| Stoichiometric and Catalytic Scavengers as Protection Against Nerve Agent Toxicity: A Mini Review |
2007 |
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| Authors:
David E. Lenz; David Yeung; J. R. Smith; Richard E. Sweeney; Lucille A. Lumley; Douglas M. Cerasoli; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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 | The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE; PharinAthene Inc.) expressed in the milk of transgenic goats has become available. This material is biochemically similar to plasma-derived HuBuChE in in vitro assays. The pharmacokinetic ... |
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| Protection Against Soman or VX Poisoning by Human Butyrylcholinesterase in Guinea Pigs and Cynomolgus Monkeys |
15 DEC 2005 |
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| Authors:
Bhupendra P. Doctor; David E. Lenz; Irwin Koplovitz; Donald M. Maxwell; Douglas M. Cerasoli; Ashima Saxena; Connie R. Clark; Chunyuan Luo; Benjamin R. Capacio; James M. Federko; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| Human butyrylcholinesterase (HuBuChE), purified from outdated human plasma, is being evaluated for efficacy against nerve agents in guinea pigs and cynomolgus monkeys. Previous studies in rodents and nonhuman primates demonstrated that pretreatment of animals with enzymes that can scavenge nerve agents could provide significant protection against behavioral and lethal effects of nerve agent intoxication. In preparation for evaluation of efficacy of HuBuChE prior to initiating an investigational new drug (IND) ... |
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| In vitro Characterization of Recombinant Human BuChE (Protexia) as a Potential Bioscavenger |
01 OCT 2005 |
21 pages |
| Authors:
David E. Lenz; D. M. Cerasoli; E. M. Griffiths; B. P. Doctor; A. Saxena; N. H. Greig; Q. S. Yu; Y. Huang; H. Wilgus; C. N. Karatzas; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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 | OBJECTIVES: (1) Demonstrate improved medical protection against nerve agents; (2) Develop a prophylactic that detoxifies nerve agents at a rate sufficient to protect against 5LD-50 exposure; (3) Prophylactic should: Be non-toxic - Product no adverse side effects - Have no adverse effect on performance - Be easy to administer - Have a long biological half-life. CONCEPT: Provide a pretreatment capable of protecting against up to 5xLD-50 of nerve agent with ... |
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| Real Life Experiences Using the WRAIR Whole Blood and Pyridostigmine Assays |
01 OCT 2005 |
12 pages |
| Authors:
Julian R. Haigh; Gregory E. Garcia; Deborah R. Moorad-Doctor; Marian S. Farah; Bhupendra P. Doctor; Shawn R. Feaster; Richard K. Gordon; David E. Lenz; Connie R. Clark; Michael A. Riel; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Walter Reed Army Institute of Research Whole Blood (WRAIR WB) cholinesterase assay rapidly determines the concentrations of both AChE and BChE in unprocessed whole blood, uses a minimally invasive blood sampling technique (finger prick), and is fully automated (using the Biomek 2000 robotic system). In human blood from volunteers given pyridostigmine bromide (30 mg single dose), RBC-AChE was maximally inhibited by about 30% after 2.5 h, with recovery to 95% ... |
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| Bioscavengers as a Pretreatment for Nerve Agent Exposure |
17 AUG 2005 |
9 pages |
| Authors:
David E. Lenz; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| The use a bioscavenger has emerged as a new approach to reduce the in vivo toxicity of chemical warfare nerve agents. As an improvement of over current treatment, a biological scavenger should have no or minimal behavioral or physiological side effects, should provide protection up to a 5 LD50 exposure and should be devoid of any behavioral or physiological side effects. Studies with equine or human butyrylcholinesterase or fetal bovine ... |
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| Analysis of Active-Site Amino-Acid Residues of Human Serum Paraoxonase Using Competitive Substrates |
2005 |
7 pages |
| Authors:
David T. Yeung; David E. Lenz; Douglas M. Cerasoli; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| Serum paraoxonase (PON1) is a calcium-dependent six-fold beta-propeller protein structurally similar to the di-isopropylfluorophosphatase (DFPase) found in the squid Loligo vulgaris. Human serum paraoxonase (HuPON1) has been shown to hydrolyze an array of substrates even though relatively little is known about its physiological role(s) or its catalytic mechanism. Through site-directed mutagenesis studies, designed from a DFPase-like homology model, and from a crystal structure of a hybrid PONl molecule, amino-acid residues ... |
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| Role of Immunogen Design in Induction of Soman-Specific Monoclonal Antibodies |
