| LRRK2 Mediated Changes in TAU Phosphorylation |
Oct 2012 |
9 pages |
| Authors:
R J Nichols; PARKINSONS INST SUNNYVALE CA
|
 | The gene encoding the protein kinase LRRK2 is the most frequently mutated gene in familial Parkinson's disease (PD). The microtubule associated protein Tau is a pathological component of Alzheimer's disease and genome wide associations studies implicate Tau in PD. In several mouse models it has been shown that Tau exhibits a LRRK2 dependent change in phosphorylation status. The confluence of evidence that these two disease proteins may intersect in disease ... |
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| Role of the Inflammasome in Asbestos-Induced Mesothelioma Formation |
Oct 2012 |
7 pages |
| Authors:
Joseph R Testa; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| The investigations proposed in this idea award grant are aimed at addressing the requirement of asbestos-induced inflammation in the pathogenesis of malignant mesothelioma (MM). Cancer-related inflammation (CRI) within the tumor microenvironment contributes to tumor progression in many human malignancies. MM tumor samples have hallmarks of CRI including macrophage infiltration and inflammatory cytokine production. We intend to evaluate the role of asbestos-induced inflammation in the formation of MM by genetically and ... |
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| Architectural and Biochemical Expressions of Mustard Gas Keratopathy: Preclinical Indicators and Pathogenic Mechanisms |
10 Aug 2012 |
12 pages |
| Authors:
Patrick McNutt; Megan Lyman; Adam Swartz; Kaylie Tuznik; Denise Kniffin; Kim Whitten; Denise Milhorn; Tracey Hamilton; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| A subset of victims of ocular sulfur mustard (SM) exposure develops an irreversible, idiotypic keratitis with associated secondary pathologies, collectively referred to as mustard gas keratopathy (MGK). MGK involves a progressive corneal degeneration resulting in chronic ocular discomfort and impaired vision for which clinical interventions have typically had poor outcomes. Using a rabbit corneal vapor exposure model, we previously demonstrated a clinical progression with acute and chronic sequelae similar to ... |
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| Disease Heterogeneity and Immune Biomarkers in Preclinical Mouse Models of Ovarian Carcinogenesis |
Aug 2012 |
18 pages |
| Authors:
Anda Vlad; MAGEE WOMENS HEALTH CORP PITTSBURGH PA
|
| Ovarian epithelial tumors are highly diverse and the exact tissue of origin is still unclear. Until recently, all five histological subtypes of ovarian epithelial tumors (serous, endometrioid, mucinous, clear cell and transitional adenocarcinomas) were believed to arise in the coelomic epithelium that covers the ovarian surface epithelium (OSE) which then undergoes metaplasia and changes to m llerian -like epithelium before malignant transformation. More recently, however, it has been suggested that ... |
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| Development of Novel Antibiotics for the Treatment of Acinetobacter and Related Pathogens |
07 Jul 2012 |
20 pages |
| Authors:
Paul J Hergenrother; ILLINOIS UNIV AT URBANA BOARD OF TRUSTEES
|
| This report describes the progress made toward the project objectives. Progress includes the identification of a novel antibacterial agent, and the development of a new paradigm for the synthesis of complex and diverse small molecules, one that can now be applied to the creation and discovery of novel antibacterial agents. |
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| Prospects for a Novel Ultrashort Pulsed Laser Technology for Pathogen Inactivation |
06 Jul 2012 |
27 pages |
| Authors:
Shaw-Wei D Tsen; Tzyy C Wu; Juliann G Kiang; Kong-Thon Tsen; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MEDICINE
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| The threat of emerging pathogens and microbial drug resistance has spurred tremendous efforts to develop new and more effective antimicrobial strategies. Recently, a novel ultrashort pulsed (USP) laser technology has been developed that enables efficient and chemical-free inactivation of a wide spectrum of viral and bacterial pathogens. Such a technology circumvents the need to introduce potentially toxic chemicals and could permit safe and environmentally friendly pathogen reduction, with a multitude ... |
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| Studies of the Tumor Microenvironment in Pathogenesis of Neuroblastoma |
Jul 2012 |
