liu.seSearch for publications in DiVA
Change search
Refine search result
2345678 201 - 250 of 9883
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 201.
    Akerstedt, Anita
    et al.
    Child and Youth Habilitat, Eksjo, Sweden .
    Risto, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Ödman, Pia
    Linköping University, Department of Medicine and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Öberg, Birgitta
    Linköping University, Department of Medicine and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Public Health Sciences.
    Evaluation of single event multilevel surgery and rehabilitation in children and youth with cerebral palsy - A 2-year follow-up study2010In: DISABILITY AND REHABILITATION, ISSN 0963-8288, Vol. 32, no 7, p. 530-539Article in journal (Refereed)
    Abstract [en]

    Method. A prospective single-subject study with AB design and 2-year follow-up, included 11 children between 8 and 18 years old with CP, Gross Motor Function Classification System I-III. Visual analyses were used to present physical function with Physical Cost Index (PCI). Descriptive statistics were used to present number of children with a clinically important change in Gross Motor Function Measure (GMFM), self-reported walking ability, and HRQOL with child health questionnaire (CHQ). Results. PCI showed a trend of lower energy cost during gait in six children and GMFM was unchanged for 10 children and improved for one child. Walking ability was improved in 10 children. Gait distance increased in all 11. Both physical and psychosocial dimensions of CHQ improved in six of nine (two missing data). Expectations of outcomes were fulfilled in seven and partly fulfilled in four. Satisfaction with care was fulfilled in 10 of 11. Conclusion. Self-reported walking ability improved after multilevel surgery and intensive rehabilitation. This result was partly supported by lower energy cost and improved HRQOL. Expectations and satisfaction were fulfilled for the majority of children.

  • 202.
    Akesson, K.
    et al.
    Jonköping University, Sweden; Jonköping University, Sweden; Jonköping University, Sweden.
    Tompa, A.
    Jonköping University, Sweden; Jonköping University, Sweden.
    Ryden, A.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Novo Nordisk Inc, WA USA.
    Faresjo, M.
    Jonköping University, Sweden; Jonköping University, Sweden; Jonköping University, Sweden.
    Low expression of CD39(+)/CD45RA(+) on regulatory T cells (T-reg) cells in type 1 diabetic children in contrast to high expression of CD101(+)/CD129(+) on T-reg cells in children with coeliac disease2015In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 180, no 1, p. 70-82Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) and coeliac disease are both characterized by an autoimmune feature. As T1D and coeliac disease share the same risk genes, patients risk subsequently developing the other disease. This study aimed to investigate the expression of T helper (Th), T cytotoxic (Tc) and regulatory T cells (T-reg) in T1D and/or coeliac disease children in comparison to healthy children. Subgroups of T cells (Th:CD4(+) or Tc:CD8(+)); naive (CD27(+)CD28(+)CD45RA(+)CCR7(+)), central memory (CD27(+)CD28(+)CD45RA(-)CCR7(+)), effector memory (early differentiated; CD27(+)CD28(+)CD45RA(-)CCR7(-) and late differentiated; CD27(-)CD28(-)CD45RA(-)CCR7(-)), terminally differentiated effector cells (TEMRA; CD27(-)CD28(-)CD45RA(+)CCR7(-)) and T-reg (CD4(+)CD25(+)FOXP3(+)CD127(-)) cells, and their expression of CD39, CD45RA, CD101 and CD129, were studied by flow cytometry in T1D and/or coeliac disease children or without any of these diseases (reference group). Children diagnosed with both T1D and coeliac disease showed a higher percentage of TEMRA CD4(+) cells (Pless than005), but lower percentages of both early and late effector memory CD8(+) cells (Pless than005) compared to references. Children with exclusively T1D had lower median fluorescence intensity (MFI) of forkhead box protein 3 (FoxP3) (Pless than005) and also a lower percentage of CD39(+) and CD45RA(+) within the T-reg population (CD4(+)CD25(+)FOXP3(+)CD127(-)) (Pless than005). Children with exclusively coeliac disease had a higher MFI of CD101 (Pless than001), as well as a higher percentage of CD129(+) (Pless than005), in the CD4(+)CD25(hi) lymphocyte population, compared to references. In conclusion, children with combined T1D and coeliac disease have a higher percentage of differentiated CD4(+) cells compared to CD8(+) cells. T1D children show signs of low CD39(+)/CD45RA(+) T-reg cells that may indicate loss of suppressive function. Conversely, children with coeliac disease show signs of CD101(+)/CD129(+) T-reg cells that may indicate suppressor activity.

  • 203.
    Akesson, Karin
    et al.
    Ryhov County Hospital, Sweden; Jonköping County Council, Sweden; University of Jonköping, Sweden.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    The influence of age, gender, insulin dose, BMI, and blood pressure on metabolic control in young patients with type 1 diabetes2015In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 16, no 8, p. 581-586Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo explore the relationship between certain clinical variables and metabolic HbA1c at diagnosis correlated to HbA1c at follow-up (p less than 0.001). There was a clear gender difference regarding HbA1c. Girls had higher values both at diagnosis and at follow-up (p less than 0.001). Girls also had lower BMI and pH at diagnosis than boys (p less than 0.001). In contrast, girls with the highest body mass index (BMI) at follow-up had higher mean HbA1c at follow-up in 2010 (p less than 0.001). Having a mother and/or a father with high BMI implied higher HbA1c at diagnosis (p less than 0.003). ConclusionsHbA1c at diagnosis seems to predict metabolic control years later. There is a gender difference at diagnosis as female patients have higher HbA1c than males at diagnosis as well as at follow up. As metabolic control is very much correlated to complications there is a need to early identify patients at risk of poor metabolic control. Even though we do not know whether a high HbA1c level is mainly due to severity of the disease or to behavioral patterns, new ways to treat and support these children, especially girls, are needed.

  • 204.
    Aksenova, Vasilisa
    et al.
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia; Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, St. Petersburg, Russia.
    Turoverova, Lidia
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia.
    Khotin, Mikhail
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Tulchinsky, Eugene
    Department of Cancer Studies and Molecular Medicine, University of Leicester, RKCSB, LRI, Leicester, UK.
    Melino, Gerry
    Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, St. Petersburg, Russia; MRC Toxicology Unit, Leicester, UK.
    Pinaev, George P
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia.
    Barlev, Nickolai
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia; Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, St. Petersburg, Russia; Department of Biochemistry, University of Leicester, Lancaster Road, Leicester, UK.
    Tentler, Dmitri
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia; Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, St. Petersburg, Russia.
    Correction: Actin-binding protein alpha-actinin 4 (ACTN4) is a transcriptional co-activator of RelA/p65 sub-unit of NF-kB (vol 4, pg 362, 2013)2018In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 76, p. 34450-34450Article in journal (Other academic)
    Abstract [en]

    [This corrects the article DOI: 10.18632/oncotarget.901.].

  • 205.
    Aksenova, Vasilisa
    et al.
    Russian Academy of Sciences, St. Petersburg, Russia.
    Turoverova, Lidia
    Russian Academy of Sciences, St. Petersburg, Russia.
    Khotin, Mikhail
    Russian Academy of Sciences, St. Petersburg, Russia.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Tulchinsky, Eugene
    University of Leicester, UK.
    Melino, Gerry
    Saint-Petersburg Technological Institute, Russia.
    Pinaev, George P.
    Russian Academy of Sciences, St. Petersburg, Russia.
    Barlev, Nicolai
    Russian Academy of Sciences, St. Petersburg, Russia.
    Tentler, Dmitri
    Russian Academy of Sciences, St. Petersburg, Russia.
    Actin-binding protein alpha-actinin 4 (ACTN4) is a transcriptional co-activator of RelA/p65 sub-unit of NF-kB2013In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 4, no 2, p. 362-372Article in journal (Refereed)
    Abstract [en]

    ACTN4 is an actin-binding protein that participates in cytoskeleton organisation. It resides both in the cytoplasm and nucleus and physically associates with various transcription factors. Here, we describe an effect of ACTN4 expression on transcriptional activity of the RelA/p65 subunit of NF-kB. We demonstrate that ACTN4 enhances RelA/p65-dependant expression of c-fos, MMP-3 and MMP-1 genes, but it does not affect TNC, ICAM1 and FN1 expression. Importantly, actin-binding domains of ACTN4 are not critical for the nuclear translocation and co-activation of RelA/p65-dependent transcription. Collectively, our data suggest that in the nucleus, ACTN4 functions as a selective transcriptional co-activator of RelA/p65.

  • 206.
    Al-Amiry, Bariq
    et al.
    Umea Univ, Sweden.
    Pantelakis, Georgios
    Umea Univ, Sweden.
    Mahmood, Sarwar
    Umea Univ, Sweden.
    Kadum, Bakir
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Brismar, Torkel B.
    Karolinska Inst, Sweden.
    Sayed-Noor, Arkan S.
    Umea Univ, Sweden.
    Does body mass index affect restoration of femoral offset, leg length and cup positioning after total hip arthroplasty?: A prospective cohort study2019In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, BMC MUSCULOSKELETAL DISORDERS, Vol. 20, no 1, article id 422Article in journal (Refereed)
    Abstract [en]

    Background

    In obese patients, total hip arthroplasty (THA) can be technically demanding with increased perioperative risks. The aim of this prospective cohort study is to evaluate the effect of body mass index (BMI) on radiological restoration of femoral offset (FO) and leg length as well as acetabular cup positioning.

    Methods

    In this prospective study, patients with unilateral primary osteoarthritis (OA) treated with THA between September 2010 and December 2013 were considered for inclusion. The perioperative plain radiographs were standardised and used to measure the preoperative degree of hip osteoarthritis, postoperative FO, leg length discrepancy (LLD), acetabular component inclination and anteversion.

    Results

    We included 213 patients (74.5% of those considered for inclusion) with a mean BMI of 27.7 (SD 4.5) in the final analysis. The postoperative FO was improper in 55% and the LLD in 15%, while the cup inclination and anteversion were improper in 13 and 23% of patients respectively. A multivariable logistic regression model identified BMI as the only factor that affected LLD. Increased BMI increased the risk of LLD (OR 1.14, 95% CI 1.04 to 1.25). No other factors included in the model affected any of the primary or secondary outcomes.

    Conclusion

    Increased BMI showed a negative effect on restoration of post-THA leg length but not on restoration of FO or positioning of the acetabular cup. Age, gender, OA duration or radiological severity and surgeon’s experience showed no relation to post-THA restoration of FO, leg length or cup positioning.

