Medicine and Health Sciences Commons^™

Mcp-1 In Colorectal Cancer: Benefits Of Exercise, Jamie Lee Mcclellan

Theses and Dissertations

The etiology of colon cancer is a complex phenomenon that involves both genetic and environmental factors. However, only about 20% have a familial basis with the largest fraction being attributed to environmental causes that can lead to chronic inflammation. Tumors associated macrophages drive the pro-inflammatory response in the tumor micro-environment and are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. In chapter 1, we examined the timing and magnitude of the intestinal inflammatory cytokine response in relation to tumorigenesis in …

Associations Between Vitamin D Status, Adiposity, And Inflammatory Biomarkers In Young Women (18 – 30 Years), Adolphina Addo-Lartey

Doctoral Dissertations

We conducted a cross-sectional analysis among 270 (18- to 30-year old) female participants in the UMass Amherst Vitamin D Status Study (n = 270) to assess the extent to which dietary intakes of calcium and vitamin D are associated with obesity markers. We also evaluated the association between serum 25-OHD concentrations and both adiposity and inflammatory biomarkers. Study participants were mostly Caucasians (84.5%) with normal BMI, although about half of women had high adiposity (total body fat ‘TBF’≥ 32%). Women reporting adequate intakes of calcium (≥ 1000 mg/day) but low intakes of vitamin D (< 600 IU/day) were more than twice as likely to have a high percentage of TBF compared to women with adequate intakes of both calcium and vitamin D. In addition, women with lower calcium intake from supplements were twice as likely to have a waist circumference ≥ 80 cm (OR = 2.04; 95% CI: 1.04 – 3.99) compared to women in the highest tertile of calcium intake. The magnitude of this association is important since among young women 18-30 years old, a waist circumference greater than 80 cm indicates central obesity and suggests increased visceral adiposity, which contributes to hyperlipidemia and other obesity-related chronic conditions. Among all women, total vitamin D, food vitamin D, and supplemental vitamin D intake were not associated with serum 25-OHD concentration (P > 0.05). However, among supplement …

Role Of Chronic Inflammation On Liver Function During Cachexia Progression In The ApcMin/+ Mouse Model, Aditi Narsale

Theses and Dissertations

Cachexia is a multifactorial syndrome that manifests during the advanced stage of chronic diseases and is characterized by a progressive loss of body mass sustained by underlying inflammation. The ApcMin/+ mouse is an established model of cachexia that exhibits a gradual loss of body mass correlating with increasing tumor burden and plasma IL – 6 levels. Moreover it also mimics other secondary characteristics observed in cachectic patients like splenomegaly, elevated plasma endotoxin levels, gut barrier dysfunction, hypogonadism and an overall hypermetabolic state. Liver controls the energy metabolism in the body by regulating glucose and lipid metabolism, glycogen storage, filtration of …

Dissecting The Roles Of Trim24 In Regulation Of Hepatic Lipid Metabolism And Inflammation, Lindsey C. Minter

Dissertations & Theses (Open Access)

DISSECTING THE ROLES OF TRIM24 IN REGULATION OF HEPATIC LIPID

METABOLISM AND INFLAMMATION

Lindsey Cauthen Minter, B.S., B.A.

Advisory Professor: Michelle C. Barton, Ph.D.

In this dissertation, I report the characterization of a new mouse model that recapitulates development of hepatocellular carcinoma (HCC) following spontaneous hepatic lipid accumulation, inflammation, and damage of liver tissue, due to complete loss of Trim24 expression. In human HCC and other cancers, TRIM24 expression is aberrantly high, while deletion of TRIM24 in the mouse has been shown to act as a liver specific tumor suppressor. The hypothesis tested here was that TRIM24, the E3 ubiquitin …

