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  • 1.
    Aaseth, Jan
    et al.
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Bjorklund, Geir
    Council Nutr and Environm Med, Norway.
    Hestad, Knut
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Dusek, Petr
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic; Gen University Hospital Prague, Czech Republic.
    Roos, Per M.
    Karolinska Institute, Sweden; St Goran Hospital, Sweden.
    Alehagen, Urban
    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.
    Treatment strategies in Alzheimers disease: a review with focus on selenium supplementation2016In: Biometals, ISSN 0966-0844, E-ISSN 1572-8773, Vol. 29, no 5, 827-839 p.Article in journal (Refereed)
    Abstract [en]

    Alzheimers disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (A beta) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce A beta production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral A beta plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.

  • 2.
    Abate, Ebba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. University of Gondar, Ethiopia.
    Belayneh, Meseret
    University of Addis Ababa, Ethiopia.
    Idh, Jonna
    Vastervik Hospital, Sweden.
    Diro, Ermias
    University of Gondar, Ethiopia.
    Elias, Daniel
    University of Southern Denmark, Denmark.
    Britton, Sven
    Karolinska Hospital, Sweden.
    Aseffa, Abraham
    Armauer Hansen Research Institute, Ethiopia.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity2015In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 9, no 8, e0003994Article in journal (Refereed)
    Abstract [en]

    Background The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB.

    Methodology Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively.

    Results A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13-103) versus 2 SFU (1-50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2-16.7) cells/mu l versus 2.4 (1.1-4.0) cells/mu l; p = 0.041) and IL-10 secreting cells (65 SFU (7-196) versus 1 SFU (0-31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients.

    Conclusions Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.

  • 3.
    Abbass, Allan
    et al.
    Dalhousie University, Canada.
    Bernier, Denise
    Dalhousie University, Canada.
    Kisely, Steve
    University of Queensland, Australia.
    Town, Joel
    Dalhousie University, Canada.
    Johansson, Robert
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Dalhousie University, Canada.
    Sustained reduction in health care costs after adjunctive treatment of graded intensive short-term dynamic psychotherapy in patients with psychotic disorders2015In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 228, no 3, 538-543 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this pilot study was to evaluate the changes in symptom severity and long-term health care cost after intensive short-term dynamic psychotherapy (ISTDP) individually tailored and administered to patients with psychotic disorders undergoing standard psychiatric care. Eleven therapists with different levels of expertise delivered an average of 13 one-hour sessions of graded ISTDP to 38 patients with psychotic disorders. Costs for health care services were compiled for a one-year period prior to the start of ISTDP (baseline) along with four one-year periods after termination. Two validated self-report scales, the Brief Symptom Inventory and the Inventory of Interpersonal Problems, were administered at intake and termination of ISTDP. Results revealed that health care cost reductions were significant for the one-year post-treatment period relative to baseline year, for both physician costs and hospital costs, and the reductions were sustained for the follow-up period of four post-treatment years. Furthermore, at treatment termination self-reported symptoms and interpersonal problems were significantly reduced. These preliminary findings suggest that this brief adjunctive psychotherapy may be beneficial and reduce costs in selected patients with psychotic disorders, and that gains are sustained in long-term follow-up. Future research directions are discussed. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 4.
    Abbass, Allan
    et al.
    Dalhousie University, Canada.
    Johansson, Robert
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Rasic, Daniel
    Dalhousie University, Canada.
    Town, Joel M.
    Dalhousie University, Canada.
    Johansson, Robert
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Long-term healthcare cost reduction with Intensive Short-term Dynamic Psychotherapy in a tertiary psychiatric service2015In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 64, 114-120 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate whether a mixed population of patients treated with Intensive Short-term Dynamic Psychotherapy (ISTDP) would exhibit reduced healthcare costs in long-term follow-up. Methods: A quasi-experimental design was employed in which data on pre- and post-treatment healthcare cost were compared for all ISTDP cases treated in a tertiary care service over a nine year period. Observed cost changes were compared with those of a control group of patients referred but never treated. Physician and hospital costs were compared to treatment cost estimates and normal population cost figures. Results: 1082 patients were included; 890 treated cases for a broad range of somatic and psychiatric disorders and 192 controls. The treatment averaged 7.3 sessions and measures of symptoms and interpersonal problems significantly improved. The average cost reduction per treated case was $12,628 over 3 follow-up years: this compared favorably with the estimated treatment cost of $708 per patient. Significant differences were seen between groups for follow-up hospital costs. Conclusions: ISTDP in this setting appears to facilitate reductions in healthcare costs, supporting the notion that brief dynamic psychotherapy provided in a tertiary setting can be beneficial to health care systems overall. (C) 2015 Elsevier Ltd. All rights reserved.

  • 5.
    Abelius, Martina S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Janefjord, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    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 Immunology and Transfusion Medicine.
    Berg, Göran
    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 Gynaecology and Obstetrics in Linköping.
    Matthiesen, Leif
    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 Gynaecology and Obstetrics in Linköping. Helsingborg Hospital, Helsingborg.
    Duchén, Karel
    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.
    Nilsson, Lennart J
    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, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity2015In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 73, no 5, 445-459 p.Article in journal (Refereed)
    Abstract [en]

    PROBLEM: How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear.

    METHOD OF STUDY: Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring.

    RESULTS: Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P < 0.001) and IL-5 expression in PBMC with fetal galectin1 (ρ = 0.91, P < 0.001). Increased expression of Th2-associated CCL22 in CBMC preceded allergy development.

    CONCLUSIONS: Gene expression locally and systemically during pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development.

  • 6.
    Abrahamsson, Thomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Jakobsson, H.E.
    Karolinska Institute, Stockholm, Sweden.
    Andersson, A.F.
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, B.
    Karolinska Institute, Stockholm, Sweden; Örebro University, Sweden .
    Engstrand, L.
    Karolinska Institute, Stockholm, Sweden; KTH Royal Institute of Technology, Stockholm, Sweden.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, 842-850 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age.

    OBJECTIVE:

    To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema.

    METHODS:

    The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and 12 months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID NCT01285830).

    RESULTS:

    Children developing asthma (n = 8) had a lower diversity of the total microbiota than non-asthmatic children at 1 week (P = 0.04) and 1 month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12 months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease.

    CONCLUSION AND CLINICAL RELEVANCE:

    Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7 years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 7.
    Abrahamsson, Thomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Sherman, Philip M.
    University of Toronto, Canada .
    Editorial Material: Multifaceted Effects of Human Milk Oligosaccharides2014In: Journal of Infectious Diseases, ISSN 0022-1899, Vol. 209, no 3, 323-324 p.Article in journal (Other academic)
    Abstract [en]

    n/a

  • 8.
    Abrahamsson, Thomas
    et al.
    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. University of Toronto, Canada.
    You Wu, Richard
    University of Toronto, Canada.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gut microbiota and allergy: the importance of the pregnancy period2015In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 77, no 1, 214-219 p.Article, review/survey (Refereed)
    Abstract [en]

    Limited microbial exposure is suggested to underlie the increase of allergic diseases in affluent countries, and bacterial diversity seems to be more important than specific bacteria taxa. Prospective studies indicate that the gut microbiota composition during the first months of life influences allergy development, and support the theory that factors influencing the early maturation of the immune system might be important for subsequent allergic disease. However, recent research indicates that microbial exposure during pregnancy may be even more important for the preventative effects against allergic disease. This review gives a background of the epidemiology, immunology, and microbiology literature in this field. It focuses on possible underlying mechanisms such as immune-regulated epigenetic imprinting and bacterial translocation during pregnancy, potentially providing the offspring with a pioneer microbiome. We suggest that a possible reason for the initial exposure of bacterial molecular patterns to the fetus in utero is to prime the immune system and/or the epithelium to respond appropriately to pathogens and commensals after birth.

  • 9.
    Adolfsson, Per I
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Bloth, Björn
    Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Futurum Academy for Health and Care, Jönköping County Council, Sweden.
    Svensson, Samuel P S
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.2015In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, no 3, 704.e15-704.e19 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the effects of zinc (Zn(2+)) concentrations on cultured benign prostatic hyperplasia (BPH) smooth muscle cell (SMC) proliferation.

    METHODS: The effects of Zn(2+) were studied in primary cultures of human BPH SMC, stimulated with either 10-μM lysophosphatidic acid (LPA) or LPA in combination with 100-nM testosterone. Deoxyribonucleic acid replication and protein synthesis using [(3)H]-thymidine and [(35)S]-methionine incorporation were measured. Furthermore, studies were performed to evaluate if Zn(2+) could potentiate the inhibitory effect of phosphodiesterase-5 blockers, on BPH SMC proliferation.

    RESULTS: Zn(2+) generated a bell-shaped concentration response, both regarding deoxyribonucleic acid replication and protein synthesis in cultured BPH SMC. Below a threshold value (approximately 200 μM), a significant mitogenic effect was seen, whereas higher concentrations inhibited SMC proliferation after stimulation with LPA. This effect was even more pronounced after stimulation of LPA in combination with testosterone. Moreover, phosphodiesterase-5 inhibitors, that is, sildenafil blocked LPA-stimulated BPH SMC proliferation. This antiproliferative effect, was significantly potentiated by coincubation with Zn(2+) in an additative manner.

    CONCLUSION: The bell-shaped concentration response of Zn(2+) on cultured BPH SMC proliferation suggests that changes in prostate Zn(2+) concentrations, during aging, diet, or inflammatory conditions, may be of importance in the pathogenesis of BPH.

