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  • 1. Agborsangaya, Calypse
    et al.
    Toriola, Adetunji T
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Surcel, Heljia-Marja
    Holl, Katsiaryna
    Parkkila, Seppo
    Tuohimaa, Pentti
    Lukanova, Annekatrin
    Lehtinen, Matti
    The effects of storage time and sampling season on the stability of serum 25-hydroxy vitamin D and androstenedione2010Inngår i: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 62, nr 1, 51-57 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Knowledge of the stability of serum samples stored in large biobanks is pivotal for reliable assessment of hormone-dependent disease risks. We studied the effects of sample storage time and season of serum sampling on the stability of 25-hydroxy vitamin D (25-OHD) and androstenedione in a stratified random sample of 402 women, using paired sera from the Finnish Maternity Cohort. Serum samples selected were donated between 6 and 24 yr ago. The storage time did not affect serum 25-OHD and androstenedione levels. However, there was a significant mean difference in the 25-OHD levels of sera withdrawn during winter (first sample) vs. during summer (second sample; -18.4 nmol/l, P ≤ 0.001). Also at the individual level, there were significant differences in average 25-OHD levels between individuals with the paired sera taken at winter–winter compared with other alternatives (summer–winter, winter–summer, and summer–summer). The androstenedione levels showed no such differences. Long-term storage does not affect serum 25-OHD and androstenedione levels, but sampling season is an important determinant of 25-OHD levels. Stored serum samples can be used to study disease associations with both hormones. However, sampling season needs to be taken into account for 25-OHD by considering matching and stratification and, if possible, serial sampling.

  • 2.
    Alamdari, Farhood Iranparvar
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi. Urologi och andrologi.
    Rasmuson, Torgny
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi. Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi. Klinisk kemi.
    Ljungberg, Börje
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi. Urologi och andrologi.
    Angiogenesis and other markers for prediction of survival in metastatic renal cell carcinoma.2007Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, Vol. 41, nr 1, 5-9 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 3. Almon, Ricardo
    et al.
    Sjöström, Michael
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Department of Laboratory Medicine, Örebro University Hospital and Department of Biomedicine, School of Health and Medical Sciences, Örebro University.
    Lactase non-persistence as a determinant of milk avoidance and calcium intake in children and adolescents2013Inngår i: Journal of nutritional science, ISSN 2048-6790, Vol. 2, nr e26, 1-5 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study examines if lactase non-persistent (LNP) children and adolescents differ from those who are lactase persistent (LP) as regards milk avoidance and Ca intake. We also studied potential differences in anthropometric features related to obesity, and examined if milk avoidance is associated with lactasepersistence status. Additionally, we aimed to determine if heterozygous subjects showed an intermediary phenotype as regards Ca intake. Furthermore, we tested if LP and LNP influence vitamin D intake. The European Youth Heart Study is an ongoing international, multi-centre cohort study primarily designed to address CVD risk factors. Children (n 298, mean age 9·6 years) and adolescents (n 386, mean age 15·6 years) belonging to the Swedish part of the European Youth Heart Study were genotyped for the LCT-13910 C > T polymorphism. Mendelian randomisation was used. Milk avoidance was significantly more common in LNP adolescents (OR 3·2; 95% CI 1·5, 7·3). LP subjects had higher milk consumption (P < 0·001). Accordingly, energy consumption derived from milk and Ca intake was lower in LNP (P < 0·05 and P < 0·001, respectively). Heterozygous subjects did not show an intermediary phenotype concerning milk consumption. LP or LNP status did not affect vitamin D intake or anthropometric variables. LNP in children and adolescents is associated with reduced intake of milk and some milk-product-related nutritional components, in particular Ca. This reduced intake did not affect the studied anthropometric variables, indicators of body fat or estimated vitamin D intake. However, independently of genotype, age and sex, daily vitamin D intake was below the recommended intakes. Milk avoidance among adolescents but not children was associated with LNP.

  • 4.
    Andersson, Britta
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi. Klinisk kemi.
    Behnam Motlagh, Parviz
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi. Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi. Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi. Klinisk kemi.
    Pharmacological modulation of lung cancer cells for potassium ion depletion2005Inngår i: Anticancer Research, ISSN 0250-7005, Vol. 25, nr 4, 2609-2616 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 5.
    Andersson, Britta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Klinisk kemi.
    Janson, Veronica
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Klinisk kemi.
    Behnam Motlagh, Parviz
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Klinisk kemi.
    Induction of apoptosis by intracellular potassium ion depletion: using the fluorescent dye PBFI in a 96-well plate method in cultured lung cancer cells.2006Inngår i: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 20, nr 6, 986-994 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 6.
    Andersson, Charlotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Li, Xingru
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Lorenz, Fryderyk
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Li, Aihong
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Reduction in WT1 Gene Expression During Early Treatment Predicts the Outcome in Patients With Acute Myeloid Leukemia2012Inngår i: Diagnostic molecular pathology (Print), ISSN 1052-9551, E-ISSN 1533-4066, Vol. 21, nr 4, 225-233 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Wilms tumor gene 1 (WT1) expression has been suggested as an applicable minimal residual disease marker in acute myeloid leukemia (AML). We evaluated the use of this marker in 43 adult AML patients. Quantitative assessment of WT1 gene transcripts was performed using real-time quantitative-polymerase chain reaction assay. Samples from both the peripheral blood and the bone marrow were analyzed at diagnosis and during follow-up. A strong correlation was observed between WT1 normalized with 2 different control genes (beta-actin and ABL1, P < 0.001). WT1 mRNA level at diagnosis was of no prognostic relevance (P > 0.05). A >= 1-log reduction in WT1 expression in bone marrow samples taken < 1 month after diagnosis significantly correlated with an improved overall survival (P = 0.004) and freedom from relapse (P = 0.010) when beta-actin was used as control gene. Furthermore, a reduction in WT1 expression by >= 2 logs in peripheral blood samples taken at a later time point significantly correlated with a better outcome for overall survival (P = 0.004) and freedom from relapse (P = 0.012). This result was achieved when normalizing against both b-actin and ABL1. These results therefore suggest that WT1 gene expression can provide useful information for minimal residual disease detection in adult AML patients and that combined use of control genes can give more informative results.

  • 7.
    Andersson, Charlotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Oji, Yusuke
    Ohlson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wang, Sihan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Li, Xingru
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Sugiyama, Haruo
    Li, Aihong
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Prognostic significance of specific anti-WT1 IgG antibody level in plasma in patients with ovarian carcinoma2014Inngår i: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 3, nr 4, 909-918 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ovarian carcinoma (OC) has a poor prognosis and lack early effective screening markers. Wilm's tumor gene 1 (WT1) is overexpressed in OCs. Therefore, it is of great interest to investigate whether WT1-specific antibody (Ab) measurements in plasma can serve as a biomarker of anti-OC response, and is of importance in relation to patient prognosis. Peripheral blood samples were obtained from a total of 103 women with ovarian tumors with median being 1 day (range 0-48 days) before operation. WT1 IgG Ab levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis of WT1 protein expression was performed on OC tissue samples. We found that low-WT1 Ab level in plasma was related to improved survival in patients diagnosed at stages III-IV and grade 3 carcinomas. Positive WT1 protein staining on OC tissue samples had a negative impact on survival in the entire cohort, both overall survival (OS) (P = 0.046) and progression-free survival (PFS) (P = 0.006), but not in the serous OC subtype. Combining WT1 IgG Ab levels and WT1 staining, patients with high-WT1 IgG Ab levels in plasma and positive WT1 protein staining in cancer tissues had shorter survival, with a significant association in PFS (P = 0.016). These results indicated that WT1 Ab measurements in plasma and WT1 staining in tissue specimens could be useful as biomarkers for patient outcome in the high-risk subtypes of OCs for postoperative individualized therapy.

