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Viall C.A.,University of Auckland | Chamley L.W.,University of Auckland | Chamley L.W.,Gravida National Center for Growth and Development
Autoimmunity Reviews | Year: 2015

Background: Antiphospholipid antibodies (aPLs) are a heterogenous group of autoantibodies associated with recurrent miscarriage, stillbirth, foetal growth restriction and premature birth. The cause of obstetric morbidity in women with aPLs is not completely understood. Workers have attempted to understand the role of aPLs in obstetric morbidity by investigating the histopathology of placentae from aPL-positive women. However, it is unclear from these diverse, and at times contradictory reports what histopathological lesions are common in the placentae of women with aPLs. This systematic review was undertaken to generate a complete picture of the placental features associated with aPLs in an attempt to understand the pathological processes that occur in pregnancies affected by aPLs. Methods: Pubmed, Scopus, Web of Science and Embase were searched on the 27th November 2014 using the keywords "placenta" OR "trophoblast" AND "antiphospholipid antibody" OR "antiphospholipid antibody syndrome". Records that were relevant and eligible were qualitatively assessed and given a score out of 24. Results: Of the 1112 records that were retrieved from the systematic search, 34 records were eligible for review, and were qualitatively scored. Of the 44 histopathological features that were reported in 580 placentae from aPL-positive women, six features appeared to be more common in the placentae of aPL-positive women compared to control women, including: placental infarction, impaired spiral artery remodelling, decidual inflammation, increased syncytial knots, decreased vasculosyncytial membranes and the deposition of complement split product C4d. Conclusion: Based on the evidence in this systematic review, a human placental aPL fingerprint has been proposed. The diversity of the human placental aPL fingerprint suggests that multiple pathological processes may occur in pregnancies affected by aPL. © 2015 Elsevier B.V. Source

Stockwell P.A.,University of Otago | Chatterjee A.,University of Otago | Chatterjee A.,Gravida National Center for Growth and Development | Rodger E.J.,University of Otago | Morison I.M.,University of Otago
Bioinformatics | Year: 2014

Motivation: The rapid development of high-throughput sequencing technologies has enabled epigeneticists to quantify DNA methylation on a massive scale. Progressive increase in sequencing capacity present challenges in terms of processing analysis and the interpretation of the large amount of data; investigating differential methylation between genome-scale data from multiple samples highlights this challenge. Results: We have developed a differential methylation analysis package (DMAP) to generate coverage-filtered reference methylomes and to identify differentially methylated regions across multiple samples from reduced representation bisulphite sequencing and whole genome bisulphite sequencing experiments. We introduce a novel fragment-based approach for investigating DNA methylation patterns for reduced representation bisulphite sequencing data. Further, DMAP provides the identity of gene and CpG features and distances to the differentially methylated regions in a format that is easily analyzed with limited bioinformatics knowledge. © The Author 2014. Source

Poynton R.A.,Gravida National Center for Growth and Development | Hampton M.B.,University of Otago
Biochimica et Biophysica Acta - General Subjects | Year: 2014

Background Peroxiredoxins (Prxs) are a class of abundant thiol peroxidases that degrade hydroperoxides to water. Prxs are sensitive to oxidation, and it is hypothesized that they also act as redox sensors. The accumulation of oxidized Prxs may indicate disruption of cellular redox homeostasis. Scope of review This review discusses the biochemical properties of the Prxs that make them suitable as endogenous biomarkers of oxidative stress, and describes the methodology available for measuring Prx oxidation in biological systems. Major conclusions Two Prx oxidation products accumulate in cells under increased oxidative stress: an intermolecular disulfide and a hyperoxidized form. Methodologies are available for measuring both of these redox states, and oxidation has been reported in cells and tissues under oxidative stress from external or internal sources. General significance Monitoring the oxidation state of Prxs provides insight into disturbances of cellular redox homeostasis, and complements the use of exogenous probes of oxidative stress. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. © 2013 Elsevier B.V. Source

Pinto T.E.,University of Auckland | Gusso S.,University of Auckland | Hofman P.L.,University of Auckland | Hofman P.L.,Gravida National Center for Growth and Development | And 5 more authors.
Diabetes Care | Year: 2014

OBJECTIVE: To better understand the cardiac limitations during exercise in adolescents with type 2 diabetes mellitus (T2DM), we measured left ventricular performance with magnetic resonance imaging (MRI) during exercise in diabetic and nondiabetic adolescents. RESEARCH DESIGN AND METHODS: Thirteen subjects with T2DM, 27 overweight/obese nondiabetic (ObeseND) subjects, and 19 nondiabetic nonobese control subjects were recruited. Cardiac (left ventricular) MRI scans were performed at rest and during submaximal exercise. RESULTS: VO2 peak indexed to fat-free mass was reduced in T2DM and ObeseND subjects compared with control subjects (P < 0.0001). Indexed cardiac output increased less during exercise and was 20% lower in T2DM subjects due to reduced stroke volume. This was a consequence of reduced ventricular filling with smaller end-diastolic volume, which decreased further during exercise in T2DM subjects, but not in ObeseND or control subjects. End-systolic volume was also smaller in T2DM subjects. These changes were associated with increased resting and exercise diastolic blood pressure, and total peripheral resistance in T2DM subjects. CONCLUSIONS: Independently of obesity, T2DM impairs cardiac function during exercise in adolescents. © 2014 by the American Diabetes Association. Source

Viall C.A.,University of Auckland | Chen Q.,University of Auckland | Chen Q.,Fudan University | Liu B.,University of Auckland | And 7 more authors.
Journal of Autoimmunity | Year: 2013

Antiphospholipid antibodies (aPL) are the strongest maternal risk factor for pre-eclampsia, a hypertensive disease of human pregnancy. Pre-eclampsia is triggered by a toxic factor released from the placenta that activates the maternal endothelium. Antiphospholipid antibodies cause the release of necrotic trophoblast debris from the placental syncytiotrophoblast and this debris can activate endothelial cells. In this study, we investigated how aPL affects syncytiotrophoblast death and production of necrotic trophoblast debris by examining the interaction between aPL and human first trimester placental explants. Human polyclonal and murine monoclonal aPL, but not control antibodies, were rapidly internalised by the syncytiotrophoblast. Inhibitors of endocytosis or the low-density lipoprotein receptor (LDLR) family, but not toll-like receptors, decreased the internalisation of aPL and prevented the release of necrotic trophoblast debris from the syncytiotrophoblast. Once internalised, aPL increased inner mitochondrial membrane leak and Cytochrome c release while depressing oxidative flux through Complex IV of the electron transport system in syncytiotrophoblast mitochondria. These data suggest that the human syncytiotrophoblast internalises aPL by antigen-dependent endocytosis involving LDLR family members. Once internalised by the syncytiotrophoblast, aPL affects the death-regulating mitochondria, causing extrusion of necrotic trophoblast debris which can activate maternal endothelial cells thereby contributing to the pathogenesis of pre-eclampsia. © 2013 Elsevier Ltd. Source

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