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The Global Economic And Health Burden Of Human Hookworm Infection., Sarah M Bartsch, Peter J. Hotez, Lindsey Asti, Kristina M Zapf, Maria Elena Bottazzi, David J. Diemert, Bruce Y Lee 2016 George Washington University

The Global Economic And Health Burden Of Human Hookworm Infection., Sarah M Bartsch, Peter J. Hotez, Lindsey Asti, Kristina M Zapf, Maria Elena Bottazzi, David J. Diemert, Bruce Y Lee

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Even though human hookworm infection is highly endemic in many countries throughout the world, its global economic and health impact is not well known. Without a better understanding of hookworm's economic burden worldwide, it is difficult for decision makers such as funders, policy makers, disease control officials, and intervention manufacturers to determine how much time, energy, and resources to invest in hookworm control.

METHODOLOGY/PRINCIPLE FINDINGS: We developed a computational simulation model to estimate the economic and health burden of hookworm infection in every country, WHO region, and globally, in 2016 from the societal perspective. Globally, hookworm infection ...


Effects Of Prebiotics On Gut Bacterial Communities And Healing Of Induced Colitis In Mice, Krystyn Elizabeth Davis 2016 University of Southern Mississippi

Effects Of Prebiotics On Gut Bacterial Communities And Healing Of Induced Colitis In Mice, Krystyn Elizabeth Davis

Master's Theses

Inflammatory Bowel Diseases (IBD) cause chronic inflammation of the gastrointestinal tract and debilitating symptoms in those suffering from the diseases. After inducing colitis in a mouse model using Dextran Sulfate Sodium (DSS), prebiotics inulin and oligofructose enriched inulin (OEI) were used as treatments to determine their effects on the gut microbial community, physiological healing process, and immune response in the mice after initial inflammation and before subsequent inflammation, or relapse. The treatment with inulin led to an increase in regulatory T cell number, but this increase was not as significant as the increase induced by the OEI. Inulin increased the ...


Blimp-1–Mediated Cd4 T Cell Exhaustion Causes Cd8 T Cell Dysfunction During Chronic Toxoplasmosis, Sujin Hwang, Dustin A. Cobb, Rajarshi Bhadra, Ben Youngblood, Imtiaz A. Khan 2016 George Washington University

Blimp-1–Mediated Cd4 T Cell Exhaustion Causes Cd8 T Cell Dysfunction During Chronic Toxoplasmosis, Sujin Hwang, Dustin A. Cobb, Rajarshi Bhadra, Ben Youngblood, Imtiaz A. Khan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported inToxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a ...


Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva 2016 University of Louisville

Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva

Electronic Theses and Dissertations

Background: Hyperhomocysteinemia (HHcy) has been observed to promote hypertension, but the mechanisms are unclear. Toll-like receptor 4 (TLR-4) is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. TLR-4 activation has been shown to promote inflammation that has been associated with pathogenesis of hypertension. In this study, we hypothesize that HHcy induces hypertension by TLR-4 activation that promotes inflammatory cytokine up-regulation (IL-1β, IL-6, TNF-α) and initiation of mitochondrial dysfunction leading to cell death and chronic vascular inflammation. Methods: To test this hypothesis, we used C57BL/6J mice (WT); Cystathionine-β-synthase deficient mice (CBS+/-) with genetic ...


In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah 2016 University of Louisville

In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah

Electronic Theses and Dissertations

Klebsiella pneumoniae causes an acute respiratory infection in human with severe outcomes and high mortality rates even with antibiotic treatment. Even with its critical clinical importance, few virulence systems have been identified for K. pneumoniae limiting the development of new therapeutic strategies. Accordingly, we performed Next Generation sequencing for the strain ATCC 43816, a virulent strain in mouse respiratory disease models, and compared its genomic data with two previously sequenced strains NTUH-K2044 and MGH 78578 for the purpose of identifying genes required for colonizing host lungs. Furthermore, the virulence potential of the three K. pneumoniae strains were tested in a ...


The Immunomodulatory Role Of Adjuvants In Vaccines Formulated With The Recombinant Antigens Ov-103 And Ov-Ral-2 Against Onchocerca Volvulus In Mice., Jessica A. Hess Ligas, Bin Zhan, April R. Torigian, John B. Patton, Nikolai Petrovsky, Tingting Zhan, Maria Elena Bottazzi, Peter J. Hotez, Thomas R. Klei, Sara Lustigman, David Abraham 2016 Thomas Jefferson University

The Immunomodulatory Role Of Adjuvants In Vaccines Formulated With The Recombinant Antigens Ov-103 And Ov-Ral-2 Against Onchocerca Volvulus In Mice., Jessica A. Hess Ligas, Bin Zhan, April R. Torigian, John B. Patton, Nikolai Petrovsky, Tingting Zhan, Maria Elena Bottazzi, Peter J. Hotez, Thomas R. Klei, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types ...


Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley 2016 George Washington University

Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia.

METHODOLOGY/PRINCIPAL FINDINGS: Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum ...


Inversion Of The Vδ1 To Vδ2 Γδ T Cell Ratio In Cvid Is Not Restored By Ivig And Is Associated With Immune Activation And Exhaustion., Dominic Paquin-Proulx, Nathália Silveira Barsotti, Bianca A N Santos, Ana Karolina B B Marinho, Cristina M Kokron, Karina I Carvalho, Myrthes T Barros, Jorge Kalil, Douglas F. Nixon, Esper G Kallas 2016 George Washington University

Inversion Of The Vδ1 To Vδ2 Γδ T Cell Ratio In Cvid Is Not Restored By Ivig And Is Associated With Immune Activation And Exhaustion., Dominic Paquin-Proulx, Nathália Silveira Barsotti, Bianca A N Santos, Ana Karolina B B Marinho, Cristina M Kokron, Karina I Carvalho, Myrthes T Barros, Jorge Kalil, Douglas F. Nixon, Esper G Kallas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Common variable immunodeficiency (CVID) is defined by low levels of IgG and IgA, but perturbations in T cells are also commonly found. However, there is limited information on γδ T cells in CVID patients. Newly diagnosed CVID patients (n = 15) were enrolled before and after intravenous IgG (IVIg) replacement therapy. Cryopreserved peripheral blood mononuclear cells were then used to study γδ T cells and CVID patients were compared to healthy controls (n = 22). The frequency and absolute count of Vδ1 γδ T cells was found to be increased in CVID (median 0.60% vs 2.64%, P <0.01 and 7.5 vs 39, P <0.01 respectively), while they were decreased for Vδ2 γδ T cells (median, 2.36% vs 0.74%,P <0.01 and 37.8 vs 13.9, P ...


Needle In The Haystack: Combining Intravital Imaging And Mathematical Modeling To Understand How Vaccine-Induced T Cells Find Malaria-Infected Cells In Murine Livers, Vitaly V. Ganusov, Ian Cockburn, Reka Kelemen 2016 University of Tennessee

Needle In The Haystack: Combining Intravital Imaging And Mathematical Modeling To Understand How Vaccine-Induced T Cells Find Malaria-Infected Cells In Murine Livers, Vitaly V. Ganusov, Ian Cockburn, Reka Kelemen

Biology and Medicine Through Mathematics Conference

No abstract provided.


Identification Of Gdf-6 Blocking Antibodies As Anti-Melanoma Therapeutics, Ejemel Monir, Danielle Wisheart, Alec Gramann, Arvind Venkatesan, Mark S. Klempner, Craig J. Ceol, Yang Wang 2016 University of Massachusetts Medical School

Identification Of Gdf-6 Blocking Antibodies As Anti-Melanoma Therapeutics, Ejemel Monir, Danielle Wisheart, Alec Gramann, Arvind Venkatesan, Mark S. Klempner, Craig J. Ceol, Yang Wang

UMass Center for Clinical and Translational Science Research Retreat

Through comparative oncogenomic studies and functional analyses, we have identified the bone morphogenetic protein (BMP) factor GDF6 as a new melanoma oncogene. The secreted, carboxy-terminal portion of GDF6 is the active form that binds to cell-surface receptors to initiate BMP signaling. Targeted antibodies directed against secreted proteins are a proven therapeutic modality in several diseases.

To develop therapeutic antibodies against the active form of GDF6, we generated a panel of monoclonal antibodies. Due to the high similarity of human and mouse GDF6 proteins, the C-terminal GDF6 protein was expressed as bacterial recombinant protein with fusion tags to enhance immunogenicity. The ...


Hiv-1 Genetic Variation Resulting In The Development Of New Quasispecies Continues To Be Encountered In The Peripheral Blood Of Well-Suppressed Patients., Will Dampier, Michael R Nonnemacher, Joshua Mell, Joshua Earl, Garth D Ehrlich, Vanessa Pirrone, Benjamas Aiamkitsumrit, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Jeffrey M Jacobson, Brian Wigdahl 2016 Drexel University College of Medicine

Hiv-1 Genetic Variation Resulting In The Development Of New Quasispecies Continues To Be Encountered In The Peripheral Blood Of Well-Suppressed Patients., Will Dampier, Michael R Nonnemacher, Joshua Mell, Joshua Earl, Garth D Ehrlich, Vanessa Pirrone, Benjamas Aiamkitsumrit, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Jeffrey M Jacobson, Brian Wigdahl

Faculty papers Kimmel Cancer Center

As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, including undetectable viral loads and CD4+ T-cell counts in the normal range, viral mutations continue to accumulate in the peripheral blood compartment over time, indicating either low level reactivation and/or replication. Using patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort, whom have been sampled longitudinally for more than 7 years, genetic change was modeled against to the dominant integrated proviral quasispecies ...


