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  • 151. Tillisch, Kirsten
    et al.
    Larsson, Mats
    Kilpatrick, Lisa
    Walter, Susanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Women With Irritable Bowel Syndrome (IBS) Show Altered Default Mode Network Connectivity2011Konferensbidrag (Refereegranskat)
  • 152.
    Toksvig-Larsen, Soren
    et al.
    Department of Orthopedics, Hässleholm Hospital, Hässleholm, and Department of Orthopedics, Clinical Sciences, Lund University , Lund.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Bisphosphonate-coated external fixation pins appear similar to hydroxyapatite-coated pins in the tibial metaphysis and to uncoated pins in the shaft: a randomized trial2013Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 84, nr 3, s. 314-318Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose External fixation pins tend to loosen with time, especially from cancellous bone. A coating that releases a bisphosphonate has been shown to improve the fixation of dental implants in humans. We now tested a bisphosphonate coating on steel pins for external fixation. The primary hypothesis was that coated pins would be better fixed in the diaphysis.

    Methods 20 patients with medial knee osteoarthritis underwent proximal tibial correction osteotomy with hemicallotasis. They received a pair of pins (Orthofix) in the tibial shaft, one bisphosphonate-coated and one uncoated. Another pair of pins was inserted in the metaphysis, near the joint. This pair was a bisphosphonate-coated pin and an HA-coated pin. All pins were inserted according to a random list. The pins were removed after the osteotomy had healed (8–15 weeks), and extraction torque served as the predetermined main outcome variable.

    Results No pins showed clinical signs of loosening. Removal torque for the shaft pins was 6.6 Nm (SD 2.2) for the bisphosphonate and 6.0 Nm (SD 2.5) for the uncoated (difference = 0.5, 95% CI: –0.03 to 1.3). Removal torque for the metaphyseal pins was 4.4 Nm (SD 1.3) for the bisphosphonate-coated and 4.2 Nm (SD 1.6) for the HA-coated (difference = 0.2, 95% CI: –0.5 to 1.0).

    Interpretation We could not show any improved cortical fixation, but the metaphyseal findings are striking. In a previous study on 19 patients with a similar layout, HA-coated and uncoated pins were compared. In the metaphysis, all 19 uncoated pins loosened before removal. It was concluded that uncoated pins could not be used in the metaphyseal region. The present results suggest that a bisphosphonate coating enables metaphyseal fixation similar to that of hydroxyapatite coatings, with no difference from uncoated pins in cortical bone.

  • 153.
    Tuominen, Rainer
    et al.
    Karolinska Institute, Sweden .
    Jonsson, Goran
    Lund University, Sweden .
    Enerbäck, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Appelqvist, Frida
    Sahlgrens University Hospital, Sweden .
    Olsson, Hakan
    Lund University, Sweden .
    Ingvar, Christian
    Lund University, Sweden .
    Hansson, Johan
    Karolinska Institute, Sweden .
    Hoiom, Veronica
    Karolinska Institute, Sweden .
    Investigation of a putative melanoma susceptibility locus at chromosome 3q292014Ingår i: Cancer Genetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 207, nr 3, s. 70-74Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Malignant melanoma, the most fatal form of skin cancer, is currently increasing in incidence in many populations. Approximately 10% of all cases occur in families with an inherited predisposition for melanoma. In Sweden, only a minor portion of such melanoma families carry a mutation in the known melanoma gene CDKN2A, and there is a need to identify additional melanoma susceptibility genes. In a recently performed genome-wide linkage screen, novel loci with suggestive evidence of linkage to melanoma were detected. In this study, we have further analyzed one region on chromosome 3q29. In all, 89 affected and 15 nonaffected family members from 42 melanoma-prone families were genotyped for 34 genetic markers. In a pooled linkage analysis of all 42 families, we detected significant evidence of linkage, with a maximum heterogeneity logarithm of odds (HLOD) score of 3.1 with 83% of the families contributing to the linkage score. The minimum critical region of linkage (defined by a 1LOD score support interval) maps to chromosome 3q29, spans 3.5 Mb of genomic sequence, and harbors 44 identified genes. Sequence variants within this region have previously been associated with cancer susceptibility. This study reports the presence of a putative novel melanoma susceptibility locus in the Swedish population, a finding that needs to be replicated in an independent study on other individuals with familial melanoma. Sequencing of genes in the region may identify novel melanoma-associated mutations.

  • 154.
    Tynngård, Nahreen
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Berlin, Gösta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Samuelsson, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Berg, Sören
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Low dose of hydroxyethyl starch impairs clot formation as assessed by viscoelastic devices2014Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 74, nr 4, s. 344-350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. High doses of the synthetic colloid hydroxyethyl starch (HES) used for plasma expansion have been associated with impaired haemostasis and hypocoagulation. Less is known about effects on clot formation in the low haemodilutional range (less than 40%). This study evaluated the effects of low haemodilution with HES and albumin on coagulation using two different viscoelastic methods. Methods. Clot formation was studied in vitro in healthy donor blood after 10% and 30% haemodilution with 60 g/L HES 130/0.4 or 50 g/L albumin with free oscillation rheometry (FOR) and rotational thromboelastography. Results. Clotting time was not significantly affected at 10% haemodilution but was prolonged with both substances at 30% dilution (p less than 0.01-0.001). The effect was significantly more pronounced with HES than with albumin. The elasticity of the clot was slightly reduced at 10% dilution with albumin, more pronounced at 10% dilution with HES (p less than 0.05), further reduced at 30% dilution with albumin and to a still greater extent at 30% dilution with HES (p less than 0.05). With albumin the functional activity of fibrinogen was not reduced in excess of the dilutional effect. HES in contrast produced a further reduction in clot elasticity than caused by mere dilution at both 10% and 30% dilutions (p less than 0.001). Conclusions. There is an adverse effect on clot formation even at low grade haemodilution with both albumin and HES. The effect on coagulation is significantly more pronounced with HES than with albumin.

  • 155.
    Tynngård, Nahreen
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Trinks, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Berlin, Gösta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    In vitro properties of platelets stored in a small container for pediatric transfusion2014Ingår i: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 54, nr 6, s. 1562-1568Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    The quality of a platelet (PLT) concentrate (PC) is affected by the number of PLTs in relation to the size and gas permeability of the container. This study evaluates the in vitro function, including hemostatic properties (clot formation and elasticity), of PLTs stored in a container of standard or small size.

    STUDY DESIGN AND METHODS:

    PCs with 30% plasma and 70% PLT additive solution were prepared from buffy coats. Two PCs were pooled and divided into the following containers: 1 unit and ½ a unit into a 1.8-L container (reference container) and ½ a unit into a 0.45-L container (test container). In a second set of experiments ¼ of a unit was stored in the reference and test containers. Swirling, PLT count, blood gases, metabolic variables, PLT activation markers, hypotonic shock response (HSR), and coagulation by free oscillation rheometry were analyzed during 7 days of storage.

