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BETA
Kågedal, Bertil
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Publications (10 of 51) Show all publications
Magnusson, K., Appelqvist, H., Cieślar-Pobuda, A., Bäck, M., Kågedal, B., Jonasson, J., . . . Nilsson, P. R. (2015). An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells. Frontiers in Chemistry, 3, Article ID 58.
Open this publication in new window or tab >>An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells
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2015 (English)In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 3, article id 58Article in journal (Refereed) Published
Abstract [en]

Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2015
Keywords
Oligothiophenes, fluorescence, cells, imaging, imidazole
National Category
Clinical Medicine Chemical Sciences Medical Biotechnology
Identifiers
urn:nbn:se:liu:diva-121813 (URN)10.3389/fchem.2015.00058 (DOI)000373364600001 ()
Note

Vid tiden för disputation förelåg publikationen som manuskript

Funding agencies:  Swedish Foundation for Strategic Research; GeCONil [POIG.02.03.01-24-099/13]; ERC from the European Research Council

Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2017-12-01Bibliographically approved
Magnusson, K., Appelqvist, H., Cieslar-Pobuda, A., Wigenius, J., Karlsson, T., Los, M. J., . . . Nilsson, P. (2015). Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte. Cytometry Part A, 87(3), 262-272
Open this publication in new window or tab >>Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte
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2015 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 87, no 3, p. 262-272Article in journal (Refereed) Published
Abstract [en]

Molecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one-sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer-related biological and pathological processes.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
Keywords
Conjugated polyelectrolyte; Fibroblast; Fluorescence; Luminescent conjugated polythiophene; Melanoma; Photoinduced toxicity
National Category
Structural Biology Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-115887 (URN)10.1002/cyto.a.22627 (DOI)000349984200009 ()25605326 (PubMedID)2-s2.0-84923259526 (Scopus ID)
Available from: 2015-03-23 Created: 2015-03-23 Last updated: 2018-09-14
Kechagias, S., Dernroth, D. N., Blomgren, A., Hansson, T., Isaksson, A., Walther, L., . . . Nystrom, F. H. (2015). Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study.. Alcohol and Alcoholism, 50(4), 399-406
Open this publication in new window or tab >>Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study.
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2015 (English)In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 50, no 4, p. 399-406Article in journal (Refereed) Published
Abstract [en]

AIM: It is generally agreed that traditional alcohol biomarkers lack in sensitivity to detect hazardous alcohol consumption. The present study was undertaken to evaluate the ability of phosphatidylethanol (PEth) and traditional alcohol markers to detect moderate alcohol consumption and to distinguish between moderate alcohol consumption and abstinence.

METHODS: Forty-four subjects, 32 females and 12 males, were included in the study. They were randomized to alcohol abstention or to alcohol consumption. Female participants consumed 150 ml of red wine (equivalent to 16 g of alcohol) per 24 h and the male participants double the amount. The study lasted for 3 months. Blood samples were drawn at the start and at the end of the study period. Blood samples were analysed for PEth, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), γ-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

RESULTS: ROC curves for the various biochemical markers were plotted in order to assess their ability to discriminate between abstention and moderate daily consumption of alcohol. PEth and CDT were the only markers with AUROCs significantly higher than 0.5, and PEth was detected in all participants randomized to alcohol consumption.

CONCLUSION: PEth was the only marker that could detect moderate intake and the present results also indicate that PEth probably can distinguish moderate alcohol consumption from abstinence.

National Category
Substance Abuse
Identifiers
urn:nbn:se:liu:diva-119707 (URN)10.1093/alcalc/agv038 (DOI)000357867100005 ()25882743 (PubMedID)
Available from: 2015-06-24 Created: 2015-06-24 Last updated: 2017-12-04
Landberg, E., Åström, E., Kågedal, B. & Påhlsson, P. (2012). Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety. Clinica Chimica Acta, 414, 58-64
Open this publication in new window or tab >>Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety
2012 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 414, p. 58-64Article in journal (Refereed) Published
Abstract [en]

Background

Carbohydrate deficient transferrin (CDT) is used for detection of alcohol abuse and follow-up. High performance liquid chromatography (HPLC) of transferrin glycoforms is highly specific for identification of alcohol abuse, but unresolved disialo- and trisialotransferrin glycoforms sometimes makes interpretation difficult. The cause of this phenomenon is unknown, cannot be explained by genetic variants of transferrin, but seems to be associated with liver disease.

Methods

Nineteen serum samples showing di–tri bridging when analyzed by HPLC were collected. Transferrin was purified by affinity chromatography, and N-linked oligosaccharides were released enzymatically. The N-glycans were further analyzed by high performance anion-exchange chromatography with pulsed amperometric detection and MALDI-TOF mass spectrometry.