  • 207.
    Alarcon, E I
    et al.
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Vulesevic, B
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Argawal, A
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Ross, A
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Bejjani, P
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Podrebarac, J
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Ravichandran, Ranjithkumar
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Phopase, Jaywant
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Suuronen, E J
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Coloured cornea replacements with anti-infective properties: expanding the safe use of silver nanoparticles in regenerative medicine.2016In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 8, no 12, p. 6484-6489Article in journal (Refereed)
    Abstract [en]

    Despite the broad anti-microbial and anti-inflammatory properties of silver nanoparticles (AgNPs), their use in bioengineered corneal replacements or bandage contact lenses has been hindered due to their intense yellow coloration. In this communication, we report the development of a new strategy to pre-stabilize and incorporate AgNPs with different colours into collagen matrices for fabrication of corneal implants and lenses, and assessed their in vitro and in vivo activity.

  • 208.
    Alarcon, Emilio I.
    et al.
    University of Ottawa, Canada; University of Ottawa, Canada; University of Ottawa, Canada.
    Udekwu, Klas I.
    Karolinska Institute, Sweden.
    Noel, Christopher W.
    University of Ottawa, Canada; .
    Gagnon, Luke B. -P.
    University of Ottawa, Canada.
    Taylor, Patrick K.
    University of Ottawa, Canada.
    Vulesevic, Branka
    University of Ottawa, Canada.
    Simpson, Madeline J.
    University of Ottawa, Canada.
    Gkotzis, Spyridon
    Karolinska Institute, Sweden.
    Islam, Mohammed Mirazul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Lee, Chyan-Jang
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Richter-Dahlfors, Agneta
    Karolinska Institute, Sweden.
    Mah, Thien-Fah
    University of Ottawa, Canada.
    Suuronen, Erik J.
    University of Ottawa, Canada.
    Scaiano, Juan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. University of Ottawa, Canada.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Safety and efficacy of composite collagen-silver nanoparticle hydrogels as tissue engineering scaffolds2015In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 7, no 44, p. 18789-18798Article in journal (Refereed)
    Abstract [en]

    The increasing number of multidrug resistant bacteria has revitalized interest in seeking alternative sources for controlling bacterial infection. Silver nanoparticles (AgNPs), are amongst the most promising candidates due to their wide microbial spectrum of action. In this work, we report on the safety and efficacy of the incorporation of collagen coated AgNPs into collagen hydrogels for tissue engineering. The resulting hybrid materials at [AgNPs] less than0.4 mu M retained the mechanical properties and biocompatibility for primary human skin fibroblasts and keratinocytes of collagen hydrogels; they also displayed remarkable anti-infective properties against S. aureus, S. epidermidis, E. coli and P. aeruginosa at considerably lower concentrations than silver nitrate. Further, subcutaneous implants of materials containing 0.2 mu M AgNPs in mice showed a reduction in the levels of IL-6 and other inflammation markers (CCL24, sTNFR-2, and TIMP1). Finally, an analysis of silver contents in implanted mice showed that silver accumulation primarily occurred within the tissue surrounding the implant.

  • 209.
    Alarcon, Emilio I
    et al.
    University of Ottawa.
    Udekwu, Klas
    Karolinska Institute.
    Skog, Mårten
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Pacioni, NataliL
    University of Ottawa.
    Stamplecoskie, Kevin G
    University of Ottawa.
    Gonzalez-Bejar, Maria
    University of Ottawa.
    Polisetti, Naresh
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Wickham, Abeni
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Richter-Dahlfors, Agneta
    Karolinska Institute.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Scaiano, Juan C
    University of Ottawa.
    The biocompatibility and antibacterial properties of collagen-stabilized, photochemically prepared silver nanoparticles2012In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 33, no 19, p. 4947-4956Article in journal (Refereed)
    Abstract [en]

    Spherical 3.5 nm diameter silver nanoparticles (AgNP) stabilized in type I collagen (AgNP@collagen) were prepared in minutes (5-15 min) at room temperature by a photochemical method initiated by UVA irradiation of a water-soluble non-toxic benzoin. This biocomposite was examined to evaluate its biocompatibility and its anti-bacterial properties and showed remarkable properties. Thus, while keratinocytes and fibroblasts were not affected by AgNP@collagen, it was bactericidal against Bacillus megaterium and E. coli but only bacteriostatic against S. epidermidis. In particular, the bactericidal properties displayed by AgNP@collagen were proven to be due to AgNP in AgNP@collagen, rather than to released silver ions, since equimolar concentrations of Ag are about four times less active than AgNP@collagen based on total Ag content. This new biocomposite was stable over a remarkable range of NaCl, phosphate, and 2-(N-morpholino)ethanesulfonic acid concentrations and for over one month at 4 degrees C. Circular dichroism studies show that the conformation of collagen in AgNP@collagen remains intact. Finally, we have compared the properties of AgNP@collagen with a similar biocomposite prepared using alpha-poly-L-Lysine and also with citrate stabilized AgNP; neither of these materials showed comparable biocompatibility, stability, or anti-bacterial activity.

  • 210.
    Alavian, S.M.
    et al.
    Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Tehran.
    Ande, S.R.
    University of Manitoba.
    Coombs, K.M.
    University of Manitoba.
    Yeganeh, B.
    University of Manitoba.
    Davoodpour, Padideh
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Hashemi, M.
    Zahedan University of Medical Sceince, Iran.
    Los, Marek Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Ghavami, S.
    University of Manitoba.
    Virus-triggered autophagy in viral hepatitis - possible novel strategies for drug development2011In: Journal of Viral Hepatitis, ISSN 1352-0504, E-ISSN 1365-2893, Vol. 18, no 12, p. 821-830Article, review/survey (Refereed)
    Abstract [en]

    . Autophagy is a very tightly regulated process that is important in many cellular processes including development, differentiation, survival and homoeostasis. The importance of this process has already been proven in numerous common diseases such as cancer and neurodegenerative disorders. Emerging data indicate that autophagy plays an important role in some liver diseases including liver injury induced by ischaemia reperfusion and alpha-1 antitrypsin Z allele-dependent liver disease. Autophagy may also occur in viral infection, and it may play a crucial role in antimicrobial host defence against pathogens, while supporting cellular homoeostasis processes. Here, the latest findings on the role of autophagy in viral hepatitis B and C infection, which are both serious health threats, will be reviewed.

  • 211.
    Al-Ayoubi, Fawzi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Eriksson, Helene
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wallon, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Uneven distribution of emergency operations and lack of trauma: a call for reorganization of acute surgical care?2012In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 20Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Subspecialisation within general surgery has today reached further than ever. However, on-call time, an unchanged need for broad surgical skills are required to meet the demands of acute surgical disease and trauma. The introduction of a new subspecialty in North America that deals solely with acute care surgery and trauma is an attempt to offer properly trained surgeons also during on-call time. To find out whether such a subspecialty could be helpful in Sweden we analyzed our workload for emergency surgery and trauma. METHODS: Linkoping University Hospital serves a population of 257 000. Data from 2010 for all patients, diagnoses, times and types of operations, surgeons involved, duration of stay, types of injury and deaths regarding emergency procedures were extracted from a prospectively-collected database and analyzed. RESULTS: There were 2362 admissions, 1559 emergency interventions; 835 were mainly abdominal operations, and 724 diagnostic or therapeutic endoscopies. Of the 1559 emergency interventions, 641 (41.1%) were made outside office hours, and of 453 minor or intermediate procedures (including appendicectomy, cholecystectomy, or proctological procedures) 276 (60.9%) were done during the evenings or at night. Two hundred and fifty-four patients were admitted with trauma and 29 (11.4%) required operation, of whom general surgeons operated on eight (3.1%). Thirteen consultants and 11 senior registrars were involved in 138 bowel resections and 164 cholecystectomies chosen as index operations for standard emergency surgery. The median (range) number of such operations done by each consultant was 6 (3--17) and 6 (1--22). Corresponding figures for senior registrars were 7 (0--11) and 8 (1--39). CONCLUSION: There was an uneven distribution of exposure to acute surgical problems and trauma among general surgeons. Some were exposed to only a few standard emergency interventions and most surgeons did not operate on a single patient with trauma. Further centralization of trauma care, long-term positions at units for emergency surgery and trauma, and subspecialisation in the fields of emergency surgery and trauma, might be options to solve problems of low volumes.

  • 212.
    Albertsson-Wikland, Kerstin
    et al.
    University of Gothenburg, Sweden.
    Mårtensson, Anton
    University of Gothenburg, Sweden; Stat Konsultgrp, Sweden.
    Savendahl, Lars
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Niklasson, Aimon
    University of Gothenburg, Sweden.
    Bang, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dahlgren, Jovanna
    University of Gothenburg, Sweden.
    Gustafsson, Jan
    Uppsala University, Sweden.
    Kriström, Berit
    Umeå University, Sweden.
    Norgren, Svante
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Pehrsson, Nils-Gunnar
    Stat Konsultgrp, Sweden.
    Oden, Anders
    Stat Konsultgrp, Sweden; Chalmers, Sweden.
    Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics2016In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 5, p. 2149-2159Article in journal (Refereed)
    Abstract [en]

    Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P amp;lt; .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P amp;lt; .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P amp;lt; .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

  • 213.
    Albrecht, Inka
    et al.
    Karolinska Institute, Sweden.
    Wick, Cecilia
    Karolinska Institute, Sweden.
    Hallgren, Asa
    Karolinska Institute, Sweden.
    Tjarnlund, Anna
    Karolinska Institute, Sweden.
    Nagaraju, Kanneboyina
    Childrens National Medical Centre, DC 20010 USA.
    Andrade, Felipe
    Johns Hopkins University, MD 21205 USA.
    Thompson, Kathryn
    Childrens National Medical Centre, DC 20010 USA.
    Coley, William
    Childrens National Medical Centre, DC 20010 USA.
    Phadke, Aditi
    Childrens National Medical Centre, DC 20010 USA.
    Diaz-Gallo, Lina-Marcela
    Karolinska Institute, Sweden.
    Bottai, Matteo
    Karolinska Institute, Sweden.
    Nennesmo, Inger
    Karolinska Institute, Sweden.
    Chemin, Karine
    Karolinska Institute, Sweden.
    Herrath, Jessica
    Karolinska Institute, Sweden.
    Johansson, Karin
    Karolinska Institute, Sweden.
    Wikberg, Anders
    Karolinska Institute, Sweden.
    Jimmy Ytterberg, A.
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Zubarev, Roman A.
    Karolinska Institute, Sweden.
    Danielsson, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Krystufkova, Olga
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic.
    Vencovsky, Jiri
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic.
    Landegren, Nils
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Wahren-Herlenius, Marie
    Karolinska Institute, Sweden.
    Padyukov, Leonid
    Karolinska Institute, Sweden.
    Kampe, Olle
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Lundberg, Ingrid E.
    Karolinska Institute, Sweden.
    Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies2015In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 125, no 12, p. 4612-4624Article in journal (Refereed)
    Abstract [en]

    Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1-negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.