  • 10.
    Adua, Eric
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Oteng Danso, Frank
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Mensah Boa-Amponsem, Oswald
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Adusei-Mensah, Frank
    University of Cape Coast, Ghana.
    Effect of Neutrophils on Nitric Oxide Production from Stimulated Macrophages2015In: Iranian Journal of Immunology, ISSN 1735-1383, E-ISSN 1735-367X, Vol. 12, no 2, 94-103 p.Article in journal (Refereed)
    Abstract [en]

    Background: During the initial phase of an infection, there is an upregulation of inducible nitric oxide synthase in the macrophages for the production of nitric oxide. This is followed by the recruitment of polymorphonuclear leukocytes (neutrophils) which release arginase. Arginase competes with inducible nitric oxide synthase for a common substrate L-arginine. Objective: To investigate whether the entry of neutrophils and release of arginase can interfere with nitric oxide production from stimulated mouse macrophages. Methods: Neutrophils were isolated from human blood and stimulated with cytodex-3 beads. Cultured macrophages were stimulated with lipopolysaccharide and interferon gamma with or without N (G)-nitro-L-arginine methyl ester or N (omega)-hydroxy-nor-L-arginine. Measurement of NO2-/NO3- and urea were done using the spectrophotometer. Results: A significantly higher level of nitric oxide production from stimulated macrophages was observed compared to control. There was a decrease in nitric oxide production when stimulated macrophages were treated with the supernatant from activated neutrophils (pless than0.05). Conclusion: Arginase from neutrophils can modulate nitric oxide production from activated macrophages which may affect the course of infection by intracellular bacteria.

  • 11.
    Agalave, Nilesh M
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Max
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Abdelmoaty, Sally
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Su, Jie
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Baharpoor, Azar
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lundbäck, Peter
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Palmblad, Karin
    Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Ulf
    Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Harris, Helena
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Svensson, Camilla I
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Spinal HMGB1 induces TLR4-mediated long-lasting hypersensitivity and glial activation and regulates pain-like behavior in experimental arthritis.2014In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 155, no 9, 1802-1813 p.Article in journal (Refereed)
    Abstract [en]

    Extracellular high mobility group box-1 protein (HMGB1) plays important roles in the pathogenesis of nerve injury- and cancer-induced pain. However, the involvement of spinal HMGB1 in arthritis-induced pain has not been examined previously and is the focus of this study. Immunohistochemistry showed that HMGB1 is expressed in neurons and glial cells in the spinal cord. Subsequent to induction of collagen antibody-induced arthritis (CAIA), Hmgb1 mRNA and extranuclear protein levels were significantly increased in the lumbar spinal cord. Intrathecal (i.t.) injection of a neutralizing anti-HMGB1 monoclonal antibody or recombinant HMGB1 box A peptide (Abox), which each prevent extracellular HMGB1 activities, reversed CAIA-induced mechanical hypersensitivity. This occurred during ongoing joint inflammation as well as during the postinflammatory phase, indicating that spinal HMGB1 has an important function in nociception persisting beyond episodes of joint inflammation. Importantly, only HMGB1 in its partially oxidized isoform (disulfide HMGB1), which activates toll-like receptor 4 (TLR4), but not in its fully reduced or fully oxidized isoforms, evoked mechanical hypersensitivity upon i.t. injection. Interestingly, although both male and female mice developed mechanical hypersensitivity in response to i.t. HMGB1, female mice recovered faster. Furthermore, the pro-nociceptive effect of i.t. injection of HMGB1 persisted in Tlr2- and Rage-, but was absent in Tlr4-deficient mice. The same pattern was observed for HMGB1-induced spinal microglia and astrocyte activation and cytokine induction. These results demonstrate that spinal HMGB1 contributes to nociceptive signal transmission via activation of TLR4 and point to disulfide HMGB1 inhibition as a potential therapeutic strategy in treatment of chronic inflammatory pain.

  • 12.
    Agholme, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Getting rid of intracellular Aβ- loss of cellular degradation leads to transfer between connected neurons2014In: Current pharmaceutical design, ISSN 1381-6128, Vol. 20, no 15, 2458-2468 p.Article in journal (Refereed)
    Abstract [en]

    The sporadic, late onset form of Alzheimers disease (AD) shares pathological hallmarks with the familial form; however, no clear reason for increased beta-amyloid (A beta) generation has been found in the former. It has long been speculated that the late onset form of AD is caused by reduced degradation and/or clearance of A beta. Indeed, both intracellular degradation systems, the proteasomal and lysosomal systems, have been shown to be defective in AD. Reduced proteasome activity increases levels of intracellular and secreted A beta. Furthermore, accumulation of improperly degraded A beta in the lysosomes causes lysosomal disruption and cell death. We recently showed that oligomeric A beta can be transmitted from one neuron to another, which causes neurotoxicity. In both the donating and receiving cells, A beta accumulates in the endo-lysosomal compartment. It is possible that ineffective degradation of A beta causes its transfer to neighboring neurons, thereby spreading AD pathology. This review summarizes the data underlying the idea of reduced A beta clearance and subsequent A beta spread in AD, and also suggests new therapeutic methods, which are aimed at targeting the degradation systems and synaptic transfer. By enhancing degradation of intracellular accumulated A beta, it can be possible to remove it and avoid A beta-induced neurodegeneration without disturbing the endogenously important pool of secreted A beta. Additionally, drugs targeted to inhibit the spread of intracellular toxic A beta aggregates may also be useful in stopping the progression of pathology, without affecting the level of A beta that normally occurs in the brain.

  • 13.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Brain size is reduced by selectionfor tameness in Red Junglefowl–correlated effects in vital organs2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 3306Article in journal (Refereed)
    Abstract [en]

    During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

  • 14.
    Ahlenius, Sven
    et al.
    Göteborgs universitet.
    Heimann, Mikael
    Göteborgs universitet.
    Larsson, Knut
    Göteborgs universitet.
    Prolongation of the ejaculation latency in the male rat by thioridazine and chlorimipramine.1979In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 65, no 2, 137-140 p.Article in journal (Refereed)
    Abstract [en]

    Thioridazine (3 mg/kg) and chlorimipramine (1.5–6.0 mg/kg) prolonged the ejaculation latency and increased the number of mounts but did not change the number of intromissions preceding ejaculation. Blockade of peripheral and central noradrenaline receptors by phentolamine and phenoxybenzamine respectively resulted in a suppression of all aspects of the sexual behavior with increasing doses. dl-5-HTP (25–100 mg/kg) in combination with an inhibitor of peripheral 5-HTP decarboxylase (benserazide, 25 mg/kg) produced, like chlorimipramine and thioridazine, a prolongation of ejaculation latency and an increase in the number of mounts preceding ejaculation. Selective inhibition of 5-HT reuptake however, by zimelidine (0–20 mg/kg) or alaproclate (0–20 mg/kg) did not affect the mating behavior. At higher doses of these drugs some animals failed to initiate sexual activities. There was an increase in the postejaculatory interval but no change in the ejaculatory latency.It is concluded that the prolonged ejaculation latencies observed following treatment with thioridazine or chlorimipramine is not due to a blockade of central or peripheral adrenergic -receptors.

  • 15.
    Ahlner, Alexandra
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    Carlsson, Mats
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    Jonsson, Bengt-Harald
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    PINT: a software for integration of peak volumes and extraction of relaxation rates2013In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 56, no 3, 191-202 p.Article in journal (Refereed)
    Abstract [en]

    We present the software Peak INTegration (PINT), designed to perform integration of peaks in NMR spectra. The program is very simple to run, yet powerful enough to handle complicated spectra. Peaks are integrated by fitting predefined line shapes to experimental data and the fitting can be customized to deal with, for instance, heavily overlapped peaks. The results can be inspected visually, which facilitates systematic optimization of the line shape fitting. Finally, integrated peak volumes can be used to extract parameters such as relaxation rates and information about low populated states. The utility of PINT is demonstrated by applications to the 59 residue SH3 domain of the yeast protein Abp1p and the 289 residue kinase domain of murine EphB2.

  • 16.
    Ahlstrand, I.
    et al.
    School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Thyberg, Ingrid
    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, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. School of Health Sciences, Jönköping University, Jönköping, Sweden; School of Occupational Therapy and Social Work, CHIRI, Curtin University, Perth, WA, Australia.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Björk, Mathilda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center. School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project2015In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, no 4, 259-264 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: To study differences regarding pain and activity limitations during the 3 years following diagnosis in women and men with contemporary treated early RA compared with their counterparts who were diagnosed 10 years earlier. Method: This study was based on patients recruited to the Early Intervention in RA (TIRA) project. In the first cohort (TIRA-1) 320 patients were included in time for diagnosis during 1996-1998 and 463 patients were included in the second cohort (TIRA-2) during 2006-2009. Disease activity, pain intensity (Visual Analogue Scale, VAS), bodily pain (BP) in the 36-item Short Form Health Survey (SF-36), activity limitations (Health Assessment Questionnaire, HAQ), and medication were reported at inclusion and at follow-up after 1, 2, and 3 years. Results: Disease activity, pain, and activity limitations were pronounced at inclusion across both genders and in both cohorts, with some improvement observed during the first year after diagnosis. Disease activity did not differ between cohorts at inclusion but was significantly lower at the follow-ups in the TIRA-2 cohort, in which the patients were prescribed traditional disease-modifying anti-rheumatic drugs (DMARDs) and biological agents more frequently. In TIRA-2, patients reported significantly lower pain and activity limitations at all follow-ups, with men reporting lower pain than women. Women reported significantly higher activity limitations at all time points in TIRA-2. Conclusions: Pain and activity limitations were still pronounced in the contemporary treated early RA cohort compared with their counterparts diagnosed 10 years earlier and both of these factors need to be addressed in clinical settings.