8 pages |
| Authors:
Shahab Asgharzadeh; CHILDREN'S HOSPITAL LOS ANGELES CA
|
| The NBL-Tag neuroblastoma mice were crossed with B-cell deficient mice in order to determine the effect of B-cell activity on tumor growth characteristics. Homozygous deficient B-Cell mice and heterozygous NBL-Tag mice were established. The NBL-Tag/B-cell deficient mice lacked B-cells as expected using flow cytometry analyses and immunohistochemistry. However, the lack of B-cells did not alter the growth patterns of NBL-Tag tumor formation as imaged by MRI. Studies using anti-B cell ... |
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| The Use of Comprehensive Molecular Profiling with Network and Control Theory to Better Understand GWI and Model Therapeutic Strategies |
Jul 2012 |
125 pages |
| Authors:
Nancy G Klimas; Mary A Fletcher; VETERANS ADMINISTRATION MEDICAL CENTER MIAMI FL
|
| The objective of this study is to improve our understanding of GWI pathogenesis in two ways through integration across several of the body s regulatory systems of data and knowledge collected from disparate sources, and by mapping of the coordinated interactions between these physiologic systems and the potential for altered wiring of these signaling networks in GWI. Using comprehensive molecular profiling, network and control theory the overarching objective of this ... |
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| Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions |
Jul 2012 |
13 pages |
| Authors:
Michael Whitfield; Elizabeth Blankenhorn; Carol Artlett; TRUSTEES OF DARTMOUTH COLL HANOVER NH OFFICE OF SPONSORED PROJECTS
|
| We have shown a clear time dependence on the gene expression in the skin of the Tsk2/+ mice. The mouse most resembles human SSc at a narrowly defined time point (4 wks of age) which means studies that use this model as a surrogate for human SSc, must use specific time points in their analysis. We have pinpointed at least one candidate gene in the interval for Tsk2/+ and have ... |
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| Regulation of mTOR by Nutrients |
Jul 2012 |
114 pages |
| Authors:
Kun-Liang Guan; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| The mammalian target of rapamycin complex 1, mTORC1, is constitutively activated in TSC 1 or TSC2 mutant cells and contributes to the pathogenesis of TSC. Rapamycin, which is a potent inhibitor of TORC1, is in clinical trials for TSC and related diseases. Amino acids are key signals for mTORC1 activation. We have shown that the Rag family GTPases play a critical role in mTORC1 activation in response to amino acid ... |
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| Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions |
Jul 2012 |
35 pages |
| Authors:
Elizabeth Blankenhorn; DREXEL UNIV PHILADELPHIA PA
|
| This project is focused on an animal model of the human disease, systemic sclerosis (SSc), called Tsk2/+. The SSc-like traits in Tsk2/+ heterozygotes are highly penetrant. In addition to a readily apparent skin fibrosis resulting from ECM anomalies, Tsk2/+ mice show autoimmune and inflammatory features that closely resemble human SSc features, making it useful as a pre-clinical model. In this report, we show a clear time dependence on the gene ... |
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| Quadrivalent Human Papillomavirus Vaccine Initiation, Coverage, and Compliance Among U.S. Active Component Service Women, 2006-2011 |
May 2012 |
2 pages |
| Authors:
Hala Maktabi; Sharon L Ludwig; Angelia Eick-Cost; Uma D Yerubandi; Joel G Gaydos; ARMED FORCES HEALTH SURVEILLANCE CENTER SILVER SPRING MD
|
| Human papillomavirus (HPV)is the most common sexually transmitted pathogen detected among U.S. service members. An estimated 169,682 incident diagnoses of HPV infection occurred between 2004-2009 among active component U.S. service members (rate of 2,306 cases per 100,000 person years). In 2006, a 3-dose HPV quadrivalent vaccine (HPV4), which protects against common HPV strains (types 6, 11, 16, 18) responsible for about 70 percent of cervical cancers and 80 percent of ... |
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| The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization |
11 Apr 2012 |
12 pages |
| Authors:
Bruce K Brown; Lindsay Wieczorek; Gustavo Kijak; Kara Lombardi; Jeffrey Currier; Maggie Wesberry; John C Kappes; Viseth Ngauy; Mary Marovich; Nelson Michael; WALTER REED ARMY INST OF RESEARCH ROCKVILLE MD US MILITARY HIV RESEARCH PROGRAM/DIVISION OF RETROVIROLOGY
|
