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  • 1.
    Alfredsson, Joakim
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Swahn, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Gustafsson, Kerstin
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Janzon, Magnus
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Logander, Elisabeth
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Lindahl, Tomas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction.2019Ingår i: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 30, nr 5, s. 572-578Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a large inter-individual variation in response to clopidogrel treatment, and previous studies have indicated higher risk of thrombotic events in those with high residual platelet reactivity (HPR). Less is known about individual variation over time. The aim of this prospective cohort study was to investigate intra-individual variation in platelet reactivity. Platelet aggregation in whole blood was assessed in 77 patients, at 3 days, 8 days and 6 months after admission for acute myocardial infarction and loading dose of clopidogrel. All patients were treated with aspirin and clopidogrel through 6-month follow-up. We found a significant increase in median ADP-stimulated aggregation from third to eighth day (195 vs. 250 AU*min, p-value = 0.001) but not from day 8 to 6 months (250 vs. 223 AU*min, p-value = 0.666). There was no significant change in the overall rate of HPR (15.6% vs 20.8%, p-value 0.503) or low platelet reactivity (LPR) (37.7% vs 33.8%, p-value = 0.609) from day 8 to 6-month follow-up. In contrast, more than one in four changed HPR status, 15.6% from non-HPR to HPR and 10.4% HPR to non-HPR. A shift in LPR status appeared even more frequent, occurring in about one of three patients. In spite of similar median aggregation and rate of HPR during 6-month follow-up, about one in four of the patients changed HPR status and one in three changed LPR status. This may be important information for a concept of risk stratification based on a single aggregation value early after an acute coronary syndromes.

  • 2.
    Apostolou, Eirini
    et al.
    Univ Athens, Greece; Univ Athens, Greece.
    Moustardas, Petros
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Acad Athens, Greece.
    Iwawaki, Takao
    Kanazawa Med Univ, Japan.
    Tzioufas, Athanasios G.
    Univ Athens, Greece; Univ Athens, Greece.
    Spyrou, Ioannis
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Ablation of the Chaperone Protein ERdj5 Results in a Sjogrens Syndrome-Like Phenotype in Mice, Consistent With an Upregulated Unfolded Protein Response in Human Patients2019Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, artikel-id 506Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Sjogrens syndrome (SS) is a chronic autoimmune disorder that affects mainly the exocrine glands. Endoplasmic reticulum (ER) stress proteins have been suggested to participate in autoimmune and inflammatory responses, either acting as autoantigens, or by modulating factors of inflammation. The chaperone protein ERdj5 is an ER-resident disulfide reductase, required for the translocation of misfolded proteins during ER-associated protein degradation. In this study we investigated the role of ERdj5 in the salivary glands (SGs), in association with inflammation and autoimmunity. Methods: In situ expression of ERdj5 and XBP1 activation were studied immunohistochemically in minor SG tissues from primary SS patients and non-SS sicca-complaining controls. We used the mouse model of ERdj5 ablation and characterized its features: Histopathological, serological (antinuclear antibodies and cytokine levels), and functional (saliva flow rate). Results: ERdj5 was highly expressed in the minor SGs of SS patients, with stain intensity correlated to inflammatory lesion severity and anti-SSA/Ro positivity. Moreover, SS patients demonstrated higher XBP1 activation within the SGs. Remarkably, ablation of ERdj5 in mice conveyed many of the cardinal features of SS, like spontaneous inflammation in SGs with infiltrating T and B lymphocytes, distinct cytokine signature, excessive cell death, reduced saliva flow, and production of anti-SSA/Ro and anti-SSB/La autoantibodies. Notably, these features were more pronounced in female mice. Conclusions: Our findings suggest a critical connection between the function of the ER chaperone protein ERdj5 and autoimmune inflammatory responses in the SGs and provide evidence for a new, potent animal model of SS.

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  • 3.
    Azharuddin, Mohammad
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Roberg, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken.
    Dhara, Ashis Kumar
    Natl Inst Technol Durgapur, India.
    Jain, Mayur Vilas
    Lund Univ, Sweden.
    D´arcy, Padraig
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Slater, Nigel K. H.
    Univ Cambridge, England.
    Patra, Hirak Kumar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Cambridge, England.
    Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 20066Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-imensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.

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  • 4.
    Azharuddin, Mohammad
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Zhu, Geyunjian H.
    Univ Cambridge, England.
    Das, Debapratim
    Indian Inst Technol Guwahati, India.
    Ozgur, Erdogan
    Hacettepe Univ, Turkey.
    Uzun, Lokman
    Hacettepe Univ, Turkey.
    Turner, Anthony P. F.
    Cranfield Univ, England.
    Patra, Hirak Kumar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Cambridge, England.
    A repertoire of biomedical applications of noble metal nanoparticles2019Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 55, nr 49, s. 6964-6996Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Noble metals comprise any of several metallic chemical elements that are outstandingly resistant to corrosion and oxidation, even at elevated temperatures. This group is not strictly defined, but the tentative list includes ruthenium, rhodium, palladium, silver, osmium, iridium, platinum and gold, in order of atomic number. The emerging properties of noble metal nanoparticles are attracting huge interest from the translational scientific community and have led to an unprecedented expansion of research and exploration of applications in biotechnology and biomedicine. Noble metal nanomaterials can be synthesised both by top-down and bottom up approaches, as well as via organism-assisted routes, and subsequently modified appropriately for the field of use. Nanoscale analogues of gold, silver, platinum, and palladium in particular, have gained primary importance owing to their excellent intrinsic properties and diversity of applications; they offer unique functional attributes, which are quite unlike the bulk material. Modulation of noble metal nanoparticles in terms of size, shape and surface functionalisation has endowed them with unusual capabilities and manipulation at the chemical level, which can lead to changes in their electrical, chemical, optical, spectral and other intrinsic properties. Such flexibility in multi-functionalisation delivers Ockhams razor to applied biomedical science. In this feature article, we highlight recent advances in the adaptation of noble metal nanomaterials and their biomedical applications in therapeutics, diagnostics and sensing.

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  • 5.
    Balla, Hajnal Zsuzsanna
    et al.
    Orebro Univ, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Ström, Jakob
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Orebro Univ, Sweden.
    Evaluation of commercial, wireless dermal thermometers for surrogate measurements of core temperature2019Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, nr 1-2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Extensive research has been devoted to developing methods for assessing core body temperature, and to determine which method is most accurate. A number of wireless dermal thermometers for home use are presently available, but their relation to core body temperature and suitability for use in clinical research has hitherto not been assessed. The current study aimed to evaluate such thermometers by comparing them to the results of a rectal thermometer. Four wireless dermal thermometers for home use (FeverSmart, iThermonitor, Quest Temp Sitter, and Thermochron iButton) were applied to 15 patients during 24 h, and rectal temperature was measured at four occasions. Pearson correlation revealed moderate correlation for the Feversmart (r = 0.75), iThermonitor (r = 0.79), and Thermochron iButton (r = 0.71) systems. The Quest Temp Sitter system malfunctioned repeatedly, and the correlation (r = 0.29) for this method should therefore be assessed with caution. All dermal thermometers rendered lower average temperatures than Terumo c405 (Feversmart -0.70 +/- 0.65 degrees C; iThermonitor -0.77 +/- 0.53 degrees C, Quest Temp Sitter -1.18 +/- 0.66 degrees C, and Thermochron iButton -0.87 +/- 0.65 degrees C). Sensitivity of the dermal thermometers for detecting core temperatures amp;gt;= 38.0 degrees C was low, ranging from 0.33 to 0.6, but improved to 0.60 to 0.80 after adjusting temperatures by the methods average deviation from rectal temperature. The results from the dermal thermometers tested here showed an insufficient correlation to core temperature to be used for core temperature monitoring in clinical research and practice. Unfortunately, other options for non-invasive temperature measurements are few. The two thermometers with the least unsatisfactory performance profile in our evaluations were the Feversmart and iThermonitor systems.

