Warren James Strittmatter

Warren James Strittmatter
Professor Emeritus of Neurology

Apolipoprotein (apoE) has been recently implicated in the pathogenesis of Alzheimer's disease (A.D.). One of the apoE alleles, e4, behaves as an autosomal co-dominant trait in the majority of late-onset and sporadic A.D.. The aopE4 gene dose is a major risk-factor susceptibility gene for A.D. with homozygosity for this allele virtually sufficient to cause disease by age 80, and with 50% of homozygous patients developing disease by age 68. Incontrast, the e2 and e3 alleles decrease the probability of disease, and increase the age of onset. Thus the inherited apoE allele determines in part, the risk of developing A.D., and determines the rate of disease progression. Interactions of apoE protein with other molecules is therefore critical in the disease process, with isoforms-specific interactions of apoE determining th eprobability, and rate, of disease expression.
The three common protein isoforms of apoE; E2, E3, E4, differ from each other by one amino acid, which determines their profoundly differing interactions with other proteins. In vitro, apoE4 binds BA peptide faster, and with a different pH dependence, than does apoE3. This isoform-specific difference observed in vitro correlates with the greater BA peptide amyloid burden deposited in situ in homozygous e4 A.D. patients, compared with homozygous e3 A.D. patients. Paired-helical filaments of the neurofibrillary tangle are composed of tau protein. ApoE3 avidly binds tau in vitro, forming a complex not disociated by boiling in SDS. In contrast, apoE4 does not form such a complex. Isoform-specific interactions of apoE with tau could alter tau function or metabolism.

Current Appointments & Affiliations

Professor Emeritus of Neurology, Neurology, Behavioral Neurology, Neurology 2014

Contact Information

227H Bryan Res Bldg, Durham, NC 27710
Duke Box 2900, Durham, NC 27710
warren@neuro.duke.edu (919) 684-0053

Background
Education, Training, & Certifications
- M.D., Duke University 1973
Previous Appointments & Affiliations
- Professor of Neurology, Neurology, Behavioral Neurology, Neurology 1994 - 2014
- Professor of Neurobiology, Neurobiology, Basic Science Departments 1994 - 2013
- Chief, Division of Neurology in the Department of Medicine, Neurology, Clinical Science Departments 1998 - 2011
- Associate Professor of Medicine, Neurology, Clinical Science Departments 1993 - 1994
- Associate in the Department of Medicine, Medicine, Clinical Science Departments 1991 - 1993
Research
Selected Grants
- Trangenic Mouse Model of Alzheimer's Disease awarded by National Institutes of Health 2003 - 2006
- Manipulation of polyglutamine-protein interactions awarded by National Institutes of Health 2000 - 2003
- Alzheimer'S Disease Research Center awarded by National Institutes of Health 1985 - 1999
- Alzheimer'S Disease Research Center awarded by National Institutes of Health 1985 - 1999
- Apolipoprotein E/Tau Interactions In Alzheimer'S Disease awarded by National Institutes of Health 1994 - 1997
- Apolipoprotein E/Tau Interactions In Alzheimers Disease awarded by National Institutes of Health 1994 - 1997
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Popiel, H Akiko, Toshihide Takeuchi, James R. Burke, Warren J. Strittmatter, Tatsushi Toda, Keiji Wada, and Yoshitaka Nagai. “Inhibition of protein misfolding/aggregation using polyglutamine binding peptide QBP1 as a therapy for the polyglutamine diseases.” Neurotherapeutics 10, no. 3 (July 2013): 440–46. https://doi.org/10.1007/s13311-013-0184-7.
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  - Strittmatter, Warren J. “Bathing the brain.” J Clin Invest 123, no. 3 (March 2013): 1013–15. https://doi.org/10.1172/JCI68241.
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  - Strittmatter, Warren J. “Alzheimer’s disease: the new promise.” J Clin Invest 122, no. 4 (April 2012): 1191. https://doi.org/10.1172/jci62745.
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  - Strittmatter, Warren J. “Medicine. Old drug, new hope for Alzheimer's disease.” Science 335, no. 6075 (March 23, 2012): 1447–48. https://doi.org/10.1126/science.1220725.
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  - Swaminathan, Madhav, Alina Nicoara, Barbara G. Phillips-Bute, Nicolas Aeschlimann, Carmelo A. Milano, G Burkhard Mackensen, Mihai V. Podgoreanu, et al. “Utility of a simple algorithm to grade diastolic dysfunction and predict outcome after coronary artery bypass graft surgery.” Ann Thorac Surg 91, no. 6 (June 2011): 1844–50. https://doi.org/10.1016/j.athoracsur.2011.02.008.
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  - Heinzen, Erin L., Anna C. Need, Kathleen M. Hayden, Ornit Chiba-Falek, Allen D. Roses, Warren J. Strittmatter, James R. Burke, Christine M. Hulette, Kathleen A. Welsh-Bohmer, and David B. Goldstein. “Genome-wide scan of copy number variation in late-onset Alzheimer's disease.” J Alzheimers Dis 19, no. 1 (2010): 69–77. https://doi.org/10.3233/JAD-2010-1212.
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  - Need, Anna C., Dongliang Ge, Michael E. Weale, Jessica Maia, Sheng Feng, Erin L. Heinzen, Kevin V. Shianna, et al. “A genome-wide investigation of SNPs and CNVs in schizophrenia.” Plos Genet 5, no. 2 (February 2009): e1000373. https://doi.org/10.1371/journal.pgen.1000373.
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  - Weinberg, J. B., A. D. Volkheimer, M. Mihovilovic, N. Jiang, Y. Chen, K. Bond, J. O. Moore, et al. “Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia.” Leukemia 22, no. 12 (December 2008): 2184–92. https://doi.org/10.1038/leu.2008.241.
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  - Lai, Thung-S, Yusha Liu, Tim Tucker, Kurt R. Daniel, David C. Sane, Eric Toone, James R. Burke, Warren J. Strittmatter, and Charles S. Greenberg. “Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries.” Chem Biol 15, no. 9 (September 22, 2008): 969–78. https://doi.org/10.1016/j.chembiol.2008.07.015.
