp, Div Clin Neurosci, Turku, Finland.
    Suotunen, Timo
    Univ Turku, Turku PET Ctr, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland.
    Rummukainen, Jaana
    Kuopio Univ Hosp, Dept Clin Pathol, Kuopio, Finland.
    Herukka, Sanna-Kaisa
    Kuopio Univ Hosp, Neurol NeuroCtr, Kuopio, Finland;Univ Eastern Finland, Inst Clin Med, Neurol, Kuopio, Finland.
    Nerg, Ossi
    Kuopio Univ Hosp, Neurol NeuroCtr, Kuopio, Finland.
    Koivisto, Anne M.
    Kuopio Univ Hosp, Neurol NeuroCtr, Kuopio, Finland;Univ Eastern Finland, Inst Clin Med, Neurol, Kuopio, Finland.
    Rauramaa, Tuomas
    Kuopio Univ Hosp, Dept Clin Pathol, Kuopio, Finland;Univ Eastern Finland, Inst Clin Med, Pathol, Kuopio, Finland.
    Någren, Kjell
    Odense Univ Hosp, PET & Cyclotron Unit, Dept Nucl Med, Odense, Denmark.
    Hiltunen, Mikko
    Univ Eastern Finland, Inst Biomed, Kuopio, Finland.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Rinne, Jaakko
    Turku Univ Hosp, Dept Neurosurg, Clin Neurosci, Turku, Finland.
    Jääskeläinen, Juha E.
    Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland;Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland.
    Soininen, Hilkka
    Univ Eastern Finland, Inst Clin Med, Neurol, Kuopio, Finland.
    Leinonen, Ville
    Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland;Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland;Univ Oulu, Unit Clin Neurosci, Neurosurg, Oulu, Finland;Oulu Univ Hosp, Med Res Ctr, Oulu, Finland.
    [C-11]PIB PET Is Associated with the Brain Biopsy Amyloid-beta Load in Subjects Examined for Normal Pressure Hydrocephalus2019Inngår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, nr 4, s. 1343-1351Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-beta (A beta) pathology. Objective: To compare the [C-11]PIB PET uptake in the patients with suspected iNPH to A beta and hyperphosphorylated-tau (HP tau) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) A beta, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD). Methods: Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for A beta and HP tau in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [C-1(1)]PIB PET. A beta, total tau, and P tau(181) were measured by ELISA from the ventricular (n= 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3 +/- 2.4 years, range 3-1). Results: [C-11]PIB uptake in the right frontal cortex (rho = 0.60, p < 0.01) and the combined neocortical [C-11]PIB uptake score (rho = 0.61, p < 0.01) were associated with a higher A beta load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [C-11]PIB uptake was also associated with the ventricular CSF A beta (rho = -0.58, p = 0.03). Conclusions: The findings show that [C-11]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of A beta pathology in the patients with iNPH might also warrant treatment with current AD drugs.

  • 295.
    Rising, Anna
    et al.
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, S-75007 Uppsala, Sweden.;Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Cederlund, Ella
    Karolinska Inst, Dept Med Biochem & Biophys MBB, S-17177 Stockholm, Sweden..
    Palmberg, Carina
    Karolinska Inst, Ctr Prote Karolinska PKKI, S-17177 Stockholm, Sweden..
    Uhlhorn, Henrik
    Natl Vet Inst SVA, Dept Pathol & Wildlife Dis, S-75189 Uppsala, Sweden..
    Gaunitz, Stefan
    Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Nordling, Kerstin
    Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Agren, Erik
    Natl Vet Inst SVA, Dept Pathol & Wildlife Dis, S-75189 Uppsala, Sweden..
    Ihse, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Westermark, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Tjernberg, Lars
    Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Jornvall, Hans
    Karolinska Inst, Dept Med Biochem & Biophys MBB, S-17177 Stockholm, Sweden..
    Johansson, Jan
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, S-75007 Uppsala, Sweden.;Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Systemic AA amyloidosis in the red fox (Vulpes vulpes)2017Inngår i: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 26, nr 11, s. 2312-2318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model.

