Medicine and Health Sciences Commons^™

Role Of Ataxia Telangiectasia Mutated Kinase In Western-Type Diet-Induced Cardiac Outcomes Under Basal And Ischemic Conditions, Mary Wingard

Electronic Theses and Dissertations

Ataxia-telangiectasia mutated kinase (ATM), a serine/threonine kinase, plays a role in DNA damage repair, redox sensing, and metabolism. In the heart, ATM contributes significantly in the myocardial infarction (MI)-induced cardiac remodeling with effects on fibrosis, hypertrophy, apoptosis and inflammation. This study investigates the role of ATM deficiency in 14 weeks Western-type diet (WD)-induced cardiac outcomes prior to and 1-day post-MI in a sex-specific manner using wild-type (WT) and ATM heterozygous knockout (hKO) mice. In male mice, ATM deficiency induced rapid body weight gain and preload-associated dysfunction, while WT mice displayed afterload-associated dysfunction 14 weeks post-WD. Myocyte apoptosis and hypertrophy were …

The Influence Of Strength In Load-Velocity Relationships In The Back Squat, Thaddeus Light

Electronic Theses and Dissertations

Load-velocity relationships may vary between people of different strength levels and across different loads. The purpose of this dissertation was to investigate how external loads influence the velocity characteristics of the back squat exercise, and the influence of strength on these variables. Healthy male students with a history of resistance training completed repetitions at specified intensities of their estimated one-repetition maximum (1RM) until they reached 1RM. Back squat 3D motion analysis was captured using four Vicon T010 cameras (Vicon Motion Systems Ltd.; Oxford, UK) and Vicon Nexus 1.8.5 software. Data were transported into R custom coding statistical analysis software (version …

The Study Of Alcoholic Liver Diseases, Seun Emmanuel Owoseni

Electronic Theses and Dissertations

Excessive alcohol consumption is the primary contributing factor in the development of alcoholic liver diseases (ALD). Nicotine contained in tobacco is a major addictive alkaloid, which enhances the effects of ALDs. The major enzyme involved in nicotine metabolism is cytochrome P450 2A5 (CYP2A5) which is produced in the liver. Alcohol can stimulate the CYP2A5 enzyme. We utilized cyp2a5-/- knockout mice in this research to examine the effects of CYP2A5.

The cyp2a5-/- mice and wild-type (WT) mice were fed liquid ethanol diet with or without nicotine to induce ALD. Nicotine enhancing effects on ALD were observed in WT mice but not …

Success Rates Of Second Semester Anatomy Students In Online And On-Ground Classes At A Community College In East Tennessee, William Sproat

Electronic Theses and Dissertations

Educators expect the number of institutions offering online courses and the number of students enrolling in these courses to increase as many students, particularly nontraditional students, discover the advantages of online content delivery. Online courses require new methods of communication between students and faculty as well as discovering new ways to build relationships, earn student trust, conduct appropriate assessment, and deliver useful course content. Many institutions—public, private, and for-profit—offer a wide variety of online coursework but faculty, employers, and the public have expressed concerns about the quality of online course content. In particular, online delivery of coursework in the natural …

Role Of Ataxia Telangiectasia Mutated Kinase In The Healing Process Of The Heart Following Myocardial Infarction, Laura L. Daniel

Electronic Theses and Dissertations

Ataxia telangiectasia (AT), caused by mutations in the gene encoding ataxia telangiectasia mutated kinase (ATM), is a rare autosomal recessive disorder. AT individuals exhibit neuronal degeneration and are predisposed to cancer. Carriers of this disorder are predisposed to cancer and ischemic heart disease. Heart disease, mostly due to myocardial infarction (MI), is a leading cause of death in the US. Following MI, release of catecholamines in the heart stimulates β- adrenergic receptors (β-AR). Our lab has shown that β-AR stimulation increases ATM expression in the heart and myocytes, and ATM plays an important role in β-AR-stimulated myocardial remodeling with effects …

Characterization Of Murine Cardiac Cholinergic Innervation And Its Remodeling In Type 1 Diabetes., Abigail Marie Mabe

Electronic Theses and Dissertations

Murine models have become increasingly popular to study various aspects of cardiovascular diseases due to their ease of genetic manipulation. Unfortunately, there has been little effort put into describing the distribution of autonomic nerves in the mouse heart, making it difficult to compare current findings from clinical and experimental models related to cardiovascular diseases. Furthermore, determination of the requirements for the development of this system and its maintenance in adult mice remains largely unexplored. This study represents the first detailed mapping of cholinergic neuroanatomy of the mouse heart based on immunohistochemical staining using true cholinergic markers. We found cholinergic innervation …

In Vitro Assessment Of The Toxicity Of Cocaine And Its Metabolites In The Human Umbilical Artery, Tessa L. Long

