Diseases Commons^™

Comorbidity And Quality Of Life Of Hiv-Positive Adults Living In Supportive Housing, Rose Sharp

Dissertations

Problem: Life expectancy for people living with HIV significantly increased with widespread use of antiretroviral therapy, resulting in population increases in comorbidity prevalence. The increased burden of living with both HIV and comorbidities lowers health-related quality of life (HRQoL).

Methods: Using a descriptive, correlational, cross-sectional design, a convenience sample of HIV-positive adults was selected from seven supportive housing communities. Comorbidities were assessed using a modified Self-Administered Comorbidity Questionnaire, and HRQoL using the Patient-Reported Outcome Measurement Information System Scale v1.2 – Global Health.

Results: A sample of 17 (N = 17) adults reported a mean of 4.2 (SD = …

Can Viruses Cause Lupus?, Stephen I. Reeder

Selected Honors Theses

Like so many autoimmune diseases, the exact cause of systemic lupus erythematosus (SLE) remains unknown. Evidence points to both genetics and environment playing roles in the onset of the disease, but neither acts independent of the other. Genetics are the easier of the two to study with recent advances in the field making it easier to isolate genes shared by individuals with the disease. However, genetic studies reveal that there is almost certainly an environmental component to the development of SLE. The underlying pathology and existing research on environmental contributors to the development of SLE suggest that viruses could potentially …

Plasma Proteins That May Cause Parkinson’S Disease And Multiple Sclerosis: A Mendelian Randomization Study, Brigid A. Staley

Dissertations and Theses

Multiple sclerosis (MS) and Parkinson’s disease (PD) are progressively disabling neurologic disorders that profoundly affect quality of life and shorten life expectancy. There is no cure for either disease, and current treatments only alleviate symptoms and may cause serious side effects. The causes of MS and PD are not well understood. Previous epidemiologic studies have documented numerous environmental risk factors for both diseases. However, these studies are inherently prone to bias from confounding which may generate spurious results. The lack of unbiased evidence on environmental causes of MS and PD has been a critical barrier to fully understanding their pathophysiology. …

Cancer-Targeting Immunostimulatory Peptides As An Immunotherapeutic Approach To Cancer, Rachel Montel

Seton Hall University Dissertations and Theses (ETDs)

This dissertation reports the synthesis and biological applications of bifunctional trimeric peptides with B7H6-derived NKp30 binding motifs that serve to activate an immunocytotoxic response in natural killer cells and a GRP78-binding motif that can target tumors that express surface GRP78. In this manner the cancer-targeting immunostimulatory peptides are anticipated to directly bind and activate effector NK92-MI cells while also recognizing and binding to target A549 tumor cells to facilitate NK cell-dependent immunocytotoxicity of the targeted tumors. The NKp30 binding peptide motifs are derived from the tumor associated B7H6 antigen that is often downregulated or shed from the surface of tumors …

The Role Of Regulator Of G Protein Signaling 2 In Inflammatory Cytokine Release In Endotoxemia In Mice, Xin Tong Ma

Electronic Thesis and Dissertation Repository

In sepsis, lipopolysaccharide (LPS) activates toll-like receptor 4 to stimulate the release of inflammatory cytokines (e.g. tumor necrosis factor-alpha, TNF-α), leading to cardiac dysfunction. Regulator of G protein signaling 2 (RGS2) limits G protein-coupled receptor signaling by increasing the rate of G protein deactivation or inhibiting G protein-effector interactions. We hypothesized that RGS2 deficiency would enhance proinflammatory responses in endotoxemia. Adult wild-type and RGS2^-/- C57BL/6 mice and neonatal cardiomyocytes were treated with LPS and assessed for inflammatory responses and cardiac function. Myocardial TNF-α expression was higher in RGS2^-/- mice during endotoxemia. Additionally, cardiac function was impaired in …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Modulation Of Inflammatory Pathway By Inflammatory Inhibitor Jsh-23 Mitigates Diabetic Retinopathy., Rubens Petit Homme

Electronic Theses and Dissertations

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). Its pathology is consisted of the breakdown of the blood-retinal barrier (BRB), particularly the inner blood-retinal barrier (iBRB). The exact mechanism that leads to the iBRB impairment and the development of DR has not been elucidated yet. However, chronic inflammation that is hallmark of the type I DM has recently become a key focus in DR study. Hyperglycemia causes dysregulation of nuclear factor-kappa B (NF-kB); and its constant activation increases the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular adhesion molecule-1 (ICAM-1) in the …

Characterizing T Cell Phenotype In Patients With Hypersensitivity Reactions To Sulfamethoxazole And Beta-Lactam Antibiotics, Christine Caron

Electronic Thesis and Dissertation Repository

Delayed drug hypersensitivity reactions (DHRs) are idiosyncratic, T-cell mediated, and can present days after exposure to the culprit drug, resulting in varying degrees of skin rashes. We hypothesize that differences in activated peripheral T cell subsets and types of mediators released produce different clinical phenotypes of drug hypersensitivity reactions to sulphnamides and beta-lactam antibiotics.

