| Global Gene Expression Analysis to Unambiguously Identify Host Gene Responses Characteristic of Exposure to Biothreat Agents |
DEC 2004 |
9 pages |
| Authors:
Rasha Hammamieh; Marti Jett; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD DEPT OF MOLECULAR PATHOLOGY
|
 | We are studying the complex interaction between various biological pathogens and the host to understand the basis infectious or biothreat-induced diseases and to identify host defense strategies and the mechanisms by which they are regulated. Although gene response profiles show unique signatures quite rapidly after exposure, they also have the potential to reveal phases of progression of illness to a) provide stage-specific diagnosis and b) identification of potential molecular targets ... |
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| Identification of a Bacteria Using Phylogenetic Relationships Revealed by MS/MS Sequencing of Tryptic Peptides Derived From Cellular Proteins |
DEC 2004 |
9 pages |
| Authors:
J. P. Dworzanski; H. Wick; A. P. Snyder; S. V. Deshpande; R. Chen; L. Li; GEO-CENTERS INC ABERDEEN PROVING GROUND MD
|
| Genomes of all priority bacterial pathogens for biodefense purposes and more than one hundred other bacteria have been sequenced. In addition four hundred bacterial genome-sequencing projects are in progress. These achievements provide new possibilities for reliable identification of bacteria on a molecular level by retrieving their genomic information. We present a mass spectrometric approach to link these resources with genomic information encoded in bacterial proteins. Amino acid sequencing of tryptic ... |
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| Simultaneous Genomic Detection of Multiple Enteric Bacterial and Viral Pathogens, Including Sars-CoV and RVFV |
DEC 2004 |
7 pages |
| Authors:
S. Payne; C. J. Peters; S. Makino; K. Oliver; C. Weiss; S. Kornguth; L. Carruthers; R. Chin; TEXAS UNIV AT AUSTIN
|
| A multiplexed screening system to detect pathogenicity islands (PI) of bacteria causing enteric disease and pathogenicity factors (PF) associated with the SARS-associated coronavirus (SARS-CoV) and Rift Valley Fever Virus (RVFV) has been developed. This system is based upon the Luminex xMAP" System, a multiplexed assay platform that combines high sample throughput (up to 600 samples/hour) with high information content per sample (up to 100 parameters tested simultaneously per sample). Pathogenic ... |
|
| Process Development For Bacteriorhodopsin Expressed In Escherichia Coli |
DEC 2004 |
3 pages |
| Authors:
Chundakkadu Krishna; Patricia E. Anderson; Joseph F. Kragl; Michael S. Horsmon; GEO-CENTERS INC ABERDEEN PROVING GROUND MD
|
| The Army is increasingly dependent on computers and electronic tools to achieve high levels of situational awareness on the battlefield (Opportunities in Biotechnology for Future Army Applications, National Research Council, 2001). With silicon based technologies reaching their technological limits, biologically derived or inspired materials such as protein-based memory systems are viable alternate technologies for the future which will increase their usefulness for Army applications. Bacteriorhodopsin, a light activated protein with ... |
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| Antimicrobial Peptides for Use in Biosensing Applications |
DEC 2004 |
8 pages |
| Authors:
J. W. Soares; K. M. Morin; C. M. Mello; ARMY NATICK RESEARCH DEVELOPMENT AND ENGINEERING CENTER MA
|
| Current pathogen detection systems lack the stability, sensitivity, and time-independent functionality required for real-time biosensing in the field. Antibodies exhibit specificity for pathogenic bacteria but lack the sensitivity to detect reduced pathogen levels and the stability needed for detection in harsh environments. We are investigating naturally occurring antimicrobial peptides (AMPs) for pathogen detection due to their intrinsic stability in harsh environments, ease of synthesis, and broad range of activity and ... |
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| Using Advanced Hybrid Stochastic Methods to Design Biological Gene Networks That Rapidly Respond To Harmful Substance Detection |
DEC 2004 |
3 pages |
| Authors:
Howard Salis; Yiannis Kaznessis; MINNESOTA UNIV MINNEAPOLIS DEPT OF CHEMICAL ENGINEERING AND MATERIALS SCIENCE
|
| Force protection during both peacetime and combat is extremely important to the safety and efficiency of the Army. Currently, the detection of harmful biological organisms involves microbiological culturing and biochemical tests that require at least three hours and access to a laboratory. Chemical tests for the detection of harmful chemical toxins are faster, but still require a mobile laboratory. On the battlefield, access to a laboratory may be limited and ... |