  • 296.
    Rollborn, Niclas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Åkerfeldt, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Nordin, Gunnar
    Equalis, Uppsala, Sweden.
    Xu, Xiao Yan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Mandic-Havelka, Aleksandra
    Karolinska Univ Hosp, Karolinska Inst, Clin Chem, Dept Mol Med & Surg, Stockholm, Sweden.
    Hansson, Lars-Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Analysis of HbA1c on an automated multicapillary zone electrophoresis system.2017Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, nr 1, s. 15-18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hemoglobin A1c (HbA1c) is a frequently requested laboratory test and there is thus a need for high throughput instruments for this assay. We evaluated a new automated multicapillary zone electrophoresis instrument (Capillarys 3 Tera, Sebia, Lisses, France) for analysis of HbA1c in venous samples. Routine requested HbA1c samples were analyzed immunologically on a Roche c6000 instrument (n = 142) and then with the Capillarys 3 Tera instrument. The Capillarys 3 Tera instrument performed approximately 70 HbA1c tests/hour. There was a strong linear correlation between Capillarys 3 Tera and Roche Tina-Quant HbA1c Gen 3 assay (y = 1.003x - 0.3246 R(2 )= .996). The total CV for the 12 capillaries varied between 0.8 and 2.2% and there was a good agreement between duplicate samples (R(2 )= .997). In conclusion, the Capillarys 3 Tera instrument has a high assay capacity for HbA1c. It has a good precision and agreement with the Roche Tina-Quant HbA1c method and is well suited for high volume testing of HbA1c.

  • 297. Roomans, Godfried M
    et al.
    Dragomir, Anca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    X-ray microanalysis in the scanning electron microscope2014Inngår i: Electron Microscopy: Methods and Protocols / [ed] John Kuo, New York: Humana Press, 2014, 3rd, Vol. 1117, s. 639-661Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    X-ray microanalysis conducted using the scanning electron microscope is a technique that allows the determination of chemical elements in bulk or semi-thick specimens. The lowest concentration of an element that can be detected is in the order of a few mmol/kg or a few hundred parts per million, and the smallest amount is in the order of 10(-18) g. The spatial resolution of the analysis depends on the thickness of the specimen. For biological specimen analysis, care must be taken to prevent displacement/loss of the element of interest (usually ions). Protocols are presented for the processing of frozen-hydrated and freeze-dried specimens, as well as for the analysis of small volumes of fluid, cell cultures, and other specimens. Aspects of qualitative and quantitative analysis are covered, including limitations of the technique.

  • 298. Rosmarin, Dan
    et al.
    Palles, Claire
    Church, David
    Domingo, Enric
    Jones, Angela
    Johnstone, Elaine
    Wang, Haitao
    Love, Sharon
    Julier, Patrick
    Scudder, Claire
    Nicholson, George
    Gonzalez-Neira, Anna
    Martin, Miguel
    Sargent, Daniel
    Green, Erin
    McLeod, Howard
    Zanger, Ulrich M
    Schwab, Matthias
    Braun, Michael
    Seymour, Matthew
    Thompson, Lindsay
    Lacas, Benjamin
    Boige, Valérie
    Ribelles, Nuria
    Afzal, Shoaib
    Enghusen, Henrik
    Jensen, Søren Astrup
    Etienne-Grimaldi, Marie-Christine
    Milano, Gérard
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Gusella, Milena
    Lecomte, Thierry
    Laurent-Puig, Pierre
    Martinez-Balibrea, Eva
    Sharma, Rohini
    Garcia-Foncillas, Jesus
    Kleibl, Zdenek
    Morel, Alain
    Pignon, Jean-Pierre
    Midgley, Rachel
    Kerr, David
    Tomlinson, Ian
    Genetic Markers of Toxicity From Capecitabine and Other Fluorouracil-Based Regimens: Investigation in the QUASAR2 Study, Systematic Review, and Meta-Analysis2014Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, nr 10, s. 1031-1039Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Fluourouracil (FU) is a mainstay of chemotherapy, although toxicities are common. Genetic biomarkers have been used to predict these adverse events, but their utility is uncertain.