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  • 6.
    Bandyopadhyay, Souvik K.
    et al.
    GlaxoSmithKline Asia Pvt. Ltd., Bangalore, India.
    Azharuddin, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Dasgupta, Anjan K.
    Department of Biochemistry, University of Calcutta, Kolkata, India.
    Ganguli, Bhaswati
    Department of Statistics, University of Calcutta, Kolkata, India.
    SenRoy, Sugata
    Department of Statistics, University of Calcutta, Kolkata, India.
    Patra, Hirak Kumar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Wolfson College, University of Cambridge, Cambridge, United Kingdom; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
    Deb, Suryyani
    Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, Kolkata, India.
    Probing ADP Induced Aggregation Kinetics During Platelet-Nanoparticle Interactions: Functional Dynamics Analysis to Rationalize Safety and Benefits2019Ingår i: Frontiers in Bioengineering and Biotechnology, E-ISSN 2296-4185, Vol. 7, s. 163-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Platelets, one of the most sensitive blood cells, can be activated by a range of external and internal stimuli including physical, chemical, physiological, and/or non-physiological agents. Platelets need to respond promptly during injury to maintain blood hemostasis. The time profile of platelet aggregation is very complex, especially in the presence of the agonist adenosine 5′-diphosphate (ADP), and it is difficult to probe such complexity using traditional linear dose response models. In the present study, we explored functional analysis techniques to characterize the pattern of platelet aggregation over time in response to nanoparticle induced perturbations. This has obviated the need to represent the pattern of aggregation by a single summary measure and allowed us to treat the entire aggregation profile over time, as the response. The modeling was performed in a flexible manner, without any imposition of shape restrictions on the curve, allowing smooth platelet aggregation over time. The use of a probabilistic framework not only allowed statistical prediction and inference of the aggregation signatures, but also provided a novel method for the estimation of higher order derivatives of the curve, thereby allowing plausible estimation of the extent and rate of platelet aggregation kinetics over time. In the present study, we focused on the estimated first derivative of the curve, obtained from the platelet optical aggregometric profile over time and used it to discern the underlying kinetics as well as to study the effects of ADP dosage and perturbation with gold nanoparticles. In addition, our method allowed the quantification of the extent of inter-individual signature variations. Our findings indicated several hidden features and showed a mixture of zero and first order kinetics interrupted by a metastable zero order ADP dose dependent process. In addition, we showed that the two first order kinetic constants were ADP dependent. However, we were able to perturb the overall kinetic pattern using gold nanoparticles, which resulted in autocatalytic aggregation with a higher aggregate mass and which facilitated the aggregation rate.

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  • 7.
    Boknäs, Niklas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
    Macwan, Ankit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Södergren, Anna L.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Ramström, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Örebro University, School of Medical Sciences, Örebro, Sweden.
    Platelet function testing at low platelet counts: When can you trust your analysis?2019Ingår i: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, ISSN 2475-0379, Vol. 3, nr 2, s. 285-290Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Although flow cytometry is often brought forward as a preferable method in the setting of thrombocytopenia, the relative effects of low sample counts on results from flow cytometry-based platelet function testing (FC-PFT) in comparison with light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) has not been reported. Objectives: To compare the effects of different sample platelet counts (10, 50, 100, and 200x10(9)L(-1)) on platelet activation measured with FC-PFT, LTA, and MEA using the same anticoagulant and agonist concentrations as for the commercial MEA test. Methods: Platelets were stimulated with two commonly used platelet agonists (ADP [6.5 mu molL(-1)] and PAR1-AP [TRAP, 32 mu molL(-1)]). The specified sample platelet counts were obtained by combining platelet-rich and platelet poor hirudinized plasma in different proportions with or without red blood cells. Results: For FC, P-selectin exposure and PAC-1 binding was reduced at 10x10(9)L(-1) after stimulation with PAR1-AP (by approximately 20% and 50%, respectively), but remained relatively unchanged when ADP was used as agonist (n=9). The platelet count-dependent effects observed with PAR1-AP were eliminated when samples were pre-incubated with apyrase, implying that reduced purinergic signaling was the main underlying factor (n=5). Both aggregometry-based PFTs showed a 50% reduction at 50x10(9)L(-1) and more than 80% reduction at 10x10(9)L(-1), irrespective of agonist used (n=7). Conclusions: Although FC-PFT is generally preferable to aggregometry-based PFTs in situations with low sample platelet counts, a careful optimization of experimental parameters is still required in order to eliminate platelet count-related effects.

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  • 8.
    Boud, David
    et al.
    Deakin University, Geelong, Australia / University of Technology, Sydney, Australia / Middlesex University, London, UK.
    Nyström, Sofia
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Pedagogik och vuxnas lärande. Linköpings universitet, Utbildningsvetenskap. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Abrandt Dahlgren, Madeleine
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Gustavsson, Johanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Kelly, Michelle
    Curtin University, Perth, Australia.
    O’Keeffe, Dara
    Royal College of Surgeons in Ireland, Dublin, Ireland.
    Learning through observation2019Ingår i: Interprofessional Simulation in Health Care: Materiality, Embodiment, Interaction / [ed] Madeleine Abrandt Dahlgren, Hans Rystedt, Li Felländer-Tsai & Sofia Nyström, Cham: Springer, 2019, s. 115-137Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    This chapter has a particular focus on the observers’ role in simulation-based learning activities. Simulation-based learning is often organised so that participants rotates between active participation in the scenario and participation as observers. The research examples provided show that the conditions for learning are related to the locations where and the ways the observers are situated, and to how the instructions to the observers are formulated. Arguments are put forward that the observers’ role in simulation has unexploited potential for developing skills of noticing.

  • 9.
    Chasapis, Christos T.
    et al.
    Hellas Forth, Greece.
    Makridakis, Manousos
    Acad Athens BRFAA, Greece.
    Damdimopoulos, Anastassios E.
    Karolinska Inst, Sweden.
    Zoidakis, Jerome
    Acad Athens BRFAA, Greece.
    Lygirou, Vasiliki
    Acad Athens BRFAA, Greece.
    Mavroidis, Manolis
    Acad Athens BRFAA, Greece.
    Vlahou, Antonia
    Acad Athens BRFAA, Greece.
    Miranda-Vizuete, Antonio
    Univ Seville, Spain.
    Spyrou, Giannis
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Vlamis-Gardikas, Alexios
    Univ Patras, Greece.
    Implications of the mitochondrial interactome of mammalian thioredoxin 2 for normal cellular function and disease2019Ingår i: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 137, s. 59-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Multiple thioredoxin isoforms exist in all living cells. To explore the possible functions of mammalian mitochondrial thioredoxin 2 (Trx2), an interactome of mouse Trx2 was initially created using (i) a monothiol mouse Trx2 species for capturing protein partners from different organs and (ii) yeast two hybrid screens on human liver and rat brain cDNA libraries. The resulting interactome consisted of 195 proteins (Trx2 included) plus the mitochondrial 16S RNA. 48 of these proteins were classified as mitochondrial (MitoCarta2.0 human inventory). In a second step, the mouse interactome was combined with the current four-membered mitochondrial sub-network of human Trx2 (BioGRID) to give a 53-membered human Trx2 mitochondrial interactome (52 interactor proteins plus the mitochondrial 16S RNA). Although thioredoxins are thiol-employing disulfide oxidoreductases, approximately half of the detected interactions were not due to covalent disulfide bonds. This finding reinstates the extended role of thioredoxins as moderators of protein function by specific non-covalent, protein-protein interactions. Analysis of the mitochondrial interactome suggested that human Trx2 was involved potentially in mitochondrial integrity, formation of iron sulfur clusters, detoxification of aldehydes, mitoribosome assembly and protein synthesis, protein folding, ADP ribosylation, amino acid and lipid metabolism, glycolysis, the TCA cycle and the electron transport chain. The oxidoreductase functions of Trx2 were verified by its detected interactions with mitochondrial peroxiredoxins and methionine sulfoxide reductase. Parkinsons disease, triosephosphate isomerase deficiency, combined oxidative phosphorylation deficiency, and lactate dehydrogenase b deficiency are some of the diseases where the proposed mitochondrial network of Trx2 may be implicated.