  • 214.
    Al-Chalabi, Ammar
    et al.
    Kings Coll London, England.
    Andersen, Peter M.
    Umeå University, Sweden.
    Chandran, Siddharthan
    University of Edinburgh, Scotland.
    Chio, Adriano
    University of Torino, Italy.
    Corcia, Philippe
    CHU Tours, France.
    Couratier, Philippe
    CHU Limoges, France.
    Danielsson, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    de Carvalho, Mamede
    University of Lisbon, Portugal; H Santa Maria CHLN, Portugal.
    Desnuelle, Claude
    CHU Nice, France.
    Grehl, Torsten
    Alfried Krupp Hospital, Germany.
    Grosskreutz, Julian
    Jena University Hospital, Germany.
    Holmoy, Trygve
    Kershus University of Lorenskog, Norway.
    Ingre, Caroline
    Karolinska Institute, Sweden.
    Karlsborg, Merete
    Bispebjerg Hospital, Denmark.
    Kleveland, Grethe
    Sykehuset Innlandet, Norway.
    Christoph Koch, Jan
    University of Medical Gottingen, Germany.
    Koritnik, Blaz
    University of Medical Centre Ljubljana, Slovenia.
    KuzmaKozakiewicz, Magdalena
    Medical University of Warsaw, Poland.
    Laaksovirta, Hannu
    University of Helsinki, Finland.
    Ludolph, Albert
    University of Ulm, Germany.
    McDermott, Christopher
    University of Sheffield, England.
    Meyer, Thomas
    University of Medical Berlin, Germany.
    Mitre Ropero, Bernardo
    Sahlgrens University Hospital, Sweden.
    Mora Pardina, Jesus
    Hospital San Rafael, Spain.
    Nygren, Ingela
    Uppsala University, Sweden.
    Petri, Susanne
    Hannover Medical Sch, Germany.
    Povedano Panades, Monica
    University of Bellvitge, Spain.
    Salachas, Francois
    Hop Salptriere, France.
    Shaw, Pamela
    University of Sheffield, England.
    Silani, Vincenzo
    University of Milan, Italy; University of Milan, Italy.
    Staaf, Gert
    Lund University, Sweden.
    Svenstrup, Kirsten
    Bispebjerg Hospital, Denmark.
    Talbot, Kevin
    University of Oxford, England.
    Tysnes, Ole-Bjorn
    Haukeland University of Sjukehus, Norway.
    Van Damme, Philip
    University of Leuven, Belgium; VIB Centre Brain and Disease Research, Belgium; University Hospital Leuven, Belgium.
    van der Kooi, Anneke
    University of Amsterdam Centre, Netherlands.
    Weber, Markus
    Kantonssp St Gallen, Switzerland.
    Weydt, Patrick
    University of Bonn, Germany.
    Wolf, Joachim
    Diakonissen Hospital, Germany.
    Hardiman, Orla
    Trinity Coll Dublin, Ireland.
    van den Berg, Leonard H.
    University of Medical Centre Utrecht, Netherlands.
    July 2017 ENCALS statement on edaravone2017In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, no 7-8, p. 471-474Article in journal (Refereed)
    Abstract [en]

    n/a

  • 215.
    Aldonyte, R
    et al.
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Tunaitis, V
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Surovas, A
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Suriakaite, K
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Jarmalaviciute, A
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Magnusson, Karl-Erik
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Pivoriunas, A
    Vilnius University, Zygimantu 9, Vilnius LT-01102, Lithuania.
    Effects of major human antiprotease alpha-1-antitrypsin on the motility and proliferation of stromal cells from human exfoliated deciduous teeth2010In: e-biomed: Journal of Regenerating Medicine, ISSN 1524-8909, Vol. 5, no 4, p. 633-643Article in journal (Refereed)
    Abstract [en]

    AIM: Intrinsic tissue regeneration mechanisms are still not fully understood. The destruction/reconstruction processes are usually in fine balance; however, this can be easily destroyed, for example in the environment of chronic inflammation. One of the major proteins present at the inflammatory sites is the multifunctional protein alpha-1-antitrypsin (AAT). In this study, potential therapeutic effects of this major human antiprotease on progenitor cells are assessed.

    MATERIALS & METHODS: Stromal cells from human exfoliated deciduous teeth (SHEDs) were used, which are similar to the mesenchymal stromal cells isolated from other tissues. SHEDs were cultivated in the presence of subphysiological, physiological and inflammatory concentrations of AAT, and their proliferation and motility traits were assayed. Some intracellular signaling pathways, AAT internalization by SHEDs and their matrix metalloprotease profile were studied in parallel.

    RESULTS: Physiologic and inflammatory concentrations of AAT significantly increased the cell proliferation rate, induced phosphorylation of several key protein kinases and increased the amount of secreted active gelatinases. Moreover, cells exposed to physiologic and inflammatory levels of AAT were able to invade and migrate more efficiently. Subphysiologic AAT levels did not change cell behavior significantly.

    CONCLUSION: AAT at physiologic and inflammatory concentrations positively modulates the proliferation and motility of SHEDs in vitro. These results suggest the importance of AAT in the maintenance and regulation of tissue progenitor cells in vivo.

  • 216.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hermansson, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Somasunduram, Konduri
    Centre for Social Medicine, Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Bangal, Vidyadhar
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Patil, Ashok
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Chandekar, Pratibha
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Johansson, AnnaKarin
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Nurse-based antenatal and child health care in rural India, implementation and effects - an Indian-Swedish collaboration2012In: Rural and remote health, ISSN 1445-6354, Vol. 12, no 3Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Improving maternal and child health care are two of the Millennium Development Goals of the World Health Organization. India is one of the countries worldwide most burdened by maternal and child deaths. The aim of the study was to describe how families participate in nurse-based antenatal and child health care, and the effect of this in relation to referrals to specialist care, institutional deliveries and mortality.

    METHODS:

    The intervention took place in a remote rural area in India and was influenced by Swedish nurse-based health care. A baseline survey was performed before the intervention commenced. The intervention included education program for staff members with a model called Training of Trainers and the establishment of clinics as both primary health centers and mobile clinics. Health records and manuals, and informational and educational materials were produced and the clinics were equipped with easily handled instruments. The study period was between 2006 and 2009. Data were collected from antenatal care and child healthcare records. The Chi-square test was used to analyze mortality differences between years. A focus group discussion and a content analysis were performed.

    RESULTS:

    Families' participation increased which led to more check-ups of pregnant women and small children. Antenatal visits before 16 weeks among pregnant women increased from 32 to 62% during the period. Women having at least three check-ups during pregnancy increased from 30 to 60%. Maternal mortality decreased from 478 to 121 per 100 000 live births. The total numbers of children examined in the project increased from approximately 6000 to 18 500 children. Infant mortality decreased from 80 to 43 per 1000 live births. Women and children referred to specialist care increased considerably and institutional deliveries increased from 47 to 74%.

    CONCLUSION:

    These results suggest that it is possible in a rural and remote area to influence peoples' awareness of the value of preventive health care. The results also indicate that this might decrease maternal and child mortality. The education led to a more patient-friendly encounter between health professionals and patients.

  • 217.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Gender and Medicine. Linköping University, Faculty of Health Sciences.
    Lundberg, Ulf
    Division of Biological Psychology, Department of Psychology, Stockholm University, Stockholm, Sweden.
    Wijma, Klaas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Psychology. Linköping University, Faculty of Health Sciences.
    Fear, pain and stress hormones during childbirth2005In: Journal of Psychosomatic Obstetrics and Gynaecology, ISSN 0167-482X, E-ISSN 1743-8942, Vol. 26, no 3, p. 153-165Article in journal (Refereed)
    Abstract [en]

    Aims. To investigate the course of fear, pain and stress hormones during labor, and the associations between fear, pain, stress hormones and duration of labor in nulliparous women with and without epidural analgesia (EDA).

    Method.  One day during gestation weeks 37–39, urinary and salivary samples were collected to measure catecholamines and cortisol. Hourly during labor, the participants answered the Delivery Fear Scale and a pain intensity scale, and urinary and salivary samples were collected to measure stress hormones.

    Results. The course of fear, pain and stress hormones differed throughout labor in women with and without EDA. Pain and cortisol increased throughout labor in women without EDA. Women who received EDA had more fear, but not more pain, before the administration of the EDA than women who did not receive EDA. Pain, fear and catecholamines decreased when women received EDA, but fear and pain increased again later in labor. Fear and pain correlated, as well as levels of fear in the different phases of labor. During phase one of labor epinephrine and duration of the phase were negatively correlated.

    Conclusion.  The course of fear, pain and concentrations of stress hormones differed, highly influenced by the administration of EDA. Fear and pain correlated more pronounced than stress hormones and fear, pain and duration of labor.

  • 218.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medicine and Care, Nursing Science. Linköping University, Faculty of Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Gender and Medicine. Linköping University, Faculty of Health Sciences.
    Wijma, Klaas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Psychology. Linköping University, Faculty of Health Sciences.
    Fear of childbirth before, during, and after childbirth2006In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 85, no 1, p. 56-62Article in journal (Refereed)
    Abstract [en]

    Background. Only scanty research exists about the relationship between women's expectations during pregnancy and their experiences as reported during the actual process of labor and afterwards. The aims of the present study were: 1. to investigate the associations between fear of childbirth during pregnancy and postpartum and fear and pain during early active labor (phase 1: cervix dilatation 3–5 cm), and 2. to explore possible differences regarding fear of childbirth during pregnancy and postpartum between women who did or did not receive epidural analgesia during labor.

    Methods. Fear of childbirth was measured in 47 nulliparous women during gestation weeks 37–39 by means of the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ version A). During early active labor we measured women's fear (Delivery Fear Scale) and their experiences of pain (a pain intensity scale). Finally, fear after childbirth (W-DEQ version B) was measured two hours, two days, and five weeks after delivery.

    Results. A positive correlation appeared between fear of childbirth during pregnancy, postpartum, and early active labor. There were no differences in fear of childbirth during late pregnancy between women who received epidural analgesia and those who did not. Postpartum fear was higher in the women who had received epidural analgesia.

