| 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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| Biomarkers in the Detection of Prostate Cancer in African Americans |
Sep 2012 |
106 pages |
| Authors:
William E Grizzle; Sandra M Gaston; ALABAMA UNIV IN BIRMINGHAM
|
| All IRBs have been approved by the participating sites and the DOD. Dr. Grizzles laboratory has completed a pilot analysis by Luminex multiplex immunoassay of serum using two panels of biomarkers, cancer biomarkers (e.g., CA19.9) and inflammatory cytokines (e.g., IL- 17a), to identify potential biomarkers that are differentially expressed. Molecular features that are not differentially expressed and for which there are not apparent racial differences will be excluded in future ... |
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| Genes Associated with Food Allergy and Eosinophilic Esophagitis |
Sep 2012 |
6 pages |
| Authors:
David Broide; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| The ingestion of food antigens plays an essential role in the development of eosinophilic esophagitis (EE) as total removal of dietary antigens by using an amino acid based oral formula improves clinical symptoms and esophageal histology in 98% of patients with EE within a month. EE is thought to be mediated by both IgE and non-IgE mediated food allergy. In this study we are particularly interested in identifying genes in ... |
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| UV-Induced Triggering of a Biomechanical Initiation Switch Within Collagen Promotes Development of a Melanoma-Permissive Microenvironment in the Skin |
Sep 2012 |
18 pages |
| Authors:
Peter Brooks; MAINE MEDICAL CENTER PORTLAND
|
| The overall objective of our proposal was to test whether UV irradiation facilitates the exposure of the HU177 cryptic collagen epitope which may represent an early solid state biomechanical initiation switch that promotes inflammation, skin damage and the creation of a melanoma permissive niche. Our current studies suggest that UV-mediated structural alterations in collagen type-I, collagen type-IV and Matrigel (trademark) differentially alter the ability of human melanoma cells, human dermal ... |
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| Effect of Intraperitoneal Radiotelemetry Instrumentation on Voluntary Wheel Running and Surgical Recovery in Mice |
Sep 2012 |
10 pages |
| Authors:
Bryan G Helwig; Jermaine A Ward; Michael D Blaha; Lisa R Leon; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA THERMAL AND MOUNTAIN MEDICINE DIVISION
|
| Radiotelemetry transmitters support tracking of physiologic variables in conscious animals, but the size of the transmitter may alter animal health and behavior. We hypothesized that the size of the device adversely affects body weight, food intake, water intake, circadian core temperature, activity, voluntary running patterns, and the health of internal organs and that these negative effects can be minimized with smaller transmitter devices. Male C57BL/6J mice (weight, 20 to 24 ... |
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| Blast Injuries And Heterotopic Ossification |
Aug 2012 |
7 pages |
| Authors:
K A Alfieri; J A Forsberg; B K Potter; WALTER REED NATIONAL MILITARY MEDICAL CENTER BETHESDA MD
|
| Heterotopic ossification (HO) is perhaps the single most significant obstacle to independence, functional mobility, and return to duty for combat-injured veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Recent research into the cause(s) of HO has been driven by a markedly higher prevalence seen in these wounded warriors than encountered in previous wars or following civilian trauma. To that end, research in both civilian and military laboratories continues to ... |
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| Medical Surveillance Monthly Report. Volume 19, Number 8 |
Aug 2012 |
25 pages |
| Authors:
Francis L O'Donnell; John F Brundage; Ellen R Wertheimer; Denise S Olive; Leslie L Clark; ARMED FORCES HEALTH SURVEILLANCE CENTER SILVER SPRING MD
|
| Viruses are the most common causes of meningitis, a condition characterized by inflammation of the protective membranes that surround the brain and spinal cord. During the 10-year surveillance period, there were 3,205 confirmed cases, 724 probable cases, and 2,495 suspected cases of viral meningitis among active and reserve component members. In all three categories of cases, the most common diagnoses were meningitis due to enteroviruses; however a majority of these ... |
