Medicine and Health Sciences Commons^™

Prenatal Genetic Diagnosis Using Transcervically Derived And Immunomagnetically Isolated Trophoblast Cells, Swati Bajpayee

Honors College Theses

Trophoblast cells migrate from the placenta into the endocervical canal early in the first trimester and can be collected non-invasively by transcervical sampling (TCS), potentially providing fetal DNA for prenatal genetic diagnosis. Experiments were conducted to separate fetal cells from maternal cells within the TCS specimens and use the fetal cells to perform genetic analysis. Trophoblast cells were efficiently isolated from TCS specimens during weeks 5-18 of gestation using HLA-G antibody coupled to magnetic nanoparticles. Immunofluorescence microscopy revealed that 99% of isolated cells expressed the chorionic gonadotropin β subunit (β-CG), while the non-bound cell fraction expressed none. Immunomagnetically isolated cells …

Patients' And Caregivers' Inside Perspectives: Living With A Left-Ventricular Assist Device As Destination Therapy, Linda Marcuccilli

Wayne State University Dissertations

Left-ventricular assist devices (LVADs) have improved the quality of life for many patients with advanced heart failure. Past research focused on technology issues and survival rates, but patients' and caregivers' perspectives of living with an LVAD as a destination therapy (e.g., permanent alternative to transplant) was not explored. Roy's adaptation model provided a framework to guide an understanding of how participants adjusted and accepted living with destination therapy. A hermeneutic-phenomenology as described by van Manen was used to explore and describe the essence of destination therapy from patients' and caregivers' perspectives in order to understand the meaning of this experience. …

A Role For Reactive Oxygen Species In Photodynamic Therapy, Michael Price

Wayne State University Dissertations

Photodynamic therapy (PDT) is based on the ability of certain photosensitizing agents to selectively localize in neoplastic cells and their vasculature. Subsequent irradiation at a wavelength corresponding to a photosensitizer absorbance band excites the photosensitizer molecules, leading to energy transfer reactions and fluorescence. It was initially concluded that the phototoxic effect occurred when energy from the excited state of the photosensitizer was transferred to dissolved oxygen to form singlet oxygen. This product has a very brief half-life and will cause cellular damage only in the immediate vicinity of its formation. But an excited-state photosensitizer can also interact with oxygen to …

The Proton-Coupled Folate Transporter: Biology And Therapeutic Applications To Cancer, Sita Desmoulin

Wayne State University Dissertations

Folates are essential cofactors of tumor cell proliferation and survival required for nucleotide biosynthesis and amino acid metabolism. In cancer therapy, inhibition of folate-dependent metabolic pathways has been achieved through the use of antifolates. Unfortunately, the efficacy of many clinically approved antifolates is limited by a lack of tumor selectivity. Facilitative transport of folates into mammalian cells is achieved by the reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). As PCFT is a folate-proton symporter with an acidic pH optimum, PCFT may provide a mechanism for targeting cytotoxic antifolates to tumors, based on their acidic microenvironments. To establish the …

Modulation Of Anti-Tumor Immune Response By Tgf-Β-Inducible Early Gene 1 (Tieg1), Andi Cani

Wayne State University Theses

Cancer immunotherapy has had limited clinical efficacy partly because regulatory T cells (Treg) suppress the immune response to tumor-associated antigens. Inducible regulatory T cells (iTreg), which are converted from naïve CD4 T cells by TGF-β, an abundant cytokine in the tumor microenvironment, may contribute to this immune suppression. Induction of Foxp3 by TGF-β is mediated by the transcription factor TIEG1 and abrogation of this protein prevents Foxp3 expression. We are testing the hypothesis that blockade of TIEG1 to prevent iTreg conversion will enhance immune response in DNA vaccination to the tumor associated antigen Her-2. Wild type and TIEG1 knockout mice …

A Novel Interaction Between 12-Lipoxygenase And Β4 Integrin Plays A Role In Cancer Progression, Sangeeta Joshi

Wayne State University Dissertations

No abstract provided.

