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1.
  • Thomas, HS, et al. (author)
  • 2019
  • swepub:Mat__t
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  • Griffin, M. J., et al. (author)
  • The Herschel-SPIRE instrument and its in-flight performance
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L3-
  • Journal article (peer-reviewed)abstract
    • The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 mu m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194-671 mu m (447-1550 GHz). The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4' x 8', observed simultaneously in the three spectral bands. Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired. The spectrometer has an approximately circular field of view with a diameter of 2.6'. The spectral resolution can be adjusted between 1.2 and 25 GHz by changing the stroke length of the FTS scan mirror. Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data. For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view. The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling. Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products. The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 1.5-2.
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  • Clarke, Robert, et al. (author)
  • Lowering blood homocysteine with folic acid based supplements : Meta-analysis of randomised trials
  • 1998
  • In: British Medical Journal. - : BMJ. - 0959-8146. ; 316:7135, s. 894-898
  • Research review (peer-reviewed)abstract
    • Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B-12 or B-6. Design: Meta-analysis of randomised controlled trials that assessed the effects of folic acid based supplements on blood homocysteine concentration. Multivariate regression analysis was used to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-12 or B-6. Subjects: Individual data on 1114 people included in 12 trials. Findings: The proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pretreatment blood homocysteine concentrations (P < 0.001) and at lower pretreatment blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 μmol/l and of folate of 12 nmol/l (approximate average concentrations for Western populations), dietary folic acid reduced blood homocysteine concentrations by 25% (95% confidence interval 23% to 28%; P < 0.001), with similar effects in the range of 0.5-5 mg folic acid daily. Vitamin B-12 (mean 0.5 mg daily) produced an additional 7% (3% to 10%) reduction in blood homocysteine. Vitamin B-6 (mean 16.5 mg daily) did not have a significant additional effect. Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 μmol/l to 8-9 μmol/l). Large scale randomised trials of such regimens in high risk populations are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease.
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  • Schelin, M. E.C., et al. (author)
  • Widespread non-joint pain in early rheumatoid arthritis
  • 2021
  • In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 50:4, s. 271-279
  • Journal article (peer-reviewed)abstract
    • Objective: The aim of the study was to assess the development of widespread non-joint pain (WNP) in a cohort of patients with early rheumatoid arthritis (RA), the associated health-related quality of life (HRQoL), and clinical and demographic risk factors for WNP. Method: Incident cases with RA, from the Swedish population-based study Epidemiological Investigation of Rheumatoid Arthritis (EIRA), with a follow-up of at least 3 years, constituted the study population. WNP was defined as pain outside the joints in all four body quadrants and was assessed at the 3 year follow-up. Patients who reported WNP were compared to patients without WNP regarding HRQoL, measured by the Short Form-36, at 3 years, and clinical and demographic characteristics at the time of RA diagnosis. Results: A total of 749 patients constituted the study sample, of whom 25 were excluded after reporting already having severe pain before RA diagnosis. At the 3 year follow-up, 8% of the patients reported having WNP as well as statistically significant worse HRQoL. At the time of RA diagnosis, the patients with WNP had worse pain and pain-related features, while no difference was seen in the inflammatory parameters. Conclusion: WNP occurs in a substantial subset of patients with RA, also early in the course of the disease, and the HRQoL for these patients is significantly reduced. Patients who develop WNP at 3 years are already distinguishable at the time of diagnosis by displaying more pronounced pain ratings together with an average level of inflammatory disease activity.
