Clarence A. Broomfield
United States Department of the Army
Molecular biologyEnzymeChemistryImmunologySerineProteaseKeratinocyteCytokineNerve agentAcetylcholinesteraseButyrylcholinesteraseAntidoteSomanSulfur mustardProteolysisAcid anhydride hydrolaseToxicityCholinesteraseActive siteBiochemistryStereochemistryBiologyPharmacology
86Publications
30H-index
2,181Citations
Publications 81
Newest
#1Brian C. Geyer (ASU: Arizona State University)H-Index: 12
#2Latha Kannan (ASU: Arizona State University)H-Index: 6
Last. Tsafrir S. Mor (Biodesign Institute)H-Index: 23
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The concept of using cholinesterase bioscavengers for prophylaxis against organophosphorous nerve agents and pesticides has progressed from the bench to clinical trial. However, the supply of the native human proteins is either limited (e.g., plasma-derived butyrylcholinesterase and erythrocytic acetylcholinesterase) or nonexisting (synaptic acetylcholinesterase). Here we identify a unique form of recombinant human butyrylcholinesterase that mimics the native enzyme assembly into tetramers; this...
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Poisoning via organophosphorus (OP) nerve agents occurs when the OP binds and inhibits the enzyme acetylcholinesterase (AChE). This enzyme is responsible for the metabolism of the neurotransmitter acetylcholine (ACh) which transmits signals between nerves and several key somatic regions. When AChE is inhibited, the signal initiated by ACh is not properly terminated. Excessive levels of ACh result in a cholinergic crisis, and in severe cases can lead to death. Current treatments for OP poisoning ...
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#1Patrick MassonH-Index: 68
#2Florian NachonH-Index: 43
Last. Oksana LockridgeH-Index: 67
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Abstract Wild-type human butyrylcholinesterase (BuChE) has proven to be an efficient bioscavenger for protection against nerve agent toxicity. Human acetylcholinesterase (AChE) has a similar potential. A limitation to their usefulness is that both cholinesterases (ChEs) react stoichiometrically with organophosphosphorus (OP) esters. Because OPs can be regarded as pseudo-substrates for which the dephosphylation rate constant is almost zero, several strategies have been attempted to promote the de...
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#1Carmen M. ArroyoH-Index: 12
Last. Brennie E. HackleyH-Index: 12
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Abstract : The central nervous system (CNS) is an immuneprivileged site where the role of immune cells and mediators in brain injury caused by organophosphates (OP) is poorly understood. Many mediators have been identified in nervous system tissue. For instance, interleukin-6 (IL-6), a cytokine that acts on a wide range of tissue influencing cell growth and differentiation, is an agonist for vascular endothelial growth factor (VEGF). CNS cells producing IL-6 include astrocytes, macrophages, micr...
#1Carmen M. Arroyo (DA: United States Department of the Army)H-Index: 12
#2Damon L. Burman (DA: United States Department of the Army)H-Index: 3
Last. Clarence A. Broomfield (DA: United States Department of the Army)H-Index: 30
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Studies were conducted to examine the effect of two vesicant chemical warfare agents (VCWA), one of them an arsenical, on cytokine gene expression in normal human epidermal keratinocyte (NHEK) cells. We tested 2,2′-dichlorethylsulfide (sulfur mustard, military designation HD) and 2,chlorovinyldichloroarsine (Lewisite, military designation L), which have significant differences in their chemical, physical, and toxicological properties. Human tumor necrosis factor-alpha (hTNF-α) cytokine was detec...
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#1Fred M. CowanH-Index: 9
Last. William J. SmithH-Index: 20
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The Multi-Threat Medical Countermeasure (MTMC) hypothesis has been proposed with the aim of developing a single countermeasure drug with efficacy against different pathologies caused by multiple classes of chemical warfare agents. Although sites and mechanisms of action and the pathologies caused by different chemical insults vary, common biochemical signaling pathways, molecular mediators, and cellular processes provide targets for MTMC drugs. This article will review the MTMC hypothesis for bl...
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#1Carmen M. ArroyoH-Index: 12
#2Damon L. BurmanH-Index: 3
Last. Brennie E. Hackley (DA: United States Department of the Army)H-Index: 12
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Abstract The proinflammatory cytokine human interleukin-6 (hIL-6) plays an important role in the early and late courses of inflammation, trauma, and wound healing caused by sulfur mustard (HD). Previously, we demonstrated that hIL-6 might be involved in the early event of structural changes of the signal transducer glycoprotein, which indirectly initiates the cascade of events, such as skin irritation and blister formation observed in the pathophysiology of HD injury. In this present work, we fo...
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#2Andreea Ticu BoeckH-Index: 4
Last. Clarence A. BroomfieldH-Index: 30
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Human butyrylcholinesterase (BChE, EC 3.1.1.8) is an efficient scavenger of nerve agents and organophosphorus (OP) pesticides; one molecule of BChE inactivates one molecule of OP in a suicide reaction that irreversibly inhibits BChE. By contrast the BChE mutant, G117H, inactivates many molecules of OP. The OP makes a covalent bond with the active site serine and then the serine is dephosphorylated by the action of His117. In an effort to understand the mechanism by which His 117 achieves dephosp...
#1Carmen M. ArroyoH-Index: 12
#2Robert K. Kan (DA: United States Department of the Army)H-Index: 12
Last. Clarence A. BroomfieldH-Index: 30
view all 8 authors...
p: The regulatory effects of the active form of vitamin D, 1-α, 25-dihydroxyvitamin D 3 (1-α, 25 (OH) 2 D 3 ) were assessed on the cytokine and chemokine secretion induced by sulfur mustard on human skin fibroblasts and human epidermal keratinocytes. Stimulation of human skin fibroblasts with sulfur mustard (10 -4 M for 24 hr at 37°) resulted in approximately a 5 times increase in the secretion of interleukin-6 and over a 10 times increase for interleukin-8, which was inhibited by 1-α, 25 (OH) 2...
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Despite the contrasts in chemistry and toxicity, for blister and nerve chemical warfare agents there may be some analogous proteolytic and inflammatory mediators and pathological pathways that can be pharmacological targets for a single-drug multi-threat medical countermeasure. The dermal-epidermal separation caused by proteases and bullous diseases compared with that observed following exposure to the blister agent sulfur mustard (2,2'-dichlorodiethyl sulfide) has fostered the hypothesis that s...
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