Cancer Genes Hypermethylated in Human Embryonic Stem Cells

Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation

Feasibility of source images of computed tomographic angiography to detect the extent of ischemia in hyperacute stroke

Copyright 2002 S. Karger AG, Basel.Background and Purpose: Computed tomographic angiography (CTA) is suggested to be a promising tool for patient selection for thrombolytic therapy of acute stroke. It does not only provide information on intracranial vasculature, but also on the capacity of the collateral circulation and the pattern of poorly perfused brain tissue. The objective of our study was to evaluate whether the presence and size of critically hypoperfused tissue assessed with flow positron emission tomography (PET) as a gold standard can reliably be identified on CTA source images. Methods: Fifteen potential candidates for early thrombolysis underwent CTA 65-170 min (mean 107 min) after the onset of acute anterior circulation stroke. Regional cerebral perfusion was measured between 27 and 86 min (mean 59 min) later with [O-15]-H2O and PET, and the volume of critically hypoperfused cortical tissue was assessed. CTA source images were evaluated by a neuroradiologist and an experienced stroke neurologist. The patients were classified into three groups according to the presumed size of the perfusion deficit on CTA (large, small, no perfusion deficit). Results: PET revealed the presence of critical cortical hypoperfusion in 10 patients, 5 had no critical cortical hypoperfusion. The neuroradiologist correctly identified the presence of a perfusion deficit in all patients, the neurologist had two false negative and one false positive ratings. Concerning the size of the perfusion deficit, there was considerable inaccuracy in both raters. Conclusions: The usefulness of CTA source images in yielding information about the perfusion state of stroke patients in clinical routine should not be overestimated