1,721,121 research outputs found
AMD. Studies on pathogenesis, treatment and prevention of age-related macular degeneration
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120582.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 20 december 2013Promotores : Hoyng, C.B., Daha, M.R. Co-promotores : Hollander, A.I. den, Klevering, B.J
Preferential binding of unusually long peptides to MHC class I and its influence on the selection of target peptides for T cell recognition
No full textA classic feature of antigen presentation for CD8 T cell recognition is that MHC class I molecules generally present peptides of 8-10 amino acids in length. However, recent studies have demonstrated that peptides of >10 residues play a significant role in immune surveillance by T cells restricted by some HLA class I alleles. In the present study, we describe several examples of unusually long viral peptides of 11 or 12 residues, recognized by CTLs in the context of HLA-B35. Interestingly, all these immunogenic peptides completely encompass shorter canonical length sequences that conform to the HLA-B35 binding motif, but which fail to stimulate detectable T cell responses. The mechanism for this phenomenon appears to involve the preferential binding to HLA-B35 of the atypically long CD8 T cell target peptides over the overlapping canonical length sequences. These data suggest that the peptide length specificity of some HLA class I alleles is broad, allowing peptides of >10 residues to sometimes dominate over canonical length class I ligands as targets for T cell recognition
Role of IgM and C-reactive protein in ischemia reperfusion injury
Full text linkIschemia-reperfusion injury (IRI) is a pathophysiological event that occurs in many clinical conditions, ranging from surgery, acute artery occlusion to transplantation. Complement activation is thought to be a crucial step in IRI, because complement inhibition and complement deficiency considerably attenuate irreversible injury. However, the specific complement pathway remains unclear. All three complement pathways: the classical, the alternative, and the mannose-binding lectin dependent pathway may be involved in the development of IRI, depending on the model, the tissue, and the time course of inflammation. Ischemia leads to the exposition of neoantigens on the jeopardized tissues, which could be recognized by C-reactive protein (CRP) and natural IgM antibodies. The binding of CRP and IgM to these neoepitopes is followed by complement activation. In this thesis, we demonstrated that both proteins bind to jeopardized tissues and activate the complement system, in particular intestines from rats subjected to IRI. Furthermore, it was shown that IgM levels against altered phospholipids correlated with the levels of inflammatory mediators in patients subjected to tissue damage suggesting that IgM participates in amplification of inflammation. The development of strategies to prevent binding of CRP and/or IgM is an attractive approach for a therapy for reducing IRI.UBL - phd migration 201
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
Complement and disease : activation and control
Full text linkActivation of the complement system provides an important mechanism of defense of an organism against invading pathogens. In the healthy individual this defense is finely regulated to prevent attack of the complement system against cells and tissues of the host, however in abnormal situations this regulation can be out of balance. In the present thesis we look at a mouse model where the classical pathway of complement, in conjunction with anti-C1q autoantibodies, is shown to be involved in the development of renal disease (Chapter 2). In Chapter 3, a novel mouse model of complement-mediated glomerulonephritis is described. This model seems to be dependent on the alternative pathway of complement activation as well as on Fc receptors, and provides a novel tool to dissect the contribution of different effector systems in renal inflammation.Then the natural complement-inhibitory properties of the defensin Human Neutrophil Peptide-1 and the extracellular matrix molecules decorin and biglycan are investigated, which are presented to play a role in the regulation of complement in vitro, which hopefully can be extended to in vivo situations of health and disease in the near future (Chapter 4 & 5). The thesis is concluded with a general discussion in Chapter 6.UBL - phd migration 201
Modulated rat dendritic cells in renal transplantation models : immune regulation and graft outcome
Full text linkFollowing allograft transplantation, the immune system is triggered to induce an immunogenic response against the non-self organ. To prevent the induction of this immunogenic response, recipients are treated with immunosuppressive medication. The majority of these medications target T cells, which play a key role in the rejection process, and thereby prevent acute rejection in most of the recipients. Non-specific targeting of these T cells not only prevents acute rejection, it also prevents responses against pathogens or tumor growth. In addition, long-term use of immunosuppressive agents may cause organ failure due to toxic effects on the organ [1]. Therefore, the ultimate goal is to develop a therapy, which targets alloreactive T cells, allowing a normal response against pathogens and tumors, in the absence of chronic use of immunosuppressive agents. Various strategies have been employed to induce such a donor-specific tolerance, amongst which treatment with immature DC [2]. These immature DC have, in contrast to mature DC, the capacity to induce tolerogenic responses and are therefore an attractive candidate for cellular therapy. The studies presented in this thesis demonstrate that in fully mismatched kidney transplantation models, administration of modulated donor-derived DC to recipient__s results in regulation of recipient__s immune response. Both the donor-specific hyporesponsiveness of recipient T cells and the reduced influx of CD8+ T cells into the graft of LPS-DexDC treated recipients indicate a positive effect of this treatment. However, optimization of this treatment is necessary, since no prolonged allograft survival was induced. Several mechanisms, which are not regulated by LPS-DexDC, may be responsible for the observed rejection, amongst which the preformed alloantibodies, increased levels of C3 in the graft and the increased influx of NK cells. Additional studies are required to explore the modulating effects of antibodies which block co-stimulation and/or short courses of immunosuppressive drugs as a co-treatment in these settings.This work was supported by the EU grants QLRT-2001-01215 LSHB-CT-2004-512090 (RISET)UBL - phd migration 201
Pathogenic role of (S)IgA in IgA nephropathy
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Primary IgA nephropathy (IgAN) is the most common form of primary
glomerulonephritis world wide and leads to end stage renal disease in
30-50% of patients. The hallmark of IgAN is the deposition of IgA1 in
the mesangial area of the kidney. Since the inflammatory response which
leads to progressive renal disease, is triggered and sustained by the
deposition of IgA in the renal mesangium, it is important to determine
by which mechanisms binding to mesangial cells (MC) occurs. Most likely
both the intrinsic renal features, as well as circulating factors, such
as structural alterations in serum IgA molecules are thought to be
involved in the pathogenesis of IgAN.
In this thesis we concentrated on two aspects. First identify and
further characterize the IgA binding receptors potentially playing a
role in IgA nephropathy, including FcRI/CD89, Fc/µR. Furthermore, we
characterized the different molecular forms of IgA with special
attention to the specific glycosylation patterns. Finally, we found a
clear deposition of SIgA in the glomeruli of IgA nephropathy patients.
Altogether, the data presented in this thesis support a role for SIgA in
the pathogenesis of a subpopulation of IgAN patients.LEI Universiteit LeidenDutch kidney foundation, Jurriaansestichting, 3A-out foundationniet-projectgebonden outpu
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