Omcp Mediated Cowpox Virulence And Its Dependence On The Immune Receptors Nkg2d And Fcrl5., Michel Muzi Sun 2016 Washington University in St. Louis

Omcp Mediated Cowpox Virulence And Its Dependence On The Immune Receptors Nkg2d And Fcrl5., Michel Muzi Sun

Arts & Sciences Electronic Theses and Dissertations

Viruses with large DNA genomes, such as cowpox virus, encode many open-reading frames involved in the modulation of the host immune system, facilitating escape from immune detection or downregulation of specific aspects of the host immune response. Investigation of virally-encoded immunoevasins has been instrumental in understanding host-pathogen interactions. Here, we focus on the cowpox virus immunoevasin Orthopoxvirus MHC Class I-like Protein (OMCP) and demonstrate for the first time that OMCP facilitates cowpox virus virulence in vivo. We have previously documented that OMCP binds the activating receptor NKG2D on NK cells as well as the orphan receptor FCRL5 on innate B ...


The Resolution Phase Of Nk Cell Proliferation And Ifn Production Following Viral Infection Are Highly Regulated Processes., Leslie Abigail Fogel 2016 Washington University in St. Louis

The Resolution Phase Of Nk Cell Proliferation And Ifn Production Following Viral Infection Are Highly Regulated Processes., Leslie Abigail Fogel

Arts & Sciences Electronic Theses and Dissertations

In response to MCMV infection, NK cells undergo three distinct phases of proliferation: the non-specific phase mediated by pro-proliferative cytokines; the specific phase mediated by recognition of an MCMV-encoded protein by an NK cell activating receptor, Ly49H; and the resolution phase, whose mechanism is unknown. MCMV infection of RAG mice, which lack all adaptive immune cells, results in prolonged proliferation of NK cells despite similar viral titers compared to wildtype mice. Interestingly, there are different kinetics for Ly49H+ and Ly49H- NK cells. We have identified several additional markers that may distinguish NK cells that have been specifically activated through their ...


Role Of Atg16l1 In Uropathogenic E. Coli Pathogenesis, Jane Symington 2016 Washington University in St. Louis

Role Of Atg16l1 In Uropathogenic E. Coli Pathogenesis, Jane Symington

Arts & Sciences Electronic Theses and Dissertations

Urinary tract infections (UTIs) are among the most common infectious diseases and are primarily caused by uropathogenic E. coli (UPEC). Given the greater incidence of antibiotic resistance among UPEC isolates, it is vital to determine factors and pathways important for an effective host response to UPEC in order to improve therapeutic options for combating UTIs. Autophagy is a cellular degradation pathway that plays important roles in pathogen control and modulation of innate immunity. One essential autophagy protein, ATG16L1, has been further implicated in controlling inflammation due to a common variant of ATG16L1 being associated with increased risk of Crohns disease ...


Genetic Predisposition And M1 Macrophage Polarization Created By Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation, Matthew A. Dale 2016 University of Nebraska Medical Center

Genetic Predisposition And M1 Macrophage Polarization Created By Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation, Matthew A. Dale

Theses & Dissertations

Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Evidence has demonstrated a profound influence of genetic background on AAA formation. The work presented herein discusses two studies: the first demonstrates how genetic components can enhance the susceptibility to AAA formation and the second demonstrates how ECM degradation enhances AAA progression by influencing inflammatory cell phenotypes. An understanding of the pathways involved in AAA pathogenesis can help not only to identify potential patients at risk of AAA development, a heritable disease in which the incriminating component has yet to be ...


A Conserved Dna Repeat Promotes Selection Of A Diverse Repertoire Of Trypanosoma Brucei Surface Antigens From The Genomic Archive., Galadriel Hovel-Miner, Monica R. Mugnier, Benjamin Goldwater, George A. M. Cross, F. Nina Papavasiliou 2016 George Washington University

A Conserved Dna Repeat Promotes Selection Of A Diverse Repertoire Of Trypanosoma Brucei Surface Antigens From The Genomic Archive., Galadriel Hovel-Miner, Monica R. Mugnier, Benjamin Goldwater, George A. M. Cross, F. Nina Papavasiliou

Microbiology, Immunology, and Tropical Medicine Faculty Publications

African trypanosomes are mammalian pathogens that must regularly change their protein coat to survive in the host bloodstream. Chronic trypanosome infections are potentiated by their ability to access a deep genomic repertoire of Variant Surface Glycoprotein (VSG) genes and switch from the expression of one VSG to another. Switching VSG expression is largely based in DNA recombination events that result in chromosome translocations between an acceptor site, which houses the actively transcribed VSG, and a donor gene, drawn from an archive of more than 2,000 silent VSGs. One element implicated in these duplicative gene conversion events is a DNA ...