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  - Osorio, Cristina, Patrick M. Sullivan, Dong Ning He, Brian E. Mace, John F. Ervin, Warren J. Strittmatter, and Oscar Alzate. “Mortalin is regulated by APOE in hippocampus of AD patients and by human APOE in TR mice.” Neurobiol Aging 28, no. 12 (December 2007): 1853–62. https://doi.org/10.1016/j.neurobiolaging.2006.08.011.
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  - Hamuro, Lora, Guangtao Zhang, Timothy J. Tucker, Christopher Self, Warren J. Strittmatter, and James R. Burke. “Optimization of a polyglutamine aggregation inhibitor peptide (QBP1) using a thioflavin T fluorescence assay.” Assay Drug Dev Technol 5, no. 5 (October 2007): 629–36. https://doi.org/10.1089/adt.2007.083.
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  - Mihovilovic, Mirta, Jennifer B. Robinette, Robert M. DeKroon, Patrick M. Sullivan, and Warren J. Strittmatter. “High-fat/high-cholesterol diet promotes a S1P receptor-mediated antiapoptotic activity for VLDL.” J Lipid Res 48, no. 4 (April 2007): 806–15. https://doi.org/10.1194/jlr.M600201-JLR200.
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  - O’Grady, Gwen, Abee L. Boyles, Marcy Speer, Frank DeRuyter, Warren Strittmatter, and Gordon Worley. “Apolipoprotein E alleles and sensorineural hearing loss.” Int J Audiol 46, no. 4 (April 2007): 183–86. https://doi.org/10.1080/14992020601145294.
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  - DeKroon, Robert, Jennifer B. Robinette, Anita B. Hjelmeland, Emma Wiggins, Morven Blackwell, Mirta Mihovilovic, Makoto Fujii, et al. “APOE4-VLDL inhibits the HDL-activated phosphatidylinositol 3-kinase/Akt Pathway via the phosphoinositol phosphatase SHIP2.” Circ Res 99, no. 8 (October 13, 2006): 829–36. https://doi.org/10.1161/01.RES.0000245479.03190.9f.
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  - Halford, Jonathan, Gandis Mazeika, Susan Slifer, Marcy Speer, Ann M. Saunders, Warren J. Strittmatter, and Joel C. Morgenlander. “APOE2 allele increased in tardive dyskinesia.” Mov Disord 21, no. 4 (April 2006): 540–42. https://doi.org/10.1002/mds.20768.
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  - Puranam, Kasturi L., Guanghong Wu, Warren J. Strittmatter, and James R. Burke. “Polyglutamine expansion inhibits respiration by increasing reactive oxygen species in isolated mitochondria.” Biochem Biophys Res Commun 341, no. 2 (March 10, 2006): 607–13. https://doi.org/10.1016/j.bbrc.2006.01.007.
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  - Kenan, Daniel J., Warren J. Strittmatter, and James R. Burke. “Phage display screening for peptides that inhibit polyglutamine aggregation.” Methods Enzymol 413 (2006): 253–73. https://doi.org/10.1016/S0076-6879(06)13014-1.
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  - Blackman, James A., Gordon Worley, and Warren J. Strittmatter. “Apolipoprotein E and brain injury: implications for children.” Dev Med Child Neurol 47, no. 1 (January 2005): 64–70. https://doi.org/10.1017/s0012162205000113.
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  - Colton, C. A., Q. Xu, J. R. Burke, S. Y. Bae, J. K. Wakefield, A. Nair, W. J. Strittmatter, and M. P. Vitek. “Disrupted spermine homeostasis: a novel mechanism in polyglutamine-mediated aggregation and cell death.” J Neurosci 24, no. 32 (August 11, 2004): 7118–27. https://doi.org/10.1523/JNEUROSCI.1233-04.2004.
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  - Popiel, Helena A., Yoshitaka Nagai, Osamu Onodera, Takashi Inui, Nobuhiro Fujikake, Yoshihiro Urade, Warren J. Strittmatter, James R. Burke, Atsushi Ichikawa, and Tatsushi Toda. “Disruption of the toxic conformation of the expanded polyglutamine stretch leads to suppression of aggregate formation and cytotoxicity.” Biochem Biophys Res Commun 317, no. 4 (May 14, 2004): 1200–1206. https://doi.org/10.1016/j.bbrc.2004.03.161.
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  - Lai, T. -. S., T. Tucker, J. R. Burke, W. J. Strittmatter, and C. S. Greenberg. “Effect of tissue transglutaminase on the solubility of proteins containing expanded polyglutamine repeats.” J Neurochem 88, no. 5 (March 2004): 1253–60. https://doi.org/10.1046/j.1471-4159.2003.02249.x.
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  - Colton, Carol A., Leila K. Needham, Candice Brown, Danielle Cook, Karima Rasheed, James R. Burke, Warren J. Strittmatter, Donald E. Schmechel, and Michael P. Vitek. “APOE genotype-specific differences in human and mouse macrophage nitric oxide production.” J Neuroimmunol 147, no. 1–2 (February 2004): 62–67. https://doi.org/10.1016/j.jneuroim.2003.10.015.
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  - DeKroon, Robert M., Mirta Mihovilovic, Zoe V. Goodger, Jennifer B. Robinette, Patrick M. Sullivan, Ann M. Saunders, and Warren J. Strittmatter. “ApoE genotype-specific inhibition of apoptosis.” J Lipid Res 44, no. 8 (August 2003): 1566–73. https://doi.org/10.1194/jlr.M300097-JLR200.
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  - Nagai, Yoshitaka, Nobuhiro Fujikake, Katsuhito Ohno, Hiroyuki Higashiyama, Helena A. Popiel, Julia Rahadian, Masamitsu Yamaguchi, Warren J. Strittmatter, James R. Burke, and Tatsushi Toda. “Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila.” Hum Mol Genet 12, no. 11 (June 1, 2003): 1253–59. https://doi.org/10.1093/hmg/ddg144.
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  - Bedlack, R. S., D. Edelman, J. W. Gibbs, D. Kelling, W. Strittmatter, A. M. Saunders, and J. Morgenlander. “APOE genotype is a risk factor for neuropathy severity in diabetic patients.” Neurology 60, no. 6 (March 25, 2003): 1022–24. https://doi.org/10.1212/01.wnl.0000056689.50682.94.