Electronic Theses and Dissertations

An in vitro model was used to assess the effect of cocaine and its metabolites on the umbilical artery. Objectives were to pharmacologically confirm the presence of adrenergic innervation using tyramine, evaluate the ability of cocaine, benzoylecgonine, norcocaine and cocaethylene to potentiate vasoconstriction by serotonin and norepinephrine, examine the ability of ketanserin to block the enhanced vasoconstriction produced by cocaine, and determine displacement of 3 H-ketanserin by serotonin, norepinephrine, tyramine and mianserin. The vasoconstrictive effect of tyramine (100 μM) was enhanced in the presence of cocaine by 257%. Vasoconstrictive effects of serotonin and norepinephrine were significantly enhanced by cocaine by …

Quantal Mechanisms Underlying Stimulation-Induced Augmentation And Potentiation, Hong Cheng

Electronic Theses and Dissertations

Repetitive stimulation of motor nerves causes an increase in the number of packets of transmitter ("quanta") that can be released in the ensuing period. This represents a type of conditioning, in which synaptic transmission may be enhanced by prior activity. Despite many studies of this phenomenon, there have been no investigations of the quantal mechanisms underlying these events, due to the rapid changes in transmitter output and the short time periods involved. To examine this problem, a method was developed in which estimates of the quantal release parameters could be obtained over very brief periods (3 s). Conventional microelectrode techniques …

Gross And Histological Features Of A Myofascial Trigger Point In The Upper Trapezius, Kathryn E. Levee

Electronic Theses and Dissertations

The purpose of this study was to precisely locate, in living humans, a myofascial trigger point associated with the upper portion of the trapezius muscle (TrP1) that refers pain to the head and neck and to determine if this point is associated with anatomical structures. This study is descriptive and utilizes data from measurements of the location of TrP1 in relation to anatomical landmarks, of pressure sensitivity overlying the trigger point and electromyography recordings in localizing the trigger point. Information obtained from living humans was used to determine anatomical correlation to structures in cadavers. Results indicated there is little variability …

Cytokines And Ovulation In The Mouse Ovary, Jong G. Kim

Electronic Theses and Dissertations

Ovulation has been hypothesized as an inflammatory process. Interleukin(IL)-1$\alpha$, IL-1$\beta$ and tumor necrosis factor(TNF)-$\alpha$ are potent cytokines produced from macrophages and various other cell types, and are pivotal components of inflammation. Although previous studies have investigated cytokine activities in the reproductive system, there is little information on their precise localization and activities during the periovulatory period. To investigate the role of cytokines in ovulation, experiments were designed to determine the immunohistochemical localization and time specific production of cytokines IL-1 and TNF-$\alpha$ using a mouse model at 36h, 12h, 6h, 2h before ovulation, and at 6h and 18h after ovulation in …

Microcirculation: Electrophysiological Basis For The Response Of Endothelial Cells To Inflammatory Mediators-Bradykinin, Kai Miao

Electronic Theses and Dissertations

Using conventional microelectrodes, I studied the electrical basis for determining the resting V$\sb{\rm m}$ in intact EC's from hamsters. The resting V$\sb{\rm m}$ were found to be $-$40 mV for aortic EC's and $-$43 mV for vena caval EC's. The contributions of ions to the resting V$\sb{\rm m}$ of aortic EC's were compared in terms of the transference number (t$\sb{\rm ion}$). To develop a technique for in situ monitoring changes in V$\sb{\rm m}$ of postcapillary venular EC's in the hamster mesentery, a voltage-sensitive fluorescent probe, bisoxonol, was used to load the cells and the fluorescence signals were analyzed under an …

Differential Role Of The Endothelium In Regulating Microvascular Blood Flow, Tao Tang

Electronic Theses and Dissertations

The vascular endothelial cell (EC) plays an important role in regulating vascular tone and local blood flow by sensing chemical and mechanical stimuli on the vascular wall and releasing a host of vasoactive substances upon activations of endogenous or exogenous vasoactive substances. The central hypothesis is that local control of blood now and autoregulatory behavior in the microcirculation is distinctive at different levels of the vasculature and is dependent on the cellular activities of the EC and its interaction with the local environment. The in vivo as well as the ex vivo, flow-controlled preparations of the hamster cheek pouch were …

Denervation Supersensitivity Of The Rat Vas Deferens: A Role For Protein Kinase C, Sonny T. Abraham

Electronic Theses and Dissertations

A role for protein kinase C (PKC) in the denervation-induced supersensitivity of the rat vas deferens was investigated. Chronic, surgical denervation of the rat vas deferens (up to 8 days) resulted in tissues that produced enhanced contractile responses to norepinephrine (NE) in isolated organ baths. Single challenges of NE (10 $\mu$M) produced 0.6 $\pm$ 0.1 g of maximal tension in the control vas whereas in the paired, denervated tissue 2.2 $\pm$ 0.3 g of tension was recorded (n = 6). Cumulative concentration-effect curves to NE produced in the denervated vas deferens were shifted 18-fold to the left of the control …

Characterization Of The Vasoactivity Of Tachykinins In Isolated Rat Kidney: Functional Studies And In Vitro Receptor Autoradiography, Yuejin Chen

