Johns Hopkins University School of Medicine

About: Johns Hopkins University School of Medicine is a healthcare organization based out in Baltimore, Maryland, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.

Wild-type p53 is a cell cycle checkpoint determinant following irradiation.

Abstract: Cell cycle checkpoints appear to contribute to an increase in cell survival and a decrease in abnormal heritable genetic changes following exposure to DNA damaging agents. Though several radiation-sensitive yeast mutants have been identified, little is known about the genes that control these responses in mammalian cells. Recent studies from our laboratory have demonstrated a close correlation between expression of wild-type p53 genes in human hematopoietic cells and their ability to arrest in G1 phase after certain types of DNA damage. In the present study, this correlation was first generalized to nonhematopoietic mammalian cells as well. A cause and effect relationship between expression of wild-type p53 and the G1 arrest that occurs after gamma irradiation was then established by demonstrating (i) acquisition of the G1 arrest after gamma irradiation following transfection of wild-type p53 genes into cells lacking endogenous p53 genes and (ii) loss of the G1 arrest after irradiation following transfection of mutant p53 genes into cells with wild-type endogenous p53 genes. A defined role for p53 (the most commonly mutated gene in human cancers) in a physiologic pathway has, to our knowledge, not been reported previously. Furthermore, these experiments illustrate one way in which a mutant p53 gene product can function in a "dominant negative" manner. Participation of p53 in this pathway suggests a mechanism for the contribution of abnormalities in p53 to tumorigenesis and genetic instability and provides a useful model for studies of the molecular mechanisms of p53 involvement in controlling the cell cycle.

DNA topoisomerase poisons as antitumor drugs.

Abstract: PERSPECTIVES AND SUMMARY .. . . ...... . ... 351 MAMMALIAN DNA TOPOISOMERASES . . . . . . . . . . . . ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... 353 Mammalian DNA Topoisomerase I . . . . . .. 353 Mammalian DNA Topoisomerase II 356 MAMMALIAN DNA TOPOISOMERASE II POISONS . . . . . . ... . . . ..... . . . . . . . . . . . . . . . . . . . . . 358 Intercalative Antitumor Drugs . .. . . 358 Nortintercalative Antitumor Epipodophyliotoxirts .... 361 Altered Regulation of Topoisomerase II in Tumor Cells......... . . . . . ..... 363 MAMMALIAN DNA TOPOISOMERASE I POISONS-CAMPTOTHECINS . . . ....... 364 BACTERIAL DNA TOPOISOMERASE II POISONS-QUINOLONE ANTIBIOTICS . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366 POSSIBLE MECHANISM(S) OF CELL KILLING BY MAMMALIAN TOPOISOMERASE POISONS . . . . . . . . . . . . . . . ....... . . . . . . . . . . . . . 368 Inhibition of DNA Synthesis . . 368 Inhibition of Cell Division .. . .. 369 DNA Degradation..... ... . . 370 OTHER CELLULAR RESPONSES AND DRUG RESISTANCE . . ...... 370

Adult neurogenesis in the mammalian central nervous system

Abstract: Forty years since the initial discovery of neurogenesis in the postnatal rat hippocampus, investigators have now firmly established that active neurogenesis from neural progenitors continues throughout life in discrete regions of the central nervous systems (CNS) of all mammals, including humans. Significant progress has been made over the past few years in understanding the developmental process and regulation of adult neurogenesis, including proliferation, fate specification, neuronal maturation, targeting, and synaptic integration of the newborn neurons. The function of this evolutionarily conserved phenomenon, however, remains elusive in mammals. Adult neurogenesis represents a striking example of structural plasticity in the mature CNS environment. Advances in our understanding of adult neurogenesis will not only shed light on the basic principles of adult plasticity, but also may lead to strategies for cell replacement therapy after injury or degenerative neurological diseases.