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  - Panov, Alexander V., James R. Burke, Warren J. Strittmatter, and J Timothy Greenamyre. “In vitro effects of polyglutamine tracts on Ca2+-dependent depolarization of rat and human mitochondria: relevance to Huntington's disease.” Arch Biochem Biophys 410, no. 1 (February 1, 2003): 1–6. https://doi.org/10.1016/s0003-9861(02)00585-4.
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  - Panov, Alexander V., Claire-Anne Gutekunst, Blair R. Leavitt, Michael R. Hayden, James R. Burke, Warren J. Strittmatter, and J Timothy Greenamyre. “Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines.” Nat Neurosci 5, no. 8 (August 2002): 731–36. https://doi.org/10.1038/nn884.
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  - Shimohata, Takayoshi, Aki Sato, James R. Burke, Warren J. Strittmatter, Shoji Tsuji, and Osamu Onodera. “Expanded polyglutamine stretches form an 'aggresome'.” Neurosci Lett 323, no. 3 (May 3, 2002): 215–18. https://doi.org/10.1016/s0304-3940(02)00162-3.
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  - Strittmatter, Warren J., and Carol Bova Hill. “Molecular biology of apolipoprotein E.” Curr Opin Lipidol 13, no. 2 (April 2002): 119–23. https://doi.org/10.1097/00041433-200204000-00002.
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  - Ren, H., Y. Nagai, T. Tucker, W. J. Strittmatter, and J. R. Burke. “Amino acid sequence requirements of peptides that inhibit polyglutamine-protein aggregation and cell death.” Biochem Biophys Res Commun 288, no. 3 (November 2, 2001): 703–10. https://doi.org/10.1006/bbrc.2001.5783.
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  - Fullerton, S. M., G. A. Shirman, W. J. Strittmatter, and W. D. Matthew. “Impairment of the blood-nerve and blood-brain barriers in apolipoprotein e knockout mice.” Exp Neurol 169, no. 1 (May 2001): 13–22. https://doi.org/10.1006/exnr.2001.7631.
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  - Dranovsky, A., I. Vincent, L. Gregori, A. Schwarzman, D. Colflesh, J. Enghild, W. Strittmatter, P. Davies, and D. Goldgaber. “Cdc2 phosphorylation of nucleolin demarcates mitotic stages and Alzheimer's disease pathology.” Neurobiol Aging 22, no. 4 (2001): 517–28. https://doi.org/10.1016/s0197-4580(00)00248-7.
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  - Strittmatter, W. J. “Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms.” Biochem Soc Symp, no. 67 (2001): 101–9. https://doi.org/10.1042/bss0670101.
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  - Bedlack, R. S., W. J. Strittmatter, and J. C. Morgenlander. “Apolipoprotein E and neuromuscular disease: a critical review of the literature.” Arch Neurol 57, no. 11 (November 2000): 1561–65. https://doi.org/10.1001/archneur.57.11.1561.
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  - Chew, S. T., M. F. Newman, W. D. White, P. J. Conlon, A. M. Saunders, W. J. Strittmatter, K. Landolfo, H. P. Grocott, and M. Stafford-Smith. “Preliminary report on the association of apolipoprotein E polymorphisms, with postoperative peak serum creatinine concentrations in cardiac surgical patients.” Anesthesiology 93, no. 2 (August 2000): 325–31. https://doi.org/10.1097/00000542-200008000-00008.
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  - Saunders, A. M., M. K. Trowers, R. A. Shimkets, S. Blakemore, D. J. Crowther, T. A. Mansfield, D. M. Wallace, W. J. Strittmatter, and A. D. Roses. “The role of apolipoprotein E in Alzheimer's disease: pharmacogenomic target selection.” Biochim Biophys Acta 1502, no. 1 (July 26, 2000): 85–94. https://doi.org/10.1016/s0925-4439(00)00035-1.
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  - Nagai, Y., T. Tucker, H. Ren, D. J. Kenan, B. S. Henderson, J. D. Keene, W. J. Strittmatter, and J. R. Burke. “Inhibition of polyglutamine protein aggregation and cell death by novel peptides identified by phage display screening.” J Biol Chem 275, no. 14 (April 7, 2000): 10437–42. https://doi.org/10.1074/jbc.275.14.10437.
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  - Strittmatter, W. J. “Apolipoprotein E and Alzheimer's disease.” Ann N Y Acad Sci 924 (2000): 91–92. https://doi.org/10.1111/j.1749-6632.2000.tb05565.x.
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  - Cooper, A. J., K. F. Sheu, J. R. Burke, W. J. Strittmatter, V. Gentile, G. Peluso, and J. P. Blass. “Pathogenesis of inclusion bodies in (CAG)n/Qn-expansion diseases with special reference to the role of tissue transglutaminase and to selective vulnerability.” J Neurochem 72, no. 3 (March 1999): 889–99. https://doi.org/10.1046/j.1471-4159.1999.0720889.x.
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  - Nagai, Y., O. Onodera, J. Chun, W. J. Strittmatter, and J. R. Burke. “Expanded polyglutamine domain proteins bind neurofilament and alter the neurofilament network.” Exp Neurol 155, no. 2 (February 1999): 195–203. https://doi.org/10.1006/exnr.1998.6991.
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  - Moulder, K. L., O. Onodera, J. R. Burke, W. J. Strittmatter, and E. M. Johnson. “Generation of neuronal intranuclear inclusions by polyglutamine-GFP: analysis of inclusion clearance and toxicity as a function of polyglutamine length.” J Neurosci 19, no. 2 (January 15, 1999): 705–15. https://doi.org/10.1523/JNEUROSCI.19-02-00705.1999.
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  - Nagai, Y., O. Onodera, W. J. Strittmatter, and J. R. Burke. “Polyglutamine domain proteins with expanded repeats bind neurofilament, altering the neurofilament network.” Ann N Y Acad Sci 893 (1999): 192–202. https://doi.org/10.1111/j.1749-6632.1999.tb07826.x.
