Olav Klingenberg

• Grimholt, Runa Marie; Fjeld, Bente; Selsås, Hilde; Schwettmann, Lutz & Klingenberg, Olav (2019). Hb Aalesund (HBA2: c.400_406delAGCACCG), an Unstable α-Globin Variant Found in a Norwegian Patient Causing Moderate Hemolytic Anemia and Falsely High Hb A1c Using Ion Exchange High Performance Liquid Chromatography.. Hemoglobin.  ISSN 0363-0269.  43(2), s 122- 125 . doi: 10.1080/03630269.2019.1614048
• Grimholt, Runa Marie; Harteveld, Cornelis; Arkesteijn, Sandra G J; Fjeld, Bente & Klingenberg, Olav (2018). Characterization of Two Deep Intronic Variants on the β-Globin Gene with Inconsistent Interpretations of Clinical Significance. Hemoglobin.  ISSN 0363-0269.  42(2), s 126- 128 . doi: 10.1080/03630269.2018.1473255 Fulltekst i vitenarkiv.
• Grimholt, Runa Marie; Vestli, Anne; Urdal, Petter; Bechensteen, Anne Grete; Fjeld, Bente; Dalhus, Bjørn & Klingenberg, Olav (2018). Hb Oslo [β42(CD1)Phe→Ile; HBB: c.127T>A]: A novel unstable hemoglobin variant found in a Norwegian patient. Hemoglobin.  ISSN 0363-0269.  42(2), s 78- 83 . doi: 10.1080/03630269.2018.1468773 Fulltekst i vitenarkiv.
• Klingenberg, Olav; Furuset, Torill; Hestbråten, Camilla Røising; Hallberg, Marit Hansen; Steiro, Astrid; Orset, Iren Røstbakken & Berg, Jens Petter (2017). HbA1c analysis by capillary electrophoresis?comparison with chromatography and an immunological method. Scandinavian Journal of Clinical and Laboratory Investigation.  ISSN 0036-5513.  77(6), s 458- 464 . doi: 10.1080/00365513.2017.1338747 Fulltekst i vitenarkiv.
• Sagedal, Solbjørg; Sandvik, Leiv; Klingenberg, Olav & Sandset, Per Morten (2017). β-Thromboglobulin may not reflect platelet activation during haemodialysis with the HeprAN membrane. Scandinavian Journal of Clinical and Laboratory Investigation.  ISSN 0036-5513.  77(8), s 679- 684 . doi: 10.1080/00365513.2017.1397288
• Berntsen, Natalie Lie; Klingenberg, Olav; Juran, Brian D.; Benito De Valle, Maria; Lindkvist, Björn; Lazaridis, Konstantinos N.; Boberg, Kirsten Muri; Karlsen, Tom Hemming & Hov, Johannes Espolin Roksund (2015). Association between HLA haplotypes and increased serum levels of IgG4 in patients with primary sclerosing cholangitis. Gastroenterology.  ISSN 0016-5085.  148(5), s 924- 927.e2 . doi: 10.1053/j.gastro.2015.01.041
• Sudmann, Åshild Amelie; Piehler, Armin; Klingenberg, Olav & Urdal, Petter (2015). Six-day stability of erythrocyte and reticulocyte parameters in-vitro: A comparison of blood samples from healthy, iron-deficient, and thalassemic individuals. Scandinavian Journal of Clinical and Laboratory Investigation.  ISSN 0036-5513.  75(3), s 247- 253 . doi: 10.3109/00365513.2014.1000370
• Grimholt, Runa Marie; Urdal, Petter; Klingenberg, Olav & Piehler, Armin (2014). Rapid and reliable detection of alpha-globin copy number variations by quantitative real-time PCR. BMC hematology..  ISSN 2052-1839. . doi: 10.1186/2052-1839-14-4
• Urdal, Petter; Amundsen, Erik Koldberg; Toska, Karin & Klingenberg, Olav (2014). Automated alarm to detect antigen excess in serum free immunoglobulin light chain kappa and lambda assays. Scandinavian Journal of Clinical and Laboratory Investigation.  ISSN 0036-5513.  74(7), s 575- 581 . doi: 10.3109/00365513.2014.915426
• Bachmann-Harildstad, Gregor; Stenklev, Niels Chr.; Myrvoll, Elin Alise; Jablonski, Greg & Klingenberg, Olav (2011). Beta-Trace Protein as a Diagnostic Marker for Perilymphatic Fluid Fistula: A Prospective Controlled Pilot Study to Test a Sample Collection Technique. Otology and Neurotology.  ISSN 1531-7129.  32(1), s 7- 10 . doi: 10.1097/MAO.0b013e3181fc74d0
• Henriksson, Carola Elisabeth; Hellum, Marit Synnøve; Haug, Kari Bente Foss; Aass, Hans Christian; Joø, Gun Brit; Øvstebø, Reidun; Trøseid, Anne-Marie Siebke; Klingenberg, Olav & Kierulf, Peter (2011). Anticoagulant effects of an antidiabetic drug on monocytes in vitro. Thrombosis Research.  ISSN 0049-3848.  128(5), s E100- E106 . doi: 10.1016/j.thromres.2011.07.007
• Sagedal, Solbjørg; Witczak, Bartlomiej J; Osnes, Kåre; Hartmann, Anders; Os, Ingrid; Eikvar, Lars Kristian; Klingenberg, Olav & Brosstad, Frank Roger (2011). A Heparin-Coated Dialysis Filter (AN69 ST) Does Not Reduce Clotting during Hemodialysis when Compared to a Conventional Polysulfone Filter (F x 8). Blood Purification.  ISSN 0253-5068.  32(3), s 151- 155 . doi: 10.1159/000325227
• Jensen, Torstein; Kierulf, Peter; Sandset, Per Morten; Klingenberg, Olav; Joø, Gun Brit; Godal, Hans Chr & Skjønsberg, Ole Henning (2007). Fibrinogen and fibrin induce synthesis of proinflammatory cytokines from peripheral blood mononuclear cells. Thrombosis and Haemostasis.  ISSN 0340-6245.  97(5), s 822- 829 . doi: 10.1160/TH07-01-0039 Vis sammendrag

