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  • 1.
    Bjartmar, Lisa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet.
    Alkhori, Liza
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ruud, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Marcusson, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och cytologi.
    Long-term treatment with antidepressants, but not environmental stimulation, induces expression of NP2 mRNA in hippocampus and medial habenula2010Ingår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1328, s. 24-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neuronal Pentraxin 2 (NP2, Narp), known to mediate clustering of glutamatergic AMPA receptors at synapses, is involved in activity-dependent synaptogenesis and synaptic plasticity. In experimental settings, antidepressant treatment as well as a stimulating environment has a positive influence on cognition and hippocampal plasticity. This study demonstrates that NP2 mRNA is robustly expressed in the hippocampus and the medial habenula (MHb), both regions implicated in cognitive functions. Furthermore, NP2 mRNA expression is enhanced in the hippocampal subregions as well as in the MHb after long-term treatment with antidepressant drugs of various monoaminergic profiles, indicating a common mode of action of different antidepressant drugs. This effect occurs at the time frame where clinical response is normally achieved. In contrast, neither environmental enrichment nor deprivation has any influence on long-term NP2 mRNA expression. These findings support an involvement of NP2 in the pathway of antidepressant induced plasticity, but not EE induced plasticity; that NP2 might constitute a common link for the action of different types of antidepressant drugs and that the MHb could be a putative region for further studies of NP2.

  • 2.
    Christiansen Clifford, Jenny
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Färm, Gunilla
    Department of Dermatology, University Hospital, 701 85 Örebro, Sweden.
    Eid-Forest, Ruth
    Department of Dermatology, University Hospital, 701 85 Örebro, Sweden.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Hudkliniken US.
    Cederbrant, Karin
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Hultman, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och cytologi.
    Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold2006Ingår i: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 55, nr 2, s. 101-112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    10% of patch-tested patients have a positive reaction to gold. Most lack clinical symptoms, but allergic contact dermatitis (ACD) to gold is increasing. In this study, 77 dermatological outpatients were divided into 3 groups depending on epicutaneous patch test outcomes: a group positive to gold (EPI+), a group negative to gold (EPI-), and a group with irritant reactions to gold (EPI-IR). Lymphocytes were stimulated in vitro with gold sodium thiosulfate. Proliferation was assessed using the lymphocyte transformation test (LTT), and cytokine secretion was assessed using a multibead array (Luminex; Linco Research Inc., St. Charles, MO, USA), in order to evaluate whether an in vitro method with high diagnostic accuracy could be devised. The EPI+ group showed a significantly increased secretion of interferon (IFN)-gamma, interleukin (IL)-2, and IL-13 and also showed a significantly higher stimulation indexes for LTT, compared to the other 2 subject groups. Sensitivity and specificity were calculated for all methods individually and combined, but IFN-gamma assessment alone was the most accurate method for identifying ACD to gold, with sensitivity and specificity of 81.8% and 82.1%, respectively. This method also identified 87.5% of the EPI-IR subjects as non-allergic. Therefore, assessment of secretion of IFN-gamma should be a valuable complement to patch test for diagnosing gold allergy.

  • 3.
    Farnebäck, Malin
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Håkansson, Annika
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Håkansson, Leif
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Gustafsson, Bertil
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och cytologi. Linköpings universitet, Hälsouniversitetet.
    Kågedal, Bertil
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Expression of tumor associated transcripts in malignant melanoma metastases: with methodological aspectsManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Several antigens expressed in malignant melanoma are involved in the immunological surveillance of the tumor. The mRNAs of these antigens, especially tyrosinase, have also been used in the detection of minimal residual disease in the blood of melanoma patients. We have therefore analyzed the expression of tyrosinase, TRP-1, TRP-2, MART-1/Melan-A, MAGE-A3, MAGE-A12, S-100 and GD2 synthase by real-time PCR in snap frozen sections from 28 regional and systemic metastases. Treatment with cisplatinum, dacarbazine and interferon-α2b was given to 15 patients before surgery. The transcript concentrations varied widely between individual metastases. However, in general the pigment-related transcripts and that of S-100 were found at higher levels than those of MAGE-A3, MAGE-A12 and GD2 synthase. Significant correlations (p<0.001) were found between tyrosinase and MART-1/Melan-A and between MAGE-A3 and MAGE-A12. TRP-2 and GD2 synthase were both influenced by the treatment, TRP-2 expression was increased in the metastases from treated patients, whereas GD2 synthase expression was decreased. Furthermore, a decrease in tyrosinase expression was found in metastases without tumor-infiltrating lymphocytes. ln this work normalization by the section area contra normalization by housekeeping genes was also evaluated and similar results were obtained with both methods.

