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Role Of Amyloid Beta Assembly State In The Human Immune Response, Deepa Viswanathan

Dissertations

Alzheimer’s disease (AD) is a slowly progressing neurodegenerative disease that leads to dementia. Histopathological hallmarks that characterize AD are senile plaques formed by extracellular deposition of Amyloid beta (Aβ) peptide and intracellular aggregates of hyperphosphorylated tau protein. The plaques, which are found in the brain parenchyma, comprise both 40 and 42 residue Aβ. Aggregation of Aβ is an established pathogenic mechanism in AD, but little is known about the initiation of this process in vivo. Several studies have revealed significant inflammatory markers such as activated microglia and cytokines surrounding the plaques. Plaques are a hallmark of AD, but they are …

Tobacco-Induced Changes To Porphyromonas Gingivalis Gene Expression, Phenotype And Host-Pathogen Interactions., Juhi Bagaitkar

Electronic Theses and Dissertations

Tobacco smoke is a strong and independent risk factor for several chronic systemic diseases and also increases susceptibility to a multitude of bacterial infections, including periodontal infections. Periodontitis is a chronic inflammatory disease of the supporting tissues of the periodontium caused by its chief etiological agent, Porphyromonas gingivalis . Smokers are more prone to persistent infections by P. gingivalis , and harbor higher numbers of P. gingivalis than non-smokers. However, smokers show reduced clinical signs of inflammation compared to non-smokers, making diagnosis of periodontal disease in smokers problematic. While several studies delineate the different mechanisms of how tobacco smoke alters …

The Role Of Muc1 Splice Variants In Dry Eye And Inflammation., Yoannis Imbert-Fernandez

Electronic Theses and Dissertations

Mucin 1 (MUC1) is a plasma membrane-bound glycoprotein that plays a protective role in corneal epithelial cells. Two full-length splice variants of MUCl: MUCl/B and MUCl/A, that differ by the inclusion of 27 bp from intron 1 and a SNP in MUCl/A, but have identical C-terminal cytoplasmic domain (CD) sequences, were identified in human conjunctival tissue. I tested the hypothesis that MUC1 splice variants are key immunoregulators that act on the ocular surface to protect the ocular surface from inflammation and that their expression correlates with dry eye status. The expression of MUC1/A and MUCl/B splice variant was examined in …

Dietary Milk Fat Globule Membrane Reduces The Incidence Of Aberrant Crypt Foci In Fischer-344 Rats And Provides Protections Against Gastrointestinal Stress In Mice Treated With Lipopolysaccharide, Dallin R. Snow

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Milk fat globule membrane surrounds the fat droplets of milk. It is a biopolymer containing primarily membrane glycoproteins and polar lipids which contribute to its properties as a possible neutraceutical. The aims of the studies were to determine if dietary milk fat globule membrane: (1) confers protection against colon carcinogenesis; and (2) promotes gut mucosal integrity while decreasing inflammation compared to diets containing corn oil or anhydrous milk fat.

Aim 1. Three dietary treatments differing only in the fat source were formulated: (1) AIN-76A, corn oil; (2) AIN-76A, anhydrous milk fat; and (3) AIN-76A, 50% milk fat globule membrane, 50% …

Activation Of The Innate Immune Response By The Alzheimer's Amyloid Beta Protein Via Toll-Like Receptors, Udan Lourdes Maria

Dissertations

Alzheimer’s Disease (AD) is the most common form of neurodegenerative disease characterized by the generation and deposition of amyloid beta plaques and the formation of neurofibrillary tangles. A wealth of data now demonstrate that inflammation is a prominent feature in AD pathology and a potential therapeutic target for the treatment and prevention of the disease. The emergence of evidence linking amyloid beta protein (Aβ), the primary component of senile plaques, to inflammation has led to new insights into understanding AD pathology. Aβ, a protein fragment resulting from cleavage of human amyloid precursor protein (APP), primarily exists in two forms: a …

Arsenic In Drinking Water Causes Gene Expression Changes In The Liver Related To Inflammation And Metabolic Dysfunction And Accelerates Atherosclerosis In Apoe-/-Mice, Matthew R. Zajack

Electronic Theses and Dissertations

Arsenic exposure in drinking-water is a significant worldwide health problem. It causes adverse human health effects, such as cancer, increases the risks for others such as cardiovascular disease, and accelerates atherosclerosis. In this study, we analyze arsenic-induced gene expression changes in the liver of ApoE-knockout mice given 49 ppm arsenic in drinking-water. We hypothesize chronic arsenic exposure accelerates atherosclerosis by disrupting liver homeostasis, causing aberrant gene expression changes. Networks revealed hubs on 3 stress-response MAP kinase pathways, ERK, JNK, and p38. Pathways revealed mitochondrial dysfunction and oxidative phosphorylation enrichment from the gene set. Transcription factor binding site analysis revealed specific …