    RESULTS:

    Swirling was well preserved and pH was acceptable (6.4-7.4) during storage of PLTs in both containers. Glycolysis and PLT activation were higher when storing ½ and ¼ of a unit in the reference container and storage of ¼ of a unit in the reference container resulted in the largest decrease in HSR. The clotting time was similar whereas the clot elasticity was slightly lower for PLTs when stored as ½ and ¼ of a unit in the reference container.

    CONCLUSION:

    Storage of a low number of PLTs benefits by storage in a small container in terms of better maintained in vitro properties.

  • 156.
    Vegfors, Jenny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Psoriasin For Better or for Worse in Sickness and in Health: The Role of Psoriasin in Angiogenesis and Differentation of Epithelial Cells2014Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyper-proliferative skin disorder psoriasis. Both breast cancer and psoriasis are diseases which are characterized by hyperproliferation and a disturbed differentiation of the epithelial cells as well as a pronounced angiogenesis. The potential role of psoriasin in angiogenesis and the epithelial differentiation remain unclear.

    The aim of this thesis was to investigate the cellular effects of psoriasin in angiogenesis and the differentiation processes, with special emphasis on breast cancer and psoriasis.

    We found that psoriasin expression was induced in mammary epithelial cells and keratinocytes by oxidative stress. Psoriasin expression was shown to induce vascular endothelial growth factor (VEGF) expression and several other pro-angiogenic factors in epithelial cells. Upon down-regulation of psoriasin, H2O2-induced expression of VEGF was decreased as well as the pro-angiogenic factors heparin-binding EGF-like growth factor (HBEGF) and matrix metalloproteinase (MMP)-1. Extracellular psoriasin contributed to the subsequent induction of proliferation, migration and tube formation of endothelial cells. The proliferative effect of psoriasin was shown to be mediated by the receptor for advanced glycation end products (RAGE). Furthermore, psoriasin induced reactive oxygen species (ROS) in both endothelial and epithelial cells through the action of RAGE, and contributed to the expression of the pro-angiogenic factors in endothelial cells.

    The expression of psoriasin was up-regulated in mammary epithelial cells and keratinocytes in response to differentiation-inducing stimuli and was shown to be regulated by pathways involved in epithelial cell differentiation. Upon psoriasin down-regulation the shift towards a more differentiated CD24+-phenotype of mammary epithelial cells was abolished. Furthermore, the expression of the differentiation markers involucrin, desmoglein 1, transglutaminase 1 and CD24 was decreased in keratinocytes upon down-regulation of psoriasin expression. In vivo we demonstrated a gradient of psoriasin expression in the psoriatic epidermis, with intense expression in the suprabasal differentiated layers, and a similar staining pattern between psoriasin and the differentiation marker CD24 in DCIS tumors.

    In conclusion, our findings describe psoriasin as a mediator in the angiogenic process and a contributor of epithelial cell differentiation. Consequently, psoriasin is possibly a contributor to the development and progression of breast cancer and psoriasis and a potential target in the treatment of these diseases.

    Delarbeten
    1. Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation
    Öppna denna publikation i ny flik eller fönster >>Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation
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    2012 (Engelska)Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 134, nr 1, s. 71-80Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Psoriasin (S100A7), originally identified in psoriasis, is a calcium-binding protein belonging to the multigenic S100 family. In high-grade ductal carcinoma in situ, psoriasin was identified as one of the most abundant transcripts. We have previously shown that psoriasin was induced by reactive oxygen species (ROS). Moreover, the downregulation of psoriasin by short hairpin RNA (shRNA) led to the reduced expression of vascular endothelial growth factor (VEGF) and inhibited tumor growth in vivo. The aim of the present study was to investigate whether psoriasin could have direct effects on endothelial cells. In this study we demonstrated that psoriasin increased VEGF expression in mammary epithelial cells. The treatment of endothelial cells with recombinant psoriasin increased proliferation comparable to that of recombinant VEGF protein. No change in proliferation was seen when endothelial cells were infected with psoriasin-expressing adenoviruses, suggesting that the proliferative effect of psoriasin was mediated by a specific receptor. Treatment with sRAGE, targeting the receptor for advanced glycation end products (RAGE), thus inhibited endothelial cell proliferation and tube formation enhanced by recombinant psoriasin. We showed that VEGF expression was not induced by hydrogen peroxide, when psoriasin was silenced by shRNA, which led to the hypothesis that psoriasin induces ROS. Indeed, psoriasin was shown to induce ROS in both endothelial and epithelial cells. Moreover, sRAGE inhibited the psoriasin-dependent generation of ROS in endothelial cells. Finally, treatment with antioxidant Bcl-2 protein abolished the effect of psoriasin on endothelial cell proliferation. Our data suggest that psoriasin expression in mammary epithelial cells leads to increased endothelial cell proliferation in a paracrine manner through RAGE. Psoriasin may therefore play a role in breast cancer progression by promoting oxidative stress response and angiogenesis.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-76132 (URN)10.1007/s10549-011-1920-5 (DOI)22189627 (PubMedID)000306437500008 (Scopus ID)
    Anmärkning

    funding agencies|Swedish Cancer Society||Swedish Psoriasis Association||Assar Gabrielsson Foundation||Welander Foundation||Tore Nilsson Foundation||

    Tillgänglig från: 2012-03-28 Skapad: 2012-03-28 Senast uppdaterad: 2017-12-07
    2. Psoriasin (S100A7) contributes to stress-induced angiogenesis in psoriasis by the regulation of angiogenic factors in keratinocytes and promotion of angiogenic properties of dermal endothelial cells
    Öppna denna publikation i ny flik eller fönster >>Psoriasin (S100A7) contributes to stress-induced angiogenesis in psoriasis by the regulation of angiogenic factors in keratinocytes and promotion of angiogenic properties of dermal endothelial cells
    2014 (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    The S100 protein psoriasin, S100A7, is highly expressed in psoriasis. Vascular modifications occur early in the development of psoriasis and angiogenesis is one of the key features in the pathogenesis of the disease. This study aims to define the angiogenic properties of psoriasin in keratinocytes and to investigate the effects on dermal endothelial cells, thereby promoting angiogenesis in psoriasis. We showed that psoriasin expression, demonstrated by qPCR, is induced by hydrogen peroxide (H2O2) in keratinocytes and by cellular stress, such as hypoxia and cobalt chloride (CoCl2). Down-regulation of psoriasin, by siRNA, decreased the H2O2-induced expression of VEGF, heparin-binding EGF-like growth factor (HB-EGF) and matrix metalloproteinase (MMP)-1, and counteracted the reduction of the anti-angiogenic factor thrombospondin (THBS)-1. Extracellularly psoriasin was found to induce cell proliferation, migration and tube formation to a similar degree as VEGF and to induce the pro-angiogenic factors VEGF and IL-8 in dermal endothelial cells. Furthermore, we demonstrated that psoriasin-induced migration was mediated by the phosphoinositide-3-kinase (PI3K) and nuclear factor-kappa beta (NF-κB) signaling pathways. In conclusion, psoriasin is induced by cellular stress conditions and amplifies H2O2-induced expression of angiogenic factors relevant for psoriasis in keratinocytes. Moreover, psoriasin contributes to key features of the angiogenic process by inducing proliferation, migration and tube formation and increasing pro-angiogenic factors in dermal endothelial cell. Altogether, our data suggest that psoriasin is promoted by oxidative stress and mediate angiogenesis in psoriasis.