  • 10.
    Deb, Suryyani
    et al.
    Maulana Abul Kazam Azad Univ Technol, India.
    Boknäs, Niklas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Sjöström, Clara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Tharmakulanathan, Anjana
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Lotfi, Kourosh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Ramström, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Orebro Univ, Sweden.
    Varying effects of tyrosine kinase inhibitors on platelet function-A need for individualized CML treatment to minimize the risk for hemostatic and thrombotic complications?2020Ingår i: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 9, nr 1, s. 313-323Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Since their introduction, tyrosine kinase inhibitors (TKIs, eg, imatinib, nilotinib, dasatinib, bosutinib, ponatinib) have revolutionized the treatment of chronic myeloid leukemia (CML). However, long-term treatment with TKIs is associated with serious adverse events including both bleeding and thromboembolism. Experimental studies have shown that TKIs can cause platelet dysfunction. Herein, we present the first side-by-side investigation comparing the effects of currently used TKIs on platelet function and thrombin generation when used in clinically relevant concentrations. A flow cytometry multiparameter protocol was used to study a range of significant platelet activation events (fibrinogen receptor activation, alpha granule, and lysosomal exocytosis, procoagulant membrane exposure, and mitochondrial permeability changes). In addition, thrombin generation was measured in the presence of TKIs to assess the effects on global hemostasis. Results show that dasatinib generally inhibited platelet function, while bosutinib, nilotinib, and ponatinib showed less consistent effects. In addition to these general trends for each TKI, we observed a large degree of interindividual variability in the effects of the different TKIs. Interindividual variation was also observed when blood from CML patients was studied ex vivo with whole blood platelet aggregometry, free oscillation rheometry (FOR), and flow cytometry. Based on the donor responses in the side-by-side TKI study, a TKI sensitivity map was developed. We propose that such a sensitivity map could potentially become a valuable tool to help in decision-making regarding the choice of suitable TKIs for a CML patient with a history of bleeding or atherothrombotic disease.

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  • 11.
    Gawria, Ghassaan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Tillmar, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Landberg, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    A comparison of stability of chemical analytes in plasma from the BD Vacutainer (R) Barricor (TM) tube with mechanical separator versus tubes containing gel separator2020Ingår i: Journal of clinical laboratory analysis (Print), ISSN 0887-8013, E-ISSN 1098-2825, Vol. 34, nr 2, artikel-id e23060Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is a need of prolonged stability of certain chemical analytes in lithium heparin tubes with separators. A new tube with a mechanical separator has recently been launched (Barricor (TM)), which according to the manufacturer may have these benefits. The aim of this study was to evaluate stability performance of this tube in comparison with plasma gel tubes under clinically realistic circumstances. Methods: Blood was collected in tubes containing lithium heparin with different separators; gel separator (Vacutainer (R) PST (TM), Becton Dickinson and Vacuette (R), Greiner bio-one) and mechanical separator (Vacutainer (R) Barricor (TM), Becton Dickinson). All tubes had an aspiration volume of 3 mL and were centrifuged at similar time and force. Tubes were transported manually or by car. Seven analytes from 122 patients were analyzed after 3 to 80 hours by Cobas c701 (Roche). Results The Barricor (TM) tube showed increased stability of phosphate and potassium and similar stability of aspartate aminotransferase, glucose, homocysteine, lactate dehydrogenase, and magnesium compared with gel tubes. Maximal allowable bias for phosphate was exceeded after 68 hours for Barricor (TM) tubes compared with 29 or 35 hours for gel tubes and for potassium after 40 hours for Barricor (TM) tubes vs 9 or 12 hours for gel tubes. Transportation did not affect stability. Hemolysis index was slightly lower in Barricor tubes than in gel tubes (P = .01). Conclusion Implementing the new Barricor (TM) tube will improve stability of potassium and phosphate in plasma. Blood sampling facilities far from the laboratory may benefit from using these tubes, thus diminishing preanalytical errors.

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  • 12.
    Heenkenda, Menikae Kanchena
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Malmström, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Närvårdskliniken.
    Lysiak, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Mudaisi, Munila
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Bratthall, Charlotte
    Dist Hosp, Sweden.
    Milos, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Strandeus, Michael
    Ryhov Hosp, Sweden.
    Åkesson, Lisa
    Linköpings universitet, Institutionen för tema. Linköpings universitet, Filosofiska fakulteten.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Uppugunduri, Srinivas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Osman, Abdimajid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Assessment of genetic and non-genetic risk factors for venous thromboembolism in glioblastoma - The predictive significance of B blood group2019Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 183, s. 136-142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Venous thromboembolism (VTE) is a common problem among patients with glioblastoma multi-forme (GBM) and with some other cancers. Here, we evaluated genetic and non-genetic potential risk factors for VTE among GBM patients. Materials and methods: A cohort of 139 patients treated with concomitant radiotherapy and temozolomide were included in the study. Next generation sequencing and genotyping approaches were applied to assess genetic risk factors in the haemostatic system. Clinical data including surgery, reoperation as well as blood group and patient information such as age and gender were available from patient records. Logistic regression analysis was performed to asses VTE risk. Results: In the study 47 patients (34%) were diagnosed for VTE during the course of their disease. When genetic and non-genetic potential risk factors were evaluated, only B blood group was found to be significantly associated with VTE incidence (odds ratio [OR] = 6.91; confidence interval [CI] = 2.19-24.14; P = 0.001). In contrast, A and O blood groups did not correlate with VTE risk. Frontal lobe tumor location also seemed to slightly increase VTE risk compared to other brain sites (OR = 3.14; CI = 1.1-10.7) although the significance level was at borderline (P = 0.05). Current study identified B blood group as the component in non-O blood groups that is responsible for increased VTE risk. Conclusion: In conclusion, these results suggest for the first time that B blood group is predictive for VTE incidence among patients with glioblastoma, information that may be potentially valuable when selecting GBM patients who are at risk for VTE for anticoagulant prophylaxis.

    Publikationen är tillgänglig i fulltext från 2020-10-22 14:11
  • 13.
    Hopwood, Nick
    et al.
    University of Technology Sydney, Sydney, Australia / University of StellenboschStellenboschSouth Africa.
    Ahn, Song-ee
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Pedagogik och vuxnas lärande. Linköpings universitet, Utbildningsvetenskap.
    Rimpiläinen, Sanna
    University of StrathclydeGlasgowScotland.
    Dahlberg, Johanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Nyström, Sofia
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Pedagogik och vuxnas lärande. Linköpings universitet, Utbildningsvetenskap. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Johnson, Ericka
    Linköpings universitet, Institutionen för tema, Tema Genus. Linköpings universitet, Filosofiska fakulteten.
    Doing interprofessional simulation: Bodily enactments in interprofessional simulation2019Ingår i: Interprofessional simulation in health care: Materiality, embodiment, interaction / [ed] Madeleine Abrandt Dahlgren, Hans Rystedt, Li Felländer-Tsai and Sofia Nyström, Cham, Schweiz: Springer, 2019, 1, s. 91-113Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    This chapter illustrate how the social and material arrangements for interprofessional simulation produces different conditions for learning. The first section focuses on the emerging medical knowing, affective knowing and communicative knowing in the socio-material arrangements of three locations involved in the simulation, i.e. the simulation room, the observation room and the reflection room, during the course of events in the scenario. The second section focuses on emerging rhythms of collaboration. Different ways of relating to the manikin as a technical, medical and human body, and the relevance of these findings for simulation pedagogy are described.