  • 8.
    Andersson, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Behnam-Motlagh, Parviz
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hedman, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rapid induction of long-lasting drug efflux activity in brain vascular endothelial cells but not malignant glioma following irradiation2002Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 19, nr 1, 1-9 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The influence of radiotherapy on malignant glioma multidrug resistance to chemotherapy was evaluated because patients with glioma often are treated with a combination of radiotherapy and chemotherapy. Multidrug resistance gene (MDR1, mdr1a, and mdr1b) transcripts were found in human and rat glioma cell lines. P-Glycoprotein (Pgp) was immunohistochemically detected in glioma cell lines and in the rat brain vascular endothelial cell line (RBE4). A multidrug resistance pump efflux activity assay demonstrated increased calcein efflux of RBE4 endothelial cells, but not glioma cells, 2 h after irradiation and still increased 14 d after irradiation. The increased efflux was equally inhibited by verapamil with or without irradiation. In the rat intracranial glioma model (BT4C), Pgp was demonstrated in capillary endothelial cells of the tumor tissue and surrounding normal brain, but not in tumor cells. The expression of gene transcripts or Pgp was not affected by irradiation. The results indicate that long-lasting verapamil-resistant drug efflux mechanisms are activated in brain endothelial cells after irradiation. The results might explain the poor efficacy of chemotherapy following radiotherapy and contribute to consideration of new treatment strategies in the management of malignant glioma.

  • 9.
    Andersson, Ulrika
    et al.
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Johansson, David
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Behnam-Motlagh, Parviz
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Johansson, Mikael
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Malmer, Beatrice
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Treatment schedule is of importance when gefitinib is combined with irradiation of glioma and endothelial cells in vitro.2007Inngår i: Acta Oncologica, ISSN 0284-186X, Vol. 46, nr 7, 951-960 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 10.
    Antonyuk, Svetlana V
    et al.
    Molecular Biophysics Group, School of Biological Sciences, University of Liverpool.
    Strange, Richard W
    Molecular Biophysics Group, School of Biological Sciences, University of Liverpool.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Hasnain, S Samar
    Molecular Biophysics Group, School of Biological Sciences, University of Liverpool.
    The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution: insights into heparin and collagen binding2009Inngår i: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 388, nr 2, 310-326 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Extracellular superoxide dismutase (SOD3) is a homotetrameric copper- and zinc-containing glycoprotein with affinity for heparin. The level of SOD3 is particularly high in blood vessel walls and in the lungs. The enzyme has multiple roles including protection of the lungs against hyperoxia and preservation of nitric oxide. The common mutation R213G, which reduces the heparin affinity of SOD3, is associated with increased risk of myocardial infarctions and stroke. We report the first crystal structure of human SOD3 at 1.7 A resolution. The overall subunit fold and the subunit-subunit interface of the SOD3 dimer are similar to the corresponding structures in Cu-Zn SOD (SOD1). The metal-binding sites are similar to those found in SOD1, but with Asn180 replacing Thr137 at the Cu-binding site and a much shorter loop at the zinc-binding site. The dimers form a functional homotetramer that is fashioned through contacts between two extended loops on each subunit. The N- and C-terminal end regions required for tetramerisation and heparin binding, respectively, are highly flexible. Two grooves fashioned by the tetramer interface are suggestive as the probable sites for heparin and collagen binding.

  • 11. Arfvidsson, Berndt
    et al.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Norgren, Lars
    S100B concentrations increase perioperatively in jugular vein blood despite limited metabolic and inflammatory response to clinically uneventful carotid endarterectomy2015Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 53, nr 1, 111-117 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Our aim was to test the hypothesis that metabolic and inflammatory responses of the brain perioperatively during carotid endarterectomy (CEA) might affect blood brain barrier (BBB) integrity. Methods: Twenty patients with >70% stenosis of internal carotid artery (ICA) were prospectively included. Surgery was performed under general anaesthesia. Blood was sampled from ipsilateral internal jugular vein and radial artery: just before, during, and after ICA clamping S100B protein, glucose, lactate, 20 amino acids, and key cytokines were analysed. Results: Jugular vein S100B increased during clamping and reperfusion, while a marginal systemic increase was recorded, unrelated to stump pressure during clamping. Glucose increased during clamping in jugular vein blood and even more systemically, while jugular lactate values were higher than systemic values initially. Most amino acids did not differ significantly between jugular vein and systemic levels: glutamic acid and aspartic acid decreased during surgery while asparagine increased. Jugular vein interleukin (IL)-6 showed a transient non-significant increase during clamping and decreased systemically. IL-8 and IL-10 increased over time. Conclusions: Rising jugular vein S100B concentrations indicated reduced BBB integrity, and marginal secondary increase of S100B systemically. Limited ischaemic effects on the brain during cross-clamping, unrelated to S100B concentrations, were confirmed by lower brain glucose levels and higher lactate levels than in systemic blood. The lack of increased jugular vein glutamic acid disproves any major ischaemic brain injury following CEA. The inflammatory response was limited, did not differ greatly between jugular and systemic blood, and was unrelated to S100B.

  • 12. Armstrong, Scott A
    et al.
    Mabon, Meghann E
    Silverman, Lewis B
    Li, Aihong
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Gribben, John G
    Fox, Edward A
    Sallan, Stephen E
    Korsmeyer, Stanley J
    FLT3 mutations in childhood acute lymphoblastic leukemia.2004Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 103, nr 9, 3544-3546 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Activating mutations of the FLT3 receptor tyrosine kinase are common in acute myelogenous leukemia (AML) but are rare in adult acute lymphoblastic leukemia (ALL). We have recently shown that FLT3 is highly expressed and often mutated in ALLs with rearrangement of the mixed lineage leukemia (MLL) gene on chromosome 11q23. Because hyperdiploid ALL samples also show high-level expression of FLT3, we searched for the presence of FLT3 mutations in leukemic blasts from 71 patients with ALL. The data show that approximately 25% (6 of 25) of hyperdiploid ALL samples possess FLT3 mutations, whereas only 1 of 29 TEL/AML1-rearranged samples harbored mutations (P =.04, Fisher exact test). Three mutations are novel in-frame deletions within a 7-amino acid region of the receptor juxtamembrane domain. Finally, 3 samples from patients whose disease would relapse harbored FLT3 mutations. These data suggest that patients with hyperdiploid or relapsed ALL might be considered candidates for therapy with newly described small-molecule FLT3 inhibitors.

