| Predicting Attrition, Performance, Reenlistment, and Hospitalizations from the Smoking History of Women Prior to Entering the Navy |
FEB 2006 |
45 pages |
| Authors:
Terry L. Conway; SAN DIEGO STATE UNIV FOUNDATION CA
|
 | This study of women sailors examined whether tobacco use prior to entering the Navy predicted subsequent career outcomes related to length of service, early attrition, misconduct, and hospitalizations over a possible 7-8 year follow-up. For almost 5,500 women entering the U.S. Navy between March 1996 - March 1997, who participated in Operation Stay Quit (OSQ) (USAMRMC Grant #DAMD17-95-1-5075), smoking history data were merged with personnel and medical data from the ... |
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| Identification of Gene Expression Changes in Whole Blood Indicative of Exposure to Chemicals with Different Target Organ Toxicity |
FEB 2006 |
16 pages |
| Authors:
Victor Chan; Andrea Stapleton; Armando Soto; Kyung Yu; Nicholas DelRaso; ALION SCIENCE AND TECHNOLOGY CORP DAYTON OH
|
| Toxicogenomic profiling is a molecular approach to capture the global, transcriptomic response of a biological system caused by perturbations resulted from chemical exposure. Coupled with advanced bioinformatic techniques, it allows for the elucidation of the molecular mechanisms of chemical toxicity, as well as the identification of novel biomarkers predictive for chemical exposure. In an effort to investigate if gene expression changes in whole blood can serve as novel biomarkers indicative ... |
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| Identification of Sildenafil (Viagra) and Its Metabolite (UK 103,320) in Six Aviation Fatalities |
FEB 2006 |
14 pages |
| Authors:
Robert D. Johnson; Russell J. Lewis; FEDERAL AVIATION ADMINISTRATION OKLAHOMA CITY OK CIVIL AEROMEDICAL INST
|
| During the investigation of aviation accidents, postmortem samples from victims are submitted to the Federal Aviation Administration's Civil Aerospace Medical Institute for toxicological analysis. This report presents a rapid and reliable method for the identification and quantitation of sildenafil (Viagra ) and its active metabolite, UK-103,320. This procedure utilizes sildenafil-d8 as an internal standard for more accurate and reliable quantitation. The method incorporates solid-phase extraction and LC/MS/MS and MS/MS/MS utilizing ... |
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| De Ontwikkeling van een PBPK Model voor VX; Stand van Zaken V013-813 en 207C (The Development of a PBPK Model for VX: Status Report) |
FEB 2006 |
|
| Authors:
H. C. Trap; TNO DEFENSE SECURITY AND SAFETY RIJSWIJK (NETHERLANDS)
|
 | As a follow-up on the development of the PBPK model for soman in the guinea pig and man a new model is being developed for VX. This report describes in short the work and results which has led to this model. Based on the Physiology (Physiologically-Based) of the investigated species the 'fate' or kinetics (Pharmaco Kinetics) of a compound can be predicted after an intoxication in several organs or compartments ... |
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| Predicting Dose-Response Relationships of Acute Cadmium Hepatoxicity and Metallothionein Regulation in the Rat Via In Vitro to In Vivo Extrapolation |
FEB 2006 |
44 pages |
| Authors:
Jeffery M. Gearhart; Diane M. Todd; John M. Frazier; Ellen L. Ebel; Jeffrey S. Eggers; Teresa R. Sterner; ALION SCIENCE AND TECHNOLOGY CORP DAYTON OH
|
| The purpose of this effort was to utilize cadmium, a known toxicant of environmental and occupational concern, to develop an understanding of the relationships between chemical kinetics (rates of chemical movement into the body) and cellular dynamics (cellular response to chemical entering the cells) in order to predict early target organ toxicity and refine/validate a biologically-based kinetic model. This effort involved three studies. The first measured cadmium kinetics over 24 ... |
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| Patterns of Antibody Response in Humans to the Anthrax Vaccine Adsorbed (AVA) Primary (six-dose) Series |
24 JAN 2006 |
8 pages |
| Authors:
Phillip R. Pittman; Sarah L. Norris; Julio G. Oro; David Bedwell; Timothy L. Cannon; Kelly T. McKee; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| The antibody profile during and after the six-dose primary vaccination series with anthrax vaccine adsorbed (AVA, BiothraxTM)was characterized in 86 human volunteers. Ninety-three percent of recipients developed IgG antibodies to Bacillus anthracis protective antigen (PA) after two doses, and 100% were seropositive after dose #3. Geometric mean concentrations (GMC) of IgG to PA measured before and after each dose were significantly lower after injection #3 (peak GMC = 146.65 micrograms ... |
