Medicine and Health Sciences Commons^™

Safety And Immunoreactivity Of A Xenogeneic Dna Plasmid Vaccine Expressing Human Tyrosinase In Tumor-Bearing Horses, Luis Miguel Lembcke Perez Prieto

Doctoral Dissertations

Melanomas are among the most common skin tumors in horses (second only to sarcoids), with prevalence rates reaching as high as 80% in adult gray horses. Despite the wide availability of measures of local control, there are currently no systemic therapies that can effectively prevent spread, or treat metastatic or locally advanced/non-resectable melanoma in horses. A form of gene immunotherapy based on a plasmid DNA construct containing a xenogeneic form of the antigen tyrosinase have been developed and optimized for targeting cancer in both humans and dogs; and have demonstrated significant immunoreactivity and clinical benefit in the treatment of melanocytic …

Growth Regulation Of Pancreatic Cancer Cells And Their Normal Cells Of Origin By Nicotinic Acetylcholine Receptors, Mohammed Hussein Al-Wadei

Doctoral Dissertations

Pancreatic cancer is the fourth leading cause of cancer mortality with a five-year survival rate of less than 5 %. It shows no symptoms until it has reached an advanced stage upon which it has metastasized to distant organs limiting therapeutic options. Several studies have identified smoking, alcohol, diabetes and pancreatitis as risk factors for pancreatic cancer. While smoking is a well-documented risk factor for this malignancy, there still remains a controversy on whether alcohol can act as a risk factor itself or cooperatively enhances the effects of other risk factors.

Previous reports provide evidence that nicotinic acetylcholine receptors (nAChRs) …

Toward Personalized Medicine: The Potential Role Of Rna Interference In Plasma Cell Dyscrasia, Jonathan E Phipps

Doctoral Dissertations

A major contributor to mortality in patients with plasma cell dyscrasias (PCDs); i.e., multiple myeloma, light chain deposition disease and AL amyloidosis is the deposition as insoluble aggregates of monoclonal immunoglobulin light chain proteins (LC) in the kidneys and other organs. Currently anti-plasma cell chemotherapies are used to reduce LC synthesis, and slow deposition. While effective, these treatments are toxic, non-specific, expensive, and might not be appropriate in all cases, making the identification of an alternate means of reducing toxic LC species desirable. To this end, we have investigated whether RNA interference (RNAi) could achieve these goals.

Human (RPMI 8226, …

Heifer Estrous Cycle Stage Impacts Luteinizing And Growth Hormone Response To Kisspeptin, Brian K. Whitlock, Joseph A. Daniel, Robyn R. Wilborn, Barbara P. Steele, James L. Sartin

Animal Science Publications and Other Works

The reproductive neuropeptide, kisspeptin (KP), may have a role in regulation of growth hormone (GH) secretion. Expression of KP and its receptor (Kiss1r) are developmentally and hormonally regulated. This study was conducted to determine the effects of KP on plasma concentrations of luteinizing hormone (LH) and GH in pubertal heifers during different functional reproductive stages. Heifers received a single injection of KP (100 pmole / kg) or saline intravenously during proestrus, estrus, and diestrus, and serial blood samples were collected for 3 hours to determine the response of both LH and GH after treatment. Mean concentrations of LH were increased …

Effect Of Kisspeptin On Regulation Of Growth Hormone, Brian K. Whitlock, Joseph A. Daniel, Robyn R. Wilborn, Herris S. Maxwell, Barbara P. Steele, James L. Sartin

Animal Science Publications and Other Works

Kisspeptin ( KP ), a neuroendocrine regulator of reproduction, is hypothesized to be an integrator of metabolism and hormones critical to the regulation of reproduction. Lactation is associated with enhanced growth hormone (GH) responsiveness and reduced fertility. Our study was designed to determine the effects of lactation on KP-stimulated GH and luteinizing hormone (LH) secretion. Five non-lactating and five lactating dairy cows were used in the study. Experiments were conducted with lactating cows at weeks 1, 5 and 11 after parturition. The experimental treatments ( saline and KP [100 and 400 pmol / kg body weight]) were given intravenously and …

Immunologic Risk Prediction Model For Kidney Graft Function, Christina Diane Bishop