Results

The HPLC-analysis showed three different types of glycoform patterns. The N-glycans from fifteen samples showed patterns with increased number of triantennary structures containing one or two fucose residues. One sample contained an increased amount of triantennary glycans without fucose. Three samples showed a glycosylation pattern similar to normal transferrin.

Conclusions

The di–tri bridging phenomenon was associated with alterations in transferrin glycosylation in the majority of cases. Transferrin contained a higher extent of triantennary and often fucosylated N-linked oligosaccharides. These results may be important in future diagnostic approaches to liver diseases.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Transferrin, CDT, Di-tri bridging, Glycosylation, Liver disease
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-88368 (URN)10.1016/j.cca.2012.07.026 (DOI)000312685400014 ()
Note

Funding Agencies|Medical Research Council of Southeast Sweden||

Available from: 2013-04-03 Created: 2013-02-04 Last updated: 2017-12-06Bibliographically approved
Bellanti, F., Kågedal, B. & Della Pasqua, O. (2011). Do pharmacokinetic polymorphisms explain treatment failure in high-risk patients with neuroblastoma?. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 67, S87-S107
Open this publication in new window or tab >>Do pharmacokinetic polymorphisms explain treatment failure in high-risk patients with neuroblastoma?
2011 (English)In: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, ISSN 0031-6970, Vol. 67, p. S87-S107Article, review/survey (Refereed) Published
Abstract [en]

Purpose Neuroblastoma is the most common extracranial solid tumour in childhood. It accounts for 15% of all paediatric oncology deaths. In the last few decades, improvement in treatment outcome for high-risk patients has not occurred, with an overall survival rate andlt;30-40%. Many reasons may account for such a low survival rate. The aim of this review is to evaluate whether pharmacogenetic factors can explain treatment failure in neuroblastoma. Methods A literature search based on PubMeds database Medical Subject Headings (MeSH) was performed to retrieve all pertinent publications on current treatment options and new classes of drugs under investigation. One hundred and fifty-eight articles wer reviewed, and relevant data were extracted and summarised. Results and conclusions Few of the large number of polymorphisms identified thus far showed an effect on pharmacokinetics that could be considered clinically relevant. Despite their clinical relevance, none of the single nucleotide polymorphisms (SNPs) investigated can explain treatment failure. These findings seem to reflect the clinical context in which anti-tumour drugs are used, i.e. in combination with multi-modal therapy. In addition, many pharmacogenetic studies did not assess (differences in) drug exposure, which could contribute to explaining pharmacogenctic associations. Furthermore, it remains unclear whether the significant activity of new drugs on different neuroblastoma cell lines translates into clinical efficacy, irrespective of resistance or myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) amplification. Elucidation of the clinical role of pharmacogenetic factors in the treatment of neuroblastoma demands an integrated pharmacokinetic pharmacodynamic approach to the analysis of treatment response data.

Place, publisher, year, edition, pages
Springer Science Business Media, 2011
Keywords
Neuroblastoma, Pharmacogenetics, Pharmacokinetics, Cytotoxic drugs, Modelling andamp, simulation, PKPD modelling
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68823 (URN)10.1007/s00228-010-0966-3 (DOI)000290738000011 ()
Available from: 2011-06-08 Created: 2011-06-08 Last updated: 2014-10-22
Fyrberg, A., Peterson, C., Kågedal, B. & Lotfi, K. (2011). Induction of fetal hemoglobin and ABCB1 gene expression in 9-β-D-arabinofuranosylguanine-resistant MOLT-4 cells. Cancer Chemotherapy and Pharmacology, 68(3), 583-591
Open this publication in new window or tab >>Induction of fetal hemoglobin and ABCB1 gene expression in 9-β-D-arabinofuranosylguanine-resistant MOLT-4 cells
2011 (English)In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 68, no 3, p. 583-591Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To characterize resistance mechanisms to the nucleoside analog 9-β-D-arabinofuranosylguanine (AraG) in the T-cell acute lymphoblastic leukemia cell line MOLT-4 and its AraG-resistant variant.

METHODS: A gene expression microarray analysis was performed, as well as gene expression and enzyme activity measurements of key enzymes in the activation of AraG. Cytotoxicity of AraG and cross-resistance to other compounds were evaluated using a standard cytotoxicity assay.