| The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative ... |
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| An In Silico Model of Endotoxic Shock Mediators (Briefing Charts) |
12 Mar 2012 |
30 pages |
| Authors:
Meghan K Makley; Jeff M Gearhart; Mark Lisanby; Charles E Hack; Lee Poeppelman; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE WRIGHT-PATTERSON AFB OH
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| Biologically-based in silico models of pathogen-host interactions are being designed in our lab to predict the time-course of pathogenic infection in humans. Macrophages respond to lipopolysaccharides (LPS), including the release of potent lipid autacoids, causing a cascade of events leading to endotoxic shock. However, animals have been shown to vary in response and susceptibility to E. coli endotoxin: guinea pig hamster mouse. To establish a sound basis for ... |
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| Pathogenesis of Acute and Delayed Corneal Lesions After Ocular Exposure to Sulfur Mustard Vapor |
Mar 2012 |
12 pages |
| Authors:
Patrick McNutt; Tracey Hamilton; Marian Nelson; Angela Adkins; Adam Swartz; Richard Lawrence; Denise Milhorn; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Sulfur mustard (SM) exposure results in dose-dependent morbidities caused by cytotoxicity and vesication. Although lesions resulting from ocular exposure often resolve clinically, an idiopathic delayed mustard gas keratopathy (MGK) can develop after a moderate or severe exposure. Sequelae include persistent keratitis, recurring epithelial lesions, corneal neovascularization, and corneal degeneration, which can lead to impaired vision or loss of sight. The purpose of this effort is to correlate structural changes with ... |
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| Molecular Characterization of Human MUC16 (CA125) in Breast Cancer |
Feb 2012 |
11 pages |
| Authors:
Srustidhar Das; NEBRASKA UNIV MEDICAL CENTER OMAHA
|
| The proposed study was aimed at understanding the role of MUC16 cytoplasmic tail (MUC16CT) in MUC16 mediated breast cancer pathogenesis and progression. To achieve this we proposed to understand the role of MUC16CT by carrying out over expression of MUC16CT in BC cells followed by performing various established in vitro and in vivo functional studies. To this end, we have generated FLAG-tagged MUC16CT-114FL and 114dCT stable transfectants in MDAMB231 and ... |
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| The Isolation and Characterization of Human Prostate Cancer Stem Cells |
Feb 2012 |
14 pages |
| Authors:
Ganesh Palapattu; METHODIST HOSPITAL HOUSTON TX
|
| The overall objective of this proposal is to develop a durable cure for lethal prostate cancer through the elucidation of the role of cancer stem cells in the pathogenesis of the disease. During the past year, we have made the following significant findings/observations: i)3D culture of human prostate cancer cells with magnetic nanoparticles is not optimal for tumor initiation studies, ii) in vitro co-culture of human prostate cancer cells (established ... |
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| Exopolysaccharide Productivity and Biofilm Phenotype on Oral Commensal Bacteria as Pathogenesis of Chronic Periodontitis |
Jan 2012 |
15 pages |
| Authors:
Takeshi Yamanaka; Kazuyoshi Yamane; Chiho Mashimo; Takayuki Nambu; Hugo Maruyama; Kai-Poon Leung; Hisanori Fukushima; ARMY DENTAL COMMAND FORT SAM HOUSTON TX
|
| Exopolysaccharide (EPS) productivities in many bacteria have been associated with pathogenicity in mammalian hosts as providing extracellular matrices to form biofilm (Costerton et al., 1995). Bacteria assuming biofilm-forming capacity have enormous advantages in establishing persistent infections (Costerton et al., 1999). Chronic periodontitis is caused by dental plaque known as a complex biofilm which consists of several hundred different species of bacteria (Chen, 2001; Socransky and Haffajee, 2002; Lovegrove, 2004). While ... |
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| Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans |
01 Oct 2011 |
52 pages |
| Authors:
Pierre Massion; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| During our first year of research, we demonstrated a localized field cancerization phenomenon on gene expression in the airway of patients with lung cancer, and we identified several pathways preferentially activated in the airway adjacent to tumors. In addition, we have identified markers of stem cells in the airway that may represent tumor-initiating cells of the airway and are evaluating profiles of these cells. We have identified Snail as a ... |