    Nationell ämneskategori
    Reumatologi och inflammation Hälsovetenskaper
    Identifikatorer
    urn:nbn:se:liu:diva-110028 (URN)
    Tillgänglig från: 2014-09-01 Skapad: 2014-09-01 Senast uppdaterad: 2015-04-09Bibliografiskt granskad
    3. The Expression of Psoriasin (S100A7) and CD24 Is Linked and Related to the Differentiation of Mammary Epithelial Cells
    Öppna denna publikation i ny flik eller fönster >>The Expression of Psoriasin (S100A7) and CD24 Is Linked and Related to the Differentiation of Mammary Epithelial Cells
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    2012 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 12Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyperproliferative skin disorder psoriasis. The gene that encodes psoriasin and many other S100 genes are located within a gene cluster on chromosome region 1q21, known as the epidermal differentiation complex. This cluster contains genes for several differentiation markers that play important roles in the terminal differentiation of the epidermis. The purpose of the present study was to evaluate the role of psoriasin in the differentiation process of mammary epithelial cells. Normal mammary epithelial cells (MCF10A) cultured in confluence and suspension, conditions known to induce psoriasin expression, demonstrated a shift towards a more differentiated phenotype indicated by an increase in the expression of the luminal differentiation markers CD24 and MUC1 and the reduced expression of the breast stem cell marker CD44. The expression of psoriasin and MUC1 was most pronounced in the CD24(+)-enriched fraction of confluent MCF10A cells. The shift towards a more differentiated phenotype was abolished upon the downregulation of psoriasin using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Using specific inhibitors, we showed that psoriasin and CD24 expression was regulated by reactive oxygen species (ROS) and the nuclear factor (NF)-kappa B signaling pathways. While immunohistochemical analyses of DCIS showed heterogeneity, the expression of psoriasin and CD24 showed a similar staining pattern. Our findings suggest that the expression of psoriasin is linked to the luminal differentiation marker CD24 in mammary epithelial cells. Psoriasin demonstrated an essential role in the shift towards a more differentiated CD24(+) phenotype, supporting the hypothesis that psoriasin plays a role in the differentiation of luminal mammary epithelial cells.

    Ort, förlag, år, upplaga, sidor
    Public Library of Science, 2012
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-88366 (URN)10.1371/journal.pone.0053119 (DOI)000312829100122 ()
    Anmärkning

    Funding Agencies|Ingrid Asp Foundation||Swedish Cancer Society||Swedish Psoriasis Association||Welander Foundation||

    Tillgänglig från: 2013-02-04 Skapad: 2013-02-04 Senast uppdaterad: 2017-12-06
    4. Psoriasin (S100A7) is regulated by protein kinase C (PKC) and contributes to keratinocyte differentiation by regulating the expression of epidermal differentiation markers
    Öppna denna publikation i ny flik eller fönster >>Psoriasin (S100A7) is regulated by protein kinase C (PKC) and contributes to keratinocyte differentiation by regulating the expression of epidermal differentiation markers
    2014 (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Psoriasis is a chronic inflammatory skin disease that is characterized by hyperproliferation and a disturbed maturation of the epidermal cells. The differentiation process of keratinocytes in active psoriatic lesions differs from that of normal epidermis, denoted by an altered expression of differentiation markers. Psoriasin, a protein which is highly expressed in psoriasis, is located within the epidermal differentiation complex (EDC), a gene cluster that contains several genes that are important in the terminal differentiation of the human epidermis. The potential role of psoriasin in keratinocyte differentiation remain however unclear. The aim of this present study was to investigate the possible involvement of psoriasin in keratinocyte differentiation. We demonstrated, by immunohistochemical staining, a gradient of psoriasin expression in the psoriatic epidermis, from an undefined or weak expression in the basal layer to an intense expression in the suprabasal differentiated layers. The expression of psoriasin was up-regulated in cultured keratinocytes in response to stimuli known to induce differentiation, such as an elevation of extracellular calcium or  12-Otetradecanoylphorbol-13-acetate (TPA). Down-regulation of psoriasin expression, by siRNA, resulted in decreased expression of the differentiation markers involucrin, desmoglein 1, transglutaminase 1 and CD24. Inhibition of protein kinase C (PKC) counteracted the calciuminduced expression of psoriasin and involucrin. In summary, our data demonstrate that psoriasin is regulated by the PKC signaling pathway and contributes to keratinocyte differentiation by the regulation of differentiation markers.

    Nationell ämneskategori
    Reumatologi och inflammation Hälsovetenskaper
    Identifikatorer
    urn:nbn:se:liu:diva-110030 (URN)
    Tillgänglig från: 2014-09-01 Skapad: 2014-09-01 Senast uppdaterad: 2015-04-09Bibliografiskt granskad
  • 157.
    Vegfors, Jenny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Bivik, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ekman, Anna-Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Enerbäck, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Psoriasin (S100A7) contributes to stress-induced angiogenesis in psoriasis by the regulation of angiogenic factors in keratinocytes and promotion of angiogenic properties of dermal endothelial cells2014Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    The S100 protein psoriasin, S100A7, is highly expressed in psoriasis. Vascular modifications occur early in the development of psoriasis and angiogenesis is one of the key features in the pathogenesis of the disease. This study aims to define the angiogenic properties of psoriasin in keratinocytes and to investigate the effects on dermal endothelial cells, thereby promoting angiogenesis in psoriasis. We showed that psoriasin expression, demonstrated by qPCR, is induced by hydrogen peroxide (H2O2) in keratinocytes and by cellular stress, such as hypoxia and cobalt chloride (CoCl2). Down-regulation of psoriasin, by siRNA, decreased the H2O2-induced expression of VEGF, heparin-binding EGF-like growth factor (HB-EGF) and matrix metalloproteinase (MMP)-1, and counteracted the reduction of the anti-angiogenic factor thrombospondin (THBS)-1. Extracellularly psoriasin was found to induce cell proliferation, migration and tube formation to a similar degree as VEGF and to induce the pro-angiogenic factors VEGF and IL-8 in dermal endothelial cells. Furthermore, we demonstrated that psoriasin-induced migration was mediated by the phosphoinositide-3-kinase (PI3K) and nuclear factor-kappa beta (NF-κB) signaling pathways. In conclusion, psoriasin is induced by cellular stress conditions and amplifies H2O2-induced expression of angiogenic factors relevant for psoriasis in keratinocytes. Moreover, psoriasin contributes to key features of the angiogenic process by inducing proliferation, migration and tube formation and increasing pro-angiogenic factors in dermal endothelial cell. Altogether, our data suggest that psoriasin is promoted by oxidative stress and mediate angiogenesis in psoriasis.