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| Applying Classical Microbial Identification Strategies to Microarray Platforms |
DEC 2004 |
8 pages |
| Authors:
M. Theodore; N. Boggs; H. Le; H. Ho; W. Bethea; J. Jackman; JOHNS HOPKINS UNIV LAUREL MD APPLIED PHYSICS LAB
|
| In the event of a BW attack, rapid and sensitive methods are needed for accurate identification of bacteria to the species level. Current rapid methods for species-specific identification require clean extraction of pure nucleic acid and require amplification of signals starting material by PCR. Significant microbial expertise may be required to evaluate a sample containing microorganisms so that the correct PCR primers can be selected for positive identification before any ... |
|
| Genetic Radiotherapy of Prostate Cancer |
DEC 2004 |
105 pages |
| Authors:
Donald J. Buchsbaum; ALABAMA UNIV IN BIRMINGHAM
|
| The goal to achieve a high intra-tumoral concentration of 5-fluoro- uracil (5-FU) via molecular chemotherapy employing adenoviral (Ad) vectors encoding the genes for somatostatin receptor subtype 2(SSTr2) and cytosine deaminase (CD) which converts the prodrug 5-fluoro-cytosine (5-FC) to 5-FU under control of the cyclo-oxygenase-2 (Cox-2) tumor-specific promoter was achieved. We evaluated novel two-gene Ad vectors: (1) a native fiber Ad (AdCMVCDCMVSSTr2) and (2) Ad under control of the Cox-2 promoter ... |
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| Evolutionary and Functional Relationships of Colonization Factor Antigen I and Other Class 5 Adhesive Fimbriae of Enterotoxigenic Escherichia coli |
DEC 2004 |
13 pages |
| Authors:
Ravi P. Anantha; Annette L. McVeigh; Lanfong H. Lee; Mary K. Agnew; Frederick J. Cassels; Daniel A. Scott; Thomas S. Whittam; Stephen J. Savarino; NAVAL SUBMARINE MEDICAL RESEARCH LAB GROTON CT
|
| Colonization factor antigen I (CFA/I) is the archetype of eight genetically related fimbriae of enterotoxigenic Escherichia coli (ETEC) designated class 5 fimbriae. Assembled by the alternate chaperone pathway, these organelles comprise a rigid stalk of polymerized major subunits and an apparently tip-localized minor adhesive subunit. We examined the evolutionary relationships of class 5-specific structural proteins and correlated these with functional properties. We sequenced the gene clusters encoding coli surface antigen ... |
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| Phenotypic Profiles of Enterotoxigenic Escherichia coli Associated With Early Childhood Diarrhea in Rural Egypt |
DEC 2004 |
9 pages |
| Authors:
Hind I. Shaheen; Sami B. Khalil; Malla R. Rao; Remo A. Elyazeed; Thomas F. Wierzba; Jr. Peruski Leonard F.; Shannon Putnam; Armando Navarro; Badria Z. Morsy; Alejandro Cravioto; John D. Dlemens; Ann-Mari Svennerholm; Stephen J. Savarino; NAVAL SUBMARINE MEDICAL RESEARCH LAB GROTON CT
|
| Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity and mortality in young children in countries with limited resources. We determined the phenotypic profiles of 915 ETEC diarrheal isolates derived from Egyptian children under 3 years of age who participated in a 3-year population-based study. For each strain, we ascertained enterotoxin and colonization factor (CF) expression, the O:H serotype, and antimicrobial susceptibility. Sixty-one percent of the strains expressed heat-stable enterotoxin (ST) ... |
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| Population Structure and Evolution of the Bacillus cereus Group |
DEC 2004 |
13 pages |
| Authors:
Fergus G. Priest; Margaret Barker; Les W. Baillie; Edward C. Holmes; Martin C. Maiden; HERIOT-WATT UNIV EDINBURGH (UNITED KINGDOM)
|
| Representative strains of the Bacillus cereus group of bacteria, including Bacillus anthracis (11 isolates), B. cereus (38 isolates), Bacillus mycoides (1 isolate), Bacillus thuringiensis (53 isolates from 17 serovars), and Bacillus weihenstephanensis (2 isolates) were assigned to 59 sequence types (STs) derived from the nucleotide sequences of seven alleles, glpF, gmk, ilvD, pta, pur, pycA, and tpi. Comparisons of the maximum likelihood (ML) tree of the concatenated sequences with individual ... |
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| Identification of Aedes aegypti and Its Respective Life Stages by Real-Time Polymerase Chain Reaction |
DEC 2004 |
8 pages |
| Authors:
James C. McAvin; David E Bowles; James A. Swaby; Keith W. Blount; Jamie A. Blow; Miguel Quintana; John R. Hickman; Daniel H. Atchley; Debra M. Niemeyer; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| An Aedes aegypti-specific, fluorogenic probe hydrolysis (Taq-Man), polymerase chain reaction assay was developed for real-time screening using a field-deployable thermocycler. Laboratory-based testing of A. aegypti, A. aegypti (Trinidad strain), Culex pipiens, Culex quinquefasciatus, Anopheles stephensi, and Ochlerotatus taeniorhynchus individual adult mosquitoes and mixed pools (n = 10) demonstrated 100% concordance in both in vitro sensitivity (six of six samples) and specificity (10 of 10 samples). A single adult A. aegypti ... |
