Medicine and Health Sciences Commons^™

The Long-Term Teratogenic Effect Of Prenatal Alcohol Exposure On The Somatosensory And Motor Cortex Of Rats, Tyson Chappell

Theses and Dissertations (ETD)

The primary goal of this dissertation was to examine the long-term effect of prenatal alcohol exposure (PAE) on the primary somatosensory (SI) and primary motor cortex (MI). For over 30 years, PAE has been shown to produce a triad of symptoms (growth deficits, craniofacial dysmorphologies and central nervous system disruptions) diagnosed as fetal alcohol syndrome (FAS) in children and adults. Since low to moderate levels of prenatal alcohol exposure are less likely to produce FAS symptoms in children, the term “PAE” in this dissertation typically refers to heavy/abusive/chronic levels of prenatal alcohol exposure (in humans this equates to 5+ drinks/per …

The Cystic Fibrosis Transmembrane Conductance Regulator: Regulation By Hsp-90, Kevin Marrs

Theses and Dissertations (ETD)

The hypothesis of this project is that a functionally relevant association exists between CFTR and Hsp90. In testing this hypothesis, (a) the association of CFTR and Hsp90 is confirmed via crosslinking and immunoprecipitation of CFTR from stably transfected HEK-293 cells, electrophoretic separation of cross-linked proteins, and protein identification via SDS-PAGE, western blotting, and mass spectrometry. Also, this hypothesis is tested by (b) functionally assessing the effect of Hsp90 on CFTR function via Ussing chamber analysis, two-electrode voltage clamp analysis, preliminary in vivoanimal studies, and protein phosphorylation. The HEK-293 Flag-CFTR cells used in this study allows for a high degree …

Theoretical And Experimental Evaluation Of Spatial Resolution In A Variable Resolution X-Ray Computed Tomography Scanner, Roman Melnyk

Theses and Dissertations (ETD)

A variable resolution x-ray (VRX) computed tomography (CT) scanner can image objects of various sizes with greatly improved spatial resolution. The scanner employs an angulated discrete detector and achieves the resolution boost by matching the detector angulation to the scanner field of view (FOV) determined by the size of an object being imaged. A comprehensive evaluation of spatial resolution in an experimental version of the VRX CT scanner is presented in this dissertation. Two components of this resolution were evaluated – the pre-reconstruction spatial resolution, described by the detector presampling modulation transfer function (MTF), and the post-reconstruction spatial resolution, given …

Tetraspanin Kai1/Cd82 Inhibits Cell Migration-Related Cellular Events Via Reorganizing Actin Network, Wei Liu

Theses and Dissertations (ETD)

To determine how tetraspanin KAI1/CD82, a tumor metastasis suppressor, inhibits cell migration, we assessed which motility-related cellular events are altered by KAI1/CD82 and how KAI1/CD82 regulates these events. We found that KAI1/CD82-overexpressing cancer cells exhibit various morphologies but typically display elongated cellular extensions and a lack of lamellipodia. Live imaging demonstrated that the formation of lamellipodia and retraction of extensions were deficient upon KAI1/CD82 overexpression.

The deficiency in developing motility-related cellular events was accompanied by defects in actin cortical network and stress fiber formations. Notably, actin polymerization was attenuated by KAI1/CD82. Although Rac1 activity was diminished upon KAI1/CD82 expression, Rac1 …

Humanized Chimeric Receptors In The Therapy Of Multiple Sclerosis, Ioana Moisini

Theses and Dissertations (ETD)

The role of autoreactive, antigen-specific T-cells in the development of autoimmunity has long been documented. T-cells expressing chimeric receptors are specifically redirected against such cells and have been proven to suppress autoimmune encephalomyelitis, the murine model of multiple sclerosis. We here demonstrate the ability of humanized chimeric receptors to suppress experimental autoimmune encephalomyelitis (EAE) in a humanized mouse model by redirecting T lymphocytes against autoreactive T-cells. The receptors were synthesized by linking the 84-102 epitope of human myelin basic protein (MBP) to the extracellular and transmembrane domains of the beta chain of human major histocompatibility complex (MHC) class II molecule …

Uncovering P53 Mutations And Abnormal Gene Expression In Pediatric Adrenocortical Cancer, Alina Nico West

Theses and Dissertations (ETD)

