| The Immune Status of Kupffer Cells Profoundly Influences their Responses to Infectious Plasmodium berghei sporozoites |
18 MAY 2005 |
13 pages |
| Authors:
Nick Steers; Robert Schwenk; David J. Bacon; Dmitri Berenzon; Jackie Williams; Urszula Krzych; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD DEPT OF IMMUNOLOGY/DIV OF COMMUNICABLE DISEASES
|
 | Multi-factorial immune mechanisms underlie protection induced with radiation-attenuated Plasmodia sporozoites (gamma-spz). Spz pass through Kupffer cells (KC) before invading hepatocytes but the involvement of KC in protection is poorly understood. In this study we investigated whether gamma-spz-immune KC respond to infectious spz in a manner that is distinct from the response of naive KC to infectious spz. KC were isolated from (1) naive, (2) spz-infected, (3) gamma-spz-immune, and (4) gamma-spz-immune-challenged ... |
|
| Control of Mammary Differentiation by Ras-Dependent Signal Transduction Pathways |
MAY 2005 |
55 pages |
| Authors:
Mary L. Cutler; Maria G. Cerrito; Treasa Chopp; Weihan Wang; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLEMD
|
| Mammary epithelial cells undergo periodic cycles of growth, differentiation and apoptosis during pregnancy and lactation. These processes are initiated by a complex series of signals that include mammotrophic hormones and locally-derived growth factors. This study determined the mechanism by which Ras activation, an important mitogenic signal transduction pathway that is frequently activated in breast carcinoma, inhibits mammary differentiation and apoptosis. The Ras pathway is activated by EGF stimulation of HC11 ... |
|
| Resolution of the Spatial Distribution of the Bacteriophage MS2 Protein and RNA Components |
MAY 2005 |
23 pages |
| Authors:
Deborah A. Kuzmanovic; Iiya Elashvili; Charles H. Wick; Catherine O'Connell; Susan Krueger; GEO-CENTERS INC ABERDEEN PROVING GROUND MD
|
| Small-angle neutron scattering (SANS) and the contrast variation technique were used to determine the spatial relationship of the individual components of the MS2 virion (protein shell and genomic RNA). Our results show that (a) the MS2 RNA is tightly compacted within the virion, confined to a radius of 83 +/- lA and (0) the MS2 coat protein shell extends to a radius of 136 + 2A and has a thickness ... |
|
| Generic Therapy after Exposure to Biological Warfare Agents: Validation of an in Vitro Dendritic Cell Culture System |
MAY 2005 |
|
| Authors:
d. van der kleif; M. Pohuijs; TNO DEFENSE SECURITY AND SAFETY RIJSWIJK (NETHERLANDS)
|
 | The threat of the use of biological weapons, including bacteria, has increased. Bacterial resistance to antibiotics increasingly becomes a problem. Vaccination of military personnel against biothreat agents may be an option, however there is a broad range of biothreat agents, which may become even broader as a result of genetic engineering. Moreover, vaccination against multiple agents may cause undesired effects. A more generic approach to prevent the effects of a ... |
|
| An All-Atom Model of the Pore-Like Structure of Hexameric VP40 from Ebola: Structural Insights into the Monomer-Hexamer Transition |
30 APR 2005 |
12 pages |
| Authors:
Tam L. Nguyen; Guy Schoehn; Winfried Weissenhorn; Ann R. Hermone; James C. Burnett; Rekha G. Panchal; Connor McGrath; Dan W. Zaharevitz; M. J. Aman; Rick Gussio; Sina Bavari; NATIONAL CANCER INST FREDERICK MD
|
| The matrix protein VP40 is an indispensable component of viral assembly and budding by the Ebola virus. VP40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the Ebola viral life cycle. While the X-ray structures of monomeric and octameric VP40 have been determined, the structure of hexameric VP40 has only been solved by three-dimensional electron microscopy (EM) ... |
|
| Identification, Cloning, Expression, and Characterization of the Gene for Plasmodium knowlesi Surface Protein Containing an Altered Thrombospondin Repeat Domain |
27 APR 2005 |
9 pages |
| Authors:
Babita Mahajan; Dewal Jani; Rana Chattopadhyay; Rana Nagarkatti; Hong Zheng; Victoria Majam; Walter Weiss; Sanjai Kumar; Dharmendar Rathore; FOOD AND DRUG ADMINISTRATION ROCKVILLE MD
|
| Proteins present on the surface of malaria parasites that participate in the process of invasion and adhesion to host cells are considered attractive vaccine targets. Aided by the availability of the partially completed genome sequence of the simian malaria parasite Plasmodium knowlesi, we have identified a 786-bp DNA sequence that encodes a 262-amino-acid-long protein, containing an altered version of the thrombospondin type I repeat domain (SPATR). Thrombospondin type 1 repeat ... |
