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  • 1.
    Abdurahman, Samir
    et al.
    Division of Clinical Microbiology, Department of Laboratory Medicine F68, Karolinska University Hospital, Stockholm, Sweden.
    Barqasho, Babilonia
    Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nowak, Piotr
    Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Cuong, Do Duy
    Infectious Diseases Department, Bach Mai Hospital, Hanoi, Viet Nam .
    Amogné, Wondwossen
    Department of Medicine, Faculty of Medicine, University, Addis Abeba, Ethiopia .
    Larsson, Mattias
    Division of Global Health (IHCAR), Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden; Oxford University Clinical Research Unit (OUCRU), Hanoi, Viet Nam .
    Lindquist, Lars
    Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden .
    Marrone, Gaetano
    Division of Global Health (IHCAR), Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden .
    Sönnerborg, Anders
    Division of Clinical Microbiology, Department of Laboratory Medicine F68, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Pattern of microbial translocation in patients living with HIV-1 from Vietnam, Ethiopia and Sweden2014In: Journal of the International AIDS Society, ISSN 1758-2652, E-ISSN 1758-2652, Vol. 17, p. 18841-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.

    METHODS: Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples were obtained from a subset of the Vietnamese (n=24) in whom antiretroviral therapy (ART) and tuberculostatics were given. Plasma lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent assay.

    RESULTS: All three biomarkers were significantly increased in patients living with HIV-1 from all countries as compared to controls. No differences were found between males and females. Vietnamese and Ethiopian patients had significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes. ART reduced these levels for the Vietnamese. Vietnamese patients given tuberculostatics at initiation of ART had significantly lower levels of anti-flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did not develop opportunistic infection.

    CONCLUSIONS: Higher MT is common in patients living with HIV compared to healthy individuals, and in patients from LMICs compared to patients from a high-income country. Treatment with tuberculostatics decreased MT while higher levels of MT are associated with a poorer clinical outcome.

  • 2.
    Abedi, Mohammad R.
    et al.
    Örebro University Hospital. Department of Laboratory Medicine, Section for Transfusion Medicine.
    Doverud, Ann-Charlotte
    Department of Laboratory Medicine, Section for Transfusion Medicine, Örebro University Hospital. Örebro, Sweden.
    Preparation and Pathogen Inactivation of Double Dose Buffy Coat Platelet Products using the INTERCEPT Blood System2012In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 70, article id UNSP e4414Article in journal (Refereed)
    Abstract [en]

    Blood centers are faced with many challenges including maximizing production yield from the blood product donations they receive as well as ensuring the highest possible level of safety for transfusion patients, including protection from transfusion transmitted diseases. This must be accomplished in a fiscally responsible manner which minimizes operating expenses including consumables, equipment, waste, and personnel costs, among others.

    Several methods are available to produce platelet concentrates for transfusion. One of the most common is the buffy coat method in which a single therapeutic platelet unit (>= 2.0 x10(11) platelets per unit or per local regulations) is prepared by pooling the buffy coat layer from up to six whole blood donations. A procedure for producing "double dose" whole blood derived platelets has only recently been developed.

    Presented here is a novel method for preparing double dose whole blood derived platelet concentrates from pools of 7 buffy coats and subsequently treating the double dose units with the INTERCEPT Blood System for pathogen inactivation. INTERCEPT was developed to inactivate viruses, bacteria, parasites, and contaminating donor white cells which may be present in donated blood. Pairing INTERCEPT with the double dose buffy coat method by utilizing the INTERCEPT Processing Set with Dual Storage Containers (the "DS set"), allows blood centers to treat each of their double dose units in a single pathogen inactivation processing set, thereby maximizing patient safety while minimizing costs. The double dose buffy coat method requires fewer buffy coats and reduces the use of consumables by up to 50% (e.g. pooling sets, filter sets, platelet additive solution, and sterile connection wafers) compared to preparation and treatment of single dose buffy coat platelet units. Other cost savings include less waste, less equipment maintenance, lower power requirements, reduced personnel time, and lower collection cost compared to the apheresis technique.

  • 3.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Hematology, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Persson, Lennart
    Örebro University Hospital. Department of Infectious diseases, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious diseases & Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 6, p. 539-544Article in journal (Refereed)
    Abstract [en]

    The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

  • 4.
    Almroth, G.
    et al.
    Department of Nephrology, Institution of medicine and health sciences, Linköping University, Linköping, Sweden.
    Lönn, Johanna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Uhlin, F.
    Department of Nephrology, Institution of medicine and health sciences, Linköping University, Linköping, Sweden.
    Brudin, L.
    Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden; Department of Physiology, County Hospital, Kalmar, Sweden.
    Andersson, B.
    Department of Clinical Immunology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Hahn-Zoric, M.
    Department of Clinical Immunology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Sclerostin, TNF-alpha and Interleukin-18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients2016In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 83, no 1, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNF-alpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.

  • 5. Amoudruz, Petra
    et al.
    Holmlund, Ulrika
    Schollin, Jens
    Örebro University, School of Health and Medical Sciences.
    Sverremark-Ekström, Eva
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Maternal country of birth and previous pregnancies are associated with breast milk characteristics2009In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 20, no 1, p. 19-29Article in journal (Refereed)
    Abstract [en]

    Populations in high infectious exposure countries are at low risk of some immune-mediated diseases such as Crohn's disease and allergy. This low risk is maintained upon immigration to an industrialized country, but the offspring of such immigrants have a higher immune-mediated disease risk than the indigenous population. We hypothesize that early life exposures in a developing country shape the maternal immune system, which could have implications for the offspring born in a developed country with a low infectious load. The aim of this study was to investigate if exposures in childhood (indicated by country of origin) and subsequent exposures influence immunologic characteristics relevant to stimulation of offspring. Breast milk components among 64 mothers resident in Sweden, 32 of whom immigrated from a developing country, were examined using the ELISA and Cytometric Bead Array methods. Immigrants from a developing country had statistically significantly higher levels of breast milk interleukin-6 (IL-6), IL-8 and transforming growth factor-beta1. A larger number of previous pregnancies were associated with down-regulation of several substances, statistically significant for soluble CD14 and IL-8. The results suggest that maternal country of birth may influence adult immune characteristics, potentially relevant to disease risk in offspring. Such a mechanism may explain the higher immune-mediated disease risk among children of migrants from a developing to developed country. Older siblings may influence disease risk through the action of previous pregnancies on maternal immune characteristics.

  • 6.
    Asfaw Idosa, Berhane
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Sahdo, Berolla
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Balcha, Ermias
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Kelly, Anne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Särndahl, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    C10X polymorphism in the CARD8 gene is associated with bacteraemia2014In: Immunity, inflammation and disease, E-ISSN 2050-4527, Vol. 2, no 1, p. 13-20Article in journal (Refereed)
    Abstract [en]

    The NLRP3 inflammasome is an intracellular multi-protein complex that triggers caspase-1 mediated maturation of interleukin-1β (IL-1β); one of the most potent mediators of inflammation and a major cytokine produced during severe infections, like sepsis. However, the excessive cytokine levels seem to stage for tissue injury and organ failure, and high levels of IL-1β correlates with severity and mortality of sepsis. Instead, recent data suggest caspase-1 to function as a guardian against severe infections. CARD8 has been implied to regulate the synthesis of IL-1β via interaction to caspase-1. In recent years, polymorphism of CARD8 (C10X) per se or in combination with NLRP3 (Q705K) has been implicated with increased risk of inflammation. The aim was to investigate the correlation of these polymorphisms with severe blood stream infection. Human DNA was extracted from blood culture bottles that were found to be positive for microbial growth (i.e. patients with bacteraemia). Polymorphisms Q705K in the NLRP3 gene and C10X in the CARD8 gene were genotyped using TaqMan genotyping assay. The results were compared to healthy controls and to samples from patients with negative cultures. The polymorphism C10X was significantly over-represented among patients with bacteraemia as compared to healthy controls, whereas patients with negative blood culture were not associated with a higher prevalence. No association was observed with polymorphism Q705K of NLRP3 in either group of patients. Patients carrying polymorphism C10X in the CARD8 gene are at increased risk of developing bacteraemia and severe inflammation.

  • 7.
    Assadi, G.
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Saleh, R.
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Hadizadeh, F.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Vesterlund, L.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Bonfiglio, F.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Törkvist, L.
    Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden.
    Eriksson, A. S.
    Gatroenterology Unit, Department of Internal Medicine, Sahlgren's University Hospital/Östra, Göteborg, Sweden.
    Harris, H. E.
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Sundberg, E.
    Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    D'Amato, M.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    LACC1 polymorphisms in inflammatory bowel disease and juvenile idiopathic arthritis2016In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 17, no 4, p. 261-264Article in journal (Refereed)
    Abstract [en]

    The function of the Laccase domain-containing 1 (LACC1) gene is unknown, but genetic variation at this locus has been reported to consistently affect the risk of Crohn's disease (CD) and leprosy. Recently, a LACC1 missense mutation was found in patients suffering from monogenic forms of CD, but also systemic juvenile idiopathic arthritis. We tested the hypothesis that LACC1 single nucleotide polymorphisms (SNPs), in addition to CD, are associated with juvenile idiopathic arthritis (JIA, non-systemic), and another major form of inflammatory bowel disease, ulcerative colitis (UC). We selected 11 LACC1 tagging SNPs, and tested their effect on disease risk in 3855 Swedish individuals from three case-control cohorts of CD, UC and JIA. We detected false discovery rate corrected significant associations with individual markers in all three cohorts, thereby expanding previous results for CD also to UC and JIA. LACC1's link to several inflammatory diseases suggests a key role in the human immune system and justifies further characterization of its function(s).

