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  • 1.
    Andersson, Charlotta
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Significance of Wilms’ tumor gene 1 as a biomarker in acute leukemia and solid tumors2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Wilms’ tumor gene 1 (WT1) is a zinc finger transcriptional regulator with crucial functions in embryonic development. Originally WT1 was described as a tumor suppressor gene, but later studies have shown oncogenic properties of WT1 in a variety of tumors. Because of its dual functions in tumorigenesis, WT1 has been described as a chameleon gene. In this thesis, the significance of WT1 as a biomarker was investigated in acute myeloid leukemia (AML), clear cell renal cell carcinoma (ccRCC), ovarian carcinoma (OC) and childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

    Previous studies have suggested that expression of WT1 is a potential marker for detection of minimal residual disease (MRD) in AML. We aimed to define expression of WT1 as an MRD marker in AML. In adult AML patients, we found that a reduction of WT1 expression in bone marrow (≥ 1-log) detected less than 1 month after diagnosis was associated with an improved overall survival (OS) and freedom from relapse (FFR). In peripheral blood, a reduction of WT1 expression (≥ 2-log) detected between 1 and 6 months after treatment initiation was associated with an improved OS and FFR.

    WT1 harbor pathogenic genetic variants in a considerable proportion of AML and T-lymphoblastic leukemia (T-ALL), but mutations have not been reported in BCP-ALL. We aimed to evaluate the clinical impact of WT1 mutations and single nucleotide polymorphisms (SNPs) in BCP-ALL. Pathogenic mutations in the WT1 gene were rarely seen in childhood BCP-ALL. However, five WT1 SNPs were identified. In survival analyses, WT1 SNP rs1799925 was found to be associated with worse OS, indicating that WT1 SNP rs1799925 may be a useful marker for clinical outcome in childhood BCP-ALL. We also explored whether WT1 mutations and SNPs in ccRCC could be used as biomarkers for risk and treatment stratification. We therefore examined whether SNPs or mutations in WT1 were associated with WT1 expression and clinical outcome. Sequencing analysis revealed that none of the previously reported WT1 mutations were found in ccRCC; however, we identified six different WT1 SNPs. Our data suggest that pathogenic WT1 mutations are not involved in ccRCC, and the prognostic significance of WT1 SNPs in ccRCC is considerably weak. However, a favorable OS and disease-specific survival were found in the few cases harboring the homozygous minor allele.

    OC has a poor prognosis, and early effective screening markers are lacking. Serous OCs are known to express the WT1 protein. Overexpressed oncogenic proteins can be considered potential candidate antigens for cancer vaccines and T-cell therapy. It was therefore of great interest to investigate whether anti-WT1 IgG antibody (Ab) measurements in plasma could serve as biomarkers of anti-OC response. We found limited prognostic impact, but the results indicated that anti-WT1 IgG Ab measurements in plasma and WT1 staining in tissue specimens could be potential biomarkers for patient outcome in the high-risk subtypes of OCs.

    In conclusion, the results of this thesis indicate that WT1 gene expression can provide information about MRD of patients with AML, and WT1 SNP rs1799925 may be used as a biomarker for predicting clinical outcome in childhood BCP-ALL. In ccRCC, the prognostic significance of WT1 SNPs is weak and limited to the subgroup of patients that are homozygous for the minor allele. In OCs anti-WT1 IgG Ab measurement in plasma and WT1 staining in tissue specimens could possibly be used as biomarkers for predicting patient outcome in the high-risk subtypes of OCs.

  • 2.
    Backlund, Christoffer
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Prevalence of Fusobacterium necrophorum and emm-types of Group A Streptococci in tonsillitis in Umeå2018Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 3.
    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, s. 655-673Kapittel i bok, del av antologi (Fagfellevurdert)
  • 4.
    Berggren Söderlund, Maria
    et al.
    Klinisk kemi och transfusionsmedicin, Kronoberg.
    Ridefelt, Peter
    Klinisk kemi och farmakologi, Akademiska sjukhuset Uppsala.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Vitaminer och spårämnen2018Inngår i: Laurells Klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson & Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, s. 681-703Kapittel i bok, del av antologi (Fagfellevurdert)
  • 5.
    Boman, Jens
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Gaydos, Charlotte
    Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
    Juto, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Quinn, Thomas C
    Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
    Failure to detect Chlamydia trachomatis in cell culture by using a monoclonal antibody directed against the major outer membrane protein1997Inngår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 35, nr 10, s. 2679-2680Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two commercially available monoclonal antibodies for cell culture confirmation of Chlamydia trachomatis were compared in two prospective studies and one large retrospective study. In total, more than 33,000 genital specimens were cultured in parallel and stained with both antibodies, one of which was directed against the major outer membrane protein (MOMP) and one uf which was directed against the lipopolysaccharide (LPS). We found the anti-LPS-based assay to be more sensitive and as specific as the anti-MOMP-based assay for C. trachomatis cell culture confirmation of genital specimens.

  • 6.
    Brattsand, Göran
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Isaksson, Anders
    Klinisk kemi, Labmedicin Skåne.
    Bjellerup, Per
    Laboratoriemedicin Västmanland, Västerås.
    Becker, Charlotte
    Klinisk kemi, Labmedicin Skåne.
    Endokrina sjukdomar2018Inngår i: Laurells Klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson & Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, s. 283-344Kapittel i bok, del av antologi (Fagfellevurdert)
  • 7.
    Figueira, Joao
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Öhman, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls2016Inngår i: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 12, nr 8, s. 2562-2571Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Saliva is a biofluid that is sensitive to metabolic changes and is straightforward to collect in a non-invasive manner, but it is seldom used for metabolite analysis when studying neurodegenerative disorders. We present a procedure for both an untargeted and targeted analysis of the saliva metabolome in which nuclear magnetic resonance (NMR) spectroscopy is used in combination with multivariate data analysis. The applicability of this approach is demonstrated on saliva samples selected from the 25 year prospective Betula study, including samples from dementia subjects with either Alzheimer's disease (AD) or vascular dementia at the time of sampling or who developed it by the next sampling/assessment occasion five years later, and age-, gender-, and education-matched control individuals without dementia. Statistically significant multivariate models were obtained that separated patients with dementia from controls and revealed seven discriminatory metabolites. Dementia patients showed significantly increased concentrations of acetic acid (fold change (fc) = 1.25, p = 2 x 10(-5)), histamine (fc = 1.26, p = 0.019), and propionate (fc = 1.35, p = 0.002), while significantly decreased levels were observed for dimethyl sulfone (fc = 0.81, p = 0.005), glycerol (fc = 0.79, p = 0.04), taurine (fc = 0.70, p = 0.007), and succinate (fc = 0.62, p = 0.008). Histamine, succinate, and taurine are known to be important in AD, and acetic acid and glycerol are involved in related pathways. Dimethyl sulfone and propionate originate from the diet and bacterial flora and might reflect poorer periodontal status in the dementia patients. For these seven metabolites, a weak but statistically significant pre-diagnostic value was observed. Taken together, we present a robust and general NMR analysis approach for studying the saliva metabolome that has potential use for screening and early detection of dementia.

