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Institution

Johns Hopkins University School of Medicine

HealthcareBaltimore, Maryland, United States
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.


Papers
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Journal ArticleDOI
TL;DR: It is shown that eNampt does not exert insulin-mimetic effects in vitro or in vivo but rather exhibits robust NAD biosynthetic activity, suggesting a vital framework for the regulation of glucose homeostasis.

812 citations

Journal ArticleDOI
TL;DR: It is concluded that DNA strand breaks were sufficient for initiating p53-dependent signal transduction after finding that introduction of nucleases into cells by electroporation stimulated rapid p53 protein elevations.
Abstract: The tumor suppressor protein p53 serves as a critical regulator of a G1 cell cycle checkpoint and of apoptosis following exposure of cells to DNA-damaging agents. The mechanism by which DNA-damaging agents elevate p53 protein levels to trigger G1/S arrest or cell death remains to be elucidated. In fact, whether damage to the DNA template itself participates in transducing the signal leading to p53 induction has not yet been demonstrated. We exposed human cell lines containing wild-type p53 alleles to several different DNA-damaging agents and found that agents which rapidly induce DNA strand breaks, such as ionizing radiation, bleomycin, and DNA topoisomerase-targeted drugs, rapidly triggered p53 protein elevations. In addition, we determined that camptothecin-stimulated trapping of topoisomerase I-DNA complexes was not sufficient to elevate p53 protein levels; rather, replication-associated DNA strand breaks were required. Furthermore, treatment of cells with the antimetabolite N(phosphonoacetyl)-L-aspartate (PALA) did not cause rapid p53 protein increases but resulted in delayed increases in p53 protein levels temporally correlated with the appearance of DNA strand breaks. Finally, we concluded that DNA strand breaks were sufficient for initiating p53-dependent signal transduction after finding that introduction of nucleases into cells by electroporation stimulated rapid p53 protein elevations. While DNA strand breaks appeared to be capable of triggering p53 induction, DNA lesions other than strand breaks did not. Exposure of normal cells and excision repair-deficient xeroderma pigmentosum cells to low doses of UV light, under conditions in which thymine dimers appear but DNA replication-associated strand breaks were prevented, resulted in p53 induction attributable to DNA strand breaks associated with excision repair. Our data indicate that DNA strand breaks are sufficient and probably necessary for p53 induction in cells with wild-type p53 alleles exposed to DNA-damaging agents.

809 citations

Journal ArticleDOI
TL;DR: Inhibitors of human immunodeficiency virus (HIV)encoded protease, combined with nucleoside analogues with antiretroviral activity, cause profound and sustained suppression of viral replication, reduce morbidity, and prolong life in patients with HIV infection.
Abstract: Inhibitors of human immunodeficiency virus (HIV)–encoded protease, combined with nucleoside analogues with antiretroviral activity, cause profound and sustained suppression of viral replication, reduce morbidity, and prolong life in patients with HIV infection.1–3 Recent guidelines recommend that initial treatment of all HIV-infected patients include the administration of an HIV-protease inhibitor.4 The HIV-Encoded Protease The HIV protease, encoded in the 5' end of the pol gene, is expressed as part of the gag–pol polyprotein (Figure 1A, Figure 1B, and Figure 1C). This gene encodes a 99-amino-acid protein. Homodimers of this protein have the aspartyl protease activity that is typical of retroviral proteases; monomers . . .

809 citations

Journal ArticleDOI
26 Jan 1973-Science
TL;DR: In mouse somatosensory cortex there are discrete cytoarchitectonic units, called "barrels".
Abstract: In mouse somatosensory cortex there are discrete cytoarchitectonic units, called "barrels." Each barrel is related to one sensory vibrissa on the muzzle. Individual vibrissae were carefully injured at birth; 12 to 43 days later, the corresponding barrels proved to be absent. Evidently the sensory periphery has an important influence on the structure of the somatosensory cortex.

809 citations

Journal ArticleDOI
TL;DR: The second article on evidence-based statistics explores the inductive Bayesian approach to measuring evidence and combining information and addresses the epistemologic uncertainties that affect beliefs in the absence of evidence.
Abstract: The second article on evidence-based statistics explores the inductive Bayesian approach to measuring evidence and combining information and addresses the epistemologic uncertainties that affect al...

809 citations


Authors

Showing all 44754 results

NameH-indexPapersCitations
Robert Langer2812324326306
Bert Vogelstein247757332094
Solomon H. Snyder2321222200444
Steven A. Rosenberg2181204199262
Kenneth W. Kinzler215640243944
Hagop M. Kantarjian2043708210208
Mark P. Mattson200980138033
Stuart H. Orkin186715112182
Paul G. Richardson1831533155912
Aaron R. Folsom1811118134044
Gonçalo R. Abecasis179595230323
Jie Zhang1784857221720
Daniel R. Weinberger177879128450
David Baker1731226109377
Eliezer Masliah170982127818
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023149
2022622
20216,078
20205,107
20194,444
20183,848