  • 8.
    Athlin, Simon
    et al.
    Örebro University Hospital.
    Kaltoft, Margit
    Statens Serum Institut, Copenhagen, Denmark.
    Slotved, Hans-Christian
    Statens Serum Institut, Copenhagen, Denmark.
    Herrmann, Björn
    Uppsala University, Uppsala, Sweden.
    Holmberg, Hans
    Örebro University Hospital.
    Konradsen, Helle Bossen
    Statens Serum Institut, Copenhagen, Denmark.
    Strålin, Kristoffer
    Örebro University Hospital, Örebro, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 11, p. 1541-1549Article in journal (Refereed)
    Abstract [en]

    We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P < 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and <1 in 17 patients. Patients ≥65 years old had a lower median Ig titer ratio than did younger patients (P < 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P < 0.05 for both comparisons after adjustment for age). Ig titer ratios of <1 were predominantly noted in patients with serotypes with a thick capsule. In 8 patients with pneumococcal DNA detected in plasma, the three patients with the highest DNA load had the lowest Ig titer ratios. In conclusion, a high antibody response was associated with serotypes with a thin capsule and medium/high invasive potential, although a low antibody response was associated with serotypes with a thick capsule and a high pneumococcal plasma load.

  • 9.
    Bang, Charlotte Sahlberg
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kruse, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Demirel, Isak
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Önnberg, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Persson, Katarina
    Örebro University, School of Medicine, Örebro University, Sweden.
    Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).2014In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 66, p. 29-35Article in journal (Refereed)
    Abstract [en]

    Carbon monoxide (CO) releasing molecules (CO-RMs) have been shown to inhibit growth of commensal Escherichia coli (E. coli). In the present study we examined the effect of CORM-2 on uropathogenic E. coli (UPEC) that produces extended-spectrum β-lactamase (ESBL). Viability experiments showed that CORM-2 inhibited the growth of several different ESBL-producing UPEC isolates and that 500 μM CORM-2 had a bactericidal effect within 4 h. The bactericidal effect of CORM-2 was significantly more pronounced than the effect of the antibiotic nitrofurantoin. CORM-2 demonstrated a low level of cytotoxicity in eukaryotic cells (human bladder epithelial cell line 5637) at the concentrations and time-points where the antibacterial effect was obtained. Real-time RT-PCR studies of different virulence genes showed that the expression of capsule group II kpsMT II and serum resistance traT was reduced and that some genes encoding iron acquisition systems were altered by CORM-2. Our results demonstrate that CORM-2 has a fast bactericidal effect against multiresistant ESBL-producing UPEC isolates, and also identify some putative UPEC virulence factors as targets for CORM-2. CO-RMs may be candidate drugs for further studies in the field of finding new therapeutic approaches for treatment of uropathogenic ESBLproducing E. coli.

  • 10.
    Bengtsson, Torbjörn
    et al.
    Örebro University, School of Medical Sciences.
    Zhang, Boxi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Selegård, Robert
    Örebro University, School of Medical Sciences. Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Wiman, Emanuel
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Aili, Daniel
    Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Dual action of bacteriocin PLNC8 alpha beta through inhibition of Porphyromonas gingivalis infection and promotion of cell proliferation2017In: Pathogens and Disease, E-ISSN 2049-632X, Vol. 75, no 5, article id ftx064Article in journal (Refereed)
    Abstract [en]

    Periodontitis is a chronic inflammatory disease that is characterised by accumulation of pathogenic bacteria, including Porphyromonas gingivalis, in periodontal pockets. The lack of effective treatments has emphasised in an intense search for alternative methods to prevent bacterial colonisation and disease progression. Bacteriocins are bacterially produced antimicrobial peptides gaining increased consideration as alternatives to traditional antibiotics. We show rapid permeabilisation and aggregation of P. gingivalis by the two-peptide bacteriocin PLNC8 alpha beta. In a cell culture model, P. gingivalis was cytotoxic against gingival fibroblasts. The proteome profile of fibroblasts is severely affected by P. gingivalis, including induction of the ubiquitin-proteasome pathway. PLNC8 alpha beta enhanced the expression of growth factors and promoted cell proliferation, and suppressed proteins associated with apoptosis. PLNC8 alpha beta efficiently counteracted P. gingivalis-mediated cytotoxicity, increased expression of a large number of proteins and restored the levels of inflammatory mediators. In conclusion, we show that bacteriocin PLNC8 alpha beta displays dual effects by acting as a potent antimicrobial agent killing P. gingivalis and as a stimulatory factor promoting cell proliferation. We suggest preventive and therapeutical applications of PLNC8 alpha beta in periodontitis to supplement the host immune defence against P. gingivalis infection and support wound healing processes.

  • 11.
    Bergström, Ida
    et al.
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Lundberg, Anna K.
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Jönsson, Simon
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences. IRiSC - Inflammatory Response and Infection Susceptibility Centre.
    Ernerudh, Jan
    Department of Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Jonasson, Lena
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Annexin A1 in blood mononuclear cells from patients with coronary artery disease: Its association with inflammatory status and glucocorticoid sensitivity2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174177Article in journal (Refereed)
    Abstract [en]

    Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.

  • 12.
    Bjørkeng, Eva
    et al.
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway.
    Rasmussen, Gunlög
    Örebro University, School of Medical Sciences.
    Sundsfjord, Arnfinn
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway; Department of Microbiology and Infection Control, Reference Centre for Detection of Antimicrobial Resistance, University Hospital of North-Norway, Tromsø, Norway.
    Sjöberg, Lennart
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hegstad, Kristin
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway; Department of Microbiology and Infection Control, Reference Centre for Detection of Antimicrobial Resistance, University Hospital of North-Norway, Tromsø, Norway.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Department of Infectious Diseases and Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Clustering of polyclonal VanB-type vancomycin-resistant Enterococcus faecium in a low-endemic area was associated with CC17-genogroup strains harbouring transferable vanB2-Tn5382 and pRUM-like repA containing plasmids with axe-txe plasmid addiction systems2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 4-5, p. 247-258Article in journal (Refereed)
    Abstract [en]

    VanB-type vancomycin-resistant Enterococcus faecium isolates (n = 17) from 15 patients at the Örebro University hospital in Sweden during a span of 18 months was characterized. All patients had underlying disorders and received broad-spectrum antimicrobial therapy. Pulsed-field gel electrophoresis (PFGE) grouped 14 isolates in three PFGE types and three isolates in unique PFGE patterns. All isolates had multi-locus sequence types [ST17 (n = 5); ST18 (n = 3); ST125 (n = 7); ST262 (n = 1); ST460 (n = 1)] belonging to the successful hospital-adapted clonal complex 17 (CC17), harboured CC17-associated virulence genes, were vanB2-positive and expressed diverse vancomycin minimum inhibitory concentration (MICs; 8 to > 256 mg/L). Isolate 1 had a unique PFGE type and a chromosomal transferable vanB2-Tn5382 element. Interestingly, the other five PFGE types had Tn5382 located on plasmids containing pRUM-like repA and a plasmid addiction system (axe-txe) shown by co-hybridization analysis of PFGE-separated S1-nuclease digested total DNA. The resistance plasmids were mainly of 120-kb and supported intraspecies vanB transfer. Two strains were isolated from patient 6 and we observed a possible transfer of the vanB2-resistance genes from PFGE type III ST460 to a more successful PFGE type I ST125. This latter PFGE type I ST125 became the predominant type afterwards. Our observations support the notion that vanB-type vancomycin-resistant Enterococcus faecium can persist in a low-endemic area through successful clones and plasmids with stability functions in hospital patients with known risk factors.