We recruited participants with previous DHRs to sulfamethoxazole or beta-lactams . Peripheral blood mononuclear cells were isolated from participants. T-cell subset proliferation and activation was assessed by T-cell specific surface markers using 3H- thymidine incorporation and flow cytometry, and secreted cytokines were measured using bead-based detection. …

Development And Evaluation Of A Heterogenous Virus-Like Particle (Vlp) Formulation To Achieve Hiv-1 Latency Reversal And Cure., Joshua P. Pankrac

Electronic Thesis and Dissertation Repository

HIV-1 is the etiological agent behind acquired immune deficiency syndrome (AIDS) – a chronic, life-threatening condition that compromises host immune function. After nearly four decades and despite ongoing global efforts, HIV-1 persists in nearly 38 million individuals worldwide. Of this population, only 60% have access to life-saving combination antiretroviral therapy (cART), clearly emphasizing the need to realize a cure. Unfortunately, the establishment of replication-competent provirus in resting CD4+ T lymphocytes represents a significant barrier to HIV-1 curative research. The viral reservoir is highly stable and has a half-life of ~44 months. Therefore, it is unlikely that infection will naturally exhaust …

Exploration Of The Complex Relationship Among Multilevel Predictors Of Prep Use Among Men Who Have Sex With Men In The United States, Kristina M. Rodriguez

Dissertations and Theses

Background: Men who have sex with men (MSM) remain the group most heavily affected by HIV in the United States (US), with MSM of color further disproportionately represented. In July 2012, the US Food and Drug Administration (FDA) approved the use of tenofovir disoproxil fumarate plus emtricitabine (TDF-FTC, Truvada) for use as pre-exposure prophylaxis (PrEP) in HIV-negative adults who are at high-risk of HIV infection. Despite its effectiveness, PrEP prescriptions are reaching only a small proportion of those who could benefit from the drug and prescription rates vary both by race and geographic region. The goal of this dissertation was …

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.

Filifactor Alocis: Resilience And Manipulation Against Neutrophil Effector Functions In A Dysbiotic Oral Environment., Max N. Rogers

College of Arts & Sciences Senior Honors Theses

Periodontitis is a multifactorial chronic inflammatory infectious disease that affects around 50% of the adult population in the USA. Neutrophils, which are the primary immune cells recruited to restore health at sites of infection, are profuse in the gingival space during oral infections. In a community-wide effort, pathogenic oral bacteria hijack neutrophil effector functions to evade killing, resulting in an uncontrollable inflammatory loop that leads into inflammation-mediated tissue injury. One of these harmful emerging oral pathogens, Filifactor alocis, has been shown to evade neutrophil killing and contribute to disease progression. The purpose of this study is to gain a …

Gut Pathophysiology In Mouse Models Of Social Behavior Deficits, Kyla Scott

Undergraduate Honors Theses

Autism spectrum disorders (ASD) encompass neurodevelopment disorders characterized by atypical patterns of development that impact multiple areas of functioning beginning in early childhood. The etiology of ASD is unknown and there are currently no preventative treatment options. Gastrointestinal symptoms are commonly associated comorbidities. The microbiota-gut-brain axis is a multidirectional communication chain that connects the central and enteric nervous system that relates brain function to peripheral intestinal functions. Changes within this axis have been postulated in ASD. For example, the “leaky gut theory” proposes that chronic inflammation is linked to alterations in the bacterial profiles of the gut microbiome and subsequent …

“A Moral Imperative To Prevent Aids”: Race And Religion In Atlanta’S Aids Activism, 1981-1993, Madison Bailey

Honors Theses

The early years of the AIDS epidemic marked a tumultuous period of American history, calling into question the authority of doctors and the ability of scientists to cure disease. Already marginalized groups, such as gay men and intravenous drug users, appeared to be most vulnerable to a deadly virus with no cure or effective treatments. In the face of discrimination, activists rose up to provide necessary services for AIDS patients and advocate on their behalf. This activism uniquely characterized the early AIDS epidemic and permanently changed the field of biomedical research. The current historiography of AIDS activism tends to focus …