  Fibrinogen in plasma includes three main fractions; high-molecular-weight (HMW)-fibrinogen, low-molecular-weight (LMW)-fibrinogen, and very-low-molecular-weight (LMW')-fibrinogen. During acute-phase conditions, plasma fibrinogen levels and the HMW-/LMW-fibrinogen ratio increase rapidly due to increased synthesis of HMW-fibrinogen. The consequences of elevated plasma fibrinogen levels and local deposition of fibrin in inflammatory tissues observed during acute-phase conditions are not clear. We wanted to investigate proinflammatory effects of fibrinogen and fibrin on peripheral blood mononuclear cells (PBMC) as reflected by altered mRNA expression and synthesis of the proinflammatory cytokines IL-6, TNF-alpha and IL-1beta, and to explore the significance of altered HMW-/LMW-fibrinogen ratio. PBMC were isolated from whole blood using Lymphoprep((R)). HMW-fibrinogen was separated from unfractioned fibrinogen by ammonium sulphate precipitation. Cells were incubated with unfractioned fibrinogen, HMW-fibrinogen or fibrin. Cytokine levels in cell lysates were determined using ELISA assays. Real-time PCR was used for mRNA quantification. We found that fibrinogen significantly increased mRNA levels, and induced synthesis of the proinflammatory cytokines IL-6 and TNF-alpha in PBMC in a dose dependent manner. Median (25, 75 percentile) IL-6 and TNF-alpha concentrations were 12 (5, 40) pg/ml and 16 (0,61) pg/ml, respectively. Median mRNA quantity was increased 12.3- (6.6, 48.6) and 1.7- (1.5, 6.5) fold for IL-6 and TNF-alpha compared to controls. The stimulatory effect of unfractioned fibrinogen was not significantly different from HMW-fibrinogen. Fibrinogen and fibrin were equally effective in promoting cytokine synthesis from PBMC. The results support that fibrin and fibrinogen may actively modulate the inflammatory process by inducing synthesis of proinflammatory cytokines from PBMC.

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• Fjeld, Bente; Sudmann-Day, Åshild Amelie; Grimholt, Runa Marie & Klingenberg, Olav (2019). Kan pasienten ha talassemi eller en hemoglobinvariant?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  139(17) . doi: 10.4045/tidsskr.19.0121
• Grimholt, Runa Marie; Fjeld, Bente; Klingenberg, Olav & Piehler, Armin P (2017). Alfa-thalassemi på avveie – sjeldne former for alfa-thalassemi funnet hos norske pasienter. Vis sammendrag