  • 13.
    Brehony, Carina
    et al.
    Dept Zool, Univ Oxford, Oxford, England..
    Trotter, Caroline L.
    Dept Vet Med, Univ Cambridge, Cambridge, England.
    Ramsay, Mary E.
    Publ Hlth England, London, England.
    Chandra, Manosree
    Publ Hlth England, London, England.
    Jolley, Keith A.
    Dept Zool, Univ Oxford, Oxford, England.
    van der Ende, Arie
    Dept Med Microbiol, Netherlands Reference Lab Bacterial Meningitis, Acad Med Ctr, Univ Amsterdam, Amsterdam, Netherlands.
    Carion, Francoise
    Meningococcal Reference Lab, Sci Inst Publ Hlth, Brussels, Belgium.
    Berthelsen, Lene
    Neisseria & Streptococcus Reference Lab, Statens Serum Inst, Copenhagen, Denmark.
    Hoffmann, Steen
    Neisseria & Streptococcus Reference Lab, Statens Serum Inst, Copenhagen, Denmark.
    Hardardottir, Hjordis
    Dept Microbiol, Landspitali Univ Hosp, Reykjavik, Iceland.
    Vazquez, Julio A.
    Meningococcal Reference Lab, Madrid, Spain.
    Murphy, Karen
    Irish Meningococcal & Meningitis Reference Lab, Dublin, Ireland.
    Toropainen, Maija
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Canica, Manuela
    Dept Infect Dis, Lab Antimicrobial Resistance, Natl Inst Hlth Dr Ricardo Jorge, Lisbon, Portugal.
    Ferreira, Eugenia
    Dept Infect Dis, Lab Antimicrobial Resistance, Natl Inst Hlth Dr Ricardo Jorge, Lisbon, Portugal.
    Diggle, Mathew
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, UK.
    Edwards, Giles F.
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, UK.
    Taha, Muhamed-Kheir
    Inst Pasteur, Natl Reference Ctr Meningococci, Institut Pasteur, Paris, France.
    Stefanelli, Paola
    Dept Infect Parasit & Immune Mediated Dis, Ist Super Sanita, Rome, Italy.
    Kriz, Paula
    Natl Reference Lab Meningococcal Infect, Natl Inst Publ Hlth, Prague, Czech Republic.
    Gray, Steve J.
    Meningococcal Reference Unit, Manchester Royal Infirm, Manchester, England.
    Fox, Andrew J.
    Meningococcal Reference Unit, Manchester Royal Infirm, Manchester, England.
    Jacobsson, Susanne
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Claus, Heike
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Vogel, Ulrich
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Tzanakaki, Georgina
    Natl Meningococcal Reference Lab, Natl Sch Publ Hlth, Athens, Greece.
    Heuberger, Sigrid
    Natl Reference Ctr Meningococci, Inst Med Microbiol & Hyg, Graz, Austria.
    Caugant, Dominique A.
    Dept Bacteriol & Immunol, Norwegian Inst Publ Hlth, Oslo, Norway.
    Frosch, Matthias
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Maiden, Martin C. J.
    Dept Zool, Univ Oxford, Oxford, England.
    Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 6, p. 847-853Article in journal (Refereed)
    Abstract [en]

    New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and >= 25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.

  • 14.
    Brew, Bronwyn K.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lundholm, Cecilia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Gong, Tong
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet; Sweden Pediatric Allergy and Pulmonology Unit,t Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    The familial aggregation of atopic diseases and depression or anxiety in children2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 6, p. 703-711Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Children with asthma and atopic diseases have an increased risk of depression or anxiety. Each of these diseases have strong genetic and environmental components, therefore it seems likely that there is a shared liability rather than causative risk.

    OBJECTIVE: To investigate the existence and nature of familial aggregation for the comorbidity of atopic diseases and depression or anxiety.

    METHODS: Participants came from the Childhood and Adolescent Twin Study in Sweden (CATSS), n= 14197. Current and ever asthma, eczema, hayfever and food-allergy were reported by parents. Internalizing disorders were identified using validated questionnaires. Familial co-aggregation analysis compared monozygotic MZ twins and same-sex dizygotic DZ twins for atopic disease in one twin with internalizing disorder in the other to test for genetic liability. Several familial liability candidates were also tested including parental education, recent maternal psychological stress, childhood family trauma and parental country of birth.

    RESULTS: Familial co-aggregation analysis found that if one twin had at least one current atopic disease the partner twin was at risk of having an internalizing disorder regardless of their own atopic status (Adjusted OR 1.22 (95% CI 1.08, 1.37). Similar results were found for each atopic disease ever and current. MZ associations were not higher than DZ associations suggesting that the liability is not genetic in nature. Including other familial candidates to the models made little difference to effect estimates.

    CONCLUSIONS AND CLINICAL RELEVANCE: Atopic diseases and depression or anxiety tend to occur together in families, therefore when treating for one disease the physician should consider comorbidity in both the individual and the individual's siblings. We did not find evidence to support a genetic explanation for comorbidity and further exploration is needed to disentangle the environmental and epigenetic reasons for familial aggregation.

  • 15.
    Broeker, Michael
    et al.
    Novartis Vaccines & Diagnost GmbH, Marburg, Germany.
    Bukovski, Suzana
    Univ Hosp Infect Dis Dr Fran Mihaljevic, Zagreb, Croatia.
    Culic, Davor
    Haemophilus & Meningococcus Reference Lab, Ctr Microbiol, Inst Publ Hlth, Srbija, Serbia.
    Jacobsson, Susanne
    Örebro University Hospital.
    Koliou, Maria
    Unit Surveillance & Control Communicable Dis, Minist Hlth, Nikosia, Cyprus.
    Kuusi, Markku
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Simoes, Maria Joao
    Inst Nacl Saude Dr Ricardo Jorge, Lisbon, Portugal.
    Skoczynska, Anna
    Natl Reference Ctr Bacterial Meningitis, Natl Med Inst, Warsaw, Poland.
    Toropainen, Maija
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Taha, Muhamed-Keir
    Invas Bacterial Infect Unit, Inst Pasteur, Paris, France.
    Tzanakaki, Georgina
    Natl Meningitis Reference Lab, Natl Sch Publ Hlth, Athens, Greece.
    Meningococcal serogroup Y emergence in Europe High importance in some European regions in 20122014In: Human Vaccines & Immunotherapeutics, ISSN 2164-5515, E-ISSN 2164-554X, Vol. 10, no 6, p. 1725-1728Article in journal (Refereed)
    Abstract [en]

    Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal. 1,2 Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low.

  • 16.
    Butwicka, Agnieszka
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden;.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden .
    Frisén, Louise
    Child and Adolescent Psychiatry Research Center, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Child and Adolescent Psychiatry Research Center, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States.
    Celiac disease is associated with childhood psychiatric disorders: A Population-Based Study2017In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 184, p. 87-93.e1, article id S0022-3476(17)30153-1Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine the risk of future childhood psychiatric disorders in celiac disease, assess the association between previous psychiatric disorders and celiac disease in children, and investigate the risk of childhood psychiatric disorders in siblings of celiac disease probands.

    STUDY DESIGN: This was a nationwide registry-based matched cohort study in Sweden with 10 903 children (aged <18 years) with celiac disease and 12 710 of their siblings. We assessed the risk of childhood psychiatric disorders (any psychiatric disorder, psychotic disorder, mood disorder, anxiety disorder, eating disorder, psychoactive substance misuse, behavioral disorder, attention-deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and intellectual disability). HRs of future psychiatric disorders in children with celiac disease and their siblings was estimated by Cox regression. The association between previous diagnosis of a psychiatric disorder and current celiac disease was assessed using logistic regression.

    RESULTS: Compared with the general population, children with celiac disease had a 1.4-fold greater risk of future psychiatric disorders. Childhood celiac disease was identified as a risk factor for mood disorders, anxiety disorders, eating disorders, behavioral disorders, ADHD, ASD, and intellectual disability. In addition, a previous diagnosis of a mood, eating, or behavioral disorder was more common before the diagnosis of celiac disease. In contrast, siblings of celiac disease probands were at no increased risk of any of the investigated psychiatric disorders.

    CONCLUSIONS: Children with celiac disease are at increased risk for most psychiatric disorders, apparently owing to the biological and/or psychological effects of celiac disease.

  • 17. Chiu Götlind, Y. Y.
    et al.
    Raghavan, S.
    Bland, P. W.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    CD4+FoxP3+ regulatory T cellsare functionally active in the Gαi2−/− mouse, but do not prevent thedevelopment of colitis2010Conference paper (Other academic)
  • 18.
    Davey, Dvora Joseph
    et al.
    Mozambique HIV care and treatment - Ark, Maputo, Mozambique; Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles CA, USA.
    Nhavoto, José Antonio
    Örebro University, Örebro University School of Business. Department of Mathematics and Informatics, Eduardo Mondlane University, Maputo, Mozambique.
    Augusto, Orvalho
    Department of Community Health, Eduardo Mondlane University, Maputo, Mozambique.
    Ponce, Walter
    Mozambique HIV care and treatment - Ark, Maputo, Mozambique.
    Traca, Daila
    Mozambique HIV care and treatment - Ark, Maputo, Mozambique.
    Nguimfack, Alexandre
    Mozambique HIV care and treatment - Ark, Maputo, Mozambique.
    de Sousa, Cesar Palha
    Department of Community Health, Eduardo Mondlane University, Maputo, Mozambique.
    SMSaude: Evaluating Mobile Phone Text Reminders to Improve Retention in HIV Care for Patients on Antiretroviral Therapy in Mozambique2016In: Journal of Acquired Immune Deficiency Syndromes, ISSN 1525-4135, E-ISSN 1944-7884, Vol. 73, no 2, p. E23-E30Article in journal (Refereed)
    Abstract [en]

    Objective: We evaluated whether regular mobile phone text reminders improved patients' retention in antiretroviral therapy (ART) care in Mozambique.

    Design: SMSaude was a randomized control trial of HIV-infected patients on ART who received regular text message reminder vs. standard of care at 3 public health facilities in Maputo Province, Mozambique. The primary outcome was retention in HIV care. Between November 2011 and March 2012, 830 eligible HIV-infected patients on ART were randomized 1: 1 to the text reminder intervention or standard of care.

    Methods: We used Kaplan-Meier estimators and log-rank tests to compare proportions of patients who received SMS reminders who were retained in HIV care compared to the control group who received standard of care. Post hoc analyses were performed using Cox proportional hazards models stratified by urban/rural facility and when initiated ART (<= 3 months vs. >3 months). Hazard ratios and confidence intervals (CIs) are reported. Analysis was with intention to treat.

