1,721,018 research outputs found
Peripheral blood dendritic cells in human healthy and pathological pregnancy
No full textPregnancy provides a major challenge to the maternal immune system, which must tolerate fetal alloantigens encoded by paternal genes for allowing the fetus to grow and develop in the uterus despite being recognized. Dendritic cells (DCs) are widely distributed potent antigen-presenting cells that bridge the arms of innate and adaptive immunity. They can either promote or prevent immune activation, thus playing a central role in the control of immune tolerance. DCs in pregnant women have been characterized mainly at the maternal-decidual interface, where their state of activation has emerged as one of the key players influencing the feto-maternal immunological equilibrium. Growing evidences indicate that during pregnancy also DCs circulating in the peripheral blood, which is the most accessible source of DCs, undergo changes that may be relevant to the adaptation of maternal immune responses needed to allow fetal growth. Moreover, alterations of circulating DCs that may likely reflect alterations occurring in the decidua have also been described in pathological pregnancies, such as in pregnancies complicated by intrauterine growth restriction or pre-eclampsia
Peripheral blood dendritic cells in human healthy and pathological pregnancy
No full textPregnancy provides a major challenge to the maternal immune system, which must tolerate fetal alloantigens encoded by paternal genes for allowing the fetus to grow and develop in the uterus despite being recognized. Dendritic cells (DCs) are widely distributed potent antigen-presenting cells that bridge the arms of innate and adaptive immunity. They can either promote or prevent immune activation, thus playing a central role in the control of immune tolerance. DCs in pregnant women have been characterized mainly at the maternal-decidual interface, where their state of activation has emerged as one of the key players influencing the feto-maternal immunological equilibrium. Growing evidences indicate that during pregnancy also DCs circulating in the peripheral blood, which is the most accessible source of DCs, undergo changes that may be relevant to the adaptation of maternal immune responses needed to allow fetal growth. Moreover, alterations of circulating DCs that may likely reflect alterations occurring in the decidua have also been described in pathological pregnancies, such as in pregnancies complicated by intrauterine growth restriction or pre-eclampsia
Sarcoma di Kaposi. Il laboratorio: news
No full textIl sarcoma di Kaposi (KS) è una malattia linfangioproliferativa strettamente associata ad infezione cronica da HHV-8 (human herpesvirus-8), che ne è considerato l’agente eziologico. HHV-8 è un virus pleiotropico, in grado di infettare numerosi tipi cellulari, compresi linfociti B, monociti e progenitori endoteliali circolanti che rappresentano i principali reservoirs virali. Nei pazienti con KS, ognuno di questi tipi cellulari va incontro a profonde alterazioni dovute all'infezione da HHV-8, sia per effetti diretti dell'infezione sia per effetti indiretti mediati dalla produzione di citochine ed altri mediatori solubili. In particolare, l'infezione dei linfociti B induce uno squilibrio nelle sottopopolazioni B circolanti, favorendo l’espansione del compartimento B preimmune. Queste alterazioni non sembrerebbero in grado di compromettere in modo significativo le funzioni immuni difensive nei pazienti con KS, ma potrebbero essere particolarmente rilevanti nello sviluppo di altre malattie linfoproliferative associate ad infezione da HHV-8. L'infezione della linea mieloide si accompagna a profonde alterazioni a carico delle cellule dendritiche, che svolgono un ruolo centrale nel controllo delle malattie infettive e tumorali. L'infezione dei progenitori endoteliali ne induce l'acquisizione di un fenotipo riconducibile a quello delle spindle cells, tipiche delle lesioni sarcomatose. E' verosimile, pertanto, che i progenitori endoteliali infettati da HHV-8 siano i precursori putativi delle spindle cells. Tali cellule darebbero origine alle lesioni tipiche del KS in microambienti favorevoli e con il contributo di monociti, cellule dendritiche e linfociti che, a causa delle alterazioni indotte da HHV-8, fornirebbero il supporto adeguato allo sviluppo del tumore
Detection of circulating endothelial progenitor cells in cardiovascular diseases
No full textIntroduction: Endothelial progenitor cells (EPCs) are bone marrow-derived cells playing a critical role in adult vasculogenesis and endothelial homeostasis, as they are recruited to sites of endothelial injury where they contribute to blood vessel formation and repair. Since their first description in 1997, EPCs have stimulated considerable interest among scientists due to the observation that variations in their number and function are associated with many pathological conditions including cardiovascular, cancer, and metabolic diseases. However, comparative interpretation of clinical studies on EPCs is still hampered by the lack of standardized methods employed for EPC quantification and analysis.
Methods: Two main approaches are currently used to study circulating EPCs. One approach consists in identifying and selecting EPCs by cell surface phenotype using fluorescently labeled antibodies and flow cytometry directly performed on peripheral blood samples. The second approach consists in isolating and expanding EPCs in vitro, starting from peripheral blood samples. Key advantages, limits and critical methodological aspects of each approach will be illustrated.
Results: EPC variations observed in pathological conditions will be shown, mainly focused on the involvement of EPCs in cardiovascular diseases. The behaviour of EPCs during particular physiologic challenges, such as systemic hypoxia exposure and physical exercise, will also be described in order to provide some insight into the role and function of EPCs in human physiopathology.