  • 14.
    Jackmann, Natalja
    et al.
    Univ Childrens Hosp, Sweden.
    Makitie, Outi
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Harila-Saari, Arja
    Univ Childrens Hosp, Sweden.
    Gustafsson, Jan
    Univ Childrens Hosp, Sweden.
    Dernroth, Dzeneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Frisk, Per
    Univ Childrens Hosp, Sweden.
    Vitamin D status in children with leukemia, its predictors, and association with outcome2020Ingår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, artikel-id e28163Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Children and adolescents with leukemia are potentially at high risk of vitamin D inadequacy, which may have clinical relevance for skeletal morbidity, infections, and cancer outcome. This study aimed to evaluate vitamin D status at the time of diagnosis to investigate its predictors and association with overall survival in children with leukemia. Procedure We included all 295 children and adolescents diagnosed with leukemia at our institution between 1990 and 2016 who had available serum sample from the time of diagnosis. We analyzed serum 25-hydroxyvitamin D and parathyroid hormone levels and correlated them with clinical data. Results The 25-hydroxyvitamin D level was deficient (amp;lt; 25 nmol/L), insufficient (25-50 nmol/L), sufficient (50-75 nmol/L), and optimal (amp;gt; 75 nmol/L) in 6.4%, 26.8%, 39.7%, and 27.1% of the children, respectively. Older age and a more recent time of sampling (calendar year) predicted lower 25-hydroxyvitamin D level. In preschool children (age amp;lt;= 6 years), lower 25-hydroxyvitamin D level was also associated with acute myeloid leukemia, and a 25-hydroxyvitamin D level amp;lt; 50 nmol/L was associated with inferior overall survival. In school-aged children (age amp;gt; 6 years), the 25-hydroxyvitamin D level showed significant seasonal variation. Conclusion It remains unclear whether vitamin D supplementation in pediatric leukemia patients will improve outcome.

  • 15.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    An experimental study of methods for the analysis of variance components in the inference of laboratory information2020Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurement uncertainty (MU) can be estimated and calculated by different procedures, representing different aspects and intended use. It is appropriate to distinguish between uncertainty determined under repeatability and reproducibility conditions, and to distinguish causes of variation using analysis of variance components. The intra-laboratory MU is frequently determined by repeated measurements of control material(s) of one or several concentrations during a prolonged period of time. We demonstrate, based on experimental results, how such results can be used to identify the repeatability, pure reproducibility and intra-laboratory variance as the sum of the two. Native patient material was used to establish repeatability using the Dahlberg formula for random differences between measurements and an expanded Dahlberg formula if a non-random difference, e.g. bias, was expected. Repeatability and reproducibility have different clinical relevance in intensive care compared to monitoring treatment of chronic diseases, comparison with reference intervals or screening.

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  • 16.
    Kristoffersen, Laila
    et al.
    Department of Neonatology, St. Olavs University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Støen, Ragnhild
    Department of Neonatology, St. Olavs University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Bergseng, Håkon
    Department of Neonatology, St. Olavs University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Follestad, Turid
    Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
    Theodorsson, Elvar
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Vederhus, Bente
    Department of Pediatrics, Haukeland University Hospital, Bergen, Norway; Faculty of Health and Social Science, Western Norway University of Applied Sciences, Bergen, Norway.
    Adde, Lars
    Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Clinic of Clinical Services, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
    Austeng, Dordi
    Department of Neuromedicine and Movement Science (INB), Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Ophthalmology, St. Olavs University Hospital, Trondheim, Norway.
    Skin-to-skin contact during eye examination did not reduce pain compared to standard care with parental support in preterm infants2019Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, nr 8, s. 1434-1440Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: We compared the pain relieving effect of skin-to-skin contact versus standard care in the incubator during screening for retinopathy of prematurity.

    METHODS: This randomised crossover study included 35 preterm infants of less than 32 weeks of gestational age admitted to St Olavs University Hospital, Trondheim, Norway, between January 2014 and June 2016. Randomisation was for skin-to-skin with one of the parents or standard care with supportive positioning by parents for the first of two consecutive eye examinations. The pain score was measured twice using the Premature Infant Pain Profile (PIPP) during and after the eye examination. The infants' movement activity was video recorded after the examination.

    RESULTS: There was no difference in mean pain scores with skin-to-skin contact versus standard care during (10.2 vs. 10.3, p = 0.91) or after (7.0 vs. 6.8, p = 0.76) the procedure. Independent of the randomisation group, PIPP scores were lower than previous comparable studies have found. Bouts of movement activity were also the same whether the examination was conducted in skin-to-skin position or in the incubator (p = 0.91).

    CONCLUSION: Skin-to-skin contact during the eye examination did not provide additional pain relief compared to standard care where the parents were already a part of the multidimensional approach.

  • 17.
    Leijon, Ingemar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Bladh, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Finnström, Orvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Gäddlin, Per-Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Futurum, Sweden.
    Nelson Follin, Nina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala. Karolinska Univ Hosp, Sweden.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Sydsjö, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Self-reported mental health and cortisol activity at 27-28 years of age in individuals born with very low birthweight2019Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim

    To assess mental health outcomes of very low birthweight (VLBW, <1500 g) subjects to adulthood and to examine salivary cortisol and hair cortisol levels and their relation to birth characteristics and mental health.

    Methods

    A Swedish regional cohort of 56 VLBW subjects and 55 full‐term controls were assessed at the ages 27‐28 with adult self‐reported scales and the mean of 2 days diurnal salivary cortisol and hair cortisol. The cohorts had been assessed at 15 years of age with youth self‐reported scales.

    Results

    There were no differences between the groups in youth self‐reported scales and adult self‐reported scores. The 24 participating VLBW girls scored lower on youth self‐reported scales externalising and total problem scores than the control girls. In adulthood, the 21 participating VLBW women had significantly higher morning concentrations of salivary cortisol than control women, P = .014. No significant associations were found between cortisol concentrations and adult self‐reported scales internalising, externalising and total scores.

    Conclusion

    Self‐reported mental health in VLBW subjects was comparable with normal birthweight controls indicating a satisfying transition from adolescence to adulthood. VLBW females had higher morning salivary cortisol concentrations, suggesting a gender difference. We found no correlations between cortisol and mental health.

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  • 18.
    Liest, Lisbeth
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Omran, Ahmed Shaker
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Mikiver, Rasmus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Uppugunduri, Srinivas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    RMI and ROMA are equally effective in discriminating between benign and malignant gynecological tumors: A prospective population-based study2019Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, nr 1, s. 24-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Our primary objective was to test the hypothesis that human epididymal protein 4 (HE4) and risk of ovarian malignancy index outperform the CA 125 and risk of malignancy index tests in categorizing a pelvic mass into high or low risk of malignancy in a Swedish population. Furthermore, cut-off values needed to be defined for HE4 and ROMA in premenopausal and postmenopausal women prior to their introduction to clinical practice. A third objective was to investigate the correlation between HE4 levels in serum and urine. Material and methods Women with a pelvic mass scheduled for surgery were recruited from nine hospitals in south-east Sweden. Preoperative blood samples were taken for analyzing CA125 and HE4 as well as urine samples for analyzing HE4. Results We enrolled a total of 901 women, of whom 784 were evaluable. In the premenopausal and postmenopausal groups, no significant differences were found for sensitivity, positive and negative predictive value, either for RMI vs ROMA or for CA125 vs HE4 using a fixed specificity of 75%. Cut-off values indicating malignancy were established for HE4 and ROMA in premenopausal and postmenopausal women. We found no correlation between HE4 concentration in serum and urine. Conclusions We could not confirm that ROMA had diagnostic superiority over RMI in categorizing women with a pelvic mass into low-risk or high-risk groups for malignancy in a Swedish population. We have defined cut-off values for HE4 and ROMA. The lack of correlation between serum and urine HE4 obviates the introduction of urine HE4 analysis in clinical diagnostics.

  • 19.
    Löwing Svensson, Lukas
    Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Framtidens laboratorieläkare bör bidra mer med råd och tolkningar [The future of laboratory medicine, the future laboratory physician]2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Utvecklingen inom laboratoriemedicin går dels mot robustare patientnära instrument, dels mot dataintensiva kartläggningar av gener.

    Demografiska förändringar med framför allt en åldrande befolkning leder till ett ökat behov av diagnostik.

    Klokt utnyttjande av vår arsenal av test krävs för att kunna fortsätta ge värdeskapande svar till allt fler.