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  - Fullerton, S. M., W. J. Strittmatter, and W. D. Matthew. “Peripheral sensory nerve defects in apolipoprotein E knockout mice.” Exp Neurol 153, no. 1 (September 1998): 156–63. https://doi.org/10.1006/exnr.1998.6872.
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  - Scott, B. L., K. Welch, V. deSerrano, N. C. Moss, A. D. Roses, and W. J. Strittmatter. “Human apolipoprotein E accelerates microtubule polymerization in vitro.” Neurosci Lett 245, no. 2 (April 3, 1998): 105–8. https://doi.org/10.1016/s0304-3940(98)00180-3.
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  - Guyton, J. R., S. E. Miller, M. E. Martin, W. A. Khan, A. D. Roses, and W. J. Strittmatter. “Novel large apolipoprotein E-containing lipoproteins of density 1.006-1.060 g/ml in human cerebrospinal fluid.” J Neurochem 70, no. 3 (March 1998): 1235–40. https://doi.org/10.1046/j.1471-4159.1998.70031235.x.
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  - Cooper, A. J., K. F. Sheu, J. R. Burke, O. Onodera, W. J. Strittmatter, A. D. Roses, and J. P. Blass. “Inhibition of α-ketoglutarate-and pyruvate dehydrogenase complexes in E. coli by a glutathione S-transferase containing a pathological length poly-Q domain: A possible role of energy deficit in neurological diseases associated with poly-Q expansions?” Age (Omaha) 21, no. 1 (January 1998): 25–30. https://doi.org/10.1007/s11357-998-0004-x.
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  - Cooper, A. J., K. F. Sheu, J. R. Burke, W. J. Strittmatter, and J. P. Blass. “Glyceraldehyde 3-phosphate dehydrogenase abnormality in metabolically stressed Huntington disease fibroblasts.” Dev Neurosci 20, no. 4–5 (1998): 462–68. https://doi.org/10.1159/000017344.
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  - De Serrano, V., A. A. Ribeiro, W. J. Strittmatter, and L. D. Spicer. “Nmr investigation of a microtubule binding region peptide from human tau (τ) protein.” Protein and Peptide Letters 4, no. 3 (December 1, 1997): 165–72.
  - Cooper, A. J., K. R. Sheu, J. R. Burke, O. Onodera, W. J. Strittmatter, A. D. Roses, and J. P. Blass. “Transglutaminase-catalyzed inactivation of glyceraldehyde 3-phosphate dehydrogenase and alpha-ketoglutarate dehydrogenase complex by polyglutamine domains of pathological length.” Proc Natl Acad Sci U S A 94, no. 23 (November 11, 1997): 12604–9. https://doi.org/10.1073/pnas.94.23.12604.
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  - Onodera, O., J. R. Burke, S. E. Miller, S. Hester, S. Tsuji, A. D. Roses, and W. J. Strittmatter. “Oligomerization of expanded-polyglutamine domain fluorescent fusion proteins in cultured mammalian cells.” Biochem Biophys Res Commun 238, no. 2 (September 18, 1997): 599–605. https://doi.org/10.1006/bbrc.1997.7337.
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  - Gutman, C. R., W. J. Strittmatter, K. H. Weisgraber, and W. D. Matthew. “Apolipoprotein E binds to and potentiates the biological activity of ciliary neurotrophic factor.” J Neurosci 17, no. 16 (August 15, 1997): 6114–21. https://doi.org/10.1523/JNEUROSCI.17-16-06114.1997.
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  - Cooper, A. J., K. F. Sheu, J. R. Burke, O. Onodera, W. J. Strittmatter, A. D. Roses, and J. P. Blass. “Polyglutamine domains are substrates of tissue transglutaminase: does transglutaminase play a role in expanded CAG/poly-Q neurodegenerative diseases?” J Neurochem 69, no. 1 (July 1997): 431–34. https://doi.org/10.1046/j.1471-4159.1997.69010431.x.
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  - Onodera, O., A. D. Roses, S. Tsuji, J. M. Vance, W. J. Strittmatter, and J. R. Burke. “Toxicity of expanded polyglutamine-domain proteins in Escherichia coli.” Febs Lett 399, no. 1–2 (December 9, 1996): 135–39. https://doi.org/10.1016/s0014-5793(96)01301-4.
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  - Saunders, A. M., O. Hulette, K. A. Welsh-Bohmer, D. E. Schmechel, B. Crain, J. R. Burke, M. J. Alberts, W. J. Strittmatter, J. C. Breitner, and C. Rosenberg. “Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease.” Lancet 348, no. 9020 (July 13, 1996): 90–93. https://doi.org/10.1016/s0140-6736(96)01251-2.
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  - Chuang, D. M., and R. Ishitani. “A role for GAPDH in apoptosis and neurodegeneration.” Nat Med 2, no. 6 (June 1996): 609–10. https://doi.org/10.1038/nm0696-609.
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  - Fleming, L. M., K. H. Weisgraber, W. J. Strittmatter, J. C. Troncoso, and G. V. Johnson. “Differential binding of apolipoprotein E isoforms to tau and other cytoskeletal proteins.” Exp Neurol 138, no. 2 (April 1996): 252–60. https://doi.org/10.1006/exnr.1996.0064.
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  - Burke, J. R., J. J. Enghild, M. E. Martin, Y. S. Jou, R. M. Myers, A. D. Roses, J. M. Vance, and W. J. Strittmatter. “Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH.” Nat Med 2, no. 3 (March 1996): 347–50. https://doi.org/10.1038/nm0396-347.
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  - Montine, T. J., D. Y. Huang, W. M. Valentine, V. Amarnath, A. Saunders, K. H. Weisgraber, D. G. Graham, and W. J. Strittmatter. “Crosslinking of apolipoprotein E by products of lipid peroxidation.” J Neuropathol Exp Neurol 55, no. 2 (February 1996): 202–10. https://doi.org/10.1097/00005072-199602000-00009.
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  - Roses, A. D., G. Einstein, J. Gilbert, M. Goedert, S. H. Han, D. Huang, C. Hulette, et al. “Morphological, biochemical, and genetic support for an apolipoprotein E effect on microtubular metabolism.” Ann N Y Acad Sci 777 (January 17, 1996): 146–57. https://doi.org/10.1111/j.1749-6632.1996.tb34413.x.