Doctoral Dissertations

Clinicians lack appropriate non-invasive methods to be able to predict, diagnose, and reduce the risk of rejection in the years following kidney transplantation. Protocol biopsies and monitoring of serum creatinine levels are the most common methods of monitoring graft function after transplant; however, they have several negative aspects. Use of traditional factors regarding donors and recipients such as Human Leukocyte Antigen (HLA) DNA typing, pre-transplant anti-HLA antibody levels, and basic demographics (age, ethnicity/race, gender), has proved inadequate for post-transplant graft monitoring past the first few years. We propose that by utilizing immunologic factors available to clinicians across the United States, …

Role Of Il-17 And Th17 Cells In Hsv Induced Ocular Immunopathology, Amol Sahebrao Suryawanshi

Doctoral Dissertations

Herpes simplex virus (HSV) infection of the cornea leads to a blinding immuno-inflammatory condition of the eye also called stromal keratitis (SK). SK immunopathology is characterized by the infiltration of CD4⁺ T cells of Th1 phenotype as well as the development of new blood vessels into the normally avascular cornea. Studies in mouse models of SK have firmly established the role of CD4⁺ T cells, and particularly of Th1 phenotype, as the principal mediators of SK immunopathology. However, with the recent discovery of IL-17A and Th17 cells, the role of this cytokine as well as Th17 cells remains …

The Effect Of Kisspeptin Receptor Agonist (Ftm080) On Luteinizing Hormone In Sheep, Brian K. Whitlock, Joseph A. Daniel, Maria Hes, Barbara P. Steele, James L. Sartin, S. Oishi, N. Fujii

Animal Science Publications and Other Works

Kisspeptin receptor (Kiss1r) agonists with increased half-life and similar efficacy to kisspeptin (KP) in vitro potentially may provide beneficial applications in breeding management of many species. However, many of these agonists have not been tested in vivo. This study was designed to test the effect of a Kiss1r agonist (FTM080) on luteinizing hormone (LH) in vivo. Sheep were treated with FTM080 (500 pmol/kg BW) or sterile water in a 2-ml bolus via the jugular cannula. Serial blood samples were collected every 15-min before (1 hr) and after (1 hr) treatment. Intravenous (IV) injection of FTM080 increased (P < 0.05) LH plasma concentrations through the 45-min sample following treatment. Moreover, the area under the curve of LH in the period from 0 to 60-min following FTM080 treatment was also increased (P < 0.05). These data provide evidence to suggest that FTM080 stimulates the gonadotropic axis of ruminants in vivo.

Mechanism Of Phospholipid Induction Of Cell Migration, Dongwei Wu

Doctoral Dissertations

Lysophosphatidic acid (LPA) is a potent bioactive lipid component of oxidized low density lipoproteins (oxLDL). High concentrations of LPA have been detected in human atherosclerotic plaques. Our data has shown that LPA highly induces smooth muscle cell (SMC) migration. Cyr61, a matricellular protein, which also accumulates in human atherosclerotic plaques, has been implicated in the injury-induced neointimal formation. Smooth muscle cell migration is a key event in the development of atherosclerosis, and it contributes to the progressive growth of atherosclerotic lesions. Data generated by this study demonstrate that LPA markedly induces Cyr61 expression in mouse aortic smooth muscle cells (MASMC). …

Development Of An Autonomous Mammalian Lux Reporter System, Daniel Michael Close

Doctoral Dissertations

Since its characterization, the definitive shortcoming of the bacterial luciferase (lux) bioluminescent reporter system has been its inability to express at a functional level in the eukaryotic cellular background. While recent developments have allowed for lux function in the lower eukaryote Saccharomyces cerevisiae, they have not provided for autonomous function in higher eukaryotes capable of serving as human biomedical proxies. Here it is reported for the first time that, through a process of poly-bicistronic expression of human codon-optimized lux genes, it is possible to autonomously produce a bioluminescent signal directly from mammalian cells. The low background of …

Study Of The Structure And Function Of Cxc Chemokine Receptor 2, Hae Ryong Kwon

Masters Theses

It has been shown that the amino terminus and second extracellular loop (EC2) of CXCR2 are crucial for ligand binding and receptor activation. The lack of an ionic lock motif in the third intracellular loop of CXCR2 focuses an investigation of the mechanism by which these two extracellular regions contribute to receptor recognition and activation.