    Ett ökat informationsutbyte mellan laboratorium och patientjournal, för att skapa mer förädlade svarsrapporter, är sannolikt och önskvärt.

    En högre grad av samverkan mellan kliniker och framtidens laboratorieläkare är en förutsättning för att möta dessa utmaningar.

  • 20.
    Macwan, Ankit
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Boknäs, Niklas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Ntzouni, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Ramström, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Orebro Univ, Sweden.
    Gibbins, Jonathan M.
    Univ Reading, England.
    Faxälv, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Gradient-dependent inhibition of stimulatory signaling from platelet G protein-coupled receptors2019Ingår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 104, nr 7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    As platelet activation is an irreversible and potentially harmful event, platelet stimulatory signaling must be tightly regulated to ensure the filtering-out of inconsequential fluctuations of agonist concentrations in the vascular milieu. Herein, we show that platelet activation via G protein-coupled receptors is gradient-dependent, i.e., determined not only by agonist concentrations per se but also by how rapidly concentrations change over time. We demonstrate that gradient-dependent inhibition is a common feature of all major platelet stimulatory G protein-coupled receptors, while platelet activation via the non-G protein-coupled receptor glycoprotein VI is strictly concentration-dependent. By systematically characterizing the effects of variations in temporal agonist concentration gradients on different aspects of platelet activation, we demonstrate that gradient-dependent inhibition of protease-activated receptors exhibits different kinetics, with platelet activation occurring at lower agonist gradients for protease-activated receptor 4 than for protease-activated receptor 1, but shares a characteristic bimodal effect distribution, as gradient-dependent inhibition increases over a narrow range of gradients, below which aggregation and granule secretion is effectively shut off. In contrast, the effects of gradient-dependent inhibition on platelet activation via adenosine diphosphate and thromboxane receptors increase incrementally over a large range of gradients. Furthermore, depending on the affected activation pathway, gradient-dependent inhibition results in different degrees of refractoriness to subsequent autologous agonist stimulation. Mechanistically, our study identifies an important role for the cyclic adenosine monophosphate-dependent pathway in gradient-dependent inhibition. Together, our findings suggest that gradient-dependent inhibition may represent a new general mechanism for hemostatic regulation in platelets.

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  • 21.
    Magnusson, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Schedvin, Göran
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    D-vitaminanalyser i primärvård måste användas ändamålsenligt [Appropriate use of vitamin D assessments in primary health care]: Ny strategi i Östergötland för införande och uppföljning av analyser gav bra resultat [Impact of new strategies for the introduction and follow-up of analyses in Östergötland]2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, s. 1-4Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Hälso- och sjukvårdslagen föranstaltar om en kostnadseffektiv och jämlik diagnostik inom den svenska hälso- och sjukvården. Samtidigt ökar efterfrågan på laboratorietest mer än annan medicinsk aktivitet, och utvecklingen leder även till att utbudet av laboratorietest ökar [1]. Vårdens generella resursbrist har lett till ökad betoning på värdeskapande testanvändning globalt [2] med fokus på såväl underanvändning av test (försenar korrekt diagnos och adekvat behandling) som överanvändning (medför överdiagnostik och resursslöseri) [3].Som en följd av denna utveckling har laboratorieverksamheten inom Region Östergötland initierat strategier med syfte att åstadkomma en mer rationell användning av laboratoriemedicinska analyser. Detta har skett genom en aktivare uppföljning av beställningsmönster åtföljd av information och feedback i relation till observerade beställningsmönster. År 2016 initierades s k KRAMA-strategier (KRAMA = Kompetensgruppen för rationell användning av medicinsk diagnostik i alla delar av vårdkedjan) (Figur 1). En viktig ambition var att överge ett passivt testinförande till förmån för ett mer effektivt införande i kombination med aktiv uppföljning av beställningsmönster.

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    D-vitaminanalyser i primärvårdmåste användas ändamålsenligt [Appropriate use of vitamin D assessments in primary health care]: Ny strategi i Östergötland för införande och uppföljning av analyser gav bra resultat [Impact of new strategies for the introduction and follow-up of analyses in Östergötland]
  • 22.
    Ognissanti, Damiano
    et al.
    Chalmers Univ Technol, Sweden; Univ Gothenburg, Sweden.
    Bjurman, Christian
    Univ Gothenburg, Sweden.
    Holzmann, Martin J.
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Petzold, Max
    Univ Gothenburg, Sweden.
    Cvijovic, Marija
    Chalmers Univ Technol, Sweden; Univ Gothenburg, Sweden.
    Hammarsten, Ola
    Univ Gothenburg, Sweden.
    Cardiac troponin T concentrations and patient-specific risk of myocardial infarction using the novel PALfx parameter2019Ingår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 66, s. 21-28Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Myocardial infarction (MI) is more likely if the heart damage biomarker cardiac troponin T (cTnT) is elevated in a blood sample from a patient with chest pain. There is no conventional method to estimate the risk of MI at a specific cTnT concentration. The purpose of this study was to evaluate the performance of a novel method that converts cTnT concentrations to patient-specific risks of MI. Methods: Admission cTnT measurements in 15,425 ED patients from three hospitals with a primary complaint of chest pain, with or without a clinical diagnosis of MI, were Box-Cox-transformed to normality density functions to calculate the percentage with MI among patients with a given cTnT concentration, the parametric predictive value among lookalikes (PALfx). The ability of the PALfx to generate stable risk estimates of MI was examined by bootstrapping and expressed as the coefficient of variation (CV). Results: Four age and sex-specific subgroups above or below 60 years of age with distinct cTnT distributions were identified among patients without MI. The cTnT distributions across subgroups with MI were similar, allowing us to use all admissions with MI to calculate the PALfx in the four subgroups. For instance, at a baseline cTnT concentration of 7 ng/L, a female patient amp;lt;60 years would have a 0.5% risk of MI whereas a male patient amp;gt;60 years would have a 1.9% risk of MI. To assess the stability of the PALfx method we bootstrapped smaller and smaller subsets of the 15,422 ED visits. We found that 1950 patients without MI and 50 patients with MI were sufficient to limit the variation of the PALfx with a CV of 0.8-5.4%, close to the CV using the entire dataset. The MI risk estimates were similar when data from the three hospitals were used separately to derive the PALfx equations. Conclusions: The PALfx can be used to estimate the risk of MI at patient-specific cTnT concentrations with acceptable margins of error. The patient-specific risk of disease using the PALfx could complement decision limits.

  • 23.
    Patra, Hirak Kumar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Department of Chemical Engineering and Biotechnology, Cambridge University, Cambridge, UK; Wolfson College, University of Cambridge, Cambridge, UK.
    Azharuddin, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Massachusetts Eye and Ear and Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, USA.
    Papapavlou, Georgia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Deb, Suryyani
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Department of Biochemistry, University of Calcutta, Calcutta, India; Department of Biotechnology, Maulana Abul Kalam Azad University of Technology (MAKAUT), West Bengal, India.
    Osterrieth, Johannes
    Department of Chemical Engineering and Biotechnology, Cambridge University, Philippa Fawcett Drive, Cambridge, UK.
    Zhu, Geyunjian Harry
    Department of Chemical Engineering and Biotechnology, Cambridge University, Philippa Fawcett Drive, Cambridge, UK.
    Romu, Thobias
    Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Dhara, Ashis K.
    Centre for Image Analysis, Uppsala University, Uppsala, Sweden; Department of Electrical Engineering, National Institute of Technology Durgapur, West Bengal, India.
    Jafari, Mohammad Javad
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Gadheri, Amineh
    Department of Oncology‐Pathology, Karolinska Institute, Stockholm, Sweden.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Rajan, Madhavan S.
    Department of Ophthalmology, Cambridge University Hospitals NHS Trust and Vision and Eye Research Institute (VERI), Anglia Ruskin University, Cambridge, UK.
    Slater, Nigel K. H.
    Department of Chemical Engineering and Biotechnology, Cambridge University, Philippa Fawcett Drive, Cambridge, UK.
    Rational Nanotoolbox with Theranostic Potential for Medicated Pro-Regenerative Corneal Implants2019Ingår i: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 29, nr 38, artikel-id 1903760Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cornea diseases are a leading cause of blindness and the disease burden is exacerbated by the increasing shortage around the world for cadaveric donor corneas. Despite the advances in the field of regenerative medicine, successful transplantation of laboratory‐made artificial corneas is not fully realized in clinical practice. The causes of failure of such artificial corneal implants are multifactorial and include latent infections from viruses and other microbes, enzyme overexpression, implant degradation, extrusion or delayed epithelial regeneration. Therefore, there is an urgent unmet need for developing customized corneal implants to suit the host environment and counter the effects of inflammation or infection, which are able to track early signs of implant failure in situ. This work reports a nanotoolbox comprising tools for protection from infection, promotion of regeneration, and noninvasive monitoring of the in situ corneal environment. These nanosystems can be incorporated within pro‐regenerative biosynthetic implants, transforming them into theranostic devices, which are able to respond to biological changes following implantation.