  • 13.
    Arslan, Alan A
    et al.
    Department of Environmental Medicine, New York University School of Medicine.
    Clendenen, Tess V
    Department of Environmental Medicine, New York University School of Medicine.
    Koenig, Karen L
    Department of Environmental Medicine, New York University School of Medicine.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Enquist, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Ågren, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Lukanova, Annekatrin
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    Sjodin, Hubert
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Zeleniuch-Jacquotte, Anne
    Department of Environmental Medicine, New York University School of Medicine.
    Shore, Roy E
    Radiation Effects Research Foundation, Hiroshima, Japan.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Toniolo, Paolo
    Department of Environmental Medicine, New York University School of Medicine.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Circulating vitamin d and risk of epithelial ovarian cancer2009Inngår i: Journal of oncology, ISSN 1687-8450, Vol. 2009, 672492-672500 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OH)D) and the risk of subsequent invasive epithelial ovarian cancer (EOC). The 25(OH)D levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OH)D levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59-2.01). In addition, there was no evidence of an interaction effect between VDR SNP genotype or haplotype and circulating 25(OH)D levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist.

  • 14.
    Behnam-Mothlag, Parviz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Tyler, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Karlsson, Terese
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Cisplatin Resistance in Malignant Pleural Mesothelioma2012Inngår i: Mesotheliomas: Synonyms and Definition, Epidemiology, Etiology, Pathogenesis, Cyto-Histopathological Features, Clinic, Diagnosis, Treatment, Prognosis / [ed] Alexander Zubritsky, Zagreb: InTech, 2012, Vol. 11, 169-186 s.Kapittel i bok, del av antologi (Fagfellevurdert)
  • 15.
    Behnam-Motlagh, Parviz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Tyler, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy2010Inngår i: Toxins, ISSN 2072-6651, Vol. 2, nr 10, 2467-2477 s.Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    A major problem with anti-cancer drug treatment is the development of acquired multidrug resistance (MDR) of the tumor cells. Verotoxin-1 (VT-1) exerts its cytotoxicity by targeting the globotriaosylceramide membrane receptor (Gb3), a glycolipid associated with multidrug resistance. Gb3 is overexpressed in many human tumors and tumor cell lines with inherent or acquired MDR. Gb3 is co-expressed and interplays with the membrane efflux transporter P-gp encoded by the MDR1 gene. P-gp could act as a lipid flippase and stimulate Gb3 induction when tumor cells are exposed to cancer chemotherapy. Recent work has shown that apoptosis and inherent or acquired multidrug resistance in Gb3-expressing tumors could be affected by VT-1 holotoxin, a sub-toxic concentration of the holotoxin concomitant with chemotherapy or its Gb3-binding B-subunit coupled to cytotoxic or immunomodulatory drug, as well as chemical manipulation of Gb3 expression. The interplay between Gb3 and P-gp thus gives a possible physiological approach to augment the chemotherapeutic effect in multidrug resistant tumors.

  • 16.
    Bergemalm, Daniel
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Mutant superoxide dismutase-1-caused pathogenesis in amyotrophic lateral sclerosis2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a devastating disease that affects people in their late mid-life, with fatal outcome usually within a few years. The progressive degeneration of neurons responsible for muscle movement (motor neurons) throughout the central nervous system (CNS) leads to muscle wasting and paralysis, and eventually affects respiratory function. Most cases have no familial background (sporadic) whereas about 10% of cases have relatives affected by the disease. A substantial number of familial cases are caused by mutations in the gene encoding superoxide dismutase-1 (SOD1). Since the initial discovery of this relationship about 17 years ago, numerous workers have tried to identify the pathogenicity of mutant SOD1 but without any final agreement or consensus regarding mechanism. The experiments in this thesis have been aimed at finding common pathogenic mechanisms by analyzing transgenic mouse models expressing mutant SOD1s with widely different properties.

        Mitochondrial pathology and dysfunction have been reported in both ALS patients and murine models. We used density gradient ultracentrifugation for comparison of mitochondrial partitioning of SOD1 in our transgenic models. It was found that models with high levels of mutant protein, overloaded mitochondria with high levels of SOD1-protein whereas models with wild type-like levels of mutant protein did not. No significant association of the truncation mutant G127X with mitochondria was found. Thus, if mitochondrial dysfunction and pathology are fundamental for ALS pathogenesis this is unlikely to be caused by physical association of mutant SOD1 with mitochondria.

        Density gradient ultracentrifugation was used to study SOD1 inclusions in tissues from an ALS patient with a mutant SOD1 (G127X). We found large amounts in the ventral horns of the spinal cord but also in the liver and kidney, although at lower levels. This showed that such signs of the disease can also be found outside the CNS.

        This method was used further to characterize SOD1 inclusions with regard to the properties of mutant SOD1 and the presence of other proteins. The inclusions were found to be complex detergent-sensitive structures with mutant SOD1 reduced at disulfide C57-C146 being the major inclusion protein, constituting at least 50% of the protein content. Ten co-aggregating proteins were isolated, some of which were already known to be present in cellular inclusions. Of great interest was the presence of several proteins that normally reside in the endoplasmic reticulum (ER), which is in accordance with recent data suggesting that the unfolded protein response (UPR) has a role in ALS.

        To obtain unbiased information on the pathogenesis of mutant SOD1, we performed a total proteome study on spinal cords from ALS transgenic mice. By multivariate analysis of the 1,800 protein spots detected, 420 (23%) were found to significantly contribute to the difference between transgenic and control mice. From 53 proteins finally identified, we found pathways such as mitochondrial function, oxidative stress, and protein degradation to be affected by the disease. We also identified a previously uncharacterized covalent SOD1 dimer.

       In conclusion, the work described in this thesis suggests that mutant SOD1 affects the function of mitochondria, but not mainly through direct accumulation of SOD1 protein. It also suggests that SOD1 inclusions, present in both the CNS and peripheral tissues, mainly consist of SOD1 but they also trap proteins involved in the UPR. This might be deleterious as motor neurons, unable to renew themselves, are dependent on proper protein folding and degradation.

  • 17.
    Bergemalm, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Forsberg, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jonsson, P Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Graffmo, Karin S
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Changes in the spinal cord proteome of an amyotrophic lateral sclerosis murine model determined by differential in-gel electrophoresis2009Inngår i: Molecular and cellular proteomics, ISSN 1535-9484, Vol. 8, nr 6, 1306-1317 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons resulting in progressive paralysis. To date, more than 140 different mutations in the gene encoding CuZn-superoxide dismutase (SOD1) have been associated with ALS. Several transgenic murine models exist in which various mutant SOD1s are expressed. We have used differential in-gel electrophoresis (DIGE) to analyze the changes in the spinal cord proteome induced by expression of the unstable SOD1 truncation mutant G127insTGGG (G127X) in mice. Unlike mutants used in most other models, G127X lacks SOD activity and is present at low levels, thus reducing the risk of overexpression artifacts. The mice were analyzed at their peak body weights, just before onset of symptoms. Variable importance plot (VIP) analysis showed that 420 of 1,800 detected protein spots contributed significantly to the differences between the groups. By MALDI-TOF MS analysis, 54 proteins were identified. One spot was found to be a covalently linked mutant SOD1 dimer, apparently analogous to SOD1 immunoreactive bands migrating at double the molecular weight of SOD1 monomers previously detected in humans and mice carrying mutant SOD1s and in sporadic ALS cases. Analyses of affected functional pathways, and the subcellular representation of alterations suggest that the toxicity exerted by mutant SODs induces oxidative stress and affects mitochondria, cellular assembly/organization, and protein degradation.