    Conclusions. Pregnant women who fear childbirth are prone to report fear during the actual labor and postpartum. The administration of epidural analgesia is not a sufficient response to women's fear during the process of labor.

  • 219.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Cystatin C and NT-proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients with heart failure: results from a 10-year study in primary care2009In: EUROPEAN JOURNAL OF HEART FAILURE, ISSN 1388-9842, Vol. 11, no 4, p. 354-360Article in journal (Refereed)
    Abstract [en]

    Heart failure (HF) is common among the elderly patients. It is essential to identify those at high risk in order to optimize the use of resources. We aimed to evaluate whether a combination of two biomarkers might give better prognostic information about the risk of cardiovascular (CV) mortality in patients with symptoms associated with HF, compared with only one biomarker. Four hundred and sixty-four primary health-care patients (mean age 73 years, range 65-87) with symptoms of HF were examined. All patients were evaluated using Doppler echocardiography and blood samples, including measurement of cystatin C and NT-proBNP. The patients were followed over a 10-year period. Patients with serum cystatin C levels within the highest quartile had almost three times the risk (HR: 2.92; 95% CI: 1.23-4.90) of CV mortality compared with those patients who had levels within the first, second, or third quartiles. If, at the same time, the patient had a plasma concentration of NT-proBNP within the highest quartile, the risk increased to andgt; 13 times (HR: 13.61; 95% CI: 2.56-72.24) during 10 years of follow-up or andgt; 17 times (HR: 17.04; 95% CI: 1.80-163.39) after 5 years of follow-up. Combined analysis of cystatin C and NT-proBNP could provide important prognostic information among elderly patients in the community with symptoms of HF.

  • 220.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure.2010In: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, ISSN 1473-5733, Vol. 21, no 1, p. 62-9Article in journal (Refereed)
    Abstract [en]

    Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.

  • 221.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Johansson, Peter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Björnstedt, Mikael
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 5, p. 1860-1866Article in journal (Refereed)
    Abstract [en]

    Background

    Selenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking.

    Methods

    A 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention.

    The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan–Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied.

    Results

    During a follow up time of 5.2 years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P = 0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months; P = 0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P = 0.03).

    Conclusion

    Long-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography.

  • 222.
    Alehagen, Urban
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Björnstedt, Mikael
    Division of Pathology F42, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Post, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Relatively high mortality risk in elderly Swedish subjects with low selenium status2016In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 70, no 1, p. 91-96Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: 

    The daily dietary intake of selenium (Se), an essential trace element, is still low in Sweden in spite of decades of nutritional information campaigns and the effect of this on the public health is presently not well known. The objective of this study was to determine the serum Se levels in an elderly Swedish population and to analyze whether a low Se status had any influence on mortality.

    Subjects/Methods: 

    Six-hundred sixty-eight (n=668) elderly participants were invited from a municipality and evaluated in an observational study. Individuals were followed for 6.8 years and Se levels were re-evaluated in 98 individuals after 48 months. Clinical examination of all individuals included functional classification, echocardiography, electrocardiogram and serum Se measurement. All mortality was registered and endpoints of mortality were assessed by Kaplan–Meier plots, and Cox proportional hazard ratios adjusted for potential confounding factors were calculated.

    Results: 

    The mean serum Se level of the study population (n=668) was 67.1 μg/l, corresponding to relatively low Se intake. After adjustment for male gender, smoking, ischemic heart disease, diabetes, chronic obstructive pulmonary disease and impaired heart function, persons with serum Se in the lowest quartile had 43% (95% confidence interval (CI): 1.02–2.00) and 56% (95% CI: 1.03–2.36) increased risk for all-cause and cardiovascular mortality, respectively. The result was not driven by inflammatory effects on Se concentration in serum.

    Conclusion: 

    The mean serum Se concentration in an elderly Swedish population was 67.1 μg/l, which is below the physiological saturation level for several selenoprotein enzymes. This result may suggest the value of modest Se supplementation in order to improve the health of the Swedish population.

  • 223.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Svensson, Erland
    Swedish Def Research Agency, Sweden.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, p. e0137680-Article in journal (Refereed)
    Abstract [en]

    Background/Objectives Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q(10) , important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality. Subjects/Methods 437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots. Results The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group. Conclusion CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q(10) combined. A reduced cardiovascular mortality could be demonstrated in the active group, irrespective of biomarker level. This result should be regarded as hypothesis-generating, and it is hoped it will stimulate more research in the area.

  • 224.
    Aleman, Soo
    et al.
    Departments of Gastroenterology and Hepatology, Karolinska University Hospital/Karolinska Institutet, Stockholm.
    Endalib, Sanam
    Departments of Gastroenterology and Hepatology, Karolinska University Hospital/Karolinska Institutet, Stockholm.
    Stal, Per
    Departments of Gastroenterology and Hepatology, Karolinska University Hospital/Karolinska Institutet, Stockholm.
    Loof, Lars
    Clinincal Research Centre, Västerås.
    Lindgren, Stefan
    Skåne University Hospital, Lund/Malmö.
    Sandberg-Gertzen, Hanna
    Örebro University Hospital, Örebro.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Olsson, Sigvard
    Sahlgrenska University Hospital, Göteborg.
    Danielsson, Ake
    Umeå University Hospital, Umeå.
    Wallerstedt, Sven
    Sahlgrenska University Hospital, Göteborg.
    Hultcrantz, Rolf
    Departments of Gastroenterology and Hepatology, Karolinska University Hospital/Karolinska Institutet, Stockholm.
    Health check-ups and family screening allow detection of hereditary hemochromatosis with less advanced liver fibrosis and survival comparable with the general population2011In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 46, no 9, p. 1118-1126Article in journal (Refereed)
    Abstract [en]

    Objective. The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected. Patients and methods. 373 patients with hemochromatosis detected through routine health checkups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.9 +/- 5.8 years. The degree of liver fibrosis and survival were analyzed. Results. Overall survival among these patients was not significantly different from that of a matched normal population. The patients diagnosed through health check-ups and family screening were detected at an earlier age and had the highest rate of survival. Liver biopsy at the time of diagnosis revealed cirrhosis in 9% of those detected through the health check-ups and 5% in the case of family screening, compared with 13% for the group with arthralgia, 17% for other diseases/symptoms and 42% for liver disease. Conclusion. Health check-ups and family screening allow detection of hereditary hemochromatosis at an earlier age and with less advanced liver fibrosis, although a few of these patients have already developed cirrhosis. Our study indicates that iron indices should be included in health check-ups, and if abnormal, should lead to further investigation.

  • 225.
    Alevronta, Eleftheria
    et al.
    Karolinska Institute, Sweden; Sahlgrens Acad, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    al-Abany, Massoud
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Nyberg, Tommy
    Karolinska Institute, Sweden.
    Lind, Helena
    Karolinska Institute, Sweden.
    Waldenstrom, Ann-Charlotte
    Sahlgrens Acad, Sweden; Sahlgrens University Hospital, Sweden.
    Olsson, Caroline
    Sahlgrens Acad, Sweden; Gothenburg University, Sweden.
    Dunberger, Gail
    Karolinska Institute, Sweden; Ersta Skondal University of Coll, Sweden.
    Bergmark, Karin
    Karolinska Institute, Sweden; Sahlgrens Acad, Sweden; Sahlgrens University Hospital, Sweden.
    Steineck, Gunnar
    Karolinska Institute, Sweden; Sahlgrens Acad, Sweden.
    Lind, Bengt K.
    Karolinska Institute, Sweden.
    Time-dependent dose-response relation for absence of vaginal elasticity after gynecological radiation therapy2016In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 120, no 3, p. 537-541Article in journal (Refereed)
    Abstract [en]

    Background and purpose: To investigate the dose-response relation between the dose to the vagina and the patient-reported symptom absence of vaginal elasticity and how time to follow-up influences this relation. Material and methods: The study included 78 long-term gynecological cancer survivors treated between 1991 and 2003 with external beam radiation therapy. Of those, 24 experienced absence of vaginal elasticity. A normal tissue complication model is introduced that takes into account the influence of time to follow-up on the dose-response relation and the patients age. The best estimates of the dose-response parameters were calculated using Probit, Probit-Relative Seriality (RS) and Probit-time models. Log likelihood (LL) values and the Akaike Information Criterion (AIC) were used to evaluate the model fit. Results: The dose-response parameters for absence of vaginal elasticity according to the Probit and Probit-time models with the 68% Confidence Intervals (CI) were: LL = 39.8, D-50 = 49.7 (47.2-52.4) Gy, gamma(50) =1.40 (1.12-1.70) and LL = 37.4, D-50 = 46.9 (43.5-50.9) Gy, gamma(50) = 1.81 (1.17-2.51) respectively. Conclusions: The proposed model, which describes the influence of time to follow-up on the dose response relation, fits our data best. Our data indicate that the steepness of the dose-response curve of the dose to the vagina and the symptom absence of vaginal elasticity increases with time to follow-up, while D-50 decreases. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 226.
    Alexandre, Campos
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Apraiz, Itzaso
    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
    da Fonseca, Rute R
    The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
    Cristobal, Susana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Shotgun analysis of the marine mussel Mytilus edulis hemolymph proteome and mapping the innate immunity elements.2015In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 15, no 23-24, p. 4021-4029Article in journal (Refereed)
    Abstract [en]

    The marine mussel innate immunity provides protection to pathogen invasion and inflammation.In this regard, the mussel hemolymph takes a main role in the animal innate response.Despite the importance of this body fluid in determining the physiological condition of theanimal, little is known about the molecular mechanisms underlying the cellular and humoralresponses. In this work, we have applied aMS (nano-LC-MS/MS) strategy integrating genomicand transcriptomic data with the aim to: (i) identify the main protein functional groups thatcharacterize hemolymph and (ii) to map the elements of innate immunity in the marine musselMytilus edulis hemolymph proteome. After sample analysis and first protein identificationbased onMS/MS data comparison, proteins with unknown functions were annotated with blastusing public database (nrNCBI) information. Overall 595 hemolymph proteins were identifiedwith high confidence and annotated. These proteins encompass primary cellular metabolicprocesses: energy production and metabolism of biomolecules, as well as processes related tooxidative stress defence, xenobiotic detoxification, drug metabolism, and immune response.A group of proteins was identified with putative immune effector, receptor, and signalingfunctions in M. edulis. Data are available via ProteomeXchange with identifier PXD001951(http://proteomecentral.proteomexchange.org/dataset/PXD001951).