  • 158.
    Vegfors, Jenny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Ekman, Anna-Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Bivik, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Enerbäck, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Psoriasin (S100A7) is regulated by protein kinase C (PKC) and contributes to keratinocyte differentiation by regulating the expression of epidermal differentiation markers2014Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Psoriasis is a chronic inflammatory skin disease that is characterized by hyperproliferation and a disturbed maturation of the epidermal cells. The differentiation process of keratinocytes in active psoriatic lesions differs from that of normal epidermis, denoted by an altered expression of differentiation markers. Psoriasin, a protein which is highly expressed in psoriasis, is located within the epidermal differentiation complex (EDC), a gene cluster that contains several genes that are important in the terminal differentiation of the human epidermis. The potential role of psoriasin in keratinocyte differentiation remain however unclear. The aim of this present study was to investigate the possible involvement of psoriasin in keratinocyte differentiation. We demonstrated, by immunohistochemical staining, a gradient of psoriasin expression in the psoriatic epidermis, from an undefined or weak expression in the basal layer to an intense expression in the suprabasal differentiated layers. The expression of psoriasin was up-regulated in cultured keratinocytes in response to stimuli known to induce differentiation, such as an elevation of extracellular calcium or  12-Otetradecanoylphorbol-13-acetate (TPA). Down-regulation of psoriasin expression, by siRNA, resulted in decreased expression of the differentiation markers involucrin, desmoglein 1, transglutaminase 1 and CD24. Inhibition of protein kinase C (PKC) counteracted the calciuminduced expression of psoriasin and involucrin. In summary, our data demonstrate that psoriasin is regulated by the PKC signaling pathway and contributes to keratinocyte differentiation by the regulation of differentiation markers.

  • 159.
    Vigren, Lina
    et al.
    Lund University, Sweden .
    Tysk, Curt
    Örebro University Hospital, Sweden University of Örebro, Sweden .
    Ström, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Kilander, Anders F.
    Sahlgrens University Hospital, Sweden .
    Hjortswang, Henrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Bohr, Johan
    Örebro University Hospital, Sweden University of Örebro, Sweden .
    Benoni, Cecilia
    Lund University, Sweden .
    Larson, Lasse
    Sahlgrens University Hospital, Sweden .
    Sjoberg, Klas
    Lund University, Sweden .
    Celiac disease and other autoimmune diseases in patients with collagenous colitis2013Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, nr 8, s. 944-950Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims. Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Methods. Patients with CC answered questionnaires about demographic data and disease activity. The patients files were scrutinized for information about autoimmune diseases. Results. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjogrens syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Conclusion. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

  • 160.
    Vikingsson, Svante
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Andersson, David
    Skåne University Hospital, Sweden; Danderyd Hospital, Sweden.
    Almer, Sven
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken. Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Hindorf, Ulf
    Skåne University Hospital, Sweden.
    Novel assay to improve therapeutic drug monitoring of thiopurines in inflammatory bowel disease2014Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, nr 12, s. 1702-1709Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: The thiopurines are widely used in the treatment of inflammatory bowel disease, but are limited by poor dose effect relationship. The objective was to assess the ability of a novel assay, determining the mono-, di-, and triphosphates, of thioguanine as well as methylthioinosine as individual metabolites in erythrocytes, to predict clinical outcome compared to a routine assay, determining metabolites as sums. Methods: Samples from 79 patients with Crohns disease or ulcerative colitis treated with azathioprine or mercaptopurine were analysed by both assays. Clinical status was determined by the Harvey-Bradshaw and Walmsley indices. The genotypes of thiopurine methyltransferase (TPMT) and inosine triphosphatase were determined. Results: TPMT wild-type patients with thioguanine nucleotide (TGN) levels below the cut-off level were more likely to have active disease when TGN was measured by the novel assay (p = 0.02), and when thioguanosine triphosphate (TGTP) was measured separately (p = 0.01). When TGN was measured by the routine assay the correlation was not evident (p = 0.12). Neither TGN levels nor TGTP correlated to disease activity in TPMT deficient patients. Patients with methyl thioinosine nucleotide (meTIN) levels above 1500 pmol/8 x 10less than^greater than8 RBCs were more likely to have active disease (p = 0.07). We observed good correlations between the mono-, di-, and triphosphates and their respective sums (R-2 greater than 0.88). Conclusions: The novel TGN assay was better in predicting clinical outcome compared to the routine assay, while determination of TGTP had no clinical advantage and TGTP ratio was not correlated to disease activity. (C) 2014 European Crohns and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  • 161.
    Vogt, Hartmut
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Bråbäck, Lennart
    Occupational & Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Kling, Anna-Maria
    Department of Analysis and Prevention, Swedish Institute for Cummunicable Disease Control (SMI), Stockholm, Solna, Sweden.
    Grünewald, Maria
    Department of Analysis and Prevention, Swedish Institute for Cummunicable Disease Control (SMI), Stockholm, Solna, Sweden.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Pertussis Immunization in Infancy and Adolescent Asthma Medication2014Ingår i: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 134, nr 4, s. 721-728Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Lack of infections might contribute to increased risk of asthma among children according to the ‘hygiene hypothesis’. Childhood immunization may play a causal role in the development of asthma.

    Objective: To determine whether pertussis immunization in infancy is associated with asthma medication in adolescence.

    Design, Settings and Participants: After 14 years of no general pertussis vaccination, almost 80,000 children were immunized for pertussis during a 12-month period in a vaccination trial. They were compared with almost 100,000 non-vaccinated children born during a 6-month period before and after the vaccination trial in a Swedish national cohort study. Information concerning dispensed prescribed asthma medication for each individual in the cohort during 2008–2010 was obtained from the National Prescription database. Multivariable regression models were used to calculate the effect size of vaccination on dispensed asthma medication (Odds ratios and 95% confidence intervals), both in an intent-to-treat model as well as per protocol. The large study size also enabled us to detect very small effects.

    Main Outcome Measure: Dispensed prescribed asthma medication at the age of 15 years occurring after pertussis immunization in infancy.