  • 18.
    Bergemalm, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Forsberg, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Srivastava, Vaibhav
    Graffmo, Karin S
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wingsle, Gunnar
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Superoxide dismutase-1 and other proteins in inclusions from transgenic amyotrophic lateral sclerosis model mice2010Inngår i: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 114, nr 2, 408-418 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mutant superoxide dismutase-1 (SOD1) causes amyotrophic lateral sclerosis (ALS) through a cytotoxic mechanism of unknown nature. A hallmark in ALS patients and transgenic mouse models carrying human SOD1 (hSOD1) mutations are hSOD1-immunoreactive inclusions in spinal cord ventral horns. The hSOD1 inclusions may block essential cellular functions or cause toxicity through sequestering of other proteins. Inclusions from four different transgenic mouse models were examined after density gradient ultracentrifugation. The inclusions are complex structures with heterogeneous densities and are disrupted by detergents. The aggregated hSOD1 was mainly composed of subunits that lacked the native stabilizing intra-subunit disulfide bond. A proportion of subunits formed hSOD1 oligomers or was bound to other proteins through disulfide bonds. Dense inclusions could be isolated and the protein composition was analyzed using proteomic techniques. Mutant hSOD1 accounted for half of the protein. Ten other proteins were identified. Two were cytoplasmic chaperones, four were cytoskeletal proteins, and 4 were proteins that normally reside in the endoplasmic reticulum (ER). The presence of ER proteins in inclusions containing the primarily cytosolic hSOD1 further supports the notion that ER stress is involved in ALS.

  • 19.
    Bergemalm, Daniel
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Forsberg, Karin
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Srivastava, Vaibhav
    Sveriges lantbruksuniversitet.
    Graffmo, Karin S.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Andersen, Peter M.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurologi.
    Brännström, Thomas
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Wingsle, Gunnar
    Sveriges lantbruksuniversitet.
    Marklund, Stefan L.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Superoxide dismutase-1 and other proteins in inclusions from transgenic amyotrophic lateral sclerosis model miceManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Mutant superoxide dismutase-1 (SOD1) causes amyotrophic lateral sclerosis (ALS) through a cytotoxic mechanism of unknown nature. A hallmark in ALS patients and transgenic mouse models carrying human SOD1 (hSOD1) mutations are hSOD1-immunoreactive inclusions in spinal cord ventral horns. The hSOD1 inclusions may block essential cellular functions or cause toxicity through sequestering of other proteins. Inclusions from 4 different transgenic mouse models were examined after density gradient ultracentrifugation. The inclusions are complex structures with heterogeneous densities and are disrupted by detergents. The aggregated hSOD1 was mainly composed of subunits that lacked the native stabilizing intrasubunit disulfide bond. A proportion of subunits formed hSOD1 oligomers or was bound to other proteins through disulfide bonds. Dense inclusions could be isolated and the protein composition was analyzed using proteomic techniques. Mutant hSOD1 accounted for half of the protein. Ten other proteins were identified. Two were cytoplasmic chaperones, 4 were cytoskeletal proteins, and 4 were proteins that normally reside in the endoplasmic reticulum (ER). The presence of ER proteins in inclusions containing the primarily cytosolic hSOD1 further supports the notion that ER stress is involved in ALS.

  • 20.
    Bergemalm, Daniel
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Jonsson, P Andreas
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Graffmo, Karin S
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Andersen, Peter M
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurologi.
    Brännström, Thomas
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Rehnmark, Anna
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan L
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Overloading of stable and exclusion of unstable human superoxide dismutase-1 variants in mitochondria of murine amyotrophic lateral sclerosis models2006Inngår i: Journal of Neuroscience, ISSN 0270-6474, Vol. 26, nr 16, 4147-4154 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 21.
    Berggren Söderlund, Maria
    et al.
    Klinisk kemi, labmedicin Skåne.
    Nilsson-Ehle, Herman
    Sahlgrenska universitetssjukhuset Göteborg.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Jonsson, Magnus
    Klinisk kemi, labmedicin Skåne.
    Vitaminer och spårämnen2012Inngår i: Laurells klinisk kemi i praktisk medicin / [ed] Nilsson Ehle P, Berggren Söderlund M, Theodorsson E, Lund: Studentlitteratur, 2012, 9, 655-673 s.Kapittel i bok, del av antologi (Fagfellevurdert)
  • 22.
    Birve, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Neuwirth, Christoph
    Weber, Markus
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Nilsson, Ann-Charloth
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Jonsson, Per Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    A novel SOD1 splice site mutation associated with familial ALS revealed by SOD activity analysis2010Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 19, nr 21, 4201-4206 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    More than 145 mutations have been found in the gene CuZn-Superoxide dismutase (SOD1) in patients with amyotrophic lateral sclerosis (ALS). The vast majority are easily detected nucleotide mutations in the coding region. In a patient from a Swiss ALS family with half-normal erythrocyte SOD1 activity, exon flanking sequence analysis revealed a novel thymine to guanine mutation 7 bp upstream of exon 4 (c.240-7T>G). The results of splicing algorithm analyses were ambiguous, but five out of seven analysis tools suggested a potential novel splice site that would add six new base pairs to the mRNA. If translated, this mRNA would insert Ser and Ile between Glu78 and Arg79 in the SOD1 protein. In fibroblasts from the patient, the predicted mutant transcript and the mutant protein were both highly expressed, and despite the location of the insertion into the metal ion-binding loop IV, the SOD1 activity appeared high. In erythrocytes, which lack protein synthesis and are old compared with cultured fibroblasts, both SOD1 protein and enzymic activity was 50% of controls. Thus, the usage of the novel splice site is near 100%, and the mutant SOD1 shows the reduced stability typical of ALS-associated mutant SOD1s. The findings suggests that this novel intronic mutation is causing the disease and highlights the importance of wide exon-flanking sequencing and transcript analysis combined with erythrocyte SOD1 activity analysis in comprehensive search for SOD1 mutations in ALS. We find that there are potentially more SOD1 mutations than previously reported.

  • 23. Bleie, O
    et al.
    Refsum, Helga
    Ueland, Per Magne
    Vollset, Stein Emil
    Guttormsen, Anne Berit
    Nexo, Ebba
    Schneede, Jörn
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Nordrehaug, Jan Erik
    Nygård, Ottar
    Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention.2004Inngår i: Am J Clin Nutr, ISSN 0002-9165, Vol. 80, nr 3, 641-8 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 24.
    Blind, Ravna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    First time myocardial infarction and renal function, evaluation of different models for estimation of GFR.2014Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 25.
    Boklund, Kajsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Jämförelse av citratkoncentration i koagulationsprovtagningsrör: Jämförelse av citratkoncentrationerna 3,8 % och 3,2 % i koagulationsprovtagningsrör och dess effekter på analysresultat i samband med rörposttransport2014Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 26.
    Brattsand, Göran
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Nordin, Gunnar
    Isaksson, Anders
    Bjellerup, Per
    Stridsberg, Mats
    Hård, Lena
    Ankarberg Lindgren, Carina
    Becker, Charlotte
    Gustafsson, Sven
    Larsson, Kerstin
    Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar -Något också för Norden?2012Inngår i: Klinisk Biokemi i Norden, ISSN 1101-2013, Vol. 24, nr 4, 20-27 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Equalis och Svensk Förening för Klinisk Kemi (SFKK) rekommenderar att de kliniska laboratorierna i Sverige använder enhetliga måttenheter vid hormonbestämningar för ökad jämförbarhet och patientsäkerhet. Vid analys i serum eller plasma med nuvarande metoder rekommenderas följande enheter:

    • Adrenokortikotropt hormon (ACTH): pmol/L

    • Insulin: mIE/L

    • Parathormon (PTH): pmol/L

    • Prolaktin: mIE/L

    • Tillväxthormon (GH): μg/L

    • Östradiol: pmol/L

    • Aldosteron: pmol/L

    • Reninkoncentration: mIE/L

  • 27.
    Brattsand, Göran
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Nordin, Gunnar
    Isaksson, Anders
    Bjellerup, Per
    Stridsberg, Mats
    Hård, Lena
    Ankarberg-Lindgren, Carina
    Becker, Charlotte
    Gustafsson, Sven
    Larsson, Kerstin
    Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar för säkrare vård2012Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 39-40, 1773-1773 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 28. Breimer, Lars H
    et al.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Is ferrotoxicity a new great public health challenge?2015Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 61, nr 4, 667-668 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 29. Breimer, Lars H
    et al.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Shedded cell membrane proteins in plasma: pure waste, or informative biomarkers of pathophysiological processes?2015Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, Vol. 75, nr 6, 441-443 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 30.
    Broberg, Annette
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Betydelse av provtagningsrör för faktorer i fibrinolysen2014Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 31. Brotherton, Terrell
    et al.
    Polak, Meraida
    Kelly, Crystal
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Andersen, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Glass, Jonathan D
    A novel ALS SOD1 C6S mutation with implications for aggregation related toxicity and genetic counseling2011Inngår i: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders, ISSN 1466-0822, E-ISSN 1471-180X, Vol. 12, nr 3, 215-219 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this report we describe an ALS family with a novel missense SOD1 mutation with substitution of serine for cysteine at the sixth amino acid (C6S). This mutation has interesting implications for the role of disulfides in causing disease. After identification of the ALS proband, we examined 17 members of an extended family and performed DNA mutation analysis on 21 family members. The level and activity of SOD1 in C6S carriers and wild-type family members was analyzed in erythrocytes. We found that the C6S mutation results in disease with an autosomal dominant mode of inheritance and markedly reduced penetrance. The S6 mutated protein demonstrates high stability relative to the C6 wild-type protein. The specific dismutation activity of S6 SOD1 is normal. In conclusion, C6S is a novel FALS associated mutation with reduced disease penetrance, long survival time and a phenotype very different from the other SOD1 mutations reported in codon C6. This mutation may provide insight into the role of SOD1 structural changes in disease.

  • 32.
    Bruce, Stephen J
    et al.
    Umeå Plant Science Center, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Cloarec, Olivier
    Technologie Servier, 45000 Orleans, France.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Moritz, Thomas
    Umeå Plant Science Center, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Evaluation of a protocol for metabolic profiling studies on human blood plasma by combined ultra-performance liquid chromatography/mass spectrometry: From extraction to data analysis2009Inngår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 372, nr 2, 237-249 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The investigation presented here describes a protocol designed to perform high-throughput metabolic profiling analysis on human blood plasma by ultra-performance liquid chromatography/mass spectrometry (UPLC/MS). To address whether a previous extraction protocol for gas chromatography (GC)/MS-based metabolic profiling of plasma could be used for UPLC/MS-based analysis, the original protocol was compared with similar methods for extraction of low-molecular-weight compounds from plasma via protein precipitation. Differences between extraction methods could be observed, but the previously published extraction method was considered the best. UPLC columns with three different stationary phases (C8, C18, and phenyl) were used in identical experimental runs consisting of a total of 60 injections of extracted male and female plasma samples. The C8 column was determined to be the best for metabolic profiling analysis on plasma. The acquired UPLC/MS data of extracted male and female plasma samples was subjected to principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS–DA). Furthermore, a strategy for compound identification was applied here, demonstrating the strength of high-mass-accuracy time-of-flight (TOF)/MS analysis in metabolic profiling.

  • 33.
    Bölenius, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Brulin, Christine
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Lindkvist, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Söderberg, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    A content validated questionnaire for assessment of self reported venous blood sampling practices2012Inngår i: BMC Research Notes, ISSN 1756-0500, Vol. 5, 39- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Venous blood sampling is a common procedure in health care. It is strictly regulated by national and international guidelines. Deviations from guidelines due to human mistakes can cause patient harm. Validated questionnaires for health care personnel can be used to assess preventable "near misses"--i.e. potential errors and nonconformities during venous blood sampling practices that could transform into adverse events. However, no validated questionnaire that assesses nonconformities in venous blood sampling has previously been presented. The aim was to test a recently developed questionnaire in self reported venous blood sampling practices for validity and reliability.

    FINDINGS: We developed a questionnaire to assess deviations from best practices during venous blood sampling. The questionnaire contained questions about patient identification, test request management, test tube labeling, test tube handling, information search procedures and frequencies of error reporting. For content validity, the questionnaire was confirmed by experts on questionnaires and venous blood sampling. For reliability, test-retest statistics were used on the questionnaire answered twice. The final venous blood sampling questionnaire included 19 questions out of which 9 had in total 34 underlying items. It was found to have content validity. The test-retest analysis demonstrated that the items were generally stable. In total, 82% of the items fulfilled the reliability acceptance criteria.

    CONCLUSIONS: The questionnaire could be used for assessment of "near miss" practices that could jeopardize patient safety and gives several benefits instead of assessing rare adverse events only. The higher frequencies of "near miss" practices allows for quantitative analysis of the effect of corrective interventions and to benchmark preanalytical quality not only at the laboratory/hospital level but also at the health care unit/hospital ward.

  • 34.
    Bölenius, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Lindkvist, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Brulin, Christine
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Nilsson, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Institutionen för omvårdnad i Örnsköldsvik.
    Söderberg, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Impact of a large-scale educational intervention program on venous blood specimen collection practices2013Inngår i: BMC Health Services Research, ISSN 1472-6963, Vol. 13, nr 1, 463- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Phlebotomy performed with poor adherence to venous blood specimen collection (VBSC) guidelines jeopardizes patient safety and may lead to patient suffering and adverse events. A first questionnaire study demonstrated low compliance to VBSC guidelines, motivating an educational intervention of all phlebotomists within a county council. The aim was to evaluate the impact of a large-scale educational intervention program (EIP) on primary health care phlebotomists' adherence to VBSC guidelines. We hypothesised that the EIP would improve phlebotomists' VBSC practical performance.

    METHODS: The present study comprise primary health care centres (n = 61) from two county councils in northern Sweden. The final selected study group consisted of phlebotomists divided into an intervention group (n = 84) and a corresponding control group (n = 79). Both groups responded to a validated self-reported VBSC questionnaire twice. The EIP included three parts: guideline studies, an oral presentation, and an examination. Non-parametric statistics were used for comparison within and between the groups.

    RESULTS: Evaluating the EIP, we found significant improvements in the intervention group compared to the control group on self-reported questionnaire responses regarding information search (ES = 0.23-0.33, p < 0.001-0.003), and patient rest prior to phlebotomy (ES = 0.27, p = 0.004). Test request management, patient identity control, release of venous stasis, and test tube labelling had significantly improved in the intervention group but did not significantly differ from the control group (ES = 0.22- 0.49, p = < 0.001- 0.006). The control group showed no significant improvements at all (ES = 0--0.39, p = 0.016-0.961).

