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Search Results: 1 - 10 of 5736 matches for " Facchetti Fabio "
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Type I interferon-dependent gene MxA in perinatal HIV-infected patients under antiretroviral therapy as marker for therapy failure and blood plasmacytoid dendritic cells depletion
Raffaele Badolato, Claudia Ghidini, Fabio Facchetti, Federico Serana, Alessandra Sottini, Marco Chiarini, Elena Spinelli, Silvia Lonardi, Alessandro Plebani, Luigi Caimi, Luisa Imberti
Journal of Translational Medicine , 2008, DOI: 10.1186/1479-5876-6-49
Abstract: Circulating pDC were identified by flow cytometry using anti-BDCA-2 monoclonal antibody and by measuring BDCA-2 mRNA by real-time PCR, while tissue-resident pDC were identified by immunohistochemistry. mRNA for interferon-alpha and MxA, a gene that is specifically induced by interferon-alpha, was quantified in peripheral blood cells by real-time PCR, while serum interferon-alpha protein was measured by ELISA.While median values of pDC, both in terms of percentage and absolute number, were not statistically different from age-matched controls, interferon-alpha mRNA was increased in HIV-infected patients. However, in a group of patients with long disease duration, having a low number of both pDC and CD4+ lymphocytes and a significant increase of serum interferon-alpha, MxA mRNA was produced at high level and its expression directly correlated with HIV RNA copy numbers. Furthermore in patients displaying a low CD4+ blood cell count, a severe depletion of pDC in the tonsils could be documented.HIV replication unresponsive to antiretroviral treatment in perinatal-infected patients with advanced disease and pDC depletion may lead to interferon-alpha expression and subsequent induction of MxA mRNA. Thus, the latter measurement may represent a valuable marker to monitor the clinical response to therapy in HIV patients.Over the last 10 years the use of antiretroviral therapy (ART) in HIV-infected children has resulted in noticeable benefit as indicated by increased survival [1,2]. However, poor adherence to prescriptions and the high rates of virus replication that are characteristic of perinatal infection [3] often lead to higher virological set points in children compared to adults and lower rates of attainment of undetectable viral loads. Therefore, the identification of immunological correlates of immune reconstitution and early predictors of antiretroviral failure in HIV-treated children are needed. Concomitantly with loss of CD4+ cells, children with HIV infection disp
Autocatalytic Loop, Amplification and Diffusion: A Mathematical and Computational Model of Cell Polarization in Neural Chemotaxis
Paola Causin ,Giuseppe Facchetti
PLOS Computational Biology , 2009, DOI: 10.1371/journal.pcbi.1000479
Abstract: The chemotactic response of cells to graded fields of chemical cues is a complex process that requires the coordination of several intracellular activities. Fundamental steps to obtain a front vs. back differentiation in the cell are the localized distribution of internal molecules and the amplification of the external signal. The goal of this work is to develop a mathematical and computational model for the quantitative study of such phenomena in the context of axon chemotactic pathfinding in neural development. In order to perform turning decisions, axons develop front-back polarization in their distal structure, the growth cone. Starting from the recent experimental findings of the biased redistribution of receptors on the growth cone membrane, driven by the interaction with the cytoskeleton, we propose a model to investigate the significance of this process. Our main contribution is to quantitatively demonstrate that the autocatalytic loop involving receptors, cytoplasmic species and cytoskeleton is adequate to give rise to the chemotactic behavior of neural cells. We assess the fact that spatial bias in receptors is a precursory key event for chemotactic response, establishing the necessity of a tight link between upstream gradient sensing and downstream cytoskeleton dynamics. We analyze further crosslinked effects and, among others, the contribution to polarization of internal enzymatic reactions, which entail the production of molecules with a one-to-more factor. The model shows that the enzymatic efficiency of such reactions must overcome a threshold in order to give rise to a sufficient amplification, another fundamental precursory step for obtaining polarization. Eventually, we address the characteristic behavior of the attraction/repulsion of axons subjected to the same cue, providing a quantitative indicator of the parameters which more critically determine this nontrivial chemotactic response.
Metabolic Adaptation Processes That Converge to Optimal Biomass Flux Distributions
Claudio Altafini?,Giuseppe Facchetti
PLOS Computational Biology , 2015, DOI: 10.1371/journal.pcbi.1004434
Abstract: In simple organisms like E.coli, the metabolic response to an external perturbation passes through a transient phase in which the activation of a number of latent pathways can guarantee survival at the expenses of growth. Growth is gradually recovered as the organism adapts to the new condition. This adaptation can be modeled as a process of repeated metabolic adjustments obtained through the resilencings of the non-essential metabolic reactions, using growth rate as selection probability for the phenotypes obtained. The resulting metabolic adaptation process tends naturally to steer the metabolic fluxes towards high growth phenotypes. Quite remarkably, when applied to the central carbon metabolism of E.coli, it follows that nearly all flux distributions converge to the flux vector representing optimal growth, i.e., the solution of the biomass optimization problem turns out to be the dominant attractor of the metabolic adaptation process.