Pediatric adrenocortical cancer is extremely rare and often fatal (approximately 0.3-0.4 cases per million worldwide; 50% 5-year survival). The incidence of pediatric adrenocortical cancer in southern Brazil is 10-15 times higher than the worldwide incidence. Due to the rarity of adrenocortical cancer, especially in children, underlying gene dysregulation and mechanisms of tumorigenesis of the adrenal gland are very poorly described in the literature. However, it is well-known that the tumor suppressor p53, which is mutated in over 50% of all human cancers, is commonly mutated in pediatric adrenocortical cancer. In addition, evidence strongly suggests that if a child has adrenocortical …

Enzyme Architecture And Flexibility Affect Dna Topoisomerase I Function, Mariè Van Der Merwe

Theses and Dissertations (ETD)

DNA topoisomerase I (Top1) is a highly conserved enzyme composed of four domains: a positively charged N-terminus; a DNA binding/core domain that circumscribes duplex DNA; a non-conserved linker domain; and a C-terminal/catalytic domain. Top1 catalyzes changes in DNA topology by transient cleavage of a single DNA strand and the concomitant formation of a phosphotyrosyl linkage between the enzyme and the 3’ DNA end. This covalent Top1-DNA complex is the binding site for camptothecin (CPT), which selectively inhibits religation of the cleaved DNA strand. CPT binding stabilizes the covalent complex, while the collision of replication forks with CPT-Top1-DNA adducts produces DNA …

Role Of Medial Prefrontal Cortical Group Ii Metabotropic Glutamate Receptor In The Development Of Cocaine Sensitization, Xiaohu Xie

Theses and Dissertations (ETD)

The current studies examined the role of medial prefrontal cortical (mPFC) group II metabotropic glutamate receptors (mGluR_2/3) in the development of cocaine sensitization. Initial studies demonstrated that intra-mPFC injection of the mGluR_2/3 receptor agonist, APDC, dose-dependently reduced acute behavioral response to cocaine (0.015-15 nmol/side with significant effects starting at 1.5nmol/side). The effects of APDC were prevented by intra-mPFC co-injections of an mGluR_2/3 antagonist, LY341495 (1.5 nmol/side). Repeated intra-mPFC APDC (1.5 nmol/side) injections also prevented the initiation of behavioral and neurochemical sensitization, which is defined as enhanced nucleus accumbens (NAc) dopamine response to cocaine. Once sensitization was …

Development And Evaluation Of Brain Tumor Targeted Liposome Delivery System For Paclitaxel, Murali Krishna Divi

Theses and Dissertations (ETD)

Primary brain tumors are a relatively common cause of cancer-related deaths. High-grade gliomas are the most common type of primary brain cancer, and the affected patients have a median survival of less than 1 year. Almost all malignant gliomas are incurable with the present standards of healthcare. Currently accepted therapeutic adjuvants to surgery, such as radiotherapy and chemotherapy, provide only a minor improvement in the disease course and life expectancy for patients diagnosed with malignant gliomas. Often, chemotherapy has failed to make any significant impact on the prognosis of disease because of significant local and systemic toxicity, problems with transport …

The Role Of Multi-Drug Resistance Associated Protein 4 And P-Glycoprotein In Resistance Of Neuroblastoma To Topotecan And Irinotecan, Patricia Kellie Turner

Theses and Dissertations (ETD)

High-risk neuroblastoma presents a significant therapeutic challenge because the 5-year survival rate remains less than 30% despite the use of surgery, multi-agent chemotherapy, radiation, and autologous bone marrow transplant. Novel therapeutic modalities are under development. The camptothecin analogs topotecan and irinotecan have been identified as successful cytotoxic agents. For topotecan, pharmacokinetically guided dosing to achieve a systemic exposure associated with preclinical anti-tumor activity in neuroblastoma xenograft models is feasible and has elicited favorable responses in children with high-risk neuroblastoma. However, some children with high-risk disease did not respond to the putatively effective topotecan systemic exposure. These children represent a subset …

Age-Associated Hepatic Drug Transporter Expression And Its Implications For Pediatric Pharmacotherapyflexibility Affect Dna Topoisomerase I Function, Lisa Tang

Theses and Dissertations (ETD)