|
| Medical Surveillance Monthly Report (MSMR). Volume 10, Number 6, November/December 2004 |
Dec-2004 |
21 pages |
| Authors:
ARMED FORCES HEALTH SURVEILLANCE CENTER SILVER SPRING MD
|
| Leishmaniasis is a zoonotic disease caused by protozoa of the genus Leishmania-the parasite is transmitted to humans through bites of female sand flies. The disease is endemic in many regions of Africa, South and Central America, southern Europe, Asia, and the Middle East. Clinical expressions of leishmaniasis are dependent on the infecting species and host immune responses. Cutaneous, mucosal, and visceral leishmaniasis, the three major clinical forms, are manifestations of ... |
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| Rare Case of Fatal Yellow Fever Vaccine-associated Viscerotropic Disease |
Dec-2004 |
5 pages |
| Authors:
Gregg Gerasimon; Kristie Lowry; MADIGAN ARMY MEDICAL CENTER TACOMA WA
|
| This report describes a case of yellow fever vaccine associated viscerotropic disease (YEL-AVD) that occurred after vaccination in a 22-year-old female. Our patient presented with a clinical syndrome of fever, headache, nausea, and vomiting, which quickly progressed to multiorgan failure and ultimately death on hospital day 4. YEL-AVD is an extremely rare condition reported only a few times in the literature. The yellow fever vaccine is a known stimulus of ... |
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| Human Leukocyte Antigen-DQ8 Transgenic Mice: A Model to Examine the Toxicity of Aerosolized Staphylococcal Enterotoxin B |
30 NOV 2004 |
11 pages |
| Authors:
Chad J. Roy; Kelly L. Warfield; Brent C. Welcher; Raoul F. Gonzales; Tom Larsen; Julie Hanson; Chella S. David; Theresa Krakauer; Sina Bavari; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD VIROLOGY DIV
|
| Staphylococcal enterotoxins (SEs) belong to a large group of bacterial exotoxins that cause severe immunopathologies, especially when delivered as an aerosol. SEs elicit the release of lethal amounts of cytokines by binding to major histocompatibility complex (MHC) class II and cross-linking susceptible T-cell receptors. Efforts to develop effective therapeutic strategies to protect against SEs delivered as an aerosol have been hampered by the lack of small animal models that consistently ... |
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| Macrophage Responses to B. Anthracis |
29 NOV 2004 |
5 pages |
| Authors:
Scott N. Peterson; INSTITUTE FOR GENOMIC RESEARCH ROCKVILLE MD
|
| Using DNA microarrays, we have established the gene expression patterns of B. anthracis cells throughout the entire process of sporulation. Over 2,000 genes displayed growth-phase dependent gene expression, 900 of these corresponding to sporulation-specific gene expression events. In a separate study, we compared 19 strains from the B. cereus group to B. anthracis, Ames using comparative genome hybridization (CGH). This comparison indicated that horizontal gene acquisition within this group of ... |
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| Verification of Commercial Decontamination Technologies in Bench-Scale Studies Using Bacillus anthracis Spores |
17 NOV 2004 |
28 pages |
| Authors:
M. L. Taylor; J. V. Rogers; Y. W. Choi; W. R. Richter; K. R. Riggs; C. L. Sabourin; J. S. Chang; BATTELLE MEMORIAL INST COLUMBUS OH
|
| Briefing reported on the testing of biological efficacy of three anthrax decontamination fumigation techniques on various materials, both porous and nonporous. Fumigants examined were hydrogen peroxide gas, formaldehyde gas, and chlorine dioxide. |
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| Enhanced Peroxide Resistance of In Vitro Mutagenized Fluorideresistant Klebsiella pneumoniae Ureases for Catalytic Buffering of Agent Decontamination Reactions |
17 NOV 2004 |
9 pages |
| Authors:
Ilona J. Fry; Joseph J. Defrank; GEO-CENTERS INC ABERDEEN PROVING GROUND MD
|
| Catalytic buffering is an advanced method of pH control for the enzyme-based Advanced Catalytic Enzyme System (ACES) and oxidative surety agent decontamination technologies. Ammonia production from urea by urease neutralizes the production of Oalkylphosphonic acids resulting from the hydrolysis of Nerve agents such as Sarin and VX. Fluoride production from Sarin hydrolysis inhibits native urease at low mM concentrations. Hydrogen peroxide, used in oxidative nerve agent treatment, is also potent ... |