  • 17.
    Ahlstrand, Inger
    et al.
    Jonköping University, Sweden.
    Björk, Mathilda
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Jonköping University, Sweden.
    Thyberg, Ingrid
    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, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Jonköping University, Sweden; Curtin University, Australia.
    Pain and difficulties performing valued life activities in women and men with rheumatoid arthritis2015In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 34, no 8, 1353-1362 p.Article in journal (Refereed)
    Abstract [en]

    This study aimed to examine the difficulties with performing valued life activities in relation to pain intensity in women and men with rheumatoid arthritis (RA). In total, 737 persons with RA (73 % women) from three rheumatology units in Sweden responded to a questionnaire measuring performance of 33 valued life activities and self-rated pain. The relationships between performance of valued life activities (VLAs) and pain (measured by visual analogue scale (VAS)) were analysed based on gender. Multiple linear regression analyses were conducted with the total VLA score as dependent variable. Women reported more pain and difficulties in performing valued life activities than men. Across genders, 85 % reported at least one valued life activity affected by RA. Significantly more women than men encountered difficulties in performing some activities such as cooking, gardening and meeting new people. Women reported higher pain intensity (35 mm) than men (31 mm). Almost all 33 difficulty ratings for valued life activities were higher among persons with high pain (greater than 40 mm) than persons with lower pain. Difficulty ratings for valued life activities correlated positively with pain in persons with lower pain, but not among those with high pain. The results highlight the importance of addressing pain, especially among women with RA, as they reported pain to impact on their valued life activities. Interestingly, this was evident also in women with lower levels of pain.

  • 18.
    Aho, Nikolas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Proczkowska-Björklund, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Victimization, polyvictimization , and health in Swedish adolescents2016In: Adolescent Health, Medicine and Therapeutics, ISSN 1179-318X, Vol. 7, 89-99 p.Article in journal (Refereed)
    Abstract [en]

    The main objective of this article was to study the relationship between the different areas of victimization (eg, sexual victimization) and psychological symptoms, taking into account the full range of victimization domains. The final aim was to contribute further evidence regarding the bias that studies that focus on just one area of victimization may be introduced into our psychological knowledge. The sample included 5,960 second-year high school students in Sweden with a mean age of 17.3 years (range =16–20 years, standard deviation =0.652), of which 49.6% were females and 50.4% males. The Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children were used to assess victimization and psychological problems separately. The results show that a majority of adolescents have been victimized, females reported more total events and more sexual victimization and childhood maltreatment, and males were more often victims of conventional crime. The majority of victimization domains as well as the sheer number of events (polyvictimization [PV]) proved to be harmful to adolescent health, affecting females more than males. PV explained part of the health effect and had an impact on its own and in relation to each domain. This suggests the possibility that PV to a large degree explains trauma symptoms. In order to understand the psychological effects of trauma, clinicians and researchers should take into account the whole range of possible types of victimization.

  • 19.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Polypeptide-Based Nanoscale Materials2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Self-assembly has emerged as a promising technique for fabrication of novel hybrid materials and nanostructures. The work presented in this thesis has been focused on developing nanoscale materials based on synthetic de novo designed polypeptides. The polypeptides have been utilized for the assembly of gold nanoparticles, fibrous nanostructures, and for sensing applications.

    The 42-residue polypeptides are designed to fold into helix-loop-helix motifs and dimerize to form four-helix bundles. Folding is primarily driven by the formation of a hydrophobic core made up by the hydrophobic faces of the amphiphilic helices. The peptides have either a negative or positive net charge at neutral pH, depending on the relative abundance of Glu and Lys. Charge repulsion thus prevents homodimerization at pH 7 while promoting hetero-dimerization through the formation of stabilising salt bridges. A Cys incorporated in position 22, located in the loop region, allowed for directed, thiol-dependent, immobilization on planar gold surfaces and gold nanoparticles. The negatively charged (Glu-rich) peptide formed homodimers and folded in solution at pH < 6 or in the presence of certain metal ions, such as Zn2+. The folding properties of this peptide were retained when immobilized directly on gold, which enabled reversible assembly of gold nanoparticles resulting in aggregates with well-defined interparticle separations. Particle aggregation was found to induce folding of the immobilized peptides but folding could also be utilized to induce aggregation of the particles by exploiting the highly specific interactions involved in both homodimerization and hetero-association. The possibility to control the assembly of polypeptide-functionalized gold nanoparticles was utilized in a colorimetric protein assay. Analyte binding to immobilized ligands prevented the formation of dense particle aggregates when subjecting the particles to conditions normally causing extensive aggregation. Analyte binding could hence easily be distinguished by the naked eye. Moreover, the peptides were utilized to assemble gold nanoparticles on planar gold and silica substrates.

    Fibrous nanostructures were realized by linking monomers through a disulphide-bridge. The disulphide-linked peptides were found to spontaneously assemble into long and extremely thin peptide fibres as a result of a propagating association mediated by folding into four-helix bundles.

    List of papers
    1. Alpha-helix-inducing dimerization of synthetic polypeptide scaffolds on gold
    Open this publication in new window or tab >>Alpha-helix-inducing dimerization of synthetic polypeptide scaffolds on gold
    Show others...
    2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 6, 2480-2487 p.Article in journal (Refereed) Published
    Abstract [en]

    Designed, synthetic polypeptides that assemble into four-helix bundles upon dimerization in solution were studied with respect to folding on planar gold surfaces. A model system with controllable dimerization properties was employed, consisting of negatively and positively charged peptides. Circular dichroism spectroscopy and surface plasmon resonance based measurements showed that at neutral pH, the peptides were able to form heterodimers in solution, but unfavorable electrostatic interactions prevented the formation of homodimers. The dimerization propensity was found to be both pH- and buffer-dependent. A series of infrared absorption−reflection spectroscopy experiments of the polypeptides attached to planar gold surfaces revealed that if the negatively charged peptide was immobilized from a loading solution where it was folded, its structure was retained on the surface provided it had a cysteine residue available for anchoring to gold. If it was immobilized as random coil, it remained unstructured on the surface but was able to fold through heterodimerization if subsequently exposed to a positively charged polypeptide. When the positively charged peptide was immobilized as random coil, heterodimerization could not be induced, probably because of high-affinity interactions between the charged primary amine groups and the gold surface. These observations are intended to pave the way for future engineering of functional surfaces based on polypeptide scaffolds where folding is known to be crucial for function.

    Place, publisher, year, edition, pages
    ACS Publications, 2005
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-15115 (URN)10.1021/la048029u (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2014-10-08Bibliographically approved
    2. Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles
    Open this publication in new window or tab >>Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles
    Show others...
    2006 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, Vol. 128, no 7, 2194 -2195 p.Article in journal (Refereed) Published
    Abstract [en]

    This communication reports the first steps in the construction of a novel, nanoparticle-based hybrid material for biomimetic and biosensor applications. Gold nanoparticles were modified with synthetic polypeptides to enable control of the particle aggregation state in a switchable manner, and particle aggregation was, in turn, found to induce folding of the immobilized peptides.

    Place, publisher, year, edition, pages
    ACS Publications, 2006
    Keyword
    Not aviable
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-14041 (URN)10.1021/ja057056j (DOI)
    Available from: 2006-09-28 Created: 2006-09-28 Last updated: 2014-10-08Bibliographically approved
    3. Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles
    Open this publication in new window or tab >>Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles
    Show others...
    2008 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, Vol. 130, no 17, 5780-5788 p.Article in journal (Refereed) Published
    Abstract [en]

    Reversible assembly of gold nanoparticles controlled by the homodimerization and folding of an immobilized de novo designed synthetic polypeptide is described. In solution at neutral pH, the polypeptide folds into a helix–loop–helix four-helix bundle in the presence of zinc ions. When immobilized on gold nanoparticles, the addition of zinc ions induces dimerization and folding between peptide monomers located on separate particles, resulting in rapid particle aggregation. The particles can be completely redispersed by removal of the zinc ions from the peptide upon addition of EDTA. Calcium ions, which do not induce folding in solution, have no effect on the stability of the peptide decorated particles. The contribution from folding on particle assembly was further determined utilizing a reference peptide with the same primary sequence but containing both D and L amino acids. Particles functionalized with the reference peptide do not aggregate, as the peptides are unable to fold. The two peptides, linked to the nanoparticle surface via a cysteine residue located in the loop region, form submonolayers on planar gold with comparable properties regarding surface density, orientation, and ability to interact with zinc ions. These results demonstrate that nanoparticle assembly can be induced, controlled, and to some extent tuned, by exploiting specific molecular interactions involved in polypeptide folding.

    Place, publisher, year, edition, pages
    ACS Publications, 2008
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-15116 (URN)10.1021/ja711330f (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2014-10-08Bibliographically approved
    4. Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds
    Open this publication in new window or tab >>Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds
    Show others...
    2008 (English)In: Proceedings SPIE, Vol. 6885, Photonic Biosensing and Microoptics, 2008, 688506-1-688506-8 p.Conference paper, Published paper (Refereed)
    Abstract [en]

    Heterodimerization between designed helix-loop-helix polypeptides was utilized in order to assemble gold nanoparticles on planar substrates. The peptides were designed to fold into four-helix bundles upon dimerization. A Cys-residue in the loop region was used to immobilize one of the complementary peptides on a maleimide containing SAM on planar gold substrates whereas the second peptide was immobilized directly on gold nanoparticles. Introducing the peptide decorated particles over a peptide functionalized surface resulted in particle assembly. Further, citrate stabilized particles were assembled on amino-silane modified glass and silicon substrates. By subsequently introducing peptides and gold nanoparticles, particle-peptide hybrid multi layers could be formed.

    Keyword
    Heterodimerization, polypeptides, gold nanoparticles, four-helix bundle, helix-loop-helix, self-assembly
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-15118 (URN)10.1117/12.775806 (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2014-10-08Bibliographically approved
    5. Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides
    Open this publication in new window or tab >>Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides
    Show others...
    2008 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, Vol. 47, no 30, 5554-5556 p.Article in journal (Refereed) Published
    Place, publisher, year, edition, pages
    Wiley InterScience, 2008
    Keyword
    fibers, helical structures, nanostructures, polypeptides, self-assembly
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-15120 (URN)10.1002/anie.200801155 (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2014-10-08Bibliographically approved
    6. Assembly of Polypeptide-Functionalized Gold Nanoparticles through a Heteroassociation- and Folding-Dependent Bridging
    Open this publication in new window or tab >>Assembly of Polypeptide-Functionalized Gold Nanoparticles through a Heteroassociation- and Folding-Dependent Bridging
    2008 (English)In: Nano letters (Print), ISSN 1530-6984, Vol. 8, no 8, 2473-2478 p.Article in journal (Refereed) Published
    Abstract [en]

    Gold nanoparticles were functionalized with a synthetic polypeptide, de novo-designed to associate with a charge complementary linker polypeptide in a folding-dependent manner. A heterotrimeric complex that folds into two disulphide-linked four-helix bundles is formed when the linker polypeptide associates with two of the immobilized peptides. The heterotrimer forms in between separate particles and induces a rapid and extensive aggregation with a well-defined interparticle spacing. The aggregated particles are redispersed when the disulphide bridge in the linker polypeptide is reduced.