Activin A Induces Langerhans Cell Differentiation In Vitro and in Human Skin Explants
Tiziana Musso, Sara Scutera, William Vermi, Roberta Daniele, Michele Fornaro, Carlotta Castagnoli, Daniela Alotto, Maria Ravanini, Irene Cambieri, Laura Salogni, Angela Rita Elia, Mirella Giovarelli, Fabio Facchetti, Giampiero Girolomoni, Silvano Sozzani
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003271
Abstract: Langerhans cells (LC) represent a well characterized subset of dendritic cells located in the epidermis of skin and mucosae. In vivo, they originate from resident and blood-borne precursors in the presence of keratinocyte-derived TGFβ. Ιn vitro, LC can be generated from monocytes in the presence of GM-CSF, IL-4 and TGFβ. However, the signals that induce LC during an inflammatory reaction are not fully investigated. Here we report that Activin A, a TGFβ family member induced by pro-inflammatory cytokines and involved in skin morphogenesis and wound healing, induces the differentiation of human monocytes into LC in the absence of TGFβ. Activin A-induced LC are Langerin+, Birbeck granules+, E-cadherin+, CLA+ and CCR6+ and possess typical APC functions. In human skin explants, intradermal injection of Activin A increased the number of CD1a+ and Langerin+ cells in both the epidermis and dermis by promoting the differentiation of resident precursor cells. High levels of Activin A were present in the upper epidermal layers and in the dermis of Lichen Planus biopsies in association with a marked infiltration of CD1a+ and Langerin+ cells. This study reports that Activin A induces the differentiation of circulating CD14+ cells into LC. Since Activin A is abundantly produced during inflammatory conditions which are also characterized by increased numbers of LC, we propose that this cytokine represents a new pathway, alternative to TGFβ, responsible for LC differentiation during inflammatory/autoimmune conditions.
Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH): revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma
Chung-Che Chang, Xiaobo Zhou, Jesalyn J Taylor, Wan-Ting Huang, Xianwen Ren, Federico Monzon, Yongdong Feng, Pulivarthi H Rao, Xin-Yan Lu, Facchetti Fabio, Susan Hilsenbeck, Chad J Creighton, Elaine S Jaffe, Ching-Ching Lau
Journal of Hematology & Oncology , 2009, DOI: 10.1186/1756-8722-2-47
Abstract: Examination of genomic data in PL revealed that the most frequent segmental gain (> 40%) include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related) cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation.To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related) than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.Plasmablastic lymphoma (PL), one of the most frequent oral malignancies in human immunodeficiency virus (HIV) infected patients, was first characterized by Delecluse et al [1]. They proposed that this constituted a new subtype of diffuse large B cell lymphoma (DLBCL); it was suggested as a distinct entity based on its blastic morphology, its clinical behavior involving predominantly extramedullary sites (particularly oral cavity), and its limited antigenic phenotype data suggesting differentiation toward plasmacytic differentiation (CD20-, CD79a+ and VS38c+). The incidence of PL has increased following the introduction of highly active antiretroviral therapy (HAART) [2,3]. By WHO Classification, PL is categorized as a subtype of DLBCL associated with HIV and Epstein-Barr virus [1,4,5].Recent morph
Nodular Lymphocyte Predominant Hodgkin Lymphoma and T Cell/Histiocyte Rich Large B Cell Lymphoma - Endpoints of a Spectrum of One Disease?
Sylvia Hartmann, Claudia D?ring, Christina Jakobus, Benjamin Rengstl, Sebastian Newrzela, Thomas Tousseyn, Xavier Sagaert, Maurilio Ponzoni, Fabio Facchetti, Chris de Wolf-Peeters, Christian Steidl, Randy Gascoyne, Ralf Küppers, Martin-Leo Hansmann
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0078812
Abstract: In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T cell/histiocyte rich large B cell lymphoma (THRLBCL) is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL with considerable histopathologic overlap compared to THRLBCL. Especially THRLBCL-like NLPHL, a diffuse form of NLPHL, often presents a histopathologic pattern similar to THRLBCL, suggesting a close relationship between both lymphoma entities. To corroborate this hypothesis, we performed gene expression profiling of microdissected tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. In unsupervised analyses, the lymphomas did not cluster according to their entity. Moreover, even in supervised analyses, very few consistently differentially expressed transcripts were found, and for these genes the extent of differential expression was only moderate. Hence, there are no clear and consistent differences in the gene expression of the tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. Based on the gene expression studies, we identified BAT3/BAG6, HIGD1A, and FAT10/UBD as immunohistochemical markers expressed in the tumor cells of all three lymphomas. Characterization of the tumor microenvironment for infiltrating T cells and histiocytes revealed significant differences in the cellular composition between typical NLPHL and THRLBCL cases. However, THRLBCL-like NLPHL presented a histopathologic pattern more related to THRLBCL than NLPHL. In conclusion, NLPHL and THRLBCL may represent a spectrum of the same disease. The different clinical behavior of these lymphomas may be strongly influenced by differences in the lymphoma microenvironment, possibly related to the immune status of the patient at the timepoint of diagnosis.