  • 4.
    Kågedal, Bertil
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Farnebäck, Malin
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Håkansson, Annika
    Department of Oncology, University Hospital MAS and Lund University, Malmö, Sweden.
    Gustafsson, Bertil
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och cytologi. Linköpings universitet, Hälsouniversitetet.
    Håkansson, Leif
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet.
    How useful are housekeeping genes?: variable expression in melanoma metastases2007Ingår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 45, nr 11, s. 1481-1487Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is a certain difference in opinion regarding the optimal choice of housekeeping genes used as normalization factors in gene expression analysis. We have therefore examined the suitability of three housekeeping genes, hypoxanthine phosphoribosyl transferase, β-glucuronidase and β2-micro-globulin, for normalization of expression data from melanoma metastases.

    Methods: The expression of the three housekeeping genes was quantified by quantitative reverse transcription PCR in snap-frozen sections from 44 melanoma metastases, of which 19 were from patients treated with cisplatinum, dacarbazine and interferon-α2b.

    Results: The expression of each housekeeping gene varied considerably between the different metastases. Histopathological examination of the tissue sections revealed variation in the amount of tumor cells in the tissue, necrosis, varying degrees of lymphocyte infiltration, and lymph node remnants. Based on this examination, 16 biopsies were omitted from further analysis because they had cracked, contained empty or necrotic areas, or were dominated by lymph node tissue. Even in sections with more than 90% tumor cells, a wide variation in the expression of the three housekeeping genes was found. The amount of lymphatic infiltrate in the tumors can have an effect on the expression of housekeeping genes in the meta-stases, whereas treatment did not seem to influence the expression.

    Conclusions: We conclude that the choice of housekeeping genes can have great impact on the normalization of specific genes in melanoma metastases. Furthermore, in the analysis of mRNA expression in tumor tissue, microscopic examination is of great importance to evaluate the integrity and cellular composition of the biopsy.

  • 5.
    Nilsdotter-Augustinsson, Åsa
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Briheim, Gunnas
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Herder, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och cytologi.
    Ljunghusen, O.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Wahlström, Ola
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Öhman, Lena
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Inflammatory response in 85 patients with loosened hip prostheses: A prospective study comparing inflammatory markers in patients with aseptic and septic prosthetic loosening2007Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 78, nr 5, s. 629-639Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Over the past decades, prosthetic hip joints have improved the quality oflife for many patients. The most common complications are aseptic biornechanical failures and prosthetic joint infections. For prosthetic hip joints, delayed low-grade infections are seen most often and they are also most difficult to distinguish from aseptic mechanical failures. A prospective study was conducted to campare inilammatory markers in patients diagnosed with aseptic or septic prosthetic loosenffig. The diagnostic criteria were based on the decisions of experienced orthoperlic surgeons and microbiological analys is of periprosthetic tissue samplestaken perioperatively. Coagulase-negative staphylococci were the most common pathogens in the infected patients. Pre- or perioperative results for C-reactive protein and erytlu-ocyte sedimentation rate were valuable tools for diagnosing most, hut not all, low virulence infections. White blood cell count in synavial fluid was an important marker of infection, which was not the case for lactate. Levels of the cytokines turnor necrosis factor-α, interleukin-1 ß. and interleukin-6 in synavial fluid were significantly higher in the infected group. Patterus of inilammatory cell infiltration in periprosthetic tissue differed significantly between the groups, and infiltration of polymorphonuclear cells proved to be the best marker of distinguish between septic and aseptic loosenffig. Treatment and outcome are described for the infected patients.