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| Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans |
Oct 2011 |
62 pages |
| Authors:
Ignacio Wistuba; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Different localized field effect phenomenon occurs in patients with lung adenocarcinoma and squamous cell carcinoma histologies. |
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| Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alterations in CNS Development |
Oct 2011 |
21 pages |
| Authors:
Mark D Noble; ROCHESTER UNIV NY
|
| The goals of our work are to develop means of identifying cells, and individuals, that present with a more basal oxidized redox state and to identify molecular mechanisms that functionally integrate such an oxidized state with observations that the multiple environmental insults suggested to be involved in autism pathogenesis also occur in many children that do not develop ASD. This suggests there is an underlying vulnerability phenotype that makes some ... |
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| The STRONG STAR Multidisciplinary PTSD Research Consortium |
Sep 2011 |
24 pages |
| Authors:
Randy Strong; Alan Frazer; David Morilak; TEXAS UNIV AT SAN ANTONIO HEALTH SCIENCE CENTER
|
| The hypothesis addressed by this project is that early life exposure to stress or glucocorticoids produces a distinct neurochemical and behavioral phenotype characterized by life-long vulnerability to stressors that trigger PTSD. During the past year, we completed studies on our prenatal stress model (PNS). We found that PNS creates a sensitization to conditioned fear in the adult offspring, and a resistance to the extinction of conditioned fear, but only after ... |
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| Deregulation of miRNAs Contributes to Development and Progression of Prostate Cancer |
Sep 2011 |
29 pages |
| Authors:
Ralph W deVere White; CALIFORNIA UNIV DAVIS
|
| This DOD grant aims to identify biomolecules that are crucial in the pathogenesis of prostate cancer. In the first year we found that miR-125b directly targets p53, Puma and Bak1. In the 2nd year, we focused on Aim 2 and have obtained exciting results: 1) miR-125b promotes prostatic tumor growth and also induces castrate-resistant growth in a mouse model; 2) miR-125-mediated suppression of apoptosis signaling contributes to the growth of ... |
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| Lung Cancer Prevention Through Prophylactic Vaccination Against Endogenous Retroviral Antigens |
Sep 2011 |
13 pages |
| Authors:
Hyam Levitsky; JOHNS HOPKINS UNIV BALTIMORE MD
|
| No form of disease prevention has had greater success than prophylactic immunization. Whereas therapeutic cancer vaccines have only marginal evidence of clinical efficacy, prophylactic vaccination against tumor-associated antigens can confer life-long protection in both transplantable and transgenic cancer models. Yet most non-virally associated cancers lack candidate antigens that could be targeted for human cancer prevention. Endogenous Retroviral sequences and other transposable elements (TEs) comprise almost 40% of the human genome. ... |
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| Elucidation of Molecular Alterations in Precursor Lesions of Ovarian Serous Carcinoma |
Aug 2011 |
10 pages |
| Authors:
Robert J Kurman; JOHN HOPKINS SCHOOL OF PUBLIC HEALTH BALTIMORE MD
|
| The objectives are to 1) elucidate the pathogenesis of ovarian cancer by characterizing the early lesions, and 2) to provide biomarkers for early ovarian cancer detection. Both goals will be facilitated by this Consortium Development plan which is a collaborative, interdisciplinary program that will establish the infrastructure to coordinate research. The research sites include Johns Hopkins University, Toronto University, Memorial Sloan Kettering Cancer Center, and Yale University. The Coordination center ... |
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| Volunteer Challenge With Enterotoxigenic Escherichia coli That Express Intestinal Colonization Factor Fimbriae CS17 and CS19 |
01 Jul 2011 |
6 pages |
| Authors:
Robin McKenzie; Chad K Porter; Joyce A Cantrell; Barbara DeNearing Aisling; Shannon L Grahek; Stephanie A Sincock; Colleen Woods; Peter Sebeny; David A Sack; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD ENTERIC DISEASES DEPT
|