    CONCLUSIONS: The present study demonstrated several significant improvements on phlebotomists' adherence to VBSC practices. Still, guideline adherence improvement to several crucial phlebotomy practices is needed. We cannot conclude that the improvements are solely due to the EIP and suggest future efforts to improve VBSC. The program should provide time for reflections and discussions. Furthermore, a modular structure would allow directed educational intervention based on the specific VBSC guideline flaws existing at a specific unit. Such an approach is probably more effective at improving and sustaining adherence to VBSC guidelines than an EIP containing general pre-analytical practices.

  • 35.
    Bölenius, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Söderberg, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Lindkvist, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Brulin, Christine
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Minor improvement of venous blood specimen collection practices in primary health care after a large-scale educational intervention2013Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, Vol. 51, nr 2, 303-310 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Venous blood specimen collection is a common health care practice that has to follow strict guidelines, non-compliance among sampling staff may compromise patient safety. We evaluated a large-scale 2 h educational intervention that emphasised guideline adherence to assess possible improvements of venous blood specimen collection practices.

    Methods: Blood specimen haemolysis is usually caused by inadequate venous blood specimen collection and handling, reflecting overall pre-analytical handling. We monitored haemolysis of serum samples with haemolysis index corresponding to ≥150 mg/L of free haemoglobin for specimens sent from 11 primary health care centres and analysed on a Vitros 5,1 clinical chemistry analyser before (2008, n=6652 samples) and after (2010, n=6121 samples) the intervention.

    Results: The total percentage of haemolysed specimens was 11.8% compared to 10.5% (p=0.022) before the intervention. As groups, rural primary health care centres demonstrated a significant reduction [Odds ratios (OR)=0.744] of haemolysed specimens after intervention, whereas urban primary health care centres demonstrated a significant increase (OR=1.451) of haemolysis.

    Conclusions: A large-scale 2 h educational intervention to make venous blood specimen collection staff comply with guideline practices had minor effects on collection practices. Educational interventions may be effective in wards/care centres demonstrating venous blood specimen collection practices with larger deviations from guidelines.

  • 36. Chen, Tianhui
    et al.
    Lukanova, Annekatrin
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Zeleniuch-Jacquotte, Anne
    Wulff, Marianne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Johansson, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Schock, Helena
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Toniolo, Paolo
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    IGF-I during primiparous pregnancy and maternal risk of breast cancer2010Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 121, nr 1, 169-175 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previously, we reported that insulin-like growth factor (IGF)-I during early pregnancy is positively associated with maternal risk of breast cancer. To further explore this association, we designed a new study limited to women who donated a blood sample during their first pregnancy ending with childbirth. A case-control study was nested within the Northern Sweden Maternity Cohort in which repository since 1975, serum specimens remaining after early pregnancy screening for infectious diseases had been preserved. Study subjects were selected among women who donated a blood sample during the full-term pregnancy that led to the birth of their first child. Two hundred and forty-four women with invasive breast cancer were eligible. Two controls, matching the index case for age and date at blood donation were selected (n = 453). IGF-I was measured in serum samples on an Immulite 2000 analyzer. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. A significant positive association of breast cancer with IGF-I was observed, with OR of 1.73 (95% CI: 1.14-2.63) for the top tertile, P < 0.009. Subgroup analyses did not indicate statistical heterogeneity of the association by ages at sampling and diagnosis or by lag time to cancer diagnosis, although somewhat stronger associations with risk were observed in women < or = age 25 at index pregnancy and for cases diagnosed within 15 years of blood donation. The results of the study add further evidence for an adverse effect of elevated IGF-I concentrations during early reproductive life on risk of breast cancer.

  • 37. Chen, Tianhui
    et al.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Zeleniuch-Jacquotte, Anne
    Wulff, Marianne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Afanasyeva, Yelena
    Schock, Helena
    Johansson, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Toniolo, Paolo
    Lukanova, Annekatrin
    Maternal hormones during early pregnancy: a cross-sectional study2010Inngår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 21, nr 5, 719-727 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Little is known about correlates of first-trimester pregnancy hormones as in most studies maternal hormones have been measured later in gestation. We examined the associations of maternal characteristics and child sex with first-trimester maternal concentrations of four hormones implicated in breast cancer: human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), insulin-like growth factor (IGF)-I, and IGF-II. METHODS: About 338 serum samples donated to the Northern Sweden Maternity Cohort (NSMC), 1975-2001, during the first trimester of uncomplicated pregnancies, were analyzed for the hormones of interest as a part of a case-control study. The associations of maternal characteristics and child sex with hormone concentrations were investigated by correlation, general linear regression, and multivariate regression models. RESULTS: In the first trimester, greater maternal age was inversely correlated with IGF-I and IGF-II. In comparison with women carrying their first child, already parous women had higher IGF-I but lower hCG. Greater maternal weight and smoking were inversely correlated with hCG. No differences in hormone levels by child sex were observed. CONCLUSIONS: Our analyses indicated that potentially modifiable maternal characteristics (maternal weight and smoking) influence first-trimester pregnancy maternal hormone concentrations.

  • 38. Chen, Tianhui
    et al.
    Surcel, Helja-Marja
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Kaasila, Marjo
    Lakso, Hans-Ake
    Schock, Helena
    Kaaks, Rudolf
    Koskela, Pentti
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Pukkala, Eero
    Zeleniuch-Jacquotte, Anne
    Toniolo, Paolo
    Lehtinen, Matti
    Lukanova, Annekatrin
    Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer2011Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, nr 2, 324-336 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This is the first prospective study providing initial evidence that elevated androgens play a role in the pathogenesis of SCST. Impact: Our study may note a particular need for larger confirmatory investigations on sex steroids and NEOC. Cancer Epidemiol Biomarkers Prev; 20(2); 324-36. ©2010 AACR.

  • 39. Clarke, Robert
    et al.
    Grimley Evans, J
    Schneede, J
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Nexo, E
    Bates, C
    Fletcher, A
    Prentice, A
    Johnston, C
    Ueland, P M
    Refsum, H
    Sherliker, P
    Birks, J
    Whitlock, G
    Breeze, E
    Scott, J M
    Vitamin B12 and folate deficiency in later life.2004Inngår i: Age and ageing, ISSN 0002-0729, Vol. 33, nr 1, 34-41 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 40. Clarke, Robert
    et al.
    Sherliker, Paul
    Hin, Harold
    Nexo, Ebba
    Hvas, Anne Mette
    Schneede, Joern
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Birks, Jacqueline
    Ueland, Per M
    Emmens, Kathleen
    Scott, John M
    Molloy, Anne M
    Evans, John Grimley
    Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin.2007Inngår i: Clinical Chemistry, ISSN 0009-9147, Vol. 53, nr 5, 963-970 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Impaired vitamin B(12) function and decreased vitamin B(12) status have been associated with neurological and cognitive impairment. Current assays analyze total vitamin B(12) concentration, only a small percentage of which is metabolically active. Concentrations of this active component, carried on holotranscobalamin (holoTC), may be of greater relevance than total vitamin B(12). METHODS: We compared the utility of serum holoTC with conventional vitamin B(12) for detection of vitamin B(12) deficiency in a population-based study of older people, using increased methylmalonic acid (MMA) concentrations as a marker of metabolic vitamin B(12) deficiency in the overall population (n = 2403) and in subsets with normal (n = 1651) and abnormal (n = 752) renal function. RESULTS: Among all participants, 6% had definite (MMA >0.75 micromol/L) and 16% had probable (MMA >0.45 micromol/L) metabolic vitamin B(12) deficiency. In receiver operating characteristic curves for detection of definite vitamin B(12) deficiency, holoTC had a greater area under the curve (AUC) compared with vitamin B(12) in all participants (0.85 vs 0.76; P <0.001) and in subsets with normal (AUC: 0.87 vs 0.79; P <0.001) and abnormal (AUC: 0.85 vs 0.74; P = 0.002) renal function. Similar findings were observed for detection of moderate vitamin B(12) deficiency. Whereas the positive predictive value for both holoTC and vitamin B(12) was greater for detection of probable than definite vitamin B(12) deficiency, both tests were associated with more false-positive than true-positive test results. CONCLUSIONS: HoloTC has a modestly superior diagnostic accuracy compared with conventional vitamin B(12) for the detection of vitamin B(12) deficiency, but neither test can be recommended to screen asymptomatic populations.