  • 6.
    Terman, Alexei
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet. Laboratory of Clinical Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
    Kurz, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Gustafsson, Bertil
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och cytologi. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Brunk, Ulf
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    The involvement of lysosomes in myocardial aging and disease2008Ingår i: Current Cardiology Reviews, ISSN 1573-403X, Vol. 4, nr 2, s. 107-115Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The myocardium is mainly composed of long-lived postmitotic cells with, if there is any at all, a very low rate of replacement through the division and differentiation of stem cells. As a consequence, cardiac myocytes gradually undergo pronounced age-related alterations which, furthermore, occur at a rate that inversely correlates with the longevity of species. Basically, these alterations represent the accumulation of structures that have been damaged by oxidation and that are useless and often harmful. These structures (so-called 'waste' materials), include defective mitochondria, aberrant cytosolic proteins, often in aggregated form, and lipofuscin, which is an intralysosomal undegradable polymeric substance. The accumulation of 'waste' reflects the insufficient capacity for autophagy of the lysosomal compartment, as well, as the less than perfect functioning of proteasomes, calpains and other cellular digestive systems. Senescent mitochondria are usually enlarged, show reduced potential over their inner membrane, are deficient in ATP production, and often produce increased amounts of reactive oxygen species. The turnover of damaged cellular structures is hindered by an increased lipofuscin loading of the lysosomal compartment. This particularly restricts the autophagic turnover of enlarged, defective mitochondria, by diverting the flow of lysosomal hydrolases from autophagic vacuoles to lipofuscin-loaded lysosomes where the enzymes are lost, since lipofuscin is not degradable by lysosomal hydrolases. As a consequence, aged lipofuscin-rich cardiac myocytes become overloaded with damaged mitochondria, leading to increased oxidative stress, apoptotic cell death, and the gradual development of heart failure. Defective lysosomal function also underlies myocardial degeneration in various lysosomal storage diseases, while other forms of cardiomyopathies develop due to mitochondrial DNA mutations, resulting in an accumulation of abnormal mitochondria that are not properly eliminated by autophagy. The degradation of iron-saturated ferritin in lysosomes mediates myocardial injury in hemochromatosis, an acquired or hereditary disease associated with iron overload. Lysosomes then become sensitized to oxidative stress by the overload of low mass, redox-active iron that accumulates when iron-saturated ferritin is degraded following autophagy. Lysosomal destabilization is of importance in the induction and/or execution of programmed cell death (either classical apoptotic or autophagic), which is a common manifestation of myocardial aging and a variety of cardiac pathologies. © 2008 Bentham Science Publishers Ltd.

  • 7.
    Vitak, B
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Radiologi. Linköpings universitet, Hälsouniversitetet.
    Olsen, K E
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och cytologi. Linköpings universitet, Hälsouniversitetet.
    Månson, Jan-Christer
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och cytologi. Linköpings universitet, Hälsouniversitetet.
    Arnesson, Lars-Gunnar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Stål, Olle
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Tumour characteristics and survival in patients with invasive interval breast cancer classified according to mammographic findings at the latest screening: a comparison of true interval and missed interval cancers1999Ingår i: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 9, nr 3, s. 460-469Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate whether different mammographic categories of interval cancer classified according to findings at the latest screening are associated with different distributions of prognostic factors or with different survival rates. The series consisted of all patients with invasive interval cancer detected from May 1978 to August 1995 (n = 544). The tumours were evaluated with regard to age, radiological category, interval between the latest screen and diagnosis and tumour characteristics at the time of diagnosis. We investigated possible relationships between the survival rate of patients with interval cancer and the interval between the latest screen and diagnosis, tumour characteristics and radiological category of the interval tumours. The study focused on comparison of patients with true interval and missed interval cancer. Women with mammographically occult tumours were younger than those in the other radiological categories. Comparisons of true interval cancers with overlooked or misinterpreted tumours showed equal distributions of age, tumour size, TNM stage and lymph node status. The overlooked or misinterpreted tumours showed significantly higher proportions of grade-I tumours (22 vs 11 %), tumours with low S-phase fraction (SPF; 44 vs 24 %) and oestrogen receptor (ER) positive tumours (72 vs 57 %). However, analyses of survival rates disclosed no clear differences between the two radiological categories. Radiological category and interval between the latest screen and diagnosis were not genuine predictors of the prognosis in patients with invasive interval breast cancer. No certain prognostic difference existed between true interval cancers and overlooked or misinterpreted interval breast cancers, despite higher proportions of grade-I tumours, ER positive tumours and tumours with low SPF in the latter group.

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