  • 8.
    Franklin, Oskar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Billing, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundberg, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Öhlund, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Nyström, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundin, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Plasma micro-RNA alterations appear late in pancreatic cancer2018Inngår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 267, nr 4, s. 775-781Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The aim of this research was to study whether plasma microRNAs (miRNA) can be used for early detection of pancreatic cancer (PC) by analyzing prediagnostic plasma samples collected before a PC diagnosis. Background: PC has a poor prognosis due to late presenting symptoms and early metastasis. Circulating miRNAs are altered in PC at diagnosis but have not been evaluated in a prediagnostic setting. Methods: We first performed an initial screen using a panel of 372 miRNAs in a retrospective case-control cohort that included early-stage PC patients and healthy controls. Significantly altered miRNAs at diagnosis were then measured in an early detection case-control cohort wherein plasma samples in the cases are collected before a PC diagnosis. Carbohydrate antigen 19–9 (Ca 19–9) levels were measured in all samples for comparison. Results: Our initial screen, including 23 stage I-II PC cases and 22 controls, revealed 15 candidate miRNAs that were differentially expressed in plasma samples at PC diagnosis. We combined all 15 miRNAs into a multivariate statistical model, which outperformed Ca 19–9 in receiver-operating characteristics analysis. However, none of the candidate miRNAs, individually or in combination, were significantly altered in prediagnostic plasma samples from 67 future PC patients compared with 132 matched controls. In comparison, Ca 19–9 levels were significantly higher in the cases at <5 years before diagnosis. Conclusion: Plasma miRNAs are altered in PC patients at diagnosis, but the candidate miRNAs found in this study appear late in the course of the disease and cannot be used for early detection of the disease.

  • 9.
    Grankvist, Kjell
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Gomez, Ruben
    Nybo, Mads
    Lima-Oliveira, Gabriel
    von Meyer, Alexander
    Preanalytical aspects on short- and long-term storage of serum and plasma2019Inngår i: Diagnosis, ISSN 2194-8011, Vol. 6, nr 1, s. 51-56Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Following an ordered clinical chemistry plasma/serum test, ideally the venous blood specimen is adequately collected at a health care facility, then swiftly transported to and readily handled, analyzed and sometimes interpreted at a clinical chemistry laboratory followed by a report of the test result to the ordering physician to finally handle the result. However, often there are practical as well as sample quality reasons for short-or long-term storage of samples before and after analysis. If there are specific storage needs, the preanalytical handling practices are specified in the laboratory's specimen collection instructions for the ordered test analyte. Biobanking of specimens over a very long time prior to analysis includes an often neglected preanalytical challenge for preserved quality of the blood specimen and also involves administrative and additional practical handling aspects (specified in a standard operating procedure SOP) when demands and considerations from academic, industry, research organizations and authorities are included. This short review highlights some preanalytical aspects of plasma/serum short-and long-term storage that must be considered by clinicians, laboratory staff as well as the researchers.

  • 10.
    Grankvist, Kjell
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Hammarsten, Ola
    Institutionen för Biomedicin, Göteborgs universitet.
    Berggren Söderlund, Maria
    Klinisk kemi och transfusionsmedicin, Kronoberg.
    Theodorsson, Elvar
    Institutionen för klinisk och experimentell medicin, Linköpings universitet.
    Laboratoriernas verksamhet2018Inngår i: Laurells Klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson & Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, s. 13-30Kapittel i bok, del av antologi (Fagfellevurdert)
  • 11.
    Gylling, Björn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ulvik, Arve
    Bevital AS, Laboratory building, Bergen, Norway.
    Ueland, Per Magne
    Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
    Midttun, Øivind
    Bevital AS, Laboratory building, Bergen, Norway.
    Schneede, Jørn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Häggström, Jenny
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk2019Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, nr 5, s. 68s. 947-956Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: One-carbon metabolism biomarker are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs.

    Objective: We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk.

    Design: The relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1211 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5´-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression.

    Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).

    Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.

