1,720,979 research outputs found
ZAP70 deficiency in humans is associated with abnormalities of thymic stromal cells: implications for T cell tolerance
No full textInteraction between developing thymocytes and thymic stromal
cells is essential to promote T lymphocyte development and maturation of thymic stromal cells, thereby permitting also negative selection of selfreactive T cells and generation of natural regulatory T (nTreg) cells. Here we provide the first detailed analysis of thymic architecture and stromal cell composition in patients with ZAP70 deficiency. We demonstrate that ZAP70 deficiency in humans is permissive for the generation of cortical and medullary thymic epithelial cells, for the expression of AIRE and for the development of nTreg cells. However, the number of AIRE+ cells and of FOXP3+ cells is significantly reduced as compared to normal thymus. Furthermore, the thymus of ZAP70-deficient patients shows impaired maturation of medullary thymic epithelial cells and depletion of all major dendritic cell subtypes. These abnormalities may account for the occurrence of Omenn syndrome and other manifestations of immune dysregulation in patients with ZAP70 deficiency. At the same time, abnormalities of thymic architecture and stromal cell maturation in patients with ZAP70 deficiency are milder than in earlier defects in T cell development, thereby accounting for the lower frequency of Omenn syndrome and of autoimmune complications in ZAP70 deficiency than in other conditions, such as RAG deficienc
Cartilage-hair hypoplasia: molecular basis and heterogeneity of the immunological phenotype.
No full textEarly defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome
No full textThymocytes and thymic epithelial cell (TEC) cross-talk is crucial to preserve thymic architecture and function, including maturation of TECs and dendritic cells, and induction of mechanisms of central tolerance.We have analyzed thymic maturation and organization in 9 infants with various genetic defects leading to complete or partial block in T-cell development. Profound abnormalities of TEC differentiation (with lack of AIRE expression) and severe reduction of thymic dendritic cells were identified in patients with Tnegative severe combined immunodeficiency, reticular dysgenesis, and Omenn syndrome. The latter also showed virtual absence of thymic Foxp3 T cells. In contrast, an IL2RG-R222C hypomorphic mutation
permissive for T-cell development allowed for TEC maturation, AIRE expression, and Foxp3 T cells. Our data provide
evidence that severe defects of thymopoiesis impinge on TEC homeostasis and may affect deletional and nondeletional
mechanisms of central tolerance, thus favoring immune dysreactive manifestations, as in Omenn syndrome
Burkitt's lymphoma in a patient with adenosine deaminase deficiency-severe combined immunodeficiency treated with polyethylene glycol-adenosine deaminase
No full textVariability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations.
No full textBackground: Cartilage hair hypoplasia is an autosomal recessive type of metaphyseal chondrodysplasia, caused by mutations in the ribonuclease mitochondrial RNA processing (RMRP) gene. Typical features of cartilage hair hypoplasia include short stature, a predisposition to malignancy, and a variable degree of impairment of cellular immunity. Objective: We sought to describe the heterogeneity of clinical and immunologic phenotype in 12 consecutive patients with RMRP mutations who were referred to 2 different institutions for immunologic evaluation.
Methods: We have retrospectively analyzed the clinical and laboratory features in 12 patients with molecular defects in the RMRP gene. T-cell repertoire was investigated by quantitating Vb families’ expression and analyzing their diversity. T-cell receptor excision circle analysis was used to study thymic output. Results: All 12 patients had significant immune abnormalities, leading to severe immune deficiency in 9. CD8 lymphocytopenia was identified as a novel phenotype associated with RMRP mutations. Significant, even intrafamilial, phenotypic heterogeneity was observed. In 3 cases, severe immunodeficiency was the only phenotypic manifestation associated with RMRP mutations, a novel finding. Mutations leading to significant immune defects were most often located in the promoter, and the first case of a compound heterozygote for 2 such mutations is reported.
Conclusion: This report broadens the spectrum of phenotypes associated with RMRP mutations and suggests that mutations in this gene should be considered when evaluating patients with combined immune deficiency, regardless of the presence of other manifestations
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
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