The Relationship Between Fam5c Snp (Rs10920501) Variability, Metabolic Syndrome, And Inflammation, In Women With Coronary Heart Disease, Jennifer L. Cline

USF Tampa Graduate Theses and Dissertations

The leading cause of death among women is coronary heart disease (CHD), a multifactorial disease with polygenic heritability estimated at 50%. Polymorphisms in the family with sequence similarity 5, member C’ (

FAM5C) gene have been associated with myocardial infarction (MI), and one single-nucleotide polymorphism (SNP) has partially accounted for linkage in an acute coronary syndrome subset. The linkage peak on FAM5C corresponds directly with a quantitative trait locus for the inflammatory biomarker monocyte chemoattractant protein 1, as well as a linkage peak to metabolic syndrome (MetS). Metabolic syndrome increases the risk of developing CHD, and MI has been positively …

The Relationship Between Fam5c Snp (Rs10920501) Variability, Metabolic Syndrome, And Inflammation, In Women With Coronary Heart Disease, Jennifer L. Cline

USF Tampa Graduate Theses and Dissertations

The leading cause of death among women is coronary heart disease (CHD), a multifactorial disease with polygenic heritability estimated at 50%. Polymorphisms in the family with sequence similarity 5, member C' (FAM5C) gene have been associated with myocardial infarction (MI), and one single-nucleotide polymorphism (SNP) has partially accounted for linkage in an acute coronary syndrome subset. The linkage peak on FAM5C corresponds directly with a quantitative trait locus for the inflammatory biomarker monocyte chemoattractant protein 1, as well as a linkage peak to metabolic syndrome (MetS). Metabolic syndrome increases the risk of developing CHD, and MI has been …

Damage-Induced Inflammation And Nociceptive Hypersensitivity In Drosophila Larvae, Daniel T. Babcock

Dissertations & Theses (Open Access)

Mounting an effective response to tissue damage requires a concerted effort from a number of systems, including both the immune and nervous systems. Immune-responsive blood cells fight infection and clear debris from damaged tissues, and specialized pain receptors become hypersensitive to promote behavior that protects the damaged area while it heals. To uncover the cellular and molecular mechanisms underlying these processes, we have developed a genetically tractable invertebrate model of damage-induced inflammation and pain hypersensitivity using Drosophila larvae.

To study wound-induced inflammation, we generated transgenic larvae with fluorescent epidermal cells and blood cells (hemocytes). Using live imaging, we monitored the …

Synthesis Of Novel Cannabinoid Ligands And Their Use As Anti-Glioma And Anti-Inflammatory Agents, Steven Neal Gurley

Theses and Dissertations (ETD)

Following the discovery of the cannabinoid receptors, research in the field of cannabinoids has grown exponentially over the last two decades. Cannabinoids have been shown to have tremendous therapeutic potential in the treatment of several pathological conditions ranging from inflammation to asthma, multiple sclerosis, Parkinson’s disease, epilepsy, glaucoma, septic shock, hemorrhagic shock, and cancer. Our research has focused on two major conditions for which cannabinoids hold great promise for drug development, namely, cancer and inflammation.

Our focus in the field of cancer has been on the devastatingly lethal brain tumor glioblastoma multiforme. Due to the high expression of the CB2 …

Preeclampsia, Autoimmunity And The At1 Receptor, Roxanna A. Irani

Dissertations & Theses (Open Access)

Preeclampsia (PE) is a disease of late pregnancy characterized by maternal hypertension and proteinuria. It is associated with preterm delivery and significant perinatal morbidity and mortality. Despite affecting ~7% of first pregnancies, there is no effective screening method to identify women at risk, nor is there a definitive treatment other than delivery of the baby and placenta. Though the pathogenesis of PE remains unclear, an imbalance in the renin-angiotensin and immune systems are thought to be major contributors. Bridging these two concepts, it has recently been shown that women with PE harbor specific autoantibodies: the angiotensin II type 1 receptor …

Stuck Together: Searching For A Model Of Peritoneal Adhesions Using The August Rat, James W. Bathe

Honors Theses

Fibrous adhesions, a by-product of the healing process, often appear post-surgically as a result of peritonitis related to the surgery. These adhesions can be either primarily "scar tissue" or excess "healthy tissue," and are the leading cause of intestinal obstruction in modern medicine. Shockingly, adhesions occur in up to 96% of patients undergoing intra-abdominal surgery. Adhesions can lead to multiple complications other than obstructions such as inadvertent enterotomy at the time of adhesiolysis, chronic pain, and female infertility. Additional complications arise from the adhesions preventing the free movement of organs and causing strangulations. The causes of the peritonitis, and therefore …