    Place, publisher, year, edition, pages
    ACS Publications, 2008
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-15121 (URN)10.1021/nl8014796 (DOI)
    Note
    The original title of this article was "Assembly of Decorated Gold Nanoparticles through a Hetero-Association and Folding-Dependent Bridging".Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2014-10-08
    7. Colorimetric Protein Sensing by Controlled Assembly of Gold Nanoparticles Functionalized with Synthetic Receptors
    Open this publication in new window or tab >>Colorimetric Protein Sensing by Controlled Assembly of Gold Nanoparticles Functionalized with Synthetic Receptors
    Show others...
    2009 (English)In: Small, ISSN 1613-6810, Vol. 5, no 21, 2445-2452 p.Article in journal (Refereed) Published
    Abstract [en]

    A strategy for colorimetric sensing of proteins, based on the induced assembly of polypeptide-functionalized gold nanoparticles, is described. Recognition was accomplished using a polypeptide sensor scaffold designed to specifically bind the model analyte, human carbonic anhydrase II (HCAII). The extent of particle aggregation, induced by the Zn2+-triggered dimerization and folding of a second polypeptide also present on the surface of the gold nanoparticle, gave a readily detectable colorimetric shift that was dependent on the concentration of the target protein. In the absence of HCAII, particle aggregation resulted in a major redshift of the plasmon peak whereas analyte binding prevented formation of dense aggregates, significantly reducing the magnitude of the redshift. The limit of detection of HCAII was estimated to be around 15 nM. The versatility of the technique was demonstrated using a second model system based on the recognition of a peptide sequence from the tobacco mosaic virus coat protein (TMVP by a recombinant antibody fragment. This strategy is proposed as a generic platform for robust and specific protein analysis that can be further developed for monitoring a wide range of target proteins.

    Keyword
    Not available.
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-15122 (URN)10.1002/smll.200900530 (DOI)
    Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2015-05-29Bibliographically approved
  • 20.
    Aili, Daniel
    et al.
    Linköping University, The Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, The Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Rydberg, Johan
    Linköping University, The Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Nesterenko, Irina
    Linköping University, The Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Björefors, Fredrik
    Linköping University, The Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Baltzer, Lars
    Division of Organic Chemistry, Department of Biochemistry and Organic Chemistry, BMC, Box 599, Uppsala University, SE-751 24 Uppsala, Sweden..
    Liedberg, Bo
    Linköping University, The Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Controlled Assembly of Gold Nanoparticles using De Novo Designed Polypeptide Scaffolds2008In: Proceedings SPIE, Vol. 6885, Photonic Biosensing and Microoptics, 2008, 688506-1-688506-8 p.Conference paper (Refereed)
    Abstract [en]

    Heterodimerization between designed helix-loop-helix polypeptides was utilized in order to assemble gold nanoparticles on planar substrates. The peptides were designed to fold into four-helix bundles upon dimerization. A Cys-residue in the loop region was used to immobilize one of the complementary peptides on a maleimide containing SAM on planar gold substrates whereas the second peptide was immobilized directly on gold nanoparticles. Introducing the peptide decorated particles over a peptide functionalized surface resulted in particle assembly. Further, citrate stabilized particles were assembled on amino-silane modified glass and silicon substrates. By subsequently introducing peptides and gold nanoparticles, particle-peptide hybrid multi layers could be formed.

  • 21.
    Aili, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Rydberg, Johan
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Nesterenko, Irina
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Björefors, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Baltzer, Lars
    Department of Biochemistry and Organic Chemistry, BMC, Box 599, Uppsala UniVersity, SE-751 24 Uppsala, Sweden.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Folding Induced Assembly of Polypeptide Decorated Gold Nanoparticles2008In: Journal of the American Chemical Society, ISSN 0002-7863, Vol. 130, no 17, 5780-5788 p.Article in journal (Refereed)
    Abstract [en]

    Reversible assembly of gold nanoparticles controlled by the homodimerization and folding of an immobilized de novo designed synthetic polypeptide is described. In solution at neutral pH, the polypeptide folds into a helix–loop–helix four-helix bundle in the presence of zinc ions. When immobilized on gold nanoparticles, the addition of zinc ions induces dimerization and folding between peptide monomers located on separate particles, resulting in rapid particle aggregation. The particles can be completely redispersed by removal of the zinc ions from the peptide upon addition of EDTA. Calcium ions, which do not induce folding in solution, have no effect on the stability of the peptide decorated particles. The contribution from folding on particle assembly was further determined utilizing a reference peptide with the same primary sequence but containing both D and L amino acids. Particles functionalized with the reference peptide do not aggregate, as the peptides are unable to fold. The two peptides, linked to the nanoparticle surface via a cysteine residue located in the loop region, form submonolayers on planar gold with comparable properties regarding surface density, orientation, and ability to interact with zinc ions. These results demonstrate that nanoparticle assembly can be induced, controlled, and to some extent tuned, by exploiting specific molecular interactions involved in polypeptide folding.

  • 22.
    Aili, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Tai, Feng-I
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Baltzer, Lars
    Department of Biochemistry andOrganic Chemistry Uppsala University, BMC, Box 576, 75123 Uppsala, Sweden.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Self-Assembly of Fibers and Nanorings from Disulfide-Linked Helix–Loop–Helix Polypeptides2008In: Angewandte Chemie International Edition, ISSN 1433-7851, Vol. 47, no 30, 5554-5556 p.Article in journal (Refereed)
  • 23.
    Aili, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Rydberg, Johan
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics . Linköping University, The Institute of Technology.
    Baltzer, Lars
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Aggregation-Induced Folding of a de novo Designed Polypeptide Immobilized on Gold Nanoparticles2006In: Journal of the American Chemical Society, ISSN 0002-7863, Vol. 128, no 7, 2194 -2195 p.Article in journal (Refereed)
    Abstract [en]

    This communication reports the first steps in the construction of a novel, nanoparticle-based hybrid material for biomimetic and biosensor applications. Gold nanoparticles were modified with synthetic polypeptides to enable control of the particle aggregation state in a switchable manner, and particle aggregation was, in turn, found to induce folding of the immobilized peptides.

  • 24.
    Aira, Naomi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Anna-Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Singh, Susmita K.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Mckay, Derek M.
    University of Calgary, Canada.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Species dependent impact of helminth-derived antigens on human macrophages infected with Mycobacterium tuberculosis: Direct effect on the innate anti-mycobacterial response2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 3, e0005390Article in journal (Refereed)
    Abstract [en]

    Background In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. Principal findings We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb. Conclusion We conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages.

  • 25.
    Ajileye, Adebisi
    et al.
    Birmingham Heartlands Hospital, England.
    Alvarez, Nataly
    Corp Invest Biol, Colombia; University of Pontificia Bolivariana, Colombia.
    Merker, Matthias
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Walker, Timothy M.
    University of Oxford, England.
    Akter, Suriya
    Institute Trop Med, Belgium.
    Brown, Kerstin
    Birmingham Heartlands Hospital, England.
    Moradigaravand, Danesh
    Wellcome Trust Sanger Institute, England.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Andres, Soenke
    Research Centre Borstel, Germany.
    Schleusener, Viola
    Research Centre Borstel, Germany.
    Omar, Shaheed V.
    Centre TB, South Africa.
    Coll, Francesc
    London School Hyg and Trop Med, England.
    Huang, Hairong
    Capital Medical University, Peoples R China.
    Diel, Roland
    University Hospital, Germany.
    Ismail, Nazir
    Centre TB, South Africa.
    Parkhill, Julian
    Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
    de Jong, Bouke C.
    Institute Trop Med, Belgium.
    Peto, Tim E. A.
    University of Oxford, England.
    Crook, Derrick W.
    University of Oxford, England; Public Health England Microbiol Serv, England.
    Niemann, Stefan
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Robledo, Jaime
    Corp Invest Biol, Colombia; University of Pontificia Bolivariana, Colombia.
    Grace Smith, E.
    Birmingham Heartlands Hospital, England.
    Peacock, Sharon J.
    Wellcome Trust Sanger Institute, England; London School Hyg and Trop Med, England; University of Cambridge, England.
    Koeser, Claudio U.
    University of Cambridge, England.
    Some Synonymous and Nonsynonymous gyrA Mutations in Mycobacterium tuberculosis Lead to Systematic False-Positive Fluoroquinolone Resistance Results with the Hain GenoType MTBDRsl Assays2017In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 61, no 4, e02169-16Article in journal (Refereed)
    Abstract [en]

    In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.

