• Hale, Daniel E (PI)
  • Douglas, Steven Daniel (PI)
  • Yudkoff, Marc (PI)
  • Pleasure, David (PI)
  • Corkey, Barbara (PI)
  • Stanley, Charles (PI)
  • Hummeler, Klaus (PI)
  • Watkins, John (PI)
  • Coates, Paul (PI)

Project: Research project

Project Details


The Program Project will address the pathogenesis of Reye's Syndrome (RS).
It is composed of four sections and six projects. The first section,
Project IA, is a central clinical core within Children's Hospital of
Philadelphia, a large children's referral hospital, with a referral base of
12 million; as well as core electron microscopic facilities. The research proposals are contained in Sections II, III, and IV. Section II - Project II - The role of ammonia toxicity in the pathogenesis
of (RS) will be addressed using in vivo and in vitro models, and newly
developed GC-mass spectrometric techniques. Section III - Projects III, IV, V - Energy metabolism in RS - This section
contains three projects which examine the mechanisms of impaired fatty acid
oxidation in RS and in genetic forms of fatty acid oxidation which mimic
RS. Abnormalities of carnitine metabolism as a primary or an acquired
defect will be specifically addressed. The genetic defects of fatty acid
oxidation will be further elucidated in vitro using fibroblasts and
leukocytes, permitting detailed characterization of the genetics and
biochemistry of the known genetic defects. Lastly, these tissues will be utilized to address the process by which
distinctive accumulation of Acyl-CoA intermediates serve to locate the site
of the defects in fatty acid oxidation. Section IV - Project VI - Studies of immunological and reticuloendothelial
systems in RS will examine the hypothesis that altered clearance of
endotoxin by the reticuloendothelial system, or that activation of the
macrophage may initiate changes which lead to mitochondrial damage and
abnormalities characteristic of RS.
Effective start/end date12/1/816/30/92


  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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