    Results: No statistically significant effect of vaccination was found, regardless of vaccination schedule or vaccine type. The prevalence rates of any dispensed anti-inflammatory medication or any asthma medication at 15 years of age were 4.6% and 7.0%, respectively. The crude odds ratios (OR) for any asthma medication and anti-inflammatory treatment in pertussis-vaccinated children after intent-to-treat analysis were 0.97 (95% CI 0.93 – 1.00) and 0.94 (0.90 – 0.98),respectively. Corresponding adjusted ORs were 0.99 (0.95 – 1.03) and 0.97 (0.92 – 1.01),respectively. Similar ORs were found after per-protocol analysis.

    Conclusion: Pertussis immunization in infancy does not increase the risk of asthma medication in adolescents. Our study presents evidence that pertussis immunization in early childhood can be considered safe with respect to long-term development of asthma.

  • 162.
    Walter, Susanna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Jones, M P.
    Macquarie University, Australia .
    Talley, N J.
    University of Newcastle, Australia .
    Kjellstrom, L
    Centre Family Med, Sweden .
    Nyhlin, H
    Karolinska Institute, Sweden .
    Andreasson, A N.
    Stockholm University, Sweden .
    Agreus, L
    Karolinska Institute, Sweden .
    Abdominal pain is associated with anxiety and depression scores in a sample of the general adult population with no signs of organic gastrointestinal disease2013Ingår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 25, nr 9, s. 741-E576Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Abdominal pain is common in the community, but only a subset meet diagnostic criteria for irritable bowel syndrome (IBS). Although anxiety and depression have been linked to IBS, the role of mood disturbances in the remainder with symptoms remains unclear. We aimed to study the associations between abdominal pain, anxiety, depression, and quality of life in the general population who were free of organic colonic disease by colonoscopy. Methods Two hundred and seventy-two randomly selected subjects from the general population, mean age 54 years (27-71), were clinically evaluated, had a colonoscopy and laboratory investigations to exclude organic gastrointestinal (GI) disease. All subjects completed GI symptom diaries for 1 week, the Rome II modular questionnaire, the Hospital Anxiety and Depression Scale, and Short Form 36. Key Results Twenty-two subjects were excluded due to organic disease; 1532 daily symptom records were available for analysis in the remainder. Thirty-four percent (n = 83) recorded at least one episode of abdominal pain on the diary. Twelve percent fulfilled Rome II criteria for IBS. Both anxiety and depression scores were higher in subjects who reported abdominal pain vs those who did not (P andlt; 0.0005 and P andlt; 0.0005). Anxiety and depression scores independently from IBS diagnosis (Rome II) predicted pain reporting and also correlated positively with pain burden. Quality of life scores were generally lower in subjects with abdominal pain. Conclusions andamp; Inferences Anxiety and depression are linked to functional abdominal pain, not only in subjects with IBS but also in otherwise healthy people with milder, subtle GI symptoms.

  • 163.
    Walter, Susanna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Jones, Michael P
    Talley, Nicholas J
    Validation of ROME III Criteria for Irritable Bowel Syndrome in a Primary Care Setting - A Pilot Study2013Konferensbidrag (Refereegranskat)
  • 164.
    Walter, Susanna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Larsson, Mats
    Tillisch, Kirsten
    IBS Patients With Normal Visceral Sensitivity Differ From HealthyControls During the Expectation but Not the Delivery of an Aversive Distension2011Konferensbidrag (Refereegranskat)
  • 165.
    Walter, Susanna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Lowén, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Mayer, Emeran A
    Tillisch, Kirsten
    Department of Medicine, David Geffen School of Medicine, Los Angeles, USA.
    Engström, Maria
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Craig, Arthur D.
    Su2113 High-Intense Rectal Urgency and Its Representation in the Brain2013Konferensbidrag (Refereegranskat)
    Abstract [en]

    Background: Several brain imaging studies have demonstrated that visceral distensions activate the insular cortex but there is limited knowledge about which  subregions of the insula underpin the feeling of rectal urgency. An isobaric rectal balloon distension can be subdivided into the inflation phase when pressure is rising (rise) and a stable phase, when the pressure is constant. The rise phase is characterized by a more distinct sensation of urgency (Akervall et al., 1988). We aimed to study the BOLD response during the rise phase of a standardized rectal distension in subregions of the insula, in healthy controls.

    Method:Twenty right-handed female healthy volunteers (mean age 32.2 yrs, range 21-54) were included. Rectal pressure sensory thresholds were determined before functional Magnetic Resonance Imaging (fMRI) while the subjects were placed in the MR  scanner. Blood Oxygen Level Dependent (BOLD) signals were measured during the rise periods (6.6-7.2 sec) of 20 rectal distensions (45mmHg). Regions of interest (ROIs) included 10 insula subregions: Left (L) and right (R) anterior ventral, anterior dorsal, posterior ventral, posterior dorsal and mid insula. Results were reported as significant if peak p-value were, 0.05 with familywise error (FWE) correction in the ROIs.

    Results: The mean values for rectal sensory thresholds for first sensation, first sensation of urgency and maximum tolerable distension were 16 mmHg (SD 3.9), 28mmHg (SD 6.2) and 55 mmHg (SD 12.3), respectively. Complete fMRI data were available from 18 subjects. The rise period of the rectal distension generated significant BOLD activation in the right hemisphere in the anterior dorsal, anterior ventral, mid and posterior ventral parts of the insula. On the left side BOLD activity was generated in mid, posterior ventral and posterior dorsal parts of the insula but not in the anterior insula. Akervall S et al, 1988, Manovolumetry: A new method for investigation of anorectal function. Gut 29:614-623.

  • 166.
    Wang, Lirui
    et al.
    University of California San Diego, USA .
    Hartmann, Phillipp
    University of California San Diego, USA.
    Haimerl, Michael
    University of California San Diego, USA.
    Bathena, Sai P
    University of Nebraska, Omaha, USA .
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Almer, Sven
    Karolinska Institutet, Solna, Karolinska University Hospital Stockholm.
    Alnouti, Yazen
    University of Nebraska, Omaha, USA .
    Hofmann, Alan F
    University of California San Diego, USA.
    Schnabl, Bernd
    University of California San Diego, USA.
    Nod2 deficiency protects mice from cholestatic liver disease by increasing renal excretion of bile acids2014Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 60, nr 6, s. 1259-1267Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND & AIMS: Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis.

    METHODS: We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2(-/-) mice.

    RESULTS: Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2(-/-) mice than wild type mice following bile duct ligation for 3weeks. In contrast to wild type mice, Nod2(-/-) mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1β in a Nod2 dependent fashion.

    CONCLUSIONS: Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte.