  • 41.
    Connolly-Andersen, Anne-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Sundberg, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Baudin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Larsson, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Dunne, Eimear
    Clinical Research Centre, Royal College of Surgeons in Ireland, Dublin .
    Kenny, Dermot
    Clinical Research Centre, Royal College of Surgeons in Ireland, Dublin .
    Lindahl, Tomas L.
    Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Ramström, Sofia
    Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Nilsson, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Increased Thrombopoiesis and Platelet Activation in Hantavirus-Infected Patients2015Inngår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 212, nr 7, 1061-1069 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Thrombocytopenia is a common finding during viral hemorrhagic fever, which includes hemorrhagic fever with renal syndrome (HFRS). The 2 main causes for thrombocytopenia are impaired thrombopoiesis and/or increased peripheral destruction of platelets. In addition, there is an increased intravascular coagulation risk during HFRS, which could be due to platelet activation. Methods. Thrombopoiesis was determined by quantification of platelet counts, thrombopoietin, immature platelet fraction, and mean platelet volume during HFRS. The in vivo platelet activation was determined by quantification of soluble P-selectin (sP-selectin) and glycoprotein VI (sGPVI). The function of circulating platelets was determined by ex vivo stimulation followed by flow cytometry analysis of platelet surface-bound fibrinogen and P-selectin exposure. Intravascular coagulation during disease was determined by scoring for disseminated intravascular coagulation (DIC) and recording thromboembolic complications. Results. The levels of thrombopoietin, immature platelet fraction, and mean platelet volume all indicate increased thrombopoiesis during HFRS. Circulating platelets had reduced ex vivo function during disease compared to follow-up. Most interestingly, we observed significantly increased in vivo platelet activation in HFRS patients with intravascular coagulation (DIC and thromboembolic complications) as shown by sP-selectin and sGPVI levels. Conclusions. HFRS patients have increased thrombopoiesis and platelet activation, which contributes to intravascular coagulation.

  • 42. Cornes, Michael P.
    et al.
    Church, Stephen
    van Dongen-Lases, Edmee
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Guimaraes, Joao T.
    Ibarz, Mercedes
    Kovalevskaya, Svetlana
    Kristensen, Gunn B. B.
    Lippi, Giuseppe
    Nybo, Mads
    Sprongl, Ludek
    Sumarac, Zorica
    Simundic, Ana-Maria
    The role of European Federation of Clinical Chemistry and Laboratory Medicine Working Group for Preanalytical Phase in standardization and harmonization of the preanalytical phase in Europe2016Inngår i: Annals of Clinical Biochemistry, ISSN 0004-5632, E-ISSN 1758-1001, Vol. 53, nr 5, 539-547 s.Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Patient safety is a leading challenge in healthcare and from the laboratory perspective it is now well established that preanalytical errors are the major contributor to the overall rate of diagnostic and therapeutic errors. To address this, the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for Preanalytical Phase (EFLM WG-PRE) was established to lead in standardization and harmonization of preanalytical policies and practices at a European level. One of the key activities of the WG-PRE is the organization of the biennial EFLM-BD conference on the preanalytical phase to provide a forum for National Societies (NS) to discuss their issues. Since 2012, a year after the first Preanalytical phase conference, there has been a rapid growth in the number of NS with a working group engaged in preanalytical phase activities and there are now at least 19 countries that have one. As a result of discussions with NS at the third conference held in March 2015 five key areas were identified as requiring harmonisation. These were test ordering, sample transport and storage, patient preparation, sampling procedures and management of unsuitable specimens. The article below summarises the work that has and will be done in these areas. The goal of this initiative is to ensure the EFLM WG-PRE produces work that meets the needs of the European laboratory medicine community. Progress made in the identified areas will be updated at the next preanalytical phase conference and show that we have produced guidance that has enhanced standardisation in the preanalytical phase and improved patient safety throughout Europe.

  • 43.
    Dahlin, Anna M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study2008Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 32, nr 2, 304-314 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this nested case-referent study, we related plasma concentrations of vitamin B12 to the risk of colorectal cancer, taking into consideration prediagnostic plasma folate and total homocysteine concentrations. Subjects were 226 cases and double matched referents from the population-based Northern Sweden Health and Disease Study. Follow-up times from recruitment to diagnosis ranged from 0.1 to 12.7 years, with a median of 4.2 years. Plasma vitamin B12 concentrations were inversely associated with the risk of rectal cancer: univariate odds ratio for the highest versus lowest quintile 0.34 (95% confidence interval (95% CI) 0.13-0.83), p(trend) = 0.004. Risk estimates were attenuated slightly but remained statistically significant after adjustment for body mass index, current smoking, recreational and occupational physical activity, alcohol intake and prediagnostic plasma folate and total homocysteine concentrations: OR 0.30 (95% CI 0.08-0.99), p(trend) = 0.025. The corresponding univariate and fully adjusted odds ratios for colon cancer were 1.25 (CI 0.66-2.36), p(trend) = 0.185 and 1.42 (CI 0.67-3.05), p(trend) = 0.113, respectively. The observed over-risk was attributable to left-sided colon cancer. Interaction analyses including vitamin B12, folate and homocysteine were in line with the results for vitamin B12 alone. In conclusion, these results suggest that increasing levels of plasma vitamin B12, alone or together with other factors involved in one-carbon metabolism, may reduce the risk of rectal cancer, whereas for colon cancer, the association appears to be less clear.

  • 44.
    Dahlén, Gösta
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    The Pre-beta1 lipoprotein phenomenon in relation to serum cholesteroland triglyceride levels, the Lp(a) lipoprotein and coronary heartdisease1974Doktoravhandling, med artikler (Annet vitenskapelig)
  • 45. Danielsson, Jens
    et al.
    Awad, Wael
    Saraboji, Kadhirvel
    Kurnik, Martin
    Lang, Lisa
    Leinartaite, Lina
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Logan, Derek T
    Oliveberg, Mikael
    Global structural motions from the strain of a single hydrogen bond2013Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, nr 10, 3829-3834 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The origin and biological role of dynamic motions of folded enzymes is not yet fully understood. In this study, we examine the molecular determinants for the dynamic motions within the beta-barrel of superoxide dismutase 1 (SOD1), which previously were implicated in allosteric regulation of protein maturation and also pathological misfolding in the neurodegenerative disease amyotrophic lateral sclerosis. Relaxation-dispersion NMR, hydrogen/deuterium exchange, and crystallographic data show that the dynamic motions are induced by the buried H43 side chain, which connects the backbones of the Cu ligand H120 and T39 by a hydrogen-bond linkage through the hydrophobic core. The functional role of this highly conserved H120-H43-T39 linkage is to strain H120 into the correct geometry for Cu binding. Upon elimination of the strain by mutation H43F, the apo protein relaxes through hydrogen-bond swapping into a more stable structure and the dynamic motions freeze out completely. At the same time, the holo protein becomes energetically penalized because the twisting back of H120 into Cu-bound geometry leads to burial of an unmatched backbone carbonyl group. The question then is whether this coupling between metal binding and global structural motions in the SOD1 molecule is an adverse side effect of evolving viable Cu coordination or plays a key role in allosteric regulation of biological function, or both?

