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  1. Article ; Online: The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.

    Jareid, Mie / Snapkov, Igor / Holden, Marit / Busund, Lill-Tove Rasmussen / Lund, Eiliv / Nøst, Therese Haugdahl

    PloS one

    2021  Volume 16, Issue 8, Page(s) e0256442

    Abstract: Epithelial ovarian cancer (EOC) has a 5-year relative survival of 50%, partly because markers of early-stage disease are not available in current clinical diagnostics. The aim of the present study was to investigate whether EOC is associated with ... ...

    Abstract Epithelial ovarian cancer (EOC) has a 5-year relative survival of 50%, partly because markers of early-stage disease are not available in current clinical diagnostics. The aim of the present study was to investigate whether EOC is associated with transcriptional profiles in blood collected up to 7 years before diagnosis. For this, we used RNA-stabilized whole blood, which contains circulating immune cells, from a sample of EOC cases from the population-based Norwegian Women and Cancer (NOWAC) postgenome cohort. We explored case-control differences in gene expression in all EOC (66 case-control pairs), as well as associations between gene expression and metastatic EOC (56 pairs), serous EOC (45 pairs, 44 of which were metastatic), and interval from blood sample collection to diagnosis (≤3 or >3 years; 34 and 31 pairs, respectively). Lastly, we assessed differential expression of genes associated with EOC in published functional genomics studies that used blood samples collected from newly diagnosed women. After adjustment for multiple testing, this nested case-control study revealed no significant case-control differences in gene expression in all EOC (false discovery rate q>0.96). With the exception of a few probes, the log2 fold change values obtained in gene-wise linear models were below ±0.2. P-values were lowest in analyses of metastatic EOC (80% of which were serous EOC). No common transcriptional profile was indicated by interval to diagnosis; when comparing the 100 genes with the lowest p-values in gene-wise tests in samples collected ≤3 and >3 years before EOC diagnosis, no overlap in these genes was observed. Among 86 genes linked to ovarian cancer in previous publications, our data contained expression values for 42, and of these, tests of LIME1, GPR162, STAB1, and SKAP1, resulted in unadjusted p<0.05. Although limited by sample size, our findings indicated less variation in blood gene expression between women with similar tumor characteristics.
    MeSH term(s) Adaptor Proteins, Vesicular Transport/blood ; Cell Adhesion Molecules, Neuronal/blood ; Cohort Studies ; Cystadenocarcinoma, Serous/blood ; Cystadenocarcinoma, Serous/epidemiology ; Cystadenocarcinoma, Serous/genetics ; Cystadenocarcinoma, Serous/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Proteins/blood ; Neoplasm Proteins/genetics ; Norway/epidemiology ; Ovarian Neoplasms/blood ; Ovarian Neoplasms/epidemiology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Phosphoproteins/blood ; Receptors, G-Protein-Coupled/blood ; Receptors, Lymphocyte Homing/blood ; Transcriptome/genetics
    Chemical Substances Adaptor Proteins, Vesicular Transport ; Cell Adhesion Molecules, Neuronal ; Gpr162 protein, human ; LIME1 protein, human ; Neoplasm Proteins ; Phosphoproteins ; Receptors, G-Protein-Coupled ; Receptors, Lymphocyte Homing ; SKAP1 protein, human ; STAB1 protein, human
    Language English
    Publishing date 2021-08-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0256442
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Trajectories of gene expression, seasonal influenza, and within-host seasonal immunity: transfer value to covid-19

    Lund, Eiliv / Holden, Marit / Busund, Lill-Tove Rasmussen / Snapkov, Igor / Shvetsov, Nikita / Holden, Lars

    medRxiv

    Abstract: As a novel approach we will combine trajectories or longitudinal studies of gene expression with information on annual influenza epidemics. Seasonality of gene expression in immune cells from blood could be a consequence of within-host seasonal immunity ... ...

    Abstract As a novel approach we will combine trajectories or longitudinal studies of gene expression with information on annual influenza epidemics. Seasonality of gene expression in immune cells from blood could be a consequence of within-host seasonal immunity interacting with the seasonal pandemics of influenza (flu) in temperate regions and, thus, with potential valuable analogy transfer to the proposed seasonal development of covid-19. Here we operationalized within-host immunity as genes with both a significant seasonal term and a significant flu term in the sine-cosine model. Information on gene expression was based on microarray using RNase buffered blood samples collected randomly from a population-based cohort of Norwegian middle-aged women in 2003-2006, The Norwegian Women and Cancer (NOWAC) study. The unique discovery (N=425) and replication (N=432) design were based on identical sampling and preprocessing. Data on proportion of sick leaves due to flu, and the flu intensities per week was obtained from the National Institute of Public Health, giving a semi-ecological analysis. The discovery analysis found 2942 (48.1%) significant genes in a generalized seasonal model over four years. For 1051 within-host genes both the seasonal and the flu term were significant. These genes followed closely the flu intensities. The trajectories showed slightly more genes with a maximum in early winter than in late summer. Moving the flu intensity forward in time indicated a better fit 3-4 weeks before the observed influenza. In the replication analyses, 369 genes (35.1% of 1051) were significant. Exclusion of genes with unknown functions and with more than a season in difference reduced the number of genes in the discovery dataset to 305, illustrating the variability in the measurements and the problem in assessing weak biological relationships. Thus, we found for the first time a clear seasonality in gene expression with marked responses to the annual seasonal influenza in a unique discovery - replication design. Hypothetically, this could support the within-host seasonal immunity concept.
    Keywords covid19
    Language English
    Publishing date 2022-03-11
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.03.01.22271679
    Database COVID19

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  3. Article ; Online: Global blood gene expression profiles following a breast cancer diagnosis-Clinical follow-up in the NOWAC post-genome cohort.

    Olsen, Karina Standahl / Holden, Marit / Thalabard, Jean-Christophe / Rasmussen Busund, Lill-Tove / Lund, Eiliv / Holden, Lars

    PloS one

    2021  Volume 16, Issue 3, Page(s) e0246650

    Abstract: Objective: This explorative study aimed to assess if there are any time-dependent blood gene expression changes during the first one to eight years after breast cancer diagnosis, which can be linked to the clinical outcome of the disease.: Material ... ...

    Abstract Objective: This explorative study aimed to assess if there are any time-dependent blood gene expression changes during the first one to eight years after breast cancer diagnosis, which can be linked to the clinical outcome of the disease.
    Material and methods: A random distribution of follow-up time from breast cancer diagnosis till blood sampling was obtained by a nested, matched case-control design in the Norwegian Women and Cancer Post-genome Cohort. From 2002-5, women were invited to donate blood samples, regardless of any cancer diagnosis. At end of the study period in 2015, any cancer diagnoses in the 50 000 participants were obtained via linkage to the Norwegian Cancer Registry. For each breast cancer patient (n = 415), an age- and storage time-matched control was drawn. The design gave a uniform, random length of follow-up time, independent of cancer stage. Differences in blood gene expression between breast cancer cases and controls were identified using the Bioconductor R-package limma, using a moving window in time, to handle the varying time elapsed from diagnosis to blood sample.
    Results: The number of differentially expressed genes between cases and controls were close to 2,000 in the first year after diagnosis, but fell sharply the second year. During the next years, a transient second increase was observed, but only in women with metastatic disease who later died, both compared to invasive cases that survived (p<0,001) and to metastatic cases that survived (p = 0.024). Among the differentially expressed genes there was an overrepresentation of heme metabolism and T cell-related processes.
    Conclusion: This explorative analysis identified changing trajectories in the years after diagnosis, depending on clinical stage. Hypothetically, this could represent the escape of the metastatic cancer from the immune system.
    MeSH term(s) Adult ; Aged ; Breast Neoplasms/blood ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics ; Cohort Studies ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Genomics ; Humans ; Middle Aged ; Registries
    Language English
    Publishing date 2021-03-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0246650
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Transcriptomic signals in blood prior to lung cancer focusing on time to diagnosis and metastasis.

    Nøst, Therese H / Holden, Marit / Dønnem, Tom / Bøvelstad, Hege / Rylander, Charlotta / Lund, Eiliv / Sandanger, Torkjel M

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 7406

    Abstract: Recent studies have indicated that there are functional genomic signals that can be detected in blood years before cancer diagnosis. This study aimed to assess gene expression in prospective blood samples from the Norwegian Women and Cancer cohort ... ...

    Abstract Recent studies have indicated that there are functional genomic signals that can be detected in blood years before cancer diagnosis. This study aimed to assess gene expression in prospective blood samples from the Norwegian Women and Cancer cohort focusing on time to lung cancer diagnosis and metastatic cancer using a nested case-control design. We employed several approaches to statistically analyze the data and the methods indicated that the case-control differences were subtle but most distinguishable in metastatic case-control pairs in the period 0-3 years prior to diagnosis. The genes of interest along with estimated blood cell populations could indicate disruption of immunological processes in blood. The genes identified from approaches focusing on alterations with time to diagnosis were distinct from those focusing on the case-control differences. Our results support that explorative analyses of prospective blood samples could indicate circulating signals of disease-related processes.
    MeSH term(s) Biomarkers, Tumor/blood ; Case-Control Studies ; Cell-Free Nucleic Acids ; Cohort Studies ; Computational Biology ; Data Analysis ; Female ; Gene Expression Profiling/methods ; Humans ; Leukocytes/metabolism ; Lung Neoplasms/diagnosis ; Lung Neoplasms/genetics ; Neoplasm Metastasis ; Neoplasm Staging ; Norway ; Time Factors ; Transcriptome
    Chemical Substances Biomarkers, Tumor ; Cell-Free Nucleic Acids
    Language English
    Publishing date 2021-04-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-86879-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: User-Intended Doppler Measurement Type Prediction Combining CNNs With Smart Post-Processing.

    Gilbert, Andrew / Holden, Marit / Eikvil, Line / Rakhmail, Mariia / Babic, Aleksandar / Aase, Svein Arne / Samset, Eigil / McLeod, Kristin

    IEEE journal of biomedical and health informatics

    2021  Volume 25, Issue 6, Page(s) 2113–2124

    Abstract: Spectral Doppler measurements are an important part of the standard echocardiographic examination. These measurements give insight into myocardial motion and blood flow, providing clinicians with parameters for diagnostic decision making. Many of these ... ...

    Abstract Spectral Doppler measurements are an important part of the standard echocardiographic examination. These measurements give insight into myocardial motion and blood flow, providing clinicians with parameters for diagnostic decision making. Many of these measurements are performed automatically with high accuracy, increasing the efficiency of the diagnostic pipeline. However, full automation is not yet available because the user must manually select which measurement should be performed on each image. In this work, we develop a pipeline based on convolutional neural networks (CNNs) to automatically classify the measurement type from cardiac Doppler scans. We show how the multi-modal information in each spectral Doppler recording can be combined using a meta parameter post-processing mapping scheme and heatmaps to encode coordinate locations. Additionally, we experiment with several architectures to examine the tradeoff between accuracy, speed, and memory usage for resource-constrained environments. Finally, we propose a confidence metric using the values in the last fully connected layer of the network and show that our confidence metric can prevent many misclassifications. Our algorithm enables a fully automatic pipeline from acquisition to Doppler spectrum measurements. We achieve 96% accuracy on a test set drawn from separate clinical sites, indicating that the proposed method is suitable for clinical adoption.
    MeSH term(s) Algorithms ; Automation ; Humans ; Neural Networks, Computer ; Ultrasonography
    Language English
    Publishing date 2021-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2695320-1
    ISSN 2168-2208 ; 2168-2194
    ISSN (online) 2168-2208
    ISSN 2168-2194
    DOI 10.1109/JBHI.2020.3029392
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Multi-focus cluster labeling.

    Eikvil, Line / Jenssen, Tor-Kristian / Holden, Marit

    Journal of biomedical informatics

    2015  Volume 55, Page(s) 116–123

    Abstract: Document collections resulting from searches in the biomedical literature, for instance, in PubMed, are often so large that some organization of the returned information is necessary. Clustering is an efficient tool for organizing search results. To help ...

    Abstract Document collections resulting from searches in the biomedical literature, for instance, in PubMed, are often so large that some organization of the returned information is necessary. Clustering is an efficient tool for organizing search results. To help the user to decide how to continue the search for relevant documents, the content of each cluster can be characterized by a set of representative keywords or cluster labels. As different users may have different interests, it can be desirable with solutions that make it possible to produce labels from a selection of different topical categories. We therefore introduce the concept of multi-focus cluster labeling to give users the possibility to get an overview of the contents through labels from multiple viewpoints. The concept for multi-focus cluster labeling has been established and has been demonstrated on three different document collections. We illustrate that multi-focus visualizations can give an overview of clusters along axes that general labels are not able to convey. The approach is generic and should be applicable to any biomedical (or other) domain with any selection of foci where appropriate focus vocabularies can be established. A user evaluation also indicates that such a multi-focus concept is useful.
    MeSH term(s) Data Mining/methods ; Documentation/classification ; Documentation/statistics & numerical data ; MEDLINE/classification ; MEDLINE/statistics & numerical data ; Machine Learning ; Natural Language Processing ; Pattern Recognition, Automated/methods ; User-Computer Interface ; Vocabulary, Controlled
    Language English
    Publishing date 2015-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2057141-0
    ISSN 1532-0480 ; 1532-0464
    ISSN (online) 1532-0480
    ISSN 1532-0464
    DOI 10.1016/j.jbi.2015.03.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book ; Online: Automated Left Ventricle Dimension Measurement in 2D Cardiac Ultrasound via an Anatomically Meaningful CNN Approach

    Gilbert, Andrew / Holden, Marit / Eikvil, Line / Aase, Svein Arne / Samset, Eigil / McLeod, Kristin

    2019  

    Abstract: Two-dimensional echocardiography (2DE) measurements of left ventricle (LV) dimensions are highly significant markers of several cardiovascular diseases. These measurements are often used in clinical care despite suffering from large variability between ... ...

    Abstract Two-dimensional echocardiography (2DE) measurements of left ventricle (LV) dimensions are highly significant markers of several cardiovascular diseases. These measurements are often used in clinical care despite suffering from large variability between observers. This variability is due to the challenging nature of accurately finding the correct temporal and spatial location of measurement endpoints in ultrasound images. These images often contain fuzzy boundaries and varying reflection patterns between frames. In this work, we present a convolutional neural network (CNN) based approach to automate 2DE LV measurements. Treating the problem as a landmark detection problem, we propose a modified U-Net CNN architecture to generate heatmaps of likely coordinate locations. To improve the network performance we use anatomically meaningful heatmaps as labels and train with a multi-component loss function. Our network achieves 13.4%, 6%, and 10.8% mean percent error on intraventricular septum (IVS), LV internal dimension (LVID), and LV posterior wall (LVPW) measurements respectively. The design outperforms other networks and matches or approaches intra-analyser expert error.

    Comment: Best paper award at Smart Ultrasound Imaging Workshop (SUSI) MICCAI 2019
    Keywords Electrical Engineering and Systems Science - Image and Video Processing ; Computer Science - Computer Vision and Pattern Recognition
    Subject code 006
    Publishing date 2019-11-06
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Genetic contribution of catechol-O-methyltransferase variants in treatment outcome of low back pain

    Omair Ahmad / Lie Benedicte / Reikeras Olav / Holden Marit / Brox Jens

    BMC Musculoskeletal Disorders, Vol 13, Iss 1, p

    a prospective genetic association study

    2012  Volume 76

    Abstract: Abstract Background Treatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability. Genetic variants of catechol-O-methyltransferase ( COMT ) gene have previously been shown to be ... ...

    Abstract Abstract Background Treatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability. Genetic variants of catechol-O-methyltransferase ( COMT ) gene have previously been shown to be associated with pain sensitivity and pain medication. This study examines the association between COMT polymorphisms and 7–11 year change in Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for LBP as clinical outcome variables in patients treated with surgical instrumented lumbar fusion or cognitive intervention and exercise. Methods 93 unrelated patients with chronic LBP for duration of >1 year and lumbar disc degeneration (LDD) were treated with lumbar fusion ( N = 60) or cognitive therapy and exercises ( N = 33). Standardised questionnaires assessing the ODI, VAS LBP, psychological factors and use of analgesics, were answered by patients both at baseline and at 7–11 years follow-up. Four SNPs in the COMT gene were successfully genotyped. Single marker as well as haplotype association with change in ODI and VAS LBP, were analyzed using Haploview, linear regression and R-package Haplostats. P-values were not formally corrected for multiple testing as this was an explorative study. Results Association analysis of individual SNPs adjusted for covariates revealed association of rs4633 and rs4680 with post treatment improvement in VAS LBP ( p = 0.02, mean difference ( β) = 13.5 and p = 0.02, β = 14.2 respectively). SNPs, rs4633 and rs4680 were found to be genotypically similar and in strong linkage disequilibrium (LD). A significant association was found with covariates, analgesics ( p = 0.001, β = 18.6); anxiety and depression ( p = 0.008, β = 15.4) and age ( p = 0.03, mean difference per year ( β) = 0.7) at follow-up. There was a tendency for better improvement among heterozygous patients compared to the homozygous. No association was observed for the analysis of the common haplotypes, these SNPs were situated on. Conclusions Results suggest an influence of genetic variants of COMT gene in describing the variation in pain after treatment for low back pain. Replication in large samples with testing for other pain related genes is warranted.
    Keywords Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Diseases of the musculoskeletal system ; RC925-935
    Subject code 616
    Language English
    Publishing date 2012-05-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Each pregnancy linearly changes immune gene expression in the blood of healthy women compared with breast cancer patients.

    Lund, Eiliv / Nakamura, Aurelie / Snapkov, Igor / Thalabard, Jean-Christophe / Olsen, Karina Standahl / Holden, Lars / Holden, Marit

    Clinical epidemiology

    2018  Volume 10, Page(s) 931–940

    Abstract: Background: There is a large body of evidence demonstrating long-lasting protective effect of each full-term pregnancy (FTP) on the development of breast cancer (BC) later in life, a phenomenon that could be related to both hormonal and immunological ... ...

    Abstract Background: There is a large body of evidence demonstrating long-lasting protective effect of each full-term pregnancy (FTP) on the development of breast cancer (BC) later in life, a phenomenon that could be related to both hormonal and immunological changes during pregnancies. In this work, we studied the pregnancy-associated differences in peripheral blood gene expression profiles between healthy women and women diagnosed with BC in a prospective design.
    Methods: Using an integrated system epidemiology approach, we modeled BC incidence as a function of parity in the Norwegian Women and Cancer (NOWAC) cohort (165,000 women) and then tested the resulting mathematical model using gene expression profiles in blood in a nested case-control study (460 invasive case-control pairs) of women from the NOWAC postgenome cohort. Lastly, we undertook a gene set enrichment analysis for immunological gene sets.
    Results: A linear trend fitted the dataset precisely showing an 8% decrease in risk of BC for each FTP, independent of stratification on other risk factors and lasting for decades after a woman's last FTP. Women with six children demonstrated 48% reduction in the incidence of BC compared to nulliparous. When we looked at gene expression, we found that 756 genes showed linear trends in cancer-free controls (false discovery rate [FDR] 5%), but this was not the case for any of the genes in BC cases. Gene set enrichment analysis of immunologic gene sets (C7 collection in Molecular Signatures Database) revealed 215 significantly enriched human gene sets (FDR 5%).
    Conclusion: We found marked differences in gene expression and enrichment profiles of immunologic gene sets between BC cases and healthy controls, suggesting an important protective effect of the immune system on BC risk.
    Language English
    Publishing date 2018-08-06
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2494772-6
    ISSN 1179-1349
    ISSN 1179-1349
    DOI 10.2147/CLEP.S163208
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Signalling pathways identified in salivary glands from primary Sjögren's syndrome patients reveal enhanced adipose tissue development.

    Aqrawi, Lara A / Jensen, Janicke Liaaen / Øijordsbakken, Gunnvor / Ruus, Ann-Kristin / Nygård, Ståle / Holden, Marit / Jonsson, Roland / Galtung, Hilde Kanli / Skarstein, Kathrine

    Autoimmunity

    2018  Volume 51, Issue 3, Page(s) 135–146

    Abstract: A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little ... ...

    Abstract A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions. We now aimed to examine the development of adipocytes in the SG microenvironment, and delineate their possible involvement in immune reactions. A microarray analysis was performed on SG from 6 pSS patients and 6 non-SS controls, where the expression levels of genes involved in adipose tissue development, inflammatory responses, and lymphoma development were assessed. Real-time PCR was carried out on SG from 14 pSS patients and 15 non-SS controls to account for IL6, IL10, and IL17 mRNA levels. Immunohistochemical staining of frozen SG tissue using IL17 was also conducted. Our results indicate signalling pathways identified in SG of pSS patients displayed genes leading to prominent adipose tissue development and reduced mitochondrial fatty acid beta-oxidation (ARID5B, OXCT1, BDH1, SOX8, HMGCS2, FTO, ECHS1, PCCA, ACADL and ACADVL), inflammatory responses (IL1R1, IL7R, IL10RA, IL15, IL18RAP, CCL2, CCL5, CCL22, CXCR6, CD14, and CD48), and lymphoma development via JAK-STAT signalling (STAT2, TYK2, EBI3, FAS, TNFRSF1B, MAP3K8, HMOX1, LTB, TNF, STAT1, and BAK1). Genes involved in interferon production and signalling were also detected (IRF1, IRF9, and IRF7), in addition to IL6, IL10, and IL17. Higher mRNA levels of IL6, IL17 and IL10 were observed in the SG of pSS patients compared to controls. Moreover, IL17 positive cells were detected mostly interstitially in the SG and around adipocytes, also within the focal infiltrates. In conclusion, adipocyte development seems to be more prominent in the SG of pSS patients, where adipose tissue replacement is also evident. Whether this is due to disease progression, or the repair process, remains to be investigated. Detection of IL17 positive adipocytes in the target organ suggests their involvement in immune reactions.
    MeSH term(s) Adipocytes/cytology ; Adipocytes/metabolism ; Adipose Tissue/metabolism ; Adult ; Aged ; Cellular Microenvironment/immunology ; Female ; Humans ; Inflammation/immunology ; Interleukin-10/genetics ; Interleukin-17/genetics ; Interleukin-6/genetics ; Lymphoma/genetics ; Lymphoma/pathology ; Male ; Middle Aged ; RNA, Messenger/genetics ; Salivary Glands/pathology ; Signal Transduction/genetics ; Signal Transduction/immunology ; Sjogren's Syndrome/immunology ; Sjogren's Syndrome/pathology
    Chemical Substances IL10 protein, human ; IL17A protein, human ; IL6 protein, human ; Interleukin-17 ; Interleukin-6 ; RNA, Messenger ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2018-03-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1025450-x
    ISSN 1607-842X ; 0891-6934
    ISSN (online) 1607-842X
    ISSN 0891-6934
    DOI 10.1080/08916934.2018.1446525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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