    Results: Patients who received text messages had lower attrition from HIV care at 12 months, though the difference was nonsignificant (RR: 0.68, 95% CI: 0.41 to 1.13). Among urban patients, text messages improved retention in HIV care (RR: 0.54, 95% CI: 0.31 to 0.95). Intervention patients newly initiated on ART (<3 months) had lower attrition than control patients (HR: 0.54; 95% CI: 0.23 to 0.91), especially urban newly initiated patients (HR: 0.20, 95% CI: 0.06 to 0.64). Text messages had no effect on retention among rural patients.

    Conclusions: Text messages did not improve retention in HIV care for all patients on ART but improved retention in care of urban patients and those who recently started ART and received text reminders compared with standard of care.

  • 19.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden .
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Erratum to: Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, article id 36Article in journal (Refereed)
  • 20.
    Demirel, Isak
    et al.
    Örebro University, School of Medical Sciences.
    Persson, Alexander
    Örebro University, School of Medical Sciences.
    Brauner, Annelie
    Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Persson, Katarina
    Örebro University, School of Medical Sciences.
    Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells2018In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 8, article id 81Article in journal (Refereed)
    Abstract [en]

    The NLRP3 inflammasome and IL-1 beta release have recently been suggested to be important for the progression of urinary tract infection (UTI). However, much is still unknown regarding the interaction of UPEC and the NLRP3 inflammasome. The purpose of this study was to elucidate what virulence factors uropathogenic Escherichia coil (UPEC) use to modulate NLRP3 inflammasome activation and subsequent IL-1 beta release and the role of NLRP3 for UPEC colonization of bladder epithelial cells. The bladder epithelial cell line 5637, CRISPR/Cas9 generated NLRP3, caspase-1 and mesotrypsin deficient cell lines and transformed primary bladder epithelial cells (HBLAK) were stimulated with UPEC isolates and the non-pathogenic MG1655 strain. We found that the UPEC strain CFT073, but not MG1655, induced an increased caspase-1 activity and IL-1 beta release from bladder epithelial cells. The increase was shown to be mediated by et-hemolysin activation of the NLRP3 inflammasome in an NE-kappa B-independent manner. The effect of-hemolysin on IL-1 beta release was biphasic, initially suppressive, later inductive. Furthermore, the phase-locked type-1-fimbrial ON variant of CFT073 inhibited caspase-1 activation and IL-1 beta release. In addition, the ability of CFT073 to adhere to and invade NLRP3 deficient cells was significantly reduced compare to wild-type cells. The reduced colonization of NLRP3-deficient cells was type-1 fimbriae dependent. In conclusion, we found that the NLRP3 inflammasome was important for type-1 fimbriae-dependent colonization of bladder epithelial cells and that both type-1 fimbriae and alpha-hemolysin can modulate the activity of the NLRP3 inflammasome.

  • 21.
    El Marghani, Ahmed
    Örebro University, Department of Natural Sciences.
    Cell signaling in inflammatory diseases and development of antiinflammatory drugs2008Licentiate thesis, monograph (Other academic)
  • 22.
    Elgbratt, Kristina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Jansson, Andreas
    Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    A quantitative study of the mechanisms behind thymic atrophy in G alpha i2-deficient mice during colitis development2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 5, article id e36726Article in journal (Refereed)
    Abstract [en]

    Mice deficient for the G protein subunit G alpha i2 spontaneously develop colitis, a chronic inflammatory disease associated with dysregulated T cell responses. We and others have previously demonstrated a thymic involution in these mice and an aberrant thymocyte dynamics. The G alpha i2(-/-) mice have a dramatically reduced fraction of double positive thymocytes and an increased fraction of single positive (SP) thymocytes. In this study, we quantify a number of critical parameters in order to narrow down the underlying mechanisms that cause the dynamical changes of the thymocyte development in the G alpha i2(-/-) mice. Our data suggest that the increased fraction of SP thymocytes results only from a decreased number of DP thymocytes, since the number of SP thymocytes in the Gai2(-/-) mice is comparable to the control littermates. By measuring the frequency of T cell receptor excision circles (TRECs) in the thymocytes, we demonstrate that the number of cell divisions the G alpha i2(-/-) SP thymocytes undergo is comparable to SP thymocytes from control littermates. In addition, our data show that the mature SP CD4(+) and CD8(+) thymocytes divide to the same extent before they egress from the thymus. By estimating the number of peripheral TREC+ T lymphocytes and their death rate, we could calculate the daily egression of thymocytes. G alpha i2(-/-) mice with no/mild and moderate colitis were found to have a slower export rate in comparison to the control littermates. The quantitative measurements in this study suggest a number of dynamical changes in the thymocyte development during the progression of colitis.

  • 23. Eliasson, Henrik
    et al.
    Olcén, Per
    Sjöstedt, Anders
    Jurstrand, Margareta
    Bäck, Erik
    Örebro University, School of Health and Medical Sciences.
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences.
    Kinetics of the immune response associated with tularemia: comparison of an enzyme-linked immunosorbent assay, a tube agglutination test, and a novel whole-blood lymphocyte stimulation test2008In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 15, no 8, p. 1238-1243Article in journal (Refereed)
    Abstract [en]

    We have developed and evaluated a novel and simplified whole-blood lymphocyte stimulation assay that focuses on the measurement of gamma interferon after 24 h of stimulation with whole-cell tularemia antigen and a tularemia enzyme-linked immunosorbent assay (ELISA) based on highly purified lipopolysaccharide antigen. Comparison of the kinetics of the two assays and those of the traditional tube agglutination test shows that the cellular immune response can be detected earlier by the lymphocyte stimulation assay. This test already shows a high proportion of positive results during the first week after the onset of the disease, may be applicable in everyday laboratory practice, and has the potential of changing routine diagnostics for tularemia. The new ELISA has a high sensitivity and becomes positive to a high degree during the second week of disease. 

  • 24.
    Fant, F.
    et al.
    Department of Anesthesiology and Intensive Care, University Hospital, Örebro, Sweden.
    Tina, Elisabet
    Örebro University Hospital. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Research Centre.
    Sandblom, D.
    Department of Urology and the Health Academy, Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olof
    Department of Urology and the Health Academy, Örebro University Hospital, Örebro, Sweden.
    Magnuson, A.
    Clinical Epidemiology and Biostatistical Unit, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.
    Axelsson, Kjell
    Department of Anesthesiology and Intensive Care, University Hospital, Örebro, Sweden.
    Gupta, Anil
    Department of Anesthesiology and Intensive Care, University Hospital, Örebro, Sweden.
    Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy2013In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 110, no 5, p. 747-757Article in journal (Refereed)
    Abstract [en]

    Background: Epidural anaesthesia and analgesia has been shown to suppress the neurohormonal stress response, but its role in the inflammatory response is unclear. The primary aim was to assess whether the choice of analgesic technique influences these processes in patients undergoing radical retropubic prostatectomy.

    Methods: Twenty-six patients were randomized to Group P (systemic opioid-based analgesia) or Group E (thoracic epidural-based analgesia) perioperatively. Induction and maintenance of anaesthesia followed a standardized protocol. The following measurements were made perioperatively: plasma cortisol, glucose, insulin, C-reactive proteins, leucocyte count, plasma cytokines [interleukin (IL)-6, tumour necrosis factor (TNF)-alpha], and pokeweed mitogen-stimulated cytokines [interferon (IFN)-gamma, IL-2, IL-12p70, IL-10, IL-4, and IL-17]. Other parameters recorded were pain, morphine consumption, and perioperative complications.

    Results: Plasma concentration of cortisol and glucose were significantly higher in Group P compared with Group E at the end of surgery, the mean difference was 232 nmol litre(-1) [95% confidence interval (CI) 84-381] (P=0.004) and 1.6 mmol litre(-1) (95% CI 0.6-2.5) (P=0.003), respectively. No significant differences were seen in IL-6 and TNF-alpha at 24 h (P=0.953 and 0.368, respectively) and at 72 h (P=0.931 and 0.691, respectively). IL-17 was higher in Group P compared with Group E, both at 24 h (P=0.001) and 72 h (P=0.018) after operation. Pain intensity was significantly greater in Group P compared with Group E (P<0.05) up to 24 h.

    Conclusions: In this small prospective randomized study, thoracic epidural analgesia reduced the early postoperative stress response but not the acute inflammatory response after radical retrobupic prostatectomy, suggesting that other pathways are involved during the acute phase reaction.