  • 26.
    Albrecht, Matthew A.
    et al.
    Curtin University, Australia .
    Stuart, Geoffrey W.
    La Trobe University, Australia .
    Falkmer, Marita
    Curtin University, Australia, Jonköping University, Sweden .
    Ordqvist, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Leung, Denise
    Curtin University, Australia .
    Foster, Jonathan K.
    Curtin University, Australia Health Department WA, Australia .
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Brief Report: Visual Acuity in Children with Autism Spectrum Disorders2014In: Journal of autism and developmental disorders, ISSN 0162-3257, E-ISSN 1573-3432, Vol. 44, no 9, 2369-2374 p.Article in journal (Refereed)
    Abstract [en]

    Recently, there has been heightened interest in suggestions of enhanced visual acuity in autism spectrum disorders (ASD) which was sparked by evidence that was later accepted to be methodologically flawed. However, a recent study that claimed children with ASD have enhanced visual acuity (Brosnan et al. in J Autism Dev Disord 42:2491-2497, 2012) repeated a critical methodological flaw by using an inappropriate viewing distance for a computerised acuity test, placing the findings in doubt. We examined visual acuity in 31 children with ASD and 33 controls using the 2 m 2000 Series Revised Early Treatment Diabetic Retinopathy Study chart placed at twice the conventional distance to better evaluate possible enhanced acuity. Children with ASD did not demonstrate superior acuity. The current findings strengthen the argument that reports of enhanced acuity in ASD are due to methodological flaws and challenges the reported association between visual acuity and systemising type behaviours.

  • 27.
    Alexander, Helen K.
    et al.
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba.
    Booy, Evan P.
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada .
    Xiao, Wenyan
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba.
    Ezzati, Peyman
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba.
    Baust, Heinrich
    Department of Radiooncology, University of Erlangen, Erlangen, Germany .
    Los, Marek Jan
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    Selected technologies to control genes and their products for experimental and clinical purposes2007In: Archivum Immunologiae et Therapiae Experimentalis, ISSN 0004-069X, E-ISSN 1661-4917, Vol. 55, no 3, 139-149 p.Article in journal (Refereed)
    Abstract [en]

    "On-demand" regulation of gene expression is a powerful tool to elucidate the functions of proteins and biologically-active RNAs. We describe here three different approaches to the regulation of expression or activity of genes or proteins. Promoter-based regulation of gene expression was among the most rapidly developing techniques in the 1980s and 1990s. Here we provide basic information and also some characteristics of the metallothionein-promoter-based system, the tet-off system, Muristerone-A-regulated expression through the ecdysone response element, RheoSwitch (R), coumermycin/novobiocin-regulated gene expression, chemical dimerizer-based promoter activation systems, the "Dual Drug Control" system, "constitutive androstane receptor"-based regulation of gene expression, and RU486/mifepristone-driven regulation of promoter activity. A large part of the review concentrates on the principles and usage of various RNA interference techniques (RNAi: siRNA, shRNA, and miRNA-based methods). Finally, the last part of the review deals with historically the oldest, but still widely used, methods of temperature-dependent regulation of enzymatic activity or protein stability (temperature-sensitive mutants). Due to space limitations we do not describe in detail but just mention the tet-regulated systems and also fusion-protein-based regulation of protein activity, such as estrogen-receptor fusion proteins. The information provided below is aimed to assist researchers in choosing the most appropriate method for the planned development of experimental systems with regulated expression or activity of studied proteins.

  • 28.
    Alfredsson, Joakim
    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. Duke University, NC 27710 USA.
    Alexander, Karen P.
    Duke University, NC 27710 USA.
    Multiple Chronic Conditions in Older Adults with Acute Coronary Syndromes2016In: Clinics in Geriatric Medicine, ISSN 0749-0690, E-ISSN 1879-8853, Vol. 32, no 2, 291-+ p.Article in journal (Refereed)
    Abstract [en]

    Older adults presenting with acute coronary syndromes (ACSs) often have multiple chronic conditions (MCCs). In addition to traditional cardiovascular (CV) risk factors (ie, hypertension, hyperlipidemia, and diabetes), common CV comorbidities include heart failure, stroke, and atrial fibrillation, whereas prevalent non-CV comorbidities include chronic kidney disease, anemia, depression, and chronic obstructive pulmonary disease. The presence of MCCs affects the presentation (eg, increased frequency of type 2 myocardial infarctions [MIs]), clinical course, and prognosis of ACS in older adults. In general, higher comorbidity burden increases mortality following MI, reduces utilization of ACS treatments, and increases the importance of developing individualized treatment plans.

  • 29.
    Amundstuen Reppe, Linda
    et al.
    Nordic University, Norway; Norwegian University of Science and Technology, Norway; St Olavs Hospital, Norway.
    Spigset, Olav
    Norwegian University of Science and Technology, Norway; St Olavs Hospital, Norway.
    Kampmann, Jens Peter
    Bispebjerg Hospital, Denmark.
    Damkier, Per
    Odense University Hospital, Denmark.
    Rolighed Christensen, Hanne
    Bispebjerg Hospital, Denmark.
    Böttiger, Ylva
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Schjott, Jan
    Haukeland Hospital, Norway; University of Bergen, Norway; Haukeland Hospital, Norway.
    Quality assessment of structure and language elements of written responses given by seven Scandinavian drug information centres2017In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 73, no 5, 623-631 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to identify structure and language elements affecting the quality of responses from Scandinavian drug information centres (DICs). Six different fictitious drug-related queries were sent to each of seven Scandinavian DICs. The centres were blinded for which queries were part of the study. The responses were assessed qualitatively by six clinical pharmacologists (internal experts) and six general practitioners (GPs, external experts). In addition, linguistic aspects of the responses were evaluated by a plain language expert. The quality of responses was generally judged as satisfactory to good. Presenting specific advice and conclusions were considered to improve the quality of the responses. However, small nuances in language formulations could affect the individual judgments of the experts, e.g. on whether or not advice was given. Some experts preferred the use of primary sources to the use of secondary and tertiary sources. Both internal and external experts criticised the use of abbreviations, professional terminology and study findings that was left unexplained. The plain language expert emphasised the importance of defining and explaining pharmacological terms to ensure that enquirers understand the response as intended. In addition, more use of active voice and less compressed text structure would be desirable. This evaluation of responses to DIC queries may give some indications on how to improve written responses on drug-related queries with respect to language and text structure. Giving specific advice and precise conclusions and avoiding too compressed language and non-standard abbreviations may aid to reach this goal.

  • 30.
    Andersson, Cecilia
    et al.
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Kolmodin, Martin
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Ivarsson, Sten-Anders
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Carlsson, Annelie
    Department of Pediatrics, Lund University, Sweden.
    Forsander, Gun
    Department of Pediatrics, Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Lindblad, Bengt
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Kockum, Ingrid
    Department of Clinical Neurosciences, Karolinska Institute, Stockholm, Sweden.
    Marcus, Claude
    Division of Pediatrics, Department of Clinical Science, Intervention and Technology Karolinska Institute, Stockholm, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ortqvist, Eva
    Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
    Lernmark, Ake
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Elding Larsson, Helena
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Törn, Carina
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Islet cell antibodies (ICA) identify autoimmunity in children with new onset diabetes mellitus negative for other islet cell antibodies2014In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 15, no 5, 336-344 p.Article in journal (Refereed)
    Abstract [en]

    AIMS: The aim of this study was to explore whether islet cell antibodies (ICA) could be identified in children with newly onset diabetes mellitus but negative for autoantibodies against glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), insulin (IAA), or any of the three variants with arginine (R), tryptophan (W), or glutamine (Q) at position 325 of the zinc transporter 8 (ZnT8A).

    METHODS: A population-based analysis of autoantibodies was performed from 1 May 2005 to 2 September 2010 in Swedish children newly diagnosed with diabetes. ICA was analyzed with an enzyme-linked immunosorbent assay and if positive, reanalyzed in the classical ICA immunofluorescence assay, in 341 samples among 3545 children who had been tested negative for all of GADA, IA-2A, IAA, or ZnT8A (R, W, Q).

    RESULTS: An isolated positivity for ICA was identified in 5.0% (17/341) of the newly diagnosed children. The levels of ICA in positive subjects ranged from 3 to 183 JDF-U (median 30). This finding increased the diagnostic sensitivity of islet autoimmunity as 3204/3545 patients (90.4%) were islet autoantibody positive without the ICA analyses and 3221 patients (90.9%) were positive with the inclusion of ICA.

    CONCLUSIONS: The finding of an isolated positivity for ICA despite negativity for GADA, IA-2A, IAA, and ZnT8A (R, W, Q) suggests that still another yet unidentified autoantigen(s) may contribute to the ICA immunofluorescence. Hence, ICA is important to analyze in type 1 diabetes children and adolescents that would otherwise be islet autoantibody negative.

  • 31.
    Andersson, Erik
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Hedman, Erik
    Karolinska Institutet, Stockholm, Sweden.
    Enander, Jesper
    Karolinska Institutet, Stockholm, Sweden.
    Radu Djurfeldt, Diana
    Karolinska Institutet, Stockholm, Sweden.
    Ljótsson, Brjánn
    Karolinska Institutet, Stockholm, Sweden.
    Cervenka, Simon
    Karolinska Institutet, Stockholm, Sweden.
    Isung, Josef
    Karolinska Institutet, Stockholm, Sweden.
    Svanborg, Cecilia
    Karolinska Institutet, Stockholm, Sweden.
    Mataix-Cols, David
    Karolinska Institutet, Stockholm, Sweden.
    Kaldo, Viktor
    Karolinska Institutet, Stockholm, Sweden.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Inst, Div Psychiat, Dept Clin Neurosci, Stockholm, Sweden.
    Lindefors, Nils
    Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Karolinska Institutet, Stockholm, Sweden.
    D-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants: A Randomized Clinical Trial.2015In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 72, no 7, 659-667 p.Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: It is unclear whether d-cycloserine (DCS), a partial N-methyl-d-aspartate agonist that enhances fear extinction, can augment the effects of exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD).

    OBJECTIVES: To examine whether DCS augments the effects of CBT for OCD and to explore (post hoc) whether concomitant antidepressant medication moderates the effects of DCS.

    DESIGN, SETTING, AND PARTICIPANTS: A 12-week, double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4, 2012, and September 26, 2013. Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial. The main analysis was by intention-to-treat population.

    INTERVENTIONS: All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo, administered 1 hour before each of 5 exposure and response prevention tasks.

    MAIN OUTCOMES AND MEASURES: Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up. Remission was defined as a score of 12 or lower on the Y-BOCS.

