1,721,010 research outputs found
ANALYSIS OF A “NOVEL” SUBSET OF CD34+ HAEMATOPOIETIC PRECURSORS IN PERIPHERAL BLOOD OF PATIENTS WITH CHRONIC INFLAMMATORY DISEASES
Full text linkBackground: in chronic inflammatory disorders, both infectious and non infectious, a novel population of CD34+ hemopoietic precursors is detectable in high proportions in peripheral blood (PB). These precursors display peculiar phenotypic characteristics, namely the expression of DNAM-1 (bright), an activating receptor expressed by natural killer (NK) cells and CXCR4, a chemokine receptor that suggests their recent exit from bone marrow (BM). In healthy donors (HD), these precursors are virtually undetectable in PB while they represent 10-15% of BM CD34+ cells. It is conceivable that, in chronic inflammatory processes, pro-inflammatory cytokines may favor the exit of this CD34+ subset. While their presence in PB during chronic inflammation may represent a homeostatic event to compensate an accelerated cell death, a major interest in these cells is related to their differentiating capacity, which has been analyzed in the present study. Methods: we evaluated by cytofluorimetric analysis the presence of CD34+ DNAM1bright CXCR4+ cells in different pathological conditions characterized by chronic inflammation including selected viral infections and autoimmune diseases and defined the phenotypic and functional characteristics of both NK and T cells generated in vitro from purified CD34+ DNAM1bright CXCR4+ progenitors. Results: first, we confirmed in our cohorts that patients with autoimmune diseases or with chronic viral infections display high proportions of CD34+DNAM-1brightCXCR4+ precursors, which could even outnumber the conventional CD34+DNAM-1-CXCR4- precursors. Analysis of the progenies of these cells cultured in the presence of appropriate cytokines, showed that both CD56+CD3- (NK) and CD56-CD3+ (T) cells can be generated. Comparison of the lymphoid progenies derived from precursors isolated from patients with viral infections versus patients with autoimmunity revealed a high prevalence of NK cells in the former, while, in autoimmunity, T cell progenies largely prevailed. In the first set of experiments, we focused on NK cell progenies, mostly from HIV and HCV infected patients. CD34+DNAM-1brightCXCR4+ cells gave rise, in approximately 20 days of colture, to sizeable populations of fully mature NK cells expressing KIRs, CD57, DNAM-1, NKG2D and NKG2C (a HLA-E specific activating receptor correlated with infection/sieropositivity for cytomegalovirus, CMV). This rapid differentiation towards mature NK cells was never occurring in conventional CD34+ precursors. Notably, the NKG2C+ progenies could undergo selective expansion upon NK cell colture with HLA-E-transfected 221 cell line. Further analysis of T cell progenies derived from highly purified (>99%) CD34+DNAM-1brightCXCR4+ precursors isolated from patients with autoimmune diseases, revealed the presence of both CD4+ and CD8+ T cells. Importantly, the large majority of cells expressed CXCR4 and the activating receptors DNAM-1 and NKG2D and 2B4 co-receptor. Analysis of CD4+ T cell progenies showed the presence of both Th1 star (Th1*) and Th17 subsets. Conclusions: the generation of T cells in the absence of thymic selection together with the expression of activating NK receptors capable of inducing a HLA-independent T-cell activation (or to amplify low affinity TCR responses) and the presence of Th1* and Th17 may suggest the possible involvement of these cells in the pathogenesis of self-damage in autoimmunity
Designing a Methodology for Semantic Type Tagging of Argument Positions
Full text linkA verb argument position can be described by the semantic type that characterizes the words filling that position. We investigate a number of linguistic issues underlying the tagging of an Italian corpus with the semantic types provided by the T-PAS (Typed Predicate-Argument Structure) resource. Our main interest is to evaluate whether our annotation methodology can be employed effectively for the extension of the annotation of the corpus associated with the resource. In order to achieve this goal we compare quantitative data about the tagging and qualitative data derived from the Inter-Annotator Agreement
Il trapianto di cellule staminali emopoietiche nei pazienti affetti da thalassemia major
No full textIl trapianto di cellule staminali emopoietiche (TCSE) rappresenta ancora oggi
l'unica terapia potenzialmente curativa per i pazienti affetti da talassemia majo
Natural killer cells in the treatment of high-risk acute leukaemia