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| Investigation of the Role of Stress in Inflammatory Bowel Disease Using Zebrafish as an Experimental Model |
Aug 2012 |
13 pages |
| Authors:
Efi Kokkotou; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Inflammatory bowel disease (IBD) is a chronic debilitating condition affecting 1.4 million Americans, young individuals in particular. Psychological stress and environmental factors such as diet, toxins and the microbiome contribute to disease precipitation and worsen its symptoms. War Veterans appear to be disproportionally affected by these factors. The medical management of IBD remains unsatisfactory and more than half of patients require some type of surgical intervention during their lifetime. The ... |
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| Nuclear Factor-Kappa B Activity in the Host-Tumor Microenvironment of Ovarian Cancer |
Aug 2012 |
40 pages |
| Authors:
Andrew Wilson; VANDERBILT UNIV NASHVILLE TN
|
| Overcoming tumor resistance to platinum chemotherapy is critical for prolonging life in women with advanced ovarian cancer. The nuclear factor-kappaB (NF-kB) signaling pathway is a key mediator of tumorigenesis by linking inflammatory pathways to cancer. Inhibitors of NF-kB potentiate the effects of cytotoxic agents in ovarian cancer cells. Thus, a promising strategy in ovarian cancer treatment is the combination of NF-kB inhibitors with current platinum-based regimens. Equally relevant are the ... |
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| Mission Connect Mild TBI Translational Research Consortium |
Aug 2012 |
24 pages |
| Authors:
J R Perez-Polo; Claire E Hulsebosch; Douglas S DeWitt; Raymond J Grill; TEXAS UNIV MEDICAL BRANCH AT GALVESTON
|
| Mild traumatic brain injury (mTBI), particularly mild blast injuries due to improvised exploding devices, result in long term impairment of cognition and behavior. Our hypothesis is that there are inflammatory consequences to mTBI that persist over time and in part cause the resultant pathogenesis and clinical outcomes. We used an adaptation (1 atm pressure) of the moderate to severe brain lateral fluid percussion (LFP) brain injury rat model. Our mild ... |
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| Therapeutic Inhibition of Pro-Inflammatory Signaling and Toxicity to Staphylococcal Enterotoxin B by a Synthetic Dimeric BB-Loop Mimetic of MyD88 |
27 Jul 2012 |
14 pages |
| Authors:
Teri L Kissner; Gordon Ruthel; Shahabuddin Alam; Enrique Mann; Dariush Ajami; Mitra Rebek; Eileen Larkin; Stefen Fernandez; Robert G Ulrich; Sun Ping; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Staphylococcal enterotoxin B (SEB) exposure triggers an exaggerated pro-inflammatory cytokine response that often leads to toxic shock syndrome (TSS) associated with organ failure and death. MyD88 mediates pro-inflammatory cytokine signaling induced by SEB exposure and MyD88-/- mice are resistant to SEB intoxication, suggesting that MyD88 may be a potential target for therapeutic intervention. We targeted the BB loop region of the Toll/IL-1 receptor (TIR) domain of MyD88 to develop small-molecule ... |
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| Subacute Effects of Inhaled Jet Fuel-A (JET A) on Airway and Immune Function in Rats |
16 Jul 2012 |
137 pages |
| Authors:
Lisa M Sweeney; Susan L Prues; Erin R Wilfong; James E Reboulet; Krista Hess; NAVAL MEDICAL RESEARCH UNIT DAYTON WRIGHT-PATTERSON AFB OH
|
| Two studies were conducted to assess the potential airway and immune effects following subacute (14-day) exposure of female rats to 500, 1000 or 2000 mg/m3 of Jet-A for 4 hrs/day. The first study used Sprague-Dawley rats; the second study included both Fischer 344 (F344) and Sprague-Dawley rats. In the first study, exposure to 2000 mg/m3 jet fuel may have caused significant upper airway inflammation on day 7 post-exposure, as indicated ... |
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| Interaction of Synuclein and Inflammation in Dopaminergic Neurodegeneration |
Jul 2012 |
8 pages |
| Authors:
Serge Przedborski; Vernice Jackson-Lewis; COLUMBIA UNIV NEW YORK
|