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  - Montine, T. J., V. Amarnath, M. E. Martin, W. J. Strittmatter, and D. G. Graham. “E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures.” Am J Pathol 148, no. 1 (January 1996): 89–93.
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  - Strittmatter, W. J., J. R. Burke, V. S. DeSerrano, D. Y. Huang, W. Matthew, A. M. Saunders, B. L. Scott, J. M. Vance, K. H. Weisgraber, and A. D. Roses. “Protein: protein interactions in Alzheimer's disease and the CAG triplet repeat diseases.” Cold Spring Harb Symp Quant Biol 61 (1996): 597–605.
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  - Strittmatter, W. J., and A. D. Roses. “Apolipoprotein E and Alzheimer's disease.” Annu Rev Neurosci 19 (1996): 53–77. https://doi.org/10.1146/annurev.ne.19.030196.000413.
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  - Huang, D. Y., K. H. Weisgraber, W. J. Strittmatter, and W. D. Matthew. “Interaction of apolipoprotein E with laminin increases neuronal adhesion and alters neurite morphology.” Exp Neurol 136, no. 2 (December 1995): 251–57. https://doi.org/10.1006/exnr.1995.1101.
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  - Alberts, M. J., C. Graffagnino, C. McClenny, D. DeLong, W. Strittmatter, A. M. Saunders, and A. D. Roses. “ApoE genotype and survival from intracerebral haemorrhage.” Lancet 346, no. 8974 (August 26, 1995): 575. https://doi.org/10.1016/s0140-6736(95)91411-0.
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  - Corder, E. H., A. M. Saunders, W. J. Strittmatter, D. E. Schmechel, P. C. Gaskell, J. B. Rimmler, P. A. Locke, P. M. Conneally, K. E. Schmader, and R. E. Tanzi. “Apolipoprotein E, survival in Alzheimer's disease patients, and the competing risks of death and Alzheimer's disease.” Neurology 45, no. 7 (July 1995): 1323–28. https://doi.org/10.1212/wnl.45.7.1323.
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  - Huang, D. Y., K. H. Weisgraber, M. Goedert, A. M. Saunders, A. D. Roses, and W. J. Strittmatter. “ApoE3 binding to tau tandem repeat I is abolished by tau serine262 phosphorylation.” Neurosci Lett 192, no. 3 (June 16, 1995): 209–12. https://doi.org/10.1016/0304-3940(95)11649-h.
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  - Strittmatter, W. J., and A. D. Roses. “Apolipoprotein E and Alzheimer disease.” Proc Natl Acad Sci U S A 92, no. 11 (May 23, 1995): 4725–27. https://doi.org/10.1073/pnas.92.11.4725.
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  - Corder, E. H., A. M. Saunders, W. J. Strittmatter, D. E. Schmechel, P. C. Gaskell, A. D. Roses, M. A. Pericak-Vance, G. W. Small, and J. L. Haines. “The apolipoprotein E E4 allele and sex-specific risk of Alzheimer's disease.” Jama 273, no. 5 (February 1, 1995): 373–74.
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  - Roses, A. D., A. M. Saunders, M. A. Alberts, W. J. Strittmatter, D. Schmechel, E. Gorder, and M. A. Pericak-Vance. “Apolipoprotein E E4 allele and risk of dementia.” Jama 273, no. 5 (February 1, 1995): 374–75.
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  - Nakagawa, Y., T. Kitamoto, H. Furukawa, K. Ogomori, and J. Tateishi. “Apolipoprotein E in Creutzfeldt-Jakob disease.” Lancet 345, no. 8941 (January 7, 1995): 68.
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  - Roses, A. D., A. M. Saunders, W. J. Strittmatter, D. E. Schmechel, M. A. Pericak-Vance, and B. Hyman. “Apolipoprotein E in Creutzfeldt-Jacob disease.” Lancet 345, no. 8941 (January 7, 1995): 69.
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  - Huang, D. Y., M. Goedert, R. Jakes, K. H. Weisgraber, C. C. Garner, A. M. Saunders, M. A. Pericak-Vance, D. E. Schmechel, A. D. Roses, and W. J. Strittmatter. “Isoform-specific interactions of apolipoprotein E with the microtubule-associated protein MAP2c: implications for Alzheimer's disease.” Neurosci Lett 182, no. 1 (November 21, 1994): 55–58. https://doi.org/10.1016/0304-3940(94)90204-6.
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  - Strittmatter, W. J., A. M. Saunders, M. Goedert, K. H. Weisgraber, L. M. Dong, R. Jakes, D. Y. Huang, M. Pericak-Vance, D. Schmechel, and A. D. Roses. “Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.” Proc Natl Acad Sci U S A 91, no. 23 (November 8, 1994): 11183–86. https://doi.org/10.1073/pnas.91.23.11183.
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  - Goedert, M., W. J. Strittmatter, and A. D. Roses. “Alzheimer's disease. Risky apolipoprotein in brain.” Nature 372, no. 6501 (November 3, 1994): 45–46. https://doi.org/10.1038/372045a0.
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  - Han, S. H., G. Einstein, K. H. Weisgraber, W. J. Strittmatter, A. M. Saunders, M. Pericak-Vance, A. D. Roses, and D. E. Schmechel. “Apolipoprotein E is localized to the cytoplasm of human cortical neurons: a light and electron microscopic study.” J Neuropathol Exp Neurol 53, no. 5 (September 1994): 535–44. https://doi.org/10.1097/00005072-199409000-00013.
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  - Schwarzman, A. L., L. Gregori, M. P. Vitek, S. Lyubski, W. J. Strittmatter, J. J. Enghilde, R. Bhasin, J. Silverman, K. H. Weisgraber, and P. K. Coyle. “Transthyretin sequesters amyloid beta protein and prevents amyloid formation.” Proc Natl Acad Sci U S A 91, no. 18 (August 30, 1994): 8368–72. https://doi.org/10.1073/pnas.91.18.8368.
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  - Sanan, D. A., K. H. Weisgraber, S. J. Russell, R. W. Mahley, D. Huang, A. Saunders, D. Schmechel, T. Wisniewski, B. Frangione, and A. D. Roses. “Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3.” J Clin Invest 94, no. 2 (August 1994): 860–69. https://doi.org/10.1172/JCI117407.