The Effect Of Mutations In Prmt5 On Its Ability To Oligomerize, Rachel Scarl

Senior Honors Projects

Atherosclerosis is a cardiovascular disease caused by a chronic inflammatory response in the cells lining blood vessels, vascular endothelial cells. In these cells, a network of interacting proteins regulates inflammation. One of these proteins, PRMT5, regulates the inflammatory response by methylating other proteins involved in inflammation. For PRMT5 to carry out its function, it must first oligomerize with itself and various other proteins. In this study, I determined whether mutations to specific PRMT5 methylation sites affect its ability to oligomerize. By expressing PRMT5 in HEK293 cells and studying the effects of adding a chemical cross-linking agent, DMS, I was able …

Cervical Remodeling/Ripening At Term And Preterm Delivery: The Same Mechanism Initiated By Different Mediators And Different Effector Cells, Juan Miguel Gonzalez Velez

Wayne State University Dissertations

Premature cervical remodeling/ripening is believed to contribute to preterm delivery (PTD), the leading cause of perinatal morbidity and mortality. Despite considerable research, the causes of term and PTD remain unclear, and there is no effective treatment for PTD. We tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied cervical remodeling at term.

We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS)and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophage infiltration and increased serum C3adesArg and C5adesArg …

Symptoms, Cytokines, And Quality Of Life Of Patients With Chronic Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation, Debra Kelly

Theses and Dissertations

Introduction: Chronic graft-versus-host disease (cGVHD) is a serious complication following allo-HSCT characterized by immune dysregulation, organ dysfunction, risk for infection, and distressing symptoms. Complications may include scleroderma, hepatic dysfunction and bronchiolitis obliterans. Advances in allo-HSCT for many hematologic dyscrasias (e.g. acute and chronic leukemias, aplastic anemia, and myelodysplastic syndrome) have improved survival which has generated a renewed focus on survivorship issues. Distressing symptoms are noted as negatively impacting quality of life (QoL). The relationship between inflammation and behavioral responses may impact symptoms. Examining patterns and levels of inflammation with symptoms is relevant. Objective: The aims of this study were to …

Effect Of Tumor Necrosis Factorα On Expression Of Heme-Oxgenase1 In Human Gingival Fibroblasts, Jay Patel

PCOM Biomedical Studies Student Scholarship

Periodontitis is a chronic inflammatory disease that is characterized by activation of gingival fibroblasts to produce matrix metalloproteinases and other inflammatory mediators that contribute to destruction of tissues surrounding the teeth. In the United States, 22% of adults have a mild form of periodontal disease and 13% suffer from a severe form of the disease. In addition to tooth loss, periodontitis is associated with increased risk of several conditions, including diabetes, osteoporosis, rheumatoid arthritis and cardiovascular disease. Heme oxygenase-1 (HO-1) is activated by a wide variety of stressful stimuli and levels are increased in inflamed tissues. HO-1 degrades free heme, …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

Conservative Treatment Of De Quervain’S Tenosynovitis In Occupational Therapy: A Retrospective Outcome Study, Kevin R. Lang, Brittney S. Gibson, Kayleigh M. Oppenhuizen

Hand and Upper Extremity

Objective: De Quervain’s tenosynovitis (DQ) is a painful condition characterized by pain and inflammation at the first dorsal compartment of the wrist. This condition affects the wrist and thumb, and generally decreases an individual’s performance and engagement in daily occupations. Conservative management with occupational therapy (OT) can assist to diminish the associated symptoms and facilitate recovery of function; however, it is unclear what interventions are the most effective. The purpose of this study was to determine the effectiveness of conservative OT interventions for individuals diagnosed with DQ.

