Kettering University

About: Kettering University is a education organization based out in Flint, Michigan, United States. It is known for research contribution in the topics: Cancer & RNA. The organization has 6842 authors who have published 7689 publications receiving 337503 citations. The organization is also known as: GMI Engineering & Management Institute & General Motors Institute.

The effect of prior breast biopsy method and concurrent definitive breast procedure on success and accuracy of sentinel lymph node biopsy.

Abstract: It has been suggested that sentinel lymph node (SLN) biopsy for breast cancer may be less accurate after excisional biopsy of the primary tumor compared with core needle biopsy. Furthermore, some have suggested an improved ability to identify the SLN when total mastectomy is performed compared with lumpectomy. This analysis was performed to determine the impact of the type of breast biopsy (needle vs. excisional) or definitive surgical procedure (lumpectomy vs. mastectomy) on the accuracy of SLN biopsy. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study. Patients with clinical stage T1–2, N0 breast cancer were eligible. All patients underwent SLN biopsy and completion level I/II axillary dissection. Statistical comparison was performed by χ2 analysis. A total of 2206 patients were enrolled in the study. There were no statistically significant differences in SLN identification rate or false-negative rate between patients undergoing excisional versus needle biopsy. The SLN identification and false-negative rates also were not statistically different between patients who had total mastectomy compared with those who had a lumpectomy. Excisional biopsy does not significantly affect the accuracy of SLN biopsy, nor does the type of definitive surgical procedure.

Mycobacteria exploit three genetically distinct DNA double‐strand break repair pathways

Abstract: Bacterial pathogens rely on their DNA repair pathways to resist genomic damage inflicted by the host. DNA double-strand breaks (DSBs) are especially threatening to bacterial viability. DSB repair by homologous recombination (HR) requires nucleases that resect DSB ends and a strand exchange protein that facilitates homology search. RecBCD and RecA perform these functions in Escherichia coli and constitute the major pathway of error-free DSB repair. Mycobacteria, including the human pathogen M. tuberculosis, elaborate an additional error-prone pathway of DSB repair via non-homologous end-joining (NHEJ) catalysed by Ku and DNA ligase D (LigD). Little is known about the relative contributions of HR and NHEJ to mycobacterial chromosome repair, the factors that dictate pathway choice, or the existence of additional DSB repair pathways. Here we demonstrate that Mycobacterium smegmatis has three DSB repair pathway options: HR, NHEJ and a novel mechanism of single-strand annealing (SSA). Inactivation of NHEJ or SSA is compensated by elevated HR. We find that mycobacterial RecBCD does not participate in HR or confer resistance to ionizing radiation (IR), but is required for the RecA-independent SSA pathway. In contrast, the mycobacterial helicase-nuclease AdnAB participates in the RecA-dependent HR pathway, and is a major determinant of resistance to IR and oxidative DNA damage. These findings reveal distinctive features of mycobacterial DSB repair, most notably the dedication of the RecBCD and AdnAB helicase-nuclease machines to distinct repair pathways.

Radiation pneumonitis and fibrosis: a complication of radioiodine treatment of pulmonary metastases from cancer of the thyroid.

Abstract: INTRODUCTION THIS paper has been prompted by the observation that large doses of radioiodine given to patients with pulmonary metastases from thyroid cancer may produce severe pulmonary damage. Although this is a complication of radioiodine therapy heretofore unreported, it has been observed following roentgen irradiation directed to the chest. From the latter studies, the pathologic anatomy of radiation-induced pulmonary fibrosis and a rough notion of the dosage of x-ray irradiation required to produce it, has been obtained (1, 2). The present report describes in some detail the histories of 2 patients in whom fatal pulmonary fibrosis and pneumonitis developed. It also describes briefly our experience in other patients with pulmonary metastases from carcinoma of the thyroid who received one or more large doses of I131. Two of these patients have symptoms of pulmonary insufficiency, probably secondary to pulmonary fibrosis. CLINICAL MATERIAL AND METHODS Radioiodine as I131 was given orally in doses rangin...

A genome-wide transgenic resource for conditional expression of Drosophila microRNAs

Abstract: microRNAs (miRNAs) are endogenous short RNAs that mediate vast networks of post-transcriptional gene regulation. Although computational searches and experimental profiling provide evidence for hundreds of functional targets for individual miRNAs, such data rarely provide clear insight into the phenotypic consequences of manipulating miRNAs in vivo. We describe a genome-wide collection of 165 Drosophila miRNA transgenes and find that a majority induced specific developmental defects, including phenocopies of mutants in myriad cell-signaling and patterning genes. Such connections allowed us to validate several likely targets for miRNA-induced phenotypes. Importantly, few of these phenotypes could be predicted from computationally predicted target lists, thus highlighting the value of whole-animal readouts of miRNA activities. Finally, we provide an example of the relevance of these data to miRNA loss-of-function conditions. Whereas misexpression of several K box miRNAs inhibited Notch pathway activity, reciprocal genetic interaction tests with miRNA sponges demonstrated endogenous roles of the K box miRNA family in restricting Notch signaling. In summary, we provide extensive evidence that misexpression of individual miRNAs often induces specific mutant phenotypes that can guide their functional study. By extension, these data suggest that the deregulation of individual miRNAs in other animals may frequently yield relatively specific phenotypes during disease conditions.