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Effects Of Agonistic Anti-Cd137 Antibody On Chikungunya Virus Infection And B Cell Responses, Jun Hong 2020 Washington University in St. Louis

Effects Of Agonistic Anti-Cd137 Antibody On Chikungunya Virus Infection And B Cell Responses, Jun Hong

Arts & Sciences Electronic Theses and Dissertations

CD137, a member of the tumor necrosis factor receptor superfamily of cell surface proteins, acts as a costimulatory receptor on T cells, natural killer cells, B cell subsets, and some dendritic cells. Agonistic anti-CD137 monoclonal antibody (MAb) therapy has been combined with other chemotherapeutic agents in human cancer trials. Based on its ability to promote tumor clearance, we hypothesized that anti-CD137 MAb might activate immune responses and resolve chronic viral infections. We evaluated anti-CD137 MAb therapy in a mouse infection model of chikungunya virus (CHIKV), an alphavirus that causes chronic polyarthritis in humans and is associated with reservoirs of CHIKV …


Regulation And Function Of Trem2-Dependent Pathways In Neurodegeneration, Wilbur Madison Song 2020 Washington University in St. Louis

Regulation And Function Of Trem2-Dependent Pathways In Neurodegeneration, Wilbur Madison Song

Arts & Sciences Electronic Theses and Dissertations

Carriers of the R47H allele of the microglia-specific lipid receptor TREM2 have a greatly increased risk of developing Alzheimerճ disease. The objective of this dissertation is to develop further mechanistic knowledge about how TREM2 is regulated and how TREM2 mutations affect microglia and neurodegeneration. Using an in vitro reporter assay, we find that several AD risk-associated TREM2 mutations decrease ligand-dependent activation. Using humanized TREM2 mice, we find that in vivo, the R47H mutation leads to reduced microglia activation and response to A_, as well as decreased shedding of soluble TREM2. These results suggest that TREM2 is protective during disease. We …


The Enzymatic Function Of The Tir Domain: From Axon Degeneration To Innate Immunity, Kow Essuman 2020 Washington University in St. Louis

The Enzymatic Function Of The Tir Domain: From Axon Degeneration To Innate Immunity, Kow Essuman

Arts & Sciences Electronic Theses and Dissertations

The Toll/Interleukin-1 Receptor (TIR) domain is an evolutionarily ancient protein domain conserved from bacteria to eukaryotes, and is an essential signaling component of innate immunity pathways. In animal innate immunity, TIR domains have primarily been described for their scaffolding function in assembling protein complexes in host defense. In plant immunity, TIR domains are key components of the intracellular Nucleotide Binding Leucine rich repeat (NLR) immune receptors that confer resistance to pathogens. These NLR receptors trigger cell death and an immune response upon activation, but their mechanism has remained elusive. In bacteria, TIR domain proteins have been suggested to function as …


Identification And Characterization Of A Novel Non-Homologous End Joining Factor Mri, Putzer Joseph Hung 2020 Washington University in St. Louis

Identification And Characterization Of A Novel Non-Homologous End Joining Factor Mri, Putzer Joseph Hung

Arts & Sciences Electronic Theses and Dissertations

Non-homologous end joining (NHEJ) is the predominant DNA double-strand break (DSB) repair pathway in G1-phase cells. In particular, developing lymphocytes utilize NHEJ to repair physiologic DSBs generated during the processes of antigen receptor gene assembly and class-switch recombination (CSR). Thus, proper regulation of NHEJ is important not only for immune repertoire diversification, but also for the prevention of chromosomal translocations or deletions that can arise from misrepaired DSBs. The XRCC4-like factor (XLF) has been strongly implicated in promoting NHEJ, presumably by tethering broken DNA ends together in a sleeve-like complex, but its necessity appears to be cell context-dependent. While XLF …


Metabolic Requirements Of Nk Cell Responses To Viral Infection, Annelise Yoo Mah-Som 2020 Washington University in St. Louis

Metabolic Requirements Of Nk Cell Responses To Viral Infection, Annelise Yoo Mah-Som