  • 25.
    Fritsch Fredin, Maria
    et al.
    Astra-Zeneca, Mölndal.
    Hultin, Leif
    Astra-Zeneca, Mölndal.
    Hyberg, Gina
    Astra-Zeneca, Mölndal.
    Rehnström, Erika
    Astra-Zeneca, Mölndal.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences.
    Melgar, Silvia
    Astra-Zeneca, Mölndal.
    Jansson, Liselotte
    Astra-Zeneca, Mölndal.
    Predicting and monitoring colitis development in mice by micro-computed tomography2008In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 4, p. 491-499Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Computed tomography (CT) has been developed as a tool for monitoring human inflammatory bowel disease (IBD). The aim of this study was to evaluate colon wall thickness as a noninvasive marker in the dextran sodium sulfate (DSS) mouse model of colitis using micro-CT. METHODS: Mice were examined by micro-CT 1, 2, or 4 times between day 0 (d0) and d26 after induction of colitis to document the kinetics of changes in colon wall thickness and its relation to colitis development. RESULTS: DSS-treated mice displayed a significantly thicker colon wall at all timepoints (days 5, 8, 12, 19, and 26) investigated compared to healthy controls. Colon wall thickness showed a good correlation to the macroscopic grading of colitis (r = 0.81). The increase in colon wall thickness occurred mainly during the acute phase of colitis (between days 5 and 12) and did not progress much further in the chronic phase of colitis (d26). Colon wall thickness at d26 was thereby predicted by measurements at d12. All mice did not respond equally to DSS and this difference was manifest during the first 2 weeks of colitis, providing an important tool in stratifying responders from nonresponders. CONCLUSIONS: While the potential impact of handling and anesthesia should be considered on repeated micro-CT, irradiation exposure during repeated micro-CT did not affect the development of colitis. Thus, the results suggest that micro-CT can be used for monitoring and prediction of the inflammatory response in mouse colitis in future therapeutic studies.

  • 26.
    Gasperov, Nina Milutin
    et al.
    Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
    Farkas, Sanja A.
    Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences, Unit of Clinical Chemistry, Umeå University, Umeå, Sweden.
    Grce, Magdalena
    Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
    Epigenetic activation of immune genes in cervical cancer2014In: Immunology Letters, ISSN 0165-2478, E-ISSN 1879-0542, Vol. 162, no 2, p. 256-257Article in journal (Refereed)
    Abstract [en]

    Immune system provides us protection from infectious pathogens and tumors formation during lifetime. Cervical cancer (CC), and its cause, human papillomavirus (HPV) are both challenges for the immune system. We present here evidence of epigenetic activation of immune system genes in CC. Illumina Infinium Human Methylation 450 K BeadChip identified genes, which were all significantly hypomethylated in CC tissue versus normal tissue. The GeneMANIA computer program identified a tight network between those genes. The most strongly correlated genes based on their function are immune effectors' process (AIM2, BST2, BTN3A3, and IL12RB1) and response to virus related genes (AIM2, BST2, and IL12RB1). Thus, activation of those genes through demethylation is probably triggered by HPV oncogenes. In conclusion, the immune system of women who do not develop CC is probably activated earlier through DNA demethylation.

  • 27.
    Golparian, Daniel
    et al.
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Analytical specificity and sensitivity of the novel dual-target GeneProof Neisseria gonorrhoeae PCR kit for detection of N-gonorrhoeae2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 11, p. 955-958Article in journal (Refereed)
    Abstract [en]

    Detection of Neisseria gonorrhoeae relies increasingly on nucleic acid amplification tests (NAATs). The specificity of many gonococcal NAATs has been suboptimal and supplementary testing remains recommended in Europe and several additional countries. The novel dual-target GeneProofNeisseria gonorrhoeae PCR kit, targeting porA pseudogene and 16S rRNA gene, showed a high specificity and sensitivity when isolates of non-gonococcal Neisseria and related species (n=144), and gonococci (n=104) were tested. However, rare gonococcal porA mutants were only detected in the 16S rRNA gene target and two non-gonococcal isolates showed a low-level cross-reactivity in the 16S rRNA gene target. The detection limit for both targets was 1.5 copies per reaction.

  • 28.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ghiboub, M.
    Frenche Comte Univ, Besancon, France.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    The role of IL-37 on cytokine responses downstream of TLR4 and TLR5 signalling in intestinal epithelial cells2014In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 143, p. 94-95Article in journal (Other academic)
  • 29.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Institute of Infection, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Tysk, Curt
    Örebro University Hospital. Division of Gastroenterology, Department of Medicine, Örebro University, Örebro, Sweden.
    Hultgren, Olof
    Örebro University Hospital.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment2015In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 132458Article in journal (Refereed)
    Abstract [en]

    Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX(3)CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX(3)CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses.

  • 30. Göranzon, C.
    et al.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Kumawat, Ashok Kumar
    Halfvarson, Jonas
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Eriksson, J.
    Bohr, J.
    Nyhlin, Nils
    Immunohistokemisk karakterisering av lymfocyter vid microscopisk kolit2011In: Gastrokuriren, ISSN 1651-0453, Vol. 16, no 29, p. PO16-PO16Article in journal (Other academic)
  • 31. Göranzon, C.
    et al.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Kumawat, Ashok Kumar
    Halfvarson, Jonas
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Eriksson, S.
    Bohr, Johan
    Nyhlin, Nils
    Immunohistochemical characterization of lymphocytes in microscopic colitis2010Conference paper (Other academic)
  • 32.
    Günaltay, Sezin
    Örebro University, School of Medical Sciences.
    Dysregulated mucosal immune responses in microscopic colitis patients2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC) is a common cause of chronic watery diarrhea. The diagnosis relies on typical histopathological changes observed upon microscopic examination. The studies in this thesis investigated innate and adaptive immune responses in the colonic mucosa of MC patients, also comparing patients with active disease (CC and LC) and histopathologically in remission (CC/LC-HR). We first analyzed expression of interleukin-1/Toll-like receptor (IL-1/TLR) signaling regulators in MC patients (Paper I). Our results showed enhanced IRAK-M, microRNA-146a, -155 and -21 expressions, whereas IL-37 gene expression was reduced in CC and LC patients as compared to non-inflamed controls. These results suggest different pathophysiological mechanisms in MC patients. The mixed inflammatory cell infiltrations seen in the lamina propria of MC patients might be a result of dysregulated expression of chemotactic mediators. In Paper II, we showed that MC patients display mainly an increased expression of chemokines and chemokine receptors in active disease as compared to noninflamed controls. In Paper III, we examined if the decreased IL-37 expression seen in Paper I could mediate the upregulation of chemokines seen in Paper II. We showed that a relatively small reduction in the ability of epithelial cells to produce IL-37 results in mainly increased chemokine expressions in a pattern similar to the findings in Paper II. In order to understand the nature of infiltrating T cells commonly observed in MC patients, we analyzed the T cell receptor (TCR) β chains in colonic biopsies of MC patients (Paper IV). Our results showed significant differences in TCRβ repertoire, which suggests selectively expanded T cell clones in active MC and histopathologically in remission patients. Altogether, these results i) increase the knowledge of MC pathogenesis by showing changes in TLR signaling regulators, enhanced chemokine and their receptor expressions involved in a mixed immune cell infiltrations and selectively expanded T cell clones in CC and LC patients, as well as in histopathological remission ii) might potentially increase the possibility of more target-specific therapies based on IL-37 induction, chemokines or chemokine receptor inhibitions, or hindering T cell infiltration according to TCR clonality.

    List of papers
    1. Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis
    Open this publication in new window or tab >>Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis
    Show others...
    2014 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 34, p. 12249-12259Article in journal (Refereed) Published
    Abstract [en]

    AIM: To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients.

    METHODS: Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction.

    RESULTS: IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001).

    CONCLUSION: The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

    Place, publisher, year, edition, pages
    WJG Press, 2014
    Keywords
    Interleukin-37, MicroRNA, Lymphocytic colitis, Collagenous colitis, Ulcerative colitis
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-37676 (URN)10.3748/wjg.v20.i34.12249 (DOI)000341719100033 ()2-s2.0-84909606787 (Scopus ID)
    Note

    Funding Agencies:

    Research Committee of Örebro County Council

    Örebro University

    Available from: 2014-10-13 Created: 2014-10-13 Last updated: 2018-06-10Bibliographically approved
    2. Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment
    Open this publication in new window or tab >>Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment
    Show others...
    2015 (English)In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 132458Article in journal (Refereed) Published
    Abstract [en]

    Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX(3)CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX(3)CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses.