    Publikationen är tillgänglig i fulltext från 2020-07-15 00:01
  • 24.
    Rajan, Meenu Rohini
    et al.
    Univ Gothenburg, Sweden.
    Sotak, Matus
    Univ Gothenburg, Sweden.
    Barrenas, Fredrik
    Univ Gothenburg, Sweden; Uppsala Univ, Sweden.
    Shen, Tong
    Univ Calif Davis, CA 95616 USA.
    Borkowski, Kamil
    Univ Calif Davis, CA 95616 USA.
    Ashton, Nicholas J.
    Univ Gothenburg, Sweden; Kings Coll London, England; NIHR Biomed Res Ctr Mental Hlth, England; Biomed Res Unit Dementia South London, England; Maudsley NHS Fdn, England.
    Biorserud, Christina
    Univ Gothenburg, Sweden.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Ramström, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Orebro Univ, Sweden.
    Scholl, Michael
    Univ Gothenburg, Sweden; UCL, England.
    Lindahl, Per
    Univ Gothenburg, Sweden.
    Fiehn, Oliver
    Univ Calif Davis, CA 95616 USA.
    Newman, John W.
    Univ Calif Davis, CA 95616 USA; ARS, CA USA.
    Perkins, Rosie
    Univ Gothenburg, Sweden.
    Wallenius, Ville
    Univ Gothenburg, Sweden.
    Lange, Stephan
    Univ Gothenburg, Sweden; Univ Calif San Diego, CA 92103 USA.
    Borgeson, Emma
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 15385Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The search for biomarkers associated with obesity-related diseases is ongoing, but it is not clear whether plasma and serum can be used interchangeably in this process. Here we used high-throughput screening to analyze 358 proteins and 76 lipids, selected because of their relevance to obesity-associated diseases, in plasma and serum from age- and sex-matched lean and obese humans. Most of the proteins/lipids had similar concentrations in plasma and serum, but a subset showed significant differences. Notably, a key marker of cardiovascular disease PAI-1 showed a difference in concentration between the obese and lean groups only in plasma. Furthermore, some biomarkers showed poor correlations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis. Collectively, our results show that the choice of biofluid may impact study outcome when screening for obesity-related biomarkers and we identify several markers where this will be the case.

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  • 25.
    Ramström, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Orebro Univ, Sweden.
    Arachidonic acid causes lysis of blood cells and ADP-dependent platelet activation responses in platelet function tests2019Ingår i: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 30, nr 8, s. 1001-1007Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The use of arachidonic acid (AA) to stimulate platelets is considered as a specific approach to study aspirin treatment efficacy. However, very high concentrations of AA are used, and it has been previously reported that AA can induce cell lysis in other settings. Several clinical studies have reported decreased responses to AA in whole blood tests in the presence of clopidogrel. Our aim was to investigate whether unspecific effects contribute to AA-induced aggregation and platelet activation in light transmission aggregometry (LTA) in platelet-rich plasma (PRP), and in assays using whole blood, multiple electrode aggregometry (MEA, Multiplate?), and flow cytometry. We report that cell lysis, especially of red blood cells, does occur at concentrations of AA used in the clinical tests and that ADP is very important for the AA-induced platelet activation responses. In flow cytometry, very limited platelet activation was detected before reaching AA concentrations in the millimolar range, where cell lysis also occurred, making it problematic to develop a reliable flow cytometry assay using AA as reagent. We conclude that cell lysis and ADP release contribute to AA-induced platelet responses, most markedly in whole blood assays. This finding could potentially explain some differences between studies comparing methods using whole blood and PRP and also how clopidogrel treatment could influence AA-induced aggregation results in previously published studies. Our findings highlight some issues with AA as reagent for platelet activation, which also have an impact on how platelet activation assays using AA should be interpreted.

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  • 26.
    Schedvin, Göran
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Omran, Ahmed
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Automatiserad reflexanalys måste införas på rätt sätt [Appropriate implementation of automated reflex testing]2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Det är erkänt svårt både att införa nya metoder i sjukvården och att utmönstra gamla.

    Reflexanalyser innebär att en diagnostisk analys auto­matiskt kompletteras med ytterligare en analys beroende på resultatet av den första analysen i syfte att göra dia­gnostiken mer medicinskt och ekonomiskt effektiv.  

    För att utnyttja denna effektivitetsvinst fullt ut bör den nya analysen införas snabbt, jämlikt och med ett tydligt målvärde för graden av användning.

    I Region Östergötland har vi infört en modell för införande av nya analyser med aktiv uppföljning i införandefasen på vårdcentrals- och läkarnivå.

    Studien indikerar att en aktiv uppföljning av beställningsmönster i införandefasen leder till snabbare införande och mindre varierad användning av den nya metoden.

  • 27.
    Singh, Sukhi
    et al.
    Univ Gothenburg, Sweden.
    Damen, Tor
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Nygren, Andreas
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Hakimi, Caroline Shams
    Univ Gothenburg, Sweden.
    Ramström, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Orebro Univ, Sweden.
    Dellborgl, Mikael
    Univ Gothenburg, Sweden.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Hesse, Camilla
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Jeppsson, Anders
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers2019Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 119, nr 5, s. 735-743Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo. Methods Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 mu g/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step. Results Infusion of adrenaline increased ADP-induced aggregation at all doses above 0.01 mu g/kg/min. The aggregation increased from median 17 (25-75th percentiles: 14-31) to 25 (21-34) aggregation units (p = 0.012) at 0.10 mu g/kg/min. Adrenaline infusion also increased ADP-induced fibrinogen receptor activation (from 29 [22-35] to 46 [38-57%]) and P-selectin expression (from 3.7 [3.0-4.3] to 7.7 [4.7-8.6%]), both p=0.012. Adrenaline infusion reduced clot formation time (97 [89-110] to 83 [76-90] seconds, p = 0.008) and increased maximum clot firmness (59 [57-60] to 62 [61-64] mm, p = 0.007). Conclusion Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations.

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  • 28.
    Sundman, Ann-Sofie
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    van Poucke, Enya
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Svensson Holm, Ann-Charlotte
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Olsen Faresjö, Åshild
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Jensen, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Roth, Lina
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Long-term stress levels are synchronized in dogs and their owners2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 7391Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study reveals, for the first time, an interspecific synchronization in long-term stress levels. Previously, acute stress, has been shown to be highly contagious both among humans and between individuals of other species. Here, long-term stress synchronization in dogs and their owners was investigated. We studied 58 dog-human dyads and analyzed their hair cortisol concentrations (HCC) at two separate occasions, reflecting levels during previous summer and winter months. The personality traits of both dogs and their owners were determined through owner-completed Dog Personality Questionnaire (DPQ) and human Big Five Inventory (BFI) surveys. In addition, the dogs activity levels were continuously monitored with a remote cloud-based activity collar for one week. Shetland sheepdogs (N = 33) and border collies (N = 25), balanced for sex, participated, and both pet dogs and actively competing dogs (agility and obedience) were included to represent different lifestyles. The results showed significant interspecies correlations in long-term stress where human HCC from both summer and winter samplings correlated strongly with dog HCC (summer: N = 57, chi(2) = 23.697, P amp;lt; 0.001, beta = 0.235; winter: N = 55, chi(2) = 13.796, P amp;lt; 0.001, beta = 0.027). Interestingly, the dogs activity levels did not affect HCC, nor did the amount of training sessions per week, showing that the HCC levels were not related to general physical activity. Additionally, there was a seasonal effect in HCC. However, although dogs personalities had little effects on their HCC, the human personality traits neuroticism, conscientiousness, and openness significantly affected dog HCC. Hence, we suggest that dogs, to a great extent, mirror the stress level of their owners.

