Abstract

This project seeks to understand the physiologic and clinical relevance of inherited differences in expression of two receptors that mediate the in initial phase of platelet adhesion to the blood vessel wall, the glycoprotein (GP) Ib-IX-V complex and the integrin a2b1. The impetus for these studies derivess from 1) our observations that there are significant differences in platelet a2b1 density among normal individuals, that these defferences correlate with inheritance of three alleles of the a2 gene, and that these differences influence platelet adhesion to collagens ex vivo; and 2) the recent findings that a single nucleotide dimorphism (T/C) within the Kozak sequence of the 5' untranslated region of the GPIbb gene influences GPIb-IX-V density, while additional GPIBa gene polymorphisms modulate GPIb-IX-V activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000833-26
Application #
6409333
Study Section
General Clinical Research Centers Committee (CLR)
Project Start
1977-12-01
Project End
2001-02-28
Budget Start
Budget End
Support Year
26
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Winn, Virginia D; Gormley, Matthew; Fisher, Susan J (2011) The Impact of Preeclampsia on Gene Expression at the Maternal-Fetal Interface. Pregnancy Hypertens 1:100-8
Delaney, Joseph A C; Scherzer, Rebecca; Biggs, Mary L et al. (2010) Associations of antiretroviral drug use and HIV-specific risk factors with carotid intima-media thickness. AIDS 24:2201-9
Pan, Warren W; Li, Jain-Dong; Huang, Shuang et al. (2010) Synergistic activation of NF-{kappa}B by bacterial chemoattractant and TNF{alpha} is mediated by p38 MAPK-dependent RelA acetylation. J Biol Chem 285:34348-54
Huang, XueSong; Chen, Ling-Yu; Doerner, Astrid M et al. (2009) An atypical protein kinase C (PKC zeta) plays a critical role in lipopolysaccharide-activated NF-kappa B in human peripheral blood monocytes and macrophages. J Immunol 182:5810-5
Mukherjee, Sumanta; Chen, Ling-Yu; Papadimos, Thomas J et al. (2009) Lipopolysaccharide-driven Th2 cytokine production in macrophages is regulated by both MyD88 and TRAM. J Biol Chem 284:29391-8
Chen, Ling-Yu; Pan, Zhixing K (2009) Synergistic activation of leukocytes by bacterial chemoattractants: potential drug targets. Endocr Metab Immune Disord Drug Targets 9:361-70
Chen, Ling-Yu; Pan, Warren W; Chen, Miao et al. (2009) Synergistic induction of inflammation by bacterial products lipopolysaccharide and fMLP: an important microbial pathogenic mechanism. J Immunol 182:2518-24
Ito, Tatsuo; Yadav, Neelu; Lee, Jaeho et al. (2009) Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification. BMC Dev Biol 9:47
Price, Richard W; Parham, Robin; Kroll, Jing Lu et al. (2008) Enfuvirtide cerebrospinal fluid (CSF) pharmacokinetics and potential use in defining CSF HIV-1 origin. Antivir Ther 13:369-74
Dawson, Arthur; Abel, Susan L; Loving, Richard T et al. (2008) CPAP therapy of obstructive sleep apnea in type 2 diabetics improves glycemic control during sleep. J Clin Sleep Med 4:538-42

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