|
| Transcriptional Analysis of In vivo Plasmodium yoelii Liver Stage Gene Expression |
26 APR 2005 |
8 pages |
| Authors:
Jr. Sacci John B.; Jose M. Ribeiro; Fengying Huang; Uzma Alama; Joshua A. Russell; Peter L. Blair; Adam Witney; Daniel J. Carucci; Abdu F. Azada; Joao C. Aguiar; MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE
|
| The transcriptional repertoire of the in vivo liver stage of Plasmodium has remained largely unidentified and seemingly not amenable to traditional molecular analysis because of the small number of parasites and large number of uninfected hepatocytes. We have overcome this obstruction by utilizing laser capture microdissection to provide a high quality source of parasite mRNA for the construction of a liver stage cDNA library. Sequencing and annotation of this library ... |
|
| Analysis of Ebola Virus and VLP Release Using an Immunocapture Assay |
25 APR 2005 |
|
| Authors:
George Kallstrom; Kelly L. Warfield; Dana L. Swenson; Shannon Mort; Rekha G. Panchal; Gordon Ruthel; Sina Bavari; M. J. Aman; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD VIROLOGY DIV
|
| Ebola virus (EBOV), an emerging pathogen, is the causative agent of a rapidly progressive hemorrhagic fever with high mortality rates. There are currently no approved vaccines or treatments available for Ebola hemorrhagic fever. Standard plaque assays are currently the only reliable techniques for enumerating the virus. Effective drug-discovery screening as well as target identification and validation require simple and more rapid detection methods. This report describes the development of a ... |
|
| HLA-A2 Supertype-Restricted Cell-Mediated Immunity by Peripheral Blood Mononuclear Cells Derived from Malian Children with Severe or Uncomplicated Plasmodium falciparum Malaria and Healthy Controls |
25 APR 2005 |
11 pages |
| Authors:
Kirsten E. Lyke; Robin B. Burges; Yacouba Cissoko; Lansana Sangare; Abdoulaye Kone; Modibo Dao; Issa Diarra; Marcelo A. Fernandez-Vina; Christopher V. Plowe; Ogobara K. Doumbo; Marcelo B. Sztein; MARYLAND UNIV BALTIMORE CENTER FOR VACCINE DEVELOPMENT
|
| Understanding HLA-restricted adaptive host immunity to defined epitopes of malarial antigens may be required for the development of successful malaria vaccines. Fourteen epitopes of preerythrocytic malarial antigens known to mediate cytotoxic T-lymphocyte responses against target cells expressing HLA-A2-restricted epitopes were synthesized and pooled based on antigen: thrombospondin-related anonymous protein (TRAP), circumsporozoite protein (CSP), and export protein 1 (Exp-1) peptides. HLA-A2 supertype (*0201, *0202, *0205, *6802) peripheral blood mononuclear cells collected ... |
|
| Testing of the Bio-Seeq (Smiths Detection Handheld PCR Instrument): Sensitivity, Specificity, and Effect of Interferents on Yersinia Pestis Assay Performance |
APR 2005 |
25 pages |
| Authors:
Kevin P. O'Connell; Patricia E. Anderson; James J. Valdes; Jennifer R. Bucher; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD RESEARCH AND TECHNOLOGY DIR
|
| Smiths Detection-Edgewood (SDE), Inc., recently developed a handheld PCR instrument, the Bio-Seeq(Federal Registration), an updated, redesigned version of a small, portable PCR instrument previously known as Handheld Advanced Nucleic Acid Analyzer (HANAA). The SDE developed the Bio-Seeq(Federal Registration) to provide a portable platform for use by first responders to detect biological threats in civilian areas. To be ready for introduction into the marketplace, the instrument must be accompanied by a ... |
|
| Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Malignancies |
APR 2005 |
7 pages |
| Authors:
Shuang Huang; SCRIPPS RESEARCH INST LA JOLLA CA
|
| Angiogenesis is essential for the growth and metastasis of solid tumors including breast cancer. In vitro and in vivo experimental models clearly demonstrate that suppressing angiogenesis leads tumor suppression. The overall goal of this proposal is to develop an adenovirus-based gene therapy approach for suppressing angiogenesis. In first year of the funding period, we have successfully constructed a human endothelial cell-targeted adenovirus gene delivery vector. In this second year of ... |
|
| TSC1 and TSC2 Gene Homologs in Schizosaccharomyces Pombe |
APR 2005 |
16 pages |
| Authors:
Elizabeth P. Henske; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| This project is focused on the TSC1 and TSC2 gene homologs in the fission yeast Schizosaccharomyces pombe (S. pombe). Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disease whose manifestations can include seizures, mental retardation, autism, and tumors of the brain, heart, kidney and skin. The TSC2 gene encodes tuberin, a 200 kD protein with homology to GTPase activating protein (GAP) for Rap I. The TSC1 gene encodes hamartin, ... |
|
| Characterization of Plasmodium falciparum Choline Transporters |
APR 2005 |
54 pages |
| Authors:
Choukri B. Mamoun; CONNECTICUT UNIV HEALTH CENTER FARMINGTON
|
| Plasmodium falciparum is the causative agent of severe human malaria. The rapid multiplication of the parasite within human red blood cells requires an active synthesis of new membranes. Choline analogs are potent antimalarial drugs. Although Choline transport has been suggested to be the target of these compounds, their exact mode of action is unknown. We identified two genes PfGAT and PfCTL1 as potential targets of these compounds. Here we report ... |
|
| Mode of Action of Invasion-Inhibitory Antibodies Directed against Apical Membrane Antigen 1 of Plasmodium falciparum |
APR 2005 |
8 pages |
| Authors:
Sheetij Dutta; J. D. Haynes; Arnoldo Barboss; Lisa A. Ware; Jeffrey D. Snavely; J. K. Moch; Alan W. Thomas; David E. Lanar; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
| Antibodies against apical membrane antigen 1 (AMA-1) of Plasmodium falciparum inhibit merozoite invasion into erythrocytes. Invasion-inhibitory polyclonal AMA-1 antibodies inhibit secondary proteolytic processing and surface redistribution of AMA-1 on merozoites. We present evidence supporting inhibition of processing and redistribution as probable causes of inhibition of invasion by polyclonal antibodies. Polyclonal anti-AMA-1 was much more inhibitory than monoclonal antibody (MAb) 4G2dc1 in an invasion assay. Although both polyclonal and monoclonal immunoglobulin ... |
|
| Human Spotted Fever Rickettsial Infections |
APR 2005 |
4 pages |
| Authors:
George B. Schoeler; Cecilia Moron; Allen Richards; Patrick J. Blair; James G. Olson; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Serum specimens from patients at 4 sites in Peru were tested for evidence of spotted fever group rickettsial infection. Results showed that 30 (18%) of 170 patients had spotted fever group rickettsial infections which likely caused their illnesses. These findings document laboratory-confirmed spotted fever from diverse areas of Peru. |
|
| Optimization of Broad-Spectrum Antimicrobial Activity for Novel Compound Classes |
APR 2005 |
110 pages |
| Authors:
Richard H. Griffey; ISIS PHARMACEUTICALS CARLSBAD CA
|
| This final report summarized the results obtained from the preparation, evaluation, and extensive SAR analysis of hundreds of compounds with an emphasis on improving the antimicrobial activity of three compound classes outlined in our original proposal. the first class include the substituted pyranosyl cytosines, the second class of compounds are the heterobiaryl guanidines, ant the third are bis-heteroarylamidrazones |
|
| Intracellular Survival of Campylobacter jejuni in Human Monocytic Cells and Induction of Apoptotic Death by Cytholethal Distending Toxin |
30 MAR 2005 |
5 pages |
| Authors:
Thomas E. Hickey; Gary Majam; Patricia Guerry; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Campylobacter jejuni 81-176 is capable of extensive replication within human monocytic cell vacuoles and induces apoptotic death via cytolethal distending toxin. |
|
| Nanofabrication of Bioselective Materials Using Diverse Nanolandscapes Displayed on Live Viruses |
28 MAR 2005 |
|
| Authors:
Eric V. Olsen; V. A. Petrenko; J. C. Sykora; G. A. Kouzmitcheva; L. B. Sorokulova; J. R. Brigati; I. H. Chen; B. A. Chin; V. J. Vodyanoy; AUBURN UNIV AL
|
| Filamentous phages, such as fd used in this study, are thread-shaped bacterial viruses. Their outer coat is a tube formed by thousands of equal copies of the major coat protein pVIII. We constructed libraries of random peptides fused to all pVIII domains and selected phages that act as probes specific for test antigens and biological threat agents. Because the viral carrier is infective, phage-borne bio-selective probes can be cloned individually ... |
|
| Protective Antigen (PA) and Toxin Neutralization (TNA) Antibody Patterns in Anthrax Vaccinees Undergoing Serial Plasmapheresis |
28 MAR 2005 |
10 pages |
| Authors:
Phillip R. Pitman; Susan F. Leitman; Julio G. Barrera-Oro; Sarah L. Norris; Nina M. Marano; Manmohan V. Ranadive; Bonnie S. Sink; Kelly T. McKee Jr; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Recipients of licensed anthrax vaccine (AVA, Biothrax ) could serve as a source of hyperimmune plasma and immunoglobulin for therapy and prophylaxis. We examined serum antibody patterns during serial weekly to biweekly plasmapheresis in 38 individuals previously vaccinated with 4-27 doses of AVA. Immunoglobin G (IgG) to protective antigen (PA) and toxin neutralization assay (TNA) antibody levels were highly correlated with r = 0.86930) and P < 0. 0001 for ... |
|
| Recombinant Phage Probes for Salmonella Typhimurium Detection |
23 MAR 2005 |
4 pages |
| Authors:
Eric V. Olsen; Iryna Sorokulova; hsuan chen; James Barbaree; Vitaly Vodyanoy; AUBURN UNIV AL
|
| Salmonella typhimurium is a leading cause of inadvertent gastrointestinal foodborne illness in the United States. Although few actual accounts of deliberate food contamination have been documented in the United States, the recent advent of biocrimes and terrorism in our country suggests that this trend will not continue, highlighting the importance of rapidly identifying biological agents, regardless of the contamination origin, as one part of a comprehensive strategic plan to secure ... |
|
| Purified Bacillus anthracis Lethal Toxin Complex Formed in Vitro and During Infection Exhibits Functional and Biological Activity |
18 MAR 2005 |
7 pages |
| Authors:
Rekha G. Panchal; Kelly M. Halverson; Wilson Ribot; Douglas Lane; Tara Kenny; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Anthrax protective antigen (PA, 83 kDa), a pore-forming protein upon protease activation to 63 kDa (PA63), translocates lethal factor (LF) and edema factor (EF) from endosomes into the cytosol of the cell. The relatively small size of the heptameric PA63 pore (^12 A) raises questions as to how large molecules like LF and EF can move through the pore. In addition, the reported high binding affinity between PA and EF/LF ... |
|
| Buoyancy-Driven Fluid Flow Generated by Bacterial Metabolism and its Proposed Relationship to Increased Bacterial Growth in Space |
18 MAR 2005 |
22 pages |
| Authors:
Robert B. Brown; David M. Klaus; Paul Todd; AIR FORCE ACADEMY COLORADO SPRINGS CO DEPT OF ASTRONAUTICS
|
| Previous investigations have reported that bacterial growth increases in space flight; however, the underlying physical mechanisms responsible for these changes have not been fully determined. As bacteria consume nutrients, they excrete by-products whose presence can influence the onset of exponential growth and affect final cell population density. It is assumed that these metabolic processes create a reduced-density fluid zone and/or a solute gradient around each cell. On Earth, this density ... |
|
| Yersinia pestis Yop Secretion Portein F: Purification, Characterization, and Protective Efficacy Against Bubonic Plague |
17 MAR 2005 |
8 pages |
| Authors:
Wieslaw Swietnicki; Bradford S. Powell; Jeremy Goodin; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Yersinia pestis is a gram-negative human pathogen that uses a type III secretion system to deliver virulence factors into human hosts. The delivery is contact-dependent and it has been proposed that polymerization of Yop secretion protein F (YscF) is used to puncture mammalian cell membranes to facilitate delivery of Yersinia outer protein effectors into host cells. To evaluate the potential immunogenicity and protective efficacy of YscF against Y. pestis, we ... |
|
| Aerogenic Vaccination With a Burkholderia mallei Auxotroph Protects Against Aerosol-Initiated Glanders in Mice |
14 MAR 2005 |
8 pages |
| Authors:
Rick L. Ulrich; Kei Amemiya; David M. Waag; Chad J. Roy; David DeShazer; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Burkholderia mallei is an obligate mammalian pathogen that causes the zoonotic disease glanders. Two live attenuated B. mallei strains, a capsule mutant and a branched-chain amino acid auxotroph, were evaluated for use as vaccines against aerosol-initiated glanders in mice. Animals were aerogenically vaccinated and serum samples were obtained before aerosol challenge with a high- dose (>300 times the LD50) of B. mallei ATCC 23344. Mice vaccinated with the capsule mutant ... |
|
| Sensitivity of Spores of Eight Bacillus Cereus Strains to Pressure- Induced Germination by Moderate Hydrostatic Pressure, Time and Temperature |
MAR 2005 |
29 pages |
| Authors:
Norasak Kalchayanand; Bibek Ray; C. P. Dunne; Anthony Sikes; WYOMING UNIV LARAMIE DEPT OF ANIMAL SCIENCE
|
| The spores of eight Bacillus cereus strains were pressurized at 138 to 483 MPa for 5 to 20 min at 25 to 70 C in order to determine the sensitive and the resistant strains to pressure-induced germination. The most sensitive strain was B. cereus QMB 476, while the most resistant strain was B. cereus ATCC 11778. Pressurization at 25 C induced spores to germinate ranged from 2.6 to 5.0 log ... |