  • 12.
    Hammarsten, Ola
    et al.
    Institutionen för Biomedicin, Göteborgs universitet.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Theodorsson, Elvar
    Institutionen för klinisk och experimentell medicin, Linköpings universitet.
    Tolkning av analysresultat2018Inngår i: Laurells Klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson & Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, s. 31-53Kapittel i bok, del av antologi (Fagfellevurdert)
  • 13. Hedin, G
    et al.
    Widerström, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Endocarditis due to Staphylococcus sciuri.1998Inngår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 17, nr 9, s. 673-5Artikkel i tidsskrift (Fagfellevurdert)
  • 14.
    Johansson, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Vollset, Stein Emil
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Key, Tim
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Ueland, Per M
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Prospective investigation of one-carbon metabolism in relation to prostate cancer risk: results from the NSHDC studyManuskript (Annet vitenskapelig)
  • 15.
    Jonsson, Sarah
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Oda, Husam
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Olsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Chlamydia trachomatis, Chlamydial Heat Shock Protein 60 and Anti-Chlamydial Antibodies in Women with Epithelial Ovarian Tumors2018Inngår i: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 11, nr 2, s. 546-551Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Chlamydia trachomatis (C. trachomatis) infection has been suggested to promote epithelial ovarian cancer (EOC) development. This study sought to explore the presence of C. trachomatis DNA and chlamydial heat shock protein 60 (chsp60) in ovarian tissue, as well as anti-chlamydial IgG antibodies in plasma, in relation to subtypes of EOC. METHODS: This cross-sectional cohort consisted of 69 women who underwent surgery due to suspected ovarian pathology. Ovarian tissue and corresponding blood samples were collected at the time of diagnosis. In ovarian tumor tissue, p53, p16, Ki67 and chsp60 were analyzed immunohistochemically, and PCR was used to detect C. trachomatis DNA. Plasma C. trachomatis IgG and cHSP60 IgG were analyzed with a commercial MIF-test and ELISA, respectively. RESULTS: Eight out of 69 women had C. trachomatis DNA in their ovarian tissue, all were invasive ovarian cancer cases (16.7% of invasive EOC). The prevalence of the chsp60 protein, C. trachomatis IgG and cHSP60 IgG in HGSC, compared to other ovarian tumors, was 56.0% vs. 37.2% P = .13, 15.4% vs. 9.3% P = .46 and 63.6% vs. 45.5% P = .33 respectively. None of the markers of C. trachomatis infection were associated with p53, p16 or Ki67. CONCLUSIONS: C. trachomatis was detected in invasive ovarian cancer, supporting a possible role in carcinogenesis of EOC. However, there were no statistically significant associations of chsp60 in ovarian tissue, or plasma anti-chlamydial IgG antibodies, with any of the subtypes of ovarian tumors.

  • 16. Kostjukovits, Svetlana
    et al.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Pekkinen, Minna
    Klemetti, Paula
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Taskinen, Mervi
    Makitie, Outi
    Decreased telomere length in children with cartilage-hair hypoplasia2017Inngår i: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 54, nr 5, s. 365-370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia caused by RMRP (RNA component of mitochondrial RNA processing endoribonuclease) gene mutations. Manifestations include short stature, variable immunodeficiency, anaemia and increased risk of malignancies, all of which have been described also in telomere biology disorders. RMRP interacts with the telomerase RT (TERT) subunit, but the influence of RMRP mutations on telomere length is unknown. We measured relative telomere length (RTL) in patients with CHH, their first-degree relatives and healthy controls and correlated RTL with clinical and laboratory features. Methods The study cohort included 48 patients with CHH with homozygous (n=36) or compound heterozygous RMRP mutations (median age 38.2 years, range 6.0-70.8 years), 86 relatives (74 with a heterozygous RMRP mutation) and 94 unrelated healthy controls. We extracted DNA from peripheral blood, sequenced the RMRP gene and measured RTL by qPCR. Results Compared with age-matched and sex-matched healthy controls, median RTL was significantly shorter in patients with CHH (n=40 pairs, 1.05 vs 1.21, p=0.017), but not in mutation carriers (n=48 pairs, 1.16 vs 1.10, p=0.224). RTL correlated significantly with age in RMRP mutation carriers (r=-0.482, p < 0.001) and non-carriers (r=-0.498, p<0.001), but not in patients (r=-0.236, p=0.107). In particular children (< 18 years) with CHH had shorter telomeres than controls (median RTL 1.12 vs 1.26, p=0.008). In patients with CHH, RTL showed no correlation with genotype, clinical or laboratory characteristics. Conclusions Telomere length was decreased in children with CHH. We found no correlation between RTL and clinical or laboratory parameters.

  • 17. Lippi, Giuseppe
    et al.
    Becan-McBride, Kathleen
    Behulova, Darina
    Bowen, Raffick A.
    Church, Stephen
    Delanghe, Joris
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Kitchen, Steve
    Nybo, Mads
    Nauck, Matthias
    Nikolac, Nora
    Palicka, Vladimir
    Plebani, Mario
    Sandberg, Sverre
    Simundic, Ana-Maria
    Preanalytical quality improvement: in quality we trust2013Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 51, nr 1, s. 229-241Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Total quality in laboratory medicine should be defined as the guarantee that each activity throughout the total testing process is correctly performed, providing valuable medical decision-making and effective patient care. In the past decades, a 10-fold reduction in the analytical error rate has been achieved thanks to improvements in both reliability and standardization of analytical techniques, reagents, and instrumentation. Notable advances in information technology, quality control and quality assurance methods have also assured a valuable contribution for reducing diagnostic errors. Nevertheless, several lines of evidence still suggest that most errors in laboratory diagnostics fall outside the analytical phase, and the pre- and postanalytical steps have been found to be much more vulnerable. This collective paper, which is the logical continuum of the former already published in this journal 2 years ago, provides additional contribution to risk management in the preanalytical phase and is a synopsis of the lectures of the 2nd European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)-Becton Dickinson (BD) European Conference on Preanalytical Phase meeting entitled "Preanalytical quality improvement: in quality we trust" (Zagreb, Croatia, 1-2 March 2013). The leading topics that will be discussed include quality indicators for preanalytical phase, phlebotomy practices for collection of blood gas analysis and pediatric samples, lipemia and blood collection tube interferences, preanalytical requirements of urinalysis, molecular biology hemostasis and platelet testing, as well as indications on best practices for safe blood collection. Auditing of the preanalytical phase by ISO assessors and external quality assessment for preanalytical phase are also discussed.

  • 18.
    Matsunaga, N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Anan, Intissar
    Rosenberg, P
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nagai, R
    Lundström, O
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Horiuchi, S
    Ando, Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Suhr, Ole B
    Advanced glycation end product is implicated in amyloid-related kidney complications2005Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 65, nr 4, s. 263-272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Kidney failure is a common complication in familial amyloidotic polyneuropathy (FAP). It has been suggested that advanced glycation end products (AGEs) play an important role in the development and pathogenesis of FAP.