Arts & Sciences Electronic Theses and Dissertations

In recent years, the field of immunometabolism – the study of how specific changes in cellular metabolism regulate the function of diverse immune cell types—has grown exponentially. Several in vitro studies have examined the metabolic regulation of natural killer (NK) cells, which are first responders for viral infection and malignant transformation; however, much less is known regarding the role of metabolism in directing NK cell responses in vivo, such as during viral infection. In order to examine how NK cell antiviral function is regulated in vivo, we used a wellcharacterized infection with murine cytomegalovirus (MCMV) to assess NK cell cytokine …


Effects Of Toxoplasma Gondii Infection On Nk Cells And Ilc1s, Eugene Park 2020 Washington University in St. Louis

Effects Of Toxoplasma Gondii Infection On Nk Cells And Ilc1s, Eugene Park

Arts & Sciences Electronic Theses and Dissertations

Natural killer cells and Type I innate lymphoid cells (ILCs) are subsets of ILCs. In C57BL/6 mice, they share expression of the surface markers NK1. 1 and NKp46, and can produce the cytokine interferon-gamma. These similarities led to the initial classification of natural killer cells and Type I ILCs together under the category of Group 1 ILCs. However, more recent studies found that natural killer cells and ILC1s develop from distinct progenitor cells and utilize transcription factor in distinct manners. Whereas ILC1s require Tbet for their development and are Eomes-independent, natural killer cells require Tbet only for terminal maturation and …


Epigenetic And Signaling Pathways Regulating The Maintenance Of Cd8 T Cell Identity And Function, Daniel Verbaro 2020 Washington University in St. Louis

Epigenetic And Signaling Pathways Regulating The Maintenance Of Cd8 T Cell Identity And Function, Daniel Verbaro

Arts & Sciences Electronic Theses and Dissertations

In response to infection, antigen specific CD4 and CD8 T cells rapidly divide to provide help to the immune system and promote cytotoxicity of infected cells, respectively. Through this rapid division, CD4 and CD8 T cells maintain silencing of the opposing lineage’s genes, which is essential to acutely eliminating pathogens. However, not all pathogens are acutely eliminated even when silencing is maintained, and the pathogen persists in the presence of activated CD8 T cells. CD8 T cells chronically exposed to antigen are phenotypically different than CD8 T cells acutely exposed to antigen, but CD8 T cell still exert control over …


Signaling Mechanisms In Adaptive Immunity, Saravanan Raju 2020 Washington University in St. Louis

Signaling Mechanisms In Adaptive Immunity, Saravanan Raju

Arts & Sciences Electronic Theses and Dissertations

The adaptive immune response consists of interplay between CD4 T cells, CD8 T cells, and B cells which function in control of pathogen in the host. T cells responding via their TCR express cytokines and costimulatory molecules that support direct effector activity and also promote high-affinity antibody generation through augmenting of B cell responses. However, the molecular components that contribute T cell function to balance viral control and the potential for host damage are incompletely understood. In this work, we establish a role for the adaptor molecule CD2AP in modulation of CD4 T cell responses to chronic LCMV infection in …


Diagnosis Of Peanut Allergy Using Continuous Likelihood Ratios, nalin ug 2020 University of Missouri-Kansas City

Diagnosis Of Peanut Allergy Using Continuous Likelihood Ratios, Nalin Ug

Research Days

No abstract provided.


Two Cases Of Severe Combined Immunodeficiency Disease With No Known Variants Identified In Genes Associated With Immunodeficiencies, Megan H. Tucker 2020 Children's Mercy Kansas City

Two Cases Of Severe Combined Immunodeficiency Disease With No Known Variants Identified In Genes Associated With Immunodeficiencies, Megan H. Tucker

Research Days

No abstract provided.


What Are The Rhetorical Strategies And Consequences Of Food Labels Regarding Health, Lifestyle, And Ethics Of Consumers With Food-Related Diseases And Allergies?, Delaney Borchers 2020 Bowling Green State University

What Are The Rhetorical Strategies And Consequences Of Food Labels Regarding Health, Lifestyle, And Ethics Of Consumers With Food-Related Diseases And Allergies?, Delaney Borchers

Master of Arts in Media and Communication Plan II Graduate Projects

In this study, it is investigated on how health, lifestyle and ethical factors of a consumer with a gluten-related disease and allergy influence their understanding and awareness of gluten-free food labels. This study was implemented through an online survey on a Facebook support group with a total of 195 respondents. The results show that consumers do have a strong awareness and understanding of the differences between certified gluten-free and non-certified gluten-free food labels. This indicates that having this strong awareness and understanding is influenced based upon a consumer’s health, lifestyle and ethical factors of following a gluten-free diet.


