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Jaipersad A.S.,University of Birmingham | Lip G.Y.H.,University of Birmingham | Silverman S.,Taipei Medical University Hospital | Shantsila E.,University of Birmingham
Journal of the American College of Cardiology | Year: 2014

New vessel formation inside the arterial wall and atherosclerotic plaques plays a critical role in pathogenesis of heart attacks and strokes. The 2 known mechanisms resulting in the formation of new vessels within the plaque are local ischemia and inflammation. Blood monocytes play an important role in both processes. First, they express receptors for vascular endothelial growth factor and some of them may serve as circulating ancestors of endothelial cells. Second, monocytes are associated with inflammation by synthesis of inflammatory molecules following their activation (e.g., after stimulation of Toll-like receptors). Neovascularization is a reparative response to ischemia, and includes 3 processes: angiogenesis, arteriogenesis, and vasculogenesis. Angiogenesis, the formation of new capillary vessels is known to occur in response to a hypoxic environment. The interaction between leukocytes and vascular wall via overexpression of various molecules facilitates the migration of inflammatory cells into the plaque microenvironment. Monocytes are intimately involved in tissue damage and repair and an imbalance of these processes may have detrimental consequences for plaque development and stability. Importantly, monocytes are comprised of distinct subsets with different cell surface markers and functional characteristics and this heterogeneity may be relevant to angiogenic processes in atherosclerosis. The aim of this review article is to present an overview of the available evidence supporting a role for monocytes in angiogenesis and atherosclerosis. Source


Su C.-M.,Taipei Medical University Hospital
Oncogene | Year: 2015

MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3’untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.Oncogene advance online publication, 18 May 2015; doi:10.1038/onc.2015.168. © 2015 Macmillan Publishers Limited Source


Andrews J.M.,Taipei Medical University Hospital | Howe R.A.,University of Wales
Journal of Antimicrobial Chemotherapy | Year: 2011

The BSAC standardized disc susceptibility testing method remains unchanged, but there are considerable changes to the interpretative criteria due to continuing harmonization with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC breakpoints. There are a number of agents for which interpretative criteria have been removed. These MIC and/or zone diameter breakpoints will be published on the BSAC web site as a 'Legacy' table; they may be used for research or comparative purposes, but are not recommended for clinical management. Notably, testing of staphylococci for susceptibility to glycopeptides by disc diffusion has been removed because this method has been found to be unreliable, particularly for the detection of low-level resistance; low-level vancomycin resistance in staphylococci is increasingly deemed to be of clinical relevance. The tables for anaerobes have been expanded to include MIC breakpoints that have been determined by EUCAST. There are currently no zone diameter breakpoints for these organisms and an MIC method is recommended if susceptibility testing is required. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source


Recent suggestions that glucagon-like peptide-1 (GLP-1)-based therapies could cause pancreatitis, and even pancreatic cancer, are based on: Animal studies: The worrying histological changes are not reproduced in all studies and are unexpectedly variable with different GLP-1-based therapies. An observational study: Singh's findings that pancreatitis is doubled with GLP-1-based therapies could relate to their use in obese patients who are prone to pancreatitis risk factors-gallstones and hypertriglyceridaemia. The other observational studies do not find an association between GLP-1-based therapies and pancreatitis. US Food and Drug Administration adverse event reporting system: The increased reports of pancreatitis and pancreatic cancer are likely to be attributable to 'notoriety bias'. A study of organ donor pancreases: Butler's findings for those on GLP-1-based therapies vs. those not, could have other explanations. Meanwhile: Meta analysis: Randomized control trials with GLP-1-based therapies do not find increased pancreatitis risk. Meta-analysis of 53 randomized controlled trials including 20 212 dipeptidyl peptidase-4 inhibitor-treated patients found a significantly reduced risk of major adverse cardiovascular events [odds ratio 0.689 (0.528-0.899), P = 0.006] for dipeptidyl peptidase-4 inhibitors compared with control subjects. Cardiovascular risk: The evidence suggests that there is more than a possibility that some of the GLP-1 receptor agonists, and possibly also some dipeptidyl peptidase-4 inhibitors, may be associated with reduced cardiovascular events. Eight ongoing long-term cardiovascular randomized controlled trials will report from September 2013 onwards. These trials should resolve the issue of pancreatitis risk and substantiate the extent of benefit. Conclusion: Whilst we should remain vigilant, currently the balance of evidence is strongly in support of GLP-1-based therapy, with benefits far outweighing potential risks. © 2013 Diabetes UK. Source


Berg J.,Taipei Medical University Hospital
Clinica Chimica Acta | Year: 2014

The United Kingdom Pathology Harmony project commenced in 2007 and has been widely mirrored around the world. This initiative evolved through three separate phases of work. Fundamental to the project has been the ability to question variation in the work of the pathology laboratory that has been in place sometimes for a very long time, and yet appears to have little scientific foundation. Work has been undertaken on a methodological approach to studying variation in reference intervals and then moving forward with consensus values. On a wider level there is much else in pathology that can be harmonised from test names and units, through to the clinical guidance we offer for using our tests and work has been undertaken in several of these areas. © 2013 Elsevier B.V. Source

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