    RESULTS: In the primary intention-to-treat analyses, DCS did not augment the effects of CBT compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50] at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week 12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction with antidepressants (clinician-rated Y-BOCS, B = -1.08; Z = -2.79; P = .005). Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group, at both posttreatment and follow-up (clinician-rated Y-BOCS: t62 = -3.00; P = .004; and t61 = -3.49; P < .001, respectively). In the DCS group, a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up (60% [95% CI, 45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P = .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%] remission rate in both groups).

    CONCLUSIONS AND RELEVANCE: The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction. Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD.

    TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01649895.

  • 32.
    Andersson, Erik
    et al.
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Hedman, Erik
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Ljotsson, Brjann
    Karolinska Institute, Sweden.
    Wikstrom, Maja
    Karolinska Institute, Sweden.
    Elveling, Elin
    Karolinska Institute, Sweden.
    Lindefors, Nils
    Karolinska Institute, Sweden.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Kaldo, Viktor
    Karolinska Institute, Sweden.
    Ruck, Christian
    Karolinska Institute, Sweden.
    Cost-effectiveness of internet-based cognitive behavior therapy for obsessive-compulsive disorder: results from a randomized controlled trial2015In: Journal of Obsessive-Compulsive and Related Disorders, ISSN 2211-3649, Vol. 4, 47-53 p.Article in journal (Refereed)
    Abstract [en]

    Obsessive-compulsive disorder (OCD) is a common and disabling disorder. Although evidence-based psychological treatments exists, such as cognitive behavior therapy (CBT), the cost-effectiveness of CBT has not been properly investigated. In this trial, we used health economic data from a recently conducted randomized controlled trial, where 101 OCD patients were allocated to either internet-based CBT (ICBT) or control condition (online support therapy). We analyzed treatment effectiveness in relation to costs, using both a societal- (including all direct and indirect costs) and a health care unit perspective (including only the direct treatment costs). Bootstrapped net benefit regression analyses were also conducted, comparing the difference in costs and effects between ICBT and control condition, with different willingness-to-pay scenarios. Results showed that ICBT produced one additional remission for an average societal cost of $931 and this figure was even lower ($672) when narrowing the perspective to treatment costs only. The cost-utility analysis also showed that ICBT generated one additional QALY to an average price of $7186 from a societal perspective and $4800 when just analyzing the treatment costs. We conclude that ICBT is a cost-effective treatment and the next step in this line of research is to compare the cost-effectiveness of ICBT with face-to-face CBT. (C) 2014 Elsevier Inc. All rights reserved.

  • 33.
    Andersson, Erik
    et al.
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Ljotsson, Brjann
    Karolinska Institute, Sweden.
    Hedman, Erik
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Enander, Jesper
    Karolinska Institute, Sweden.
    Kaldo, Viktor
    Karolinska Institute, Sweden.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Lindefors, Nils
    Karolinska Institute, Sweden.
    Ruck, Christian
    Karolinska Institute, Sweden.
    Predictors and moderators of Internet-based cognitive behavior therapy for obsessive-compulsive disorder: Results from a randomized trial2015In: Journal of Obsessive-Compulsive and Related Disorders, ISSN 2211-3649, Vol. 4Article in journal (Refereed)
    Abstract [en]

    Internet-based cognitive behavior therapy (ICBT) for obsessive-compulsive disorder (OCD) has shown efficacy in randomized trials but many patients do not respond to the treatment, we therefore need to find predictors and moderators of treatment response. In this study, we analyzed predictors of ICBT response using both post-treatment as well as 24-month outcome data. As half of the participants were randomized to receive an Internet-based booster program as an adjunct to ICBT, we also investigated moderators of ICBT with or without booster. Results showed that more severe baseline OCD symptoms predicted worse end state outcome but also higher degree of change. Furthermore, high degree of working alliance predicted better outcome but patients with primary disgust emotions had worse treatment effects. The moderator analysis also indicated that scoring high on the obsessing subscale on the Obsessive-Compulsive Inventory-Revised predicted worse treatment outcome in the booster group. In conclusion, there are some possible predictors and moderators of ICBT for OCD but more research is needed with larger and clinically representative samples. (C) 2014 Elsevier Inc. All rights reserved.

  • 34.
    Andersson, Erik
    et al.
    Karolinska Institute, Sweden.
    Ljotsson, Brjann
    Karolinska Institute, Sweden.
    Hedman, Erik
    Karolinska Institute, Sweden.
    Hesser, Hugo
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Enander, Jesper
    Karolinska Institute, Sweden.
    Kaldo, Viktor
    Karolinska Institute, Sweden.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Lindefors, Nils
    Karolinska Institute, Sweden.
    Ruck, Christian
    Karolinska Institute, Sweden.
    Testing the Mediating Effects of Obsessive Beliefs in Internet-Based Cognitive Behaviour Therapy for Obsessive-Compulsive Disorder: Results from a Randomized Controlled Trial2015In: Clinical Psychology and Psychotherapy, ISSN 1063-3995, E-ISSN 1099-0879, Vol. 22, no 6, 722-732 p.Article in journal (Refereed)
    Abstract [en]

    Although cognitive interventions for obsessive-compulsive disorder (OCD) have been tested in randomized trials, there are few trials that have tested the specific mechanisms of cognitive interventions, i.e. how they achieve their effects. In this study, we aimed to investigate the mediating effects of a short cognitive intervention in the treatment of OCD and used data from a recently conducted randomized controlled trial where 101 participants were allocated to either Internet-based CBT (ICBT) or to a control condition. Obsessive beliefs were measured at pre-treatment, at the time they had received the cognitive intervention, and also at post-treatment. Weekly OCD symptoms were measured throughout the 10 weeks of treatment. We hypothesized that (1) the ICBT group would have greater reductions in obsessive beliefs (controlling for change in OCD symptoms) after completing the cognitive intervention, and that (2) this reduction would, in turn, predict greater OCD symptom reduction throughout the rest of the treatment period. Contrary to our expectations, the longitudinal mediation analysis indicated that (1) being randomized to ICBT actually increased the degree of obsessive beliefs after receiving the cognitive intervention at weeks 1-3, and (2) increase in obsessive beliefs predicted better outcome later in treatment. However, when repeating the analysis using cross-sectional data at post-treatment, the results were in line with the initial hypotheses. Results were replicated when the control condition received ICBT. We conclude that, although obsessive beliefs were significantly reduced at post-treatment for the ICBT group, early increase rather than decrease in obsessive beliefs predicted favourable outcome. Copyright (C) 2014 John Wiley & Sons, Ltd.

  • 35.
    Andersson, Erik
    et al.
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Ljotsson, Brjann
    Karolinska Institute, Sweden.
    Hedman, Erik
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Mattson, Simon
    Karolinska Institute, Sweden.
    Enander, Jesper
    Karolinska Institute, Sweden.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Kaldo, Viktor
    Karolinska Institute, Sweden.
    Lindefors, Nils
    Karolinska Institute, Sweden.
    Ruck, Christian
    Karolinska Institute, Sweden.
    Cost-effectiveness of an internet-based booster program for patients with obsessive-compulsive disorder: Results from a randomized controlled trial2015In: Journal of Obsessive-Compulsive and Related Disorders, ISSN 2211-3649, Vol. 4, 14-19 p.Article in journal (Refereed)
    Abstract [en]

    Cognitive behavior therapy (CBT) is an effective treatment for OCD when delivered face-to-face, in group-format and also via the internet. However, despite overall large effect sizes, a considerable amount of the patients relapse. One intervention that has the potential to reduce these relapse rates is booster programs, but if booster program is a cost-effective method of preventing relapse is still unknown. We used health economical data from a recent randomized controlled trial, where patients who had undergone an internet-based CBT were randomly allocated to receive an additional booster program. Assessment points were 4-, 7-, 12- and 24-month. Health economical data were primarily analyzed using a societal perspective. Results showed that the booster program was effective in preventing relapse, and the cost of one avoided relapse was estimated to $1066-1489. Cost-effectiveness acceptability curves showed that the booster program had a 90% probability of being cost-effective given a willingness to pay of $1000-1050 the first year, but this figure grew considerably after two years ($2500-5500). We conclude that internet-based booster programs are probably a cost-effective alternative within one-year time frame and that more treatment may be needed to maintain adequate cost-effectiveness up to two years. (C) 2014 Elsevier Inc. All rights reserved.

  • 36.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Clinician-Supported Internet-Delivered Psychological Treatment of Tinnitus2015In: American Journal of Audiology, ISSN 1059-0889, E-ISSN 1558-9137, Vol. 24, no 3, 299-301 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: Internet-delivered psychological treatments for tinnitus distress have existed for more than 15 years, and there are a slowly growing number of studies. The aim of this brief report is to review the evidence and to comment on the future potentials of Internet treatments for tinnitus. Method: Studies were retrieved, and in total 6 controlled studies were included in the review with 9 different comparisons (6 in which the treatment was compared against a control group and 3 in which Internet treatment was compared against group treatment). Moreover, 2 open studies based on clinical samples in regular care were also included in the review. The outcomes for the 2 controlled sets of studies were analyzed using meta-analytic methods. Results: For the 6 studies comparing Internet treatment against a no-treatment control condition, a moderate effect size was found (Hedgess g = 0.58). The 3 studies comparing Internet treatment against face-to-face group treatments showed a small difference of Hedgess g = 0.13. Conclusions: Internet-delivered psychological treatment holds promise as a treatment alternative to other standard forms of treatment delivery, including group treatment. Larger studies are needed as well as ways to blend information technology with regular services.