Occurrence of Nodular Lymphocyte-Predominant Hodgkin Lymphoma in Hermansky-Pudlak Type 2 Syndrome Is Associated to Natural Killer and Natural Killer T Cell Defects
Luisa Lorenzi, Giovanna Tabellini, William Vermi, Daniele Moratto, Fulvio Porta, Lucia D. Notarangelo, Ornella Patrizi, Silvano Sozzani, Genevieve de Saint Basile, Sylvain Latour, David Pace, Silvia Lonardi, Fabio Facchetti, Raffaele Badolato, Silvia Parolini
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080131
Abstract: Hermansky Pudlak type 2 syndrome (HPS2) is a rare autosomal recessive primary immune deficiency caused by mutations on β3A gene (AP3B1 gene). The defect results in the impairment of the adaptor protein 3 (AP-3) complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL) in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf) + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56brightCD16? Natural Killer (NK) cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-γ production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.
Predicting and characterizing selective multiple drug treatments for metabolic diseases and cancer
Giuseppe Facchetti, Mattia Zampieri, Claudio Altafini
BMC Systems Biology , 2012, DOI: 10.1186/1752-0509-6-115
Abstract: Two different applications are considered: finding drug synergisms for human metabolic diseases (like diabetes, obesity and hypertension) and finding antitumoral drug combinations with minimal side effect on the normal human metabolism. The results we obtain are consistent with some of the available therapeutic indications and predict some new multiple drug treatments. A cluster analysis on all possible interactions among the currently available drugs indicates a limited variety on the metabolic targets for the approved drugs.The in silico prediction of drug synergism can represent an important tool for the repurposing of drug in a realistic perspective which considers also the selectivty of the therapy. Moreover, for a more profitable exploitation of drug-drug interactions, also drugs which show a too low efficacy but which have a non-common mechanism of action, can be reconsider as potential ingredients of new multicompound therapeutic indications. Needless to say the clues provided by a computational study like ours need in any case to be thoroughly evaluated experimentally.
Tensile Structures of Cables Net, Guidelines to Design and Applications  [PDF]
Fabio Rizzo
Open Journal of Civil Engineering (OJCE) , 2016, DOI: 10.4236/ojce.2016.62023
Abstract: The structural engineering design of not conventional typologies imposes a complex path that begins evaluating procedures of a preliminary design and ends with complex procedures to validate the analysis response. Any guide lines to follow are often available. About complex shapes, in particular, any details are presented in the codes to evaluate wind action and so wind tunnel experiments are necessary to valuate this. The evaluation of wind tunnel data is a complex process that often needs new and specific subroutines programmed by researchers. The difficult increases when the objective is to study a not specific building but general aspects as for examples the dependence of a generic phenomenon by a geometric sample; in this case it is necessary to design and to program numerical subroutines before and then the wind tunnel experiments. Often, these subroutines are left detached and are non-generalizable process. Purpose of this paper is to describe a complete procedure to pre- and post-process wind tunnel data with the objective to design a not convectional structure as a tensile structure. In this particular case the research aim is a parametrization of the aerodynamic behavior of Hyperbolic Paraboloid roofs, shape used for cables net. The reason of the experiments is the absence in the international codes of the pressure coefficients for these geometries. The paper describes the numerical procedure evaluated to choose a sufficient representative geometric sample, the numerical procedure evaluated to design and to construct the wind tunnel models and FE models, the numerical procedure to evaluate and to use for FEM analyses of the wind tunnel data, the numerical procedure to calculate nonlinear structural analysis, and, finally some applications. All these numerical procedures use basic theory derived for example by the cable theory, the fluid mechanic, the nonlinear geometric analysis and other. However specific codes were necessary and were programmed to apply the theories on the specific case of study; the complete methodology followed is presented. The goal is to create a free open domain where the numerical procedures evaluated are merged, added, modified by researchers with the aim to obtain a common space of use for wind engineering of not conventional structure.
Como realizar o correto descarte de resíduos de medicamentos?
Falqueto,Elda; Kligerman,Débora Cynamon; Assump??o,Rafaela Facchetti;
Ciência & Saúde Coletiva , 2010, DOI: 10.1590/S1413-81232010000800034
Abstract: the final destination of medicine residues is a relevant subject to the public health due to the pharmacological properties of each medicine, that in future will become a residue and will need to be treated. in brazil, the correct discard of the solid medicine residues is regulated by the ministry of health and also by the ministry of environment, that aim to provide the producers of medicine residues with instruments that enable them to correctly discard those residues. however, there are some obstacles that can only be overcome through the integration of all agents involved in this process. the purpose of this article is to make a critical survey of the legal instruments offered by the regulatory institutions, locating each agent and its responsibilities concerning the protection of public health and the environment.
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