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| Derivation of Human Lethal Doses |
19-Jan-2006 |
92 pages |
| Authors:
ARMY CENTER FOR ENVIRONMENTAL HEALTH RESEARCH FORT DETRICK MD
|
| Human lethal dose estimates are required, in conjunction with U.S. Army Military Exposure Guideline concentrations, to provide toxicity benchmarks for evaluation of candidate toxicity sensors for an Environmental Sentinel Biomonitor (ESB) system for drinking water protection. An approach was developed to estimate human lethal doses (lowest lethal dose - LD) for 26 Lo chemicals having varying amounts and qualities of toxicological data. Readily available toxicokinetic information was used to adjust ... |
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| Toxicity Screening of Hydrolyzed H, HD, and HT using the Bioluminescent Marine Bacterium, Vibrio Fischeri, by Means of Microtox Assay |
JAN 2006 |
15 pages |
| Authors:
Mark V. Haley; Ronald T. Checkai; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD
|
| The U.S. Army Edgewood Chemical Biological Center developed an alternative method for disposal of the chemical agent, sulfur mustard. The mineralization of HD through hot water hydrolysis with subsequent neutralization using NaOH, followed by biodegradation, has been demonstrated to be an effective technology at the Aberdeen Chemical Disposal Facility (ABCDF). In Assembled Chemical Weapons Alternative sponsored testing, the mineralization process (reaction with hot water followed by neutralization using NaOH) has ... |
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| Long-Term Outcomes of Alternative Brachytherapy Techniques for Early Prostate Cancer |
JAN 2006 |
16 pages |
| Authors:
James A. Talcott; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| All active, potentially curative treatments for clinically localized prostate cancer damage quality of life. Brachytherapy,or radioactive seed implants, theoretically may increase the target radiation dose and thus improve control of cancer. has been rapidly adopted in the U.S. despite limited long-term published outcomes, in part because of its convenience apparently attractive toxicity profile. However, our recent survey of brachytherapy patients after longer follow-up surprisingly frequent urinary incontinence and erectile dysfunction. ... |
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| Serotype-Selective, Small-Molecule Inhibitors of the Zinc Endopeptidase of Botulinum Neurotoxin Serotype A |
2006 |
15 pages |
| Authors:
Jewn G. Park; Peter C. Sill; Edward F. Makiyi; Alfonso T. Garcia-Sosa; Charles B. Millard; James J. Schmidt; Yuan-Ping Pang; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Botulinum neurotoxin serotype A (BoNTA) is one of the most toxic substances known. Currently there is no antidote to BoNTA. Small molecules identified from high-throughput screening reportedly inhibit the endopeptidase - the zinc-bound, catalytic domain of BoNTA - at a drug concentration of 20 M. However, optimization of these inhibitors is hampered by challenges including the computational evaluation of the ability of a zinc ligand to compete for coordination with ... |
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| Selection of a Battery of Rapid Toxicity Sensors for Drinking Water Evaluation |
2006 |
|
| Authors:
William H. van der Schalie; Ryan R. James; II. Gargan Thomas P.; ARMY CENTER FOR ENVIRONMENTAL HEALTH RESEARCH FORT DETRICK MD
|
| Comprehensive identification of chemical contaminants in Army field water supplies can be a lengthy process, but rapid analytical methods suitable for field use are limited. A complementary approach is to directly measure toxicity instead of individual chemical constituents. Ten toxicity sensors utilizing enzymes, bacteria, or vertebrate cells were tested to determine the minimum number of sensors that could rapidly identify toxicity in water samples containing one of 12 industrial chemicals. ... |
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| An Activity-Dependent Assay for Ricin and Related RNA N-Glycosidases Based on Electrochemiluminescence |
2006 |
9 pages |
| Authors:
William K. Keener; Victor R. Rivera; Charles C. Young; Mark A. Poli; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Synthetic biotinylated RNA substrates were cleaved by the combined actions of ricin holotoxin and a chemical agent, N,N'-dimethylethylenediamine. The annealing of the product with a ruthenylated oligodeoxynucleotide resulted in the capture of ruthenium chelate onto magnetic beads, enabling the electrochemiluminescence (ECL)-based detection of RNA N-glycosidase activities of toxins. ECL immunoassays and the activity assay exhibited similar limits of detection just below signals with 0.1ng/ml of ricin; the ECL response was ... |
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| Acetylcholinesterase Inhibition: Does it Explain the Toxicity of Organophosphorus Compounds? |
2006 |
6 pages |
| Authors:
Donald M. Maxwell; Karen M. Brecht; Irwin Koplovitz; Richard E. Sweeney; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| The hypothesis that acetylcholinesterase (AChE) inhibition is the mechanism of toxicity of organophosphorus (OP) compounds was examined by mathematically modeling the in vivo lethal effects of OP compounds and determining the amount of variation in OP toxicity that is explained by AChE inhibition. Mortality dose-response curves for several OP compounds (i.e., VX, soman, cyclosarin, sarin, tabun, diisopropylfluorophosphate and paraoxon) exhibited steep probit slopes (> 9.6) in guinea pigs. Steep probit ... |
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| Pretreatment of Human Epidermal Keratinocytes with D,L-Sulforaphane Protects Against Sulfur Mustard Cytotoxicity |
2006 |
10 pages |
| Authors:
Clark L. Gross; Eric W. Neally; Mary T. Nipwoda; William J. Smith; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Sulfur mustard (SM) is a powerful cytotoxic agent as well as a potent vesicant, mutagen, and carcinogen. This compound reacts with glutathione (GSH) and forms GSH-SM conjugates that appear to be excreted through the mercapturic acid pathway in mammals. The question of whether glutathione-S-tranferases (GST) are involved in enzymatic formation of these conjugates remains unresolved In previous studies, ethacrynic acid (EAA), a putative inhibitor of this transferase, and oltipraz, a ... |
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| Thiodiglycol, the Hydrolysis Product of Sulfur Mustard: Analysis of In Vitro Biotransformation by Mammalian Alcohol Dehydrogenases using Nuclear Magnetic Resonance |
2006 |
10 pages |
| Authors:
A. A. Brimfield; Mark J. Novak; Ernest Hodgson; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Thiodiglycol (2,2'-bis-hydroxyethylsulfide, TDG), the hydrolysis product of the chemical warfare agent sulfur mustard, has been implicated in toxicity of sulfur mustard through the inhibition of protein phosphatases in mouse liver cytosol. The absence of any inhibitory activity when TDG was present in assays of pure enzymes, however, led us to investigate the possibility for metabolic activation of TDG to inhibitory compound(s) by cytosolic enzymes. We have successfully shown that mammalian ... |
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| A Method for the Analysis of Tabun in Multisol Using Gas Chromatographic Flame Photometric Detection |
2006 |
6 pages |
| Authors:
Thomas P. Logan; Edward D. Allen; Mark R. Way; Austin T. Swift; Sunil-Datta Soni; Irwin Koplovitz; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Preparation and analysis of tabun (GA) solutions are necessary for the continued development of countermeasures to this nerve agent. GA solutions must be stable and compatible for use in the test systems chosen for study; however, GA is very unstable in saline solutions. In the past we have found GA in saline at 2 micrograms/mL to be stable for a month or less at -70 degrees C, whereas saline solutions ... |
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| Reliable Prescreening of Candidate NerveAgent Prophylaxes via 3D QSAR |
31 DEC 2005 |
28 pages |
| Authors:
Gerald H. Lushington; Jian-Xin Guo; Nora M. Wallace; KANSAS UNIV LAWRENCE
|
| Organophosphorus (OP) nerve agents are among the most toxic chemicals known to man and are notoriously easy to synthesize. As a result, their potential use against our military by insurgents, terrorists and other rogue groups remains a continuing threat. Therapeutics for countering OP toxicity exist, but do not adequately protect against some fast-acting agents (e.g., soman) without complementary support of prophylactic species. Some prophylactics do already exist, but may be ... |
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| Thermal Stress and the Physiological Response to Environmental Toxicants |
DEC 2005 |
|
| Authors:
Christopher J. Gordon; Lisa R. Leon; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA THERMAL AND MOUNTAIN MEDICINE DIVISION