Members of the ATP-binding cassette (ABC) family of drug transporter proteins translocate various endogenous and exogenous substrates across intra- and extracellular membranes. Two specific ABC transporters, the multidrug resistance 1/P-glycoprotein (MDR1/P-gp) and the multidrug resistance protein 2 (MRP2), serve as major hepatic transporters that mediate the biliary excretion of various organic anions and cations along with glutathione-, glucuronate-, or sulfate-conjugates of several drug substrates. However, very little is known about the expression of these transporters in the early infant and childhood ages of human development. We, therefore, characterized the ontogeny of these transporters by measuring their gene and protein expression. …

Cardiopulmonary Predicators Of Dysfunctional Ventilator Weaning Response After Coronary Artery Bypass Graft, Annapoorna Mary

Theses and Dissertations (ETD)

Although the majority of coronary artery bypass graft (CABG) surgery patients are extubated within 6 to 8 hours following surgery, 20% to 40% of patients remain intubated 12 hours after surgery due to dysfunctional ventilator weaning response (DVWR). DVWR associated with increased morbidity and mortality (30% to 43%) following CABG surgery. Finding significant antecedence to predict DVWR could help to identify and prevent the complications from DVWR after CABG surgery. Literature review revealed that there is an association between cardiopulmonary indicators (CPI) and DVWR after CABG surgery. Cardiopulmonary indicators are the selected hemodynamic parameters that have an association with DVWR. …

Dna Binding Specificity Of Mu Transcription Factor C And Crystallization Of C : Dna Complex, Karthik Shanmugantham

Theses and Dissertations (ETD)

The lytic cycle of phage Mu is regulated by a transcriptional cascade consisting of early, middle and late transcription. The Mor protein is an activator of the middle promoter Pm and is encoded by the last gene of the early transcript. The C protein is an activator of the four late promoters Plys, PI, PP, and Pmom and is expressed from the middle transcript. Both Mor and C proteins bind an imperfect dyad-symmetry element just upstream and overlapping the –35 region of Pm and Plys respectively. The main aims of this study was, (1) To understand the binding specificity of …

Neuroadaptive Changes In The Mesocortical Glutamatergic System During Nicotine Self-Administration And After Extinction In Rats, Fan Wang

Theses and Dissertations (ETD)

The mesocorticolimbic pathway is critical in almost all aspects of drug abuse, including nicotine. Though many of the neurochemical and molecular effects of nicotine have been well studied, nicotine’s long-term neuroadaptive effects, specifically within the mesocorticolimbic pathway, are largely undefined. Thus, in current study, we determined the neuroadaptive changes in the mesocortical glutamatergic system during chronic nicotine self-administration (SA), which emulates important aspects of nicotine intake by humans, and after extinction. In the initial study, after 18 days of nicotine SA, in the medial prefrontal cortex (mPFC), NMDA receptor subunit 2A (NR2A) and NR2B were increased by 67% and 83%, …

Synthesis Of Novel Sulfonamide-Based Calpain Inhibitors And Their Potential As Anti-Tumor Agents, Jin Xu

Theses and Dissertations (ETD)

Calpain is a class of intracellular cytoplasmic cysteine proteases.1 The enzyme participates in different intracellular signaling pathways that are mediated by Ca2+.2 The two major isoforms of calpain universally distributed in most mammalian tissues are calpain 1 (µ-calpain) and calpain 2 (m-calpain). The exact in vivo function of the enzyme is not clear, but calpain has been implicated in a variety of physiological and pathological conditions,3 such as cancer, stroke, cardiac ischaemia, muscular dystrophy, cataract and Alzheimer’s disease. Calpain inhibitors are therefore of interest as therapeutic agents and as biomedical tools.

Several potent calpain inhibitors isolated from natural sources as …

Quantitative Analysis Of First- Versus Second-Premolar Extraction Effects In Orthodontic Treatment, Robert A. Turner

Theses and Dissertations (ETD)

Malocclusions can involve arch-size tooth-size discrepancies that have to be resolved by premolar extractions. Treatment planning in such cases usually involves removing first (P1) or second premolars (P2). Choosing an extraction pattern is a learned skill that incorporates many diagnostic factors. This study compared the amounts of in-treatment tooth movement in two common extraction patterns (4/4 and 5/5) in order to gain insight into the criteria used for differential diagnosis and treatment planning. Objective: A method of cast analysis was developed to measure the anteroposterior and transverse changes in tooth positions during orthodontic treatment. Data were used (1) to …

Silver Doped Hydroxyapatite Coating On Titanium Surfaces And Its Effect On Early Bone Response And Osseointegration, Nicole Besu

Theses and Dissertations (ETD)

The clinical success of dental implants is determined mostly by surface properties of implants and interactions with surrounding tissues. Furthermore, clinical success of dental implants is directed by implant surfaces and bone cell responses that promote osseointegration and long-term stability. Hydroxyapatite (HA)-coated Titanium (Ti) implants have been widely used due to its effect on bone response. However, microbial infection is common. One material known to have anti-microbial properties is silver (Ag). However, the effects Ag has on osteoblastic activity as well as decrease bacterial load has yet to be determined.