  • 37.
    Andersson, Gerhard
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Department of Clinical Neuroscience, Division of Psychiatry, Karolinska InstitutetStockholm, Sweden.
    Bergman Nordgren, Lise
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Buhrman, M.
    Department of Psychology, Uppsala University, Box 12 25Uppsala, Sweden.
    Carlbring, P.
    Department of Psychology, Stockholm UniversityStockholm, Sweden.
    Psychological treatments for depression delivered via the internet and supported by a clinician: An update2014In: Revista de Psicopatologia y Psicologia Clinica, ISSN 1136-5420, Vol. 19, no 3, 217-225 p.Article in journal (Refereed)
    Abstract [en]

    Guided internet-delivered cognitive behaviour therapy (ICBT) has been tested in many trials since the early studies dating back to the late 1990s. The aim of this review was to investigate the most recent literature on guided ICBT for depression. We identified 11 controlled studies published between January 2013 and September 2014. Overall, large treatment effects were observed with a few exceptions. A majority (7 studies) provided some information regarding unwanted effects such as deterioration. Three studies directly compared guided ICBT against face-to-face CBT. We added an earlier study and calculated meta-analytic summary statistics for the four studies involving a total of 336 participants. The average effect size difference was Hedges g = 0.12 (95% CI: -0.08∼0.32) in the direction of favouring guided ICBT, but with no practical importance. We conclude that guided ICBT is a promising treatment for depression and mood disorders and that the research is rapidly expanding.

  • 38.
    Andersson, Gerhard
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Oticon AS, Denmark; Karolinska Institute, Sweden.
    Lunner, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Oticon AS, Denmark.
    Laplante-Lévesque, Ariane
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Oticon AS, Denmark.
    Preminger, Jill E.
    University of Louisville, KY 40292 USA.
    Internet and Audiology: A Review of the First International Meeting2015In: American Journal of Audiology, ISSN 1059-0889, E-ISSN 1558-9137, Vol. 24, no 3, 269-270 p.Article, review/survey (Refereed)
    Abstract [en]

    Purpose: The purpose of this research forum article is to describe the impetus for holding the First International Meeting on Internet and Audiology (October 2014) and to introduce the special research forum that arose from the meeting. Method: The rationale for the First International Meeting on Internet and Audiology is described. This is followed by a short description of the research sections and articles appearing in the special issue. Six articles consider the process of health care delivery over the Internet; this includes health care specific to hearing, tinnitus, and balance. Four articles discuss the development of effective Internet-based treatment programs. Six articles describe and evaluate Internet-based interventions specific to adult hearing aid users. Conclusion: The fledgling field of Internet and audiology is remarkably broad. The Second International Meeting on Internet and Audiology ocurred in September 2015.

  • 39.
    Andersson, Gerhard
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Topooco, Naira
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Havik, Odd
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Nordgreen, Tine
    University of Bergen, Norway; Haukeland Hospital, Norway.
    6 Internet-supported versus face-to-face cognitive behavior therapy for depression2016In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 16, no 1, 55-60 p.Article, review/survey (Refereed)
    Abstract [en]

    Major depression and depressive symptoms are highly prevalent and there is a need for different forms of psychological treatments that can be delivered from a distance at a low cost. In the present review the authors contrast face-to-face and Internet-delivered cognitive behavior therapy (ICBT) for depression. A total of five studies are reviewed in which guided ICBT was directly compared against face-to-face CBT. Meta-analytic summary statistics were calculated for the five studies involving a total of 429 participants. The average effect size difference was Hedges g=0.12 (95% CI: -0.06-0.30) in the direction of favoring guided ICBT. The small difference in effect has no implication for clinical practice. The overall empirical status of clinician-guided ICBT for depression is commented on and future challenges are highlighted. Among these are developing treatments for patients with more severe and long-standing depression and for children, adolescents and the elderly. Also, there is a need to investigate mechanisms of change.

  • 40.
    Andersson, Henrik
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Björnström-Karlsson, Karin
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Orexin A Phosphorylates the gamma-Aminobutyric Acid Type A Receptor beta(2) Subunit on a Serine Residue and Changes the Surface Expression of the Receptor in SH-SY5Y Cells Exposed to Propofol2015In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 93, no 11, 1748-1755 p.Article in journal (Refereed)
    Abstract [en]

    Propofol activates the gamma-aminobutyric acid type A receptor (GABA(A)R) and causes a reversible neurite retraction, leaving a thin, thread-like structure behind; it also reverses the transport of vesicles in rat cortical neurons. The awakening peptide orexin A (OA) inhibits this retraction via phospholipase D (PLD) and protein kinase CE (PKCE). The human SH-SY5Y cells express both GABA(A)Rs and orexin 1 and 2 receptors. These cells are used to examine the interaction between OA and the GABAAR. The effects of OA are studied with flow cytometry and immunoblotting. This study shows that OA stimulates phosphorylation on the serine residues of the GABA(A)R beta(2) subunit and that the phosphorylation is caused by the activation of PLD and PKCE. OA administration followed by propofol reduces the cell surface expression of the GABA(A)R, whereas propofol stimulation before OA increases the surface expression. The GABA(A)R beta(2) subunit is important for receptor recirculation, and the effect of OA on propofol-stimulated cells may be due to a disturbed recirculation of the GABA(A)R. (C) 2015 Wiley Periodicals, Inc.

  • 41.
    Andersson, Maria
    et al.
    NIDA, MD 21224 USA.
    Diao, Xingxing
    NIDA, MD 21224 USA.
    Wohlfarth, Ariane
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. NIDA, MD 21224 USA; National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Scheidweiler, Karl B.
    NIDA, MD 21224 USA.
    Huestis, Marilyn A.
    NIDA, MD 21224 USA.
    Metabolic profiling of new synthetic cannabinoids AMB and 5F-AMB by human hepatocyte and liver microsome incubations and high-resolution mass spectrometry2016In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 30, no 8, 1067-1078 p.Article in journal (Refereed)
    Abstract [en]

    RationaleAMB (methyl (1-pentyl-1H-indazole-3-carbonyl)-L-valinate)) and its fluoro analog 5F-AMB (methyl (1-(5-fluoropentyl)-1H-indazole-3-carbonyl)-L-valinate) are two new synthetic cannabinoids that are structural analogs of AB-PINACA and 5F-AB-PINACA, respectively. 5F-AMB is scheduled as an illicit drug in China, Germany, Singapore and Japan, and no metabolism data are currently available for either drug. The aim of the present work was to investigate the metabolism of AMB and 5F-AMB and propose appropriate markers to identify their intake in clinical or forensic cases. MethodsAMB and 5F-AMB were incubated in human hepatocytes (10 mol/L) to generate phase I and II metabolites, which were identified with a TripleTOF 5600(+) high-resolution mass spectrometer. AMB and 5F-AMB metabolic stability studies also were performed with human liver microsomes (HLM) to evaluate metabolic clearances, and to adequately design the human hepatocyte experiment. ResultsAMB and 5F-AMB were quickly metabolized in HLM with a 1.1 0.1 and 1.0 +/- 0.2min T-1/2, respectively. The predominant metabolic pathway for AMB and 5F-AMB in hepatocytes was ester hydrolysis, and further oxidation and/or glucuronidation. In total, 19 metabolites were identified for AMB and 17 for 5F-AMB. We describe metabolites to differentiate AMB from 5F-AMB, and metabolites that are common to both analytes due to oxidative defluorination of 5F-AMB. ConclusionsFor the first time, AMB and 5F-AMB metabolism profiles were characterized, providing valuable data for identifying these two novel psychoactive substances. The difficulties of differentiating AMB and 5F-AMB from AB-PINACA/5F-AB-PINACA metabolites also were examined. These data improve the interpretation of urinary markers after AMB and 5F-AMB intake. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA

  • 42.
    Andersson, Pär
    Linköping University, Faculty of Health Sciences, Engelska: Faculty of Health Sciences, Medical Programme.
    Immunological Effects of TBE Vaccination: Increased Expression of Transcription factor T-bet Indicates Activation of Th1-like Cellular Immunity2007Independent thesis Advanced level (professional degree), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    Tick-borne encephalitis virus is the cause of much morbidity and sometimes a fatal infection. A vaccine based on formaldehyde inactivated virus is currently the only available way of preventing disease. This vaccine gives a high rate of seroconversion but there are reports of vaccination breakthrough, even in people who have demonstrated a neutralizing antibody response. The T cell response to inactivated TBE vaccine is largely unknown, but could be of importance for the effect of the vaccine. This study characterizes aspects of the T cell response by investigating the expression of two transcription factors, T-bet and GATA-3 with RT-PCR. T-bet is expressed in CD4+ T cells of the Th1 type, while GATA-3 is expressed in CD4+ T cells of the Th2 type. Our data show that vaccination with inactivated TBE vaccine leads to increase in expression of the T-bet gene when cells of vaccinated subjects are cultured with TBE virus. In contrast, the expression of GATA-3 remains unaffected by vaccination. Thus, this study suggests that the inactivated TBE vaccine leads to a Th1-like immune response in humans.

  • 43.
    Andersson, Rolf G
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Bartonek, M
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Lindström, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Lindström, I M
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Toll, Johan B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Studies of the mechanism of desensitization of anti-IgE-mediated histamine release from human basophils1989In: Agents and actions, ISSN 0065-4299, Vol. 27, no 1-2, 25-28 p.Article in journal (Refereed)
    Abstract [en]

    Human basophils became hyporesponsive to anti-IgE when exposed to this agent in the absence of Ca2+ for more than 10 min. The desensitization process proceeded in parallel to the releasing-process. The mechanism of desensitization seems to involve a very early step in the release-reaction, since the response to phospholipase A2 and diolein, agents involved in the release-reaction, was not affected by the desensitization.