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  • 29.
    Svedlund, A.
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Hallbook, T.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Dahlgren, J.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Swolin-Eide, D.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Prospective study of growth and bone mass in Swedish children treated with the modified Atkins diet2019Ingår i: European journal of paediatric neurology, ISSN 1090-3798, E-ISSN 1532-2130, Vol. 23, nr 4, s. 629-638Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The modified Atkins diet (MAD) is a less restrictive treatment option than the ketogenic diet (KD) for intractable epilepsy and some metabolic conditions. Prolonged KD treatment may decrease bone mineralization and affect linear growth; however, long-term studies of MAD treatment are lacking. This study was designed to assess growth, body composition, and bone mass in children on MAD treatment for 24 months. Methods: Thirty-eight patients, mean age (SD) 6.1 years (4.8 years), 21 girls, with intractable epilepsy (n = 22), glucose transporter type 1 deficiency syndrome (n = 7), or pyruvate dehydrogenase complex deficiency (n = 9) were included. Body weight, height, body mass index (BMI), bone mass, and laboratory tests (calcium, phosphorus, magnesium, alkaline phosphatase, cholesterol, 25-hydroxyvitamin D, insulin-like growth factor-I and insulin-like growth factor binding protein 3) were assessed at baseline and after 24 months of MAD treatment. Results: Approximately 50% of the patients responded with more than 50% seizure reduction. Weight and height standard deviation score (SDS) were stable over 24 months, whereas median (minimum maximum) BMI SDS increased from 0.2 (-3.3 to 4.5) to 0.7 (-0.9 to 2.6), p amp;lt; 0.005. No effects were observed for bone mass (total body, lumbar spine and hip) or fat mass. Conclusions: The MAD was efficient in reducing seizures, and no negative effect was observed on longitudinal growth or bone mass after MAD treatment for 24 months. (C) 2019 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.

  • 30.
    Sydsjö, Gunilla
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Törnblom, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Gäddlin, Per-Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Finnström, Orvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Leijon, Ingemar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Nelson Follin, Nina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Women born with very low birth weight have similar menstrual cycle pattern, pregnancy rates and hormone profiles compared with women born at term2019Ingår i: BMC Women's Health, ISSN 1472-6874, E-ISSN 1472-6874, Vol. 19, nr 1, artikel-id 56Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Individuals born very preterm or with very low birth weight (VLBW) have a reduced likelihood to reproduce according to population-based register studies. Extremely low-birth weight born adults had a lower reproduction rate for both men and women in a follow-up study.

    Aim

    To investigate if being born with VLBW is associated with differences in the reproductive health, i.e. age of menarche, menstrual cycle pattern, pregnancy rates and hormone profile compared with women born at term.

    Methods

    A prospective long-term follow-up of a cohort of live-born VLBW children and their controls studied repeatedly since birth and now assessed at 26–28 years of age. Of the totally 80 girls enrolled from birth 49 women (24 VLBW women and 25 controls) participated in the current follow-up. The women’s anthropometric data and serum hormone levels were analysed.

    Results

    The reproductive hormone levels, including Anti-Mullerian Hormone, did not differ significantly between VLBW women and their controls. Both groups reported menstrual cycle irregularities and pregnancies to the same extent but the VLBW women reported 1.5 years later age of menarche. The VLBW subjects had a catch-up growth within 18 months of birth but remained on average 5 cm shorter in adult height. There were no significant differences in BMI, sagittal abdominal diameter, blood pressure or in their answers regarding life style between the VLBW women and the controls.

    Conclusion

    No differences in the reproductive hormone levels were found between VLBW women and their controls. Although age at menarche was somewhat higher in the VLBW group menstrual cycles and pregnancy rates were similar in the VLBW and control groups. Further follow-up studies are required to elucidate the health outcomes of being born VLBW.

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  • 31.
    Tubic, Bojan
    et al.
    Gothenburg Univ, Sweden.
    Zeijlon, Rickard
    Sahlgrens Univ Hosp, Sweden.
    Wennergren, Goeran
    Gothenburg Univ, Sweden.
    Obermayer-Pietsch, Barbara
    Med Univ Graz, Austria.
    Marild, Staffan
    Gothenburg Univ, Sweden.
    Dahlgren, Jovanna
    Gothenburg Univ, Sweden.
    Magnusson, Per
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Swolin-Eide, Diana
    Gothenburg Univ, Sweden.
    Randomised study of children with obesity showed that whole body vibration reduced sclerostin2019Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, nr 3, s. 502-513Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim New strategies are required to increase physical activity and improve metabolic profiles in children with obesity. We studied the effect of whole body vibration (WBV) on children with obesity on biochemical markers of energy and bone metabolism, anthropometric measurements, muscle parameters and calcaneal bone mineral density (BMD). Methods This was a randomised, prospective, controlled study of 30 children with a median age of 13 years (range 7-17) at Queen Silvia Children s Hospital, Gothenburg, Sweden, from 2013 to 2015. The target for the intervention group was to perform WBV three times a week for 12 weeks, and the study parameters were assessed at baseline and 12 weeks. Results The 16 in the WBV group achieved 51% of the planned activity, mainly at home, and were compared with 14 controls. Sclerostin, bone-specific alkaline phosphatase and carboxy-terminal collagen cross-links decreased in the WBV group (p amp;lt; 0.05) and balance improved (p amp;lt; 0.006), but osteocalcin and insulin remained unchanged. Anthropometric data, muscle strength and calcaneal BMD did not differ between the groups. Conclusion WBV did not affect most of the clinical parameters in children with obesity, but the reduction in sclerostin implies that it had direct effects on osteocytes, which are key players in bone mechanotransduction.

  • 32.
    Tufvesson Stiller, Helena
    et al.
    Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum. Dermatology, Department of Public Health and Clincal Medicine, Umeå University, Sweden.
    Mikiver, R.
    Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Uppugunduri, Srinivas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Lindholm, C.
    Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Mansson Brahme, Eva
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Schmitt-Egenolf, Marcus
    Department of Public Health and Clinical Medicine, Umeå University, Sweden.
    Health-related quality of life in patients with melanoma - characterization of a Swedish cohort2020Ingår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 182, nr 2, s. 506-508Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Abstract not available.

  • 33.
    Tynngård, Nahreen
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Ledningsstab Region Östergötland, Enheten för forskningsstöd.
    Boknäs, Niklas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Trinks, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Dreimane, Arta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Berlin, Gösta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Storage-induced change in platelet transfusion response evaluated by serial transfusions from one donor to one patient2019Ingår i: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 59, nr 2, s. 723-728Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND

    Storage of platelet concentrates (PCs) results in storage lesions with possible detrimental effects on platelet recovery after transfusion, which might affect their ability to prevent or arrest bleeding. The aim of this study was to compare the quality of PCs stored for 1 to 3 or 5 to 7 days by assessing the corrected count increment (CCI) after transfusion. To isolate the effects of storage time, we studied serial transfusions of PCs obtained from one donor and one donation, and transfused to one single recipient after storage for 1 to 3 days and 5 to 7 days.

    STUDY DESIGN AND METHODS

    Platelets were obtained from one donor by apheresis, divided into two units (>240 × 109platelets/unit) and stored for 1 to 3 and 5 to 7 days, respectively, before transfusion. The PCs were transfused on normal indications to patients undergoing treatment at the hematology ward. Platelet count was measured before and after transfusion.