RESULTS: Gene expression microarray analysis revealed that fetal hemoglobin genes and the multidrug resistance ABCB1 gene, encoding the drug efflux pump P-gp, were the most highly upregulated genes in the resistant cells, while genes traditionally associated with nucleoside analog resistance were not. Fetal hemoglobin and ABCB1 induction can be due to global DNA hypomethylation. This phenomenon was studied using AraG during a period of 4 weeks in MOLT-4 cells and the lung adenocarcinoma cell line A549, leading to up-regulation of hemoglobin gamma and ABCB1 as well as DNA hypomethylation. Inhibiting P-gp in the AraG-resistant MOLT-4 cells led to decreased proliferation, reduced hemoglobin expression, and highly induced ABCB1 expression.

CONCLUSIONS: We show that AraG can cause hypomethylation of DNA and induce the expression of the fetal hemoglobin gamma gene and the ABCB1 gene. We speculate that the induction of ABCB1/P-gp may occur in order to help with excretion of hemoglobin degradation products that would otherwise be toxic to the cells, and we present data supporting our theory that P-gp may be linked to the induction of hemoglobin.

Place, publisher, year, edition, pages
Springer, 2011
Keywords
9-β-D-arabinofuranosylguanine - Fetal hemoglobin - P-glycoprotein - Microarray - Hypomethylation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-63246 (URN)10.1007/s00280-010-1524-5 (DOI)000294345400004 ()21110023 (PubMedID)
Note
Funding Agencies|Swedish Cancer Foundation||Swedish Childhood Cancer Foundation||Signe and Olof Wallentin Foundation||Capios Research Foundation||County Council of Ostergotland||Swedish Fund for Research without Animal Experiments||Available from: 2010-12-13 Created: 2010-12-13 Last updated: 2017-12-11
Andersson, H., Steel, D., Asp, J., Dahlenborg, K., Jonsson, M., Jeppsson, A., . . . Mandenius, C.-F. (2010). Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells. JOURNAL OF BIOTECHNOLOGY, 150(1), 175-181
Open this publication in new window or tab >>Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells
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2010 (English)In: JOURNAL OF BIOTECHNOLOGY, ISSN 0168-1656, Vol. 150, no 1, p. 175-181Article in journal (Refereed) Published
Abstract [en]

Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2010
Keywords
In vitro toxicity testing, hESC-derived cardiomyocytes, Doxorubicin, Biosensors, Surface plasmon resonance. SPR
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-62153 (URN)10.1016/j.jbiotec.2010.06.023 (DOI)000283693600025 ()
Available from: 2010-11-19 Created: 2010-11-19 Last updated: 2019-01-22
Kågedal, B. (2010). Biologiska variabler i blod och urin - könsskillnader av stor betydelse för sjukdomsdiagnostik (1ed.). In: Barbro Wijma, Goldina Smirthwaite, Katarina Swanberg (Ed.), Genus och kön inom medicin- och vårdutbildningar (pp. 497-516). Lund: Studentlitteratur AB
Open this publication in new window or tab >>Biologiska variabler i blod och urin - könsskillnader av stor betydelse för sjukdomsdiagnostik
2010 (Swedish)In: Genus och kön inom medicin- och vårdutbildningar / [ed] Barbro Wijma, Goldina Smirthwaite, Katarina Swanberg, Lund: Studentlitteratur AB , 2010, 1, p. 497-516Chapter in book (Other academic)
Abstract [sv]

Kvinnor och män är delvis lika, delvis olika. Det innebär att kvinnor och män både har behov av likadan behandling och av behandling som är anpassad till det egna könets förutsättningar. Denna antologi belyser kvinnors och mäns förutsättningar och behov inom en rad olika medicinska områden och tar upp både biologiska och sociala faktorer som påverkar hälsa och behandling. Den behandlar även den roll som kön spelar inom vårdens arbetsliv samt hur köns- och genusperspektiv kan integreras inom olika typer av medicin- och vårdutbildningar. Ett av bokens teman är våld, kränkningar och diskriminering, och inom ramen för detta behandlas några av de olika maktordningar som kommer till uttryck vid behandlingar inom hälso- och sjukvården. Antologin har en stor spännvidd när det gäller ämnen och författare. Förhoppningsvis ska den bredd som antologin uppvisar, leda fram till frågeställningar där läsaren utmanar sina förgivettaganden inom både genusvetenskap och mer traditionell medicin samt väcka nya frågor: Om könet snarare ses som en konstruktion än en fysisk realitet - kan då kvinnor lika gärna äta mediciner som är utprovade på män och opereras med metoder och verktyg anpassade till mäns fysiologi? Å andra sidan - hur objektiv är den naturvetenskapligt inriktade medicinska forskningen egentligen om man börjar granska den utifrån frågeställningar om perspektivval och genus? Antologin vänder sig till lärare på utbildningar inom medicin, hälsa och vård. Andra målgrupper är studenter på sådana utbildningar, vårdpersonal och en intresserad allmänhet.

