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Abstracts distinct nuclear chromatin compaction `clumping' ; leading to apoptotic cell death; and the phenotype required mitochondrial engagement since it was prevented by a Bax-inhibiting peptide Bip V5 ; . In the present studies we investigated the role of the ERK1 2 activated pathway. Hi-FGF-2 expression caused sustained activation of total as well as nuclear ERK 1 2 assessed by western blotting and antibodies to the dually phosphorylated ERK1 2. Hi-FGF-2 exerted its effect through an intracrine route since neutralizing anti-FGF-2 did not block ERK 1 2 activation. Interestingly, a non-nuclear hi-FGF-2 mutant was found to be equally capable as nuclear hi-FGF-2 in promoting ERK1 2 activation, but did not cause chromatin clumping. Pharmacological inhibition of the ERK1 2 activating pathway significantly attenuated the effects of hi-FGF-2 on chromatin. Preventing mitochondrial dysfunction by the Bax inhibiting peptide Bip V5 did not affect ERK1 2 activation by hi-FGF-2 suggesting that ERK1 2 activation occurs upstream of, and likely contributes to, mitochondrial pro-apoptotic activation. We conclude that intracrine and sustained activation of ERK1 2 by hi-FGF-2 is necessary but not sufficient to cause chromatin clumping and cell death. Our data imply that additional signals requiring nuclear localization of hi-FGF-2 and mitochondrial death signals are needed to obtain the observed chromatin phenotype and neurontin.
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1175 Wayne State Neurosurgery and the Gurdjian Legacy Daniel B. Michael, MD, PhD L. Murray Thomas, MD Detroit, MI ; Key Words: biomechanics, traumatic brain injury, Gurdjian, neurosurgical history The establishment and early contributions of Wayne State University neurosurgery are largely due to the first Professor and Chair, E. Stephen Gurdjian, MD, PhD. Born in Smryna, Asia Minor in 1900, he earned a bachelor's degree from the American University in Beirut in 1919, and MS, MD, and PhD degrees from the University of Michigan, finishing in 1927. He was the first graduate student of the noted neuroanatomist, Elizabeth Crosby, PhD. He completed his neurosurgical residency under Dr. Max Minor Peet at the University of Michigan. Dr. Gurdjian was the third neurosurgeon to practice in Detroit, in 1930. He established the Wayne State neurosurgery residency in 1946 and became the first Chair of the Department of Neurosurgery in 1957, serving until 1970. Dr. Gurdjian espoused.
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