| Parkinson Disease (PD) is the second most common neurodegenerative disease of our aged population behind Alzheimer s Disease. Epidemiological, animal and cell culture studies have shown that inflammation is a part of the PD morphological picture. It has been suggested that -synuclein (a major component of the Lewy bodies present within dopamine neurons of the PD substantia nigra {SN}) is responsible for the observed inflammatory response in the PD brain. ... |
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| Enhancing the Phagocytic Clearance of Apoptotic Cells to Control Breast Carcinoma Progression |
Jul 2012 |
10 pages |
| Authors:
Michael R Elliott; ROCHESTER UNIV NY
|
| Macrophages have emerged as a key cell type influencing the initiation, progression and metastasis of breast cancer. Their impact on carcinogenesis is largely understood through their role in promoting a pro- or anti-inflammatory milieu. The phagocytosis of apoptotic cells by macrophages, a chief function of these cells, greatly influences the inflammatory status of macrophages. Despite the abundance of both macrophages and apoptotic cells in mammary tumors, little is known about ... |
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| Trial of Naltrexone and Dextromethorphan for Gulf War Veterans' Illness |
Jul 2012 |
6 pages |
| Authors:
William J Meggs; Kori L Brewer; Allison Mainhart; EAST CAROLINA UNIV GREENVILLE NC
|
| Approval to separate the study into a separate dextromethorphan arm and naltrexone arm from the Department of Defense Institutional Review Board was finally obtained in February 2011. We are actively screening and enrolling subjects and are very encouraged by the response. We anticipate that by the end of the current report period, we will have preliminary data. |
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| Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy |
Jul 2012 |
12 pages |
| Authors:
David J Chung; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
| The purpose of this project is to study the immunomodulatory effect of Listeria on human dendritic cells (DCs) to optimize Listeria-based DC cancer vaccines. The project aims are: 1) Compare the activation and maturation of different human DC subsets in response to Listeria infection. 2) Define the induction of CD4+/CD8+ T-cell and NK cell responses to Listeriaactivated DCs presenting a melanoma tumor-associated antigen. 3) Augment the immunogenicity of Listeria-activated DCs ... |
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| Targeting Microglia to Prevent Post-Traumatic Epilepsy |
Jul 2012 |
63 pages |
| Authors:
Daniel S Barth; COLORADO UNIV AT BOULDER
|
| The purpose of this research project is to explore anti-epileptogenic strategies in and animal model of post-traumatic epilepsy (PTE) using lateral fluid percussion injury (LFPI). Our focus is on attenuating damaging effects of hyperexcitability in the brain induced by inflammation resulting from glial cell immune responses to trauma. We are exploring two drugs, MN166 and SLC022, that are known to suppress post-traumatic glial activation and thus inflammation to evaluate their ... |
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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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| Role of IKKalpha and STAT3 in the Emergence of Castration-Resistant Prostate Cancer |
Jun 2012 |
21 pages |
| Authors:
Massimo Ammirante; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| Recent data strongly suggest that inflammation plays a key role in emergence of tumors and metastases. I previously found that androgen ablation causes infiltration of regressing prostate tumors with immune cells, including B cells, that produce lymphotoxin, which activates IKKalpha and STAT3, in prostate tumor cells that have survived hormone withdrawal, thereby accelerating the emergence of castration-resistant prostate cancer. These results suggest that the inflammatory response associated with death of ... |
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| Commensal Gut Derived Anaerobes as Novel Therapy for Inflammatory Autoimmune Diseases |
May 2012 |
39 pages |
| Authors:
Ashutosh Mangalam; Veena Taneja; MAYO CLINIC ROCHESTER MN
|
