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19. Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death

Author

Herbert, B.-S., Pitts, A. E., Baker, S. I., Hamilton, S. E., Wright, W. E., Shay, J. W., and Corey, D. R.

Subjects
Telomerase -- Research, Tumors -- Research, Epithelial cells -- Research, Science and technology
Abstract

The correlation between telomerase activity and human tumors has led to the hypothesis that tumor growth requires reactivation of telomerase and that telomerase inhibitors represent a class of chemotherapeutic agents. Herein, we examine the effects of inhibition of telomerase inside human cells. Peptide nucleic acid and 2'-O-MeRNA oligomers inhibit telomerase, leading to progressive telomere shortening and causing immortal human breast epithelial cells to undergo apoptosis with increasing frequency until no cells remain. Telomere shortening is reversible: if inhibitor addition is terminated, telomeres regain their initial lengths. Our results validate telomerase as a target for the discovery of anticancer drugs and supply general insights into the properties that successful agents will require regardless of chemical type. Chemically similar oligonucleotides are in clinical trials and have well characterized pharmacokinetics, making the inhibitors we describe practical lead compounds for testing for an antitelomerase chemotherapeutic strategy.

Published
1999

21. Correspondence.

Author

Jefferson, Th., Ford, Worthington C., Gummey Jr., Chas. Francis, Dabney, R. H., G. W. A., Thayer, James B., G. H., Kennon, A. M., Wright, W. E. C., A. M., and Jastrow, Morris

Subjects
LETTERS to the editor, PRESIDENTS of the United States, UNIVERSITIES & colleges, EDUCATION, CONSTITUTIONS
Abstract

Presents several letters to the editor. Comments on the letter written by the U.S. President Thomas Jefferson; Discussion on pedagogy in the universities of the U.S.; Comments on the Constitution of Colorado.

Published
1889

22. Correspondence.

Author

March, F. A., Shufeldt, R. W., H. J. S., G. B., M. C. L., Wright, W. E. C., de Schweinitz, Paul, and Bure, Geo L.

Subjects
LETTERS to the editor, BANKING industry, POSTAL savings banks, LEGAL investments, PROHIBITIONISTS
Abstract

Presents letter to the editor. Facts regarding Philosophical Society's Dictionary; Facts regarding postal savings banks in Canada; Facts regarding prohibitionists in Massachusetts.

Published
1887

24. MyoD, myogenin independent differentiation of primordial myoblasts in mouse somites

Author

Maria Gabriella Cusella De Angelis, Lyons, G., Sonnino, C., Angelis, L., Vivarelli, E., Farmer, K., Wright, W. E., Molinaro, M., Bouché, M., Buckingham, M., and Cossu, G.

Subjects
Muscle Proteins, Myosins, Biology, MyoD, Mice, MyoD Protein, Myotome, Myosin, medicine, Animals, Myocyte, RNA, Messenger, Cells, Cultured, Myogenin, PITX2, Myogenesis, Muscles, Cell Differentiation, Articles, Cell Biology, musculoskeletal system, Molecular biology, medicine.anatomical_structure, Gene Expression Regulation, tissues
Abstract

The accumulation of two myogenic regulatory proteins, MyoD and myogenin, was investigated by double-immunocytochemistry and correlated with myosin heavy chain expression in different classes of myoblasts in culture and during early myogenesis in vivo. During in vitro differentiation of fetal myoblasts, MyoD-positive cells were detected first, followed by the appearance of cells positive for both MyoD and myogenin and finally by the appearance of differentiated myocytes and myotubes expressing myosin heavy chain (MHC). A similar pattern of expression was observed in cultures of embryonic and satellite cells. In contrast, most myogenic cells isolated from newly formed somites, expressed MHC in the absence of detectable levels of myogenin or MyoD. In vivo, the appearance of both myogenin and MyoD proteins was only detected at 10.5 d postcoitum (d.p.c.), when terminally differentiated muscle cells could already be identified in the myotome. Parasagittal sections of the caudal myotomes of 10.5-d-old embryos showed that expression of contractile proteins preceded the expression of myogenin or MyoD and, when coexpressed, MHC and myogenin did not co-localize within all the cells of the myotome. In the limb bud, however, many myogenin (or MyoD) positive/MHC negative cells could be observed in the proximal region at day 11. During further embryonic development the expression of these proteins remained constant in all the muscle anlagens examined, decreasing to a low level during the late fetal period. Western and Northern analysis confirmed that the myogenin protein could only be detected after 10.5 d.p.c. while the corresponding message was clearly present at 9.5 d.p.c., strongly suggesting a posttranscriptional regulation of myogenin during this stage of embryonic development. These data show that the first myogenic cells which appear in the mouse myotome, and can be cultured from it, accumulate muscle structural proteins in their cytoplasm without expressing detectable levels of myogenin protein (although the message is clearly accumulated). Neither MyoD message or protein are detectable in these cells, which may represent a distinct myogenic population whose role in development remains to be established.