|
| Most toxicological and pharmacological studies are performed in laboratory animals maintained under comfortable environmental conditions. Yet, the exposure to environmental toxicants as well as to many drugs can occur under stressful environmental conditions during rest or while exercising. The intake and biological efficacy of many toxicants is exacerbated by exposure to heat stress, which can occur in several ways. The increase in pulmonary ventilation during exposure to hot environments results ... |
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| Identification of a Protein for Prostate-Specific Infection |
DEC 2005 |
6 pages |
| Authors:
Shen Pang; CALIFORNIA UNIV LOS ANGELES
|
| In this proposal, the authors will identify and clone a protein that can be used to generate an infection-specific gene therapy vector. They expect that by using this protein to modify various gene therapy vectors, they can precisely deliver cytotoxic genes into prostate cancer cells using systemic treatment, and eventually eradicate the metastatic prostate cancer cells in patients. During the second year, they continue screening their cDNA library that they ... |
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| Biocatalytic Buffering System for Detoxification of Nerve Agents |
30 NOV 2005 |
25 pages |
| Authors:
Joel L. Kaar; Richard Koepsel; Alan J. Russell; PITTSBURGH UNIV PA
|
| A major obstacle in the utility of enzymes for decontamination purposes is their sensitivity to their surrounding environment. Enzymes are only catalytically active within a narrow range of conditions including pH and temperature. Sensitivity to pH is of particular importance in hydrolysis reactions due to the generation of acidic products. In the enzymatic hydrolysis of nerve agents, to prevent inaction of the enzyme prior to complete conversion of the toxin, ... |
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| Relationships and Transformations Between Concentration-Path-Length (CL), Agents Containing Particles per Liter of Air (ACPLA), and the Number of Spores (N spores) |
NOV 2005 |
34 pages |
| Authors:
Avishai Ben-David; Alan C. Samuels; Ronny C. Robbins; James O. Jensen; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD RESEARCH AND TECHNOLOGY DIR
|
| Threat levels and detection objectives are usually given as Agent-Containing-Particles per Liter of Air (ACPLA) where agents can be taken as spores (microbes, toxins, viruses) that are "stuck" together to form an aggregate (super) particle characterized by the size distribution and the packing efficiency of the agents. The number of agents (spores), Nspores, in ACPLA is of interest for assessing the pathogenic level of threat. Most standoff sensors measure mass-column-density ... |
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| Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cylotoxic T Lymphocytes |
NOV 2005 |
17 pages |
| Authors:
Kevin T. Hogan; VIRGINIA UNIV CHARLOTTESVILLE
|
| The purpose of the research is to identify new ovarian cancer tumor antigens that can be used in the immunotherapeutic treatment of ovarian cancer. The scope of this work involves (1) identifying the peptide antigens recognized by ovarian reactive cytotoxic T lymphocytes (CTL) by using an antigen-unbiased, mass spectrometric approach to antigen identification; and (2) identify peptide antigens within the Her-2/neu, folate binding protein (FBP), and TAG proteins that give ... |
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| Epidemiology of Toxicological Factors in Civil Aviation Accident Pilot Fatalities, 1999-2003 |
NOV 2005 |
17 pages |
| Authors:
Arvind K. Chaturvedi; Kristi J. Craft; Dennis V. Canfield; James E. Whinnery; FEDERAL AVIATION ADMINISTRATION OKLAHOMA CITY OK CIVIL AEROMEDICAL INST
|
| Prevalence of drug and ethanol use in aviation is monitored by the Federal Aviation Administration (FAA). Under such monitoring, epidemiological studies for the 1989-1993 and 11994-1998 periods indicated lower percentages of the presence of illegal (abused) drugs than that of prescription and nonprescription drugs in aviation accident pilot fatalities. In continuation of these studies, an epidemiological assessment was made for an additional period of 5 years. Postmortem samples from aviation ... |
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| A Recombinant 63-kDa Form of Bacillus anthracis Protective Antigen Produced in the Yeast Saccharomyces cerevisiae Provides Protection in Rabbit and Primate Inhalational Challenge Models of Anthrax Infection |
21 OCT 2005 |
15 pages |
| Authors:
Robert W. Hepler; Rosemarie Kelly; Tessie B. McNeely; Hongxia Fan; Maria C. Losada; Hugh A. George; Andrea Woods; Leslie D. Cope; Alka Bansal; James C. Cook; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Infection by Bacillus anthracis is preventable by prophylactic vaccination with several naturally derived and recombinant vaccine preparations. Existing data suggests that protection is mediated by antibodies directed against the protective antigen (PA) component of the anthrax toxin complex. PA is an 83-kDa protein cleaved in vivo to yield a biologically active 63-kDa protein. In an effort to evaluate the potential of yeast as an expression system for the production of ... |
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| The Inhalation Toxicity of Sarin (Gb) Vapor in Rats as a Function of Equilibration Time for Ten Minute Exposures |
01 OCT 2005 |
11 pages |
| Authors:
J. S. Anthony; Mark V. Haley; James H. Manthei; Ruth A. Way; David C. Burnett; Charles L. Crouse; Kathy L. Matson; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD
|
| Characterizing the toxicity of airborne exposures to chemical warfare agents requires sensitive, accurate and reliable analytical chemistry methods as well as adequate methods for generating and controlling the test atmosphere. In addition to concentration and exposure time, it is necessary to examine what effect the chamber equilibration time (t99) has on measured biological endpoints for shorter duration inhalation exposures (i.e. less than or equal 10 minutes). The t99 is defined ... |
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| The Inhalation Toxicity of VX Aerosols Assessed in the McNamara Glove Box Facility |
01 OCT 2005 |
11 pages |
| Authors:
John C. Carpin; David A. McCaskey; Kenneth P. Cameron; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD
|
| A series of mouse nose-only inhalation exposures with VX were conducted in the recently established McNamara glove box facility for the purpose of providing LCt50 reference data for future studies in this facility and to serve as a benchmark for ranking the toxicity of other agents. Neat VX challenge aerosols were generated by feeding micro-liter quantities of agent from a loaded syringe to a custom-made air assist atomizer. Exposure concentrations ... |
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| Inflammatory Gene Response in Rat Brain Following Soman Exposure |
01 OCT 2005 |
8 pages |
| Authors:
Anthony J. Williams; Rossana Berti; Changping Yao; Rebecca A. Prince; Luisa C. Velarde; Irwin Koplovitz; Susan M. Shulz; Frank C. Tortella; Jitendra R. Dave; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF NEUROSCIENCES
|
| This study reports an upregulation of the neuro-inflammatory gene response using quantitative RT-PCR following soman exposure in rats. Male Sprague-Dawley rats were pre-treated with HI-6 (125 mg/kg, i.p.) and exposed 30 min later to 1.6x LD50 of soman (180 microgram/kg, s.c.) followed at 1 min by atropine (4 mg/kg, i.m.). Initially, a significant upregulation of TNF-alpha and VCAM- 1 mRNA levels were measured 2 h post-exposure followed at 6 h ... |
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| Determination of Regenerated Sarin (GB) in Minipig and Human Blood by Gas Chromatography-Chemical Ionization Mass Chemical Ionization Mass Spectrometry Using Isotope Dilution and Large Volume Injection |
01 OCT 2005 |
24 pages |
| Authors:
E. M. Jakubowski; Jeffrey M. McGuire; Ronald A. Evans; Jennifer L. Edwards; Stanley W. Hulet; David Burnett; Robert J. Mioduszewski; Sandra A. Thomson; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD
|
|
| Inhibition of Blood Cholinesterase Activity is a Poor Predictor of Acetylcholinesterase Inhibition in Brain Regions of Guinea Pigs Exposed to Repeated Doses of Low Levels of Soman |
01 OCT 2005 |
25 pages |
| Authors:
Sally M. Anderson; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF NEUROSCIENCES
|
|
| Toxic Effects of a Whole-body Inhalation Sarin (GB) Vapor Exposure in the Gottingen Minipig |
01 OCT 2005 |
40 pages |
| Authors:
Stanley W. Hulet; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD
|
|
| Molecular Mechanisms of Sulfur Mustard Vesicant-Induced Cell Death: Early and Late Cell Responses |
01 OCT 2005 |
25 pages |
| Authors:
Pen Zhang; Michelle Yuequi Chen; Diana Caridha; William J. Smith; Peter K. Chiang; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
|
|
| Sulfur Mustard- and Phosgene- Increased IL-8 in Human Small Airway Cell Cultures: Implications for Medical Countermeasures Against Inhalation Toxicity |
01 OCT 2005 |
8 pages |
| Authors:
Fred M. Cowan; William J. Smith; Ted S. Moran; Michelle M. Paris; Adetunji B. Williams; Alfred M. Sciuto; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Inflammation and edema are associated with respiratory and cutaneous exposure to sulfur mustard (SM) as well as with phosgene-induced lung injury. IL-8 is a key inflammatory cytokine that recruits neutrophils linked with the onset and progression of acute lung injury caused by inhalation of these chemical agents. In the present study, human lung small airway cell (SAC) cultures were exposed to either SM [25 to 400 micrometers] or phosgene [0.1 ... |
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| Repeated Exposure to Low Levels of the Chemical Warfare Agent VX Activates Cell Survival Related Gene in Mouse Brain |
01 OCT 2005 |
20 pages |
| Authors:
Jose M. Pizarro; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF NEUROSCIENCES
|
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| Antivesicant Strategies Based on DNA Repair and Apoptosis |
01 OCT 2005 |
8 pages |
| Authors:
R. Ray; K. R. Bhat; D. S. Rosenthal; B. J. Benton; D. R. Anderson; W. Holmes; J. P. Petrali; T. Hamilton; P. Ray; W. J. Smith; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| DNA is a major cellular target of the vesicant chemical warfare agent sulfur mustard (SM, bis-(2-chloroethyl) sulfide). Others and we have proposed a possible role of apoptosis in SM vesication. Our results suggest that in SM-exposed human epidermal keratinicytes (HEK), DNA damage, DNA repair, and apoptosis may be interdependent. In HEK, SM causes cell death accompanied by caspase-3 activation indicating apoptosis. The general caspase inhibitor A-VAD-FMK (benzyl oxycarbonly-Val-Ala (o-methyl-fluromethylketone)) decreases ... |
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| Application of Sirna Technology to Manipulate Factors Involved in Acetylcholine Exocytosis and Botulinum Toxicity |
01 OCT 2005 |
6 pages |
| Authors:
Hiroshi Ishida; Kelly Erickson; Prabhati Ray; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF EXPERIMENTAL THERAPEUTICS
|
| We demonstrated that the RhoB signaling pathway, regulates ACh release via actin cytoskeletal reorganization and that botulinum toxin type A (BoNT) inhibits neuroexocytosis by targeting the RhoB pathway in nerve growth factor-differentiated PC12 cells. To confirm these facts, small interfering RNA (siRNA) was used to knockout the expression of RhoB. Transfection of PC12 cells by the siRNA resulted in about 70% reduction of both mRNA and RhoB expression. This siRNA-induced ... |
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| Detoxification of Chemical Warfare Agents by the Plant Cholinergic System |
01 OCT 2005 |
7 pages |
| Authors:
Suman S. Thakur; Gregory E. Garcia; Haim N. Leader; Deborah Moorad-Doctor; Rajendra Gupta; Richard K. Gordon; Bhupendra P. Doctor; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
| Plants have cholinesterases (pChEs), anti-ChEs, and activators of ChEs. We have isolated pChE from mung bean sprout. We investigated 300 plants and found that 75% of them contained anti- ChE that inhibited ChEs. Thirty-five percent contained activators of ChEs. An activator of ChE from wheat leaf, Tritiacche-T123 , activates fetal bovine serum AChE, equine BChE, and pChE. This non-oxime natural plant product may offer a new approach to the reactivation ... |
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| Interactions of Organophosphorus and Related Compounds with Acetylcholinesterase |
01 OCT 2005 |
23 pages |
| Authors:
Margaret M. Hurley; Jeffrey B. Wright; Gerald Lushington; ARMY RESEARCH LAB ABERDEEN PROVING GROUND MD COMPUTATIONAL AND INFORMATION SCIENCES DIR
|
| The objective of this study was to understand the reversible and irreversible binding of organophosphorus (OP) and other compounds in active site of acetylcholinesterase, the role of solvent, the mechanism of oxime therapy and the "aging" mechanism through the use of theoretical modeling in order to facilitate development of new compounds for therapeutic and prophylaxis. |
|
| Investigating Toxicity and Differential Protein Expression in the Aedes aegypti Mosquito Larvae, as an in vivo Bioassay for Chemical and Biological Weapon Agents |
01 OCT 2005 |
18 pages |
| Authors:
R. S. Mackie; B. W. Gutting; A. Rayms-Keller; NAVAL SURFACE WARFARE CENTER DAHLGREN DIV VA
|
