1,720,987 research outputs found
Involvement of NOD2 in macrophage response to leishmania tropica infection
No full textBACKGROUND-AIM Leishmaniasis is a protozoan disease caused by parasites belonging to the genus Leishmania. In the human host, these parasites invade macrophages where they develop into intracellular amastigotes and multiply within phagolysosomes. Host cells can control the infection initially through the triggering of innate immune responses. NOD-like receptors (NLRs) are a family of innate immune cytosolic receptors able to recognize pathogen-associated molecular patterns. NOD1 and NOD2 detect pathogens that are able to invade and multiply intracellularly. Once stimulated, these receptors induce the activation of NF-κB and MAPKs, which lead to the transcription of genes involved in inflammation and immune responses. The aim of this work was to evaluate the role of NOD2 in some innate immune responses of macrophages infected with L. tropica. In particular, the production of TNF-a, or nitric oxide (NO), and the expression of inducible NO synthase (iNOS) were evaluated METHODS Immortalized bone marrow-derived macrophages (BMDM) from wild type (WT) C57Bl/6 or knockout (KO) mice for NOD2 were used. The levels of TNF-a released into the supernatants of BMDM-WT or -NOD2-KO treated with L. tropica were measured by ELISA. Also, the presence of nitrite was evaluated, through the Griess test, as an indication of nitric oxide (NO) production. Finally, protein and gene expression levels of iNOS were retrieved by Western blot analysis and realtime PCR, respectively. RESULTS The involvement of NOD2 in BMDM treated with L. tropica was elucidated as the levels of TNF-a or NO released from BMDM-WT infected with L. tropica were significantly higher compared to the BMDM-NOD2-KO. On the other side, the expression of iNOS (RNA and protein) was higher in BMDM-WT treated with L. tropica than in BMDM-NOD2-KO. CONCLUSIONS Altogether, these data indicated a crucial role of NOD2 for these innate immune responses of BMDM infected with L.tropica
Refinement and optimisation of the rat CFU-GM assay to incorporate the use of cryopreserved bone-marrow cells for in vitro toxicology applications
No full textThe colony-forming unit-granulocyte-macrophage (CFU-GM) assay has been validated for testing drug haematotoxicity (with both mouse bone-marrow and human cord blood cells) and for predicting in vivo human Maximal Tolerated Dose (MTD) values by extrapolating in vivo data on mouse toxicity. The rat CFU-GM assay is widely used for its capability to evaluate in vitro haematotoxicity, but no standardised procedure suitable for data comparison has been developed. A validated rat CFU-GM assay is needed for many reasons - not least because the rat is the most commonly-used species for the in vivo testing of toxicants. This report describes the refinement and optimisation of a standardised protocol for entering into the prevalidation phase of test development. The sensitivity of rat progenitors to granulocyte-macrophage-colony stimulating factor (GM-CSF), the correlation between the number of cells seeded and the number of colonies obtained, the role of mesenchymal cells on CFU-GM proliferation and the performance of the assay, and the effects of using different types of plastic dishes and sources of cytokines, are described. A standard operating procedure (SOP) based on the use of cryopreserved progenitors has been generated, to be applied to the in vitro toxicity testing of compounds. This SOP dramatically reduces the number of rats used and increases the homogeneity of the data obtaine
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
Valutazione in vitro dell'effetto di cellule staminali mesenchimali umane da midollo osseo (MSCs) sulla crescita di tumori
No full textVariations 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
Microbiological risk assessment in stem cell manipulation
No full textCell therapy based on the use of human stem cells is more complicated than transfusion or organ transplantation because cells may undergo many additional manipulations due to different treatments for isolation, expansion, differentiation, and other types of biological changes. These manipulations require the approval of regulatory agencies (other than ethical) and the processes must be monitored with more tests than the ones applied for minimally manipulated cells. The clinical safety and efficacy of transplanted cells depend on several factors such as homologous or non-homologous sources, extent of manipulation, and culture conditions. Moreover, the kind of information needed to address these issues may differ depending on whether the cells are to be used for tissue reconstruction or repair, or to recover metabolic functions. Also anatomical site, functional integration as well as duration of therapy, are crucial points that indirectly can influence safety. Many important assays have been suggested for environmental monitoring as well as to standardize microbiological controls in stem cell banks to prevent contamination. In order to guarantee safety two main aspects must be considered: one is related to the source of cells (the donor) and the other is depending on cell collection and processing. In this review we critically analyze the steps of the processes (from collection to banking) and consider the main factors involved in the clinical research (continuously in evolution) by suggesting a standardized facsimile form to use in the laboratory for the assessment of the microbiological risk related to the cell manipulations
Caratterizzazione della capacità differenziativa della linea cellulare mesenchimale murina SR-4987
No full textI recenti progressi nell'utilizzo delle cellule staminali mesenchimali (MSC) nell'ambito della medicina rigenerativa/riparativa hanno confermato la notevole versatilità di queste cellule e posto nuovi ed interessanti interrogativi circa la loro attività biologica, che può essere ulteriormente indagata e approfondita mediante modelli di MSC stabilizzate in vitro. La linea murina SR-4987,stabilizzata nel nostro laboratorio da colture a lungo termine di cellule stromali di midollo osseo, presenta caratteristiche tipiche delle MSC (morfologia,produzione di M-CSF, sensibilità a FGF-b)esprime markers B-linfocitari ed è in grado di produrre sarcomi in animali singenic
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
In vitro toxicity of clozapine, olanzapine, and quetiapine on granulocyte-macrophage progenitors (GM-CFU)
No full textIntroduction: Atypical antipsychotics may lead to agranulocytosis because of the apoptosis caused by cells binding nitrenium mols. Studies showing the direct myelotoxicity of clozapine were undertaken years ago using different assays, and thus it is difficult to compare them with those of clozapine's analogs that have been more recently reported as causing neutropenia, agranulocytosis, and thrombocytopenia. Methods: We compared the direct toxicity of clozapine, olanzapine, quetiapine, and chlorpromazine using a previously standardized GM-CFU assay validated for predicting neutropenia. Results: The results showed that all of the drugs were characterized by dose-dependent toxicity, which was greatest in the case of chlorpromazine (IC90= 10.02 +- 0.69 mg/mL), followed by olanzapine (IC90= 13.43 +- 1.23 mg/mL), clozapine (IC90= 44.71 +- 4.42 mg/mL), and quetiapine (IC90= 137.24 +- 15.36 mg/mL). Discussion: These data agree with recent clin. reports concerning the direct or mediated toxic effects of olanzapine on progenitor and committed cells (GM-CFU) and suggest that the correlation between its plasma levels and clin. effects warrants further investigation. There are no published data concerning the bone marrow pharmacokinetics of atypical antipsychotics or their possible bioactivation by the bone marrow cell compartment, but our findings suggest that they may affect hematopoiesis in different ways, such as the direct action of them or their metabolites due to bioactivation by hematopoietic cells themselves
- …