| Human challenges with enterotoxigenic Escherichia coli (ETEC) have broadened our understanding of this important enteropathogen. We report findings from the first challenge studies using ETEC-expressing colonization factor fimbria CSI7 and CSI9. LSN03-016011/A (LT, CS17) elicited a dosedependent effect, with the upper dose (6 X 10(exp 9) organisms) causing diarrhea in 88% of recipients. WS0115A (LTSTp, CSI9) also showed a dose response, with a 44% diarrhea rate at 9 X 10(exp ... |
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| The Use of Comprehensive Molecular Profiling with Network and Control Theory to Better Understand GWI and Model Therapeutic Strategies |
Jul 2011 |
104 pages |
| Authors:
Nancy G Klimas; Mary A Fletcher; SOUTH FLORIDA VETERANS AFFAIRS FOUNDATION FOR RESEARCH AND EDUCATION INC MIAMI FL
|
| The objective of this study is to improve our understanding of GWI pathogenesis in two ways through integration across several of the body s regulatory systems of data and knowledge collected from disparate sources, and by mapping of the coordinated interactions between these physiologic systems and the potential for altered wiring of these signaling networks in GWI. Using comprehensive molecular profiling, network and control theory the overarching objective of this ... |
|
| Role of Foxm1 in the Pathogenesis of Prostate Cancer |
Jul 2011 |
14 pages |
| Authors:
Tanya Kalinichenko; CHILDREN'S HOSPITAL MEDICAL CENTER CINCINNATI OH
|
| The main purpose of our work is to understand the role of Foxm1 in the development of prostate cancer, provide information about molecular mechanisms whereby Foxm1 controls epithelial cell proliferation during PCa, and determine whether the inhibition of Foxm1 may potentially be beneficial during PCa therapy, therefore leading to the development of the novel therapeutic target for prostate cancer chemotherapy. During the second year of grant support, we demonstrated that ... |
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| Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria Gonorrhoeae Strains FA1090 and MS11mkC |
31 May 2011 |
13 pages |
| Authors:
Marcia M Hobbs; P F Sparling; Myron S Cohen; William M Shafer; Carolyn D Deal; Ann E Jerse; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MICROBIOLOGY AND IMMUNOLOGY
|
| Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and reproduces the clinical features of naturally acquired gonococcal urethritis. Human inoculation studies have helped define the natural history of experimental infection with two well-characterized strains of N. gonorrhoeae, FA1090 and MS11mkC. The human model has proved useful for testing the importance of putative gonococcal virulence factors for urethral infection in men. Studies with isogenic mutants have improved our understanding ... |
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| Oxidative Lung Injury in Virus-Induced Wheezing |
May 2011 |
20 pages |
| Authors:
Roberto P Garofalo; TEXAS UNIV AT GALVESTON
|
| This project focuses on respiratory syncytial virus (RSV), the single most important pathogen causing acute respiratory-tract infections in children. RSV infections are a major precipitating factor of wheezing in asthmatic children, and they have been linked to both the development and the severity of asthma. Our group has established a multidisciplinary and highly integrated pre-clinical and translational research program that focuses on the role of oxidative injury in the pathogenesis ... |
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| The Infectious Pathogenesis Of Prostate Cancer |
Apr 2011 |
55 pages |
| Authors:
Hans-Olov Adami; Lorelei Mucci; HARVARD SCHOOL OF PUBLIC HEALTH BOSTON MA
|
| Accumulating evidence points to a role of chronic inflammation in the pathogenesis and progression of cancers, including prostate. Infections are important agents in the genesis of inflammation. For prostate cancer, several lines of evidence point to a role of infections as important agents, although no specific infection has consistently been identified. In this project, we are examining two specific infectious agents with respect to prostate cancer: T vaginalis, the most ... |
|
| A Biophysico-Computational Perspective of Breast Cancer Pathogenesis and Treatment Response |
Mar 2011 |
263 pages |
| Authors:
Valerie Weaver; CALIFORNIA UNIV SAN FRANCISCO
|
| The extracellular matrix (ECM) regulates breast homeostasis and is corrupted in breast cancers. We showed that the breast ECM progressively reorganizes into large bundles and stiffens due to high activity of ECM remodeling and cross-linking enzymes such as lysyl oxidase (LOX. The functional relevance of this was revealed through in vitro and in vivo work which revealed that ECM stiffness enhances breast cell growth, survival, migration and regulates treatment responsiveness ... |