In this study, the effect of Ag-doped HA coatings on …

Trabecular Calcium Phosphate Scaffolds For Bone Regeneration, Mark Ryan Appleford

Theses and Dissertations (ETD)

Bone tissue engineering represents a strategy for the repair or regeneration of damaged bone in the body. The science underlying this clinical therapy bridges the traditional fields of cell biology, materials science and mechanical engineering with the aim to identify how cells behave on physiologically relevant materials with natural mechanical stimuli. The objectives of this research were to develop and characterize calcium phosphate ceramic scaffolds matched to the local architecture of natural trabecular bone and to apply tissue engineering strategies for the study of cell behavior in both in vitro and in vivo models.The specific role of environment on cell …

Cephalometric Evaluation Of One-Phase And Two-Phase Treatment Alternatives In Matched Class Ii Subjects, Fredrick Jerome Burr

Theses and Dissertations (ETD)

“Early” or two-phase orthodontic treatment of Class II malocclusions is a highly debated topic in the orthodontic literature. We report here on a retrospective cephalometric study of patients with Class II, division 1 malocclusions. One group consisted of 32 consecutively treated patients who received “early” treatment with a Fränkel II appliance followed by treatment with full fixed appliance. These subjects were “matched” by sex and cephalometric value, to a subject treated with standard edgewise appliances in a single phase. Matching criteria focused on the bony facial characteristics, notably ANB, NAP, Y Axis, AOBO, FMA, overjet, and overbite. The question was …

Root Morphology And Sexual Dimorphism : Size Standards For Crown And Root Dimensions In Adolescents, William Max Couch

Theses and Dissertations (ETD)

“Early” or two-phase orthodontic treatment of Class II malocclusions is a highly debated topic in the orthodontic literature. We report here on a retrospective cephalometric study of patients with Class II, division 1 malocclusions. One group consisted of 32 consecutively treated patients who received “early” treatment with a Fränkel II appliance followed by treatment with full fixed appliance. These subjects were “matched” by sex and cephalometric value, to a subject treated with standard edgewise appliances in a single phase. Matching criteria focused on the bony facial characteristics, notably ANB, NAP, Y Axis, AOBO, FMA, overjet, and overbite. The question was …

Depth And Size Limits For The Visibility Of Veins Using The Veinviewer Imaging System, Soujanya Ganesh

Theses and Dissertations (ETD)

Administration of fluids or medication and blood draw procedures require the nurse or the phlebotomist to access the veins in patients at hospitals or phlebotomy centers. It is important to minimize the discomfort associated with sticking needles in the patient more than once and most often, necessary to find an appropriate vein within few minutes. However, problems involved in accessing veins in pediatric and obese patients make it very difficult to perform a successful stick in a short time. The VeinViewer Imaging System is an infrared imaging device that provides the nurses and phlebotomists a means for locating veins in …

Evaluation Of Osseointegration Between Two Different Modalities Of Hydroxyapatite Implant Surface Coatings: Plasma Sprayed Ha Coated Implants And Electrophoresis Deposited Nano Ha Coated Implants, Audrey Marie Selecman

Theses and Dissertations (ETD)

Purpose: The objective of this study was to evaluate the osseointegration between plasma sprayed (PS) hydroxyapatite (HA) coated implants and electrophoresis deposited (EPD) nano hydroxyapatite coated implants in an animal model. The quantity of osseointegration was inferred by interfacial strength and percent tissue-contact length.Materials and Methods: Thirty-six cylindrical implants (18 PS and 18 EPD) were placed into dog mandibles. Nine implants from each group were evaluated with pull out testing and histological studies at 12 weeks after implantation. The remaining implants were occlusally loaded for 9 months and then evaluated by pull out testing and histological studies.Results: Twelve weeks after …