The first objective of this investigation was to predict the structure of CXCR2 based on known structures of crystallized GPCRs. Rhodopsin, β2-adrenergic receptor, CXCR4 were used for homology modeling of CXCR2 structure. Highly conserved motifs found in sequence alignments of the template GPCRs were helpful …

Selected Hormonal And Neurotransmitter Mechanisms Regulating, James L. Sartin, Joseph A. Daniel, Brian K. Whitlock, Robyn R. Wilborn

Faculty Publications and Other Works -- Large Animal Clinical Sciences

Appetite control is a major issue in normal growth and in suboptimal growth performance settings. A number of hormones, in particular leptin, activate or inhibit orexigenic or anorexigenic neurotransmitters within the arcuate nucleus of the hypothalamus, where feed intake regulation is integrated. Examples of appetite regulatory neurotransmitters are the stimulatory neurotransmitters neuropeptide Y (NPY), agouti-related protein (AgRP), orexin and melanin-concentrating hormone and the inhibitory neurotransmitter, melanocyte-stimulating hormone (MSH). Examination of messenger RNA (using in situ hybridization and realtime PCR) and proteins (using immunohistochemistry) for these neurotransmitters in ruminants has indicated that physiological regulation occurs in response to fasting for several …

Regional Differences In Adipose Tissue Of The Sinclair Minipig, Suzanne Lauren Booker

Masters Theses

Adipose tissue is an endocrine organ, and its homeostatic mechanisms in normal weight, overweight and obese subjects must be elucidated. We sought to determine the basal adipose tissue biology of visceral (VIF) and subcutaneous (SQF) fat depots in 8 month old Sinclair minipigs, an animal that has been shown to be physiologically similar to humans.

Metabolic analysis showed a decrease in LDL, white blood cells (WBC), and lymphocyte percentages as the minipigs aged from 6 to 8 months (p <0.0001 and = 0.0046 and 0.0165 respectively). There were no significant changes in triglycerides, HDL, VLDL, and neutrophil percentages. There was a trend in insulin increase (P=0.0722).

Microarray analysis was performed to determine transcriptome differences between VIF and SQF. When VIF was compared to SQF, expression of a …

Changes In Plasma Concentrations Of Growth Hormone And Luteinizing Hormone In Ewes Following Central And Peripheral Treatment With Kisspeptin, Brian K. Whitlock, Joseph A. Daniel, Barbara P. Steele, James L. Sartin

Animal Science Publications and Other Works

Kisspeptin (KP), a neuroendocrine regulator of gonadotropin releasing hormone, has been hypothesized as an integrator of nutrition and hormones critical to metabolism and regulation of reproduction. Recent evidence suggests growth hormone (GH) secretion may be influenced by KP. The objective of this study was to determine if the GH stimulatory effect of KP is due to actions on the hypothalamus or anterior pituitary gland in ewes. Adult ovariectomized ewes (n=8) were fitted with intracerebroventricular (ICV) cannula to facilitate central administration of experimental treatments. Ewes received one of eight treatments [four intravenously (IV) and four ICV]. Peripheral treatments [0 (Veh), 100, …

Changes In Plasma Concentrations Of Leptin In Ewes During Pregnancy, Joseph A. Daniel, A B. Milam, M E. Gafnea, Brian K. Whitlock, D H. Keisler

Animal Science Publications and Other Works

Previous research has demonstrated circulating concentrations of leptin increase in ewes during mid pregnancy then decline in late pregnancy and early lactation. The objective of this study was to more narrowly define the timing of changes in circulating concentrations of leptin with pregnancy in ewes. Katahdin ewes (n= 19) located at latitude 34.275 and longitude -85.183 (Mount Berry, GA) were utilized. Blood samples were collected weekly via jugular veinpuncture beginning immediately before ram exposure on September 23 and continuing until 4 weeks post-lambing. Ewes were exposed to a ram fitted with a marking harness for a 63 day breeding season. …

Effect Of Leukemia Inhibitory Factor On Feed Intake And Body Temperature In Sheep, James L. Sartin, D L. Marks, Brian K. Whitlock, Joseph A. Daniel, Barbara P. Steele

Animal Science Publications and Other Works

Leukemia inhibitory factor (LIF) has been suggested to function as a potent inhibitor of feed intake in rodents. These studies were designed to determine whether LIF was found in the ovine hypothalamus and whether LIF inhibited feed intake in sheep. Sheep hypothalami were used to clone LIF to indicate presence of the gene in the hypothalamus. The sequence was similar to published data. Another group of sheep were provided intraventricular (ICV) cannulas and injected with doses of LIF at 250, 500, 1000 and 2500 ng per sheep, ICV. Feed intake was inhibited by the 1000 and 2500 ng dose (trt, …

Farm Focus - Spring 2010, Brian K. Whitlock, Matt Welborn, Maria Prado, Amy Plummer

Faculty Publications and Other Works -- Large Animal Clinical Sciences

No abstract provided.