    National Category
    Cell and Molecular Biology Immunology in the medical area
    Research subject
    Immunology
    Identifiers
    urn:nbn:se:oru:diva-44605 (URN)10.1155/2015/132458 (DOI)000353128700001 ()2-s2.0-84928473938 (Scopus ID)
    Note

    Funding Agencies:

    Örebro University Hospital Research Foundation (Nyckelfonden)

    Research Committee, Orebro County Council

    Örebro University

    Available from: 2015-05-12 Created: 2015-05-12 Last updated: 2018-06-30Bibliographically approved
    3. Reduced Il-37 production increases the spontaneous chemokine expressions in colon epithelial cells
    Open this publication in new window or tab >>Reduced Il-37 production increases the spontaneous chemokine expressions in colon epithelial cells
    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Basic Medicine
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-47897 (URN)
    Available from: 2016-02-02 Created: 2016-02-02 Last updated: 2018-01-10Bibliographically approved
    4. Oligoclonal T cell receptor repertoire in colonic biopsies of microscopic and ulcerative colitis patients
    Open this publication in new window or tab >>Oligoclonal T cell receptor repertoire in colonic biopsies of microscopic and ulcerative colitis patients
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Basic Medicine
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-47898 (URN)
    Available from: 2016-02-02 Created: 2016-02-02 Last updated: 2018-01-10Bibliographically approved
  • 33.
    Hadad, Ronza
    et al.
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, , Örebro University Hospital, Örebro, Sweden.
    Lagos, Amaya C.
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Ljungberg, Johan
    Department of Infectious Diseases, Hospital of Halmstad, Halmstad, Sweden.
    Nilsson, Peter
    Department of Clinical Microbiology & Infection Control, Hospital of Halmstad, Halmstad, Sweden.
    Jensen, Jörgen S.
    Department of Microbiology and Infection Control, Sexually Transmitted Infections, Research and Development, Statens Serum Institut, Copenhagen, Denmark.
    Fredlund, Hans
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Macrolide and fluoroquinolone resistance in Mycoplasma genitalium in two Swedish counties, 2011-20152018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 2, p. 123-127Article in journal (Refereed)
    Abstract [en]

    Mycoplasma genitalium, causing non-gonococcal non-chlamydial urethritis and associated with cervicitis, has developed antimicrobial resistance (AMR) to both the macrolide azithromycin (first-line treatment) and the fluoroquinolone moxifloxacin (second-line treatment). Our aim was to estimate the prevalence of resistance, based on genetic AMR determinants, to these antimicrobials in the M. genitalium population in two Swedish counties, Örebro and Halland, 2011-2015. In total, 672 M. genitalium positive urogenital samples were sequenced for 23S rRNA and parC gene mutations associated with macrolide and fluoroquinolone resistance, respectively. Of the samples, 18.6% and 3.2% in Örebro and 15.2% and 2.7% in Halland contained mutations associated with macrolide and fluoroquinolone resistance, respectively. The predominating resistance-associated mutations in the 23S rRNA gene was A2059G (n = 39) in Örebro and A2058G (n = 13) and A2059G (n = 13) in Halland. The most prevalent possible resistance-associated ParC amino acid alterations were S83I (n = 4) in Örebro and S83N (n = 2) in Halland. Resistance-associated mutations to both macrolides and fluoroquinolones were found in 0.7% of samples. Our findings emphasize the need for routine AMR testing, at a minimum for macrolide resistance, of all M. genitalium-positive samples and regular national and international surveillance of AMR in M. genitalium, to ensure effective patient management and rational antimicrobial use.

  • 34.
    Hadad, Ronza
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Pizza, Mariagrazia
    Novartis V&D, Siena, Italy.
    Rappuoli, Rino
    Novartis V&D, Siena, Italy.
    Fredlund, Hans
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Novel meningococcal 4CMenB vaccine antigens - prevalence and polymorphisms of the encoding genes in Neisseria gonorrhoeae2012In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 9, p. 750-760Article in journal (Refereed)
    Abstract [en]

    The first cross-protective Neisseria meningitidis vaccine (focus on serogroup B), the protein-based 4 component meningococcus serogroup B (4CMenB), includes the New Zealand outer membrane vesicle and three main genome-derived neisserial antigens (GNAs). These GNAs are fHbp (fused to GNA2091), NHBA (fused to GNA1030) and NadA. In this study, the prevalence and polymorphisms of the nucleotide and amino acid sequences of the 4CMenB antigens in a temporally and geographically diverse collection of N. gonorrhoeae isolates (n similar to=similar to 111) were investigated. All the examined GNA genes, except the nadA gene, were present in all gonococcal isolates. However, 25 isolates contained premature stop codons in the fHbp gene and/or the nhba gene, resulting in truncated proteins. Compared with the 4CMenB antigen sequences in reference strain MC58, the gonococcal strains displayed 67.095.4% and 60.994.9% identity in nucleotide sequence and amino acid sequence, respectively, in the equivalent GNA antigens. The absence of NadA, lack of universal expression of fHbp and NHBA and the uncertainty regarding the surface exposure of fHbp as well as the function of NHBA in N. gonorrhoeae will likely limit the use of the identical 4CMenB antigens in a gonococcal vaccine. However, possible cross-immunity of 4CMenB with gonococci and expression and function of the equivalent gonococcal GNAs, as well as of more appropriate GNAs for a gonococcal vaccine, need to be further examined.

  • 35.
    Hadad, Ronza
    et al.
    Örebro Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Marks, Ellen
    Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Kalbina, Irina
    Örebro University, School of Science and Technology. Örebro Life Science Center, Örebro University, Örebro, Sweden.
    Schön, Karin
    Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Lycke, Nils
    Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology. Örebro Life Science Center, Örebro University, Örebro, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Protection against genital tract Chlamydia trachomatis infection following intranasal immunization with a novel recombinant MOMP VS2/4 antigen2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, p. 1078-1086Article in journal (Refereed)
    Abstract [en]

    The asymptomatic nature of most Chlamydia trachomatis infections and the lack of appropriate effects by current prevention and management call for vaccine development. We evaluated a recombinant subunit vaccine candidate based on the major outer membrane protein variable segments 2 and 4 (MOMP VS2/4). To achieve maximal immunogenicity and ease of production and purification, MOMP VS2/4 was constructed by using highly immunogenic sequences of MOMP only, thereby minimizing the presence of hydrophobic regions, and spacing the immunogenic epitopes with a flexible amino acid sequence. A purification tag was also added. The MOMP VS2/4 was given intranasally, with or without intravaginal boost, with cholera toxin (CT) adjuvant to C57BL/6 mice, which were screened for immunogenicity and protection against a live challenge infection with C. trachomatis serovar D. Bacterial shedding, cell-mediated responses, and antibody responses were monitored. Immunized mice exhibited significantly less bacterial shedding and were better protected against infertility as compared to unimmunized control mice. Immunizations stimulated both systemic and local specific antibody (IgG1, IgG2c, and IgA) responses, and primed T cells that produced interferon-c and interleukins 13 and 17 upon challenge with recall antigen. Thus, MOMP VS2/4, in combination with CT adjuvant, stimulated Th1, Th2, and Th17 effector cells, and generated protective immunity associated with less pathology. We regard MOMP VS2/4 as a promising candidate for further development into a mucosal chlamydial vaccine.

  • 36.
    Hahn-Strömberg, Victoria
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Section for Pathology, Örebro University Hospital, Örebro, Sweden.
    Askari, Shlear
    Department of Laboratory Medicine, Section for Pathology, Örebro University Hospital, Örebro, Sweden.
    Befekadu, Rahel
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Section for Pathology, Örebro University Hospital, Örebro, Sweden.
    Matthiessen, Peter
    Örebro University Hospital. Department of Clinical Surgery, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Sune
    Örebro University, Örebro University School of Business.
    Nilsson, Torbjorn K.
    Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
    Polymorphisms in the CLDN1 and CLDN7 genes are related to differentiation and tumor stage in colon carcinoma2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 7, p. 636-642Article in journal (Refereed)
    Abstract [en]

    Tight junction is composed of transmembrane proteins important for maintaining cell polarity and regulating ion flow. Among these proteins are the tissue-specific claudins, proteins that have recently been suggested as tumor markers for several different types of cancer. An altered claudin expression has been observed in colon, prostatic, ovarian, and breast carcinoma. The aim of this study was to analyze the allele frequencies of three common single nucleotide polymorphisms (SNPs) in the genes for claudin 1 and claudin 7 in colon cancer (CC) patients and in a control population of healthy blood donors. Pyrosequencing was used to genotype the CLDN1 SNP rs9869263 (c.369C>T), and the CLDN7 SNPs rs4562 (c.590C>T) and rs374400 (c.606T>G) in DNA from 102 formalin fixed paraffin embedded (FFPE) colon cancer tissue, and 111 blood leukocyte DNA from blood/plasma donors. These results were correlated with clinical parameters such as TNM stage, tumor localization, tumor differentiation, complexity index, sex, and age. We found that there was a significant association between the CLDN1 genotype CC in tumor samples and a higher risk of colon cancer development (OR 3.0, p < 0.001). We also found that the CLDN7 rs4562 (c.590C>T) genotype CT had a higher risk of lymph node involvement (p = 0.031) and a lower degree of tumor differentiation (p = 0.028). In the control population, the allele frequencies were very similar to those in the HapMap cohort for CLDN7. The CLDN1 rs9869263 genotype (c.369C>T) was related to increased risk of colon cancer, and the CLDN7 rs4562 genotype (c.590C>T) was related to tumor differentiation and lymph node involvement in colon carcinoma. Further studies are warranted to ascertain their potential uses as biomarkers predicting tumor development, proliferation, and outcome in this disease.

  • 37.
    Hamad, Tarza
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University, Örebro, Sweden; Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University, Örebro, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Department of Infectious Diseases, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University, Örebro, Sweden.
    Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections, with focus on doxycycline2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 12, p. 1055-1060Article in journal (Refereed)
    Abstract [en]

    In recent years, coagulase-negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S.epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety-three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty-two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S.epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin.