    Material and methods. To evaluate the impact of AGEs on FAP patients' kidney dysfunction, we measured AGE in serum and urine of 28 FAP patients and 18 healthy controls by AGE-specific enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry utilizing antibodies to AGE and the receptor for AGE (RAGE) were used on kidney tissue from 3 FAP patients and 3 diabetic patients to disclose a correlation between amyloid deposits and AGE -RAGE.

    Results. The glomeruli of FAP patients were heavily deposited with amyloid and the glomerular size was enlarged. The space between Bowman's capsule and glomerulus was totally covered by the enlarged glomerulus. AGE and RAGE were deposited in glomeruli and tubuli and correlated with amyloid deposits. Decreased AGE levels in the liver-transplanted FAP patients' serum compared with that of non-transplanted patients were noted, and AGE concentration in serum tended to be higher in non-transplanted FAP patients compared with normal control subjects. There were no differences in the AGE urine levels in FAP patients compared with controls. No correlation could be found between AGE in urine and serum compared with serum albumin, serum creatinine and creatinine clearance.

    Conclusions. The accumulation of AGE, RAGE and amyloid in the kidney of FAP patients suggests that these molecules play an important role in the origin and pathogenesis of renal failure in FAP patients.

  • 19. Minkevich, Natalya I.
    et al.
    Morozova-Roche, Ludmilla A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Iomdina, Elena N.
    Rakitina, Tatiana V.
    Bogachuk, Anna P.
    Kakuev, Dmitry L.
    Smirnova, Evgeniya V.
    Babichenko, Igor I.
    Lipkin, Valery M.
    Abnormal pigment epithelium-derived factor processing in progressive myopia2016Inngår i: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 152, s. 1-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pigment Epithelium-Derived Factor (PEDF) is a secreted glycoprotein belonging to the family of non inhibitory serpins. It is known, that in cases of complicated myopia, the content of PEDF in aqueous humor of the anterior chamber is significantly reduced. Here we examined a bulk of Tenon's capsule samples obtained from various groups of myopes, to examine PEDF processing in progressive myopia. We have analyzed the distribution of full length PEDF50 and its truncated form PEDF45 in the soluble and insoluble fractions extracted from Tenon's capsule of myopic and control (non-myopic) patients using SDS-polyacrylamide gel electrophoresis, as well as monitored the proteolytic degradation of PEDF ex vivo by enzyme-linked immunosorbent assay. These results were complemented by PEDF mRNA analysis in correspondent tissues by using qPCR and immunohistochemistry analysis of PEDF distribution in normal and myopic specimens. We found that in the Tenon's capsule of patients suffering from a high myopia the level of "soluble" 45 kDa PEDF reduced by 2-fold, while the content of "insoluble" 50 kDa form of PEDF was increased by 4-fold compared to controls. Excessive amount of PEDF50 in myopic specimens have been shown to correlate with the abrogated PEDF processing rather than with an increase of its expression. Moreover, immunohistochemical staining of the myopic Tenon's capsule tissue sections revealed the halo of deposited PEDF50 in the fibroblast extracellular space. These findings suggest that in myopia limited proteolysis of PEDF is altered or abrogated. Accumulation of full-length PEDF insoluble aggregates in the fibroblast intercellular space may affect cell survival and consequently causes the destructive changes in the extracellular matrix of the eye connective tissues. As a result, the abrogation of full-length PEDF normal processing can be an important mechanism leading to biomechanical destabilization of the scleral capsule and myopia progression.

  • 20.
    Nilsson, Torbjörn K
    Deparment of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Stem cells as models in FASD research2010Inngår i: Journal of Pediatric Biochemistry, ISSN 1879-5390, Vol. 1, nr 3, s. 199-Artikkel i tidsskrift (Fagfellevurdert)
  • 21.
    Olofsson, A.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Östman, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Lundgren, E.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Amyloid: Morphology and Toxicity2002Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 40, nr 12, s. 1266-1270Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have expressed transthyretin (TTR) mutants which have significantly destabilised tetramers that aggregate into amyloid fibrils via a series of intermediates. We used atomic force microscopy to follow the morphology of aggregates during fibril formation. Initially, amorphous aggregates are formed that subsequently mature into fibrillar structures. This observation is interpreted as an optimisation of beta-strand registers. The rate of aggregation and maturation is highly temperature-dependent suggesting that entropic forces significantly contribute to stability. In addition, we identified a correlation between the presence of early formed aggregates of TTR and cytotoxicity. The toxic response was mediated via an apoptotic mechanism. The fact that early formed amorphous aggregates, but not more mature fibrils, exert a toxic response suggests that the rate of fibril formation may be a critical parameter. We propose that a slow rate of aggregation facilitates an increased concentration of a toxic intermediate.

  • 22.
    Olsson, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lövheim, Hugo
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Honkala, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Karhunen, Pekka J.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Kok, Eloise H.
    HSV presence in brains of individuals without dementia: the TASTY brain series2016Inngår i: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 9, nr 11, s. 1349-1355Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Herpes simplex virus (HSV) type 1 affects a majority of the population and recent evidence suggests involvement in Alzheimer's disease aetiology. We investigated the prevalence of HSV type 1 and 2 in the Tampere Autopsy Study (TASTY) brain samples using PCR and sero-positivity in plasma, and associations with Alzheimer's disease neuropathology. HSV was shown to be present in human brain tissue in 11/584 (1.9%) of samples in the TASTY cohort, of which six had Alzheimer's disease neuropathological amyloid beta (A beta) aggregations. Additionally, serological data revealed 86% of serum samples tested were IgG-positive for HSV. In conclusion, we report epidemiological evidence of the presence of HSV in brain tissue free from encephalitis symptoms in a cohort most closely representing the general population (a minimum prevalence of 1.9%). Whereas 6/11 samples with HSV DNA in the brain tissue had A beta aggregations, most of those with A beta aggregations did not have HSV present in the brain tissue.