|
| Demonstration of the Anaerobic Fluidized Bed Reactor for Pinkwater Treatment at McAlester Army Ammunition Plant |
MAR 2005 |
53 pages |
| Authors:
Stephen W. Maloney; Robert L. Heine; ENGINEER RESEARCH AND DEVELOPMENT CENTER CHAMPAIGN IL CONSTRUCTION ENGINEERING RESEARCH LAB
|
| This report documents a demonstration project conducted at McAlester Army Ammunition Plant in Oklahoma. The technology is based on anaerobic bacteria which attack dissolved explosives such as TNT and RDX at the nitro groups, converting them to amino groups. Once the explosives are transformed, they become amenable to aerobic degradation. This process functions as a pretreatment for the pinkwater, after which the effluent is discharged to an aerobic treatment plant ... |
|
| Evaluation of Listeria monocytogenes Based Vaccines for HER-2/Neu in Mouse Transgenic Models of Breast Cancer |
MAR 2005 |
13 pages |
| Authors:
Reshma Singh; PENNSYLVANIA UNIV PHILADELPHIA
|
| HER-2/neu is a member of the epidermal growth factor receptor family and is overexpressed in several cancers including breast, ovarian, and pancreatic cancers and is associated with poor prognosis. Patients with HER-2/ neu overexpressing tumors are capable of mounting an immune response against their tumors, but this response is not enough to stop the growth and spread of the tumors. Our lab has developed Listeria monocytogenes as a vector to ... |
|
| Lethality of Bacillus Anthracis Spores Due to Short Duration Heating Measured Using Infrared Spectroscopy |
MAR 2005 |
122 pages |
| Authors:
Kristina M. Goetz; AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH SCHOOL OF ENGINEERING AND MANAGEMENT
|
| In this research, Bacillus anthracis spores were subjected to bursts of heat lasting on the order of one second in duration using a laser system to simulate the explosive environment from an agent defeat weapon. Heating times and temperatures were varied to establish a method to characterize the relationship between heating time, heating temperature, and spore viability. Two heating temperatures were examined at three variations of heating time ranging from ... |
|
| Two New Plant-Like Pathways Link Hemoglobin Degradation to Lipid Biogenesis in Falciparum Malaria: Novel Targets for Anti-Malarial Chemotherapy |
MAR 2005 |
25 pages |
| Authors:
Choukri B. Mamoun; CONNECTICUT UNIV HEALTH CENTER FARMINGTON
|
| "Plasmodium falciparum" is the causative agent of the most severe form of human malaria. The rapid multiplication of the parasite within human erythrocytes requires an active production of new membranes. Phosphatidylcholine (PtdCho) is the most abundant phospholipid in "Plasmodium" membranes and the pathways leading to its synthesis are attractive targets for chemotherapy. In this report, the authors describe molecular and biochemical studies that provide evidence for the presence of a ... |
|
| Process Research and Development of Antibodies as Countermeasures for C. Botulinum |
MAR 2005 |
69 pages |
| Authors:
Michael Meagher; NEBRASKA UNIV LINCOLN
|
| This report describes the project to fill out shell space on the third floor of Othmer Hall, the new home for the University of Nebraska-Lincoln Biological Process Development Facility. Construction is 95% completed and all research laboratories of the BPDF are functional. The 5% includes a Master Cell Banking. The third floor is home to all process research capabilities, i.e. molecular biology, fermentation, cell culture, analytical methods, quality control, purification ... |
|
| DoD Global Emerging Infections System -- Partnering in the Fight Against Emerging Infections, Fiscal Year 2004 |
Mar-2005 |
61 pages |
| Authors:
ARMED FORCES HEALTH SURVEILLANCE CENTER SILVER SPRING MD
|
| The FY04 DoD-GEIS Consolidated Annual Report presents a description of GEIS-related activities during this, its eighth year of funded operations. Global surveillance for emerging infectious disease threats, timely recognition of and response to outbreaks, together with the key laboratory and communications infrastructure supporting public health are cornerstones of national and global security. Events of 2001 (September 11th, anthrax incidents) continue to resonate; strengthening public health systems to address naturally occurring ... |
|
| DoD Global Emerging Infections System -- Partnering in the Fight Against Emerging Infections, Fiscal Year 2005 |
Mar-2005 |
78 pages |
| Authors:
ARMED FORCES HEALTH SURVEILLANCE CENTER SILVER SPRING MD
|