| Rheumatoid arthritis (RA) and multiple sclerosis (MS) are chronic inflammatory autoimmune diseases affecting millions of people. Here we are proposing a novel approach to cure MS, by administration of a specific strain of human commensal bacteria. Recent studies have shown that intestinal microflora plays an important role in the health of the host and posses probiotics like qualities. We hypothesize that Gram-negative commensal bacteria from human gut have the potential ... |
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| Commensal Gut-Derived Anaerobes as Novel Therapy for Inflammatory Autoimmune Diseases |
May 2012 |
12 pages |
| Authors:
Veena Taneja; MAYO CLINIC ROCHESTER MN
|
| Predisposition to rheumatoid arthritis (RA) is associated with the presence of genetic factors, HLA class II molecules, DR4 and DQ8, being the strongest. Patients with RA show an imbalance of gut microbiota suggesting its role in regulation of disease. We have used HLA-DR4/ DQ8 mice to test our hypothesis that treatment with commensal bacteria like Prevotella histicola can modulate Collagen-induced arthritis (CIA). In vitro study showed that treatment of mice ... |
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| Intraosseous Hydroxocobalamin in the Treatment of Acute, Severe Cyanide Induced Cardiotoxicity in a Swine (Sus Scrofa) Model - An Alternate Administration Route for Chemical Mass Casualties |
05 Apr 2012 |
7 pages |
| Authors:
Vikhyat Bebarta; Julio Lairet; Rebecca Pitotti; Susan Boudreau; Toni Vargas; Patricia Dixon; Tylan Muncy; AIR FORCE MEDICAL WING (59TH) WILFORD HALL MEDICAL CENTER LACKLAND AFB TX
|
| To compare the rerum to baseline of mean arterial blood pressure (MAP) between 2 groups of swine in acute cyanide toxicity and treated with IV HOC or 10 HOC. We also compared blood cyanide, lactate, pH, nitrotyrosine levels, cerebral oxygenation, and inflammatory markers. 24 swine (48-52kg) were intubated, anesthetized, and instrumented (MAP and cardiac output (CO) monitoring). Cyanide was continuously infused until severe hypotension (50 per cent of baseline MAP). ... |
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| The Impact of Hazardous Chemicals on Macrophages |
Apr 2012 |
32 pages |
| Authors:
Jimmy Ballard; James Regens; OKLAHOMA UNIV OKLAHOMA CITY
|
| The goals of this study were to identify the impact of hazardous chemicals on macrophages, determine how the macrophages respond to these chemicals, and use these signatures to develop novel detection technologies. As a model for this system we selected toxic industrial chemicals and used mouse macrophages as the target cell type. |
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| Role of Inflammation and Insulin Resistance in Mouse Models of Breast Cancer |
Apr 2012 |
9 pages |
| Authors:
Jerrold Olefsky; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| We have shown that obesity increases tumor burden without significantly altering tumor morphology suggesting that the primary effect of obesity is on tumor cell proliferation. Interestingly, the origin of the obesity did not have an effect as genetic obesity due to leptin mutation or diet-induced obesity due to a high fat western diet equivalently increased tumor growth. While there was no difference in macrophage infiltration into the tumors themselves, we ... |
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| Impaired Clearance And Enhanced Pulmonary Inflammatory/Fibrotic Response To Carbon Nanotubes In Myeloperoxidase-Deficient Mice |
30 Mar 2012 |
10 pages |
| Authors:
Anna A Shvedova; Alexandr A Kapralov; Wei H Feng; Elena R Kisin; Ashley R Murray; Robert R Mercer; Claudette M St Croix; Megan A Lang; Simon C Watkins; Nagarjun V Konduru; PITTSBURGH UNIV PA
|
| Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and proinflammatory action in vivo. Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration was markedly less effective whereas the inflammatory response was more robust than in wild-type C57Bl/6 mice. Our results provide direct evidence for the ... |
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| Autophagy-Mediated Defense Response of Mouse Mesenchymal Stromal Cells (MSCs) to Challenge with Escherichia coli |
Mar 2012 |
23 pages |
| Authors:
N V Gorbunov; B R Garrison; M Zhai; D P McDaniel; G D Ledney; T B Elliott; J G Kiang; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
|