  • 23. Ottosson, Sofia
    et al.
    Andersson, Charlotta
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Li, Xingru
    Wang, Sihan
    Nilsson, Sofie
    Li, Aihong
    Analysis of single nucleotide polymorphisms and mutational status of Wilms' tumor gene 1 in childhood B-celll precursor acute lymphoblastic leukemiaManuskript (preprint) (Annet vitenskapelig)
  • 24. Paslawski, Wojciech
    et al.
    Zareba-Paslawska, Justyna
    Zhang, Xiaoqun
    Holzl, Katharina
    Wadensten, Henrik
    Shariatgorji, Mohammadreza
    Janelidze, Shorena
    Hansson, Oskar
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Andren, Per E.
    Svenningsson, Per
    alpha-synuclein-lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients2019Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 116, nr 30, s. 15226-15235Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The progressive accumulation, aggregation, and spread of alpha-synuclein (alpha SN) are common hallmarks of Parkinson's disease (PD) pathology. Moreover, numerous proteins interact with alpha SN species, influencing its toxicity in the brain. In the present study, we extended analyses of alpha SN-interacting proteins to cerebrospinal fluid (CSF). Using coimmunoprecipitation, followed by mass spectrometry, we found that alpha SN colocalize with apolipoproteins on lipoprotein vesicles. We confirmed these interactions using several methods, including the enrichment of lipoproteins with a recombinant alpha SN, and the subsequent uptake of prepared vesicles by human dopaminergic neuronal-like cells. Further, we report an increased level of ApoE in CSF from early PD patients compared with matched controls in 3 independent cohorts. Moreover, in contrast to controls, we observed the presence of ApoE-positive neuromelanin-containing dopaminergic neurons in substantia nigra of PD patients. In conclusion, the cooccurrence of alpha SN on lipoprotein vesicles, and their uptake by dopaminergic neurons along with an increase of ApoE in early PD, proposes a mechanism(s) for alpha SN spreading in the extracellular milieu of PD.

  • 25. Petillo, David
    et al.
    Orey, Stephen
    Tan, Aik Choon
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Khoo, Sok Kean
    Parkinson's Disease-related Circulating microRNA Biomarkers: a Validation Study2015Inngår i: AIMS Medical Science, ISSN 2375-1576, Vol. 2, nr 1, s. 7-14Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Parkinson's disease (PD) is the second most common neurodegenerative disease. One of the major challenges in studying this progressive neurological disorder is to identify and develop biomarkers for early detection. Recently, several blood-based microRNA (miRNA) biomarkers for PD have been reported. However, follow-up studies with new, independent cohorts have been rare. Previously, we identified a panel of four circulating miRNA biomarkers for PD (miR-1826, miR-450b-3p, miR-505, and miR-626) with biomarker performance of 91% sensitivity and 100% specificity. However, the expression of miR-450b-3p could not be detected in a new, independent validation set. In our current study, we improved the detection power by including a non-biased pre-amplification step in quantitative real-time PCR (qRT-PCR) and reevaluated the biomarker performance. We found the panel of four PD-related miRNAs achieved the predictive power of 83% sensitivity and 75% specificity in our validation set. This is the first biomarker validation study of PD which showed reproducibility and robustness of plasma-based circulating miRNAs as molecular biomarkers and qRT-PCR as potential diagnostic assay.

  • 26.
    Pettersson, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Dahlqvist, Rune
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Fish oil for prevention of thromobosis and blood lipd lowering?2007Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, nr 4, s. 250-251Artikkel i tidsskrift (Fagfellevurdert)
  • 27.
    Retz, Karolina
    Företag Unilabs .
    Quick and reliable clinical detection of H. pylori in patients with suspected infection: Evaluation of PCR, EIA and Antigen-test2016Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
  • 28.
    Spang, Christoph
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. 2Dr. Alfen, Orthopaedic Spine Center, Wuerzburg, Germany.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin. ISEH, University College London Hospitals, UK; Pure Sports Medicine Clinic, London, UK.
    Richly innervated soft tissues covering the superficial aspect of the extensor origin in patients with chronic painful tennis elbow - Implication for treatment?2017Inngår i: Journal of Musculoskeletal and Neuronal Interactions - JMNI, ISSN 1108-7161, Vol. 17, nr 2, s. 97-103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Tennis elbow is difficult to treat. The results of surgical treatments are not convincing. Treatment studies on Achilles and patellar tendinopathy targeting the richly innervated and vascularized soft tissues outside the tendon have shown promising outcomes. The innervation patterns in the fibrous/fatty tissues superficially to the elbow extensor origin have not been clarified.

    Methods: Nine tissue specimens from the fibrous/fatty tissue covering the extensor origin was taken from seven patients (mean age: 45 years) undergoing surgical treatment for chronic painful tennis elbow. The specimens were stained for morphology (haematoxylin & eosin, H&E) and immunohistochemically for general nerve marker protein gene product 9.5 (PGP 9.5) and markers for sympathetic (tyrosine hydroxylase, TH) and sensory nerve fibres (calcitonin gene-related peptide, CGRP).

    Results: All specimens contained multiple blood vessels and nerve structures indicated by morphology and immunoreactions. There was a frequent occurrence of TH reactions, especially peri-vascularly, but also in nerve fascicles. Immunoreactions for CGRP were seen in nerve fascicles and isolated nerve fibres.

    Conclusion: The results provide new information on the innervation patterns of the superficial tissues of the extensor origin and their potential as source of tennis elbow pain. Level of Evidence: IV.