  • 167.
    Wang, Ning
    et al.
    Karolinska University, Sweden .
    Truedsson, Lennart
    Lund University, Sweden .
    Elvin, Kerstin
    Karolinska Institute, Sweden .
    Andersson, Bengt A
    Sahlgrens University Hospital, Sweden .
    Ronnelid, Johan
    Uppsala University, Sweden .
    Mincheva-Nilsson, Lucia
    Umeå University, Sweden .
    Lindkvist, Annica
    Karolinska University, Sweden .
    Ludvigsson, Jonas F.
    Karolinska Institute, Sweden Örebro University Hospital, Sweden .
    Hammarstrom, Lennart
    Karolinska University, Sweden .
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Serological Assessment for Celiac Disease in IgA Deficient Adults2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 4, s. 0093180-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Selective immunoglobulin A deficiency is the most common primary immunodeficiency disorder that is strongly overrepresented among patients with celiac disease (CD). IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) serve as serological markers for CD in IgA deficient individuals, although the diagnostic value remains uncertain. The aim of this study was to investigate the prevalence of these markers in a large cohort of IgA deficient adults with confirmed or suspected CD and relate the findings to gluten free diet. Methods: Sera from 488,156 individuals were screened for CD in seven Swedish clinical immunology laboratories between 1998 and 2012. In total, 356 out of 1,414 identified IgA deficient adults agreed to participate in this study and were resampled. Forty-even IgA deficient blood donors served as controls. Analyses of IgG antibodies against tTG and DGP as well as HLA typing were performed and a questionnaire was used to investigate adherence to gluten free diet. Available biopsy results were collected. Results: Out of the 356 IgA deficient resampled adults, 67 (18.8%) were positive for IgG anti-tTG and 79 (22.2%) for IgG anti-DGP, 54 had biopsy confirmed CD. Among the 47 IgA deficient blood donors, 4 (9%) were positive for IgG anti-tTG and 8 (17%) for anti- DGP. Four were diagnosed with biopsy verified CD, however, 2 of the patients were negative for all markers. Sixty-eight of 69 individuals with positive IgG anti-tTG were HLA-DQ2/DQ8 positive whereas 7 (18.9%) of the 37 individuals positive for IgG anti-DGP alone were not. Conclusions: IgG anti- tTG seems to be a more reliable marker for CD in IgA deficient adults whereas the diagnostic specificity of anti-DGP appears to be lower. High levels of IgG antibodies against tTG and DGP were frequently found in IgA deficient adults despite adhering to gluten free diet.

  • 168.
    Weismueller, Tobias J.
    et al.
    University of Bonn, Germany; Hannover Medical Sch, Germany.
    Trivedi, Palak J.
    University of Birmingham, England; University Hospital Birmingham Queen Elizabeth, England.
    Bergquist, Annika
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Imam, Mohamad
    Mayo Clin, MN USA; University of North Dakota, ND USA.
    Lenzen, Henrike
    Hannover Medical Sch, Germany.
    Ponsioen, Cyriel Y.
    Academic Medical Centre, Netherlands.
    Holm, Kristian
    National Hospital Norway, Norway.
    Gotthardt, Daniel
    University Hospital Heidelberg, Germany.
    Faerkkilae, Martti A.
    University of Helsinki, Finland.
    Marschall, Hanns-Ulrich
    University of Gothenburg, Sweden.
    Thorburn, Douglas
    Royal Free Hospital, England.
    Weersma, Rinse K.
    University of Groningen, Netherlands; University of Medical Centre Groningen, Netherlands.
    Fevery, Johan
    University Hospital Gasthuisberg, Belgium.
    Mueller, Tobias
    Charite, Germany.
    Chazouilleres, Olivier
    Hop St Antoine, France.
    Schulze, Kornelius
    University of Medical Centre Hamburg Eppendorf, Germany.
    Lazaridis, Konstantinos N.
    Mayo Clin, MN USA.
    Almer, Sven
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Pereira, Stephen P.
    UCL, England.
    Levy, Cynthia
    University of Miami, FL USA.
    Mason, Andrew
    University of Alberta, Canada.
    Naess, Sigrid
    National Hospital Norway, Norway; National Hospital Norway, Norway; University of Oslo, Norway.
    Bowlus, Christopher L.
    University of Calif Davis, CA 95616 USA.
    Floreani, Annarosa
    University of Padua, Italy.
    Halilbasic, Emina
    Medical University of Vienna, Austria.
    Yimam, Kidist K.
    Calif Pacific Medical Centre, CA USA.
    Milkiewicz, Piotr
    Pomeranian Medical University, Poland; Medical University of Warsaw, Poland.
    Beuers, Ulrich
    Academic Medical Centre, Netherlands.
    Huynh, Dep K.
    Royal Adelaide Hospital, Australia.
    Pares, Albert
    University of Barcelona, Spain.
    Manser, Christine N.
    University Hospital Zurich USZ, Switzerland.
    Dalekos, George N.
    University of Thessaly, Greece.
    Eksteen, Bertus
    University of Calgary, Canada.
    Invernizzi, Pietro
    University of Milano Bicocca, Italy.
    Berg, Christoph P.
    University of Tubingen, Germany.
    Kirchner, Gabi I.
    University Hospital Regensburg, Germany.
    Sarrazin, Christoph
    Johann Wolfgang Goethe University Hospital, Germany.
    Zimmer, Vincent
    Saarland University, Germany.
    Fabris, Luca
    University of Padua, Italy.
    Braun, Felix
    UKSH, Germany.
    Marzioni, Marco
    University of Politecn Marche, Italy.
    Juran, Brian D.
    Mayo Clin, MN USA.
    Said, Karouk
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Rupp, Christian
    University Hospital Heidelberg, Germany.
    Jokelainen, Kalle
    University of Helsinki, Finland.
    Benito de Valle, Maria
    University of Gothenburg, Sweden.
    Saffioti, Francesca
    Royal Free Hospital, England; Royal Free Hospital, England.
    Cheung, Angela
    Mayo Clin, MN USA; University of Helsinki, Finland.
    Trauner, Michael
    Medical University of Vienna, Austria.
    Schramm, Christoph
    University of Medical Centre Hamburg Eppendorf, Germany; University of Medical Centre Hamburg Eppendorf, Germany.
    Chapman, Roger W.
    University of Oxford, England; John Radcliffe Hospital, England.
    Karlsen, Tom H.
    National Hospital Norway, Norway; National Hospital Norway, Norway; University of Oslo, Norway.
    Schrumpf, Erik
    National Hospital Norway, Norway; National Hospital Norway, Norway; University of Oslo, Norway.
    Strassburg, Christian P.
    University of Bonn, Germany.
    Manns, Michael P.
    Hannover Medical Sch, Germany.
    Lindor, Keith D.
    Mayo Clin, MN USA; Mayo Clin, AZ USA; Arizona State University, AZ USA.
    Hirschfield, Gideon M.
    University of Birmingham, England.
    Hansen, Bettina E.
    Erasmus University, Netherlands; University of Toronto, Canada; Toronto Gen Hospital, Canada.
    Boberg, Kirsten M.
    National Hospital Norway, Norway; University of Oslo, Norway.
    Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis2017Ingår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 152, nr 8, s. 1975-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND amp; AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohns disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P amp;lt;.001 and HR, 0.90; P =.03, respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P amp;lt;.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P amp;lt;.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P amp;lt;.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohns disease (HR, 1.56; P amp;lt;.001) or no IBD (HR, 1.15; P =.002). CONCLUSIONS: In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.