Conclusions: Changes in the number and function of circulating EPCs may be relevant to the study of a wide range of human diseases. If the methods for studying EPCs will be adequately standardized and adapted for routine use, EPC analysis will likely become a valuable diagnostic and prognostic non-invasive tool useful for patient follow-up
FREQUENCY, ANGIOGENIC POTENTIAL, PHENOTYPE AND MOLECULAR SIGNATURE OF ENDOTHELIAL COLONY-FORMING CELLS ISOLATED FROM PATIENTS WITH CLASSIC KAPOSI¿S SARCOMA
Full text linkAbstract
Background
Kaposi’s Sarcoma (KS) is a lymphangioproliferative disease whose causative agent is herpesvirus HHV-8. KS is characterized by hyperproliferation of HHV-8 infected spindle cells - cells of endothelial origin that represent the typical component of KS lesions. In previous studies we reported that circulating endothelial progenitor cells (EPCs), identified as CD45dim/CD34+/KDR+, are increased in patients with classic KS (cKS) and we also demonstrated that in cKS patients EPCs - isolated and cultured as Endothelial colony-forming cells (ECFCs) - are HHV-8 infected and can act as viral reservoir. Therefore, in this study we investigated whether ECFCs isolated from cKS patients are endowed with features typical of spindle cells in order to evaluate whether they may represent the precursors of spindle cells.
Moreover, in preliminary studies we surprisingly observed that not only ECFCs isolated from cKS patients but also ECFCs isolated from healthy donors expressed LYVE-1 and podoplanin – lymphatic markers expressed by spindle cells in KS lesions. Since several studies supported the hypothesis that adult lymphangiogenesis could be promoted by the presence of bone marrow derived lymphatic endothelial progenitor cells (LEPCs) we also investigated the lymphangiogenic potential of ECFCs to evaluate whether they can act also as LEPCs. In particular, we evaluated the expression of lymphatic markers in basal condition and we investigated whether the lymphatic differentiation of ECFCs could be fostered by fibronectin a component of the tumor microenvironment whose presence correlates with tumor lymphangiogenesis and metastasis. In addition, we also evaluated whether migration stimulating factor (MSF), an oncofetal isoform of fibronectin released by cancer stromal cells and tumor associated macrophages, could promote lymphatic differentiation of ECFCs.
Methods
83 cKS patients and 86 healthy HHV-8 seronegative donors were enrolled in the study. ECFCs were isolated using a protocol previously optimized in our lab. PBMCs were seeded in EGM-2 medium in culture plates coated with fibronectin and ECFC colonies were identified by microscopic visual inspection as colonies of cells with cobblestone-like morphology. Once isolated, ECFC colonies were expanded in culture plates coated with collagen. During the isolation phase, the time of appearance and the frequency of ECFC colonies were analyzed. During the following expansion phase, ECFC phenotype and the presence of HHV8-infection - assessed as expression of the viral latent nuclear antigen (LANA) - were analyzed by immunofluorescence. ECFC were functionally characterized by evaluating their cell viability, proliferative potential, vasculogenesis ability by Matrigel assay and cytokine production by ELISA. The molecular signature of ECFCs was also analyzed by gene array analysis.
To investigate the lymphatic differentiative potential of ECFCs the expression of typical lymphatic markers (PROX-1, podoplanin, LYVE-1 and VEGFR-3) was analyzed by Real Time PCR and confocal microscopy. To evaluate the possible role of fibronectin in promoting lymphatic differentiation, ECFCs were cultured on either fibronectin or collagen and the effects of stimulation with MSF were also analyzed.
Results
In our study ECFC colonies appeared earlier (p<0.001) and with higher frequency (p<0.001) when isolated from cKS patients than healthy donors. Moreover, the frequency of ECFC colonies was higher in cKS patients with rapidly evolving disease than in cKS patients with slowly evolving disease (p<0.05). All screened ECFC colonies isolated from cKS patients contained HHV8-infected cells. During the expansion phase, ECFCs isolated from cKS patients were endowed with a higher proliferative potential (p<0.05), a higher vasculogenic ability in vitro (p<0.05) and a higher production of IL-6 (p<0.05) than ECFCs isolated from healthy donors. In addition, preliminary analysis of the gene expression profile revealed that patients and healthy controls segregated by clustering, thus confirming that gene expression profile differs between ECFCs isolated from cKS patients and healthy donors.
A further relevant result of this study was the observation that ECFCs are endowed with the ability to express the typical lymphatic markers PROX-1, podoplanin, LYVE-1 and VEGFR-3. In particular, lymphatic markers were expressed by donor-derived ECFCs cultured on both fibronectin and collagen and they were upregulated by ECFC treatment with MSF (p<0.05).
Conclusion
In this study we demonstrated that ECFCs obtained from cKS patients are endowed with features that may be particularly relevant to KS pathogenesis, suggesting that ECFCs may act as putative precursors of the spindle cells and contribute to the development of KS lesions.
Moreover, we demonstrated that ECFCs isolated from peripheral blood of adult healthy donors expressed markers typical of lymphatic endothelium, suggesting that ECFCs may act also as LEPCs thus participating in lymphangiogenic and lymphovasculogenic processes
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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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