The Biology Of Reality Testing - Implications For Cognitive Education, Neil Greenberg

Faculty Publications and Other Works -- Ecology and Evolutionary Biology

• This report explores the proposition that teaching effectiveness can be enhanced by accommodating the key differences between two complementary and deeply engrained modes of reality testing, each predominantly centered in different hemispheres of the brain. • (1) Correspondence involves “reality-testing” of a percept, the cerebral representation of an experience in the world. • (2) Coherence involves “textualizing”, that is, reality-testing of a percept by how easily it relates to previous and ongoing parallel and collateral experiences. • Confidence in the validity of any percept throughout development is related to the interplay of these key processes. • As organisms develop, …

Ppar Agonists Down-Regulate The Expression Of Atp10c Mrna During Adipogenesis, A Peretich, Maria Cekanova Ms, Rndr, Phd, S Hurst, Sj Baek, Madhu Dahr

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

No abstract provided.

Farm Focus - Fall 2009, Brian K. Whitlock, Matt Welborn, Maria Prado, Amy Plummer

Faculty Publications and Other Works -- Large Animal Clinical Sciences

No abstract provided.

The Regulation Of Neuropeptide Corazonin And Its Functional Analyses In Drosophila Melanogaster, Seung-Hoon Choi

Doctoral Dissertations

Neuropeptides regulate diverse physiological processes, including homeostatic metabolism, behavior, reproduction, and development. The neuropeptide Corazonin (Crz), was first isolated from American cockroach, P. americana, as a potent cardioactive substance, and has been shown to exert diverse functions in different insects. In Drosophila, Crz expression is limited to three groups of neurons; totaling only 26 neurons out of ~10,000 neurons in a third instar larval central nervous system (CNS). In adults, Crz is expressed in 6-8 pairs of protocerebral neurons and 2 pairs of male specific abdominal ganglion. To gain insight into such tight regulatory mechanisms of …

The Effects Of 17- Beta Estradiol On G-Protein Inwardly Rectifying Potassium Channels (Girks) In Breast Cancer, Michael W. Hance

Doctoral Dissertations

Breast cancer is a leading cause of cancer death and in 2009, the American Cancer Society estimates that over 192,000 new cases of breast cancer will be diagnosed, and over 40,000 women will die from breast cancer. Estrogen (E2) is required for normal female development and reproduction, but long-term exposure is carcinogenic and considered a risk factor for breast cancer. Membrane ion channels are essential for cell proliferation and are suggested to have a role in cancer, especially potassium channels. In the present study, we investigate the effects of estrogen and the estrogen antagonist ICI182780 on G-protein inwardly rectifying potassium …

Seasonal Variation In Lake Erie Picoplankton, Star Nicole Loar

Masters Theses

Striking rates of environmental changes combined with increased demand make it essential to develop a better understanding of global freshwater resources. Seasonal hypoxia in the central basin of Lake Erie is the result of thermal stratification and lake morphology. Limnetic physics can, however, only explain part of Lake Erie‟s “behavior”: the activity(s) of the ecosystem‟s biological members can be equally important. The goal of this study was to identify picocyanobacterial community members in the central basin of Lake Erie during summer stratification and the winter season to see how they may vary with season. Identification of microbial communities under the …

Farm Focus - Spring 2009, Brian K. Whitlock, Matt Welborn, Maria Prado, Amy Plummer

Faculty Publications and Other Works -- Large Animal Clinical Sciences

No abstract provided.