| The Department of Defense Global Emerging Infections Surveillance and Response System (DoD-GEIS) activities and accomplishments for FY 2005 are detailed by DoD-GEIS supported partners throughout the remainder of this annual report. The DoD-GEIS mission is to support and coordinate DoD global surveillance, training, public health research and outbreak response capabilities for microbial threats impacting force health protection and national security. Specifically, DoD-GEIS projects support outbreak response preparation, detection, clinical investigation, ... |
|
| Dendritic Cells Endocytose Bacillus Anthracis Spores: Implications for Anthrax Pathogenesis |
15 FEB 2005 |
10 pages |
| Authors:
Katherine C. Brittingham; Gordon Ruthel; Rekha G. Panchal; Claudette L. Fuller; Wilson J. Ribot; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Phagocytosis of inhaled Bacillus anthracis spores and subsequent trafficking to lymph nodes are decisive events in the progression of inhaled anthrax because they initiate germination and dissemination of spores. Found in high frequency throughout the respiratory tract, DCs routinely take up foreign particles and migrate to the lymph nodes. However, the participation of DCs in phagocytosis and dissemination of spores was not investigated previously. We found that human DCs readily ... |
|
| Development of General Antibiotics Against Known and Unknown Pathogens |
10 FEB 2005 |
7 pages |
| Authors:
Cheng-Wei T. Chang; UTAH STATE UNIV LOGAN
|
| The initial synthetic work was started at April of 2003. The primary objectives were to synthesize hybrid sugar and aminoglycoside antibiotic with N- 1 modification. The synthesis of pyranmycin with hybrid sugar has been accomplished. The synthetic approach of N-1 modification has yielded several aminoglycosides that are active against various resistant bacteria. In addition we have devoted effort for the development of kanamycin class aminoglycosides. Several compounds with low micromolar ... |
|
| An All-Atom Model of the Pore-Like Structure of Hexameric VP40 from Ebola: Structural Insights into the Monomer-Hexamer Transition |
07 FEB 2005 |
12 pages |
| Authors:
Tam L. Nguyen; Guy Schoehn; Winfried Weissenhorn; Ann R. Hermone; James C. Burnett; Rekha G. Panchal; Connor McGrath; Dan W. Zaharevitz; M. J. Aman; Rick Gussio; Sina Bavari; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| The matrix protein VP40 is an indispensable component of viral assembly and budding by the Ebola virus. VP40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the Ebola viral life cycle. While the X-ray structures of monomeric and octameric VP40 have been determined, the structure of hexameric VP40 has only been solved by three-dimensional electron microscopy (EM) ... |
|
| Ebola Virus: The Role of Macrophages and Dendritic Cells in the Pathogenesis of Ebola Hemorrhagic Fever |
04 FEB 2005 |
8 pages |
| Authors:
Mike Bray; Thomas W. Geisbert; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. Recent studies in macaques show that major features of illness are caused by effects of viral replication on microphages and dendritic cells. Infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilation, increased vascular permeability and disseminated intravascular coagulation. However, they cannot restrict viral replication, possibly because of suppression ... |
|
| An Epidemiological Study of Leptospira-Induced Abortion in Mares in Central Kentucky (1990-2004) |
02 FEB 2005 |
126 pages |
| Authors:
David C. Hall; KENTUCKY UNIV LEXINGTON
|
| Leptospirosis can cause fetal abortion in pregnant mares. The number of abortions attributed to leptospiral infection in central Kentucky can differ greatly from year to year. This study compares years having a higher than average prevalence of leptospiral abortions to years having an average or below average prevalence of such abortions in the horse population. Environmental factors, such as temperature and precipitation, as well as geographical location using geographical information ... |
|
| Hybrid Molecular and Spin-Semiconductor Based Research |
02 FEB 2005 |
14 pages |
| Authors:
S. Datta; R. Reifenberger; D. Janes; P. Bhattacharya; D. Steel; PURDUE RESEARCH FOUNDATION LAFAYETTE IN
|
| This project has three thrusts. Thrust I is entitled "Integrated Bacteriorhodopsin-Based Photodetectors" and its objective is to enable a new class of optoelectronic devices by combining the versatility of genetically engineered biomolecules with the power of microelectronics. Thrust II is entitled "Spintronics and Magnetoelectronics" and its objective is to enable a new class of semiconductor-based spintronic devices. Thrust III is entitled "Molecular Electronics" and its objective is to develop, characterize ... |