Preterm Birth And The Perception Of Risk Among African Americans, Gwendolyn Simpson Norman

Wayne State University Dissertations

Background: African American women deliver preterm at a rate that is two to three times that of their white counterparts, and after decades of research, this disparity in birth outcomes still remains unexplained. While factors including income, education, neighborhood conditions, infection and stress have all been associated with prematurity, no combination of these factors has explained why the disparity persists. Recently, however, racism-specific stress has emerged as a possible factor contributing to this disparity. This study was designed to learn how preterm birth was explained by African Americans directly impacted by prematurity. Methods: Interviews were conducted with African American women …

Type 2 Diabetes And Insomnia: Impact On Metabolic Control, Cheryl Lee Tannas

Wayne State University Dissertations

Diabetes is one of the most serious health challenges in the United States, affecting nearly 21 million Americans. The goal of diabetes management is to maintain the blood glucose close to normal to prevent diabetic complications and therefore extending life expectancy and improving quality of life. Research now indicates a relationship of the quantity and quality of sleep to glycemic control in type 2 diabetics. No research on the impact of insomnia on diabetes prevention and/or management was found in the literature. The purpose of this 11 week intervention study was to examine the effects of participation in Cognitive Behavioral …

Substance P And The Host Immune Response, Megan Elizabeth Foldenauer

Wayne State University Dissertations

This body of work examined the mechanism by which SP regulates host immunity, specifically, its control of growth factors and TLR expression in the P. aeruginosa-infected cornea. The role of mTOR and VIP in corneal infection and inflammation also was tested.

SP has a dual role in bacterial infection, unexpectedly upregulating growth factor production. This was accompanied by macrophage-specific upregulation of pro-inflammatory cytokines, downregulation of anti-inflammatory cytokines, and upregulation of anti-apoptotic genes, as well as a decrease in arginase-producing macrophages (M2 cells), important in stromal healing in these mice. All of these lead to worsened disease, despite the stimulatory effects …

Vip And Host Immunity, Xiaoyu Jiang

Wayne State University Dissertations

The purpose of the current dissertation was to examine how VIP regulates host immunity and corneal healing, specifically, its control of growth factors and TLR expression in the P. aeruginosa infected cornea. Firstly, VIP treatment increased growth factor expression (EGF, GHF, FGF and VEGF) in infected cornea. Notably, treatment with a mixture of EGF, FGF and HGF prevented corneal perforation, reduced pro-inflammatory cytokines and bacterial plate count, while increasing anti-inflammatory cytokines and antimicrobials such as murine beta-defensin2 and 3.

We also investigated the expression of TLR-signaling pathways in P. aeruginosa infected corneas with or without VIP treatment. PCR array and …

Identifying Sm22 As A Key Player In Arterial Diseases, Jianbin Shen

Wayne State University Dissertations

Background : Expression of vascular smooth muscle cell (VSMC) cytoskeleton markers including SM22 is down-regulated in arterial diseases including atherosclerosis where inflammation and osteochondrogenesis are present. However, the role of this downregulation in arterial pathogenesis is unknown. Hypothesis : Downregulation of SM22 may actively contribute to arterial pathogenesis. Methods : Five Sm22 knockout (Sm22^-/-) mice and their wild type littermates were subjected to carotid artery denudation, an artery injury model. Analyses were conducted on carotid arteries 2 weeks after injury. Primary VSMCs were isolated from mouse aortas and investigated individually at passage 2 to 4. Sm22 knockdown was …

Role Of Thromboxane Receptor-Alpha In Prostate Cancer Progression, Prasanna Ekambaram

Wayne State University Dissertations

Thromboxane A2 (TXA2) is a major arachidonic acid metabolite that signals through TXA2 receptors (TP) to induce platelet aggregation and smooth muscle contraction. TXA2 receptors are expressed as two different isoforms in humans, namely TP-alpha (TPα) and TP-beta (TPβ), which have common and distinct signaling pathways. Of the two TP receptor isoforms, studies have shown that TPα impacts tumor growth and progression of lung cancer. Previously our studies demonstrated that activation of Thromboxane receptor by TXA2 agonists could regulate prostate cancer (PCa) cell motility and cytoskeletal reorganization through activation of Rho-A. The primary objective of this study is to investigate …

Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin

Wayne State University Dissertations

Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, compromising p53 activity. Therefore, lymphoma is a suitable model for studying therapeutic value of disrupting HDM2-p53 association by small-molecule inhibitors (SMIs). HDM2 SMIs have been developed and are currently under various stages of preclinical and clinical investigation. This study examined various molecular mechanisms associated and biological effects of two different classes of HDM2 SMIs: the spiro-oxindoles (MI-219) and cis-imidazoline (Nutlin-3) in lymphoma cell lines and patient-derived B-lymphoma cells. Surprisingly, results revealed significant quantitative and qualitative differences between these two agents. At the molecular level, effect of Nutlin-3 was generally more …