    RESULTS

    Thirty patients concluded the study according to the protocol. The mean storage time was 2.4 ± 0.7 and 5.7 ± 0.8 days for platelets transfused on Days 1 to 3 and 5 to 7, respectively. Storage for 5 to 7 days decreased the 1‐hour transfusion response as compared to platelets stored 1 to 3 days, from a CCI of 17 ± 7 to 13 ± 5. Despite this decrease, 86% of the 5 to 7 days stored PCs resulted in a CCI above the cutoff value for a successful transfusion of 7.5, which was not significantly different to PCs stored for 1 to 3 days.

    CONCLUSION

    Storage of PCs for 5 to 7 days only slightly altered the transfusion response.

  • 34.
    Uhlin, Fredrik
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US. Tallinn Univ Technol, Estonia.
    Fernström, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Knapen, Marjo H. J.
    Maastricht Univ, Netherlands.
    Vermeer, Cees
    Maastricht Univ, Netherlands.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Long-term follow-up of biomarkers of vascular calcification after switch from traditional hemodialysis to online hemodiafiltration2019Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, nr 3, s. 174-181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rapid progression of vascular calcification (VC) in hemodialysis (HD) patients is caused by several factors including inflammation and an imbalance between active inducers and inhibitors of VC. Growing evidence shows that online hemodiafiltration (ol-HDF), a combination of diffusive and convective solute transport, has positive effects on the uremic environment that affects patients on dialysis. However, we recently reported that serum 25-hydroxyvitamin D (25(OH)D) decreased after a switch from HD to ol-HDF. As a consequence of this finding, the present study was undertaken to investigate if inducers and inhibitors of VC (i.e. the inactive matrix Gla protein fractions dp-ucMGP and t-ucMGP, fetuin-A, Gla-rich protein (GRP), osteopontin (OPN), bone-specific alkaline phosphatase (BALP), and osteoprotegerin (OPG)) also are affected by ol-HDF. This non-comparative prospective study comprised 35 prevalent patients who were investigated 6, 12, and 24 months after their switch from HD to ol-HDF. Most patients had increased levels of the calcification inhibitors OPN and OPG; and of the inactive calcification inhibitor dp-ucMGP during the study period irrespective of the dialysis modality. BALP and t-ucMGP were mostly within the reference interval, but fetuin-A was mostly below the reference interval during the study period. OPN was significantly associated with BALP and parathyroid hormone, r = 0.62 and r = 0.65 (p amp;lt; .001), respectively. In conclusion, in contrast to decreased 25(OH)D levels, no differences were found for any of the measured biomarkers of VC following the switch from HD to ol-HDF. Further studies are needed to elucidate how these biomarkers can contribute to calcification risk assessment.

  • 35.
    Wei, Yong
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten. Univ Hlth Network, Canada; Struct Genom Consortium, Canada.
    Resetca, Diana
    Univ Hlth Network, Canada; Univ Toronto, Canada.
    Li, Zhe
    Yokohama City Univ, Japan.
    Johansson-Åkhe, Isak
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Ahlner, Alexandra
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Helander, Sara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Wallenhammar, Amélie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Morad, Vivian
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Raught, Brian
    Univ Hlth Network, Canada; Univ Toronto, Canada.
    Wallner, Björn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Kokubo, Tetsuro
    Yokohama City Univ, Japan.
    Tong, Yufeng
    Struct Genom Consortium, Canada; Univ Windsor, Canada.
    Penn, Linda Z.
    Univ Hlth Network, Canada; Univ Toronto, Canada.
    Sunnerhagen, Maria
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Multiple direct interactions of TBP with the MYC oncoprotein2019Ingår i: Nature Structural & Molecular Biology, ISSN 1545-9993, E-ISSN 1545-9985, Vol. 26, nr 11, s. 1035-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transcription factor c-MYC is a potent oncoprotein; however, the mechanism of transcriptional regulation via MYC-protein interactions remains poorly understood. The TATA-binding protein (TBP) is an essential component of the transcription initiation complex TFIID and is required for gene expression. We identify two discrete regions mediating MYC-TBP interactions using structural, biochemical and cellular approaches. A 2.4 -angstrom resolution crystal structure reveals that human MYC amino acids 98-111 interact with TBP in the presence of the amino-terminal domain 1 of TBP-associated factor 1 (TAF1(TAND1)). Using biochemical approaches, we have shown that MYC amino acids 115-124 also interact with TBP independently of TAF1(TAND1). Modeling reveals that this region of MYC resembles a TBP anchor motif found in factors that regulate TBP promoter loading. Site-specific MYC mutants that abrogate MYC-TBP interaction compromise MYC activity. We propose that MYC-TBP interactions propagate transcription by modulating the energetic landscape of transcription initiation complex assembly.

  • 36.
    Wilhelms, Daniel
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Akutkliniken i Linköping.
    Dock, Hua
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Brito, Haissa O.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Pettersson, Emma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Stojakovic, Andrea
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Zajdel, Joanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Engblom, David
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Theodorsson, Elvar
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Spetz Holm, Anna-Clara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    CGRP Is Critical for Hot Flushes in Ovariectomized Mice2019Ingår i: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 9, artikel-id 1452Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hot flushes are common and troublesome symptoms of menopause. The neuropeptide calcitonin gene-related peptide (CGRP) is increased in plasma during hot flushes but it has not been clear if CGRP is causally involved in the mechanism underpinning the flushes. Here, we examined the effect of interventions with CGRP in a mouse model of hot flushes based on flush-like temperature increases triggered by forced physical activity in ovariectomized mice. Compared to normal mice, ovariectomized mice reacted with an exaggerated, flush-like, temperature increase after physical exercise. This increase was completely blocked by the non-peptide CGRP-antagonist MK-8825 (-0.41 degrees Celsius, 95% CI: -0,83 to 0,012, p amp;lt; 0.0001) at a dose that had no obvious effects on locomotor activity (50 mg/kg). Further, the flush-like temperature increases were strongly attenuated in ovariectomized mice lacking alpha CGRP due to a genetic modification. Collectively, our findings suggest that CGRP is an important mediator of experimentally induced hot flushes and they identify CGRP antagonists as promising treatment candidates for women and possibly also men with hot flushes.

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  • 37.
    Zimdahl Kahlin, Anna
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Helander, Sara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Skoglund, Karin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Verksamhetsutveckling vård och hälsa.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Mårtensson, Lars-Göran
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Lindqvist Appell, Malin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Comprehensive study of thiopurine methyltransferase genotype, phenotype, and genotype-phenotype discrepancies in Sweden2019Ingår i: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 164, s. 263-272Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Thiopurines are widely used in the treatment of leukemia and inflammatory bowel diseases. Thiopurine metabolism varies among individuals because of differences in the polymorphic enzyme thiopurine methyltransferase (TPMT, EC 2.1.1.67), and to avoid severe adverse reactions caused by incorrect dosing it is recommended that the patients TPMT status be determined before the start of thiopurine treatment. This study describes the concordance between genotyping for common TPMT alleles and phenotyping in a Swedish cohort of 12,663 patients sampled before or during thiopurine treatment. The concordance between TPMT genotype and enzyme activity was 94.5%. Compared to the genotype, the first measurement of TPMT enzyme activity was lower than expected for 4.6% of the patients. Sequencing of all coding regions of the TPMT gene in genotype/phenotype discrepant individuals led to the identification of rare and novel TPMT alleles. Fifteen individuals (0.1%) with rare or novel genotypes were identified, and three TPMT alleles (TPMT*42, *43, and *44) are characterized here for the first time. These 15 patients would not have been detected as carrying a deviating TPMT genotype if only genotyping of the most common TPMT variants had been performed. This study highlights the benefit of combining TPMT genotype and phenotype determination in routine testing. More accurate dose recommendations can be made, which might decrease the number of adverse reactions and treatment failures during thiopurine treatment.

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