Institution
Worcester Foundation for Biomedical Research
About: Worcester Foundation for Biomedical Research is a based out in . It is known for research contribution in the topics: Estrone & Estrogen. The organization has 2195 authors who have published 2646 publications receiving 115809 citations. The organization is also known as: Worcester Foundation for Experimental Biology.
Topics: Estrone, Estrogen, RNA, Sperm, Microtubule
Papers published on a yearly basis
Papers
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TL;DR: Prostaglandins PGE 2 and PGF 2α depressed significantly the plasma testosterone levels when given subcutaneously to mature male rats at a dose of 500 μgm/rat/injection, b.i.d.
56 citations
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TL;DR: Findings collectively indicate that 3,4-di-OH-tam is proximate to the ultimate reactive intermediate that results in covalent binding to microsomal proteins.
Abstract: Metabolism of tamoxifen by rat and human hepatic microsomal cytochrome P450s (CYPs) forms a reactive intermediate that irreversibly binds to microsomal proteins (C. Mani and D. Kupfer, Cancer Res., 51: 6052-6058, 1991.). The current study examines the nature of the tamoxifen metabolite that is proximate to the reactive intermediate(s). The rate of covalent binding of tamoxifen metabolites, tamoxifen N-oxide, N-desmethyltamoxifen, and tamoxifen N-oxide-epoxide was approximately equal to or less than that of tamoxifen. By contrast, covalent binding of 4-hydroxytamoxifen (4-OH-tam) was 3-5-fold higher than that of tamoxifen, indicating that among the metabolites examined, 4-OH-tam or its metabolite(s) is most proximate to the reactive intermediate(s). Incubation of 4-OH-tam with liver microsomes from PCN-treated rat yielded three detectable metabolites. One was identified as 4-OH-tam N-oxide via its facile reduction back to 4-OH-tam by titanium(III) chloride. Another metabolite of 4-OH-tam, assumed to be 3,4-dihydroxytamoxifen (3,4-di-OH-tam) catechol, was demonstrated by its monomethylation with [3H]S-adenosyl-L-methionine ([3H]SAM) in presence of endogenous catechol-O-methyltransferase. Monomethylated catechol from 4-OH-tam was formed at a 3-4-fold higher rate than from tamoxifen. It was reasoned that if the catechol is most proximate metabolite to the reactive intermediate, then its methylation would reduce the formation of the reactive intermediate and result in lower rate of covalent binding. In fact, addition of radioinert SAM to incubations of tamoxifen inhibited covalent binding by 17-23%. By contrast, inclusion of 1.0 mM S-adenosyl-L-homocysteine, a potent inhibitor of catechol-O-methyltransferase-mediated methylation of 3,4-di-OH-tam, essentially overcame the inhibition of the covalent binding by SAM. Additionally, ascorbic acid and glutathione, inhibitors of covalent binding of tamoxifen, produced an elevation of methylated catechol. These findings collectively indicate that 3,4-di-OH-tam is proximate to the ultimate reactive intermediate that results in covalent binding to microsomal proteins.
56 citations
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TL;DR: The identity of tetrahymanol and wallichiniol, isolated from Tetrahymena pyriformis and Oleandra wallichii, is established and the presence in O.wallichii of a non-oxidative squalene cyclase system similar to that operating in T. p Pyriformis is suggested.
56 citations
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TL;DR: In this article, the effects of prenatal protein malnutrition on the efficacy of excitatory synaptic transmission at the level of the perforant path/dentate granule cell synapse were examined during development of perfant path kindling in chronically implanted adults rats.
56 citations
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TL;DR: It is concluded that some of the circulating estriol is directly secreted by the ovary of normal women and is significantly less than the follicular phase or oral contraceptive user values.
56 citations
Authors
Showing all 2195 results
Name | H-index | Papers | Citations |
---|---|---|---|
Robert A. Weinberg | 190 | 477 | 240903 |
Harvey F. Lodish | 165 | 782 | 101124 |
E. J. Corey | 136 | 1377 | 84110 |
Peter Palese | 132 | 526 | 57882 |
Sten Orrenius | 130 | 447 | 57445 |
Aldons J. Lusis | 127 | 673 | 73786 |
Michel Goedert | 125 | 337 | 64671 |
Frederic D. Bushman | 119 | 442 | 84206 |
Robert H. Singer | 113 | 391 | 41493 |
Joel F. Habener | 112 | 427 | 43774 |
Ryuzo Yanagimachi | 102 | 438 | 40651 |
Jaak Panksepp | 99 | 446 | 40748 |
Hagan Bayley | 97 | 344 | 33575 |
John H. Hartwig | 96 | 260 | 30336 |
Joseph Avruch | 94 | 191 | 40946 |