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| Heteropolymers: A New Class of Therapeutics for Treating Lethal Bacterial and Viral Infections |
17 NOV 2004 |
14 pages |
| Authors:
Nehal Mohamed; Steven M. Jones; Juan Li; Claudia Ferreira; Xun Chen; Barry Kreiswirth; Leslie S. Casey; George L. Spitalny; Steven E. Pincus; ELUSYS THERAPEUTICS INC PINE BROOK NJ
|
| Heteropolymers (HPs) contain a MAb directed against the Complement Receptor type 1 (CR1) on primate RBCs, chemically cross-linked to MAbs that recognize pathogens. Upon administration of HPs pathogens are bound to the HP and immobilized on RBCs, which move through the circulation to the liver and spleen where the CR1-HP-pathogen complex is phagocytosed and destroyed by tissue macrophages. A unique feature of HPs is that the anti-pathogen MAb can be ... |
|
| Identification of Bacteria Using Phylogenetic Relationships, Revealed by MS/MS Sequencing of Tryptic Peptides Derived from Cellular Proteins |
17 NOV 2004 |
27 pages |
| Authors:
Jacek P. Dworzanski; Samir Deshpande; Rui Chen; A. P. Snyder; Liang Li; Charles H. Wick; GEO-CENTERS INC ABERDEEN PROVING GROUND MD
|
| CONCLUSIONS: The results demonstrate that mass spectrometry-based proteomics approach allows for: (1) High confidence level classification and identification of bacteria based on genome traceable, proteomic similarities and differences between an analyzed micro-organism and reference bacteria; (2) Identification of pure cultures as well as mixtures of micro-organisms. |
|
| BioSim (trademark) BG Non-Biological Aerosol Simulant |
17 NOV 2004 |
11 pages |
| Authors:
David S. Alburty; Kelly L. Brown; Jennifer L. Dannehl; Andrew E. Page; Freeman Swank; Richard R. Thomas; MIDWEST RESEARCH INST KANSAS CITY MO
|
| A non-biological simulants has been developed for use as a safe effective alternative to Bacillus globigii (Bg). The simulant consists of one-micron polystyrene carrier beads with an aerodynamic diameter similar to anthrax spores, with total genomic Bg DNA attached to the surface. The DNA attachment to the bead is robust enough to withstand aerosolization and collection processes, yet reacts in a PCR-based detector using existing analytical protocols. BioSim(TradeMark) Bg can ... |
|
| Effectiveness of Vaporous Hydrogen Peroxide for the Decontamination of Representative Military Materials |
16 NOV 2004 |
6 pages |
| Authors:
D. L. Dutt; A. L. Turetsky; M. Brickhouse; J. W. Pfarr; I. F. McVey; S. L. Meilander; A. J. Janick; S. L. Schulte; A. W. Dallmier; GEO-CENTERS INC ABERDEEN PROVING GROUND MD
|
| The intentional release of biological agents has brought to the forefront the necessity of developing effective environmentally benign methods of decontamination for both the war fighter and the civilian population. While many chemical decontamination methods, including aqueous hydrogen peroxide, have been used or are under development for direct application, few vaporous methods are being evaluated for decontamination efficacy (McDonnell, G. et al., 2002). Vaporous methods include, but are not limited ... |
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| Simulated Field Trials Using an Indoor Aerosol Test Chamber |
16 NOV 2004 |
5 pages |
| Authors:
D. D. Semler; A. P. Roth; K. A. Semler; P. M. Nolan; DYCOR TECHNOLOGIES LTD EDMONTON
|
| As new and innovative methods are developed for detecting aerosolized biological weapons, these detectors must also be tested for accuracy, sensitivity and reliability. It is essential that these biological triggers are thoroughly tested before progressing to field testing as field trials are costly and time consuming. A method for testing a Fluorescent Aerodynamic Particle Sizer (FL/APS), a biological trigger detector, with rapid turn around time was developed using a small, ... |
|
| Simultaneous Genomic Detection of Multiple Enteric Bacterial and Viral Pathogens, Including SARS-CoV and RVFV |
15 NOV 2004 |
9 pages |
| Authors:
Shelley Payne; C. J. Peters; Shinji Makino; Kerry Oliver; Christy Weiss; Steve Kornguth; Lenny Carruthers; Robert Chin; TEXAS UNIV AT AUSTIN
|
| A multiplexed screening system to detect pathogenicity islands (PI) of bacteria causing enteric disease and pathogenicity factors (PF) associated with the SARS-associated coronavirus (SARS-CoV) and Rift Valley Fever Virus (RVFV) has been developed. Pathogenic bacteria contain DNA sequences (PI) that code for proteins enhancing the ability of the bacteria to cause disease in the host, while viruses possess genomic sequences (PF) that are associated with their pathogenicity. By quickly screening ... |
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| DNA Microarray Analysis of Human Monocytes Early Response Genes upon Infection with Rickettsia rickettsii |
15 NOV 2004 |
19 pages |
| Authors:
Chien-Chung Chao; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Rickettsia are arthropod-borne bacteria which have caused diseases that have had a military impact by sweeping through troops and incapacitating them, such as the so called Trench Fevers of World War I and II. Rickettsia rickettsii is commonly known as Rocky Mountain spotted fever, the most commonly fatal tick-borne disease in the United States. Differentiating rickettsial diseases from other acute tropical febrile illnesses can be difficult because of the similarities ... |
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| Use of Proteomics and the Secretome and Exosporium of Bacillus anthracis in the Development of Bacterial Ghost-Based Vaccines |
15 NOV 2004 |
33 pages |
| Authors:
Vito G. DelVecchio; Guy Patra; Tim Alefantis; Joseph Connolly; Alexander Waltz; Cesar Mujr; Akar Khan; Werner Lubitz; VITAL PROBES MAYFIELD PA
|
| The total proteins expressed by a genome at a particular moment in the life of a cell. Hundreds of thousands of proteins are studied simultaneously. |
|
| Conformational Sampling of the Botulinum Neurotoxin Serotype A Light Chain: Implications for Inhibitor Binding |
11 NOV 2004 |
11 pages |
| Authors:
James C. Burnett; James J. Schmidt; Connor F. McGrath; Tam L. Nguyen; Ann R. Hermone; Rekha G. Panchal; Jonathan L. Vennerstrom; Krishna Kodukula; Daniel W. Zaharevitz; Rick Gussio; Sina Bavari; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Botulinum neurotoxins (BoNTs) are the most potent of the known biological toxins, and consequently are listed as category A biowarfare agents. Currently, the only treatments against BoNTs include preventative antitoxins and long-term supportive care. Consequently, there is an urgent need for therapeutics to counter these enzymes--post exposure. In a previous study, we identified a number of small, nonpeptidic lead inhibitors of BoNT serotype A light chain (BoNT/A LC) metalloprotease activity, ... |
|
| A Social Structure Model for Evaluating the Effect of Response Measures on the Spread of Smallpox |
NOV 2004 |
34 pages |
| Authors:
Moshe Kress; NAVAL POSTGRADUATE SCHOOL MONTEREY CA
|
| Homogeneous mixing, where all instances of contacts between any two members of the population are equally likely, is a common assumption in modeling biodefense policies against smallpox. Such a mixing pattern is rather unlikely to represent population interaction in a modern urban setting, which typically is separated into households on one hand, and into daily meeting sites such as schools and offices, on the other hand. In this paper, we ... |
|
| Real-Time Population Health Detector |
NOV 2004 |
33 pages |
| Authors:
Gene McClellan; Mark Musen; GENERAL DYNAMICS ADVANCED INFORMATION SYSTEMS (GDAIS) ARLINGTON VA
|
| The objective of the Bio-ALIRT is to evaluate the utility of non- traditional data sources to enable early detection of potential bio-terrorist attacks. Early detection will permit prompt intervention and appropriate treatment, potentially saving large numbers of lives and avoiding widespread infection among military and civilian populations. General Dynamics (then Veridian Systems Division), in cooperation with Stanford University, performed research and evaluated bio-terrorism detection services in the Hampton Roads area ... |
|
| Quorum Sensing: A transcriptional Regulatory System Involved in the Pathogenicity of Burkholderia mallei |
NOV 2004 |
10 pages |
| Authors:
Ricky L. Ulrich; David DeShazer; Harry B. Hines; Jeffrey A. Jeddeloh; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD DIV OF TOXINOLOGY AND AEROBIOLOGY
|
| Numerous gram-negative bacterial pathogens regulate virulence factor expression by using a cell density mechanism termed quorum sensing (QS). An in silico analysis of the Burkholderia mallei ATCC 23344 genome revealed that it encodes at least two luxI and four luxR homologues. Using mass spectrometry, we showed that wild-type B. mallei produces the signaling molecules N-octanoyl- homoserine lactone and N-decanoyl-homoserine lactone. To determine if QS is involved in the virulence of ... |
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| Adenovirus and its Vector for Developing Vaccines Against Biological Warfare Agents |
NOV 2004 |
|
| Authors:
Qiaohua Wu; DEFENCE RESEARCH AND DEVELOPMENT SUFFIELD (ALBERTA)
|
 | This memorandum reviews a new platform for the development of vaccines against biological warfare (BW) agents. The noted platform uses adenovirus as a vector to deliver DNA that encodes for key antigens of BW agents. Once inside the mammalian cell, this adenovirus vectored vaccine induces rapid immune responses. This memorandum describes the basic virology of adenovirus, methods used to modify adenovirus as vaccination vector, advantages of adenovirus vector for developing ... |
|