Heterogeneous Nuclear Ribonucleoprotein K (Hnrnp K) Overexpression And Its Interaction With Runx1 Rna In Acute Myeloid Leukemia, Marisa Aitken

Dissertations & Theses (Open Access)

Acute myeloid leukemia (AML) is an often devastating hematologic malignancy with 5-year overall survival lingering near 20%. Acquiring a deeper understanding of molecular underpinnings of leukemogenesis will provide a basis for developing more effective therapeutic strategies for patients with AML.

Here, we identified overexpression of hnRNP K as a recurrent abnormality in a subset (~20%) of AML patients. High levels of this RNA-binding protein associated with inferior clinical outcomes in de novo AML. Thus, to evaluate its putative oncogenic capacity in myeloid disease, we overexpressed hnRNP K in murine hematopoietic stem and progenitor cells isolated from fetal liver cells (FLCs). …

Tobacco/Hiv-1-Induced Myeloid Cell-Derived Extracellular Vesicles In Hiv-1 Pathogenesis, Sanjana Haque

Theses and Dissertations (ETD)

Introduction. Smoking, which is highly prevalent in people living with HIV/AIDS, has been shown to exacerbate HIV-1 replication, in part via cytochrome P450 (CYP)-induced oxidative stress. CYP enzymes metabolize cigarette smoke condensate (CSC), causing oxidative stress and cytotoxicity. Our previous studies have demonstrated that CSC and specific CSC constituents, benzo(a)pyrene and nicotine, potentially induce CYPs, resulting in higher oxidative stress and subsequent exacerbation of HIV-1 replication in monocytes and macrophages. However, the exact mechanism behind tobacco-induced, oxidative stress-mediated enhancement of HIV-1 replication is still poorly understood. Extracellular vesicles (EVs) have recently gained attention for their unique nature as intercellular messengers …

Synthesis And Preliminary Ex Vivo Testing Of Sirna Targeting Tcrb: A Proposed Therapy For The Treatment Of Autoimmunity, Nicholas J. Magazine

LSU Doctoral Dissertations

Abstract

Background:

As of 2018, the United States National Institutes of Health estimate that over half a billion people worldwide are affected by autoimmune disorders. Though these conditions are prevalent, treatment options remain relatively poor, relying primarily on various forms of immunosuppression which carry potentially severe side effects and often lose effectiveness overtime. Given this, new forms of therapy are needed. We propose small-interfering RNA (siRNA) for hypervariable regions of the T-cell receptor β-chain gene (TCRb) as a highly targeted, novel means of therapy for the treatment of autoimmune disorders.

Objectives:

To develop methods to produce siRNA targeting …

Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.

First, we generated a novel transgenic animal using the epithelial-specific …

Organic Compound Farnesol Reduces Disease Severity And Onset In Mouse Model Of Multiple Sclerosis, Lacey B. Sell

EWU Masters Thesis Collection

No abstract provided.

Mast Cells As Novel Effector Cells In The Pathogenesis Of Chronic Graft-Versus-Host Disease, Ethan Strattan

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host-disease (GVHD), a condition wherein the donor cells recognize the patient tissues as non-self. GVHD can manifest anywhere from weeks to decades post-transplant and is classified as either acute or chronic GVHD, both of which are significant causes of transplant-related morbidity and mortality.

However, GVHD is a complex, multifactorial, and enigmatic disease. The factors driving GVHD at the cellular and molecular level are incompletely understood. Immunosuppression targeting T-cells has …

Quantifying The Heterogeneity Of The Immunoglobulin G N-Glycome In An Ageing Australian Population: The Busselton Healthy Ageing Study, Alyce Russell

Theses: Doctorates and Masters

The use of immunoglobulin G N-glycomics to study chronic non-communicable disorders and other complex phenotypes emerged following the Human Genome Project. The consortium discovered that most phenotypes were too complex to be explained by genetics alone. Thus, the biological importance of epigenetics was recognised; heritable modifications to gene expression rather than the genome itself. Nglycosylation is a form of epigenetic regulation known as a post-translational modification. It stabilises the immunoglobulin G structure and alters downstream responses elicited by the antibody and is extensively studied as a candidate biomarker in the post-genomic era.

The N-glycosylation of immunoglobulin G itself is complex, …