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  - Han, S. H., C. Hulette, A. M. Saunders, G. Einstein, M. Pericak-Vance, W. J. Strittmatter, A. D. Roses, and D. E. Schmechel. “Apolipoprotein E is present in hippocampal neurons without neurofibrillary tangles in Alzheimer's disease and in age-matched controls.” Exp Neurol 128, no. 1 (July 1994): 13–26. https://doi.org/10.1006/exnr.1994.1108.
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  - Roses, A. D., W. J. Strittmatter, M. A. Pericak-Vance, E. H. Corder, A. M. Saunders, and D. E. Schmechel. “Clinical application of apolipoprotein E genotyping to Alzheimer's disease.” Lancet 343, no. 8912 (June 18, 1994): 1564–65. https://doi.org/10.1016/s0140-6736(94)92960-2.
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  - Corder, E. H., A. M. Saunders, N. J. Risch, W. J. Strittmatter, D. E. Schmechel, P. C. Gaskell, J. B. Rimmler, P. A. Locke, P. M. Conneally, and K. E. Schmader. “Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease.” Nat Genet 7, no. 2 (June 1994): 180–84. https://doi.org/10.1038/ng0694-180.
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  - Weisgraber, K. H., A. D. Roses, and W. J. Strittmatter. “The role of apolipoprotein E in the nervous system.” Curr Opin Lipidol 5, no. 2 (April 1994): 110–16. https://doi.org/10.1097/00041433-199404000-00007.
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  - Whitson, J. S., M. P. Mims, W. J. Strittmatter, T. Yamaki, J. D. Morrisett, and S. H. Appel. “Attenuation of the neurotoxic effect of A beta amyloid peptide by apolipoprotein E.” Biochem Biophys Res Commun 199, no. 1 (February 28, 1994): 163–70. https://doi.org/10.1006/bbrc.1994.1209.
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  - Strittmatter, W. J., K. H. Weisgraber, M. Goedert, A. M. Saunders, D. Huang, E. H. Corder, L. M. Dong, R. Jakes, M. J. Alberts, and J. R. Gilbert. “Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype.” Exp Neurol 125, no. 2 (February 1994): 163–71. https://doi.org/10.1006/exnr.1994.1019.
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  - St George-Hyslop, P., D. C. McLachlan, T. Tsuda, E. Rogaev, H. Karlinsky, C. F. Lippa, and D. Pollen. “Alzheimer's disease and possible gene interaction.” Science 263, no. 5146 (January 28, 1994): 537. https://doi.org/10.1126/science.8290965.
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  - Roses, A. D., M. A. Pericak-Vance, A. M. Saunders, D. Schmechel, D. Goldgaber, and W. Strittmatter. “Complex genetic disease: can genetic strategies in Alzheimer's disease and new genetic mechanisms be applied to epilepsy?” Epilepsia 35 Suppl 1 (1994): S20–28. https://doi.org/10.1111/j.1528-1157.1994.tb05925.x.
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  - Sakoda, S., M. Kuriyama, M. Osame, K. Takahashi, T. Yamano, J. Sasaki, and A. Matsunaga. “Apolipoprotein E ε4.” Neurology 44, no. 12 (January 1, 1994): 2420. https://doi.org/10.1212/WNL.44.12.2420.
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  - Schmechel, D. E., A. M. Saunders, W. J. Strittmatter, B. J. Crain, C. M. Hulette, S. H. Joo, M. A. Pericak-Vance, D. Goldgaber, and A. D. Roses. “Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.” Proc Natl Acad Sci U S A 90, no. 20 (October 15, 1993): 9649–53. https://doi.org/10.1073/pnas.90.20.9649.
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  - Goldgaber, D., A. I. Schwarzman, R. Bhasin, L. Gregori, D. Schmechel, A. M. Saunders, A. D. Roses, and W. J. Strittmatter. “Sequestration of amyloid beta-peptide.” Ann N Y Acad Sci 695 (September 24, 1993): 139–43. https://doi.org/10.1111/j.1749-6632.1993.tb23042.x.
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  - Saunders, A. M., K. Schmader, J. C. Breitner, M. D. Benson, W. T. Brown, L. Goldfarb, D. Goldgaber, M. G. Manwaring, M. H. Szymanski, and N. McCown. “Apolipoprotein E epsilon 4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases.” Lancet 342, no. 8873 (September 18, 1993): 710–11. https://doi.org/10.1016/0140-6736(93)91709-u.
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  - Strittmatter, W. J., K. H. Weisgraber, D. Y. Huang, L. M. Dong, G. S. Salvesen, M. Pericak-Vance, D. Schmechel, A. M. Saunders, D. Goldgaber, and A. D. Roses. “Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease.” Proc Natl Acad Sci U S A 90, no. 17 (September 1, 1993): 8098–8102. https://doi.org/10.1073/pnas.90.17.8098.
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  - Corder, E. H., A. M. Saunders, W. J. Strittmatter, D. E. Schmechel, P. C. Gaskell, G. W. Small, A. D. Roses, J. L. Haines, and M. A. Pericak-Vance. “Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.” Science 261, no. 5123 (August 13, 1993): 921–23. https://doi.org/10.1126/science.8346443.
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  - Strittmatter, W. J., D. Y. Huang, R. Bhasin, A. D. Roses, and D. Goldgaber. “Avid binding of beta A amyloid peptide to its own precursor.” Exp Neurol 122, no. 2 (August 1993): 327–34. https://doi.org/10.1006/exnr.1993.1132.
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  - Saunders, A. M., W. J. Strittmatter, D. Schmechel, P. H. George-Hyslop, M. A. Pericak-Vance, S. H. Joo, B. L. Rosi, J. F. Gusella, D. R. Crapper-MacLachlan, and M. J. Alberts. “Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease.” Neurology 43, no. 8 (August 1993): 1467–72. https://doi.org/10.1212/wnl.43.8.1467.
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  - Strittmatter, W. J., A. M. Saunders, D. Schmechel, M. Pericak-Vance, J. Enghild, G. S. Salvesen, and A. D. Roses. “Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.” Proc Natl Acad Sci U S A 90, no. 5 (March 1, 1993): 1977–81. https://doi.org/10.1073/pnas.90.5.1977.