  • 227.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Clayton, Tim
    London School Hyg and Trop Med, England.
    Damman, Peter
    University of Amsterdam, Netherlands.
    Fox, Keith A. A.
    Royal Infirm, Scotland.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Lagerqvist, Bo
    Department of Cardiology, Cardiothoracic Centre, University Hospital, Uppsala, Sweden.
    Wallentin, Lars
    Department of Cardiology, Cardiothoracic Centre, University Hospital, Uppsala, Sweden.
    de Winter, Robbert J.
    University of Amsterdam, Netherlands.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 4, p. 522-529Article in journal (Refereed)
    Abstract [en]

    Background A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS. Methods Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis. Results Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39). Conclusions In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.

  • 228.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Gustafsson, Kerstin M
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Logander, Elisabeth
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel: Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).2015In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 2, p. 335-340Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.

    METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.

    CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.

  • 229.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Gustafsson, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Janzon, Magnus
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Logander, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction.2019In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 30, no 5, p. 572-578Article in journal (Refereed)
    Abstract [en]

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

  • 230.
    Ali Abdi, Abshir
    et al.
    East Africa University, Somalia.
    Osman, Abdimajid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Prevalence of common hereditary risk factors for thrombophilia in Somalia and identification of a novel Gln544Arg mutation in coagulation factor V2017In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 44, no 4, p. 536-543Article in journal (Refereed)
    Abstract [en]

    Thrombophilia, commonly manifested as venous thromboembolism (VTE), is a worldwide concern but little is known on its genetic epidemiology in many parts of the globe particularly in the developing countries. Here we employed TaqMan genotyping and pyrosequencing to evaluate the prevalence of known common nucleotide polymorphisms associated with thrombophilia in a Somali population in the Puntland region of Somalia. We also employed next generation sequencing (NGS) to investigate other genetic variants in a Somali patient with deep venous thrombosis (DVT). As expected, we found no existence of factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) in the Somali population. The G allele of ABO [261G/delG] polymorphism (rs8176719) was found at a frequency of 29%, similar to that observed in other African populations. We found the lowest so far reported frequency of MTHFR C677T (rs1801133) polymorphism in the Somali population (T allele frequency 1.5%). A novel and deleterious single nucleotide variation in exon 11 of coagulation factor V (c.1631A amp;gt; G) causing Gln544Arg exchange in factor V was identified in a 29 years old Somali female with DVT. The same patient was heterozygous to VKORC1 Asp36Tyr polymorphism (rs61742245) that predisposes to warfarin resistance. In conclusion, this study shows that common hereditary factors for thromboembolism found in Caucasians are either less frequent or absent in the Somali population-similar to the situation in other Africans. NGS is possibly a better choice to detect genetic risk variants for thrombosis in this ethnic group.

  • 231.
    Ali, Fatema Mohammed
    et al.
    Univ Sydney, Australia.
    Westling, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Zhao, Luke Hong Lu
    Univ Sydney, Australia.
    Corneil, Brian D.
    Univ Western Ontario, Canada.
    Camp, Aaron J.
    Univ Sydney, Australia.
    Splenius capitis: sensitive target for the cVEMP in older and neurodegenerative patients2019In: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 276, no 11, p. 2991-3003Article in journal (Refereed)
    Abstract [en]

    Background The vestibular evoked myogenic potential (VEMP) is a technique used to assess vestibular function. Cervical VEMPs (cVEMPs) are obtained conventionally from the sternocleidomastoid (SCM) muscle; however, the dorsal neck muscle splenius capitis (SPL) has also been shown to be a reliable target alongside the SCM in young subjects. Objective This study aimed to compare cVEMPs from the SCM and SPL in two positions across young, older, and Parkinsons disease (PD) patients. Method Experiments were carried out using surface EMG electrodes placed over the SCM and SPL. cVEMPs were measured using a 30 s, 126 dB sound stimulus with 222 individual tone bursts, while subjects were in a supine and head-turned posture (also known as the head elevation method), and in a seated head-turned posture. Results When comparing cVEMPs across positions, the incidence of supine and seated SCM-cVEMPs diminished significantly in older and PD patients in comparison with young subjects. However, no statistically significant differences in incidences were found in seated SPL-cVEMPs when comparing young, older and PD patients. SPL-cVEMPs were present significantly more often than seated SCM-cVEMPs in PD patients. Conclusions SPL-cVEMPs are not altered to the same extent that SCM-cVEMPs are by aging and disease and its addition to cVEMP testing may reduce false-positive tests for vestibulopathy.

  • 232.
    Ali Khan, Ghazanfar
    et al.
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Maqbool Khan, Kashif
    College of Pharmacy, University of Punjab, Lahore, Pakistan.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fick, Jerker
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Occurrence and Abundance of Antibiotics and Resistance Genes in Rivers, Canal and near Drug Formulation Facilities – A Study in Pakistan2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6Article in journal (Refereed)
    Abstract [en]

    Antibiotic resistance (AR) is a global phenomenon that has severe epidemiological ramifications world-wide. It has been suggested that antibiotics that have been discharged into the natural aquatic environments after usage or manufacture can promote the occurrence of antibiotic resistance genes (ARG). These environmental ARGs could serve as a reservoir and be horizontally transferred to human-associated bacteria and thus contribute to AR proliferation. The aim of this study was to investigate the anthropogenic load of antibiotics in Northern Pakistan and study the occurrence of ARGs in selected samples from this region. 19 sampling sites were selected; including six rivers, one dam, one canal, one sewage drain and four drug formulation facilities. Our results show that five of the rivers have antibiotic levels comparable to surface water measurements in unpolluted sites in Europe and the US. However, high levels of antibiotics could be detected in the downstream river in close vicinity of the 10 million city Lahore, 1100, 1700 and 2700 ng L−1 for oxytetracycline, trimethoprim, and sulfamethoxazole respectively. Highest detected levels were at one of the drug formulation facilities, with the measured levels of 1100, 4100, 6200, 7300, 8000, 27000, 28000 and 49000 ng L−1 of erythromycin, lincomycin, ciprofloxacin, ofloxacin, levofloxacin, oxytetracycline, trimethoprim and sulfamethoxazole respectively. ARGs were also detected at the sites and the highest levels of ARGs detected, sulI and dfrA1, were directly associated with the antibiotics detected at the highest concentrations, sulfamethoxazole and trimethoprim. Highest levels of both antibiotics and ARGs were seen at a drug formulation facility, within an industrial estate with a low number of local residents and no hospitals in the vicinity, which indicates that the levels of ARGs at this site were associated with the environmental levels of antibiotics.

  • 233.
    Ali, Neserin
    et al.
    Lund Univ, Sweden.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Wierzbicka, Aneta
    Lund Univ, Sweden.
    Pagels, Joakim
    Lund Univ, Sweden.
    Isaxon, Christina
    Lund Univ, Sweden.
    Gudmundsson, Anders
    Lund Univ, Sweden.
    Rissler, Jenny
    Lund Univ, Sweden.
    Nielsen, Jorn
    Lund Univ, Sweden.
    Lindh, Christian H.
    Lund Univ, Sweden.
    Karedal, Monica
    Lund Univ, Sweden.
    Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix2018In: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 15, article id 20Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. Methods: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. Results: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Conclusion: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.

  • 234.
    Ali, Neserin
    et al.
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Mattsson, Karin
    Center for Molecular Protein Science, Biochemistry and Structural Biology, Lund University, Lund, Sweden.
    Rissler, Jenny
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Karlsson, Helen Marg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Svensson, Christian R
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Gudmundsson, Anders
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Lindh, Christian H
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Jönsson, Bo A G
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Cedervall, Tommy
    Center for Molecular Protein Science, Biochemistry and Structural Biology, Lund University, Lund, Sweden.
    Kåredal, Monica
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.2016In: Nanotoxicology, ISSN 1743-5390, E-ISSN 1743-5404, Vol. 10, no 2, p. 226-234Article in journal (Refereed)
    Abstract [en]

    Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.

  • 235.
    Ali, Zaheer
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Mukwaya, Anthonny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Biesemeier, Antje
    Univ Tubingen, Germany.
    Ntzouni, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ramskold, Daniel
    Karolinska Inst, Sweden.
    Giatrellis, Sarantis
    Karolinska Inst, Sweden.
    Mammadzada, Parviz
    Karolinska Inst, Sweden.
    Cao, Renhai
    Karolinska Inst, Sweden.
    Lennikov, Anton
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Univ Missouri, MO 65211 USA.
    Marass, Michele
    Max Planck Inst Lung and Heart Res, Germany.
    Gerri, Claudia
    Max Planck Inst Lung and Heart Res, Germany.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Taylor, Michael
    Univ Wisconsin, WI 53706 USA.
    Deng, Qiaolin
    Karolinska Inst, Sweden.
    Peebo, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Bayer AB, Sweden.
    del Peso, Luis
    Universidad Autónoma de Madrid, Spain; Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM Madrid, Spain.
    Kvanta, Anders
    Karolinska Inst, Sweden.
    Sandberg, Rickard
    Karolinska Inst, Sweden.
    Schraermeyer, Ulrich
    Univ Tubingen, Germany.
    Andre, Helder
    Karolinska Inst, Sweden.
    Steffensen, John F.
    Univ Copenhagen, Denmark.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Cao, Yihai
    Karolinska Inst, Sweden.
    Kele, Julianna
    Karolinska Inst, Sweden.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Univ Autonoma Madrid, Spain; UAM, Spain.
    Intussusceptive Vascular Remodeling Precedes Pathological Neovascularization2019In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 7, p. 1402-1418Article in journal (Refereed)
    Abstract [en]

    Objective—

    Pathological neovascularization is crucial for progression and morbidity of serious diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. While mechanisms of ongoing pathological neovascularization have been extensively studied, the initiating pathological vascular remodeling (PVR) events, which precede neovascularization remains poorly understood. Here, we identify novel molecular and cellular mechanisms of preneovascular PVR, by using the adult choriocapillaris as a model.

    Approach and Results—

    Using hypoxia or forced overexpression of VEGF (vascular endothelial growth factor) in the subretinal space to induce PVR in zebrafish and rats respectively, and by analyzing choriocapillaris membranes adjacent to choroidal neovascular lesions from age-related macular degeneration patients, we show that the choriocapillaris undergo robust induction of vascular intussusception and permeability at preneovascular stages of PVR. This PVR response included endothelial cell proliferation, formation of endothelial luminal processes, extensive vesiculation and thickening of the endothelium, degradation of collagen fibers, and splitting of existing extravascular columns. RNA-sequencing established a role for endothelial tight junction disruption, cytoskeletal remodeling, vesicle- and cilium biogenesis in this process. Mechanistically, using genetic gain- and loss-of-function zebrafish models and analysis of primary human choriocapillaris endothelial cells, we determined that HIF (hypoxia-induced factor)-1α-VEGF-A-VEGFR2 signaling was important for hypoxia-induced PVR.