Novel Cinnamic Acid-Based Dehydropolymers For Emphysema: In Vitro And In Vivo Assessment Of Their Activities, Bhawana Saluja

Theses and Dissertations

Pulmonary emphysema is a serious worldwide illness, causing progressive and irreversible alveolar wall loss and difficulty in breathing. It is caused mostly by cigarette smoking. However, its unresolved complex and multiple pathogenic mechanisms have left this disease without effective pharmacotherapy. This project hypothesized that cinnamic acid-based dehydropolymers (DHPs), originally discovered as novel anti-coagulants, protect against emphysema through their potent triple inhibitory actions against oxidative stress, inflammation and elastase, some of the pathogenic mechanisms associated with this disease. Three in vitro inhibitory activity assays for oxidative stress, lung inflammation and neutrophil elastase (NE) were developed and used to identify the most …

Dna-Damage-Independent Mitochondrial Dysfunction Drives A Loss Of Retina Function Prior To Neuron Death In The Harlequin Mouse Model Of Aging, Alex Michael Laliberte

Digitized Theses

Although there are many aging-associated retinal diseases, the aging mechanisms which initiate retinal disease remain elusive. To investigate this problem, a model of premature aging, the harlequin mouse, was examined for deficits in retinal function, anatomy and histology, as well as changes in retinal oxidative stress, gene expression and mitochondrial DNA damage. Retinal function of the harlequin mouse, as assessed by electroretinography, was compromised in advance of change in retinal anatomy and histology. Functional deficits occurred in parallel with increased oxidative stress, assessed by in situ dihydroethidium staining. Furthermore, microarray transcriptome analysis of harlequin mice identified markers of mitochondrial stress, …

Survival And Inflammation In Patients With Heart Failure: The Impact Of Overweight, Obesity, Diabetes And Fruit And Vegetable Consumption, Heather Payne-Emerson

University of Kentucky Doctoral Dissertations

Overweight and obesity are paradoxically associated with better survival in patients with heart failure (HF). This association is poorly understood, in part because the impact of diabetes (DM) on survival of overweight and obese HF patients has not been considered. Inflammation may contribute to worse survival in overweight and obese HF patients with DM, and levels of inflammation may be associated with fruit and vegetable consumption. However, neither of these relationships has been investigated in patients with HF.

The purposes of this dissertation were to a) examine the effect of DM on survival of overweight and obese patients with HF, …

A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison

All ETDs from UAB

Chronic neutrophilic inflammation is a hallmark of numerous pulmonary diseases. It is commonly associated with declining lung function, collagen turnover, and increased protease activity. Our laboratory has recently published several articles describing a biologically active collagen breakdown product, proline-glycine-proline (PGP) and its more active amino-terminus acetylated form, N-α-PGP. PGP acts via classical chemokine receptors CXCR1 and 2 to draw neutrophils (PMNs) into sites of inflammation in what is potentially a feed-forward mechanism of disease. The tri-peptide appears to be a bio-marker in certain clinical diseases like cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The present work first details …

In Vivo Labeling Of Immune Cells For Tracking Using Magnetic Resonance Imaging, Shruti Krishnamoorthy

Digitized Theses

In the last two decades, iron oxide nanoparticles have been widely used to label cells in vivo for MRI-based tracking of cellular infiltration and inflammation in disease and injury. The goal of this thesis was to investigate the potential for in vivo labeling of immune cells in healthy mice. Healthy mice were administered iron based contrast agents intravenously (i.v) and MRI was performed longitudinally to detect and monitor signal changes in the liver, spleen, bone marrow and lymph nodes. Histology and flow cytometry were used to verify the presence of iron within cells. We show that cells in the bone …

Exercise-Induced Alterations In Melanocortin Receptor Expression And Inflammation, Tara Michelle Henagan

LSU Doctoral Dissertations

Inflammatory cytokines play a significant role in the pathogenesis of obesity-related diseases and have been implicated as integral factors in both early and late phases of atherosclerosis. Lifestyle modifications such as increasing physical activity and making dietary changes to induce weight loss are part of the primary prescription for the treatment of metabolic syndrome. Additionally, physical activity has been implicated as a potentially effective regimen for the control of inflammation, yet little is known about the anti-inflammatory mechanistic alterations induced by physical activity.

Exercise training causes acute changes in inflammation immediately post exercise, evidenced by upregulation of inflammatory cytokines and …