|
| Campylobacter jejuni Induces Secretion of Proinflammatory Chemokines from Human Intestinal Epithelial Cells |
02 FEB 2005 |
5 pages |
| Authors:
Lan Hu; Thomas E. Hickey; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Campylobacter jejuni is a common cause of diarrhea in humans. While the pathogenic mechanisms of C. jejuni are not completely understood, host inflammatory responses are thought to be contributing factors. In this report, C. jejuni 81-176 is shown to up-regulate chemokines essential to inflammatory responses. Growth-related oncogene alpha (GRO alpha), GRO gamma, macrophage inflammatory protein 1, monocyte chemoattractant protein 1 (MCP-1), and gamma interferon-inducible protein 10 (gamma IP-10) mRNA transcription ... |
|
| Identification of Biological Warfare (BW) Threat Agents Using Deoxyribonucleic Acid (DNA) Microarrays |
FEB 2005 |
24 pages |
| Authors:
Paul R. Schaudies; SCIENCE APPLICATIONS INTERNATIONAL CORPSAN DIEGO CA
|
| We developed a bioinformatic method for the identification of unique sequences within the large genomes of bacteria. In support of this contract, we have generated unique sequence and microarray data demonstrating species-level discrimination between Bacillus anthracis, vaccinia virus and Yersinia pestis and strain-level discrimination between Escherichia coli 0157:H7 and the non- virulent K-12 strain. By assaying for the presence of: 1) unique sequences at various levels of the phylogenetic tree, ... |
|
| Vasculature-Specific Adenovirus Vectors for Gene Therapy of Prostate Cancer |
FEB 2005 |
10 pages |
| Authors:
|
| In Year 1 of the project we have completed Task 1 (as per approved Statement of Work) by generating a panel of plasmid vectors for the expression of a series of modified adenovirus fiber genes. These genes encode genetic fusions of the adenovirus fiber protein, which has been stripped off its native receptor binding site by mutagenesis, with the previously identified peptides that are specific for the prostate tumor vasculature. ... |
|
| Triptolide Attenuates Endotoxin- and Staphylococcal Exotoxin-Induced T-Cell Proliferation and Production of Cytokines and Chemokines |
FEB 2005 |
16 pages |
| Authors:
Teresa Krakauer; Xin Chen; O. M. Howard; Howard A. Young; NATIONAL CANCER INST FREDERICK MD
|
| Proinflammatory cytokines mediate the toxic effects of superantigenic staphylococcal exotoxins (SE) and bacterial lipopolysaccharide (LPS). Triptolide, an oxygenated diterpene derived from a traditional Chinese medicinal herb, Tripterygium wilfordii, inhibited SE-stimulated T-cell proliferation (by 98%) and expression of interleukin 1beta, interleukin 6, tumor necrosis factor, gamma interferon, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta by human peripheral blood mononuclear cells (PBMC). It also blocked the production of these ... |
|
| Diarrheal Illness Among Deployed U.S. Military Personnel During Operation Bright Star 2001-Egypt |
FEB 2005 |
7 pages |
| Authors:
John W. Sanders; Shannon D. Putnam; Philip Gould; John Kolisnyk; Norma Merced; Vincent Barthel; Patrick J. Rozmajzl; Hind Shaheen; Salwa Fouad; Robert W. Frenck; NAVAL MEDICAL RESEARCH UNIT NO 3 FPO NEW YORK 09527
|
| In the fall of 2001, approximately 15,000 U.S. military personnel participated in a military exercise in the northwestern Egyptian desert. To assess the prevalence and impact of diarrhea and enteropathogen distribution, we conducted a post-deployment survey and a case series study. A departure convenience sampling (n = 3725) was used in the post-deployment survey. Overall, 9.3% reported diarrhea, 2.6% sought medical care, and 2.8% stopped or decreased their work for ... |
|
| Differential Effects of Dengue Virus on Infected and Bystander Dendritic Cells |
FEB 2005 |
9 pages |
| Authors:
Dupeh R. Palmer; Peifang Sun; Christina Celluzzi; John Bisbing; Somnang Pang; Wellington Sun; Mary A. Marovich; Timothy Burgess; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
| Dendritic cells (DCs) play a central role as major targets of dengue virus (DV) infections and initiators of antiviral immune responses. Previous observations showed that DCs are activated by infection, presumably acquiring the capacity to promote cell-mediated immunity. However, separate evaluations of the maturation profiles of infected and uninfected bystander cells show that infection impairs the ability of DCs to upregulate cell surface expression of costimulatory, maturation, and major histocompatibility ... |