| Symbiotic microorganisms are spatially separated from their animal host, e.g., in the intestine and skin, in a manner enabling nutrient metabolism as well as evolutionary development of protective physiologic features in the host such as innate and adaptive immunity, immune tolerance, and function of tissue barriers . The major interface barrier between the microbiota and host tissue is constituted by epithelium reticuloendothelial tissue, and mucosa-associated lymphoid tissue (MALT) . Traumatic ... |
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| Characterization and Application of a Large Animal Model of Penetrating Ballistic Brain Injury (PBBI) |
Mar 2012 |
41 pages |
| Authors:
Charles E Wade; TEXAS UNIV HEALTH SCIENCE CENTER AT HOUSTON
|
| The Purpose of the proposal titled Characterization and Application of a Large Animal Model of Penetrating Ballistic Brain Injury (PBBI) is to develop a large animal model with military relevance. Of military casualties with moderate to severe traumatic brain injuries (TBI) 15-18% are due to penetrating mechanisms. Almost all (97%) of prospective clinical trials of TBI exclude patients with PBBI and no prospective clinical trials specifically focus on PBBI. A ... |
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| Green Tea Modulation of Obesity and Breast Cancer Risk |
Mar 2012 |
7 pages |
| Authors:
Hamed Samavat; MINNESOTA UNIV MINNEAPOLIS
|
| Breast cancer continues to be the most common and second deadliest cancer of women living in the United States.1, 2 It is thought that obesity and chronic inflammation play an important role in increasing risk of breast cancer in humans. 3-5 There is evidence suggesting change in dietary habits including drinking green tea may modify the risk of breast cancer development. This decrease in breast cancer risk may be mediated ... |
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| The Toxicity of Inhaled Sulphur Mustard |
Mar 2012 |
347 pages |
| Authors:
John Jenner; DEFENCE SCIENCE AND TECHNOLOGY LAB PORTON DOWN (UNITED KINGDOM) BIOMEDICAL SCIENCES DEPT
|
| The overall objectives of the study were to understand the mechanism of action of sulfur mustard (HD) on the lung, and ultimately design therapeutic interventions to preserve pulmonary function and life. Under the previous contract (HDTRA 1-07-C-0027) a small proof of principle study investigated the toxicity of inhaled HD. Injury development was monitored in an anesthetized large white pig for 6 hours post exposure and identified dose dependent changes in ... |
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| Genetics of Eosinophilic Esophagitis |
Mar 2012 |
36 pages |
| Authors:
Marc Rothenberg; CHILDREN'S HOSPITAL MEDICAL CENTER CINCINNATI OH
|
| Eosinophilic esophagitis (EE) is an emerging worldwide food allergic disorder associated with polysensitization to multiple food allergens, resulting in greatly restricted diets and chronic gastroesophageal reflux disease-like symptoms in many individuals. EE has a strong genetic component based on the frequent presence of a familial inheritance pattern, the high sibling risk ratio (80-fold) and the demonstration that a single nucleotide polymorphism (SNP) in the eotaxin-3 gene confers disease susceptibility. In ... |
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| Urinary Level of Prostaglandin E2 Metabolite and Risk of Incident Breast Cancer |
Jan 2012 |
10 pages |
| Authors:
Sangmi Kim; NATIONAL INST OF ENVIRONMENTAL HEALTH SCIENCES RESEARCH TRIANGLE PARK NC
|
| This training grant is a Postdoctoral Fellowship Award in breast cancer research, comprising training in breast cancer research and an independent research project. During the previous year, the PI gained valuable experience in designing and conducting molecular epidemiologic studies and participated in various research projects as a leader or a collaborator. She has also acquired knowledge on breast cancer biology through various venues, incorporating new understanding of breast cancer etiology ... |
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| The Effect Of Hypotensive Resuscitation And Fluid Type On Mortality, Bleeding,Coagulation And Dysfunctional Inflammation In A Swine Grade V Liver Injury Model |
Jan 2012 |
89 pages |
| Authors:
Martin A Schreiber; OREGON UNIV HEALTH SCIENCES CENTER PORTLAND
|