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  • Agrawal, K., et al. (author)
  • Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance
  • 2022
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 150:6
  • Journal article (peer-reviewed)abstract
    • Background: Patients with asthma often suffer from frequent respiratory viral infections and reduced virus clearance. Lung resident memory T cells provide rapid protection against viral reinfections. Objective: Because the development of resident memory T cells relies on the lung microenvironment, we investigated the impact of allergen sensitization on the development of virus-specific lung resident memory T cells and viral clearance. Methods: Mice were sensitized with house dust mite extract followed by priming with X47 and a subsequent secondary influenza infection. Antiviral memory T-cell response and protection to viral infection was assessed before and after secondary influenza infection, respectively. Gene set variation analysis was performed on data sets from the U-BIOPRED asthma cohort using an IFN-γ–induced epithelial cell signature and a tissue resident memory T-cell signature. Results: Viral loads were higher in lungs of sensitized compared with nonsensitized mice after secondary infection, indicating reduced virus clearance. X47 priming induced fewer antiviral lung resident memory CD8 T cells and resulted in lower pulmonary IFN-γ levels in the lungs of sensitized as compared with nonsensitized mice. Using data from the U-BIOPRED cohort, we found that patients with enrichment of epithelial IFN-γ–induced genes in nasal brushings and bronchial biopsies were also enriched in resident memory T-cell–associated genes, had more epithelial CD8 T cells, and reported significantly fewer exacerbations. Conclusions: The allergen-sensitized lung microenvironment interferes with the formation of antiviral resident memory CD8 T cells in lungs and virus clearance. Defective antiviral memory response might contribute to increased susceptibility of patients with asthma to viral exacerbations.
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  • Cherif, M. K., et al. (author)
  • Fc gamma RIIa Polymorphism and Anti-Malaria-Specific IgG and IgG Subclass Responses in Populations Differing in Susceptibility to Malaria in Burkina Faso
  • 2012
  • In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 75:6, s. 606-613
  • Journal article (peer-reviewed)abstract
    • Fc?RIIa is known to be polymorphic; and certain variants are associated with different susceptibilities to malaria. Studies involving the Fulani ethnic group reported an ethnic difference in Fc?RIIa-R131H genotype frequencies between the Fulani and other sympatric groups. No previous studies have addressed these questions in Burkina Faso. This study aimed to assess the influence of Fc?RIIa-R131H polymorphism on anti-falciparum malaria IgG and IgG subclass responses in the Fulani and the Mossi ethnic groups living in Burkina Faso. Healthy adults more than 20 years old belonging to the Mossi or the Fulani ethnic groups were enrolled for the assessment of selected parasitological, immunological and genetic variables in relation to their susceptibility to malaria. The prevalence of the Plasmodium falciparum infection frequency was relatively low in the Fulani ethnic group compared to the Mossi ethnic group. For all tested antigens, the Fulani had higher antibody levels than the Mossi group. In both ethnic groups, a similar distribution of Fc?RIIa R131H polymorphism was found. Individuals with the R allele of Fc?RIIa had higher antibody levels than those with the H allele. This study confirmed that malaria infection affected less the Fulani group than the Mossi group. Fc?RIIa-R131H allele distribution is similar in both ethnic groups, and higher antibody levels are associated with the Fc?RIIa R allele compared to the H allele.
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  • Jevnikar, Z., et al. (author)
  • Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation
  • 2019
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 143:2, s. 577-590
  • Journal article (peer-reviewed)abstract
    • Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.
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  • Muysoms, F. E., et al. (author)
  • European Hernia Society guidelines on the closure of abdominal wall incisions
  • 2015
  • In: Hernia. - : Springer Science and Business Media LLC. - 1265-4906 .- 1248-9204. ; 19:1, s. 1-24
  • Research review (peer-reviewed)abstract
    • Background The material and the surgical technique used to close an abdominal wall incision are important determinants of the risk of developing an incisional hernia. Optimising closure of abdominal wall incisions holds a potential to prevent patients suffering from incisional hernias and for important costs savings in health care. Methods The European Hernia Society formed a Guidelines Development Group to provide guidelines for all surgical specialists who perform abdominal incisions in adult patients on the materials and methods used to close the abdominal wall. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and methodological guidance was taken from Scottish Intercollegiate Guidelines Network (SIGN). The literature search included publications up to April 2014. The guidelines were written using the AGREE II instrument. An update of these guidelines is planned for 2017. Results For many of the Key Questions that were studied no high quality data was detected. Therefore, some strong recommendations could be made but, for many Key Questions only weak recommendations or no recommendation could be made due to lack of sufficient evidence. Recommendations To decrease the incidence of incisional hernias it is strongly recommended to utilise a non-midline approach to a laparotomy whenever possible. For elective midline incisions, it is strongly recommended to perform a continuous suturing technique and to avoid the use of rapidly absorbable sutures. It is suggested using a slowly absorbable monofilament suture in a single layer aponeurotic closure technique without separate closure of the peritoneum. A small bites technique with a suture to wound length (SL/WL) ratio at least 4/1 is the current recommended method of fascial closure. Currently, no recommendations can be given on the optimal technique to close emergency laparotomy incisions. Prophylactic mesh augmentation appears effective and safe and can be suggested in high-risk patients, like aortic aneurysm surgery and obese patients. For laparoscopic surgery, it is suggested using the smallest trocar size adequate for the procedure and closure of the fascial defect if trocars larger or equal to 10 mm are used. For single incision laparoscopic surgery, we suggest meticulous closure of the fascial incision to avoid an increased risk of incisional hernias.