Published
1992

29. Review of the Tri-Agency Space Nuclear Reactor Power System Technology Program

Author

Ambrus, J. H, Wright, W. E, and Bunch, D. F

Subjects
Spacecraft Propulsion And Power
Abstract

The Space Nuclear Reactor Power System Technology Program designated SP-100 was created in 1983 by NASA, the U.S. Department of Defense, and the Defense Advanced Research Projects Agency. Attention is presently given to the development history of SP-100 over the course of its first year, in which it has been engaged in program objectives' definition, the analysis of civil and military missions, nuclear power system functional requirements' definition, concept definition studies, the selection of primary concepts for technology feasibility validation, and the acquisition of initial experimental and analytical results.

Published
1984

30. Correspondence.

Author

Wright, W. E. C. and Elliott, Henry W.

Subjects
LETTERS to the editor, SILVER question, DEBTOR & creditor, CHURCH & the world
Abstract

Presents several letters to the editor. Impact of the silver bill on the U.S. debtors; Response by a reader on the article "The Church As an Aid to Good Conduct," published in the previous issue of the "Nation"; Discussion on the wealth of the islands of Alaska.

Published
1877

34. Telomere Dynamics in Macaques and Humans

Author

Gardner, J. P., primary, Kimura, M., additional, Chai, W., additional, Durrani, J. F., additional, Tchakmakjian, L., additional, Cao, X., additional, Lu, X., additional, Li, G., additional, Peppas, A. P., additional, Skurnick, J., additional, Wright, W. E., additional, Shay, J. W., additional, and Aviv, A., additional

Published
2007
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38. Is There an Antiaging Medicine?

Author

Butler, R. N., primary, Fossel, M., additional, Harman, S. M., additional, Heward, C. B., additional, Olshansky, S. J., additional, Perls, T. T., additional, Rothman, D. J., additional, Rothman, S. M., additional, Warner, H. R., additional, West, M. D., additional, and Wright, W. E., additional

Published
2002
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41. Functional requirement of p23 and Hsp90 in telomerase complexes

Author

Holt, S. E., primary, Aisner, D. L., additional, Baur, J., additional, Tesmer, V. M., additional, Dy, M., additional, Ouellette, M., additional, Trager, J. B., additional, Morin, G. B., additional, Toft, D. O., additional, Shay, J. W., additional, Wright, W. E., additional, and White, M. A., additional

Published
1999
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50. ChemInform Abstract: Synthesis and Biological Evaluation of a Series of Parenteral 3′‐Quaternary Ammonium Cephalosporins.

Author

BROWN, R. F., primary, KINNICK, M. D., additional, MORIN, J. M. JUN., additional, VASILEFF, R. T., additional, COUNTER, F. T., additional, DAVIDSON, E. O., additional, ENSMINGER, P. W., additional, EUDALY, J. A., additional, KASHER, J. S., additional, KATNER, A. S., additional, KOEHLER, R. E., additional, KURZ, K. D., additional, LINDSTROM, T. D., additional, LUNN, W. H. W., additional, PRESTON, D. A., additional, OTT, J. L., additional, QUAY, J. F., additional, SHADLE, J. K., additional, STEINBERG, M. I., additional, STUCKY, J. F., additional, SWARTZENDRUBER, J. K., additional, TURNER, J. R., additional, WEBBER, J. A., additional, WRIGHT, W. E., additional, and ZIMMERMAN, K. M., additional

Published
1991
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