1,510 research outputs found

    Alternatively activated macrophages recruited by Brugia Malayi

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    Chitinase and Fizz family members are a generalized feature of nematode infection with selective Upregulation of Ym1 and F10.1 by antigen-presenting cells

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    Ym1 and Fizz1 are secreted proteins that have been identified in a variety of Th2-mediated inflammatory settings. We originally found Ym1 and Fizz1 as highly expressed macrophage genes in a Brugia malayi infection model. Here, we show that their expression is a generalized feature of nematode infection and that they are induced at the site of infection with both the tissue nematode Litomosoides sigmodontis and the gastrointestinal nematode Nippostrongylus brasiliensis. At the sites of infection with N. brasiliensis, we also observed induction of other chitinase and Fizz family members (ChaFFs): acidic mammalian chitinase (AMCase) and Fizz2. The high expression of both Ym1 and AMCase in the lungs of infected mice suggests that abundant chitinase production is an important feature of Th2 immune responses in the lung. In addition to expression of ChaFFs in the tissues, Ym1 and Fizz1 expression was observed in the lymph nodes. Expression both in vitro and in vivo was restricted to antigen-presenting cells, with the highest expression in B cells and macrophages. ChaFFs may therefore be important effector or wound-repair molecules at the site of nematode infection, with potential regulatory roles for Ym1 and Fizz1 in the draining lymph nodes

    Systematic Review and Meta-analysis: Use of Statins Is Associated with a Reduced Incidence of Oesophageal Adenocarcinoma

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    Purpose: Laboratory studies have suggested that statins may have useful anti-cancer effects against Barrett’s epithelial cancer lines. A variety of effects have been reported in clinical studies. Methods: We performed a systematic review and meta-analysis of the association between statin use and the development of oesophageal cancer. Multiple databases were searched for studies reporting the association of statin use and oesophageal cancer. Meta-analysis on the relationship between statin use and cancer incidence was performed. Results: Twenty publications met eligibility criteria, yielding 22 datasets for meta-analysis. All were observational studies. Population-level studies included 372,206 cancer cases and 6,086,906 controls. Studies examining adenocarcinoma development in Barrett’s oesophagus included 1057 cancers and 17,741 controls. In patients with Barrett’s oesophagus, statin use was associated with a reduced incidence of adenocarcinoma (pooled adjusted odds ratio (OR) 0.59 (95% confidence intervals 0.50–0.68)), with no heterogeneity between 11 studies. Population-based studies demonstrated more heterogeneity but showed that statin use was associated with a lower incidence of both oesophageal adenocarcinoma (OR 0.57 (0.43–0.76)) and all oesophageal cancers (OR 0.82 (0.7–0.88)). Information on statin type, dose, and duration was reported too infrequently for statistical analysis but individual studies showed a tendency to a dose- and duration-dependant decrease in cancer incidence. Conclusions: Statin use is associated with a significantly lower incidence of oesophageal adenocarcinoma. This is seen in both Barrett’s cohorts and general populations. Further studies should focus on drug, dose, and duration and the interaction with other risk and preventative factors

    Efficacy and safety profile of statins in patients with cancer: a systematic review of randomised controlled trials

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    PURPOSE: A growing body of preclinical and observational research suggests that statins have potential as a therapeutic strategy in patients with cancer. This systematic review of randomised controlled trials (RCTs) in patients with solid tumours aimed to determine the efficacy of statin therapy on mortality outcomes, their safety profile and the risk of bias of included studies. METHODS: Full-text articles comparing statin therapy versus control in solid tumours and reporting mortality outcomes were identified from Medline and Embase from conception to February 2020. A systematic review with qualitative (primarily) and quantitative synthesis was conducted. This systematic review was prospectively registered (Prospero registration CRD42018116364). RESULTS: Eleven trials of 2165 patients were included. Primary tumour sites investigated included lung, colorectal, gastro-oesophageal, pancreatic and liver. Most trials recruited patients with advanced malignancy and used sub-maximal statin doses for relatively short durations. Aside from one trial which demonstrated benefit with allocation to pravastatin 40 mg in hepatocellular carcinoma, the remaining ten trials did not demonstrate efficacy with statins. The pooled hazard ratio for all-cause mortality with allocation to pravastatin in patients with hepatocellular carcinoma in two trials was 0.69 (95% confidence interval CI 0.30-1.61). Study estimates were imprecise. There were no clinically important differences in statin-related adverse events between groups. Overall, included trials were deemed low risk of bias. CONCLUSION: The trial evidence is not sufficiently robust to confirm or refute the efficacy and safety of statins in patients with solid malignant tumours. Study and patient characteristics may explain this uncertainty. The potential role of high-dose statins in adjuvant settings deserves further research

    Resistivity monitoring for leakage and internal erosion detection at Hallby embankment dam

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    Internal erosion is one of the major reasons for embankment dam failures. Despite this, the knowledge of the temporal development of internal erosion in full scale structures is limited. Detection of internal erosion is complicated using conventional methods, and new or improved methods are appreciated. Hallby was the first Swedish embankment to get a permanently installed monitoring system intended for resistivity measurements. Daily measurements started to take place already in late 1996, which make these long term monitoring data unique. This paper includes examples of long term time series from Hallby along with some evaluation and interpretation techniques used when analysing such monitoring data. Time-lapse inversion was used to focus the variation over time and suppress artefacts due to the resistivity structure. Seasonal resistivity variations inside the dam are obvious. Increasing long term resistivity has been noticed in a particular zone in the left embankment. This zone also exhibits larger seasonal variations relative to other parts of the dam, and the variations are increasing. The observations may relate to an ongoing internal erosion process in the dam. The long term change may be indicative of a change in material properties, and the large and increasing variations may reflect higher and increasing seepage levels. In the years 2004 to 2006 the dam was upgraded and the resistivity system reinstalled. The results indicate that resistivity monitoring may have a chance of detecting development of internal erosion at an early stage. (C) 2008 Published by Elsevier B.V

    CD3- Leukocytes Present in the Human Uterus During Early Placentation: Phenotypic and Morphologic Characterization of the CD56++ Population

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    In this study, the CD3- LGL/NK cells present in the pregnant human uterus have been characterized. Phenotypic and morphologic analyses of decidual LGL revealed many similarities to the minor CD56bright+, CD16- subset in peripheral blood, but there were some important differences. The relative surface density of CD56+ is greatly increased on decidual LGL to 22 x that found on the majority of CD56 peripheral blood NK cells. The CD56bright cells in decidua show LGL morphology, whereas in peripheral blood, they are .mainly agranular. Proliferation of CD56+ cells occurs predominantly during the nonpregnant secretory (luteal) phase, indicating these CD56+ uterine LGL do not migrate as terminally differentiated cells. The appearance of CD56 cells was examined at the ultrastructural level using immunoelectron microscopy. Cells with phenotypic characteristics of decidual LGL occur in a higher percentage (1.11%) in the peripheral blood of women of reproductive age than in men (0.66%). On the basis of these results, it is proposed that the CD56bright+ uterine leukocytes represent a distinctive, hormonally regulated subset possibly adapted to control human placentation
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