Characterization Of The Effect Of Photobiomodulation On Peripheral Blood Mononuclear Cells And Cd4+ T Cells From Healthy Donors And Multiple Sclerosis Subjects., Miguel Tolentino 2020 University of Wisconsin-Milwaukee

Characterization Of The Effect Of Photobiomodulation On Peripheral Blood Mononuclear Cells And Cd4+ T Cells From Healthy Donors And Multiple Sclerosis Subjects., Miguel Tolentino

Theses and Dissertations

Multiple Sclerosis (MS) is a CD4+ T cell-mediated autoimmune demyelinating disease. The pathogenesis of MS is a combination of a pro-inflammatory autoimmune response coupled with nitrosative and oxidative stress. Mitochondrial dysfunction within the central nervous system (CNS) leads to a reduction of ATP and high concentrations of nitric oxide leads to the production of reactive oxygen and nitrogen species (ROS and RNS), resulting in oxidative and nitrosative stress that damages myelin and axons, leading to axonal loss and disease progression. Nitrosative stress is present in MS even in early stages of disease even before inflammation and the myelin destruction. The …


Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito 2020 Sunrise Health GME Consortium

Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito

HCA Healthcare Journal of Medicine

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system. Clinical manifestations include encephalopathy, motor deficits, ataxia, and meningeal signs. In most cases, ADEM is preceded by either vaccination or viral illness. Here, we present a case with neither of the two predisposing elements.

Discussion: A 28-year-old Hispanic female presenting with substance use and suicidal ideation was placed on an involuntary psychiatric hold, started on olanzapine and scheduled for a psychiatric facility transfer. The following day, she was noted to have neurological deficits when ambulating. Computed tomography of the brain showed a right frontal …


How Immune T-Cell Augmentation Can Help Prevent Covid-19: A Possible Nutritional Solution Using Ketogenic Lifestyle, Ravi k. Kamepalli MD,FIDSA,CWSP 2020 Regional Infectious diseases and infusion ctr,Inc

How Immune T-Cell Augmentation Can Help Prevent Covid-19: A Possible Nutritional Solution Using Ketogenic Lifestyle, Ravi K. Kamepalli Md,Fidsa,Cwsp

The University of Louisville Journal of Respiratory Infections

No abstract provided.


The Reliability Of Histamine Pharmacodynamic Response Phenotype Classification In Children With Allergic Disease., Shaun S Kumar, Xiaoxi Liu, Catherine M Sherwin, Bridgette Jones 2020 Children's Mercy Hospital

The Reliability Of Histamine Pharmacodynamic Response Phenotype Classification In Children With Allergic Disease., Shaun S Kumar, Xiaoxi Liu, Catherine M Sherwin, Bridgette Jones

Manuscripts, Articles, Book Chapters and Other Papers

We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenotypes predicted response plots and the sum of residuals. The intraclass correlation coefficient (ICC) was …


Food Allergy Among University Students: Uncharted Territory., Ali Hassan, Amna Alsaihati, Malak Al Shammari, Haitham Alaithan, Wejdan Al-Johani, Nouf AlShamlan, Salman Aljubran 2020 Children's Mercy Hospital

Food Allergy Among University Students: Uncharted Territory., Ali Hassan, Amna Alsaihati, Malak Al Shammari, Haitham Alaithan, Wejdan Al-Johani, Nouf Alshamlan, Salman Aljubran

Manuscripts, Articles, Book Chapters and Other Papers

Background: Food allergy is a growing global health concern, with limited studies conducted in developing countries. High-risk behavior regarding allergies is common among young adults, making them prone to severe allergic reactions. This study aimed to estimate the prevalence of food allergies among Imam Abdulrahman Bin Faisal University (IAU) students and to determine the rate of high-risk behaviors in this group.