  • 29.
    Ström, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Preanalytisk inverkan vid klinisk analys av joniserat kalcium, glukos, laktat samt zink i blodprover2014Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 30.
    Suhr, Ole B.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundgren, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Westermark, P
    One mutation, two distinct disease variants: unravelling the impact of transthyretin amyloid fibril composition2017Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, nr 4, s. 337-347Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Although hereditary transthyretin (h-ATTR) amyloidosis is a monogenetic disease, a large variation in its phenotype has been observed. The common hypothesis of amyloid fibril formation involves dissociation of the transthyretin (TTR) tetramer into monomers that after misfolding reassemble into amyloid fibrils. This notion is partly challenged by the finding of two distinct types of amyloid fibrils. One of these, type A, consists of C-terminal ATTR fragments and full-length TTR, whereas the other, type B, consists only of full-length TTR. All organs of an individual patient contain ATTR deposits of either type A or type B fibrils, and the composition in each individual remains unchanged over time. The finding of two distinct types of ATTR fibrils suggests that there are at least two different pathways in operation for ATTR fibril formation. For the most common European mutation, TTR Val30Met, ATTR fibril composition is related to the outcome of liver transplantation, which is the first successful treatment for the disease, and the penetrance of the trait. In addition, the presence of C-terminal ATTR fragments has an impact on the affinity for various tracers used for noninvasive imaging of amyloid depositions such as 99 m-technetium-diphosphono-propanodicarboxylic acid scintigraphy and positron emission tomography utilizing Pittsburgh component B, and even for the gold standard diagnostic procedure, tissue biopsy stained by Congo red and examined under polarized light. The importance of amyloid fibril composition needs to be taken into consideration when designing clinical trials of treatment modalities, and also in the evaluation of diagnostic methods such as imaging techniques.

  • 31.
    Theodorsson, Elvar
    et al.
    Linköpings universitet.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Landin, Britta
    Karolinska universitetslaboratoriet, Stockholm.
    Anemier2012Inngår i: Laurells klinisk kemi i praktisk medicin / [ed] Nilsson Ehle P, Berggren Söderlund M, Theodorsson E, Lund: Studentlitteratur, 2012, 9, s. 211-280Kapittel i bok, del av antologi (Fagfellevurdert)
  • 32.
    Theodorsson, Elvar
    et al.
    Linköpings universitet.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Nilsson Ehle, Peter
    Institutionen för laboratoriemedicin, Lund.
    Laboratoriernas verksamhet2012Inngår i: Laurells klinisk kemi i praktisk medicin / [ed] Nilsson Ehle P, Berggren Söderlund M, Theodorsson E, Lund: Studentlitteratur, 2012, 9, s. 9-22Kapittel i bok, del av antologi (Fagfellevurdert)
  • 33.
    Theodorsson, Elvar
    et al.
    Linköpings universitet.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Nilsson Ehle, Peter
    Institutionen för laboratoriemedicin, Lund.
    Tolkning av analysresultat2012Inngår i: Laurells klinisk kemi i praktisk medicin / [ed] Nilsson Ehle P, Berggren Söderlund M, Theodorsson E, Lund: Studentlitteratur, 2012, 9, s. 23-51Kapittel i bok, del av antologi (Fagfellevurdert)
  • 34. Troiano, Giuseppe
    et al.
    Boldrup, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ardito, Fatima
    Gu, Xaolian
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lo Muzio, Lorenzo
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Circulating miRNAs from blood, plasma or serum as promising clinical biomarkers in oral squamous cell carcinoma: A systematic review of current findings2016Inngår i: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 63, s. 30-37Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The purpose of this systematic review was to summarize current findings on the use of circulating miRNAs from blood, serum and plasma as cancer biomarkers in patients with oral squamous cell carcinoma. Studies were gathered after searching four different electronic databases: PUBMED, SCOPUS, Cochrane Library and Web of Science. Additional search was carried out through cross check on bibliography of selected articles. After the selection process made by two of the authors, 16 articles met the inclusion criteria and were included in the review. Results showed that circulating miRNAs from blood, serum or plasma represent promising candidates as cancer biomarkers in patients suffering from oral cancer. The possibility to predict recurrences and metastases through follow-up quantification of candidate miRNAs represents another potential feature to be addressed in future studies. However, methodological standardization and uniform sampling is needed to increase the power and accuracy of results. 

  • 35.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Folate in cancer and cardiovascular disease: prospective studies from the population-based northern Sweden health and disease study2006Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    BACKGROUND: Folate, a B-vitamin found primarily in fruits and vegetables, especially leafy greens, and other B-vitamins involved in folate metabolism are believed to protect against cancer and cardiovascular disease. Maintaining an adequate folate status ensures availability of methyl groups for DNA synthesis and for all methylation reactions in the body, and prevents the accumulation of homocysteine, a sulphur-containing amino acid that has been linked to cardiovascular disease. The aim of this thesis was to relate factors involved in folate metabolism to the risk of developing colorectal cancer (CRC), prostate cancer (PCa), stroke (ischemic and hemorrhagic), and acute myocardial infarction (AMI).

    SUBJECTS AND METHODS: These were nested case-referent studies, with 226 CRC, 254 PCa, 396 stroke (334 ischemic and 62 hemorrhagic), and 571 AMI cases, and double, matched referents from the population-based Northern Sweden Health and Disease Study.

    CRC RESULTS: A bell-shaped association was observed between plasma folate concentrations and the risk of CRC [multivariate odds ratio (OR) for the middle versus lowest quintile, 2.00 (95% CI 1.13-3.56)]. Homocysteine was not associated with CRC risk. A reduced risk was observed for the MTHFR 677C>T polymorphism [OR for TT versus CC, 0.41 (95% CI 0.19-0.85), Ptrend=0.062] that was independent of plasma folate status. Prediagnostic plasma folate concentrations were higher in cases with promoter hypermethylation in the p16 and/or hMLH1 tumor suppressor genes in CRC tissue compared to cases without promoter hypermethylation in these genes (P=0.025).

    PCa RESULTS: Increasing plasma levels of folate and vitamin B12 were associated with increased risk of PCa [OR for the highest versus lowest quartile, 1.60 (95% CI 1.03-2.49), Ptrend=0.02 for folate, and 2.63 (95% CI 1.61-4.29), Ptrend<0.001 for vitamin B12]. Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance. In multivariate analyses, the risk estimate remained statistically significant only for vitamin B12.

    STROKE RESULTS: Plasma folate concentrations were associated with the risk of hemorrhagic stroke in an inverse linear manner after adjustment for conventional risk factors including hypertension [multivariate OR for the highest versus lowest quartile, 0.21 (95% CI 0.06-0.71), Ptrend=0.008]. Risk estimates were attenuated by the inclusion of homocysteine in the model [OR 0.34 (95% CI 0.08-1.40), Ptrend=0.088]. Similar results were obtained for folate intake. Neither plasma folate levels nor folate intake demonstrated a clear association with the risk of ischemic stroke, and neither plasma nor dietary vitamin B12 was associated with the risk of either type of stroke.