    Conclusions—

    Our findings reveal that PVR involving intussusception and splitting of extravascular columns, endothelial proliferation, vesiculation, fenestration, and thickening is induced before neovascularization, suggesting that identifying and targeting these processes may prevent development of advanced neovascular disease in the future.

    Visual Overview—

    An online visual overview is available for this article.

  • 236.
    Alickovic, Emina
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, Faculty of Science & Engineering.
    Lunner, Thomas
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Eriksholm Research Centre, Oticon A/S, 20 Rortangvej, Snekkersten, Denmark.
    Gustafsson, Fredrik
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, Faculty of Science & Engineering.
    A System Identification Approach to Determining Listening Attention from EEG Signals2016In: 2016 24TH EUROPEAN SIGNAL PROCESSING CONFERENCE (EUSIPCO), IEEE , 2016, p. 31-35Conference paper (Refereed)
    Abstract [en]

    We still have very little knowledge about how ourbrains decouple different sound sources, which is known assolving the cocktail party problem. Several approaches; includingERP, time-frequency analysis and, more recently, regression andstimulus reconstruction approaches; have been suggested forsolving this problem. In this work, we study the problem ofcorrelating of EEG signals to different sets of sound sources withthe goal of identifying the single source to which the listener isattending. Here, we propose a method for finding the number ofparameters needed in a regression model to avoid overlearning,which is necessary for determining the attended sound sourcewith high confidence in order to solve the cocktail party problem.

  • 237.
    Alila-Fersi, Olfa
    et al.
    Molecular and Functional Genetics Laboratory, Faculty of Science of Sfax, University of Sfax, Tunisia.
    Tabebi, Mouna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Maalej, Marwa
    Molecular and Functional Genetics Laboratory, Faculty of Science of Sfax, University of Sfax, Tunisia.
    Belguith, Neila
    Department of Medical Genetics, Hédi Chaker Hospital, Sfax, Tunisia.
    Keskes, Leila
    Human Molecular Genetics Laboratory, Faculty of Medecine of Sfax, University of Sfax, Tunisia.
    Mkaouar-Rebai, Emna
    Molecular and Functional Genetics Laboratory, Faculty of Science of Sfax, University of Sfax, Tunisia.
    Fakhfakh, Faiza
    Molecular and Functional Genetics Laboratory, Faculty of Science of Sfax, University of Sfax, Tunisia.
    First description of a novel mitochondrial mutation in the MT-TI gene associated with multiple mitochondrial DNA deletion and depletion in family with severe dilated mitochondrial cardiomyopathy2018In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 497, no 4, p. 1049-1054Article in journal (Refereed)
    Abstract [en]

    Mitochondria are essential for early cardiac development and impaired mitochondria] function was described associated with heart diseases such as hypertrophic or dilated mitochondrial cardiomyopathy. In this study, we report a family including two individuals with severe dilated mitochondrial cardiomyopathy. The whole mitochondrial genome screening showed the presence of several variations and a novel homoplasmic mutation m.4318-4322deIC in the MT-TI gene shared by the two patients and their mother and leading to a disruption of the tRNA(IIe) secondary structure. In addition, a mitochondrial depletion was present in blood leucocyte of the two affected brother whereas a de novo heteroplasmic multiple deletion in the major arc of mtDNA was present in blood leucocyte and mucosa of only one of them. These deletions in the major arc of the mtDNA resulted to the loss of several protein-encoding genes and also some tRNA genes. The mtDNA deletion and depletion could result to an impairment of the oxidative phosphorylation and energy metabolism in the respiratory chain in the studied patients. Our report is the first description of a family with severe lethal dilated mitochondrial cardiomyopathy and presenting several mtDNA abnormalities including punctual mutation, deletion and depletion.

  • 238.
    Alim, Abdul
    et al.
    Uppsala University, Sweden; Karolinska Institute, Sweden; Uppsala University, Sweden.
    Ackermann, Paul W.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Eliasson, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Kristiansson, Per
    Uppsala University, Sweden.
    Pejler, Gunnar
    Uppsala University, Sweden; Swedish University of Agriculture Science, Sweden.
    Peterson, Magnus
    Uppsala University, Sweden.
    Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture2017In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 370, no 3, p. 451-460Article in journal (Refereed)
    Abstract [en]

    The role of inflammation and the mechanism of tendon healing after rupture has historically been a matter of controversy. The purpose of the present study is to investigate the role of mast cells and their relation to the NMDA receptor-1 (a glutamate receptor) during healing after Achilles tendon rupture. Eight female Sprague Dawley rats had their right Achilles tendon transected. Three weeks after rupture, histological quantification of mast cell numbers and their state of degranulation was assessed by histochemistry. Co-localization of mast cell tryptase (a mast cell marker) and NMDA receptor-1 was determined by immunofluorescence. The intact left Achilles tendon was used as control. An increased number of mast cells and a higher proportion of degranulated mast cells were found in the healing Achilles tendon compared to the intact. In addition, increased co-localization of mast cell tryptase and NMDA receptor-1 was seen in the areas of myotendinous junction, mid-tendon proper and bone tendon junction of the healing versus the intact tendon. These findings introduce a possible role for mast cells in the healing phase after Achilles tendon rupture.

  • 239.
    Alizadeh, Javad
    et al.
    University of Manitoba, Canada.
    Zeki, Amir A.
    Centre Comparat Resp Biol and Med, CA USA.
    Mirzaei, Nima
    University of Manitoba, Canada.
    Tewary, Sandipan
    University of Manitoba, Canada.
    Rezaei Moghadam, Adel
    University of Manitoba, Canada; University of Manitoba, Canada.
    Glogowska, Aleksandra
    University of Manitoba, Canada.
    Nagakannan, Pandian
    University of Manitoba, Canada.
    Eftekharpour, Eftekhar
    University of Manitoba, Canada.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Gordon, Joseph W.
    University of Manitoba, Canada; University of Manitoba, Canada; University of Manitoba, Canada.
    Xu, Fred. Y.
    University of Manitoba, Canada; University of Manitoba, Canada.
    Field, Jared T.
    University of Manitoba, Canada.
    Yoneda, Ken Y.
    Centre Comparat Resp Biol and Med, CA USA.
    Kenyon, Nicholas J.
    Centre Comparat Resp Biol and Med, CA USA.
    Hashemi, Mohammad
    Zehedan University of Medical Science, Iran.
    Hatch, Grant M.
    University of Manitoba, Canada; University of Manitoba, Canada.
    Hombach-Klonisch, Sabine
    University of Manitoba, Canada.
    Klonisch, Thomas
    University of Manitoba, Canada.
    Ghavami, Saeid
    University of Manitoba, Canada; University of Manitoba, Canada; Shiraz University of Medical Science, Iran.
    Mevalonate Cascade Inhibition by Simvastatin Induces the Intrinsic Apoptosis Pathway via Depletion of Isoprenoids in Tumor Cells2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 44841Article in journal (Refereed)
    Abstract [en]

    The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway. In all cancer cell types tested, simvastatin-induced cell death was not rescued by cholesterol, but was dependent on GGPP-and FPP-depletion. We confirmed that simvastatin caused the translocation of the small Rho GTPases RhoA, Cdc42, and Rac1/2/3 from cell membranes to the cytosol in U251 (glioblastoma), A549 (lung adenocarcinoma) and MDA-MB231( breast cancer). Simvastatin-induced Rho-GTP loading significantly increased in U251 cells which were reversed with MEV, FPP, GGPP. In contrast, simvastatin did not change Rho-GTP loading in A549 and MDA-MB-231. Inhibition of geranylgeranyltransferase I by GGTi-298, but not farnesyltransferase by FTi-277, induced significant cell death in U251, A549, and MDA-MB-231. These results indicate that MEV cascade inhibition by simvastatin induced the intrinsic apoptosis pathway via inhibition of Rho family prenylation and depletion of GGPP, in a variety of different human cancer cell lines.

  • 240.
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.

    Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.

    Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.

    Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.

    List of papers
    1. PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Open this publication in new window or tab >>PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Show others...
    2015 (English)In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

    National Category
    Urology and Nephrology Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-120796 (URN)10.1186/s12894-015-0080-z (DOI)000359832000001 ()26294219 (PubMedID)
    Available from: 2015-08-25 Created: 2015-08-25 Last updated: 2017-05-17
    2. Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
    Open this publication in new window or tab >>Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
    Show others...
    2017 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, no 3, p. 329-336Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing Inc., 2017
    Keywords
    #BladderCancer, #blcsm, cystectomy, lymph node metastasis, prognostic factors, sentinel node
    National Category
    Surgery
    Identifiers
    urn:nbn:se:liu:diva-136947 (URN)10.1111/bju.13700 (DOI)000407781500011 ()27797436 (PubMedID)
    Note

    Funding agencies: County Council of Ostergotland, Linkoping, Sweden

    Available from: 2017-05-01 Created: 2017-05-01 Last updated: 2018-05-03
  • 241.
    Aljabery, Firas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Halili, Shefqet
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Hildebrand, Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Vesico-Uterine Fistula after TURB in pregnancy, a rare cause of genitourinary fistula2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 2, p. 162-163Article in journal (Refereed)
    Abstract [en]

    n/a

  • 242.
    Aljabery, Firas
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lindblom, Gunnar
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Skoog, Susann
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.2015In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

  • 243.
    Aljabery, Firas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer2018In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 36, no 4, article id 159.e19Article in journal (Refereed)
    Abstract [en]

    Background

    Tumor-associated macrophages (TAMs) constitute a subset of nonneoplastic cells in tumor stroma and influence cancer progression in solid tumors. The clinical significance of TAMs in urinary bladder cancer(UBC) is controversial.

    Methods

    We prospectively studied 103 patients with stage pT1–T4 UBC treated with cystectomy and pelvic lymph node dissection. Tumor sections were immunostained with M2-specific macrophage marker CD163 and proliferation marker Ki-67. The expression of these markers in cancer cells as well as macrophage infiltration (MI) in tumor stroma was analyzed in relation to clinical data and outcome.