Methods: An online survey was conducted among IAU students enrolled between the academic years of 2008 and 2018. The survey addressed food allergies with respect to age of onset, allergy testing, self-injectable epinephrine (SIE) prescription, associated allergic conditions, and …


Enhancing Immunization Rates In Two Urban Academic Primary Care Clinics: A Before And After Assessment, Zeeshan Yacoob, Christopher Cook, Fabiana Kotovicz, Jessica J.F. Kram, Marianne Klumph, Marisa Stanley, Paul Hunter, Dennis J. Baumgardner 2020 University of Wisconsin School of Medicine and Public Health; Aurora Health Care

Enhancing Immunization Rates In Two Urban Academic Primary Care Clinics: A Before And After Assessment, Zeeshan Yacoob, Christopher Cook, Fabiana Kotovicz, Jessica J.F. Kram, Marianne Klumph, Marisa Stanley, Paul Hunter, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Purpose: Immunization rates in many cities in the United States remain suboptimal compared to Healthy People 2020 Goals and are lower than national averages. This study aimed to determine whether a lecture-based educational intervention targeted at nurses and medical assistants would improve vaccination rates.

Methods: We conducted a quality improvement study in two urban academic family medicine clinics serving a predominantly Medicaid patient population as well as a sizable proportion of refugees. The intervention consisted of 3 lectures that were delivered to clinic nurses and medical assistants. Vaccinations in 1689 patients — 872 in the 3-month preintervention period, 817 in …


Prophylaxis Of Food Allergen Sensitivity, Dustin Gottfeld 2020 Dominican University of California

Prophylaxis Of Food Allergen Sensitivity, Dustin Gottfeld

Physician Assistant Studies | Student Articles

Food allergies can have a severe and drastic effect on a person’s lifestyle, while prevention of allergic disease can help to ensure others do not have to live with this burden. There are a variety of differing hypotheses that offer explanations for the early development of food allergies, particularly peanut allergies. Two of the foremost hypotheses are the Hygiene Hypothesis and the Dual-Allergen Hypothesis. The Hygiene Hypothesis claims that the diversity of a child’s microbiota creates a beneficial balance of microorganisms which can help prevent the development of allergic disease. Alternatively, the Dual-Allergen Hypothesis states that early environmental exposure to …


Selecting The Optimal Unrelated Hematopoietic Stem Cell Transplant Donor For Relapse Prevention In Acute Myeloid Leukemia, Elizabeth Krieger, Rehan Qayyum, Amir Toor 2020 Section of Hospital Medicine, Department of Internal Medicine

Selecting The Optimal Unrelated Hematopoietic Stem Cell Transplant Donor For Relapse Prevention In Acute Myeloid Leukemia, Elizabeth Krieger, Rehan Qayyum, Amir Toor

Graduate Medical Education (GME) Resident and Fellow Research Day Posters

Introduction/Background

Hematopoietic cell transplantation (HCT) provides

a cure for patients with acute myeloid leukemia.

Natural killer cells (NK) play an important role

in graft versus leukemia (GVL) effect after HCT,

through killer immunoglobulin-like receptor (KIR)

interaction with HLA ligands. This study is

undertaken to validate our previously published

mathematical model accounting for the KIR-KIRL

interactions in a post HCT setting.

Methods

Retrospective data were obtained from the Center

for International Blood and Marrow Transplant

Registry for 2317 donor recipient pairs (DRP) who

underwent 7/8 or 8/8 HLA allelic matched

unrelated donor (URD) HCT for AML. KIR-HLA

interaction scores were calculated …


Characterizing Patch Test Findings In African American Acd Patients, Vaibhav Garg, Bruce Brod, Anthony Gaspari 2020 Thomas Jefferson University

Characterizing Patch Test Findings In African American Acd Patients, Vaibhav Garg, Bruce Brod, Anthony Gaspari

Phase 1

Introduction: Allergic Contact Dermatitis (ACD) in African Americans has not been well studied, and there is little information related to differences in patterns of ACD between African Americans and Caucasians. This paper aims to investigate relative differences in patterns of sensitization in African American ACD patients.

Methods: This study is a retrospective descriptive study. Data of ACD patients patch tested from 2009-2019 by Dr. Gaspari and Dr. Brod at TJUH and HUP/UPHS were reviewed. Patch test findings for African American and Caucasian patients were compared. Outcomes such as positive allergens, strength, clinical relevance, patient occupation, and personal product use …


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