  • 169.
    Wickström, Anne
    et al.
    Umeå University, Sweden .
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Svenningsson, Anders
    Umeå University, Sweden .
    Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 8, s. 1095-1101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    In a retrospective study, we have previously shown that work ability was improved after the initiation of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS). In another prospective trial (TYNERGY) the effect on MS-related fatigue was evaluated after 12 months of treatment with natalizumab. A comprehensive Capacity for Work Questionnaire (CWQ) was used to collect data regarding number of working hours and sickness absence. The predefined intention-to-treat analysis regarding work ability did not, however, show significant results.

    OBJECTIVES:

    The objective of this paper is to assess the amount of sick leave in RRMS before and after one year of natalizumab treatment and correlate it to fatigue and walking ability.

    METHODS:

    This is a post-hoc analysis of the complete data from the CWQ used in the TYNERGY trial.

    RESULTS:

    MS patients receiving sickness benefit before start of treatment reduced their sickness benefit by an absolute change of 33% after one year of natalizumab treatment. Younger age and improvement of walking ability correlated significantly with reduction of sick leave.

    CONCLUSIONS:

    This ad-hoc analysis of prospectively collected data supported our previous retrospective study and thus indicates a positive relationship between natalizumab treatment and improvement in work ability.

  • 170.
    Wilhelmsson, Peter
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Fryland, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Lindblom, Pontus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Sjöwall, Johanna
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin.
    Ahlm, Clas
    Division of Infectious Diseases, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Berglund, Johan
    School of Health Science, Blekinge Institute of Technology, Karlskrona, Sweden.
    Haglund, Mats
    Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
    Henningsson, Anna J
    Department of Clinical Microbiology, Division of Medical Services, Ryhov County Hospital, Jönkoping, Sweden.
    Nolskog, Peter
    Department of Communicable Disease Control and Prevention, Region Västra Götaland, Skaraborg Hospital, Skövde, Sweden.
    Nordberg, Marika
    The Åland Group for Borrelia Research, Mariehamn, Åland, Finland.
    Nyberg, Clara
    The Åland Group for Borrelia Research, Mariehamn, Åland, Finland.
    Ornstein, Katharina
    Department of Internal Medicine, Hässleholm Hospital, Hässleholm, Sweden/Department of Clinical Sciences, Lund University, Lund, Sweden.
    Nyman, Dag
    The Åland Group for Borrelia Research, Mariehamn, Åland, Finland.
    Ekerfelt, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Forsberg, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Lindgren, Per-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    A prospective study on the incidence of Borrelia infection after a tick bite in Sweden and on the Åland Islands, Finland (2008-2009)2016Ingår i: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 7, nr 1, s. 71-79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lyme borreliosis (LB) is a common and increasing tick-borne disease in Europe. The risk of acquiring a Borrelia infection after a tick bite is not fully known. Therefore, we investigated the incidence of Borrelia infection after a tick bite and if the Borrelia load and/or the duration of tick-feeding influenced the risk of infection. During 2008-2009, ticks and blood samples were collected from 1546 tick-bitten persons from Sweden and the Åland Islands, Finland. Follow-up blood samples were taken three months after the tick bite. The duration of tick feeding was microscopically estimated and Borrelia was detected and quantified in ticks by real-time PCR. Anti-Borrelia antibodies were detected in sera using ELISA assays and immunoblot.

    Even though 28 % of the participants were bitten by a Borrelia-positive tick, only 7.5% (32/428) of them developed a Borrelia infection, half of them LB. All who seroconverted removed “their” ticks significantly later than those who did not. The Borrelia load in the ticks did not explain the risk of seroconversion. Regional as well as gender differences in the Borrelia seroprevalence were found. The risk of developing a Borrelia infection after a bite by a Borrelia-infected tick is small but increases with the duration of tick feeding.

  • 171.
    Wilhelmsson, Peter
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Lindblom, Pontus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Fryland, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Forsberg, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Infektionskliniken i Östergötland.
    Lindgren, Per-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Prevalence, Diversity, and Load of Borrelia species in Ticks That Have Fed on Humans in Regions of Sweden and Åland Islands, Finland with Different Lyme Borreliosis Incidences2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 11, s. e81433-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The incidence of Lyme borreliosis (LB) in a region may reflect the prevalence of Borrelia in the tick population. Our aim was to investigate if regions with different LB incidences can be distinguished by studying the prevalence and diversity of Borrelia species in their respective tick populations. The Borrelia load in a feeding tick increases with the duration of feeding, which may facilitate a transmission of Borrelia Spirochetes from tick to host. Therefore, we also wanted to investigate how the Borrelia load in ticks that have fed on humans varies with the duration of tick feeding. During 2008 and 2009, ticks that had bitten humans were collected from four regions of Sweden and Finland, regions with expected differences in LB incidence. The duration of tick feeding was estimated and Borrelia were detected and quantified by a quantitative PCR assay followed by species determination. Out of the 2,154 Ixodes ricinus ticks analyzed, 26% were infected with Borrelia and seven species were identified. B. spielmanii was detected for the first time in the regions. The tick populations collected from the four regions exhibited only minor differences in both prevalence and diversity of Borrelia species, indicating that these variables alone cannot explain the regions different LB incidences. The number of Borrelia cells in the infected ticks ranged from fewer than ten to more than a million. We also found a lower number of Borrelia cells in adult female ticks that had fed for more than 36 hours, compared to the number of Borrelia cells found in adult female ticks that had fed for less than 36 hours.

  • 172.
    Willander, Kerstin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Kumar Dutta, Ravi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Ungerbäck, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Gunnarsson, Rebeqa
    Lund University, Sweden.
    Juliusson, Gunnar
    Lund University, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Linderholm, Mats
    Stockholms Sjukhem, Sweden.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    NOTCH1 mutations influence survival in chronic lymphocytic leukemia patients2013Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    NOTCH1 PEST domain mutations in chronic lymphocytic leukemia have recently been shown to be of prognostic relevance. Both NOTCH1 and NOTCH2 are constitutively activated in B-cell CLL but not expressed in normal B cells and may be involved in survival and resistance to apoptosis in CLL. We screened for mutations in different parts of both NOTCH1 and NOTCH2 genes and related the changes to survival and other known risk factors.