    Results

    The mean rate of CD163 and Ki-67 expressed by cancer cells were 35% and 78%, respectively. With borderline significance, MI was associated with lower rate of lymph node metastasis (P = 0.06). CD163 expression in cancer cells was proportional to MI (P<0.014). Patients with CD163-positive tumors and strong MI had significantly longer cancer-specific survival (CSS) (76 months), compared to patient with CD163-positive tumors and weak MI (28 months) (P = 0.02).

    Conclusions

    M2-specific MI tends to be inversely correlated with LN metastasis and improved CSS in UBC. MI might have protective impact in CD163-positive tumors. Expression of CD163 in cancer cells is significantly correlated with MI and might have a tumor promoting impact.

  • 244.
    Aljabery, Firas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Shabo, Ivan
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    The expression profile of p14, p53 and p21 in tumour cells is associated with disease-specific survival and the outcome of postoperative chemotherapy treatment in muscle-invasive bladder cancer2018In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 36, no 12, p. 530.e7-530.e18, article id 530.e7Article in journal (Refereed)
    Abstract [en]

    Purpose: We investigated the effects of alterations in the biological markers p14, p53, p21, and p16 in relation to tumour cell proliferation, T-category, N- category, lymphovascular invasion, and the ability to predict prognosis in patients with muscle-invasive bladder cancer (MIBC) treated with cystectomy and, if applicable, chemotherapy.

    Materials and methods: We prospectively studied patients with urinary bladder cancer pathological stage pT1 to pT4 treated with cystectomy, pelvic lymph node dissection and postoperative chemotherapy. Tissue microarrays from paraffin-embedded cystectomy tumour samples were examined for expression of immunostaining of p14, p53, p21, p16 and Ki-67 in relation to other clinical and pathological factors as well as cancer-specific survival.

    Results: The median age of the 110 patients was 70 years (range 51-87 years), and 85 (77%) were male. Pathological staging was pT1 to pT2 (organ-confined) in 28 (25%) patients and pT3 to pT4 (non-organ-confined) in 82 (75%) patients. Lymph node metastases were found in 47 patients (43%). P14 expression was more common in tumours with higher T-stages (P = 0.05). The expression of p14 in p53 negative tumours was associated with a significantly shorter survival time (P=0.003). Independently of p53 expression, p14 expression was associated with an impaired response to chemotherapy (P=0.001). The expression of p21 in p53 negative tumours was associated with significantly decrease levels of tumour cell proliferation detected as Ki-67 expression (P=0.03).

    Conclusions: The simultaneous expression of the senescence markers involved in the p53-pathway shows a more relevant correlation to the pathological outcome of MIBC than each protein separately. P14 expression in tumours with non-altered (p53-) tumours is associated with poor prognosis. P14 expression is associated with impaired response to chemotherapy. P21 expression is related to decreased tumour cell proliferation.

  • 245.
    Aljabery, Firas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Breast and Endocrine Surgery, Karolinska University Hospital, Solna Stockholm, Sweden .
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Jahnson, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.2017In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, no 3, p. 329-336Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

  • 246.
    Alkaissi, Aidah
    et al.
    Linköping University, Department of Medicine and Health Sciences, Anesthesiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Ledin, Torbjörn
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Ödkvist, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Kalman, Sigga
    Linköping University, Department of Medicine and Health Sciences, Anesthesiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Anaesthesiology and Intensive Care VHN.
    P6 acupressure increases tolerance to nausogenic motion stimulation in women with high risk for PONV2005In: Canadian Journal of Anesthesia, ISSN 1496-8975, Vol. 52, p. 703-709Article in journal (Refereed)
    Abstract [en]

    Purpose: In a previous study we noticed that P6 acupressure decreased postoperative nausea and vomiting (PONV) more markedly after discharge. As motion sickness susceptibility is increased by, for example, opioids we hypothesized that P6 acu-pressure decreased PONV by decreasing motion sickness susceptibility. We studied time to nausea by a laboratory motion challenge in a group of volunteers, during P6 and placebo acupressure.

    Methods: 60 women with high and low susceptibilities for motion sickness participated in a randomized and double-blind study with an active P6 acupressure, placebo acupressure, and a control group (n = 20 in each group). The risk score for PONV was over 50%. The motion challenge was by eccentric rotation in a chair, blindfolded and with chin to chest movements of the head. The challenge was stopped when women reported moderate nausea. Symptoms were recorded.

    Results: Mean time to moderate nausea was longer in the P6 acu-pressure group compared to the control group. P6 acupressure = 352 (259–445), mean (95% confidence interval) in seconds, control = 151 (121–181) and placebo acupressure = 280 (161–340); (P = 0.006). No difference was found between P6 and placebo acupressure or placebo acupressure and control groups. Previous severity of motion sickness did not influence time to nausea (P = 0.107). The cumulative number of symptoms differed between the three groups (P < 0.05). Fewer symptoms were reported in the P6 acupressure compared to the control group P < 0.009. Overall, P6 acupressure was only marginally more effective than placebo acupressure on the forearms.

    Conclusion: In females with a history of motion sickness P6 acu-pressure increased tolerance to experimental nauseogenic stimuli, and reduced the total number of symptoms reported.

  • 247.
    Alkaissi, Hammoudi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Identification of candidate genes involved in Mercury Toxicokinetics and Mercury Induced Autoimmunity2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    BACKGROUND: Autoimmune diseases require the involvement and activation of immune cells and occur when the body builds up an immune response against its own tissues. This process takes place due to the inability to distinguish self-antigen from foreign antigen. Systemic autoimmunity represents an important cause of morbidity and mortality in humans. The mechanisms triggering autoimmune responses are complex and involve a network of genetic factors. Genome wide association study (GWAS) is a powerful method, used to identify genetic risk factors in numerous diseases, such as systemic autoimmune diseases. The goal of GWAS is to identify these genetic risk factors in order to make predictions about who is at risk and investigate the biological process of disease susceptibility. There are several valuable mouse models to investigate the underlying mechanisms causing systemic autoimmune diseases in which mercury induced autoimmunity (HgIA) is a well- established and relevant model. HgIA in mice includes development of autoantibodies, immune complex glomerulonephritis, lymphocyte proliferation, hypergammaglobulinemia and polyclonal B cell activation. In humans, mercury exposure accumulates with considerable concentrations in kidney, liver, and brain. Toxicokinetics of Hg has been studied extensively but the key for inter-individual variation in humans are largely unclear. Differences in accumulation of renal Hg between inbred mouse strains suggest a genetic inter-strain variation regulating retention or/and excretion of Hg.

    OBJECTIVES: To find loci and candidate genes associated with phenotypes involved in the development of autoimmunity and find candidate genes involved in the regulation of renal Hg excretion.

    METHODS: MHC II (H-2s) mice were paired (A.SW x B10.S) to obtain F2 offspring exposed to 2.0 or 4.0 mg Hg in drinking water for 6 weeks. Mercury induced autoimmune phenotypes were studied with immunofluorescence (anti-nucleolar antibodies (ANoA)), ELISA anti-DNP/anti-ssDNA (polyclonal B cell activation), anti-chromatin antibodies (ACA) (4.0 mg Hg), and serum IgG1 concentrations. Mercury accumulation in kidney was performed previously and data was included as phenotype. F2 mice exposed to 2.0 mg Hg were genotyped with microsatellites for genome-wide scan with Ion Pair Reverse Phase High Performance Liquid Chromatography (IP RP HPLC). F2 mice exposed to 4.0 mg Hg were genotyped with single nucleotide polymorphisms for genomewide scan with SNP&SEQ technology platform. Quantitative trait loci (QTL) was established with R/QTL. Denaturing HPLC, next generation sequencing, conserved region analysis and genetic mouse strain comparison were used for haplotyping and fine mapping on QTLs associated with Hg concentration in kidney, development of ANoA and serum IgG1 hypergammaglobulinemia. Candidate genes (Pprc1, Bank1 and Nfkb1) verified by additional QTL were further investigated by real time polymerase chain reaction. Genes involved in the intracellular signaling together with candidate genes were included for gene expression analysis.

    RESULTS: F2 mice exposed to 2.0 mg Hg had low or no development of autoantibodies and showed no significant difference in polyclonal B cell activation in the B10.S and F2 strains. F2 mice exposed to 4.0 mg Hg developed autoantibodies and significantly increased IgG1 concentration and polyclonal B cell activation (anti-DNP). QTL analysis showed a logarithm of odds ratio (LOD) score between 2.9 – 4.36 on all serological phenotypes exposed to 4.0 mg Hg, and a LOD score of 5.78 on renal Hg concentration. Haplotyping and fine mapping associated the development of ANoA with Bank1 (B-cell scaffold protein with ankyrin repeats 1) and Nfkb1 (nuclear factor kappa B subunit 1). The serum IgG1 concentration was associated with a locus on chromosome 3, in which Rxfp4 (Relaxin Family Peptide/INSL5 Receptor 4) is a potential candidate gene. The renal Hg concentration was associated with Pprc1 (Peroxisome Proliferator-Activated Receptor Gamma, Co-activator-Related). Gene expression analysis revealed that the more susceptible A.SW strain expresses significantly higher levels of Nfkb1, Il6 and Tnf than the less susceptible B10.S strain. The A.SW strain expresses significantly lower levels of Pprc1 and cascade proteins than the B10.S strain. Development of ACA was associated with chromosomes 3, 6, 7 and 16 (LOD 3.1, 3.2, 3.4 and 6.8 respectively). Polyclonal B cell activation was associated with chromosome 2 with a LOD score of 2.9.

    CONCLUSIONS: By implementing a GWAS on HgIA in mice, several QTLs were discovered to be associated with the development of autoantibodies, polyclonal B cell activation and hypergammaglobulinemia. This thesis plausibly supports Bank1 and Nfkb1 as key regulators for ANoA development and HgIA seems to be initiated by B cells rather than T cells. GWAS on renal mercury excretion plausibly supports Pprc1 as key regulator and it seems that this gene has a protective role against Hg.

    List of papers
    1. Genome-Wide Association Study to Identify Genes Related to Renal Mercury Concentrations in Mice
    Open this publication in new window or tab >>Genome-Wide Association Study to Identify Genes Related to Renal Mercury Concentrations in Mice
    Show others...
    2016 (English)In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 124, no 7, p. 920-926Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Following human mercury (Hg) exposure, the metal accumulates in considerable concentrations in kidney, liver, and brain. Although the toxicokinetics of Hg have been studied extensively, factors responsible for interindividual variation in humans are largely unknown. Differences in accumulation of renal Hg between inbred mouse strains suggest a genetic interstrain variation regulating retention or/and excretion of Hg. A. SW, DBA/2 and BALB/C mouse strains accumulate higher amounts of Hg than B10.S.