Place, publisher, year, edition, pages
Lund: Studentlitteratur AB, 2010 Edition: 1
Keywords
Referensvärden, referensintervall
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-63977 (URN)978-91-44-05950-1 (ISBN)91-440-595-07 (ISBN)
Available from: 2011-01-10 Created: 2011-01-10 Last updated: 2013-04-18Bibliographically approved
Zdolsek, J., Kågedal, B., Lisander, B. & Hahn, R. (2010). Glomerular filtration rate is increased in burn patients. Burns, 36(8), 1271-1276
Open this publication in new window or tab >>Glomerular filtration rate is increased in burn patients
2010 (English)In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 36, no 8, p. 1271-1276Article in journal (Refereed) Published
Abstract [en]

Urinary output a key parameter guiding fluid resuscitation in burn trauma is an inadequate measure of renal function In this study the clearance of iohexol (CL) was used to follow the glomerular filtration rate during the first week after burn Nineteen adults with major burns received an intravenous bolus injection of iohexol every other day Plasma concentration of iohexol was measured over 4 h and CL was calculated by a one compartment kinetic model The results were compared to the CL as obtained by a two compartment model and also to the CL measured in 10 healthy controls The results show that CL values for burn patients were high The first day after burn median CL was 155 mL/min/1 73 m(2) (range 46-237) which exceeded that for the controls (mean 117 mL/min/1 73 m(2) P less than 0 01) However on day 7 the CL approached the expected baseline (mean 122 mL/min/1 73 m(2)) CL was 10% lower when calculated from two compartment kinetics and a correction factor of 0 9 was applied to all results obtained by the one compartment calculations to give results comparable to those from the two compartment kinetics In conclusion CL is increased early after burn The mechanism is unclear but it parallels the period of vascular dysfunction and increased cardiac output

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2010
Keywords
Burns; Iohexol clearance; Kidney function; Glomerular filtration rate; Organ dysfunction; Renal clearance; Resuscitation
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:liu:diva-63966 (URN)10.1016/j.burns.2010.03.012 (DOI)000284571000018 ()20547000 (PubMedID)
Available from: 2011-01-10 Created: 2011-01-10 Last updated: 2017-12-11Bibliographically approved
Andersson, H., Kågedal, B. & Mandenius, C.-F. (2010). Monitoring of troponin release from cardiomyocytes during exposure to toxic substances using surface plasmon resonance biosensing. ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 398(3), 1395-1402
Open this publication in new window or tab >>Monitoring of troponin release from cardiomyocytes during exposure to toxic substances using surface plasmon resonance biosensing
2010 (English)In: ANALYTICAL AND BIOANALYTICAL CHEMISTRY, ISSN 1618-2642, Vol. 398, no 3, p. 1395-1402Article in journal (Refereed) Published
Abstract [en]

Troponin T (TnT) is a useful biomarker for studying drug-induced toxicity effects on cardiac cells. We describe how a surface plasmon resonance (SPR) biosensor was applied to monitor the release of TnT from active HL-1 cardiomyocytes in vitro when exposed to cardiotoxic substances. Two monoclonal human TnT antibodies were compared in the SPR immunosensor to analyse the TnT release. The detection limit of TnT was determined to be 30 ng/ml in a direct assay set-up and to be 10 ng/ml in a sandwich assay format. Exposure of the cardiomyocytes to doxorubicin, troglitazone, quinidine and cobalt chloride for periods of 6 and 24 h gave significant SPR responses, whereas substances with low toxicity showed insignificant effects (ascorbic acid, methotrexate). The SPR results were verified with a validated immunochemiluminescence method which showed a correlation of r(2)=0.790.

Place, publisher, year, edition, pages
Springer Science Business Media, 2010
Keywords
Surface plasmon resonance, Troponin T, Cardiotoxicity, In vitro toxicity, HL-1 cardiomyocytes, Cytotoxicity screening
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-59731 (URN)10.1007/s00216-010-4041-9 (DOI)000281670400026 ()
Note

The original publication is available at www.springerlink.com: Henrik Andersson, Bertil Kågedal and Carl-Fredrik Mandenius, Monitoring of troponin release from cardiomyocytes during exposure to toxic substances using surface plasmon resonance biosensing, 2010, ANALYTICAL AND BIOANALYTICAL CHEMISTRY, (398), 3, 1395-1402. http://dx.doi.org/10.1007/s00216-010-4041-9 Copyright: Springer Science Business Media http://www.springerlink.com/

Available from: 2010-09-24 Created: 2010-09-24 Last updated: 2019-01-22
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