50 research outputs found

    Monocyte trafficking in acute and chronic inflammation

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    Environmental signals at the site of inflammation mediate rapid monocyte mobilization and dictate differentiation programs whereby these cells give rise to macrophages or dendritic cells. Monocytes participate in tissue healing, clearance of pathogens and dead cells, and initiation of adaptive immunity. However, recruited monocytes can also contribute to the pathogenesis of infection and chronic inflammatory disease, such as atherosclerosis. Here, we explore monocyte trafficking in the context of acute inflammation, relying predominantly on data from microbial infection models. These mechanisms will be compared to monocyte trafficking during chronic inflammation in experimental models of atherosclerosis. Recent developments suggest that monocyte trafficking shares common themes in diverse inflammatory diseases; however, important differences exist between monocyte migratory pathways in acute and chronic inflammation

    Predicting Response to Intravesical Bacillus Calmette-Guerin Immunotherapy: Are We There Yet? A Systematic Review

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    Contains fulltext : 193632.pdf (publisher's version ) (Closed access)CONTEXT: Bacillus Calmette-Guerin (BCG) is currently the most effective intravesical therapy for nonmuscle invasive bladder cancer, reducing not only recurrence rates but also preventing progression and reducing deaths. However, response rates to BCG vary widely and are dependent on a multitude of factors. OBJECTIVE: To review existing data on clinical, pathologic, immune, and molecular markers that allow prediction of BCG response. EVIDENCE ACQUISITION: PubMed and MEDLINE search of English language literature was conducted from its inception to July 2017 using appropriate search terms. Following systematic literature review and analysis of data, consensus voting was used to generate the content of this review. EVIDENCE SYNTHESIS: As seen in the EORTC and CUETO risk nomograms, clinicopathologic features, especially tumor stage and grade, are the most effective predictors of BCG response. Data are less robust with regards to the association of response with age, female sex, recurrent tumors, multiplicity of tumors, and the presence of carcinoma in situ. Single biomarkers, such as tumor p53 and urinary interleukin-2 expression, have had limited success in predicting BCG response, possibly due to the multifaceted nature of the generated immune response. More comprehensive biomarker panels (eg, urinary cytokines), have a more robust correlation with response, as do patterns of urinary cytologic fluorescent in-situ hybridization examination. Gene expression data correlate with disease progression, but studies examining potential associations with BCG response are limited. CONCLUSIONS: Currently, the best predictors of BCG response are clinicopathologic features such as tumor grade and stage. Panels of urinary cytokines, as well as fluorescent in-situ hybridization patterns of cytologic anomalies, appear to be promising biomarkers. The complexity of the immune response to BCG and the heterogeneity of bladder cancer suggest that future studies should amalgamate measures reflecting innate immune response and tumor/stromal gene expression before these can be adopted for clinical use. PATIENT SUMMARY: Bacillus Calmette-Guerin (BCG) immunotherapy is an effective treatment for many patients with nonmuscle invasive bladder cancer. An individual's response to BCG can be predicted by using various features of the cancer. In the future, predictive markers using molecular measures of the tumor type and the immune response to BCG may allow us to precisely know an individual's likely outcome after BCG treatment

    Grain size, composition, porosity and permeability contrasts within cross-bedded sandstones in Tertiary fluvial deposits, central Spain

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    Permeability measured with a portable probe pcrmcflmeter on outcrops of cross·bcdded sandstones ranges betwecn 0·9 and 19 O. The highest pcrmeability (2-19 0 with an avcrage of8·5 D) occurs in thc coarsest grained foresct laminae (CFL). intermediate values (2-120 with an average of 5·3 D) occur in fincr grained foreset laminac (FFL) and thc lowest values (0·9-1 0 0 with un avcrage of 4·8 D) occur in boltomsct laycrs (BL). In the cross·bcds the uverage grain sizc rangcs from medium graincd sand in the CFL to finc grained s,lnd in thc FFL and BL. In all three subf'lcies. the average size of the primary pores is approximately It/> unit smaller than the averagc grain size. The abundance of unstablc carbonatc clasts correlatcs with incrcasing avcrage grain size, micritic clasts being most abundant in the CFL. Converscly. quartz content incrcascs with decreasing grain size and is highest in the FFL and BL. Oiagenetic destruction of primary porosity by compact ion and cementation. as well �IS generation of sccondary porosity through dissolution, were controlled by the original mineralogical composition of the sand. Contrasts in grain size detcrmine the primary pore size contrasts and differences in composition bctwecn CFL. FFL and BL. Permeability contrasts reflect variations in averagc primary pore size rather than differenccs in total porosity. Probe permeability contrasts between eFL. FFL and BL depend on contrasts in llverage pore size and contrasts in mineralogical composition between the subfacies

    Comparison of gene expression profiles between human and mouse monocyte subsets.

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    Blood of both humans and mice contains 2 main monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 270 genes in humans and 550 genes in mice were differentially expressed between subsets by 2-fold or more. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous of these differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the 2 species' subsets, including CD36, CD9, and TREM-1. Other differences included a prominent peroxisome proliferator-activated receptor gamma (PPARgamma) signature in mouse monocytes, which is absent in humans, and strikingly opposed patterns of receptors involved in uptake of apoptotic cells and other phagocytic cargo between human and mouse monocyte subsets. Thus, whereas human and mouse monocyte subsets are far more broadly conserved than currently recognized, important differences between the species deserve consideration when models of human disease are studied in mice
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