    AMI RESULTS: Plasma folate concentrations demonstrated an inverse association with risk of AMI that was independent of other risk factors, including homocysteine [multivariate OR for the highest versus lowest quintile, 0.56 (95% CI 0.34-0.90), Ptrend=0.080]. For vitamin B12, no clear risk relationships were apparent. None of the risk estimates for dietary intake of folate, vitamin B12, vitamin B6, or vitamin B2 were statistically significant, although the results for folate and vitamin B12 intake were in line with those for the plasma variables.

    CONCLUSIONS: The results of these population-based, prospective studies suggest that although a high folate status may be associated with a reduced risk of cardiovascular diseases, the relationship with cancer risk seems to be more complicated. The possibility of a detrimental component to the role of folate and vitamin B12 in carcinogenesis may have implications in the ongoing debate concerning mandatory folate fortification of foods.

  • 36.
    Wallin, Olof
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Söderberg, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Thor, Johan
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Brulin, Christine
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    A questionnaire survey of error reporting practices regarding venous blood sampling in hospitalsManuskript (Annet vitenskapelig)
  • 37.
    Wang, Sen
    et al.
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
    Fan, Zheng
    Office of Teaching Affairs, Xi'an University, Xi'an, China.
    Zhou, Bing
    Key Laboratory of Hormones and Development (Ministry of Health), Key laboratory of metabolic disease (Tianjin), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
    Wang, Yingting
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
    Du, Peiru
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
    Tan, Wuhong
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
    Lammi, Mikko
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
    Guo, Xiong
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
    Roles of glycoproteins in the diagnosis and differential diagnosis of chronic and latent Keshan disease2017Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 5, artikkel-id 746Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We aimed to explore the roles of glycoproteins in the pathogenesis of chronic and latent Keshan disease (CKD and LKD), and screen the lectins as indicators of significant differences in glycoproteins of KD saliva and serum. Blood and saliva were collected from 50 CKD, 50 LKD patients and 54 normal individuals. Saliva and serum lectin microarrays and saliva and serum microarrays were used to screen and verify the differences in the levels of lectin among the three groups. In the male saliva lectin microarray, Solanum tuberosum (potato) lectin (STL) and other 9 lectins showed differences between CKD and normal; STL and other 9 lectins showed differences between LKD and normal; Aleuria aurantia lectin (AAL) and other 15 lectins showed differences between CKD and LKD. In the female saliva microarray, Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I) and other 9 lectins showed differences between CKD and normal; STL and other 7 lectins showed differences between LKD and normal; Maackia amurensis lectin I (MAL-I) and Triticum vulgaris (WGA) showed difference between CKD and LKD. In the male serum lectin microarray, Psophocarpus tetragonolobus lectin I (PTL-I) and other 16 lectins showed differences between CKD and normal; Ulexeuropaeus agglutinin I (UEA-I) and other 9 lectins showed differences between LKD and normal; AAL and other 13 lectins showed differences between CKD and LKD. In the female serum lectin microarray, WGA and other 13 lectins showed differences between CKD and normal; Euonymus europaeus lectin (EEL) and other 6 lectins showed differences between LKD and normal; MAL-I and other 14 lectins showed differences between CKD and LKD. Carbohydrate chain GlcNAc and α-Gal may play crucial roles in the pathogenesis of KD. STL may be considered the diagnostic biomarker for male CKD and LKD, while WGA may be useful in distinguishing between the two stages. STL may be considered the diagnostic biomarker for female LKD.

  • 38. Wang, Sen
    et al.
    Gao, Zongqiang
    Liu, Huan
    Meng, Peilin
    Wu, Cuiyan
    Lammi, Mikko
    School of Public Health, Xi'an Jiaotong University Health Science Center; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, People's Republic of China..
    Guo, Xiong
    Roles of glycoprotein glycosylation in the pathogenesis and effectiveness evaluation of the sodium hyaluronate treatment of an endemic osteoarthritis Kashin-Beck disease.2019Inngår i: Turkish Journal of Medical Sciences, ISSN 1300-0144, E-ISSN 1303-6165, artikkel-id 31655502Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND/AIM: We aimed to explore the roles of glycoproteins glycosylation in the pathogenesis of Kashin-Beck disease (KBD) and evaluated the effectiveness of sodium hyaluronate treatment.

    MATERIALS AND METHODS: Blood and saliva were collected from KBD patients before and after the injection of sodium hyaluronate. Normal healthy subjects were included as controls. Saliva and serum lectin microarrays and saliva and serum microarray verifications were used to screen and confirm the differences in lectin levels among the three groups.

    RESULTS: In saliva lectin microarray, bindings to Sophora Japonica Agglutinin (SJA), Griffonia (Bandeiraea) Simplicifolia Lectin I (GSL-I), Griffonia (Bandeiraea) Simplicifolia Lectin I (EEL), Maackia Amurensis Lectin II (MAL-II), Sambucus Nigra Lectin (SNA), Hippeastrum Hybrid Lectin (HHL) and Aleuria Aurantia Lectin (AAL) were higher in the untreated KBD patients than in the control group. Increased levels for HHL, MAL-II and GSL-I in the untreated KBD patients discriminated them in particular from the treated ones. Jacalin was lower in the untreated KBD patients compared to the treated KBD and the normal groups. In serum lectin microarray, HHL and Peanut Agglutinin (PNA) were increased in the untreated KBD group in comparison to the control one. AAL, Phaseolus vulgaris Agglutinin(E+L) (PHA-E+L) and PsophocarpusTetragonolobus Lectin I (PTL-I) were lower in the untreated KBD patients compared to the treated KBD and the normal groups. Hyaluronate treatment appeared to normalize SNA, AAL and MAL-II levels in saliva, and HHL, PNA, AAL, PTL-I and PHA-E+L levels in serum. Saliva reversed microarray verification confirmed significant differences between groups in SNA and Jacalin, in particular, GSL-I levels, while serum reversed microarray verification indicated that HHL, PNA and AAL levels returned to normal level after the hyaluronate treatment. Lectin blot confirmed significant differences in HHL, AAL and Jaclin in saliva, and HHL, PNA, PHA-E+L and AAL in serum.