| Antimicrobial Efficiency of Iodinated Individual Protection Filters |
NOV 2004 |
9 pages |
| Authors:
Brian K. Heimbuch; George Laventure; Robert McDonald; Eila Burr; Eric Proudfoot; Joseph Wander; APPLIED RESEARCH ASSOCIATES INC TYNDALL AFB FL
|
| The Air Force Research Laboratory (AFRL) has a broad interest in oxidizing-agent and photoactivated oxidizing agents that, when applied to textiles and other materials, will act as broad spectrum antimicrobials. For this project, poly(styrene-trimethylammonium triiodide) was incorporated into filtration devices to augment filtration. The overall goal of the project is to replace existing HEPA media with an antimicrobial membrane for both individual protection and collective protection devices. In this report ... |
|
| Characterization of Spotted Fever Group Rickettsiae in Flea and Tick Specimens From Northern Peru |
NOV 2004 |
8 pages |
| Authors:
Patrick J. Blair; Ju Jiang; George B. Schoeler; Cecilia Moron; Elizabeth Anaya; Manuel Cespedes; Christopher Cruz; Vidal Felices; Carolina Guevara; Leonardo Mendoza; Pablo Villaseca; John W. Sumner; Allen L. Richards; James G. Olson; NAVAL SUBMARINE MEDICAL RESEARCH LAB GROTON CT
|
| Evidence of spotted fever group (SFG) rickettsiae was obtained from flea pools and individual ticks collected at three sites in northwestern Peru within the focus of an outbreak of febrile disease in humans attributed, in part, to SFG rickettsia infections. Molecular identification of the etiologic agents from these samples was determined after partial sequencing of the 17-kDa common antigen gene (htrA) as well as pairwise nucleotide sequence homology with one ... |
|
| Toward the Remote Sensing of Bacterial Endospores by Raman Lidar |
26 OCT 2004 |
11 pages |
| Authors:
Elliott R. Brown; Alan W. Lee; Marie A. Celis; CALIFORNIA UNIV LOS ANGELES OFFICE OF CONTRACTS AND GRANTS ADMINISTRATION
|
| This project has developed a system of biological detection at standoff using Raman lidar, a well-known method of monitoring atmospheric gases and pollutants 1. One application of a biological agent standoff detector would be in the advanced warning of a Bacillus anthracis attack. In this work we explore the feasibility of a Raman lidar system for the remote sensing of biological agents, specifically bacterial endospores. |
|
| Exploring the Potential of Variola Virus Infection of Cynomolgus Macaques as a Model for Human Smallpox |
19 OCT 2004 |
7 pages |
| Authors:
Peter B. Jahrling; Lisa E. Hensley; Mark J. Martinez; James W. LeDuc; Kathleen H. Rubins; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Smallpox virus (variola) poses a significant threat as an agent of bioterrorism. To mitigate this risk, antiviral drugs and an improved vaccine are urgently needed. Satisfactory demonstration of protective efficacy against authentic variola will require development of an animal model in which variola produces a disease course with features consistent with human smallpox. Toward this end, cynomolgus macaques were exposed to several variola strains through aerosol and/or i.v. routes. Two ... |
|
| Pharmaceutical Development of a New Class of Antibiotics Effective Against Anthrax |
15 OCT 2004 |
7 pages |
| Authors:
Kirk R. Maples; ANACOR PHARMACEUTICALS INC PALO ALTO CA
|
| The primary goal of this program was to identify and develop a novel compound with antibiotic activity against anthrax. We initially focused on the development of borinic acid esters. The early leads did not prove to have sufficient attributes to be developed as therapeutics. Efforts then focused on optimizing the compounds to possess better pharmacokinetics and lower protein binding. By May, 2004, compounds were synthesized with low protein binding, good ... |
|
| Comparative Analysis of the Schleicher and Schuell IsoCode Stix DNA isolation Device and the Qiagen QIAamp DNA Mini Kit |
OCT 2004 |
5 pages |
| Authors:
Susan R. Coyne; Philip D. Craw; David A. Norwood; Melanie P. Ulrich; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Efficient, rapid, and reproducible procedures for isolating high- quality DNA before PCR gene amplification are essential for the diagnostic and molecular identification of pathogenic bacteria. This study evaluated the Qiagen QIAamp DNA Mini Kit and the Schleicher and Schuell IsoCode Stix DNA isolation device for isolating nucleic acid. Buffer, serum, and whole-blood samples were spiked with Bacillus anthracis Sterne vegetative cells and Yersinia pestis, while water was spiked with B. ... |
|
| Quorum Quenching: Enzymatic Disruption of N-Acylhomoserine Lactone- Mediated Bacterial Communication in Burkholderia thailandensis |
OCT 2004 |
10 pages |
| Authors:
Ricky L. Ulrich; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD BACTERIOLOGY DIV
|
