Medicine, Australia
Medicine, Australia

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Kolade O.O.,University of Queensland | O'Moore-Sullivan T.M.,Diamantina Institute for Cancer | O'Moore-Sullivan T.M.,Center for Clinical Research Excellence in Cardiovascular and Metabolic Disease | O'Moore-Sullivan T.M.,Princess Alexandra Hospital | And 11 more authors.
International Journal of Obesity | Year: 2012

Background:Body size is associated with increased brachial systolic blood pressure (SBP) and aortic stiffness. The aims of this study were to determine the relationships between central SBP and body size (determined by body mass index (BMI), waist circumference and waisthip ratio) in health and disease. We also sought to determine if aortic stiffness was correlated with body size, independent of BP.Methods:BMI, brachial BP and estimated central SBP (by SphygmoCor and radial P2) were recorded in controls (n=228), patients with diabetes (n=211), coronary artery disease (n=184) and end-stage kidney disease (n68). Additional measures of waist circumference and arterial stiffness (aortic and brachial pulse wave velocity (PWV)) were recorded in a subgroup of 75 controls (aged 51±12 years) who were carefully screened for factors affecting vascular function.Results.BMI was associated with brachial (r=0.30; P<0.001) and central SBP (r=0.29; P<0.001) in the 228 controls, but not the patient populations (r<0.13; P>0.15 for all comparisons). In the control subgroup, waist circumference was also significantly correlated with brachial SBP (r=0.29; P=0.01), but not central SBP (r=0.22; P=0.07). Independent predictors of aortic PWV in the control subgroup were brachial SBP (Β0.43; P<0.001), age (Β0.37; P<0.001), waist circumference (Β0.39; P=0.02) and female sex (Β0.24; P=0.03), but not BMI. Conclusion. In health, there are parallel increases in central and brachial SBP as BMI increases, but these relationships are not observed in the presence of chronic disease. Moreover, BP is a stronger correlate of arterial stiffness than body size. © 2012 Macmillan Publishers Limited All rights reserved.

Papathanasiou P.,Australian National University | Tunningley R.,Australian National University | Pattabiraman D.R.,Diamantina Institute for Cancer | Ye P.,Diamantina Institute for Cancer | And 7 more authors.
Blood | Year: 2010

Identification of genes that regulate the development, self-renewal, and differentiation of stem cells is of vital importance for understanding normal organogenesis and cancer; such knowledge also underpins regenerative medicine. Here we demonstrate that chemical mutagenesis of mice combined with advances in hematopoietic stem cell reagents and genome resources can efficiently recover recessive mutations and identify genes essential for generation and proliferation of definitive hematopoietic stem cells and/or their progeny. We used high-throughput fluorescenceactivated cell sorter to analyze 9 subsets of blood stem cells, progenitor cells, circulating red cells, and platelets in more than 1300 mouse embryos at embryonic day (E) 14.5. From 45 pedigrees, we recovered 6 strains with defects in definitive hematopoiesis. We demonstrate rapid identification of a novel mutation in the c-Myb transcription factor that results in thrombocythemia and myelofibrosis as proof of principal of the utility of our fluorescence-activated cell sorter-based screen. Such phenotypedriven approaches will provide new knowledge of the genes, protein interactions, and regulatory networks that underpin stem cell biology. © 2010 by The American Society of Hematology.

Lagarkova M.A.,Russian Academy of Sciences | Shutova M.V.,Russian Academy of Sciences | Bogomazova A.N.,Russian Academy of Sciences | Vassina E.M.,Russian Academy of Sciences | And 5 more authors.
Cell Cycle | Year: 2010

Reprogramming of a limited number of human cell types has been achieved through ectopic expression of four transcription factors to yield induced pluripotent stem (iPS) cells that closely resemble human embryonic stem cells (ESCs). Here, we determined functional and epigenetic properties of iPS cells generated from human umbilical vein endothelial cells (HUVEC) by conventional method of direct reprogramming. Retroviral overexpression of four transcription factors resets HUVEC to the pluripotency. Human endothelial cell-derived iPS (endo-iPS) cells were similar to human ESCs in morphology, gene expression, in vitro and in vivo differentiation capacity. Endo-iPS cells were efficiently differentiated in vitro into endothelial cells. Using genome-wide methylation profiling we show that promoter elements of endothelial specific genes were methylated following reprogramming whereas pluripotency-related gene promoters were hypomethylated similar to levels observed in ESCs. Genome-wide methylation analysis of CpG sites located in the functional regions of over than 14,000 genes indicated that human endo-ipS cells were highly similar to human ES cells, although differences in methylation levels of 46 genes were found. overall CpG methylation of promoter regions in the pluripotent cells was higher than in somatic. We also show that during reprogramming female human endo-iPS cells exhibited reactivation of the somatically silenced X chromosome. Our findings demonstrate that iPS cells can be generated from human endothelial cells and reprogramming resets epigenetic status of endothelial cells to pluripotency. © 2010 Landes Bioscience.

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