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To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem echocardiograms were compared with LV mass measurements made at necropsy in 55 patients. LV mass was calculated using M-mode LV measurements by Penn and American Society(More)
We have investigated the role of the enzyme telomerase in highly proliferative organs in successive generations of mice lacking telomerase RNA. Late-generation animals exhibited defective spermatogenesis, with increased programmed cell death (apoptosis) and decreased proliferation in the testis. The proliferative capacity of haematopoietic cells in the bone(More)
Telomere maintenance is thought to play a role in signaling cellular senescence; however, a link with organismal aging processes has not been established. The telomerase null mouse provides an opportunity to understand the effects associated with critical telomere shortening at the organismal level. We studied a variety of physiological processes in an(More)
Maintenance of telomere length and function is critical for the efficient proliferation of eukaryotic cells. Here, we examine the interactions between telomere dysfunction and p53 in cells and organs of telomerase-deficient mice. Coincident with severe telomere shortening and associated genomic instability, p53 is activated, leading to growth arrest and/or(More)
Aged humans sustain a high rate of epithelial cancers such as carcinomas of the breast and colon, whereas mice carrying common tumour suppressor gene mutations typically develop soft tissue sarcomas and lymphomas. Among the many factors that may contribute to this species variance are differences in telomere length and regulation. Telomeres comprise the(More)
Telomeres are specialized nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. Loss of telomere function is associated with rampant genetic instability and loss of cellular viability and renewal potential. The telomere also participates in processes of chromosomal repair, as evidenced by the 'capture' or de novo synthesis(More)
Maintenance of telomere length is predicted to be essential for bypass of senescence and crisis checkpoints in cancer cells. The impact of telomere dysfunction on tumorigenesis was assessed in successive generations of mice doubly null for the telomerase RNA (mTR) and the INK4a tumor suppressor genes. Significant reductions in tumor formation in vivo and(More)
A total of 357 white patients who had melanocytic nevi that fulfilled the clinical criteria for the "classic" atypical-mole (dysplastic-nevus) syndrome (100 or more melanocytic nevi; one or more melanocytic nevi 8 mm or larger in diameter; and, one or more melanocytic nevi with atypical features) were followed for the development of cutaneous malignant(More)
This study correlated the location and size of posterolateral myocardial infarcts (MIs) measured anatomically with that estimated by quantitative criteria derived from the standard 12-lead ECG. Twenty patients were studied who had autopsy-proved, single, posterolateral MIs and no confounding factors of ventricular hypertrophy or bundle branch block in their(More)