| Many species of gram-negative bacteria communicate by synthesizing, secreting, and responding to N-acylhomoserine lactones (AHLs), a mechanism termed quorum sensing. Several investigations have characterized numerous AHL- degrading enzymes (AiiA lactonases) encoded by environmental isolates of Bacillus spp. The Burkholderia thailandensis quorum system is comprised of at least three AHL synthases (AHSs) and five transcriptional regulators belonging to the LuxIR class of proteins. Expression of the Bacillus anthracis (Ames strain) AiiA ... |
|
| Electron Microscopy Analysis of Albumin Leakage Across Blood-Brain Barrier Following Microwave Exposure |
OCT 2004 |
23 pages |
| Authors:
Clyde F. Phelix; TEXAS UNIV AT SAN ANTONIO
|
| This effort was to develop the histological techniques required to process brain tissue from microwave exposed rats to identify the brain regions affected. Immunocytochemistry was utilized to detect endogenous albumin that had passed through the blood-brain barrier into the brain tissue surrounding the affected vessels. The four key objectives were met: 1) Test for ultrastructural preservation with new perfusion apparatus and when using the specialized fixative; 2) Test that the ... |
|
| Enhancing the Immune Response to Recombinant Plague Antigens |
OCT 2004 |
19 pages |
| Authors:
John D. Clements; TULANE UNIV HEALTH SCIENCE CENTER NEW ORLEANS LA
|
| The etiologic agent of plague is the Gram negative bacterium Yersinia pestis. Y. pestis is a concern as one of the microorganisms with potential for use against civilian or military populations as a biological warfare/ biological terrorism agent. In that case, the pneumonic form of plague would be the most likely outcome. This form of plague is particularly devastating because of the rapidity of onset, the high mortality, and the ... |
|
| Novel Therapeutic and Prophylactic Modalities to Protect U.S. Armed Forces Against Major Biological Threat Agents |
OCT 2004 |
93 pages |
| Authors:
Ken Alibek; GEORGE MASON UNIV FAIRFAX VA
|
| Research under current project has been carried out in three interconnected directions aimed to develop new therapeutic approaches against biological weapon threat agents, namely Bacillus anthracis and smallpox virus (using vaccinia virus model). We have successfully demonstrated new previously unexplored directions to improve anthrax antibiotic therapy by using a combination of antibiotic with apoptosis inhibitors and adenosine receptor agonists. New candidate virulence factors of B. anthracis have been suggested based ... |
|
| Biomarker Development for TLR4 Agonists |
OCT 2004 |
76 pages |
| Authors:
David H. Persing; CORIXA CORP SEATTLE WA
|
| In DARPA-supported studies, we have shown that a family of novel synthetic glycolipids known as the aminoalkyl glucosaminide phosphates (AGPs) act as potent agonists of Toll-like receptor 4 (TLR4), and that administration of AGPs to the airways results in protection against lethal challenge with virulent bacterial and viral agents. Preliminary toxicological studies indicate that intranasal delivery of the compounds is safe, and human clinical trials with aerosolized TLR4 agonists are ... |
|
| Fluorescent Immunoassay Development for PrP(Sc) Detection and Antemortem Diagnosis of TSEs |
OCT 2004 |
25 pages |
| Authors:
Richard I. Carp; RESEARCH FOUNDATION FOR MENTAL HYGIENE ALBANY NY
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| The overall goal of our study is to develop methods of high- sensitivity and high-specificity for the antemortem diagnosis of prion diseases by detecting PrPsc in biological fluids using fluorescent immunoassay. During the first year of this contract, we have focused on improving the assay sensitivity by means of new biological protocols and hardware improvement. Concentration of PrP prior to the assay using sodium phosphotungstate treatment was shown to be ... |
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| The Toxin and Virulence Database: A Resource for Signature Development and Analysis of Virulence |
OCT 2004 |
138 pages |
| Authors:
Murray A. Wolinsky; LOS ALAMOS NATIONAL LAB ALBUQUERQUE NM
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| In this joint effort with the University of Alabama at Birmingham, Walter Reed, MITRE and USAMRIID, we are developing a comprehensive database for microbial toxins and virulence factors (www.tvfac.lanl.gov). This database will contain all known toxins and virulence factors as well as their homologs. Each TVFac record and the associated gene records will be fully annotated to include all relevant sequence and structural information as well as biological, epidemiological, and ... |
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| Treatment of Primary and Metastatic Breast Cancer by an Armed Replicating Adenoviral Vector |