| To determine the efficacy of resuscitative fluids currently utilized in military and civilian settings on the physiologic response to uncontrolled hemorrhage. Scope: Swine were subjected to a couple of different models over the length of this multi-year trial. Animals either underwent just a Grade V liver injury or were subjected to the lethal triad of trauma which included hemorrhage, hypothermia and coagulopathy. Over the course of this trial animals were ... |
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| Cells, Biomarkers, and Posttraumatic Stress Disorder: Evidence for Peripheral Involvement in a Central Disease |
Jan 2012 |
13 pages |
| Authors:
James A Andrews; Kameran D Neises; NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA
|
| Posttraumatic stress disorder (PTSD) is a serious disease that involves many different factors. Recently, studies have increasingly pointed toward the development of diagnostic assays for PTSD, and some of potential biomarkers are reviewed here. Additionally, the hypothesis that peripheral blood mononuclear cells (PBMCs) exacerbate PTSD is investigated and a mechanism is proposed. PBMCs include monocytes, macrophages, and lymphocytes, and their actions are complex, acting in concert with many factors to ... |
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| Allelic Variation on Murine Chromosome 11 Modifies Host Inflammatory Responses and Resistance to Bacillus anthracis |
Dec 2011 |
16 pages |
| Authors:
Jill K Terra; Bryan France; Christopher K Cote; Amy Jenkins; Joel A Bozue; Susan L Welkos; Ragini Bhargava; Chi-Lee Ho; Margarete Mehrabian; Calvin Pan; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD BACTERIOLOGY DIV
|
| Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened ... |
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| Treatment of Shock With Adenosine Receptor Ligands |
Oct 2011 |
6 pages |
| Authors:
Gyorgy Hasko; Alexey Trepakov; Balazs Csoka; Balazs Koscso; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEWARK
|
| The purpose of the studies conducted in the first reporting period was to begin to investigate the effect of pharmacologicstimulation of A2A or A2B adenosine receptors on trauma/hemorrhagic shock-induced organ injury in rats. The A2A receptoragonist 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethyl-carboxamidoadenosine CGS21680 (0.1 and 0.5 mg/kg)exacerbated organ injury when mixed into Ringer s Lactate resuscitation fluid, which was associated with a longlastinghypotensive effect of this agent. In contrast, the A2B receptor agonist BAY 60-6583 ... |
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| Determination of Novel Strategies for Hastening Corneal Wound Healing and Reducing Tissue Inflammation |
Oct 2011 |
113 pages |
| Authors:
Jose Capo-Aponte; Peter S Reinach; GENEVA FOUNDATION LAKEWOOD WA
|
| The aim of this study is to uncover novel transient receptor potential protein vanilloid-1 (TRPV1)- linked cell signaling drug targets for more selective alleviation of trauma-induced corneal symptomology and faster restoration of normal vision. Dual specificity phosphatase (DUSP)5 and DUSP6 selectively control ERK pathway activity and proliferation in human corneal epithelial cells (HCEC). Capsaicin-induced increases in interleukin (IL)-6 and IL-8 occur primarily through phosphorylated JNK1. CB1 and TRPV1 activation induces ... |
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| Development of a Small Molecule P2X7R Antagonist as a Treatment for Acute SCI |
Oct 2011 |
14 pages |
| Authors:
Steven Goldman; ROCHESTER UNIV NY
|
| Our major focus of year 1 of this grant were Aims 1 and 4. In Aim 1, we proposed to identify a maximally effective P2X7 receptor antagonist, as well as to optimize its dose in a weight drop model of experimental spinal cord injury. Solid progress has been made. The neuroprotective effect of the highest tolerated dose of four P2X7 receptor antagonists has been tested in rats and 3 P2X7 ... |
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| Voxel-Wise Time-Series Analysis of Quantitative MRI in Relapsing-Remitting MS: Dynamic Imaging Metrics of Disease Activity Including Pre-Lesional Changes |
Oct 2011 |
9 pages |
| Authors:
Aaron S Field; WISCONSIN UNIV MADISON
|
| Previous MRI studies in MS have retrospectively analyzed normal-appearing brain tissue in locations where typical MS lesions ultimately appeared, finding pre-lesional changes in several MRI metrics. However, studies have not been entirely consistent and the development of a prototypical MS lesion cannot as yet be prospectively predicted. The primary objective of this project is to validate the preactive lesion hypothesis in MS by identifying the spatiotemporal imaging signature of white ... |
