BACKGROUND Abnormal communicating channels or fistulas between the gallbladder or common bile duct and the intestine are rare, but have potential to result in serious complications. Further complications can arise with migration of gallstones from the gallbladder to the intestines, causing distal obstruction in the ileum, intestinal hemorrhage, or intestinal perforation. High clinical suspicion is warranted for the diagnosis of Bouveret's syndrome, with anticipation of surgery to prevent distal gallstone migration that would otherwise result in unfavorable patient outcomes.
View Article and Find Full Text PDFA global surgical rotation program has been developed at La Loma Luz Adventist Hospital in San Ignacio, Belize, by the Department of Surgery at East Tennessee State University in 2014. It encompasses a one-month rotation for surgery residents to travel to Belize, accompanied by a senior surgical attending, to participate in direct patient care. Residents are able to operate under supervision and practice both perioperative and medical management.
View Article and Find Full Text PDFCarbon is one of the most important materials extensively used in industry and our daily life. Crystalline carbon materials such as carbon nanotubes and graphene possess ultrahigh strength and toughness. In contrast, amorphous carbon is known to be very brittle and can sustain little compressive deformation.
View Article and Find Full Text PDFPrim Care Companion CNS Disord
October 2015
Prim Care Companion CNS Disord
February 2015
Objective: Primary care physicians are increasingly providing psychiatric care in the United States. Unfortunately, there is limited learning opportunity or exposure to psychiatry during their residency training. This survey was conducted to assess primary care resident interaction with mental health professionals and their satisfaction, knowledge, preference, and comfort with the delivery of mental health care in primary health care settings.
View Article and Find Full Text PDFEukaryotic DNA topoisomerase I (Top1p) catalyzes the relaxation of supercoiled DNA and constitutes the cellular target of camptothecin (CPT). Mutation of conserved residues in close proximity to the active site tyrosine (Tyr(727) of yeast Top1p) alters the DNA cleavage religation equilibrium, inducing drug-independent cell lethality. Previous studies indicates that yeast Top1T722Ap and Top1N726Hp cytotoxicity results from elevated levels of covalent enzyme-DNA intermediates.
View Article and Find Full Text PDFA series of 4beta-[(4' '-benzamido)-amino]-4'-O-demethyl-epipodophyllotoxin derivatives (11-23) were designed to enhance DNA topoisomerase II inhibition, overcome drug resistance, and modulate water solubility of etoposide (1) analogues. The target compounds were synthesized and evaluated for their effects against DNA topoisomerase II and KB or 1-resistant KB-7d tumor cells in tissue culture. As compared with 1, most compounds showed superior inhibition against both KB and KB-7d cells.
View Article and Find Full Text PDFEight 4'-ester epipodophyllotoxin derivatives (9-16) were designed and synthesized with the aim to overcome drug-resistance and improve water-solubility simultaneously. These compounds were superior to etoposide (1) in causing cellular protein-linked DNA breaks and inhibiting KB and 1-resistant KB-7d cell replication. Compounds 9 and 10 showed significant inhibitory activity against DNA topoisomerase II in vitro.
View Article and Find Full Text PDFEight novel epipodophyllotoxin derivatives (6-13), which were designed to overcome drug resistance and enhance topoisomerase II inhibition, were synthesized and evaluated. Two of these compounds (7 and 8) showed better preclinical activity profiles, including cell growth inhibition, cell killing, and in vitro topoisomerase II inhibition, as compared to the prototype molecule etoposide (1). They also retained the superior drug-resistance profile of GL-331 (4), an epipodophyllotoxin derivative currently in clinical evaluation.
View Article and Find Full Text PDFTpp1 is a DNA 3'-phosphatase in Saccharomyces cerevisiae that is believed to act during strand break repair. It is homologous to one domain of mammalian polynucleotide kinase/3'-phosphatase. Unlike in yeast, we found that Tpp1 could confer resistance to methylmethane sulfonate when expressed in bacteria that lack abasic endonuclease/3'-phosphodiesterase function.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2002
When a replication fork collides with a DNA topoisomerase I (Top1) cleavage complex, the covalently bound enzyme must be removed from the DNA 3' end before recombination-dependent replication restart. Here we report that the tyrosyl-DNA phosphodiesterase Tdp1 and the structure-specific endonuclease Rad1-Rad10 function as primary alternative pathways of Top1 repair in Saccharomyces cerevisiae. Thus, tdp1 rad1 cells (including the catalytic point mutant rad1-D869A) not only are highly sensitive to the Top1 poison camptothecin but also exhibit a TOP1-dependent growth delay.
View Article and Find Full Text PDFThis study suggests there is a need to support the efforts already present to include SIDS in medical and nursing school curricula. Both programs have indicated a need for audiovisual and printed teaching materials. Consideration should be given to teaching materials that are easily updated such as computer-generated materials because of the many rapid changes that take place in SIDS research.
View Article and Find Full Text PDFDNA topoisomerase I (Top1p) catalyzes topological changes in DNA and is the cellular target of the antitumor agent camptothecin (CPT). Non-CPT drugs that target Top1p, such as indolocarbazoles, are under clinical development. However, whether the cytotoxicity of indolocarbazoles derives from Top1p poisoning remains unclear.
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