OCT 2004 |
13 pages |
| Authors:
Joanne T. Douglas; ALABAMA UNIV IN BIRMINGHAM
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| Oncolytic replication-selective adenoviruses are a new class of anticancer agents with great therapeutic potential. The ability of replication- selective viruses to amplify the initial viral dose has been exploited by engineering oncolytic adenoviruses to deliver therapeutic transgenes. In this Exploration Award, we are testing the concept that an oncolytic adenovirus can be armed with a therapeutic gene that will exert a systemic effect in the treatment of breast cancer. Breast ... |
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| Hepatitis C. Virus Infection: Mechanism of Disease Progression |
OCT 2004 |
7 pages |
| Authors:
Maria H. Sjogren; TRUE RESEARCH FOUNDATION SAN ANTONIO TX
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| An estimated 4 million individuals in the USA are chronically infected with the hepatitis C virus. Annually 8,000 to 10,000 of these subjects will die of liver-related complications and approximately 1,000 will require liver transplantation. The United States military nave rates of HCV infection similar to the general US population (1.6%). However, it is a younger population and its natural history of HCV infection has not been studied. Therefore, the ... |
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| Normal Human Astrocyte Instructions for Initiation of Cultures from Cryopreserved Cells and Subculture |
OCT 2004 |
18 pages |
| Authors:
David W. Kahler; Carmen M. Arroyo; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| This technical report outlines procedures that have been developed to provide a cost-effective way to produce large quantities of Normal Human Astrocyte (NHA) cells for studying the mechanism(s) of action of chemical warfare agents (CWAs) and medical countermeasures against CWAs. Five milliliters of a supplement provided by Clone Express was added to 467 mL of DMEM F12 media as well as 25 mL of fetal bovine serum plus 0.3 mL ... |
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| A Spontaneous Translational Fusion of Bacillus cereus PlcR and PapR Activates Transcription of PlcR-Dependent Genes in Bacillus anthracis via Binding With a Specific Palindromic Sequence |
OCT 2004 |
11 pages |
| Authors:
Andrei P. Pomerantsev; Olga M. Pomerantseva; Stephen H. Leppla; NAVAL SUBMARINE MEDICAL RESEARCH LAB GROTON CT
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| Transformation of Bacillus anthracis with plasmid pUTE29-plcR-papR carrying the native Bacillus cereus plcR-papR gene cluster did not activate expression of B. anthracis hemolysin genes, even though these are expected to be responsive to activation by the global regulator PlcR. To further characterize the action of PlcR, we examined approximately 3,000 B. anthracis transformants containing pUTE29-plcR-papR and found a single hemolytic colony. The hemolytic strain contained a plasmid having a spontaneous ... |
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| Protein-Semiconductor Integrated Photoreceivers |
30 SEP 2004 |
10 pages |
| Authors:
Pallab Bhattacharya; MICHIGAN UNIV ANN ARBOR SOLID-STATE ELECTRONICS LAB
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| Bacteriorhodopsin (bR) is a light harvesting protein in the purple membrane of microorganism called Hallobacterium Salunarum. Its high internal resistance and very small current have limited the possible applications with semiconductors. One possible solution is to apply bR with field effect transistors (FETs) for FETs' high input resistance. We have demonstrated monolithically integrated bR-semiconductor transimpedance amplifer polarization sensitive photoreceivers and phototransceivers with light emitting lasers of the 655nm peak wavelength. ... |
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| An Update on the Potential of North American Mosquitoes (Diptera: Culicidae) to Transmit West Nile Virus |
22 SEP 2004 |
8 pages |
| Authors:
Michael J. Turell; David J. Dohm; Michael R. Sardelis; Monica L. O 'Guinn; Theodore G. Andreadis; Jamie A. Blow; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD VIROLOGY DIV
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| Since first discovered in the New York City area in 1999, West Nile virus (WNV) has become established over much of the continental United States and has been responsible for >10,000 cases of severe disease and 400 human fatalities, as well as thousands of fatal infections in horses. To develop appropriate surveillance and control strategies, the identification of which mosquito species are competent vectors and how various factors influence their ... |
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Microbiology