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  • Ohlsson, Lina, et al. (author)
  • CEACAM5, KLK6, SLC35D3, POSTN, and MUC2 mRNA Analysis Improves Detection and Allows Characterization of Tumor Cells in Lymph Nodes of Patients Who Have Colon Cancer
  • 2021
  • In: Diseases of the Colon & Rectum. - : Lippincott Williams & Wilkins. - 0012-3706 .- 1530-0358. ; 64:11, s. 1354-1363
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Lymph node metastasis is the single most important prognostic risk factor for recurrence in patients with colon cancer who have undergone curative surgery. The routine method for detecting disseminated tumor cells in lymph nodes is microscopic examination of one or a few hematoxylin and eosin-stained tissue sections by a trained pathologist. This method, however, is insensitive mainly because less than 1% of the lymph node volume is examined, leading to misclassification.OBJECTIVE: This study aimed to investigate whether analysis of a selected group of biomarker mRNAs improves detection and characterization of lymph node metastases/micrometastases compared with the routine method.DESIGN: This study is a side-by-side comparison of biomarker mRNA analysis and histopathology of 185 lymph nodes from patients with colon cancer representing stages I to IV, and an investigation of the importance of lymph node tissue volume for tumor cell detection.SETTINGS: This is a collaborative study between a high-volume central hospital and a preclinical university institution.PATIENTS: Fifty-seven patients who had undergone tumor resection for colon cancer were included.MAIN OUTCOME MEASURES: The primary outcomes measured were mRNA copies per 18S rRNA copy of CEACAM5, KLK6, SLC35D3, POSTN, and MUC2 by multiplex assay and metastases/micrometastases detected by histopathology.RESULTS: The number of tumor cell-positive lymph nodes was 1.33-fold higher based on CEACAM5 mRNA levels compared with histopathological examination. Increasing the tissue volume analyzed for CEACAM5 levels from an 80-µm section to half a lymph node increased the number of positive nodes from 34 of 107 to 80 of 107 (p < 0.0001). Similarly, the number of positive nodes for the aggressiveness marker KLK6 increased from 9 of 107 to 24 of 107.LIMITATIONS: Only a limited number of individual lymph nodes per patient was available for analysis.CONCLUSIONS: mRNA analysis of CEACAM5, KLK6, and SLC35D3 improves the detection of tumor cells in lymph nodes from patients surgically treated for colon cancer, and, together with POSTN and MUC2, it further allows characterization of the tumor cells with respect to aggressiveness and the tumor cell environment. See Video Abstract at https://links.lww.com/DCR/B650.
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  • Olsson, Lina M., et al. (author)
  • CEACAM5, KLK6, SLC35D3, POSTN, and MUC2 mRNA Analysis Improves Detection and Allows Characterization of Tumor Cells in Lymph Nodes of Patients Who Have Colon Cancer
  • 2021
  • In: Diseases of the Colon and Rectum. - 0012-3706. ; 64:11, s. 1354-1363
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Lymph node metastasis is the single most important prognostic risk factor for recurrence in patients with colon cancer who have undergone curative surgery. The routine method for detecting disseminated tumor cells in lymph nodes is microscopic examination of one or a few hematoxylin and eosin-stained tissue sections by a trained pathologist. This method, however, is insensitive mainly because less than 1% of the lymph node volume is examined, leading to misclassification. OBJECTIVE: This study aimed to investigate whether analysis of a selected group of biomarker mRNAs improves detection and characterization of lymph node metastases/micrometastases compared with the routine method. DESIGN: This study is a side-by-side comparison of biomarker mRNA analysis and histopathology of 185 lymph nodes from patients with colon cancer representing stages I to IV, and an investigation of the importance of lymph node tissue volume for tumor cell detection. SETTINGS: This is a collaborative study between a high-volume central hospital and a preclinical university institution. PATIENTS: Fifty-seven patients who had undergone tumor resection for colon cancer were included. MAIN OUTCOME MEASURES: The primary outcomes measured were mRNA copies per 18S rRNA copy of CEACAM5, KLK6, SLC35D3, POSTN, and MUC2 by multiplex assay and metastases/micrometastases detected by histopathology. RESULTS: The number of tumor cell-positive lymph nodes was 1.33-fold higher based on CEACAM5 mRNA levels compared with histopathological examination. Increasing the tissue volume analyzed for CEACAM5 levels from an 80-µm section to half a lymph node increased the number of positive nodes from 34 of 107 to 80 of 107 (p < 0.0001). Similarly, the number of positive nodes for the aggressiveness marker KLK6 increased from 9 of 107 to 24 of 107. LIMITATIONS: Only a limited number of individual lymph nodes per patient was available for analysis. CONCLUSIONS: mRNA analysis of CEACAM5, KLK6, and SLC35D3 improves the detection of tumor cells in lymph nodes from patients surgically treated for colon cancer, and, together with POSTN and MUC2, it further allows characterization of the tumor cells with respect to aggressiveness and the tumor cell environment. See Video Abstract at http://links.lww.com/DCR/B650.
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  • Wagner, K, et al. (author)
  • Association of polymorphisms and haplotypes in the human growth hormone 1 (GH1) gene with breast cancer
  • 2005
  • In: Endocrine-related cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 12:4, s. 917-928
  • Journal article (peer-reviewed)abstract
    • The growth hormone 1 (GH1)/insulin-like growth factor I (IGF-I) axis plays an important role in the development of breast cancer. By binding to its receptor, GH1 stimulates the production of IGF-I and its binding protein IGFBP3, resulting in the regulation of cell proliferation, differentiation and apoptosis. The GH1 gene expression is regulated by a highly polymorphic proximal promoter and a distal locus control region (LCR) 14.5 kb upstream of the gene. We investigated the effect of single nucleotide polymorphisms (SNPs) in the LCR and in the promoter region and an intron 4 SNP (IVS4+90 T/A) on breast cancer risk in a large cohort of Polish and German familial breast cancer cases and controls. SNPs in the LCR did not show an influence on breast cancer risk, either alone or in haplotypes. Three SNPs in the promoter region (G-340T, A-68G/C and A-63T/C) showed an increased and four SNPs (A-137G, G-119T, G-93delG and T-4G) a decreased allele frequency in the cases compared with the controls. Two of the SNPs (A-137G and G-93delG) lead to a decreased breast cancer risk among the minor allele carriers in the joint analysis of the two populations (odds ratio (OR) 0.62, 95% confidence interval (95% CI) 0.44–0.89, P=0.01 and OR 0.65, 95% CI 0.47–0.90, P=0.01, respectively). Haplotype analysis with these seven promoter SNPs revealed a protective association (OR 0.61, 95% CI 0.37–1.00, P=0.04) for the haplotype GAGdAAT, containing the G-93delG variant allele, which in the single analysis already showed a protective effect. The effect was marginally stronger in combination with the LCR GC haplotype (OR 0.49, 95% CI 0.23–1.01, P=0.04).
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  • Bolad, Ahmed, et al. (author)
  • Distinct interethnic differences in IgG class/subclass and IgM antibody responses to malaria antigens but not in IgG responses to non-malarial antigens in sympatric tribes living in West Africa
  • 2005
  • In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:4, s. 380-386
  • Journal article (peer-reviewed)abstract
    • The well-established relative resistance to malaria observed in the Fulani ascompared with other sympatric tribes in West Africa has been attributed totheir higher levels of serum immunoglobulin (Ig) G antibodies to malarialantigens. In this study, we confirm and extend the previous findings by analysesof the levels of IgM, IgG and IgG subclasses of anti-malarial antibodies inasymptomatic individuals of different sympatric tribes in Burkina Faso(Fulani/Mossi) and Mali (Fulani/Dogon). The Fulani showed significantlyhigher median concentrations of anti-malarial IgG and IgM antibodies thanthe sympatric tribes at both locations. Although the overall subclass pattern ofantibodies did not differ between the tribes, with IgG1 and IgG3 as dominant,the Fulani showed consistently significantly higher levels of these subclasses ascompared with those of the non-Fulani individuals. No significant differenceswere seen in the levels of total IgG between the tribes, but the Fulani showedsignificantly higher levels of total IgM than their neighbours in both countries.While the antibody levels to some nonmalarial antigens showed the same patternof differences seen for antibody levels to malaria antigens, no significant suchdifferences were seen with antibodies to other nonmalarial antigens. In conclusion,our results show that the Fulani in two different countries show higherlevels of anti-malarial antibodies than sympatric tribes, and this appears not tobe a reflection of a general hyper-reactivity in the Fulani.
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  • Fattibene, P, et al. (author)
  • The 4th international comparison on EPR dosimetry with tooth enamel Part 1: Report on the results
  • 2011
  • In: Radiation Measurements. - : Elsevier. - 1350-4487 .- 1879-0925. ; 46:9, s. 765-771
  • Journal article (peer-reviewed)abstract
    • This paper presents the results of the 4th International Comparison of in vitro electron paramagnetic resonance dosimetry with tooth enamel, where the performance parameters of tooth enamel dosimetry methods were compared among sixteen laboratories from all over the world. The participating laboratories were asked to determine a calibration curve with a set of tooth enamel powder samples provided by the organizers. Nine molar teeth extracted following medical indication from German donors and collected between 1997 and 2007 were prepared and irradiated at the Helmholtz Zentrum Munchen. Five out of six samples were irradiated at 0.1, 0.2, 0.5, 1.0 and 1.5 Gy air kerma; and one unirradiated sample was kept as control. The doses delivered to the individual samples were unknown to the participants, who were asked to measure each sample nine times, and to report the EPR signal response, the mass of aliquots measured, and the parameters of EPR signal acquisition and signal evaluation. Critical dose and detection limit were calculated by the organizers on the basis of the calibration-curve parameters obtained at every laboratory. For calibration curves obtained by measuring every calibration sample three times, the mean value of the detection limit was 205 mGy, ranging from 56 to 649 mGy. The participants were also invited to provide the signal response and the nominal dose of their current dose calibration curve (wherever available), the critical dose and detection limit of which were also calculated by the organizers.
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  • Gronwall, C, et al. (author)
  • THE RELATIONSHIP BETWEEN DIFFERENT IGG AND IGA ANTI-MODIFIED PROTEIN AUTOANTIBODIES IN RHEUMATOID ARTHRITIS
  • 2021
  • In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 206-207
  • Conference paper (other academic/artistic)abstract
    • Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), anti-acetylated (KAc), and anti-malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. By using RA patient single-cell derived monoclonal antibodies we have previously shown that individual ACPA clones recognize small distinct citrulline-containing epitopes giving them extensive multireactivity when these epitopes are found in many peptides and proteins. Moreover, certain CCP2+ multireactive ACPA clones bind also to cabamylated and acetylated autoantigens [1].Objectives:To provide a comprehensive evaluation of serum IgG and IgA autoreactivity to different post-translational modifications in RA.Methods:We analyzed 30 different IgG and IgA AMPA reactivities to modified antigens by ELISA and autoantigen arrays, in N=1985 newly diagnosed RA patients and population controls. The study utilized both previously established (i.e IgG and IgA CCP2; IgG ACPA fine-specificities; IgG anti-Carb fibrinogen and Carb FCS; IgG and IgA Cit/Carb/KAc/Orn(Ac)-vimentin), and novel assays (e.g. IgG anti-MAA and IgG anti-acetylated histones). Association with patient characteristics such as smoking and disease activity were explored. The newly developed assays were also evaluated in SLE disease controls and CCP2+ RA-risk individuals without arthritis.Results:Carb and KAc reactivities by different assays were primarily seen in patients also positive for citrulline-reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG acetylation reactivity was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone 2B reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles.Conclusion:We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Anti-Carb and anti-KAc could be considered reactivities within the “Cit-umbrella” similar to ACPA fine-specificities, while MAA is distinctly different.References:[1]Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C. Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis. Arthritis Rheumatol. 2020 Oct;72(10):1643-1657. PMID: 32501655Caroline Grönwall: None declared, Lisa Liljefors: None declared, Holger Bang Employee of: Employee at ORGENTEC Diagnostika GmbH, Aase Hensvold: None declared, Monika Hansson: None declared, Linda Mathsson-Alm Employee of: Employee at Thermo Fisher Scientific, Lena Israelsson: None declared, Anna Svärd: None declared, Cyril CLAVEL: None declared, Elisabet Svenungsson: None declared, Iva Gunnarsson: None declared, Guy Serre: None declared, Saedis Saevarsdottir: None declared, Alf Kastbom: None declared, Lars Alfredsson: None declared, Vivianne Malmström: None declared, Johan Rönnelid: None declared, Anca Catrina: None declared, Karin Lundberg: None declared, Lars Klareskog: None declared
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  • Hedberg, Maria E., et al. (author)
  • Prevotella jejuni sp. nov., isolated from the small intestine of a child with celiac disease.
  • 2013
  • In: International journal of systematic and evolutionary microbiology. - : Microbiology Society. - 1466-5034 .- 1466-5026. ; 63:11, s. 4218-4223
  • Journal article (peer-reviewed)abstract
    • Five obligately anaerobic, Gram-negative, saccharolytic and proteolytic, non-spore-forming bacilli (CD3:27, CD3:28T, CD3:33, CD3:32 and CD3:34) are described. All five strains were isolated from the small intestine of a female child with celiac disease. The cells of the five strains were observed to be short rods or coccoid cells with longer filamentous forms seen sporadically. The organisms produced acetic acid and succinic acid as major metabolic end products. Phylogenetic analysis, based on comparative 16S rRNA gene sequence analysis revealed close relationships between CD3:27, CD3:28T and CD3:33 on one hand, between CD3:32 and P. histicola CCUG 55407T and between CD3:34 and P. melaninogenica CCUG 4944BT on the other. The strains CD3:27, CD3:28T and CD3:33 were clearly different from any other species within the genus Prevotella and most closely related to but distinct from P. melaninogenica. Based on 16S rRNA gene, RNA polymerase β-subunit gene and 60-kDa chaperonin protein subunit gene sequencing, phenotypic, chemical and biochemical properties strains CD3:27, CD3:28T and CD3:33 have been determined to represent a novel species within the genus Prevotella, named Prevotella jejuni sp. nov. Strain CD3:28T (CCUG 60371T = DSM 26989T) is the type strain of the proposed new species. All five strains were able to form homologous aggregates, in which tube-like structures were connecting individual bacteria cells. The five strains were able to bind to human intestinal carcinoma cell lines at 37 °C.
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  • Israelsson, E., et al. (author)
  • Antibody responses to a C-terminal fragment of the Plasmodium falciparum blood-stage antigen Pf332 in Senegalese individuals naturally primed to the parasite
  • 2008
  • In: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 152:1, s. 64-71
  • Journal article (peer-reviewed)abstract
    • Previous studies have shown that antibodies from humans exposed continuously to malaria recognize the Plasmodium falciparum asexual blood-stage antigen Pf332. Here we analysed the antibody responses to a C-terminal fragment of Pf332, designated C231, in individuals from Senegal, by measuring the serum levels of immunoglobulin M (IgM), IgG class and subclass and IgE antibodies. IgG antibody reactivity with crude P. falciparum antigen was detected in all the donors, while many of the children lacked or had low levels of such antibodies against C231. The antibody levels increased significantly with age for both crude P. falciparum antigen and C231, and in the older age groups most of the donors displayed antibodies to C231. This was also true for IgM, IgE and IgG subclass reactivity against C231. Moreover, the ratio of IgG1/IgG2 was considerably lower for C231 than for crude P. falciparum antigen, and in age groups 10–14 and 15–19 years the levels of IgG2 against C231 even exceeded that of IgG1. The IgG2/IgG3 ratios suggest that C231 gives similar levels of IgG2 and IgG3, except for children aged 4–9 years, where IgG3 was higher. Raw IgM, IgG class and subclass and IgE antibody levels to C231 tended to be higher in those who did not experience a malaria attack, but following linear multivariate analysis the trends were not significant.
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30.
  • Israelsson, M., et al. (author)
  • Changes in gene expression in the wood-forming tissue of transgenic hybrid aspen with increased secondary growth
  • 2003
  • In: Plant Molecular Biology. - 0167-4412 .- 1573-5028. ; 52:4, s. 893-903
  • Journal article (peer-reviewed)abstract
    • Transgenic lines of hybrid aspen with elevated levels of gibberellin (GA) show greatly increased numbers of xylem fibres and increases in xylem fibre length. These plants therefore provide excellent models for studying secondary growth. We have used cDNA microarry analysis to investigate how gene transcription in the developing xylem is affected by GA-induced growth. A recent investigation has shown that genes encoding lignin and cellulose biosynthetic enzymes, as well as a number of transcription factors and other potential regulators of xylogenesis, are under developmental-stage-specific transcriptional control. The present study shows that the highest transcript changes in our transgenic trees occurs in genes generally restricted to the early stages of xylogenesis, including cell division, early expansion and late expansion. The results reveal genes among those arrayed that are up-regulated with an increased xylem production, thus indicating key components in the production of wood.
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31.
  • Israelsson-Skogsberg, Åsa, 1968-, et al. (author)
  • 'I'm almost never sick': Everyday life experiences of children and young people with home mechanical ventilation
  • 2018
  • In: Journal of Child Health Care. - : SAGE Publications. - 1367-4935 .- 1741-2889. ; 22:1, s. 6-18
  • Journal article (peer-reviewed)abstract
    • Developments in medical technology and treatment have increased the survival rates of children with serious illnesses or injuries, including those receiving home mechanical ventilation, which is a small but growing group. The aim of this study was to explore everyday life experiences of children and young people living with home mechanical ventilation (HMV). Data were obtained through interviews with nine participants. The interviews were supported by photovoice methodology: photographs taken by the participants before or during the interviews were used to facilitate conversation. Interview data were analyzed using qualitative content analysis. The findings revealed that everyday life on a ventilator can be described as including power but simultaneously as characterized by vulnerability to the outside world, comparable to balancing on a tightrope. Various types of technology, both information and communication technology (ICT) and vital medical technology, enabled the participants to engage with the world around them. This study contributes knowledge about the experiences of children and young people with HMV, who depict their lives as good and valuable. The study also underscores, when designing plans and home support, it is necessary to take a sensible approach to personal experiences of what a good life is and what resources are needed to attain and maintain health.
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33.
  • Jurca, Manuela, et al. (author)
  • ZEITLUPE Promotes ABA-Induced Stomatal Closure in Arabidopsis and Populus
  • 2022
  • In: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 13
  • Journal article (peer-reviewed)abstract
    • Plants balance water availability with gas exchange and photosynthesis by controlling stomatal aperture. This control is regulated in part by the circadian clock, but it remains unclear how signalling pathways of daily rhythms are integrated into stress responses. The serine/threonine protein kinase OPEN STOMATA 1 (OST1) contributes to the regulation of stomatal closure via activation of S-type anion channels. OST1 also mediates gene regulation in response to ABA/drought stress. We show that ZEITLUPE (ZTL), a blue light photoreceptor and clock component, also regulates ABA-induced stomatal closure in Arabidopsis thaliana, establishing a link between clock and ABA-signalling pathways. ZTL sustains expression of OST1 and ABA-signalling genes. Stomatal closure in response to ABA is reduced in ztl mutants, which maintain wider stomatal apertures and show higher rates of gas exchange and water loss than wild-type plants. Detached rosette leaf assays revealed a stronger water loss phenotype in ztl-3, ost1-3 double mutants, indicating that ZTL and OST1 contributed synergistically to the control of stomatal aperture. Experimental studies of Populus sp., revealed that ZTL regulated the circadian clock and stomata, indicating ZTL function was similar in these trees and Arabidopsis. PSEUDO-RESPONSE REGULATOR 5 (PRR5), a known target of ZTL, affects ABA-induced responses, including stomatal regulation. Like ZTL, PRR5 interacted physically with OST1 and contributed to the integration of ABA responses with circadian clock signalling. This suggests a novel mechanism whereby the PRR proteins—which are expressed from dawn to dusk—interact with OST1 to mediate ABA-dependent plant responses to reduce water loss in time of stress.
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35.
  • Mareev, EA, et al. (author)
  • Studies of an artificially generated electrode effect at ground level
  • 1996
  • In: ANNALES GEOPHYSICAE-ATMOSPHERES HYDROSPHERES AND SPACE SCIENCES. - : SPRINGER VERLAG. - 0992-7689. ; 14:10, s. 1095-1101
  • Journal article (peer-reviewed)abstract
    • The outdoor experiments, using a metallic grid above the ground surface, have yielded well-defined vertical profiles of the space-charge density. The profiles showed strong evidence for the existence of an electrode effect, which could be named the artif
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42.
  • Stevenson-Ågren, Jean, et al. (author)
  • Factors influencing the quality of vital signs data in electronic health records : a qualitative study
  • 2018
  • In: Journal of Clinical Nursing. - New Jersey : John Wiley & Sons. - 0962-1067 .- 1365-2702. ; 27:5-6, s. 1276-1286
  • Journal article (peer-reviewed)abstract
    • Aims and objectivesTo investigate reasons for inadequate documentation of vital signs in an electronic health record.BackgroundMonitoring vital signs is crucial to detecting and responding to patient deterioration. The ways in which vital signs are documented in electronic health records have received limited attention in the research literature. A previous study revealed that vital signs in an electronic health record were incomplete and inconsistent.DesignQualitative study.MethodsQualitative study. Data were collected by observing (68 hr) and interviewing nurses (n = 11) and doctors (n = 3), and analysed by thematic analysis to examine processes for measuring, documenting and retrieving vital signs in four clinical settings in a 353-bed hospital.ResultsWe identified two central reasons for inadequate vital sign documentation. First, there was an absence of firm guidelines for observing patients’ vital signs, resulting in inconsistencies in the ways vital signs were recorded. Second, there was a lack of adequate facilities in the electronic health record for recording vital signs. This led to poor presentation of vital signs in the electronic health record and to staff creating paper “workarounds.”ConclusionsThis study demonstrated inadequate routines and poor facilities for vital sign documentation in an electronic health record, and makes an important contribution to knowledge by identifying problems and barriers that may occur. Further, it has demonstrated the need for improved facilities for electronic documentation of vital signs.Relevance to clinical practicePatient safety may have been compromised because of poor presentation of vital signs. Thus, our results emphasised the need for standardised routines for monitoring patients. In addition, designers should consult the clinical end-users to optimise facilities for electronic documentation of vital signs. This could have a positive impact on clinical practice and thus improve patient safety.
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43.
  • Stevenson-Ågren, Jean, et al. (author)
  • Recording signs of deterioration in acute patients : The documentation of vital signs within electronic health records in patients who suffered in-hospital cardiac arrest
  • 2016
  • In: Health Informatics Journal. - : Sage Publications. - 1460-4582 .- 1741-2811. ; 22:1, s. 21-33
  • Journal article (peer-reviewed)abstract
    • Vital sign documentation is crucial to detecting patient deterioration. Little is known about the documentation of vital signs in electronic health records. This study aimed to examine documentation of vital signs in electronic health records. We examined the vital signs documented in the electronic health records of patients who had suffered an in-hospital cardiac arrest and on whom cardiopulmonary resuscitation was attempted between 2007 and 2011 (n = 228), in a 372-bed district general hospital. We assessed the completeness of vital sign data compared to VitalPACTM Early Warning Score and the location of vital signs within the electronic health records. There was a noticeable lack of completeness of vital signs. Vital signs were fragmented through various sections of the electronic health records. The study identified serious shortfalls in the representation of vital signs in the electronic health records, with consequential threats to patient safety. 
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