"The Natural History Of Truth: The Neurobiology Of Belief", Neil Greenberg

Faculty Publications and Other Works -- Ecology and Evolutionary Biology

The pursuit of truth is woven into the fabric of every organism*. Any estimate of how best to survive and thrive in the reality in which we are immersed requires a sense of self, of the world, and of their relationship to each other. I wish to explore the idea that this pursuit has at its heart two complementary modes of reality testing utilizing separate cerebral systems which deal, respectively with the correspondence of experience with the world and the coherence of the experience with previous experiences: “is it real” and “does it fit?” At multiple levels of the nervous …

The Effects Of Lactation And Negative Energy Balance On Kisspeptin-Stimulated Luteinizing Hormone And Growth Hormone In Dairy Cows, Brian K. Whitlock, Joseph A. Daniel, Robyn R. Wilborn, Herris S. Maxwell, Barbara P. Steele, James L. Sartin

Animal Science Publications and Other Works

Kisspeptin, a neuroendocrine regulator of gonadotropin releasing hormone, is hypothesized to integrate nutrition and hormones critical to metabolism and the regulation of reproduction. Since the negative energy balance of early lactation is associated with reduced fertility via suppression of gonadotropin secretion and enhanced growth hormone (GH) responsiveness, this experiment was designed to determine the effects of stage of lactation and negative energy balance on kisspeptin-10 (Kp-10) stimulated luteinizing hormone (LH) and GH concentrations. Five nonlactating [5.1 ± 0.8 (SEM) years; 577 ± 19 kg body weight (BW)] and five lactating [4.1 ± 0.6 years; 608 ± 11 kg BW] multiparous …

Efficacy Of An Ankle Orthosis With A Subtalar Locking System In Restricting Ankle Kinetics And Kinematics In Lateral Cutting, Songning Zhang, Michael Wortley, Qingjian Chen, Julia Freedman, Casey Riley

Faculty Publications and Other Works -- General Biology

Introduction

The ankle joint is the most injured joint during sports participation [1]. Ankle orthoses have been shown to be effective in reducing ankle inversion injuries and are often prescribed for rehabilitation and prevention of lateral ankle sprains. Efficacy of ankle orthoses is often assessed by comparing reduction of passive inversion ROM as well as ankle kinematics between braced and unbraced movements [2,3]. However, joint kinetic responses in lateral cutting were rarely examined. Therefore, the objective of this study was to examine the effectiveness of a new semi-rigid ankle orthosis with a subtalar joint …

Gene Alterations By Peroxisome Proliferator-Activated Receptor Gamma Agonists In Human Colorectal Cancer Cells, Maria Cekanova, X Li, J Yuan, K B. Kim, Seung J. Baek

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear transcription factor that controls the genes involved in metabolism and carcinogenesis. In the present study, we examined the alteration of gene expression in HCT-116 human colorectal cancer cells by PPARgamma agonists: MCC-555 (5 microM), rosiglitazone (5 microM), and 15-deoxy-Delta12,14-prostaglandin J2 (1 microM). The long-oligo microarray data revealed a list of target genes commonly induced (307 genes) and repressed (32 genes) by tested PPARgamma agonists. These genes were analyzed by Onto-Express software and KEGG pathway analysis and revealed that PPARgamma agonists are involved in cell proliferation, focal adhesion, and several signaling pathways. …

Expression Of G-Protein Inwardly Rectifying Potassium Channels (Girks) In Lung Cancer Cell Lines, Howard Plummer 3rd, Madhu Dhar, Maria Cekanova Ms, Rndr, Phd, Hildegard Schuller

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

BACKGROUND: Previous data from our laboratory has indicated that there is a functional link between the beta-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in human breast cancer cell lines. We wanted to determine if GIRK channels were expressed in lung cancers and if a similar link exists in lung cancer. METHODS: GIRK1-4 expression and levels were determined by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. GIRK protein levels were determined by western blots and cell proliferation was determined by a 5-bromo-2'-deoxyuridine (BrdU) assay. RESULTS: GIRK1 mRNA was expressed in three of six small …

Expression And Localization Of Estrogen Receptor-Alpha Protein In Normal And Abnormal Term Placentae And Stimulation Of Trophoblast Differentiation By Estradiol, A Bukovsky, Maria Cekanova Ms, Rndr, Phd, Mr Caudle, J Wimalasena, Js Foster, Dc Henley, Rf Elder

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

Estrogens play an important role in the regulation of placental function, and 17-beta-estradiol (E2) production rises eighty fold during human pregnancy. Although term placenta has been found to specifically bind estrogens, cellular localization of estrogen receptor alpha (ER-alpha) in trophoblast remains unclear. We used western blot analysis and immunohistochemistry with h-151 and ID5 monoclonal antibodies to determine the expression and cellular localization of ER-alpha protein in human placentae and cultured trophoblast cells. Western blot analysis revealed a ~65 kDa ER-alpha band in MCF-7 breast carcinoma cells (positive control). A similar band was detected in five normal term placentae exhibiting strong …