Study Design: An exploratory retrospective review of 148 de­‐identified electronic medical records provided …

The Effect Of Obesity On Il-1Β, Il-1ra, And Leptin Following Acute Mental Stress, Heather Caslin

Theses and Dissertations

Research regarding the development of cardiovascular disease (CVD) is important because CVD is the leading cause of death in the United States (US) and many countries abroad. Risk factors, such as obesity and psychological stress, should be studied in order to understand contributing factors for CVD and the cellular mechanisms which link risk factors with the development of disease. Specifically, the combined influence of multiple risk factors on inflammation is of interest because many individuals have more than one risk factor, which additively increases an individual’s risk for CVD. Obesity is already characterized by disordered inflammation, which suggests that the …

Transformation Of Human Mast Cells By Interferon-Gamma And The Potential Role Of Myeloid Derived Suppressor Cells In Mastocytosis., Sahar Lotfi-Emran

Theses and Dissertations

Mast cells respond to a variety of signals, are associated with both increased inflammation and regulation of the immune response, and are able to interact with a variety of hematopoietic and non-hematopoietic cells. The majority of the work that highlights mast cell pleiotropic abilities has been completed in murine models. Though these models have significantly advanced our understanding of what mast cells can do, they cannot inform us as to what mast cells actually do in human beings. The goal of this dissertation is to assess fully mature, primary human mast cell function beyond the well-defined type 1 hypersensitivity function …

Epigenetic Alterations Of Toll-Like Receptors By Tet2 In Spontaneous Preterm Labor, Anuja Chumble

Theses and Dissertations

Increasing evidence implicates the presence of bacteria in intrauterine tissues as an important risk factor for spontaneous preterm labor. Epigenetic alterations of innate immunity genes may increase the mother’s sensitivity to subclinical levels of bacteria. This study examined the presence of TET2, TLR-2, and TLR-9 in intrauterine tissue, and evaluated whether epigenetic alterations of these genes, as well as IL-8, changed their expression in human decidual tissue and a macrophage cell culture. Immunohistochemicalstaining was used to detect the presence of these proteins in intrauterine tissue. Gene expression changes were evaluated in stimulated monocytes and macrophages. Fluorescence immunohistochemistry was used to …

In Utero Exposure To Second-Hand Smoke Aggravates Adult Responses To Inhaled Irritants, Rui Xiao

LSU Doctoral Dissertations

In utero exposure to second-hand smoke (SHS) has modulatory effects on adult lung responses to various irritants. To further elucidate diverse responses with different inhaled irritants and to understand how long the effects persist, we have focused on two environmentally-relevant and asthma-associated irritants--SHS and ovalbumin (OVA)--for adult mice that had been exposed in utero to SHS. We hypothesized that in utero SHS exposure aggravates lung responses to various inhaled irritants, including SHS and OVA, in adult mice beyond the age of 15 weeks; and that the responses will likely exhibit a sex bias. Pregnant BALB/c mice were exposed (days 6-19 …

Impact Of Nutrition On Cognition And Its Association With Blood And Brain Alzheimer Disease Related Biomarkers, Samantha Gardener

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the most common form of senile dementia, currently affects over 35 million people worldwide. While there is no cure or effective treatment, early intervention programs hold considerable promise. Following particular dietary patterns represents one potential intervention strategy accessible to all.

Results from previous studies investigating the association of diet, cognition and biomarkers of AD are inconsistent: Positive results have been reported (1-7), whilst others have shown no associations. Prior to this thesis, no study has assessed the relationship of four dietary patterns to cognition, blood-based and neuroimaging biomarkers of AD in a large highly-characterised ageing cohort. Participants …

The Role Of Microrna In Staphylococcal Enterotoxin B-Induced Inflammation And Acute Lung Injury, Roshni Rao

Theses and Dissertations

Staphylococcal enterotoxin B (SEB) is a potent activator of the Vβ8+T-cells leading to the proliferation of nearly 30% of the T-cell pool. As a consequence, excessive amounts of cytokine mediators are released leading to extensive tissue damage and sometimes toxic shock and death. Due to the ease with which SEB can be aerosolized anddisseminated, it is considered a biological weapon. In the current study, we investigated the pro-inflammatory effects of SEB in two mouse models of acute inflammatory lung injury. Specifically, while inflammatory cues are known to elicit changes in key transcriptional factors and gene expression, we explored for the …