    Methods

    In a cohort of 209 CLL patients, we used single strand conformation analysis to determine which of the samples carrying the NOTCH mutations and direct dideoxy sequencing was used to determine the exact nucleotide changes. Kaplan-Meier curves and log rank test were used to determine overall survival for NOTCH1 mutated cases and Cox regression analysis was used to calculate hazardous ratios.

    Results

    In the present study, we found NOTCH1 PEST domain mutations in 6.7% of the cases. A shorter overall survival was found in patients with NOTCH1 mutations compared to wildtype (p = 0.049). Further, we also examined the extracellular and the heterodimerisation domains of the NOTCH1 gene and the PEST domain and heterodimerisation domain of the NOTCH2 gene, but no mutations were found in these regions. NOTCH1 mutations were most commonly observed in patients with unmutated IGHV gene (10/14), and associated with a more aggressive disease course. In addition, NOTCH1 mutations were almost mutually exclusive with TP53 mutations. In the combined group of NOTCH1 (6.7%) or TP53 (6.2%) mutations, a significant difference in overall survival compared to the wildtype NOTCH1 and TP53 was found (p = 0.002).

    Conclusions

    Both NOTCH1 and TP53 mutations seem to be independent predictive markers for worse outcome in CLL-patients and this study emphasizes the contention that NOTCH1 mutations is a novel risk marker.

  • 173.
    Wäster, Petra
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Rosdahl, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Öllinger, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.2014Ingår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, nr 6, s. 1336-1346Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Ultraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation.

    OBJECTIVES: To evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes.

    METHODS: Primary cultures of normal human melanocytes were irradiated with UVA or UVB, and the concomitant DNA damage and redox alterations were monitored. The resulting activation of the NF-κB and AP-1 signalling pathways and subsequent apoptosis were studied.

    RESULTS: UVB irradiation causes DNA damage detected as formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of 8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, and the apoptosis signalling pathways converge into a common mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and prevents apoptosis upstream of lysosomal and mitochondrial membrane permeabilization, whereas inhibition of NF-κB by SN50 increases apoptosis.

    CONCLUSIONS: We conclude that AP-1 induces proapoptotic signalling, whereas NF-κB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced cellular damage in human melanocytes, which might in turn impact melanoma development and progression.

  • 174.
    Yamada, Naomi
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Caffeine Interaction with Glutamate Receptor Gene GRIN2A: Parkinsons Disease in Swedish Population2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 6, s. e99294-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A complex interplay between genetic and environmental factors is thought to be involved in the etiology of Parkinsons disease (PD). A recent genome-wide association and interaction study (GWAIS) identified GRIN2A, which encodes an NMDA-glutamate-receptor subunit involved in brains excitatory neurotransmission, as a PD genetic modifier in inverse association with caffeine intake. Here in, we attempted to replicate the reported association of a single nucleotide polymorphism, GRIN2A_rs4998386, and its interaction with caffeine intake with PD in patient-control study in an ethnically homogenous population in southeastern Sweden, as consistent and independent genetic association studies are the gold standard for the validation of genome-wide association studies. All the subjects (193 sporadic PD patients and 377 controls) were genotyped, and the caffeine intake data was obtained by questionnaire. We observed an association between rs4998386 and PD with odds ratio (OR) of 0.61, 95% confidence intervals (CI) of 0.39-0.96, p = 0.03, under a model excluding rare TT allele. There was also a strong significance in joint effects of gene and caffeine on PD risk (TC heavy caffeine vs. CC light caffeine: OR = 0.38, 95% CI = [0.20-0.70], p = 0.002) and gene-caffeine interaction (OR = 0.998, 95% CI = [0.991-0.999], pless than0.001). Overall, our results are in support of the findings of the GWAIS and provided additional evidence indicating PD protective effects of coffee drinking/caffeine intake as well as the interaction with glutamate receptor genotypes.

  • 175.
    Zhang, Huan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Cardell, Lars Olaf
    Division of ENT diseases Huddinge, CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Björkander, Janne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Benson, Mikael
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Wang, Hui
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Comprehensive Profiling of Peripheral Immune Cells and Subsets in Patients with Intermittent Allergic Rhinitis Compared to Healthy Controls and After Treatment with Glucocorticoids2013Ingår i: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 36, nr 4, s. 821-829Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intermittent allergic rhinitis (IAR) is a common allergic disease, which is associated with local infiltration of T cells, eosinophils, and basophils. However, changes of circulating inflammatory cells may reflect local and systemic allergic inflammation and potentially, also the response to treatment with glucocorticoids (GCs). In this study, we comprehensively profiled peripheral blood immune cells and subsets from 12 patients with IAR during the birch pollen season before and after GC treatment and nine healthy controls by flow cytometry. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified that peripheral immune cells and subsets markedly separated symptomatic patients and controls. Eosinophils, basophils, and Th2 cells contributed most to the separation. However, there was no good separation between patients before and after GC treatment. Local allergic inflammation in the nasal mucosa is associated with increased circulating Th2 cells, eosinophils, and basophils. Local GC treatment has limited effects on circulating immune cells.

  • 176.
    Östlund, Gunnel
    et al.
    Mälardalen University, Eskilstuna, Sweden .
    Björk, Mathilda
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Rehabenheten. Jönköping University, Sweden.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Thyberg, Mikael
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Valtersson, Eva
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Rehabgruppen NSC.
    Stenström, Birgitta
    Swedish Rheumatism Association, Stockholm, Sweden .
    Sverker, Annette
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Socialt arbete. Linköpings universitet, Filosofiska fakulteten. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Rehabgruppen NSC.
    Emotions related to participation restrictions as experienced by patients with early rheumatoid arthritis: a qualitative interview study (the Swedish TIRA project)2014Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 33, nr 10, s. 1403-1413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Psychological distress is a well-known complication in rheumatoid arthritis (RA), but knowledge regarding emotions and their relationship to participation restrictions is scarce. The objective of the study was to explore emotions related to participation restrictions by patients with early RA. In this study, 48 patients with early RA, aged 20-63 years, were interviewed about participation restrictions using the critical incident technique. Information from transcribed interviews was converted into dilemmas and linked to International Classification of Functioning, Disability, and Health (ICF) participation codes. The emotions described were condensed and categorized. Hopelessness and sadness were described when trying to perform daily activities such as getting up in the mornings and getting dressed, or not being able to perform duties at work. Sadness was experienced in relation to not being able to continue leisure activities or care for children. Examples of fear descriptions were found in relation to deteriorating health and fumble fear, which made the individual withdraw from activities as a result of mistrusting the body. Anger and irritation were described in relation to domestic and employed work but also in social relations where the individual felt unable to continue valued activities. Shame or embarrassment was described when participation restrictions became visible in public. Feelings of grief, aggressiveness, fear, and shame are emotions closely related to participation restrictions in everyday life in early RA. Emotions related to disability need to be addressed both in clinical settings in order to optimize rehabilitative multi-professional interventions and in research to achieve further knowledge.

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