Representative Publications:
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Fryer AD, Jacoby DB. The function of pulmonary M2 muscarinic receptors in antigen-challenged guinea pigs is restored by heparin and poly-l-glutamate. J Clin Invest 90:2292-2298, 1992.
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Jacoby DB, Gleich GJ, Fryer AD. Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. J Clin Invest 91:1314-1318, 1993.
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Fryer AD, Elbon CL, Kim AL, Xiao H-Q, Levey AI, Jacoby DB. Cultures of airway parasympathetic nerves express functional M2 muscarinic receptors. Am J Respir Cell Mol Biol 15:716-725, 1996.
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Jacoby DB, Xiao H-Q, Lee N, Chan-Li Y, Fryer AD. Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons. J. Clin Invest. 102:242-248, 1998.
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Adamko, DA, Yost BL, Gleich GJ, Fryer AD, Jacoby DB. Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection: eosinophils mediate airway hyperresponsiveness, M2 muscarinic receptor dysfunction, and antiviral effects. J Exp Med 190:1465-1478, 1999.
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Jacoby DB, Elwood T, Yost BL, Fryer AD. Neurokinin receptor antagonists in virus-infected airways: Dissociation of effects on inflammation and hyperresponsiveness. Am. J. Physiol.: Lung Cell. Mol. Physiol. 279:
L59-65, 2000
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Jacoby DB, Yost BL, Kumaravel B, Chan-Li Y, Xiao H-Q, Kawashima K, Fryer AD. Glucocorticoid treatment increases inhibitory M 2 muscarinic receptor expression and function in the airways. Am J Respir Cell Mol Biol. 24:485-491, 2001.
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Adamko DJ, Fryer AD, Bochner BS, Jacoby DB. CD8+ T lymphocytes in viral hyperreactivity and M2 muscarinic receptor dysfunction. Am J Respir Crit Care Med. 167:550-556, 2003.
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Lee AM, Fryer AD, van Rooijen N, Jacoby DB. The role of macrophages in virus-induced airway hyperresponsiveness and neuronal M2 muscarinic receptor dysfunction. Am J Physiol Lung Cell Mol Physiol. 286:
L1255-9, 2004.
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Fryer AD, Stein LH, Nie Z, Curtis DE, Evans CM, Hodgson ST, Jose PJ, Belmonte KE, Fitch E, Jacoby DB. Neuronal eotaxin and the effects of CCR3 antagonist on airway hyperreactivity and M2 receptor dysfunction. J Clin Invest, In press.
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Biosketch:
Dr. David Jacoby is Professor of Medicine, Physiology and Pharmacology and Chief of Pulmonary and Critical Care Medicine at Oregon Health and Science University. He was born in New York, and is a graduate of Princeton University and New York Medical College. He was a resident and chief resident in Internal Medicine at Temple University Hospital and did his fellowship at the Cardiovascular Research Institute at the University of California, San Francisco. He was a member of the Division of Pulmonary and Critical Care Medicine at Johns Hopkins for 13 years, where he was research director for the division. He moved to OHSU to become Division Chief in 2003.
Dr Jacoby's research focuses on viral infections of the lungs and how they cause asthma attacks. He has shown that viruses affect the efferent nerves controlling the airway smooth muscle, as well as airway sensory nerves. In the case of the efferent nerves, there is loss of function of M2 muscarinic receptors on the nerves. These inhibitory receptors normally turn off the release of acetylcholine, thereby limiting reflex bronchoconstriction. Viral infections decrease expression of the gene for this receptor, eliminating the negative feedback control of acetylcholine release and potentiating reflex bronchoconstriction. Viral infections also activate eosinophils, causing them to release major basic protein, which binds to M2 receptors blocking their function. He has also observed that eosinophils have an unexpected antiviral effect in the lungs. The mechanisms of this virus killing, and in particular the role of metabolism of bromide by eosinophil peroxidase, are another focus of his research.
More information regarding Dr. Jacoby's current research can be found at: http://physpharm.ohsu.edu/faculty/fryer/jacoby.htm
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