    PATIENTS AND METHODS: We tested candidate polymorphisms identified from a systematic literature search for associations with capecitabine toxicity in 927 patients with colorectal cancer in the Quick and Simple and Reliable trial (QUASAR2). We then performed meta-analysis of QUASAR2 and 16 published studies (n = 4,855 patients) to examine the polymorphisms in various FU monotherapy and combination therapy regimens.

    RESULTS: Global capecitabine toxicity (grades 0/1/2 v grades 3/4/5) was associated with the rare, functional DPYD alleles 2846T>A and *2A (combined odds ratio, 5.51; P = .0013) and with the common TYMS polymorphisms 5'VNTR2R/3R and 3'UTR 6bp ins-del (combined odds ratio, 1.31; P = 9.4 × 10(-6)). There was weaker evidence that these polymorphisms predict toxicity from bolus and infusional FU monotherapy. No good evidence of association with toxicity was found for the remaining polymorphisms, including several currently included in predictive kits. No polymorphisms were associated with toxicity in combination regimens.

    CONCLUSION: A panel of genetic biomarkers for capecitabine monotherapy toxicity would currently comprise only the four DPYD and TYMS variants above. We estimate this test could provide 26% sensitivity, 86% specificity, and 49% positive predictive value-better than most available commercial kits, but suboptimal for clinical use. The test panel might be extended to include additional, rare DPYD variants functionally equivalent to *2A and 2846A, though insufficient evidence supports its use in bolus, infusional, or combination FU. There remains a need to identify further markers of FU toxicity for all regimens.

  • 299.
    Ryden, Ingvar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Reference values of thirty-one frequently used laboratory markers for 75-year-old males and females2012Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, nr 3, s. 264-272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background.

    We have previously reported reference values for common clinical chemistry tests in healthy 70-year-old males and females. We have now repeated this study 5 years later to establish reference values also at the age of 75. It is important to have adequate reference values for elderly patients as biological markers may change over time, and adequate reference values are essential for correct clinical decisions.

    Methods.

    We have investigated 31 frequently used laboratory markers in 75-year-old males (n = 354) and females (n = 373) without diabetes. The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry.

    Results.

    Reference values are reported for 75-year-old males and females for 31 frequently used laboratory markers.

    Conclusion.

    There were minor differences between reference intervals calculated with and without individuals with cardiovascular diseases. Several of the reference intervals differed from Scandinavian reference intervals based on younger individuals (Nordic Reference Interval Project).

  • 300. Rydenhag, Bertil
    et al.
    Flink, Roland
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Malmgren, Kristina
    Surgical outcomes in patients with epileptogenic tumours and cavernomas in Sweden: good seizure control but late referrals.2013Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, nr 1, s. 49-53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Seizure outcome after epilepsy surgery is to an important extent related to underlying aetiology. In this study of patients who underwent epilepsy surgery with a lesional aetiology in Sweden 1990-2004, the aim was to investigate seizure outcome and prognostic factors. METHODS: All patients operated on during the time period with a histopathological diagnosis of an epileptogenic tumour (ganglioglioma (GGL), dysembryoblastic neuroepithelial tumour (DNET) and low grade astrocytoma (AST)) or a cavernous haemangioma (CAH) were identified in the population based Swedish National Epilepsy Surgery Register. Univariate and multivariate analyses were performed to determine the independent contribution of the following variables to seizure outcome: age at surgery; epilepsy duration; preoperative seizure frequency; localisation of the resection; and histopathology. RESULTS: Of the 156 identified patients who had a 2 year follow-up (103 adults and 53 children), 71% had temporal, 16% frontal and 13% parietal and occipital lobe resections. Mean presurgical epilepsy duration was 13 years in adults and 5 years in children. Main histopathological diagnosis was GGL or DNET in 67, CAH in 42 and AST in 47 patients. 77% of patients had sustained seizure freedom (with or without aura) 2 years after surgery. In the multivariate analysis, only diagnosis other than AST was independently associated with becoming seizure free. CONCLUSION: In this population based series, 120/156 patients (77%) with epileptogenic tumours and cavernomas were seizure free 2 years after surgery. Many had a very long epilepsy history. Seizure outcome can be improved if epilepsy surgery is considered earlier in patients with epileptogenic lesions.

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