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| Regeneration of Musculoskeletal Tissues by Prolonged Low-Grade Inflammation |
Oct 2011 |
9 pages |
| Authors:
Ozan Akkus; PURDUE UNIV LAFAYETTE IN
|
| Inflammation is a defense mechanism to injury that contains infection and initiates tissue repair. A potential outcome of the inflammatory process is granulomatous inflammation characterized by a large collection of macrophages. In a previous study, we observed a low-grade inflammation around a pure collagen based scaffold on implantation into the rabbit patellar tendon. Additionally, the cross-sectional areas of the tendons treated with the implant were about 40% greater compared to ... |
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| Sealing Penetrating Eye Injuries Using Photo-Activated Bonding |
Sep 2011 |
16 pages |
| Authors:
Irene E Kochevar; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| Purpose: To develop a light-activated technology (called PTB) with the potential to decrease vision loss and ocular complications in warfighters sustaining penetrating eye injuries. Scope: In year 2, the scope was to establish the treatment for direct photo-sealing of corneal lacerations, to identify the best treatment for sealing eyelid skin lacerations, and to optimize and build a prototype light delivery system that is safe for the retina. Major findings: Demonstrated ... |
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| Sealing Penetrating Eye Injuries Using Photoactivated Bonding |
Sep 2011 |
8 pages |
| Authors:
Anthony Johnson; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLE MD
|
| To develop a light-activated technology (called PTB) with the potential to decrease vision loss and ocular complications in warfighters sustaining penetrating eye injuries. Scope: In year 2, the scope was to establish the treatment for direct photo-sealing of corneal lacerations, to identify the best treatment for sealing eyelid skin lacerations, and to optimize and build a prototype light delivery system that is safe for the retina. Major findings: Demonstrated that ... |
|
| Genes Associated with Food Allergy and Eosinophilic Esophagitis |
Sep 2011 |
5 pages |
| Authors:
David Broide; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| The ingestion of food antigens plays an essential role in the development of eosinophilic esophagitis (EE) as total removal of dietary antigens by using an amino acid based oral formula improves clinical symptoms and esophageal histology in 98% of patients with EE within a month. EE is thought to be mediated by both IgE and non-IgE mediated food allergy. In this study we are particularly interested in identifying genes in ... |
|
| Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression |
Sep 2011 |
15 pages |
| Authors:
Paula J McKeown-Longo; Anthony Ambesi; Carol Horzempa; Aparna Prasad; ALBANY MEDICAL COLL NY
|
| Changes in tissue mechanics as well as increased tissue inflammation have been identified as contributory factors to the development of malignancies. These pathologies are characterized by extensive remodeling of extracellular matrix and increased tissue rigidity. Recent studies have shown that increased tissue rigidity is associated with the unfolding of the Type III domains of extracellular matrix fibronectin. During the previous funding year, we have addressed the hypothesis that changes in ... |
|
| Development Of A Vaccine Targeting Triple-Negative Breast Cancer |
Sep 2011 |
9 pages |
| Authors:
Denise Cecil; SEATTLE UNIV WA
|
| The insulin-like growth factor (IGF) pathway plays an important role in breast cancer growth and metastasis. The IGF-I receptor (IGF-IR) is over-expressed in almost 50% of triple negative breast cancers (TNBC). Thus, therapeutically targeting tumor cells which have upregulated IGF-IR may be a promising approach to treat TNBC. IGF-IR is immunogenic in breast cancer and is a potential target for active immunization. We sought to develop a vaccine that will ... |
|
| New Advanced Technologies In Stem Cell Therapy |
Sep 2011 |
52 pages |
| Authors:
Johnny Huard; PITTSBURGH UNIV PA
|