| What sets this detection method apart from others? (1) Currently, detection systems for biological warfare agents utilize PCR (polymerase chain reaction) to amplify genetic material specific to an agent, or antibodies that recognize proteins specific for known agents; (2) Current detection systems for chemical warfare agents utilize physical and chemical properties that are specific for known agents; (3) In the IAD system, we are measuring the response of an organism ... |
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| Selective Cytotoxic Phospholipids for Prostate Cancer |
OCT 2005 |
24 pages |
| Authors:
Duane D. Miller; TENNESSEE UNIV MEMPHIS
|
| The goal of this project is to build upon our discovery of two phospholipid lead compounds, serine amide phosphate (SAP) and serine diamide phosphate (SDAP), that have been shown to he selective in their cytotoxic actions in PC-3 and DU-145 prostate caner cells respectively. These agents were originally designed as part of a series of compounds to inhibit lysophosphatidic acid (LPA), a phospholid growth factor. After discovering the antiproliferation activity ... |
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| A Model DoD Systems Approach for Tobacco Cessation |
OCT 2005 |
11 pages |
| Authors:
Harry A. Lando; MINNESOTA UNIV MINNEAPOLIS
|
| Military personnel have a smoking rate of approximately 30%, and recent evidence indicates this rate is no longer decreasing. Given the costs in terms of health care expenditures and decreased troop readiness, more must be done to decrease smoking in the military. The primary objective of the study is to evaluate whether implementation of a specialized intervention program based on the recommendations of the DoD Tobacco Cessation Policy Working Group ... |
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| The Clinical Development of Thalildomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer |
OCT 2005 |
17 pages |
| Authors:
Christopher J. Logothetis; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Significant progress has been made in the understanding of key factors that regulate the cell-cell interaction in the context of the microenvironment of prostate cancer. This includes technical advances in getting information from small amounts of tissue to forward understanding of the molecular determinants of progression. We have developed tissue micro arrays (TMAs), and stained them for candidate factors implicated in stromal epithelial interaction and have demonstrated that they are ... |
|
| Inhalation of Uranium Oxide Aerosois: CNS Deposition, Neurotoxicity, and Role in Gulf War Illness |
OCT 2005 |
46 pages |
| Authors:
Johnnye L. Lewis; Graham Bench; Fletcher F. Hahn; NEW MEXICO UNIV ALBUQUERQUE
|
| This study investigates the potential for inhaled uranium oxide (UO) aerosols to penetrate the nose-brain barrier, directly enter the central nervous system (CNS), distribute within the CNS, and result in slowly developing neurotoxicity. Inhalation exposures to depleted uranium (DU) may have occurred during the GW in several scenarios of varying duration and airborne uranium concentration. Nasal inflammation could alter sensitivity to uranium uptake. Nephrotoxic and pulmonary effects are evaluated to ... |
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| The Toxicology of Chemical Mixtures Risk Assessment for Human and Ecological Receptors |
OCT 2005 |
101 pages |
| Authors:
Teresa R. Sterner; Peter J. Robinson; David R. Mattie; G. A. Burton; OPERATIONAL TECHNOLOGIES CORP BEAVERCREEK OH
|
| Mixtures of chemicals represent a concern in all areas of toxicology and a challenge to risk assessors as most sites with environmental contamination, including Department of Defense sites, involve simultaneous or sequential exposures of multiple chemicals to human or ecological receptors. A major concern with mixtures is that they may lead to outcomes (health effects) or increased toxicity (synergism) not expected from the risk characterization of individual chemicals at the ... |
|
| A Model DOD Systems Approach for Tobacco Cessation |
14 SEP 2005 |
8 pages |
| Authors:
Harry A. Lando; MINNESOTA UNIV MINNEAPOLIS
|
| Military personnel have a smoking rate of approximately 30%, and recent evidence indicates this rate is no longer decreasing. Given the costs in terms of health care expenditures and decreased troop readiness, more must be done to decrease smoking in the military. This project is a group-randomized trial to test the effectiveness of intervention programs in increasing smoking cessation rates of active duty personnel and TRICARE Prime beneficiaries. Approximately 150 ... |
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| The Relationship Between Copper Speciation and Toxicity for Larvae of the Blue Mussel Mytilus edulis: Regulatory Implications and Determination of Water Effect Ratios |