|
| Rapid Detection of Cellular Response to Biological Agents |
FEB 2005 |
135 pages |
| Authors:
Bryan R. Williams; CLEVELAND CLINIC FOUNDATION OH
|
| Our program objective is to develop simple and rapid methods for detecting at a cellular level, individual responses to environmental stresses elaborated by exposure to infectious agents such as bacteria and viruses. Our methods are based on transcript profiling and post-translational modification of proteins involved in signal transduction. Our hypothesis is that human cells respond to infectious insults to a genetically predetermined extent by stimulating the expression of sets of ... |
|
| Cross-Serotype Neutralization of Dengue Virus in Aotus nancymae Monkeys |
31 JAN 2005 |
6 pages |
| Authors:
Tadeusz J. Kochel; Douglas M. Watts; Alfonso S. Gozalo; Daniel F. Ewing; Kevin R. Porter; Kevin L. Russell; NAVAL MEDICAL RESEARCH INST DETACHMENT LIMA (PERU)
|
| Previously, we observed that serum from humans immune to dengue serotype 1 (dengue-1) neutralized the American genotype of dengue serotype 2 (American-2) to a greater extent than it neutralized the Asian genotype of dengue serotype 2 (Asian-2). To determine if this activity is protective, Aotus nancymae monkeys were infected with dengue-1 followed by either American-2 or Asian-2. Dengue-1 infected animals produced antibody with neutralizing titers of 2656 antibodies against dengue-1, ... |
|
| Clinical Use of Plasma and Plasma Fractions Chapter: Viral Inactivation Techniques |
26 JAN 2005 |
26 pages |
| Authors:
Joesph P. Pelletier; YALE UNIV NEW HAVEN CT
|
| Even though the blood supply is very safe, concerns regarding transmission of transfusion-related pathogens exist. Risks are reduced by donor screening, arm-preparation techniques, first aliquant diversion, screening for pathogens and, in many countries, pathogen reduction/eradication technology. The risk for viral infection from transfusion is now reported at 1:2,135,000 for HIV, 1:138,700-233,000 for HBV, 1:1935,000 for HCV, 1:250,000 for HTLV 1 and 2 (after screening peripherally), 1:1,000,000 HAV, 1:10,000 for parvovirus ... |
|
| Post-Renal Transplant Thrombotic Thrombocytopenic Purpura (TTP): attributable to Immunosuppression or Graft Rejection? Report of Three Cases and Literature Review |
25 JAN 2005 |
|
| Authors:
Joseph P. Pelletier; Oluwole Fadare; Yanyun Wu; YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE
|
| The immunomodulatory drug FK-506 (Tacrolimus) is a calcineurin inhibitor that, as such, indirectly inhibits the transcription of a gene encoding interleukin 2, a cytokine that is vital to the immune response process. Since its introduction in 1987, sporadic reports have appeared describing the development of thrombotic thrombocytopenic purpura (TTP) - or a similar syndrome - in patients taking this drug. Sirolimus (Rapamune) is another immunomodulatory drug with a more favorable ... |
|
| A Multiplex PCR for Detection of Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, and Bordetella pertussis in Clinical Specimens |
24 JAN 2005 |
29 pages |
| Authors:
E. A. McDonough; C. P. Barrozo; K. L. Russell; D. Metzgar; NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA
|
| A multiplex PCR was developed that is capable of detecting four of the most important bacterial agents of atypical pneumophia, Mycaplasma pneumoniae, Chlamydophia pneumoniae, Legionella pneumophila, and Bordetella pertussis in uncultured patient specimens. These organisms cause similar symptomologies and are often not diagnosed because they are difficult to identify with classical methods such as culture and serology. Given this, the overall impact of these pathogens on public health may be ... |
|
| Genetically Engineered, Live Attenuated Vaccines Protect Nonhuman Primates Against Aerosol Challenge with a Virulent IE Strain of Venezuelan Equine Encephalitis Virus |
21 JAN 2005 |
10 pages |
| Authors:
Douglas S. Reed; Cathleen M. Lind; Matthew G. Lackemeyer; Lawrence J. Sullivan; William D. Pratt; Michael D. Parker; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Two live, attenuated strains of Venezuelan equine encephalitis virus (VEE), IE1150K and V3526, were administered to macaques to determine if they could elicit protection against an aerosol challenge with virulent VEE virus of the IE variety (VEEV-IE). These viruses were rescued from full-length cDNA clones of 68U201 (VEEV-IE variety) and Trinidad donkey (VEEV-IA/B variety), respectively, and both have a furin cleavage site deletion mutation and a second-site resuscitating mutation. Both ... |
|
Microbiology