| We have isolated and characterized a population of skeletal muscle-derived stem cells (MDSCs) that display a greatly improved skeletal and cardiac muscle transplantation capacity when compared to skeletal muscle myoblasts. The MDSCs ability to withstand oxidative and inflammatory stresses appears to be the single most important factor for their improved transplantation capacity. Although the true origin of MDSCs remains unclear, their high degree of similarity with blood vessel-derived stem cells ... |
|
| Plasma Endothelial Microparticles in Multiple Sclerosis: A Novel Metric Assay of Disease Activity and Response to Treatment |
Sep 2011 |
222 pages |
| Authors:
Jonathan S Alexander; Alireza Minagar; LOUISIANA STATE UNIV IN SHREVEPORT HEALTH SCIENCE CENTER
|
| The purpose of this research project is to validate plasma microparticle profiling in multiple sclerosis with the goal of defining microparticle species which have value as predictive or prognostic biomarkers. Additionally, the findings of this project Scope: These finding apply to both civilian and military patients with MS. Major Findings: We have now linked iron deposits in specific brain structures in MS with particular microparticle species; some of these data ... |
|
| Dissecting the Molecular Mechanism of RhoC GTPase Expression in the Normal and Malignant Breast |
Sep 2011 |
29 pages |
| Authors:
John Brenner; MICHIGAN UNIV ANN ARBOR
|
| Primary inflammatory breast cancer (IBC) accounts for approximately 3% of new breast cancers in the US. This form of locally advanced breast cancer is rapidly metastatic and, because of this disease?s rapid progression, the effectiveness of aggressive multimodality treatment is limited; the 5-year disease-free, mean survival rate is less than 45%, making IBC the most lethal form of breast cancer. Here, we report that RhoC GTPase expression is regulated by ... |
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| FoxP3 as a Missing Link Between Inflammation and Breast Cancer |
Sep 2011 |
36 pages |
| Authors:
Yang Liu; MICHIGAN UNIV ANN ARBOR
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| This is the third annual report. The major achievement is establishment of a new mechanism by which Foxp3 activates gene expression. Both H4K16 acetylation and H3K4 tri-methylation are required for gene activation. However, it is still largely unclear how these modifications are orchestrated by transcriptional factors. Here we analyzed the mechanism of the transcriptional activation by FOXP3, an X-linked suppressor of autoimmune diseases and cancers. FOXP3 binds near transcriptional start ... |
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| Breast Tissue Stromal Cells Preferentially Promote Generation of M2 Macrophages: A Novel Mechanism for Tumor Supportive Properties of Breast Microenvironment |
Aug 2011 |
10 pages |
| Authors:
Peiman Hematti; Summer Hanson; Jaheyup Kim; WISCONSIN UNIV MADISON
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| Our goals were: (1) to investigate the effect of tissue-specific stromal cells, i.e. mesenchymal stromal/stem cells (MSCs) and macrophages (MQs), on growth of breast tumor cells, and (2) to test the hypothesis that MSCs of non-breast adipose tissues, in contrast to MSCs of breast tissues, precludes such tissues from becoming a site for breast cancer metastasis. We generated MSCs from normal breast and abdominal adipose tissues with phenotypic charcteristic similar ... |
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| Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model |
Aug 2011 |
13 pages |
| Authors:
Stephen M Lasley; James P O'Callaghan; Diane B Miller; ILLINOIS UNIV AT CHICAGO
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| Gulf War Illness (GWI) is a multi-symptom disorder with features characteristic of sickness behavior, including cognitive impairment, fatigue, depression, sleep disruption, and gastrointestinal and dermatological problems. Sickness behavior, a normal manifestation of an inflammatory response due to infection or injury, resolves when homeostasis is restored, but in GWI the symptoms persist, findings suggestive of a heightened or chronic neuroimmune/neuroinflammatory disorder. The expression of proinflammatory cytokines and chemokines are the basis ... |
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Reports by Keyword(s)
INFLAMMATION