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  - Huang, D., M. Martin, D. Hu, A. D. Roses, D. Goldgaber, and W. J. Strittmatter. “Binding of IgG to amyloid beta A4 peptide via the heavy-chain hinge region with preservation of antigen binding.” J Neuroimmunol 48, no. 2 (1993): 199–203. https://doi.org/10.1016/0165-5728(93)90192-2.
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  - Roses, A., M. Alberts, and W. Strittmatter. “Alzheimer's disease - reassessing the data.” Current Biology 2, no. 1 (January 1, 1992): 7–9. https://doi.org/10.1016/0960-9822(92)90400-5.
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  - Lennarz, W. J., and W. J. Strittmatter. “Cellular functions of metallo-endoproteinases.” Biochim Biophys Acta 1071, no. 2 (July 22, 1991): 149–58. https://doi.org/10.1016/0304-4157(91)90022-o.
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  - Rolak, L. A., W. Gilmer, and W. J. Strittmatter. “Low yield in the diagnostic evaluation of transient ischemic attacks.” Neurology 40, no. 5 (May 1990): 747–48. https://doi.org/10.1212/wnl.40.5.747.
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  - Pirozzolo, F. J., S. B. Inbody, P. A. Sims, W. J. Strittmatter, and D. Baskin. “Neuropathological and neuropsychological changes in Alzheimer's disease. Relationship of biologic markers to behavioral markers.” Clin Geriatr Med 5, no. 3 (August 1989): 425–40.
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  - Roe, J. L., H. R. Park, W. J. Strittmatter, and W. J. Lennarz. “Inhibitors of metalloendoproteases block spiculogenesis in sea urchin primary mesenchyme cells.” Exp Cell Res 181, no. 2 (April 1989): 542–50. https://doi.org/10.1016/0014-4827(89)90110-9.
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  - Appel, S. H., J. L. McManaman, and W. J. Strittmatter. “Will neurotrophic agents be harmful in Alzheimer's disease?” Neurobiol Aging 10, no. 5 (1989): 580–81. https://doi.org/10.1016/0197-4580(89)90136-x.
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  - Terrian, D. M., D. Johnston, B. J. Claiborne, R. Ansah-Yiadom, W. J. Strittmatter, and M. A. Rea. “Glutamate and dynorphin release from a subcellular fraction enriched in hippocampal mossy fiber synaptosomes.” Brain Res Bull 21, no. 3 (September 1988): 343–51. https://doi.org/10.1016/0361-9230(88)90146-3.
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  - Roe, J. L., H. A. Farach, W. J. Strittmatter, and W. J. Lennarz. “Evidence for involvement of metalloendoproteases in a step in sea urchin gamete fusion.” J Cell Biol 107, no. 2 (August 1988): 539–44. https://doi.org/10.1083/jcb.107.2.539.
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  - Strittmatter, W. J. “Molecular mechanisms of exocytosis: the adrenal chromaffin cell as a model system.” Cell Mol Neurobiol 8, no. 1 (March 1988): 19–25. https://doi.org/10.1007/BF00712907.
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  - Mundy, D., T. Hermann, and W. J. Strittmatter. “Specific inhibitors implicate a soluble metalloendoproteinase in exocytosis.” Cell Mol Neurobiol 7, no. 4 (December 1987): 425–37. https://doi.org/10.1007/BF00733794.
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  - Farach, H. A., and W. J. Strittmatter. “The soluble metalloendoprotease required in myoblast fusion remains intracellular.” Biochem Biophys Res Commun 147, no. 1 (August 31, 1987): 474–78. https://doi.org/10.1016/s0006-291x(87)80145-6.
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  - Farach, H. A., D. I. Mundy, W. J. Strittmatter, and W. J. Lennarz. “Evidence for the involvement of metalloendoproteases in the acrosome reaction in sea urchin sperm.” J Biol Chem 262, no. 12 (April 25, 1987): 5483–87.
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  - Mundy, D. I., and W. J. Strittmatter. “Requirement for metalloendoprotease in exocytosis: evidence in mast cells and adrenal chromaffin cells.” Cell 40, no. 3 (March 1985): 645–56. https://doi.org/10.1016/0092-8674(85)90213-2.
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  - Frederick, J. M., J. G. Hollyfield, and W. J. Strittmatter. “Inhibitors of metalloendoprotease activity prevent K+-stimulated neurotransmitter release from the retina of Xenopus laevis.” J Neurosci 4, no. 12 (December 1984): 3112–19. https://doi.org/10.1523/JNEUROSCI.04-12-03112.1984.
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  - Couch, C. B., and W. J. Strittmatter. “Specific blockers of myoblast fusion inhibit a soluble and not the membrane-associated metalloendoprotease in myoblasts.” J Biol Chem 259, no. 9 (May 10, 1984): 5396–99.
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  - Baxter, D. A., D. Johnston, and W. J. Strittmatter. “Protease inhibitors implicate metalloendoprotease in synaptic transmission at the mammalian neuromuscular junction.” Proc Natl Acad Sci U S A 80, no. 13 (July 1983): 4174–78. https://doi.org/10.1073/pnas.80.13.4174.
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  - Couch, C. B., and W. J. Strittmatter. “Rat myoblast fusion requires metalloendoprotease activity.” Cell 32, no. 1 (January 1983): 257–65. https://doi.org/10.1016/0092-8674(83)90516-0.
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  - Gagnon, C., S. Kelly, V. Manganiello, M. Vaughan, C. Odya, W. Strittmatter, A. Hoffman, and F. Hirata. “Modification of calmodulin function by enzymatic carboxyl methylation.” Nature 291, no. 5815 (1981): 515–16. https://doi.org/10.1038/291515a0.
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  - Hirata, F., J. F. Tallman, R. C. Henneberry, P. Mallorga, W. J. Strittmatter, and J. Axelrod. “Phospholipid methylation: a possible mechanism of signal transduction across biomembranes.” Prog Clin Biol Res 63 (1981): 383–88.