    CONCLUSION: HHL in saliva and serum may be valuable diagnostic biomarker of KBD, and it may be used to follow-up of the hyaluronate treatment.

  • 39.
    Wang, Ying
    et al.
    Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, People's Republic of China.
    Wu, Cuiyan
    School of Public Health, Health Science Center of Xi'an Jiaotong University, NHC Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Xi'an, People's Republic of China.
    Zhang, Yanan
    School of Public Health, Health Science Center of Xi'an Jiaotong University, NHC Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Xi'an, People's Republic of China.
    Yang, Yimin
    Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, People's Republic of China.
    Ren, Zhiwei
    Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, People's Republic of China.
    Lammi, Mikko
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). School of Public Health, Health Science Center of Xi'an Jiaotong University, NHC Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Xi'an, People's Republic of China.
    Guo, Xiong
    School of Public Health, Health Science Center of Xi'an Jiaotong University, NHC Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Xi'an, People's Republic of China.
    Screening for differentially expressed circRNA between Kashin-Beck disease and osteoarthritis patients based on circRNA chips.2019Inngår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, artikkel-id 31678276Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: This research aims to explore differentially expressed circRNA between OA and KBD and potential diagnostic biomarkers.

    METHODS: Total RNA was extracted from 5 pairs of KBD and OA knee joint cartilage specimens, and the expression of circRNAs was analyzed by Chip Scanning Analysis. The microarray data was verified by quantitative polymerase chain reaction (qRT-PCR). CircRNA-miRNA network was constructed to predict targeting microRNAs of circRNA genes. Peripheral blood samples from 25 KBD patients and 25 OA patients were collected for verification by qRT-PCR. Diagnostic value was evaluated by the area under the receiver operator characteristic (ROC) curve.

    RESULTS: A total of 1627 circRNAs were differentially expressed between OA and KBD. Five bone and joint disease-related circRNAs were chosen for qRT-PCR validation. The difference in expression profile of hsa_circRNA_0020014 was confirmed by qRT-PCR, and its circRNA-miRNA regulation network was set up. The ROC curve demonstrated that hsa_circ_0020014_CBC1 in peripheral blood could distinguish patients with KBD and OA.

    CONCLUSION: The expression profiles of circRNA were significantly different between OA and KBD. hsa_circRNA_0020014 is a potential biomarker for differential diagnosis between these two diseases.

  • 40.
    Widbom, Lovisa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Bryggkaffe är associerat med minskad risk att utveckla sent debuterande Crohn’s sjukdom2019Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 41. Widgren, K
    et al.
    Magnusson, M
    Hagstam, P
    Widerström, Micael
    Department of Communicable Disease Control and Prevention Jämtland County, Östersund, Sweden.
    Örtqvist, Åke
    Einemo, Im
    Follin, P
    Lindblom, A
    Mäkitalo, S
    Wik, O
    Österlund, A
    Grünewald, M
    Uhnoo, Ingrid
    Linde, A
    Prevailing effectiveness of the 2009 influenza A(H1N1)pdm09 vaccine during the 2010/11 season in Sweden2013Inngår i: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 18, nr 15, s. Article 5-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sixty per cent of the Swedish population received the monovalent AS03-adjuvanted pandemic influenza vaccine in the autumn of 2009. We assessed the age-specific effectiveness of this pandemic vaccine against hospitalisation with laboratory-confirmed influenza A(H1N1)pdm09 during the season 2010/11, in the age group from six months to 64 years in Sweden. The screening method was applied to available surveillance data. Our results suggest a prevailing effectiveness of 72% (95% confidence interval (CI): 63–80%) with the highest effectiveness among children, six months to nine years-old (92%, 95%CI: 80–97%). However, there were limitations in data quality and study design due to the lack of systematic recording of administered vaccinations, which underline the importance of preparing for an evaluation when planning for large public health actions. Despite these limitations, we believe the results reflect true, high prevailing vaccine effectiveness. Indeed, there were fewer deaths caused by influenza and the impact of influenza on intensive care units was less severe during the 2010/11 season in Sweden than in countries with lower pandemic vaccination coverage. The association between the pandemic vaccine and narcolepsy has increased the importance of assessing the risks and benefits of the vaccination; studies on the effectiveness and the duration of protection are needed for this.

  • 42.
    Wikberg, Maria L.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ljuslinder, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Plasma miRNA can detect colorectal cancer, but how early?2018Inngår i: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 7, nr 5, s. 1697-1705Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Colorectal cancer (CRC) is a major cause of deaths worldwide but has a good prognosis if detected early. The need for efficient, preferable non‐ or minimally invasive, inexpensive screening tools is therefore critical. We analyzed 12 miRNAs in pre‐ and postdiagnostic plasma samples to evaluate their potential as CRC screening markers. We used a unique study design with two overlapping cohorts, allowing analysis of pre‐ and postdiagnostic samples from 58 patients with CRC and matched healthy controls. Plasma concentrations of miR‐15b, ‐16, ‐18a, ‐19a, 21, ‐22, ‐25, ‐26a, ‐29c, ‐142‐5p, ‐150, and ‐192 were measured by semi‐quantitative real‐time PCR. Concentrations of miR‐18a, ‐21, ‐22, and ‐25 in plasma from patients with CRC were significantly altered compared to healthy controls. Combined as a multimarker panel, they detected CRC with an AUC of 0.93. Furthermore, levels of these three miRNAs also showed different levels in the prediagnostic case samples close to diagnosis. Only miR‐21‐levels were elevated several years before diagnosis. Plasma levels of miR‐18a, ‐21, ‐22, and ‐25 show promise as screening biomarkers for CRC. However, based on our unique analysis of prediagnostic and postdiagnostic samples from the same patients, we conclude that circulating miRNAs elevated at diagnosis may not automatically be suitable for CRC screening, if the increase occurs too close to clinical diagnosis.

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