No full textSeveral studies have shown that in patients with acute leukaemia given allogeneic haematopoietic stem cell transplantation (allo-HSCT) large part of the therapeutic effect lies on the anti-tumour effect displayed by cells of both adaptive and innate immunity. This evidence has also opened new scenarios for the treatment of patients with other haematological malignancies/solid tumours. In particular, donor-derived natural killer (NK) cells play a crucial role in the eradication of cancer cells in patients given an allograft from an HLA-haploidentical relative, especially when there is a killer inhibitory-receptor (KIR)-KIR ligand mismatched in the donor-recipient direction. Alloreactive donor-derived NK cells have been also demonstrated to kill recipient antigen-presenting cells and cytotoxic T lymphocytes, thus preventing graft-versus-host disease (GvHD) and graft rejection and to largely contribute to the defence against cytomegalovirus infection in the early post-transplant period. Several clinical studies have recently focused also on the influence of NK-cell activating receptors on the outcome of allo-HSCT recipients; in particular, B/x haplotype donors offer clinical advantages compared with A/A donors, even when the donor is an HLA-identical volunteer. Altogether, these data have provided the rationale for implementing phase I/II clinical trials based on adoptive infusion of either selected or ex vivo activated NK cells from an HLA-mismatched donor. This review summarizes the biological and clinical data on the role played by NK cells in patients with high-risk acute leukaemia, focusing also on the still unsolved issues and the future perspectives related to the approaches of adoptive NK cell therapy
Tagging Semantic Types for Verb Argument Positions
No full textVerb argument positions can be described by the semantic types that characterise the words filling that position. We investigate a number of linguistic issues underlying the tagging of an Italian corpus with the semantic types provided by the T-PAS (Typed Predicate-Argument Struc- ture) resource. We report both quantitative data about the tagging and a qualitative analysis of cases of disagreement between two annotators
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
Human innate lymphoid cells
No full textThe interest in innate lymphoid cells (ILC) has rapidly grown during the last decade. ILC include distinct cell types that are collectively involved in host protection against pathogens and tumor cells and in the regulation of tissue homeostasis. Studies in mice enabled a broad characterization of ILC function and of their developmental requirements. In humans all mature ILC subsets have been characterized and their role in the pathogenesis of certain disease is emerging. Nonetheless, still limited information is available on human ILC development. Indeed, only the cell precursors committed towards NK cells or ILC3 have been described. Here, we review the most recent finding on human mature ILC, discussing their tissue localization and function. Moreover, we summarize the available data regarding human ILC development
Antibodies Directed against a Peptide Epitope of a Klebsiella pneumoniae-Derived Protein Are Present in Ankylosing Spondylitis
Full text linkAnkylosing spondylitis (AS) is a chronic inflammatory arthritis of unknown origin. Its autoimmune origin has been suggested but never proven. Several reports have implicated Klebsiella pneumoniae as a triggering or perpetuating factor in AS; however, its role in the disease pathogenesis remains debated. Moreover, despite extensive investigations, a biomarker for AS has not yet been identified. To clarify these issues, we screened a random peptide library with pooled IgGs obtained from 40 patients with AS. A peptide (AS peptide) selected from the library was recognized by serum IgGs from 170 of 200 (85%) patients with AS but not by serum specimens from 100 healthy controls. Interestingly, the AS peptide shows a sequence similarity with several molecules expressed at the fibrocartilaginous sites that are primarily involved in the AS inflammatory process. Moreover, the peptide is highly homologous to a Klebsiella pneumoniae dipeptidase (DPP) protein. The antibody affinity purified against the AS peptide recognizes the autoantigens and the DPP protein. Furthermore, serum IgG antibodies against the Klebsiella DPP121-145 peptide epitope were detected in 190 of 200 patients with AS (95%), 3 of 200 patients with rheumatoid arthritis (1.5%) and only 1 of 100 (1%) patients with psoriatic arthritis. Such reactivity was not detected in healthy control donors. Our results show that antibodies directed against an epitope of a Klebsiella pneumoniae-derived protein are present in nearly all patients with AS. In the absence of serological biomarkers for AS, such antibodies may represent a useful tool in the diagnosis of the disease
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