  • 38.
    Hansson, Charlotta
    et al.
    Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Schön, Karin
    Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital. Sch Sci & Technol, Orebro Life Sci Ctr, Univ Orebro, Orebro, Sweden; Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden .
    Bokarewa, Maria I.
    Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
    Lycke, Nils Y.
    Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Feeding transgenic plants that express a tolerogenic fusion protein effectively protects against arthritis2016In: Plant Biotechnology Journal, ISSN 1467-7644, E-ISSN 1467-7652, Vol. 14, no 4, p. 1106-1115Article in journal (Refereed)
    Abstract [en]

    Although much explored, oral tolerance for treatment of autoimmune diseases still awaits the establishment of novel and effective vectors. We investigated if the tolerogenic CTA1(R7K)-COL-DD fusion protein can be expressed in edible plants and in this way induce oral tolerance and protect against arthritis. The fusion protein was recombinantly expressed in Arabidopsis thaliana plants, which were fed to H-2q restricted DBA/1 mice to assess the preventive effect on collagen-induced arthritis (CIA). The treatment resulted in fewer mice exhibiting disease and arthritis scores were significantly reduced. Immune suppression was evident in treated mice and serum biomarkers for inflammation as well as anti-collagen IgG responses were reduced. In spleen draining and lymph nodes, CD4+ T cell responses were reduced. Concomitant with a reduced effector T cell activity with lower IFNg, IL-13 and IL-17A production we observed an increase in IL-10 production to recall antigen stimulation in vitro, suggesting reduced Th1, Th2 and Th17 activity subsequent to upregulated IL-10 and regulatory T cell (Treg) functions. The present study shows that edible plants expressing a tolerogen were effective at stimulating CD4 T cell tolerance and in protecting against CIA disease. Our study conveys optimism as to the potential of using edible plants for oral treatment of rheumatoid arthritis.

  • 39. He, T.
    et al.
    Venema, K.
    Priebe, M. G.
    Welling, G. W.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    Vonk, R. J.
    The role of colonic metabolism in lactose intolerance2008In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 38, no 8, p. 541-547Article in journal (Refereed)
    Abstract [en]

    Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.

  • 40.
    Hederos, Carl-Axel
    et al.
    Primary Care Research Unit, Karlstad, Sweden; Karolinska Institute, Astrid Lindgrens Children's Hospital, Stockholm, Sweden; Primary Care Research Unit, BUM VC Gripen, Karlstad, Sweden.
    Hasselgren, Mikael
    Section of Family Medicine and Clinical Epidemiology, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Hedlin, Gunilla
    Karolinska Institute, Astrid Lindgrens Children's Hospital, Stockholm, Sweden.
    Bornehag, Carl-Gustaf
    Division for Public Health, Department of Social Sciences, Karlstad University, Karlstad, Sweden; Swedish National Testing and Research Institute, Borås, Sweden; International Centre for Indoor Environment and Energy, Technical University of Denmark, Copenhagen, Denmark.
    Comparison of clinically diagnosed asthma with parental assessment of children's asthma in a questionnaire2007In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 18, no 2, p. 135-141Article in journal (Refereed)
    Abstract [en]

    Epidemiological evaluations of the prevalence of asthma are usually based on written questionnaires (WQs) in combination with validation by clinical investigation. In the present investigation, we compared parental assessment of asthma among their preschool children in response to a WQ with the corresponding medical records in the same region. An International Study of Asthma and Allergies in Childhood (ISAAC)-based WQ was answered by 75% of the parents of 6295 children aged 1-6 yr. Clinically diagnosed asthma, recorded in connection with admissions to the hospital or a visit to any of the outpatient clinics in the same region, were analysed in parallel. Finally, a complementary WQ was sent to the parents of children identified as asthmatic by either or both of this approaches. In response to the WQ 5.9% were claimed to suffer from asthma diagnosed by a doctor. According to the medical records, the prevalence of clinically diagnosed asthma was 4.9%. The estimated prevalence among children requiring treatment for their asthma was 4.4%. The sensitivity of the WQ was 77%, the specificity 97.5%. In the 1-2 yr age group the sensitivity was only 22%. This WQ was able to identify 54% of the children with a medical record of asthma. Forty percent of the children claimed by their parents to be asthmatic had no medical record of asthma. An ISAAC-based parentally completed WQ provided an acceptable estimation of the prevalence of asthma in children 2-6 yr of age, although only half of the individual patients identified in this manner are the same as those identified clinically.

  • 41.
    Hesselmark, Eva
    et al.
    Center for Psychiatry Research, Department of clinical neuroscience, Karolinska Institutet, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden; University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Bejerot, Susanne
    Örebro University, School of Medical Sciences. Center for Psychiatry Research, Department of clinical neuroscience, Karolinska Institutet, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden; University Health Care Research Center, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Biomarkers for diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS): Sensitivity and specificity of the Cunningham Panel2017In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 312, p. 31-37Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Pediatric Acute Neuropsychiatric Syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are conditions marked by sudden onset of obsessive-compulsive disorder (OCD), tics, or avoidant/restrictive food intake in combination with multiple psychiatric symptoms. A diagnosis of PANS or PANDAS may be supported by the Cunningham Panel, a commercially available set of immunologic assays currently in clinical use. However, the relationship between Cunningham Panel results and patient symptoms remains unclear. This study was done to assess the diagnostic accuracy of the Cunningham Panel in patients with suspected PANS or PANDAS.

    METHOD: All Swedish patients who had taken the Cunningham Panel prior to June 2014 (n=154) were invited and 53 patients participated in the study. Based on comprehensive psychiatric assessment (the reference standard of diagnosis), subjects were classified as PANS, PANDAS, or neither. Prior Cunningham Panel test results were collected from patient records, and new blood samples were similarly analyzed within the scope of this study. In addition, results were compared to healthy controls (n=21) and a test-retest reliability analysis was performed.

    RESULTS: Sensitivities of individual biomarkers in the Cunningham Panel ranged from 15 to 60%, and specificities from 28 to 92%. Positive predictive values ranged from 17 to 40%, and negative predictive values from 44 to 74%. A majority of the healthy controls had pathological Cunningham Panel results and test-retest reliability proved insufficient.

    CONCLUSION: Clinical use of the Cunningham Panel in diagnosing PANS or PANDAS is not supported by this study.

  • 42.
    Hesselmark, Eva
    et al.
    Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bejerot, Susanne
    Örebro University, School of Medical Sciences. University Health Care Research Center, Region Örebro County, Örebro, Sweden.
    Corrigendum to Biomarkers for diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS): Sensitivity and specificity of the Cunningham Panel [J. Neuroimmunol. 312. (2017) 31-37]2017In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 313, p. 116-117Article in journal (Refereed)
  • 43.
    Holmberg, K
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Neuropediatric unit, Sachs’ Children and Youth Hospital, South General Hospital, Stockholm, Sweden.
    Lundholm, C
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Anckarsäter, H
    Institute of Neuroscience and Physiology, Forensic Psychiatry, University of Gothenburg, Gothenburg, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, C
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Lung and allergy unit, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Impact of asthma medication and familial factors on the association between childhood asthma and attention-deficit/hyperactivity disorder: a combined twin- and register-based study2015In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, no 5, p. 964-973Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Asthma and attention-deficit/hyperactivity disorder (ADHD) are prevalent in childhood and may cause functional impairment and stress in families. Previous research supports an association between asthma and ADHD in children, but several aspects of this relationship are unclear.

    OBJECTIVE: Our aim was to study whether the association between asthma and ADHD is restricted to either the inattentive or the hyperactive/impulsive symptoms of ADHD, to explore the impact of asthma severity and asthma medication and the contribution of shared genetic and environmental risk factors on the asthma-ADHD relationship.

    METHODS: Data on asthma, ADHD, zygosity and possible confounders were collected from parental questionnaires at 9 or 12 years on 20 072 twins through the Swedish Twin Register, linked to the Swedish Medical Birth Register, the National Patient Register and the Prescribed Drug Register. The association between asthma and ADHD, the impact of asthma severity and medication, was assessed by generalized estimating equations. Cross-twin-cross-trait correlations (CTCT) were estimated to explore the relative importance of genes and environment for the association.

    RESULTS: Asthmatic children had a higher risk of also having ADHD [odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16-2.02]. The association was not restricted to either of the two dimensions of ADHD. The magnitude of the association increased with asthma severity (OR 2.84, 95% CI: 1.86-4.35) for ≥ 4 asthma attacks in the last 12 months and was not affected by asthma treatment. The CTCTs possibly indicate that the genetic component in overlap of the disorders is weak.

    CONCLUSIONS AND CLINICAL RELEVANCE: Childhood asthma, especially severe asthma, is associated with ADHD. Asthma medication seems not to increase the risk of ADHD. Clinicians should be aware of the potential of ADHD in asthma. Optimal asthma care needs to be integrated with effective evaluation and treatment of ADHD in children with co-existing disorders.

  • 44.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Medicine, Örebro University, Sweden.
    The mucosal immune system in microscopic colitis2012In: Microscopic colitis / [ed] S. Miehlke, A. Münich, Basel: S. Karger, 2012, p. 33-39Conference paper (Other academic)
  • 45.
    Isaksson, Helena S.
    et al.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Farkas, Sanja A.
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Müller, Patrick
    Affymetrix core facility at Novum, BEA, Karolinska Institute, Huddinge, Sweden.
    Gustafsson, Dan
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsson, Torbjörn, K.
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Whole genome microarray expression analysis in blood leucocytes identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia2018In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 191, no 2, p. 240-251Article in journal (Refereed)
    Abstract [en]

    A child, 2 years with the "hypercalprotectinemia with hyperzincemia" clinical syndrome presented with atypical symptoms and signs, notably persistent fever of around 38°C, thrombocythaemia of >700 x 10(9) /L, and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analyzed whole-genome mRNA expression by the Affymetrix HG U133 PLUS 2.0 array on three occasions 3 to 5 months apart. Major upregulation was demonstrated for the JAK/STAT pathway including in particular CD177, S100A8, S100A9, and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors, and activators, accounting for the febrile apathic state; and the HMBG1 gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic workup of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways.