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| Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatment, and Therapeutic Modalities |
Feb 2011 |
113 pages |
| Authors:
Waun K Hong; Roy Herbst; M D ANDERSON CANCER CENTER HOUSTON TX
|
| The projects in this proposal specifically target several signal transduction pathways known to be critical for NSCLC pathogenesis including the EGFR pathway and the more downstream ras/raf/Mek/ERK pathway. These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using either small mole3cules or targeted peptide approaches. |
|
| Diversity, Replication, Pathogenicity and Cell Biology of Crimean Congo Hemorrhagic Fever Virus |
OCT 2010 |
73 pages |
| Authors:
Adolfo Garcia-Sastre; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| This research project was a result of a collaboration between three research groups aimed at elucidating basic replication processes of CCHFV with the expected outcome of providing basic research reagents and establishing the foundation of knowledge necessary for discovery of vaccines and antiviral therapeutics for Crimean Congo hemorrhagic fever. Our major findings during the total period of support were the following: We have cloned and expressed all proteins of CCHFV. ... |
|
| Advanced Medical Countermeasures Consortium |
Oct 2010 |
483 pages |
| Authors:
Milton Smith; MICHIGAN UNIV ANN ARBOR
|
| A diverse cadre of weapons of mass destruction was utilized by the group to examine pathogenesis and methods of intervention. It was determined that oxidative stress is significant component of the pathogenesis of biological and chemical weapons. Antioxidants had an ameliorate effect on both chemical and biological agents, and has the potential to be used as an ancillary treatment. Antigen presenting cells may be useful for detecting subclinical infectious disease. ... |
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| Deregulation of miRNAs Contributes to Development and Progression of Prostate Cancer |
AUG 2010 |
10 pages |
| Authors:
Ralph W. deVere White; CALIFORNIA UNIV DAVIS
|
| The overall hypothesis of our proposal is that miR-125b acts as an oncogene, contributing to the development and progression of prostate cancer. In this grant, we proposed to test the ability of aberrantly-expressed miR-125b to promote tumorigenesis and to induce AI growth in three specific aims. In the first year, our focusThe overall hypothesis of our proposal is that miR-125b acts as an oncogene, contributing to the development and progression ... |
|
| Corticosterone Administration to Promote Fear Memory Forgetting Process in an Animal Model of PTSD |
May 2010 |
15 pages |
| Authors:
He Li; Lei Zhang; Robert J Ursano; Min Jia; Stanley Smerin; Eleanore H Gamble; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLE MD
|
| Activation of glucocorticoid receptor signaling and its subsequent alterations has been implicated in the pathophysiological fear response to stress and the pathogenesis of stress-associated psychiatric disorders such as posttraumatic stress disorder (PTSD). To further examine the association between alterations in central glucocorticoid receptor signaling and the occurrence of stress-induced psychiatric symptoms, the present study, utilizing a learned helplessness stress model in rats, examines whether glucocorticoid receptor signaling activation shortly before ... |
|
| Pathogenesis of Escherichia coli O157:H7 Strain 86-24 Following Oral Infection of BALB/c Mice with an Intact Commensal Flora |
Jan 2010 |
13 pages |
| Authors:
Krystle L Mohawk; Angela R Melton-Celsa; Tonia Zangari; Erica E Carroll; Alison D O'Brien; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Escherichia coli 0 157:H7 is a food-borne pathogen that can cause hemorrhagic colitis and. occasionally. hemolytic uremic syndrome, a sequela of infection that can result in renal failure and death. Here we sought to model the pathogenesis of orally-administered E. coli 0157:H7 in BALB/c mice with an intact intestinal nora. First. we defined the optimal dose that permitted sustained fecal shedding of E. coli 0157:H7 over 7 days ( -109 ... |
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| Hypertension-Induced Vascular Remodeling Contributes to Reduced Cerebral Perfusion and the Development of Spontaneous Stroke in Aged SHRSP Rats |
Jan 2010 |
11 pages |
