Showing papers by "George L. Mutter published in 2014"

Selection of functional human sperm with higher DNA integrity and fewer reactive oxygen species.

Abstract: Fertilization and reproduction are central to the survival and propagation of a species. Couples who cannot reproduce naturally have to undergo in vitro clinical procedures. An integral part of these clinical procedures includes isolation of healthy sperm from raw semen. Existing sperm sorting methods are not efficient and isolate sperm having high DNA fragmentation and reactive oxygen species (ROS), and suffer from multiple manual steps and variations between operators. Inspired by in vivo natural sperm sorting mechanisms where vaginal mucus becomes less viscous to form microchannels to guide sperm towards egg, a chip is presented that efficiently sorts healthy, motile and morphologically normal sperm without centrifugation. Higher percentage of sorted sperm show significantly lesser ROS and DNA fragmentation than the conventional swim-up method. The presented chip is an easy-to-use high-throughput sperm sorter that provides standardized sperm sorting assay with less reliance on operators's skills, facilitating reliable operational steps.

Emergence, Involution, and Progression to Carcinoma of Mutant Clones in Normal Endometrial Tissues

Abstract: Sporadic somatic inactivation of genes such as PTEN within histologically normal endometrium (latent precancers) is an early step in endometrial carcinogenesis. We have used clone-specific mutations of PTEN to determine the fate of latent precancers over time in women who do (high risk) and do not (low risk) develop endometrial neoplasia. PTEN immunohistochemistry was performed on 45 occurrences of endometrial neoplasia and their paired antecedent benign biopsies, along with age matched sample pairs from 167 patients who did not develop a neoplasm. When PTEN-deficient cells were present at both time points, DNA sequencing was performed to determine whether they were single or multiple independent events. Loss of PTEN protein in isolated glands was common in the initial normal biopsies of high- and low-risk groups (42% and 27%, respectively, P = 0.066). Protein-deficient glands have a tendency to disappear over time in low-risk women (P = 0.047) and, even when "persistent," are infrequently (19%, 3/16) confirmed to be the same clone. Similarly, only a small proportion (6.7%, 1/15) of latent precancers seen in high-risk women are the direct progenitors of subsequent neoplasia. There is a high rate of latent precancer turnover in both low- and high-risk patients, with rare long-term persistence of unique clones, which may or may not progress to a histologic lesion. The temporal dynamics of clonal emergence, persistence, and involution are sufficiently complex that in the individual patient, the presence of a latent precancer has an unknown contribution to long-term cancer risk.