2005 |
8 pages |
| Authors:
Jennifer K. Johnson; Douglas M. Cerasoli; David E. Lenz; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| The study of monoclonal antibodies raised against defined hapten epitopes has been a useful approach to understanding antibody repertoire. The situation in which antibodies are raised against different epitopes of the same hapten but have some common recognition or binding features has been less frequently examined. To explore the latter situation, we have characterized three monoclonal antibodies previously raised against two structurally different epitopes of the same organophosphorus nerve agent ... |
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| Current Pyridostigmine Bromide and Huperzine A Studies and Future Cholinesterase Screening Using the WRAIR Whole Blood Cholinesterase Assay |
15 NOV 2004 |
11 pages |
| Authors:
Richard K. Gordon; Julian R. Haigh; Gregory E. Garcia; Deborah R. Moorad-Doctor; Marian S. Farah; Ralf Brueckner; Shawn R. Feaster; Bhupendra P. Doctor; David E. Lenz; Connie R. Clark; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Cholinesterases are highly polymorphic carboxylesterases that display broad substrate specificity and are involved in the termination of neurotransmission in cholinergic synapses and neuromuscular junctions of the central nervous system (CNS). ChEs are classified as acetylcholinesterase and butyrylcholinesterase according to their substrate specificity and sensitivity to selected inhibitors (Silver, 1974). The concentration of AChE and BChE in blood is potentially a stable biomarker of suppressed and/or heightened central and peripheral nervous ... |
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| Structure/Function Analyses of Human Serum Paraoxonase (HuPON1) Mutants Designed from a DFPase-Like Homology Model |
23 AUG 2004 |
12 pages |
| Authors:
David T. Yeung; Denis Josse; James D. Nicholson; Akhil Khanal; Christopher W. McAndrew; Brian J. Bahnson; David E. Lenz; Douglas M. Cerasoli; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| Human serum paraoxonase (HuPON1) is a calcium-dependent enzyme that hydrolyzes esters, including organophosphates and lactones, and exhibits anti-atherogenic properties. A few amino acids have been shown to be essential for the enzyme's arylesterase and organophosphatase activities. Until very recently, a three-dimensional model was not available for HuPON1, so functional roles have not been assigned to those residues. Based on sequence-structure alignment studies, we have folded the amino acid sequence of ... |
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| Decontamination and Detoxification with Sponges |
JAN 2002 |
11 pages |
| Authors:
Richard K. Gordon; Shawn R. Feaster; Alper T. Gunduz; Bhupendra P. Doctor; David E. Lenz; Donald M. Maxwell; Rudy C. Macalalag; Edward D. Clarkson; John P. Skvorak; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF BIOCHEMISTRY
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| One of the serious problems that may be encountered while caring for personnel contaminated with organophosphate (OP) chemical warfare nerve agents is the possibility that there will be crosscontamination to the medical personnel. Secondly, during combat or terrorist acts, individuals might be exposed to chemical toxins before they don their protective gear. Therefore, we have attempted to develop an enzyme immobilized polyurethane foam which can effectively decontaminate the skin and ... |
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| PHARMACOKINETICS OF SOMAN AND ITS METABOLITES IN RATS. |
06 AUG 1987 |
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| Authors:
David E. Lenz; JEANNE BOISSEAU; Donald M. Maxwell; EDWARD HEIR; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| PRIOR STUDIES OF SOMAN (GD) PHARMACOKINETICS IN RATS DID NOT ACCOUNT FOR ITS NONSPECIFIC BINDING TO CARBOXYLESTERASE (CAE) IN RODENTS. SINCE SOMAN BINDING TO CAE HAS BEEN PROPOSED TO BE AN IMPORTANT ROUTE OF IN VIVO DETOXIFICATION (MAXWELL, THESE PROCEEDINGS), THE ELUCIDATION OF THE PHARMACOKINETICS OF SOMAN UNDER CONDITIONS WHERE THESE NON-SPECIFIC IRREVERSIBLE BINDING SITES HAVE BEEN BLOCKED IS ESSENTIAL TO UNDERSTANDING THE SPECIFIC PHYSIOLOGIC ACTION OF SOMAN. MALE RATS ... |
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| A Vaccine Against Organophosphorus Poisoning |
1972 |
15 pages |
| Authors:
Ludwig A. Sternberger; Van M. Sim; William G. Kavanagh; John J. Cuculis; Howard G. Meyers; David E. Lenz; Dennis M. Hinton; EDGEWOOD ARSENAL ABERDEEN PROVING GROUND MD
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| Immunization against nerve agents constitutes the first instance that vaccination against a synthetic chemical, not occurring in nature, has been found to be pharmacologically effective. It is hoped that immunohistochemically monitored refinements will make the procedure clinically safe. |
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