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  - Strittmatter, W. J., F. Hirata, and J. Axelrod. “Regulation of the beta-adrenergic receptor by methylation of membrane phospholipids.” Adv Cyclic Nucleotide Res 14 (1981): 83–91.
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  - Gagnon, C., S. Kelly, V. Manganiello, M. Vaughn, W. Strittmatter, A. Hoffman, and F. Hirata. “Protein carboxyl-methylase modifies calmodulin function.” Annals of the New York Academy of Sciences 356 (1980): 385–86.
  - Hirata, F., J. F. Tallman, R. C. Henneberry, P. Mallorga, W. J. Strittmatter, and J. Axelrod. “Regulation of beta-adrenergic receptors by phospholipid methylation.” Adv Biochem Psychopharmacol 21 (1980): 91–97.
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  - Mallorga, P., J. F. Tallman, R. C. Henneberry, F. Hirata, W. T. Strittmatter, and J. Axelrod. “Mepacrine blocks β-adrenergic agonist-induced desensitization in astrocytoma cells.” Proceedings of the National Academy of Sciences of the United States of America 77, no. 3 I (1980): 1341–45.
  - Tallman, J. F., D. W. Gallager, P. Mallorga, J. W. Thomas, W. Strittmatter, F. Hirata, and J. Axelrod. “Studies on benzodiazepine receptors.” Advances in Biochemical Psychopharmacology 21 (1980): 277–83.
  - Strittmatter, W. J., F. Hirata, J. Axelrod, P. Mallorga, J. F. Tallman, and R. C. Henneberry. “Benzodiazepine and beta-adrenergic receptor ligands independently stimulate phospholipid methylation.” Nature 282, no. 5741 (December 20, 1979): 857–59. https://doi.org/10.1038/282857a0.
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  - Strittmatter, W. J., F. Hirata, and J. Axelrod. “Phospholipid methylation unmasks cryptic beta-adrenergic receptors in rat reticulocytes.” Science 204, no. 4398 (June 15, 1979): 1205–7. https://doi.org/10.1126/science.221977.
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  - Strittmatter, W. J., F. Hirata, and J. Axelrod. “Increased Ca2+ -ATPase activity associated with methylation of phospholipids in human erythrocytes.” Biochem Biophys Res Commun 88, no. 1 (May 14, 1979): 147–53. https://doi.org/10.1016/0006-291x(79)91709-1.
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  - Hirata, F., W. J. Strittmatter, and J. Axelrod. “beta-Adrenergic receptor agonists increase phospholipid methylation, membrane fluidity, and beta-adrenergic receptor-adenylate cyclase coupling.” Proc Natl Acad Sci U S A 76, no. 1 (January 1979): 368–72. https://doi.org/10.1073/pnas.76.1.368.
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  - Strittmatter, W. J., C. Gagnon, and J. Axelrod. “Beta adrenergic stimulation of protein carboxymethylation and amylase secretion in rat parotid gland.” J Pharmacol Exp Ther 207, no. 2 (November 1978): 419–24.
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  - Strittmatter, W. J., J. N. Davis, and R. J. Lefkowitz. “α Adrenergic receptors in rat parotid cells. I. Correlation of [³H] dihydroergocryptine binding and catecholamine stimulated potassium efflux.” Journal of Biological Chemistry 252, no. 15 (December 1, 1977): 5472–77.
  - Strittmatter, W. J., J. N. Davis, and R. J. Lefkowitz. “α Adrenergic receptors in rat parotid cells. II. Desensitization of receptor binding sites and potassium release.” Journal of Biological Chemistry 252, no. 15 (December 1, 1977): 5478–82.
  - Davis, J. N., W. J. Strittmatter, E. Hoyler, and R. J. Leefkowitz. “[3H]dihydroergocryptine binding in rat brain.” Brain Res 132, no. 2 (August 26, 1977): 327–36. https://doi.org/10.1016/0006-8993(77)90425-5.
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  - Strittmatter, W. J., J. N. Davis, and R. J. Lefkowitz. “α Adrenergic receptor regulation: parallel change in K⁺ release and [³H]dihydroergocryptine (DHE) binding in rat parotid.” Federation Proceedings 36, no. 3 (January 1, 1977).
  - Strittmatter, W. J., J. N. Davis, and R. J. Lefkowitz. “α Adrenergic receptor desensitization: Reduction in physiologic response and receptor binding sites in rat parotid acinar cells.” Clinical Research 25, no. 1 (January 1, 1977).
  - Strittmatter, W. J., and G. G. Somjen. “Depression of sustained evoked potentials and glial depolarization in the spinal cord by barbiturates and by diphenylhydantoin.” Brain Res 55, no. 2 (June 15, 1973): 333–42. https://doi.org/10.1016/0006-8993(73)90299-0.
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- Other Articles
  - Mackensen, G. B., L. K. Ti, B. G. Phillips-Bute, J. P. Mathew, M. F. Newman, H. P. Grocott, and H. P. Neurologic Outcome Research Group (NORG). “Cerebral embolization during cardiac surgery: impact of aortic atheroma burden.” Br J Anaesth, November 2003. https://doi.org/10.1093/bja/aeg234.
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  - Swaminathan, Madhav, Brian J. McCreath, Barbara G. Phillips-Bute, Mark F. Newman, Joseph P. Mathew, Peter K. Smith, James A. Blumenthal, Mark Stafford-Smith, and Mark Perioperative Outcomes Research Group. “Serum creatinine patterns in coronary bypass surgery patients with and without postoperative cognitive dysfunction.” Anesth Analg, July 2002. https://doi.org/10.1097/00000539-200207000-00001.
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  - Grigore, Alina M., Hilary P. Grocott, Joseph P. Mathew, Barbara Phillips-Bute, Timothy O. Stanley, Aimee Butler, Kevin P. Landolfo, et al. “The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery.” Anesth Analg, January 2002. https://doi.org/10.1097/00000539-200201000-00002.
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  - Tardiff, B. E., M. F. Newman, A. M. Saunders, W. J. Strittmatter, J. A. Blumenthal, W. D. White, N. D. Croughwell, R. D. Davis, A. D. Roses, and J. G. Reves. “Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center.” Ann Thorac Surg, September 1997. https://doi.org/10.1016/s0003-4975(97)00757-1.
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