| Authors:
Erica C Henning; Steven Warach; Maria Spatz; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Stroke in spontaneously-hypertensive, stroke-prone (SHRSP) rats is of particular interest because the pathogenesis is believed to be similar to that in the clinical setting. In this study, we employed multi-modal MRI-ASL, OWl, T2 , GRE, T1 (pre/post contrast)-to investigate the natural history of spontaneous cerebral infarction and the specific role of cerebral perfusion in disease development. Twelve female SHRSP rats (age: - 1 year) were Imaged within 1 to 3 ... |
|
| Identification and Functional Characterization of Somatic Mutations in Human MicroRNAs and their Responsive Elements in Target Genes in Ovarian Tumor Tissues |
May-2009 |
6 pages |
| Authors:
Hua Zhao; HEALTH RESEARCH INC BUFFALO NY
|
| Epithelial ovarian cancer (EOC) continues to be the leading cause of the death among gynecological malignancies, owing to the lack of preventive strategies, early diagnostic methods or effective therapies. Detailed understanding of molecular changes, such as, somatic mutations, in ovarian cancer holds the promise of greatly contributing to the understanding of ovarian cancer pathogenesis, with obvious implications in development of new biomarkers, prevention strategies and therapy Micro-RNAs (miRNAs) are endogenous ... |
|
| Mycoleptodiscus terrestris: An Endophyte Turned Latent Pathogen of Eurasian Watermilfoil |
Mar-2009 |
7 pages |
| Authors:
Judy F Shearer; ENGINEER RESEARCH AND DEVELOPMENT CENTER VICKSBURG MS
|
| Plants that are stressed or weakened are more susceptible to disease than healthy plants. An endophytic fungus that has the capability of becoming a latent pathogen may trigger a host-fungus interaction resulting in disease development in Eurasian watermilfoil (Myriophyllum spicatum L.) (EWM) plants when they are subjected to stress. The purpose of the present study was to determine if endophyte infected (E+) plants that are weakened by nutrient stress decline ... |
|
| The Infectious Pathogenesis of Prostate Cancer |
Mar-2009 |
12 pages |
| Authors:
Hans-Olov Adami; HARVARD SCHOOL OF PUBLIC HEALTH BOSTON MA
|
| Accumulating evidence points to a role of chronic inflammation in the pathogenesis and progression of cancers, including prostate. Infections are important agents in the genesis of inflammation. For prostate cancer, several lines of evidence point to a role of infections as important agents, although no specific infection has consistently been identified. In this project, we are examining two specific infectious agents with respect to prostate cancer: T vaginalis, the most ... |
|
| Uncoupling GP1 and GP2 Expression in the Lassa Virus Glycoprotein Complex: Implications for GP1 Ectodomain Shedding |
23-Dec-2008 |
19 pages |
| Authors:
Luis M Branco; Alex Matschiner; Joseph N Fair; Megan M Illick; Kerry A Illick; Randal Schoepp; Robert F Garry; Mary C Guttieri; BIOFACTURA INC ROCKVILLE MD
|
| Background: Sera from convalescent Lassa fever patients often contains antibodies to Lassa virus (LASV) glycoprotein 1 (GP1), and glycoprotein 2 (GP2); Immunization of non-human primates with viral vectors expressing the arenaviral glycoprotein complex (GPC) confers full protective immunity against a lethal challenge with LASV. Thus, the development of native or quasi native recombinant LASV GP1 and GP2 as soluble, uncoupled proteins will improve current diagnostics, treatment, and prevention of Lassa ... |
|
| Labeled Antimicrobial Peptides for Detection of Microorganisms |
Dec-2008 |
10 pages |
| Authors:
Steven Arcidiacono; Philip Pivarnik; Alexa Meehan; Charlene Mello; Andre Senecal; ARMY NATICK SOLDIER RESEARCH DEVELOPMENT AND ENGINEERING CENTER MA
|
| Antibodies have traditionally been used for pathogen detection but often lack stability and sensitivity. Current biosensor technologies using fluorescently labeled antibodies are generally capable of detection of 10(exp 3) to 10(exp 4)4 bacterial cells/ml. Antimicrobial peptides naturally bind to the lipopolysaccharide component of bacterial cell walls as part of their mode of action. Fluorescently labeled antimicrobial peptides (AMPs) were evaluated as a potential replacement of labeled antibodies in a sandwich ... |
|
| Tumor Suppressor Activity of the EphB2 Receptor in Prostate Cancer |
Nov-2008 |
96 pages |
| Authors:
Elena B Pasquale; BURNHAM INST LA JOLLA CA
|