Electronic Theses and Dissertations

Although tachykinins have potent vascular actions, their effect on renal resistance blood vessels is currently unknown. The vasoactive properties of tachykinins and related analogs were assessed in isolated perfused rat kidney. At a basal perfusion pressure (PP) of 75 $\pm$ 6 mm Hg (n = 5), bolus injections of substance P (SP) had no significant vasoactive effect. Following a sustained increase in baseline PP (134 $\pm$ 10 mm Hg) produced by phenylephrine (1 $\mu$M), SP evoked a dose-dependent increase in PP. The largest dose of SP increased PP by 60 $\pm$ 5 mm Hg. The vasoconstrictor response to SP was …

Enhanced Renal Sympathetic And Cardiovascular Responses To Substance P In Hypertension, Gregory W. Lindsay

Electronic Theses and Dissertations

Blood pressure, heart rate, and renal sympathetic nerve responses were measured in 9-13 week old male spontaneously hypertensive rats (SHR) and compared to those in age and sex-matched Wistar-Kyoto (WKY) rats following intravenous injection of the neuropeptide substance P (SP), the nicotinic stimulant 1,1-dimethyl-4-phenylpiperazinium (DMPP), and the adrenoceptor stimulant norepinephrine (NE). Charles River Sprague-Dawley (CD) rats were used in some studies to develop methodologies. Measurements were made in control rats and also following sinoaortic denervation, pithing, ganglion blockade, or adrenoceptor blockade. Responses were evaluated in order to determine if ganglion stimulation by SP was enhanced in SHR compared to WKY …

Changes In Intracellular Chloride During Osmotic Stress And L-Alanine Uptake In Mouse Hepatocytes, Kening Wang

Electronic Theses and Dissertations

A stable intracellular ionic environment is necessary for hepatocytes to function normally. Thus, during hypotonic shock or L-alanine uptake, hepatocytes swell and then exhibit a regulatory volume decrease (RVD), which comprises an increase in K$\sp+$ conductance (G$\sb{\rm K}$), an increased K$\sp+$ efflux, and a hyperpolarization of transmembrane potential (V$\sb{\rm m}$). Since hepatocyte intracellular Cl$\sp-$ has been demonstrated to distribute passively with V$\sb{\rm m}$, this study is designed to test the hypothesis that the hypotonic shock- or L-alanine uptake-induced hyperpolarization of V$\sb{\rm m}$ might provide an electromotive force for the efflux of hepatocyte intracellular Cl$\sp-$, which in turn would contribute osmotically …

Electrophysiology, Cell Calcium, And Mechanisms Of Hepatocyte Volume Regulation, Walid E. Khalbuss

Electronic Theses and Dissertations

The electrophysiologic technique (Reuss, L., Proc. Natl. Acad. Sci. USA 82:6014, 1985) was modified to measure changes in steady-state hepatocyte volume during osmotic stress. Hepatocytes in mouse liver slices were loaded with tetramethylammonium ion (TMA$\sp{+}$) during transient exposure of cells to nystatin. Intracellular TMA$\sp{+}$ activity (a$\sp{\rm i}\sb{\rm TMA}$) was measured with TMA$\sp{+}$-sensitive, double-barreled microelectrodes. Loading hepatocytes with TMA$\sp{+}$ did not change their membrane potential (V$\sb{\rm m}$), and under steady-state conditions a$\sp{\rm i}\sb{\rm TMA}$ remained constant over 4 min in single impalements. Hyperosmotic solutions (50, 100, & 150 mM sucrose added to media) and hyposmotic solutions (sucrose in media reduced by …

Adaptation Of Striped Bass To Sea Water Following Direct Transfer From Freshwater: Morphological, Biochemical, And Physiological Parameters, Judy A. King

Electronic Theses and Dissertations

There has been heightened interest in the biology of striped bass (Morone saxatilis) because of increased pollution in their native spawning grounds and because of their extensive use in landlocked sport fisheries. Their euryhalinity makes them an excellent species for osmoregulation studies. The objective of this research was to study the rate of adaptation of striped bass gills to sea water (3% salt) after direct transfer from freshwater using biochemical (ion transport enzyme levels), physiological (chloride efflux), and ultrastructural methods. Striped bass have specialized osmoregulatory cells located on the interlamellar and afferent surfaces of their gill filaments as shown by …

Quantitation Of Teratogenic Effects Of 5-Fluorouracil Administered To Mice In Vivo Or In Submerged Limb Culture, Theresa A. Sanders

Electronic Theses and Dissertations

This study demonstrates the use of submerged limb culture in teratologic testing. Pregnant mice were treated on day 11 of gestation (E11, plug date = E0) with 10, 20 or 40 mg of 5-fluorouracil (FU) per kg body weight. On E17, treated and untreated fetuses were examined for gross malformations and were fixed in 95% ethanol. Reduction of limb size and digital defects, including ectrodactyly (ED), syndactyly (SD), microdactyly and polydactyly were dose-dependent. In parallel studies, pregnant mice were treated on the morning of E11 and embryos were removed either 7h (E11) or 24h (E12) later for submerged limb culture. …