    OBJECTIVES: We aimed to find candidate genes associated with regulation of renal Hg concentrations.

    METHODS: A. SW, B10.S and their F1 and F2 offspring were exposed for 6 weeks to 2.0 mg Hg/L drinking water. Genotyping with microsatellites was conducted on 84 F2 mice for genome-wide scanning with ion pair reverse-phase high-performance liquid chromatography (IP RP HPLC). Quantitative trait loci (QTL) were established. Denaturing HPLC was used to detect single nucleotide polymorphisms for haplotyping and fine mapping in 184 and 32 F2 mice, respectively. Candidate genes (Pprc1, Btrc and Nfkb2) verified by fine mapping and QTL were further investigated by real-time polymerase chain reaction. Genes enhanced by Pprc1 (Nrf1 and Nrf2) were included for gene expression analysis.

    RESULTS: Renal Hg concentrations differed significantly between A. SW and B10. S mice and between males and females within each strain. QTL analysis showed a peak logarithm of odds ratio score 5.78 on chromosome 19 (p = 0.002). Haplotype and fine mapping associated the Hg accumulation with Pprc1, which encodes PGC-1-related coactivator (PRC), a coactivator for proteins involved in detoxification. Pprc1 and two genes coactivated by Pprc1 (Nrf1 and Nrf2) had significantly lower gene expression in the A. SW strain than in the B10. S strain.

    CONCLUSIONS: This study supports Pprc1 as a key regulator for renal Hg excretion.

    Place, publisher, year, edition, pages
    U.S. Department of Health and Human Services * National Institute of Environmental Health Sciences, 2016
    National Category
    Other Biological Topics
    Identifiers
    urn:nbn:se:liu:diva-131584 (URN)10.1289/ehp.1409284 (DOI)000380749300012 ()26942574 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council Branch of Medicine; County Council of Ostergotland; Linkoping University

    Available from: 2016-09-27 Created: 2016-09-27 Last updated: 2018-10-24Bibliographically approved
    2. Bank1 and NF-kappaB as key regulators in anti-nucleolar antibody development
    Open this publication in new window or tab >>Bank1 and NF-kappaB as key regulators in anti-nucleolar antibody development
    Show others...
    2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 7, article id e0199979Article in journal (Refereed) Published
    Abstract [en]

    Systemic autoimmune rheumatic disorders (SARD) represent important causes of morbidity and mortality in humans. The mechanisms triggering autoimmune responses are complex and involve a network of genetic factors. Mercury-induced autoimmunity (HgIA) in mice is an established model to study the mechanisms of the development of antinuclear antibodies (ANA), which is a hallmark in the diagnosis of SARD. A.SW mice with HgIA show a significantly higher titer of antinucleolar antibodies (ANoA) than the B10.S mice, although both share the same MHC class II (H-2). We applied a genome-wide association study (GWAS) to their Hg-exposed F2 offspring to investigate the non-MHC genes involved in the development of ANoA. Quantitative trait locus (QTL) analysis showed a peak logarithm of odds ratio (LOD) score of 3.05 on chromosome 3. Microsatellites were used for haplotyping, and fine mapping was conducted with next generation sequencing. The candidate genes Bank1 (B-cell scaffold protein with ankyrin repeats 1) and Nfkbl (nuclear factor kappa B subunit 1) were identified by additional QTL analysis. Expression of the Bank1 and Nfkb1 genes and their downstream target genes involved in the intracellular pathway (Tlr9,II6, Tnf) was investigated in mercury-exposed A.SW and B10.S mice by real-time PCR. Bank1 showed significantly lower gene expression in the A.SW strain after Hg-exposure, whereas the B10.S strain showed no significant difference. Nfkb1, Tlr9, II6 and Tnf had significantly higher gene expression in the A.SW strain after Hg-exposure, while the B10.S strain showed no difference. This study supports the roles of Bank1 (produced mainly in B-cells) and Nfkbl (produced in most immune cells) as key regulators of ANoA development in HgIA.

    Place, publisher, year, edition, pages
    PUBLIC LIBRARY SCIENCE, 2018
    National Category
    Genetics
    Identifiers
    urn:nbn:se:liu:diva-150265 (URN)10.1371/journal.pone.0199979 (DOI)000438866600014 ()30016332 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council Branch of Medicine; County Council of Ostergotland; Linkoping University

    Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2019-04-24
  • 248.
    Alkaissi, Hammoudi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Ekstrand, Jimmy
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Jawad, Aksa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nielsen, Jesper Bo
    University of Southern Denmark, Denmark.
    Havarinasab, Said
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Hultman, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Genome-Wide Association Study to Identify Genes Related to Renal Mercury Concentrations in Mice2016In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 124, no 7, p. 920-926Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Following human mercury (Hg) exposure, the metal accumulates in considerable concentrations in kidney, liver, and brain. Although the toxicokinetics of Hg have been studied extensively, factors responsible for interindividual variation in humans are largely unknown. Differences in accumulation of renal Hg between inbred mouse strains suggest a genetic interstrain variation regulating retention or/and excretion of Hg. A. SW, DBA/2 and BALB/C mouse strains accumulate higher amounts of Hg than B10.S.

    OBJECTIVES: We aimed to find candidate genes associated with regulation of renal Hg concentrations.

    METHODS: A. SW, B10.S and their F1 and F2 offspring were exposed for 6 weeks to 2.0 mg Hg/L drinking water. Genotyping with microsatellites was conducted on 84 F2 mice for genome-wide scanning with ion pair reverse-phase high-performance liquid chromatography (IP RP HPLC). Quantitative trait loci (QTL) were established. Denaturing HPLC was used to detect single nucleotide polymorphisms for haplotyping and fine mapping in 184 and 32 F2 mice, respectively. Candidate genes (Pprc1, Btrc and Nfkb2) verified by fine mapping and QTL were further investigated by real-time polymerase chain reaction. Genes enhanced by Pprc1 (Nrf1 and Nrf2) were included for gene expression analysis.

    RESULTS: Renal Hg concentrations differed significantly between A. SW and B10. S mice and between males and females within each strain. QTL analysis showed a peak logarithm of odds ratio score 5.78 on chromosome 19 (p = 0.002). Haplotype and fine mapping associated the Hg accumulation with Pprc1, which encodes PGC-1-related coactivator (PRC), a coactivator for proteins involved in detoxification. Pprc1 and two genes coactivated by Pprc1 (Nrf1 and Nrf2) had significantly lower gene expression in the A. SW strain than in the B10. S strain.

    CONCLUSIONS: This study supports Pprc1 as a key regulator for renal Hg excretion.

  • 249.
    Alkaissi, Hammoudi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Havarinasab, Said
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Nielsen, Jesper Bo
    Univ Southern Denmark, Denmark.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Hultman, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Bank1 and NF-kappaB as key regulators in anti-nucleolar antibody development2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 7, article id e0199979Article in journal (Refereed)
    Abstract [en]

    Systemic autoimmune rheumatic disorders (SARD) represent important causes of morbidity and mortality in humans. The mechanisms triggering autoimmune responses are complex and involve a network of genetic factors. Mercury-induced autoimmunity (HgIA) in mice is an established model to study the mechanisms of the development of antinuclear antibodies (ANA), which is a hallmark in the diagnosis of SARD. A.SW mice with HgIA show a significantly higher titer of antinucleolar antibodies (ANoA) than the B10.S mice, although both share the same MHC class II (H-2). We applied a genome-wide association study (GWAS) to their Hg-exposed F2 offspring to investigate the non-MHC genes involved in the development of ANoA. Quantitative trait locus (QTL) analysis showed a peak logarithm of odds ratio (LOD) score of 3.05 on chromosome 3. Microsatellites were used for haplotyping, and fine mapping was conducted with next generation sequencing. The candidate genes Bank1 (B-cell scaffold protein with ankyrin repeats 1) and Nfkbl (nuclear factor kappa B subunit 1) were identified by additional QTL analysis. Expression of the Bank1 and Nfkb1 genes and their downstream target genes involved in the intracellular pathway (Tlr9,II6, Tnf) was investigated in mercury-exposed A.SW and B10.S mice by real-time PCR. Bank1 showed significantly lower gene expression in the A.SW strain after Hg-exposure, whereas the B10.S strain showed no significant difference. Nfkb1, Tlr9, II6 and Tnf had significantly higher gene expression in the A.SW strain after Hg-exposure, while the B10.S strain showed no difference. This study supports the roles of Bank1 (produced mainly in B-cells) and Nfkbl (produced in most immune cells) as key regulators of ANoA development in HgIA.

  • 250.
    Alkass, Kanar
    et al.
    Division of Forensic Medicine, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Saitoh, Hisako
    Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
    Buchholz, Bruce A
    Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, California, USA.
    Bernard, Samuel
    Institut Camille Jordan, University of Lyon, Villeurbanne, France.
    Holmlund, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. National Board of Forensic Medicine, Linköping, Sweden.
    Senn, David R
    Center for Education and Research in Forensics, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
    Spalding, Kirsty L
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
    Druid, Henrik
    Division of Forensic Medicine, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Analysis of radiocarbon, stable isotopes and DNA in teeth to facilitate identification of unknown decedents2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 7, p. e69597-Article in journal (Refereed)
    Abstract [en]

    The characterization of unidentified bodies or suspected human remains is a frequent and important task for forensic investigators. However, any identification method requires clues to the person’s identity to allow for comparisons with missing persons. If such clues are lacking, information about the year of birth, sex and geographic origin of the victim, is particularly helpful to aid in the identification casework and limit the search for possible matches. We present here results of stable isotope analysis of 13C and 18O, and bomb-pulse 14C analyses that can help in the casework. The 14C analysis of enamel provided information of the year of birth with an average absolute error of 1.8±1.3 years. We also found that analysis of enamel and root from the same tooth can be used to determine if the 14C values match the rising or falling part of the bomb-curve. Enamel laydown times can be used to estimate the date of birth of individuals, but here we show that this detour is unnecessary when using a large set of crude 14C data of tooth enamel as a reference. The levels of 13C in tooth enamel were higher in North America than in teeth from Europe and Asia, and Mexican teeth showed even higher levels than those from USA. DNA analysis was performed on 28 teeth, and provided individual-specific profiles in most cases and sex determination in all cases. In conclusion, these analyses can dramatically limit the number of possible matches and hence facilitate person identification work.

2345678 201 - 250 of 9883
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf