1,721,188 research outputs found
De Rol van Aangeboren Lymfoïde Cellen in Chronische Colitis en Intestinale Fibrose
No full textIntestinal tissue damage and remodeling is a hallmark of inflammatory bowel disease (IBD) progression and severity. Developments in the field of immunosuppressive agents and biologicals have resulted in higher remission rates in IBD patients. However, progress in the prevention and treatment of intestinal fibrosis has been limited. Therefore, new insights in the pathogenesis of intestinal fibrosis are required to identify new pathways for intervention. The main objective of this doctoral thesis was to unravel the role of innate lymphoid cells (ILC) in chronic intestinal inflammation and remodeling in mice and men.
In a chronic murine model of inflammatory colitis, we showed that the adaptive immune system is activated with progressive induction of T helper (Th)1 and Th17 cells in mesenteric lymph nodes with increasing number of cycles of administration of dextran sulfate sodium (DSS). Inhibition of T helper cell associated cytokines or regulatory T cells did not alter the deposition of collagen. Next, we showed that fibrosis can still be induced in the absence of the adaptive immune system.
Identification of innate lymphoid cells (ILC) as mucosal, resident, cytokine-producing cells and players in liver and lung fibrosis, led us to the study of these cells in our murine model of chronic intestinal inflammation and fibrosis. In both wild type and RAG1-/- mice we observed an enrichment of interleukin (IL)-13 producing ILC2 with increasing numbers of DSS administration. However, upon antibody-mediated depletion of all ILC, no attenuation of fibrosis could be observed. These results were validated in ILC deficient mice. However, in these mice we found that in absence of ILC, recovery after withdrawal of DSS is impaired and associated with a higher mortality. To identify essential alternative innate immune players responsible for the induction of fibrosis in the absence of both ILC and the adaptive immune system, we targeted neutrophils, eosinophils and mast cells. However, our preliminary data did not illustrate a major role of these cells in our model.In the inflamed gut tissue of patients with IBD we found an increase in pro-inflammatory ILC1 and in immature NKp44- ILC3, while there was a decrease of mature NKp44+ ILC3 when compared to healthy controls. Similar but less pronounced changes in ILC1 were observed in blood, while circulating NKp44- ILC3 were decreased. Changes in mucosal and peripheral ILC subpopulations could not differentiate between Crohn's disease (CD) and ulcerative colitis (UC). In fifteen % of CD patients we observed NKp44+ ILC3 in blood, and these cells were not detected in blood of healthy
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controls or UC patients. We were able to show that current biological therapy (ustekinumab targeting the IL-12/23 cytokines, anti-tumor necrosis factor and vedolizumab) can partly restore intestinal ILC subset equilibrium with a decrease in ILC1 (except for ustekinumab) and an increase in NKp44+ ILC3. Furthermore anti-TNF therapy was also able to mobilize more NKp44+ ILC3 in circulation.
In order to translate the findings of the murine model to human disease, we characterized the cells of both the innate and adaptive immune system in the mucosa and the deeper layers of intestinal resection tissues of patients with fibrostenosing CD. In the inflamed ileum, no differences were observed between mucosa and deeper layers, reflecting the transmural nature of CD. In contrast, in the fibrotic ileum, B cells, eosinophils, mature dendritic cells and M2 macrophages were enriched. These results argue that inflammation in the deeper intestinal layers is different from the inflammatory signature seen in inflamed regions.
Overall we were able to show that ILC are not essential for the induction of fibrosis in a murine model, arguing for redundancy of ILC in intestinal remodelling. However, both in mice and CD patients with intestinal remodelling, an enrichment of other innate immunity cells including neutrophils, eosinophils and monocytes point to a major role of the myeloid cell lineage in intestinal fibrosis.status: Publishe
Studie van inflammatie en fibrose in een model van chronische inflammatoire colitis
No full textCrohns disease is in essence a transmural disease in which chronic intestinal inflammation leads to perforating ulcers (due to insufficient mucosal healing) and intestinal wall fibrosis (due to excessive healing). Despite the clinical importance of fibrosis in IBD, until now, there is no clue about the time course, the pathophysiology or the treatment, nor are there good markers of fibrosis in serum, imaging tools or good animal models to study fibrosis. Therefore, the general aim of this study was to develop a chronic model of relapsing murine colitis mimicking human disease in order to acquire in depth knowledge on the mechanisms responsible for intestinal fibrosis. Next, we aimed to search for non-invasive imaging tools to assess intestinal inflammation and fibrosis. We have set up a reliable chronic colitis model in mice by exposing them to repeated cycles of administration of DSS followed by a recovery period. In this chronic model of inflammatory colitis which pathologically mimics human CD, we showed that the adaptive immune system is activated with induction of Th1 and Th17 cells in MLNs. This effect is progressive with an increasing number of cycles of administration of DSS. Inhibition of T cell associated cytokines IFN-gamma and IL-17F during the chronic phase of inflammation did not alter the deposition of collagen. Anti-IL-17A slightly promoted fibrosis. Next, we showed that fibrosis can be induced by chronic DSS colitis in RAG-1 deficient mice on the C57BL/6 background, suggesting that the adaptive immune system is not crucial for fibrogenesis in chronic DSS colitis. Furthermore, transcriptomic analysis of colonic gene expression in the different phases of inflammation and fibrosis, provided information on the differential regulation of genes during inflammation, fibrosis and recovery. During prolonged recovery after the induction of fibrosis, an upregulation of keratins was observed. A type I IFN-related gene signature could be identified in chronic colitis in RAG-1 KO mice as compared to WT mice. Finally, we showed that in vivo T2 relaxometry is a promising non-invasive assessment tool of inflammation and fibrosis of the bowel wall in murine colitis. Furthermore, in a clinical setting, MRI T2 relaxometry of the pelvis was feasible in patients with IBD and a histogram shift compared to healthy volunteers reminiscent of chronic DSS colitis was observed.status: Publishe
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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