| Mutations have been recently identified in the EphB2 receptor gene in prostate cancer suggesting that EphB2, a member of the large Eph receptor tyrosine kinase family, is a tumor suppressor in prostate cancer. Consistent with a tumor suppressor activity, we found that EphB2 is more highly expressed in non-transformed BPH-1 prostate epithelial cells than in several prostate cancer cell lines. Furthermore, EphB2 expression was rapidly lost in stably transfected DU145 ... |
|
| Diversity, Replication, Pathogenicity and Cell Biology of Crimean Congo Hemorrhagic Fever Virus |
Oct-2008 |
63 pages |
| Authors:
Adolfo Garcia-Sastre; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| This research project was a result of a collaboration between three research groups aimed at elucidating basic replication processes of CCHFV with the expected outcome of providing basic research reagents and establishing the foundation of knowledge necessary for discovery of vaccines and antiviral therapeutics for Crimean Congo hemorrhagic fever. Our major findings during the total period of support were the following: We have cloned and expressed all proteins of CCHFV. ... |
|
| Exploration of the Effectiveness of Social Distancing on Respiratory Pathogen Transmission Implicates Environmental Contributions |
Sep-2008 |
9 pages |
| Authors:
Michael P Broderick; Christian J Hansen; Kevin R Russell; NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA DEPT OF RESPIRATORY DISEASE RESEARCH
|
| Respiratory pathogen transmission is multifactoral with person-to-person aerosolized fomite and environmental contribution is usually difficult to determine the effect of each of these on disease transmission dynamics and on interventions. The high controllable military recruit training environment is an ideal setting for further exploration and understanding of these dynamic respiratory illness (FRI) rates consistently hover at epidemic levels. The living space population size introduction of potent individuals and pathogen environmental ... |
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| Randomized Trial of Neuroprotective Effects of Erythropoietin in Patients Receiving Adjuvant Chemotherapy for Breast Cancer: Positron Emission Tomography and Neuropsychological Study |
Sep-2008 |
12 pages |
| Authors:
James Abraham; WEST VIRGINIA UNIV RESEARCH CORP MORGANTOWN
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| Animal Research Study Amendment An amendment to the study was initiated in April 2005 to include animal experiments. As per published literature, proinflammatory cytokines play a role in the pathogenesis of cognitive dysfunction. The experiments were designed to assess the cytokines before and after chemotherapy in a rat model. We have established an experimental animal model to study chemotherapy-induced cognitive dysfunction observed in the clinical setting. In this model administration ... |
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| Medical Surveillance Monthly Report (MSMR). Volume 15, Number 6, July-August 2008 |
Aug-2008 |
37 pages |
| Authors:
Steven Tobler; Mark V Rubertone; John F Brundage; Robert F DeFraites; Ellen Wertheimer; ARMED FORCES HEALTH SURVEILLANCE CENTER SILVER SPRING MD
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| Since October 1985, the U.S. military has conducted routine screening for antibodies to HIV-1 among civilian applicants for U.S. military service. Since 1986, all members of the active and reserve components of the U.S. Armed Forces have been periodically screened for antibodies to HIV-1. This report summarizes prevalences and trends of HIV-1 antibody seropositivity among civilian applicants for military service and members of the active and reserve components of the ... |
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| A Disruption of ctpA Encoding Carboxy-Terminal Protease Attenuates Burkholderia mallei and Induces Partial Protection in CD1 Mice |
03-Jun-2008 |
11 pages |
| Authors:
Aloka B Bandara; David DeShazer; Thomas J Inzana; Nammalwar Sriranganathan; Gerhardt G Schurig; Stephen M Boyle; VIRGINIA-MARYLAND REGIONAL COLL OF VETERINARY MEDICINE BLACKSBURG VA
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| Burkholderia mallei is the etiologic agent of glanders in solipeds (horses, mules and donkeys), and incidentally in carnivores and humans. Little is known about the molecular mechanisms of B. mallei pathogenesis. The putative carboxy-terminal processing protease (CtpA) of B. mallei is a member of a novel family of endoproteases involved in the maturation of proteins destined for the cell envelope. All species and isolates of Burkholderia carry a highly conserved ... |
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