  • 46.
    Jacobsson, Susanne
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Neisseria meningitidis, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Neisseria meningitidis, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Hedberg, Sara Thulin
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Neisseria meningitidis carriage in Swedish teenagers associated with the serogroup W outbreak at the World Scout Jamboree, Japan 20152018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 4, p. 337-341Article in journal (Refereed)
    Abstract [en]

    The aims of the study were to estimate the carrier state of Neisseria meningitidis in Swedish teenagers and its association with an outbreak at the World Scout Jamboree in 2015 as well as to compare sensitivity of throat versus nasopharyngeal swab for optimal detection of carriage. In total, 1 705 samples (cultures n = 32, throat swabs n = 715, nasopharyngeal swabs n = 958) from 1 020 Jamboree participants were collected and sent to the National Reference Laboratory for Neisseria meningitidis for culture and molecular analysis. The overall positivity for N. meningitidis was 8% (83/1 020), whereas 2% (n = 22) belonged to a known sero/genogroup while the majority (n = 61) were non-groupable. Throat sample is clearly the sampling method of choice, in 56 individuals where both throat and nasopharynx samples were taken, N. meningitidis was detected in both throat and nasopharynx in eight individuals, in 46 individuals N. meningitidis was only detected in the throat and in two individuals only in the nasopharynx. Carriage studies are important to provide knowledge of the current epidemiology and association between carrier isolates and disease-causing isolates in a given population. Therefore, planning for a carriage study in Sweden is in progress.

  • 47.
    Jayaprakash, Kartheyaene
    et al.
    Örebro University, School of Medical Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Gunaltay, Sezin
    Örebro University, School of Medical Sciences.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Bengtsson, Torbjörn
    Örebro University, School of Medical Sciences.
    PKC, ERK/p38 MAP kinases and NF-B targeted signalling play a role in the expression and release of IL-1β  and CXCL8 in Porphyromonas gingivalis-infected THP1 cells2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 7, p. 623-633Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis is a keystone pathogen in periodontitis and is gaining importance in cardiovascular pathogenesis. Protease-activated receptors (PARs), toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) on monocytes recognize the structural components on P. gingivalis, inducing inflammatory intermediates. Here, we elucidate the modulation of PARs, TLRs, NODs, and the role of MAPK and NF-B in IL-1 and CXCL8 release. THP1 cells were stimulated with P. gingivalis wild-type W50 and its isogenic gingipain mutants: Rgp mutant E8 and Kgp mutant K1A. We observed modulation of PARs, TLRs, NOD, IL-1 and CXCL8 expression by P. gingivalis. Gingipains hydrolyse IL-1 and CXCL8, which is more evident for IL-1 accumulation at 24 h. Inhibition of PKC (protein kinase C), p38 and ERK (extracellular signal-regulated kinases) partially reduced P. gingivalis-induced IL-1 at 6 h, whereas PKC and ERK reduced CXCL8 at both 6 and 24 h. Following NF-B inhibition, P. gingivalis-induced IL-1 and CXCL8 were completely suppressed to basal levels. Overall, TLRs, PARs and NOD possibly act in synergy with PKC, MAPK ERK/p38 and NF-B in P. gingivalis-induced IL-1 and CXCL8 release from THP1 cells. These pro-inflammatory cytokines could affect leucocytes in circulation and exacerbate other vascular inflammatory conditions such as atherosclerosis.

  • 48.
    Jayaprakash, Kartheyaene
    et al.
    Department of Medical Sciences, Örebro University, Örebro, Sweden.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Bengtsson, Torbjörn
    Örebro University, School of Medical Sciences.
    Porphyromonas gingivalis-induced inflammatory responses in THP1 cells are altered by native and modified low-density lipoproteins in a strain-dependent manner2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 8, p. 667-677Article in journal (Refereed)
    Abstract [en]

    Strong epidemiological evidence supports an association between cardiovascular and periodontal disease and furthermore, the periodontopathogen Porphyromonas gingivalis has been identified in blood and from atheromatous plaques. Blood exposed to P.gingivalis shows an increased protein modification of low-density lipoprotein (LDL). In this study, we investigate the inflammatory responses of THP1 cells incubated with P.gingivalis and the effects of native or modified LDL on these responses. Reactive oxygen species (ROS) and IL-1 were observed in THP1 cells following infection with P.gingivalis ATCC33277 and W50. Caspase 1 activity was quantified in THP1 cells and correlated with IL-1 accumulation. Oxidized LDL (oxLDL) induced IL-1 release and CD36 expression on THP1 cells. Modified LDL co-stimulated with ATCC33277 exhibited regulatory effects on caspase 1 activity, IL-1 release and CD36 expression in THP1 cells, whereas W50 induced more modest responses in THP1 cells. In summary, we show that P.gingivalis is capable of inducing pro-inflammatory responses in THP1 cells, and native and modified LDL could alter these responses in a dose- and strain-dependent manner. Strain-dependent differences in THP1 cell responses could be due to the effect of P.gingivalis proteases, presence or absence of capsule and proteolytic transformation of native and modified LDL.

  • 49.
    Johansson, Karin
    et al.
    Department of Laboratory Medicine, Molecular Diagnostics, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Hanna
    Department of Laboratory Medicine, Molecular Diagnostics, Örebro University Hospital, Örebro, Sweden.
    Norén, Torbjörn
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Clostridium difficile infection diagnostics: evaluation of the C. DIFF Quik Chek Complete assay, a rapid enzyme immunoassay for detection of toxigenic C. difficile in clinical stool samples2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 11, p. 1016-1020Article in journal (Refereed)
    Abstract [en]

    Diagnostic testing for Clostridium difficile infection (CDI) has, in recent years, seen the introduction of rapid dual-EIA (enzyme immunoassay) tests combining species-specific glutamate dehydrogenase (GDH) with toxin A/B. In a prospective study, we compared the C. DIFF Quik Chek Complete test to a combination of selective culture (SC) and loop-mediated isothermal amplification (LAMP) of the toxin A gene. Of 419 specimens, 68 were positive in SC including 62 positive in LAMP (14.7%). The combined EIA yielded 82 GDH positives of which 47 were confirmed toxin A/B positive (11%) corresponding to a sensitivity and specificity of 94% for GDH EIA compared to SC and for toxin A/B EIA a sensitivity of 71% and a specificity of 99% compared to LAMP. Twenty different PCR ribotypes were evenly distributed except for UK 081 where only 25% were toxin A/B positive compared to LAMP. We propose a primary use of a combined GDH toxin A/B EIA permitting a sensitive 1-h result of 379 of 419 (90%, all negatives plus GDH and toxin EIA positives) referred specimens. The remaining 10% being GDH positive should be tested for toxin A/B gene on the same day and positive results left to a final decision by the physician.

  • 50.
    Jönsson, Agnez
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Foerster, Sunniva
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden; Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hamasuna, Ryoichi
    Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Lindberg, Magnus
    Örebro University, School of Medical Sciences. Department of Dermatovenerology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Jensen, Jörgen Skov
    Department of Microbiology and Infection Control, Sexually Transmitted Infections, Research and Development, Statens Serum Institut, Copenhagen, Denmark.
    Ohnishi, Makoto
    Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    In vitro activity and time-kill curve analysis of sitafloxacin against a global panel of antimicrobial-resistant and multidrug-resistant Neisseria gonorrhoeae isolates2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 1, p. 29-37Article in journal (Refereed)
    Abstract [en]

    Treatment of gonorrhoea is a challenge worldwide because of emergence of resistance in N. gonorrhoeae to all therapeutic antimicrobials available and novel antimicrobials are imperative. The newer-generation fluoroquinolone sitafloxacin, mostly used for respiratory tract infections in Japan, can have a high in vitro activity against gonococci. However, only a limited number of recent antimicrobial-resistant isolates from Japan have been examined. We investigated the sitafloxacin activity against a global gonococcal panel (250 isolates cultured in 1991-2013), including multidrug-resistant geographically, temporally and genetically diverse isolates, and performed time-kill curve analysis for sitafloxacin. The susceptibility to sitafloxacin (agar dilution) and seven additional therapeutic antimicrobials (Etest) was determined. Sitafloxacin was rapidly bactericidal, and the MIC range, MIC50 and MIC90 was ≤0.001-1, 0.125 and 0.25 mg/L, respectively. There was a high correlation between the MICs of sitafloxacin and ciprofloxacin; however, the MIC50 and MIC90 of sitafloxacin were 6-fold and >6-fold lower, respectively. Sitafloxacin might be an option for particularly dual antimicrobial therapy of gonorrhoea and for cases with ceftriaxone resistance or allergy. However, further in vitro and particularly in vivo evaluations of potential resistance, pharmacokinetics/pharmacodynamics and ideal dosing for gonorrhoea, as well as performance of randomized controlled clinical, trials are crucial.

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