  • 44.
    Andin, Josefine
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Linnaeus Centre HEAD.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Linnaeus Centre HEAD.
    Fransson, Peter
    Karolinska institutet, Department of Clinical Neuroscience.
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Linnaeus Centre HEAD.
    Rudner, Mary
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Linnaeus Centre HEAD.
    Deaf signers are less reliant than hearing non-signers on fact retrieval from verbal long term memory during arithmetic processing: fMRI evidence2015Conference paper (Refereed)
  • 45.
    Andin, Josefine
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Fransson, Peter
    Karolinska institutet, Department of Clinical Neuroscience.
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Rudner, Mary
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Greater reliance on magnitude manipulation during mental arithmetic in deaf signers compared to hearing non-signers: fMRI evidence2015Conference paper (Refereed)
    Abstract [en]

    Evidence suggests that the lag reported in mathematics for deaf signers derives from difficulties related to verbal processing of numbers, whereas magnitude processing seems unaffected by deafness. Neuroimaging evidence from hearing individuals suggests that verbal processing of numbers engages primarily left angular gyrus (lAG), whereas magnitude processing engages primarily the horizontal portion of the right intraparietal sulcus (rHIP). In a ROI analysis of brain imaging data from 16 adult deaf signers and 16 adult hearing non-signers, who did not differ on sex, age or education, we examined if activity in lAG and rHIP changed as a result of task (multiplication vs subtraction) and group (deaf signers and hearing non-signers). We found a significant main effect of brain region (F(1,30) = 117.00, p < .001, η_p^2 = .80) and an interaction effect between region and group (F(1,30) = 20.70, p < .001, η_p^2 = .41). Further analyses showed that there were no significant differences in average activation between groups in lAG (F(1,30) = 0.16, p = .70). However, in rHIP deaf signers showed significantly greater average activation compared to non-signers (F(1,30) = 15.20, p < .001, η_p^2 = .34). There were no significant differences in activation between subtraction and multiplication (F(1,30) = 0.66, p = .42) and no behavioural differences between groups (F(1,30) = 1.70, p = .20). These results suggest that when engaging in arithmetic tasks deaf signers successfully make use of qualitatively difference processes, compared to hearing non-signers, with stronger emphasis on brain regions relating to magnitude manipulation.

  • 46.
    Andin, Josefine
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Fransson, Peter
    Karolinska Institute, Sweden.
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Rudner, Mary
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Phonology and arithmetic in the language-calculation network2015In: Brain and Language, ISSN 0093-934X, E-ISSN 1090-2155, Vol. 143, 97-105 p.Article in journal (Refereed)
    Abstract [en]

    Arithmetic and language processing involve similar neural networks, but the relative engagement remains unclear. In the present study we used fMRI to compare activation for phonological, multiplication and subtraction tasks, keeping the stimulus material constant, within a predefined language-calculation network including left inferior frontal gyrus and angular gyrus (AG) as well as superior parietal lobule and the intraparietal sulcus bilaterally. Results revealed a generally left lateralized activation pattern within the language-calculation network for phonology and a bilateral activation pattern for arithmetic, and suggested regional differences between tasks. In particular, we found a more prominent role for phonology than arithmetic in pars opercularis of the left inferior frontal gyrus but domain generality in pars triangularis. Parietal activation patterns demonstrated greater engagement of the visual and quantity systems for calculation than language. This set of findings supports the notion of a common, but regionally differentiated, language-calculation network. (C) 2015 The Authors. Published by Elsevier Inc.

  • 47.
    Andin, Josefine
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Linköping University, Linnaeus Centre HEAD.
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Linköping University, Linnaeus Centre HEAD.
    Rudner, Mary
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Linköping University, Linnaeus Centre HEAD.
    Simple spans in deaf signers and hearing nonsigners2010In: Behavioural Neurology, ISSN 0953-4180, E-ISSN 1875-8584, Vol. 23, no 4, 207-208 p.Article in journal (Refereed)
  • 48.
    André, Malin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department Public Health and Caring Science, Sweden.
    Grondal, Hedvig
    Uppsala University, Sweden.
    Strandberg, Eva-Lena
    Lund University, Sweden; Blekinge County Council, Sweden.
    Brorsson, Annika
    Lund University, Sweden; Skåne Reg, Sweden.
    Hedin, Katarina
    Lund University, Sweden; Kronoberg County Council, Sweden.
    Uncertainty in clinical practice - an interview study with Swedish GPs on patients with sore throat2016In: BMC Family Practice, ISSN 1471-2296, E-ISSN 1471-2296, Vol. 17, no 56Article in journal (Refereed)
    Abstract [en]

    Background: Uncertainty is inevitable in clinical practice in primary care and tolerance for uncertainty and concern for bad outcomes has been shown to vary between physicians. Uncertainty is a factor for inappropriate antibiotic prescribing. Evidence-based guidelines as well as near-patient tests are suggested tools to decrease uncertainty in the management of patients with respiratory tract infections. The aim of this paper was to describe strategies for coping with uncertainty in patients with pharyngotonsillitis in relation to guidelines. Methods: An interview study was conducted among a strategic sample of 25 general practitioners (GPs). Results: All GPs mentioned potential dangerous differential diagnoses and complications. Four strategies for coping with uncertainty were identified, one of which was compliant with guidelines, "Adherence to guidelines", and three were idiosyncratic: "Clinical picture and C-reactive protein (CRP)", "Expanded control", and "Unstructured". The residual uncertainty differed for the different strategies: in the strategy "Adherence to guidelines" and " Clinical picture and CRP" uncertainty was avoided, based either on adherence to guidelines or on the clinical picture and near-patient CRP; in the strategy " Expanded control" uncertainty was balanced based on expanded control; and in the strategy "Unstructured" uncertainty prevailed in spite of redundant examination and anamnesis. Conclusion: The majority of the GPs avoided uncertainty and deemed they had no problems. Their strategies either adhered to guidelines or comprised excessive use of tests. Thus use of guidelines as well as use of more near-patient tests seemed associated to reduced uncertainty, although the later strategy at the expense of compliance to guidelines. A few GPs did not manage to cope with uncertainty or had to put in excessive work to control uncertainty.

  • 49.
    Arehart, Kathryn
    et al.
    University of Colorado, CO 80309 USA.
    Souza, Pamela
    Northwestern University, IL USA.
    Kates, James
    University of Colorado, CO 80309 USA.
    Lunner, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Oticon AS, Denmark.
    Syskind Pedersen, Michael
    Oticon AS, Denmark.
    Relationship Among Signal Fidelity, Hearing Loss, and Working Memory for Digital Noise Suppression2015In: Ear and Hearing, ISSN 0196-0202, E-ISSN 1538-4667, Vol. 36, no 5, 505-516 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: This study considered speech modified by additive babble combined with noise-suppression processing. The purpose was to determine the relative importance of the signal modifications, individual peripheral hearing loss, and individual cognitive capacity on speech intelligibility and speech quality. Design: The participant group consisted of 31 individuals with moderate high-frequency hearing loss ranging in age from 51 to 89 years (mean = 69.6 years). Speech intelligibility and speech quality were measured using low-context sentences presented in babble at several signal-to-noise ratios. Speech stimuli were processed with a binary mask noise-suppression strategy with systematic manipulations of two parameters (error rate and attenuation values). The cumulative effects of signal modification produced by babble and signal processing were quantified using an envelope-distortion metric. Working memory capacity was assessed with a reading span test. Analysis of variance was used to determine the effects of signal processing parameters on perceptual scores. Hierarchical linear modeling was used to determine the role of degree of hearing loss and working memory capacity in individual listener response to the processed noisy speech. The model also considered improvements in envelope fidelity caused by the binary mask and the degradations to envelope caused by error and noise. Results: The participants showed significant benefits in terms of intelligibility scores and quality ratings for noisy speech processed by the ideal binary mask noise-suppression strategy. This benefit was observed across a range of signal-to-noise ratios and persisted when up to a 30% error rate was introduced into the processing. Average intelligibility scores and average quality ratings were well predicted by an objective metric of envelope fidelity. Degree of hearing loss and working memory capacity were significant factors in explaining individual listeners intelligibility scores for binary mask processing applied to speech in babble. Degree of hearing loss and working memory capacity did not predict listeners quality ratings. Conclusions: The results indicate that envelope fidelity is a primary factor in determining the combined effects of noise and binary mask processing for intelligibility and quality of speech presented in babble noise. Degree of hearing loss and working memory capacity are significant factors in explaining variability in listeners speech intelligibility scores but not in quality ratings.

  • 50.
    Armstrong, Andrea
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Mattsson, Niklas
    Sahlgrens University Hospital, Sweden University of Calif San Francisco, CA 94143 USA .
    Appelqvist, Hanna
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Janefjord, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Sandin, Linnea
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Agholme, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Olsson, Bob
    Sahlgrens University Hospital, Sweden .
    Svensson, Samuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. AlzeCure Fdn.
    Blennow, Kaj
    Sahlgrens University Hospital, Sweden .
    Zetterberg, Henrik
    Sahlgrens University Hospital, Sweden UCL Institute Neurol, England .
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimers Disease2014In: Neuromolecular medicine, ISSN 1535-1084, E-ISSN 1559-1174, Vol. 16, no 1, 150-160 p.Article in journal (Refereed)
    Abstract [en]

    The success of future intervention strategies for Alzheimers disease (AD) will likely rely on the development of treatments starting early in the disease course, before irreversible brain damage occurs. The pre-symptomatic stage of AD occurs at least one decade before the clinical onset, highlighting the need for validated biomarkers that reflect this early period. Reliable biomarkers for AD are also needed in research and clinics for diagnosis, patient stratification, clinical trials, monitoring of disease progression and the development of new treatments. Changes in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are among the first alterations observed in an AD brain. In this study, we performed a targeted search for lysosomal network proteins in human cerebrospinal fluid (CSF). Thirty-four proteins were investigated, and six of them, early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were significantly increased in the CSF from AD patients compared with neurological controls. These results were confirmed in a validation cohort of CSF samples, and patients with no neurochemical evidence of AD, apart from increased total-tau, were found to have EEA1 levels corresponding to the increased total-tau levels. These findings indicate that increased levels of LAMP-1, LAMP-2, LC3, Rab3 and Rab7 in the CSF might be specific for AD, and increased EEA1 levels may be a sign of general neurodegeneration. These six lysosomal network proteins are potential AD biomarkers and may be used to investigate lysosomal involvement in AD pathogenesis.

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