Effects Of Tricalcium Phosphate Coated Titanium On Adjacent Early Bone Formation, Bristol Williams

Theses and Dissertations (ETD)

Dental implants are the gold standard of restorative dentistry today. Implants have been used for several years in Orthopedics. Dental implants are an important treatment option for several patients today. When a patient is fully or partially dentate, they are given the opportunity to restore their dentition in ways similar to their natural oral cavity. The past literature states that titanium is one of the first metals used in implant placement. There have been many improvements made on this material. Most modifications have been used in order to promote more bone growth around these implants. Several different coating materials have …

Molecular Mechanism Of Tetraspanin Cd9 Mediated Cell Motility, Jayaprakash Kotha

Theses and Dissertations (ETD)

CD9, a member of the tetraspanin superfamily of proteins participates in the regulation of cell adhesive functions such as cell migration. The mechanisms underlying CD9 mediated cell migration are not known. In the current study, we investigated the molecular basis for the CD9 promoted cell migration. Our findings show that the phosphatidylinositol-3 kinase (PI-3K) inhibitors, wortamannin and LY294002 inhibited CD9 promoted cell motility in Chinese hamster ovary (CHO) cells. In contrast, inhibitors targeting protein kinase C or mitogen-activated protein kinase had no effect on CD9 driven CHO cell motility. Furthermore, inhibition of PI-3K activity in CHO cells by dominant/negative PI-3K …

Gastric Myoelectrical Activity In Patients With Diabetes, Sandra Luberata Holmes

Theses and Dissertations (ETD)

This descriptive, correlational study investigated the associations among gastric myoelectrical activity (GMA), upper gastrointestinal (GI) symptoms, and glucose control. The study also attempted to determine whether any relationship existed between upper GI symptoms, glucose control, age, or length of diagnosis and pattern of GMA identified using electrogastrography (EGG). A total of 25 persons participated in the study. The sample was comprised of 7 healthy controls, 5 patients diagnosed with type 1 diabetes, and 13 patients diagnosed with type 2 diabetes. Electrogastrography was performed for 30 minutes in the fasting state and continued at 30-minute intervals for a total of 1-1/2 …

Health Barriers, Health Perceptions, And Cardiovascular Risk Factors Of Adolescent Black American Males, Desmarie Jackson Decuir

Theses and Dissertations (ETD)

Area of Investigation: Cardiovascular (CV) diseases are the leading cause of death among Black American adult males. Health behaviors that contribute to CV disease are probably learned during adolescence yet few researchers have studied the factors that influence health promotion behaviors in adolescent Black American males. This study described the health barriers, health perceptions (health self-efficacy and health status), and CV risk factors reported by and the influence of these variables on health promotion behaviors of a sample of Black American adolescent males without known CV disease.

Methods and Procedures: A descriptive correlation study design was used to …

Novel Carbopol-Wax Blends For Controlled Release Oral Dosage Forms, Natarajansoundarapandian Mariageraldrajan

Theses and Dissertations (ETD)

Carbopol is crosslinked acrylic acid. Carbopol can be used in developing formulations for transdermal, oral, rectal use. It is forms strong gel in low concentration. Therefore, it can be used in low concentration in developing controlled release formulations. This increases the cost effectiveness and number of formulation options. In spite of its effectiveness, carbopol is one of the most efficient however underutilized polymer in oral controlled drug delivery system development. This is attributed to the difficulty in processing the carbopol. Carbopol has poor flow characteristics and stickiness. Objective of our research is to eliminate processing difficulties of carbopol using hot …

Probing The Role Of Nascent Helicity In Protein Function: P27kip1 As A Regulator Of The Cell Cycle, Steve Otieno

Theses and Dissertations (ETD)

p27^kip1 binds to and regulates the activity of cyclin-dependent kinases (Cdks) which are the master timekeepers of the cell division cycle. Members of the p27 family of proteins, also including p21 and p57, are called cyclin-dependent kinase inhibitors (CKIs). The amino terminal domain of p27 inhibits Cdk activity and is referred to as the kinase inhibitory domain (KID). The KID is comprised of a cyclin-binding domain (D1) and a Cdk binding domain (D2) joined by a 22 residue linker domain (LH). Structural analysis of the KID in solution before binding its Cdk targets revealed that D1 and D2 are …