07 SEP 2005 |
4 pages |
| Authors:
James W. Moffett; WOODS HOLE OCEANOGRAPHIC INSTITUTION MA
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| Copper toxicity to larvae of the blue mussel Mytilus edulis was quantified in chemically defined media to determine the relationship between concentrations of the free aquo Cu2+ ion and toxicity. The objective was to generate robust relationships to predict the effects of water chemistry on the toxic effects of copper and assess their ecological and regulatory implications. We found a robust relationship exists, suggesting that this species, a key organism ... |
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| The Thermal Stabilization of Vaccines Against Agents of Bioterrorism |
SEP 2005 |
292 pages |
| Authors:
C. R. Middaugh; KANSAS UNIV CENTER FOR RESEARCH INC LAWRENCE
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| Vaccines are without doubt the most powerful approach currently available for the prevention of the deleterious effects of toxins and infectious agents that might be used in a bioterrorism against civilians or military personnel. Recent disclosures have indicated that numerous countries/or terrorists organizations may possess biological weapons that could indeed be used for this purpose. Likely, agents include anthrax, botulinum toxin, smallpox, tularemia, plague, and Venezuelan equine encephalitis. With the ... |
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| Augmentation of a Novel Enzyme/Pro-Drug Gene Therapy "Distant Bystander Effect" to Target Prostate Cancer Metastasis |
SEP 2005 |
49 pages |
| Authors:
Bing Zhang; Pamela J. Russell; NEW SOUTH WALES UNIV SYDNEY (AUSTRALIA)
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| Prostate cancer is now the second highest cause of cancer death in men in Western society. New treatments are needed for late stage disease that has become refractory to hormone removal. We are using gene therapy, alone and in combination with hormones called cytokines that stimulate the immune system. The concept is that delivering a cell-killing agent to an accessible organ, coupled with help from the immune system can promote ... |
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| Blood-Brain Barrier Transport of Uranium |
SEP 2005 |
42 pages |
| Authors:
Michael Aschner; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
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| Recent studies of Gulf War veterans with depleted uranium (DU) embedded fragments in their soft tissues point to DU-induced effects on neurobehavioral and cognitive function. These observations are corroborated by electrophysiological changes in hippocampal slices isolated from rats embedded with DU fragments. Notably, studies from the same group also suggest, for the first time, that uranium accumulates within brain tissue. It is presently unknown how uranium is transported into the ... |
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| Disruption of Dopaminergic and Cholinergic Function in Military Deployment Implications to Parkinson's Disease |
SEP 2005 |
19 pages |
| Authors:
Gary W. Miller; EMORY UNIV ATLANTA GA
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| The goal of this project is to evaluate the potential of pesticides and other compounds used by the military for their potential to damage the brain dopamine system and increase the risk for Parkinson's disease. Notable research accomplishments over the past year include the following: Deltamethrin increased the expression of DAT, TH, and VMAT2, locomotor activity in C57BL mice exposed during development. We further identified transcription factors that underlie this ... |
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| Therapy After Exposure to Toxins (I) |
SEP 2005 |
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| Authors:
M. Polhuijs; A. M. de Vries; W. E. Kaman; TNO DEFENSE SECURITY AND SAFETY RIJSWIJK (NETHERLANDS)
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| During their duties, military personnel can be exposed to military relevant toxins. Then, efficient therapy is needed. Alternative antibodies, aptamers, can be used to neutralise and remove the toxins from the body. Aptamers are developed by means of the SELEX technology (Systematic Evolution of Ligands by EXponential enrichment). The results obtained in this report suggest that it is worthwhile to further develop aptamers against the neurotoxin saxitoxin. Development of aptamers ... |
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Toxicology