  • 46. Dewi, Nikmah Utami
    et al.
    Boshuizen, Hendriek C.
    Johansson, Mattias
    Vineis, Paolo
    Kampman, Ellen
    Steffen, Annika
    Tjonneland, Anne
    Halkjaer, Jytte
    Overvad, Kim
    Severi, Gianluca
    Fagherazzi, Guy
    Boutron-Ruault, Marie-Christine
    Kaaks, Rudolf
    Li, Kuanrong
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    Klinaki, Eleni
    Tumino, Rosario
    Palli, Domenico
    Mattiello, Amalia
    Tagliabue, Giovanna
    Peeters, Petra H.
    Vermeulen, Roel
    Weiderpass, Elisabete
    Gram, Inger Torhild
    Maria Huerta, Jose
    Agudo, Antonio
    Sanchez, Maria-Jose
    Ardanaz, Eva
    Dorronsoro, Miren
    Ramon Quiros, Jose
    Sonestedt, Emily
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Key, Tim
    Khaw, Kay-Tee
    Wareham, Nick
    Cross, Amanda J.
    Norat, Teresa
    Riboli, Elio
    Fanidi, Anouar
    Muller, David
    Bueno-de-Mesquita, H. Bas
    Anthropometry and the Risk of Lung Cancer in EPIC2016Inngår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 184, nr 2, 129-139 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)(2)) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings.

  • 47. Dhonukshe-Rutten, Rosalie A M
    et al.
    van Dusseldorp, Marijke
    Schneede, Jörn
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    de Groot, Lisette C P G M
    van Staveren, Wija A
    Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents.2005Inngår i: European Journal of Nutrition, ISSN 1436-6207, Vol. 44, nr 6, 341-347 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Cobalamin deficiency is prevalent in vegetarians and has been associated with increased risk of osteoporosis. AIM OF THE STUDY: To examine the association between cobalamin status and bone mineral density in adolescents formerly fed a macrobiotic diet and in their counterparts. METHODS: In this cross-sectional study bone mineral density (BMD) and bone mineral content (BMC) were determined by DEXA in 73 adolescents (9-15 y) who were fed a macrobiotic diet up to the age of 6 years followed by a lacto-(-ovo-) vegetarian or omnivorous diet. Data from 94 adolescents having consumed an omnivorous diet throughout their lives were used as controls. Serum concentrations of cobalamin, methylmalonic acid (MMA) and homocysteine were measured and calcium intake was assessed by questionnaire. Analysis of covariance (MANCOVA) was performed to calculate adjusted means for vitamin B12 and MMA for low and normal BMC and BMD groups. RESULTS: Serum cobalamin concentrations were significantly lower (geometric mean (GM) 246 pmol/L vs. 469 pmol/L) and MMA concentrations were significantly higher (GM 0.27 micromol/L vs. 0.16 micromol/L) in the formerly macrobiotic-fed adolescents compared to their counterparts. In the total study population, after adjusting for height, weight, bone area, percent lean body mass, age, puberty and calcium intake, serum MMA was significantly higher in subjects with a low BMD (p = 0.0003) than in subjects with a normal BMD. Vitamin B12 was significantly lower in the group with low BMD (p = 0.0035) or BMC (p = 0.0038) than in the group with normal BMD or BMC. When analyses were restricted to the group of formerly macrobiotic-fed adolescents, MMA concentration remained higher in the low BMD group compared to the normal BMD group. CONCLUSIONS: In adolescents, signs of an impaired cobalamin status, as judged by elevated concentrations of methylmalonic acid, were associated with low BMD. This was especially true in adolescents fed a macrobiotic diet during the first years of life, where cobalamin deficiency was more prominent.

  • 48. Dzialanski, Zbigniew
    et al.
    Barany, Michael
    Engfeldt, Peter
    Magnuson, Anders
    Olsson, Lovisa A.
    Nilsson, Torbjörn K.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?2016Inngår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, nr 3, 248-252 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist. Aim: To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test. Methods: A retrospective study using an oral lactose load test (n = 487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n = 274). Results: Mean hydrogen levels in exhaled air at 120 min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups. Conclusions: Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance. 

  • 49.
    Ekblom, Kim
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Oxidants and antioxidants in cardiovascular disease2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background

    Cardiovascular diseases, including myocardial infarction and stroke, are the main reason of death in Sweden and Western Europe. High iron stores are believed to produce oxygen radicals, which is the presumed putative mechanism behind lipid peroxidation, atherosclerosis and subsequent cardiovascular disease. Iron levels are associated with the hemochromatosis associated HFE single nucleotide polymorphisms C282Y and H63D.

    Bilirubin is an antioxidant present in relatively high levels in the human body. Several previous studies have found an association between high bilirubin levels and a lower risk for cardiovascular disease. Bilirubin levels are highly influenced by the common promoter polymorphism TA-insertion UGT1A1*28, the main reason for benign hyperbilirubinemia in Caucasians.

    There is a lack of prospective studies on both the association of iron and bilirubin levels, and the risk for myocardial infarction and ischemic stroke.

    Material and methods

    Iron, transferrin iron saturation, TIBC, ferritin and bilirubin were analyzed and HFE C282Y, HFE H63D and UGT1A1*28 were determined in myocardial infarction and stroke cases, and their double matched referents within the Northern Sweden Health and Disease Study Cohort.

    Results

    There were no associations between iron levels in the upper normal range and risk for myocardial infarction or stroke. No associations were seen for HFE-genotypes, except for a near fivefold increase in risk for myocardial infarction in HFE H63D homozygous women.

    Plasma bilirubin was lower in cases vs. referents both in the myocardial infarction and the stroke cohort. Despite a strong gene-dosage effect on bilirubin levels in both cases and referents, the UGT1A1*28 polymorphism did not influence the risk for myocardial infarction or stroke.

    Conclusion

    High iron stores are not associated with increased risk for neither myocardial infarction, nor stroke. There was no association between UGT1A1*28 and the risk for myocardial infarction or stroke. Consequently data suggests that other factors, which also may lower bilirubin, are responsible for the elevated risk observed in conjunction with lower bilirubin levels.

  • 50.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Hultdin, Johan
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Carlberg, Bo
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Strand, Tage
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Anticoagulant treatment at a specialized outpatient anticoagulant therapy unit, a descriptive study.2005Inngår i: Thromb J, ISSN 1477-9560, Vol. 3, 20- s.Artikkel i tidsskrift (Fagfellevurdert)
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