Impact Of Epigallocatechin-3-Gallate (Egcg), A Broad-Spectrum Anti-Inflammatory, In Controlling Intestinal Factors Contributing To Inflammatory Bowel Disease., Gerald Wayne Dryden, Jr. 2016 University of Louisville

Impact Of Epigallocatechin-3-Gallate (Egcg), A Broad-Spectrum Anti-Inflammatory, In Controlling Intestinal Factors Contributing To Inflammatory Bowel Disease., Gerald Wayne Dryden, Jr.

Electronic Theses and Dissertations

This dissertation explores the role of epigallocatechin-3-gallate (EGCG), as a potential treatment for patients with inflammatory bowel disease (IBD). IBD is a common disorder that causes a great deal of suffering. Our understanding of the etiologies, pathogenic mechanisms, and treatment targets continues to evolve. Many new therapeutic targets are making their way through the pharmaceutical pipelines. However, not all patients benefit from these therapies. EGCG has long been studied as an anti-cancer agent. Most of our understanding of this compound comes from the oncologic literature. As the pathways of oncology and inflammation converge, new lessons can be taken from the ...


Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall 2016 University of Louisville

Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall

Electronic Theses and Dissertations

Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral ...


Use Of Ultraviolet Light Irradiated Multiple Myeloma Cells As Immunogens To Generate Tumor Specific Cytolytic T Lymphocytes, Charles A. Gullo PhD, William Y.K. Hwang, Chye K. Poh, Melvin Au, Geraline Cow, Gerrard Teoh 2016 Marshall University

Use Of Ultraviolet Light Irradiated Multiple Myeloma Cells As Immunogens To Generate Tumor Specific Cytolytic T Lymphocytes, Charles A. Gullo Phd, William Y.K. Hwang, Chye K. Poh, Melvin Au, Geraline Cow, Gerrard Teoh

Charles Gullo

Background:

As the eradication of tumor cells in vivo is most efficiently performed by cytolytic Tlymphocytes (CTL), various methods for priming tumor-reactive lymphocytes have been developed. In this study, a method of priming CTLs with ultraviolet (UV)-irradiated tumor cells, which results in termination of tumor cell proliferation, apoptosis, as well as upregulation of heat shock proteins (HSP) expression is described.

Methods:

Peripheral blood mononuclear cells (PBMC) were primed weekly with UV-irradiated or mitomycin-treated RPMI 8226 multiple myeloma cells. Following three rounds of stimulation over 21 days, the lymphocytes from the mixed culture conditions were analyzed for anti-MM cell reactivity ...


Decoupling Of Normal Cd40/Interleukin-4 Immunoglobulin Heavy Chain Switch Signal Leads To Genomic Instability In Sgh-Mm5 And Rpmi 8226 Multiple Myeloma Cell Lines, William Y.K Hwang, Charles A. Gullo PhD, Jie Shen, Chee Kok Poh, S. C. Tham, G. Cow, M. Au, E. W. E. Chan, G. Teoh 2016 Duke University

Decoupling Of Normal Cd40/Interleukin-4 Immunoglobulin Heavy Chain Switch Signal Leads To Genomic Instability In Sgh-Mm5 And Rpmi 8226 Multiple Myeloma Cell Lines, William Y.K Hwang, Charles A. Gullo Phd, Jie Shen, Chee Kok Poh, S. C. Tham, G. Cow, M. Au, E. W. E. Chan, G. Teoh

Charles Gullo

The processes mediating genomic instability and clonal evolution are obscure in multiple myeloma (MM). Acquisition of new chromosomal translocations into the switch region of the immunoglobulin heavy chain (IgH) gene (chromosome 14q32) in MM, often heralds transformation to more aggressive disease. Since the combined effects of CD40 plus interleukin-4 (IL-4) mediate IgH isotype class switch recombination (CSR), and this process involves DNA double strand break repair (DSBR), we hypothesized that CD40 and/or IL-4 activation of MM cells could induce abnormal DNA DSBR and lead to genomic instability and clonal evolution. In this study, we show that MM cell lines ...


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