Institution
Johns Hopkins University School of Medicine
Healthcare•Baltimore, 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 & Medicine. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.
Topics: Population, Medicine, Cancer, Transplantation, Gene
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TL;DR: It is reported that sulforaphane and three synthetic analogues, designed as potent phase 2 enzyme inducers, block the formation of mammary tumors in Sprague-Dawley rats treated with single doses of 9,10-dimethyl-1,2-benzanthracene.
Abstract: Sulforaphane [1-isothiocyanato-4-(methyl-sulfinyl)butane] was recently isolated from one variety of broccoli as the major and very potent inducer of phase 2 detoxication enzymes in murine hepatoma cells in culture Since phase 2 enzyme induction is often associated with reduced susceptibility of animals and their cells to the toxic and neoplastic effects of carcinogens and other electrophiles, it was important to establish whether sulforaphane could block chemical carcinogenesis In this paper we report that sulforaphane and three synthetic analogues, designed as potent phase 2 enzyme inducers, block the formation of mammary tumors in Sprague-Dawley rats treated with single doses of 9,10-dimethyl-1,2-benzanthracene The analogues are exo-2-acetyl-exo-6-isothiocyanatonorbornane, endo-2-acetyl-exo-6-isothiocyanatonorbornane, and exo-2-acetyl-exo-5-isothiocyanatonorbornane When sulforaphane and exo-2-acetyl-exo-6-isothiocyanatonorbornane were administered by gavage (75 or 150 mumol per day for 5 days) around the time of exposure to the carcinogen, the incidence, multiplicity, and weight of mammary tumors were significantly reduced, and their development was delayed The analogues endo-2-acetyl-exo-6-isothiocyanatonorbornane and exo-2-acetyl-exo-5-isothiocyanatonorbornane were less potent protectors Thus, a class of functionalized isothiocyanates with anticarcinogenic properties has been identified These results validate the thesis that inducers of phase 2 enzymes in cultured cells are likely to protect against carcinogenesis
705 citations
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TL;DR: Examination of various biochemical characteristics of the GABAnergic nervous system in the rat brain was made between 15 days of gestation and adulthood, finding the rise in the density of the apparent postsynaptic GABA receptor after 8 days postpartum correlates best with the increase in the activity of glutamic acid decarboxylase, a presynaptic marker.
704 citations
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TL;DR: L1 elements are highly repeated mammalian DNA sequences whose structure suggests dispersal by retrotransposition and represents a potential source of the reverse transcriptase activity necessary for dispersion of the many classes of mammalian retroelements.
Abstract: L1 elements are highly repeated mammalian DNA sequences whose structure suggests dispersal by retrotransposition A consensus L1 element encodes a protein with sequence similarity to known reverse transcriptases The second open reading frame from the human L1 element L12A was expressed as a fusion protein targeted to Ty1 virus-like particles in Saccharomyces cerevisiae and shown to have reverse transcriptase activity This activity was eliminated by a missense mutation in the highly conserved amino acid motif Y/F-X-D-D Thus, L1 represents a potential source of the reverse transcriptase activity necessary for dispersion of the many classes of mammalian retroelements
703 citations
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TL;DR: The results of this study suggest that superoxide radicals are involved in the pathogenesis of ischemic mucosal lesions and that the enzyme xanthine oxidase is the source ofsuperoxide radicals in the isChemic small bowel.
703 citations
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TL;DR: The mitochondrial benzodiazepine receptor has been solubilized with retention of reversible ligand binding, and the associated subunits were characterized, finding that VDAC and ADC, outer and inner mitochondrial membrane channel proteins, respectively, together with the 18-kDa subunit, may comprise mBzR at functionally important transport sites at the junction of two mitochondrial membranes.
Abstract: The mitochondrial benzodiazepine receptor (mBzR) has been solubilized with retention of reversible ligand binding, and the associated subunits were characterized. mBzR comprises immunologically distinct protein subunits of 18-, 30-, and 32-kDa. The 18-kDa protein is labeled by the isoquinoline carboxamide mBzR ligand [3H]PK14105, whereas the 30- and 32-kDa subunits are labeled by the benzodiazepine (Bz) ligands [3H]flunitrazepam and [3H]AHN-086. Selective antibodies and reagents identify the 32- and 30-kDa proteins as the voltage-dependent anion channel (VDAC) and the adenine nucleotide carrier (ADC), respectively. While isoquinoline carboxamide and Bz ligands target different subunits, they interact allosterically, as the binding of Bz and isoquinoline carboxamide ligands is mutually competitive at low nanomolar concentrations. Moreover, eosin-5-maleimide and mercuric chloride inhibit [3H]PK11195 binding to the intact receptor via sulfhydryl groups that are present in ADC. VDAC and ADC, outer and inner mitochondrial membrane channel proteins, respectively, together with the 18-kDa subunit, may comprise mBzR at functionally important transport sites at the junction of two mitochondrial membranes.
703 citations
Authors
Showing all 44754 results
Name | H-index | Papers | Citations |
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Robert Langer | 281 | 2324 | 326306 |
Bert Vogelstein | 247 | 757 | 332094 |
Solomon H. Snyder | 232 | 1222 | 200444 |
Steven A. Rosenberg | 218 | 1204 | 199262 |
Kenneth W. Kinzler | 215 | 640 | 243944 |
Hagop M. Kantarjian | 204 | 3708 | 210208 |
Mark P. Mattson | 200 | 980 | 138033 |
Stuart H. Orkin | 186 | 715 | 112182 |
Paul G. Richardson | 183 | 1533 | 155912 |
Aaron R. Folsom | 181 | 1118 | 134044 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
Jie Zhang | 178 | 4857 | 221720 |
Daniel R. Weinberger | 177 | 879 | 128450 |
David Baker | 173 | 1226 | 109377 |
Eliezer Masliah | 170 | 982 | 127818 |