  Bakgrunn: Alfa-thalassemi er en av de vanligste monogene sykdommene i verden og skyldes i hovedsak delesjoner av alfa-globingenene, som gir nedsatt eller ingen produksjon av alfa-globinkjeder. Sekvensvarianter og delesjoner av det regulerende området oppstrøms for alfa-globingenene, HS-40, forekommer langt sjeldnere. Alfa-thalassemi er hyppig forkommende i områder der malaria er eller har vært vanlig. Med dagens globale migrasjonsmønster er hemoglobinopatier blitt stadig vanligere forekommende også i det norske helsevesen, men hos individer av norsk opprinnelse er det svært sjelden. Her beskriver vi tre former for alfa-thalassemi påvist hos etnisk norske pasienter. Material og metode: Pasientene ble diagnostisert gjennom rutinemessig hemoglobinopati-utredning ved Avdeling for medisinsk biokjemi, Oslo universitetssykehus, Ullevål. Standard hemoglobinopati-utredning, som innebærer analytisk hematologi, måling av ferritin og CRP, hemoglobintyping og gap-PCR som påviser de syv vanligste delesjonene som gir alfa-thalassemi, ble utført på alle pasientene. DNA sekvensering av alfa-globingenene ble brukt til å påvise sekvensvarianter og sanntids PCR ble brukt til å påvise sjeldne delesjoner i alfa-globin genclusteret. Resultater: To nye delesjoner, (αα)Aurora Borealis og (--)NOR ble påvist ved sanntids PCR hos til sammen ni pasienter fra henholdsvis en og to familier. (αα)Aurora Borealis fører til alfa-thalassemi ved at det regulatoriske området, HS-40, er deletert. (--)NOR er et resultat av homolog overkryssing og rammer begge alfa-globingenene. I tillegg ble det påvist en sjelden sekvensvariant i HBA2 genet som gir alfa-thalassemi hos åtte pasienter fra fem ulike familier. Alle pasientene var av norsk opprinnelse og hadde mikrocytose med eller uten anemi. Konklusjon: Selv om thalassemi er svært sjelden hos etnisk norske individer, skal muligheten for bærertilstand likevel ikke utelukkes.

• Grimholt, Runa Marie; Fjeld, Bente; Piehler, Armin & Klingenberg, Olav (2017). Chasing the Northern Light - (--)NOR and (αα) Aurora Borealis; two novel deletions causing alpha-thalassemia found in Norwegian patients.. Vis sammendrag

  Introduction: Alpha-thalassemia is one of the most common monogenic diseases worldwide and is caused by reduced or absent synthesis of alpha-globin chains, most commonly due to deletions of one or more of the alpha-globin genes. Sequence variants that alter gene expression or deletions involving upstream regulatory elements are less frequent. Alpha-thalassemia occurs with high frequency in tropical and subtropical regions of the world. For people of Northern European origin, inherited hemoglobin disorders, such as alpha-thalassemia, are extremely rare. Here, we describe two novel deletions causing alpha-thalassemia found in patients of Norwegian origin. Materials and Methods: The study patients were diagnosed during routine hemoglobinopathy evaluation carried out at the Department of Medical Biochemistry, Oslo University Hospital, Norway. The patients were selected for their thalassemic phenotype, despite Norway as country of origin. All samples went through standard hemoglobinopathy evaluation. Quantitative real-time PCR copy number variation (CNV) analysis was applied to detect uncommon deletions in the alpha-globin gene cluster. Deletion breakpoints were characterized using gap-PCR and DNA sequencing. Results: Two novel deletions, (--)NOR and (αα)Aurora Borealis, were identified in altogether nine patients from two and one families, respectively, all of Norwegian origin presenting with microcytosis. The (--)NOR deletion was a result of homologous recombination deleting both alpha-globin genes. The (αα)Aurora Borealis deletion caused alpha-thalassemia by affecting the upstream regulatory element, HS-40, leaving the alpha-globin genes intact. Conclusions: Even though inherited hemoglobin disorders are extremely rare in indigenous Northern Europeans, the possibility of a carrier state should not be ignored.

• Klingenberg, Olav (2017). Hemoglobin amino acids by the numbers. Scandinavian Journal of Clinical and Laboratory Investigation.  ISSN 0036-5513.  77(1), s 1- 1 . doi: 10.1080/00365513.2017.1267428
• Grimholt, Runa Marie; Sudmann, Åshild Amelie; Piehler, Armin; Urdal, Petter & Klingenberg, Olav (2014). Hb Ullevaal [β78(EF2)Leu→Val; HBB: c.235C>G], a New Hemoglobin Variant Interfering with Hb A1c Measurement Using a Cation Exchange High Performance Liquid Chromatography Method. Hemoglobin.  ISSN 0363-0269.  38(2), s 130- 132 . doi: 10.3109/03630269.2013.858640
• Hausken, Jon; Klingenberg, Olav; Mørkrid, Lars; Rollag, Halvor; Foss, Aksel & Midtvedt, Karsten (2012). Elevated Troponin I and NT-proBNP at the Time of Transplantation May Predict a Major Adverse Cardiac Event in the Early Postoperative Period After Renal Transplantation. Transplantation.  ISSN 0041-1337.  94(2), s E15- E16 . doi: 10.1097/TP.0b013e31825b7633

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