Browsing by Subject "Medical Anatomy"
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Item Androgens and Cardiovascular Disease(1998-05-01) Dickerman, Rob D.; Walter J. McConathy; Thomas Yorio; Robert GracyDickerman, Rob D., Androgens and Cardiovascular Disease Doctor of Philosophy (Biomedical Sciences), May 1998; 111 pp; 10 tables, bibliography, 197 titles. Anabolic steroids are commonly used by many muscle and strength dependent athletes due to their ability to enhance the hypertrophic effects of resistance training. The use of anabolic steroids by bodybuilders appears to carry significant health risks, most commonly reported are sudden death, myocardial infarction and cardiomyopathy. To investigate the effects of anabolic steroids on cardiovascular risks, a study was designed to analyze the effects of androgens on lipoprotein levels and structure/function of the heart. For the study on lipid-related risk, twelve competitive bodybuilders were recruited for a comprehensive analysis of serum apolipoprotein A-I, B, total cholesterol, HDL-cholesterol, LDL-cholesterol, and testosterone. Serum total cholesterol, HDL- and LDL-cholesterol, apolipoproteins A-I and Be were significantly lower in androgen-users. Consistent with previous reports, androgens were associated with decreases in HDL-cholesterol and apolipoprotein A-I. However, androgens were also associated with reduced serum total cholesterol, LDL-cholesterol and apolipoprotein B. Despite the significantly higher total cholesterol/HDL-cholesterol ratio, the low levels of serum total cholesterol levels (percentile) in the androgen-users raises questions as to whether there is increased risk for cardiovascular disease and the exact role of androgens in cardiovascular risk. To investigate the effects of anabolic steroids in pathologic concentric left ventricular hypertrophy, the effects of androgens on left ventricular size and function were analyzed. Previous investigations conducted on left ventricular size and function have yielded inconclusive results. Problems existing in each of the previous investigations were small body mass, short length of myocardial exposure time to resistance training (years of training), significantly different body mass between steroid-users and steroid-free subjects and monitoring/reporting of steroid use. These problems may have contributed to the discrepancies between studies. Therefore, we selectively recruited eight competitive heavy weight drug-free bodybuilders and eight matched competitive weight bodybuilders on self-directed regimens of anabolic steroids for examination of left ventricular size and function via echocardiography. Increases in left ventricular posterior wall (LVPW) and ventricular septal thickness (VST) were apparent in the steroid-user group (p [less than] 0.05). Ratio of echocardiographic findings to body mass index (BMI) revealed a significantly smaller left ventricular and diastolic dimension (LVDEd/BMI, p [less than] 0.05) in the steroid-user. The smaller LVDEd in steroid-users is coupled with a significantly disproportionate septal and posterior wall thickness in steroid-users. There was no direct evidence of diastolic dysfunction. Thus it appears from these studies that androgens alter lipoproteins leading to a questionable increased risk for cardiovascular disease and may potentiate concentric left ventricular hypertrophy without affecting cardiac function.Item Delta Opiod Receptor: Parasympathetic Location and Changing Phenotypes in Canine Heart(2007-07-01) Deo, Shekhar H.; James L. Caffrey; H. Fred Downey; Michael SmithDeo, Shekhar H., Delta Opioid Receptor: Parasympathetic Location and Changing Phenotypes in Canine Heart. Doctor of Philosophy (Integrative Physiology), July 23, 112 pp, 4 tables, 24 figures. Delta opioid receptors (DOR) have long been implicated in the complex mechanism of ischemic preconditioning (IPC). Repeated arterial occlusion of the SA node artery in IPC protocol progressively raised the nodal encephalin concentrations and improved vagal transmission during a subsequent extended occlusion. This vagatonic effect was reversed by the DOR-1 antagonist, BNTX. The present thesis tested whether the IPC protocol, the prolonged occlusion or a combination of both was required to demonstrate the vagotonic effect. The study also tested whether the evolution of the vagotonic effect during occlusion might be attributed to erosion of completing vagolytic effects. A progressive improvement in vagal transmission was observed during the IPC protocol. The vagotonic effect was not observed during sham occlusions or during occlusions in animals pretreated with a DOR-1 antagonist. Following the IPC protocol, exogenous MEAP reduced vagal transmission under both normal and occluded conditions. The magnitude of the vagolytic effects was however significantly reduced and eroded further over time compared to time matched shams. The loss of the response was not altered by prior DOR-1. The magnitude of the vagolytic effects was however significantly reduced and eroded further over time compared to time matched shams, however the failure of DOR-1 blockade to slow that process suggests that the PC mediated erosion is independent of receptor activation by DOR-1 agonists. Although DORs are associated with IPC, their precise location remains unconfirmed. DOR and autonomic markers vesicular acetylcholine transporter (VAChT) and tyrosine hydroxylase (TH) were labeled in tissue sections and synaptosomes from canine atrium and SA node. Synapsin I verified the neural character of labeled structures. Acetylcholine and norepinephrine content indicated both cholinergic and adrenergic synaptosomes are present. VAChT and TH signals indicated more than 80% of synapsin positive synaptosomes were cholinergic and less than 8% were adrenergic. Western blots of synaptosomal extracts confirmed by two DOR bands at molecular weights corresponding to reports for DOR monomers and dimmers. The preferential association of DORs with cholinergic nerve terminals supports the hypothesis that post-ganglionic prejunctional DORs regulate local vagal transmission within the heart.Item Function of Differentially Expressed Intracellular Calcium Channels in Retinal Neurons(2008-05-01) Nixon, Everett Sheldon; Peter Koulen; Raghu Krishnamoorthy; Rong MaNixon, Everett, Function of differentially expressed intracellular calcium channels in retinal neurons. Doctor of Philosophy (Pharmacology and Neuroscience), May, 2008, pp154, 17 illustrations. The retina, a specialized part of the central nervous system (CNS) is the innermost layer of the eye responsible for capturing light and converting the light response into a signal that can be transmitted through the optic nerve and onto the brain for interpretation. The ability of the retina to perceive light is dependent on its sensory neurons and the neural circuitry present that initiate the primary stage of processing the image being visualized, which then transmits an electrical signal down the optic nerve to the brain for processing and ultimately visual perception. In the vertical pathway of the visual process that involves the photoreceptor cells, bipolar cells and the ganglion cells, glutamate is the main excitatory neurotransmitter. Communication between these cells is dependent upon the release of glutamate into the synaptic region within both the outer plexiform layer and inner plexiform layer, a process that is Ca2+ regulated. In neurons, Ca2+ regulates a plethora of processes such as gene expression, cell death, synaptic plasticity and neurotransmitter release since it serves as a critical intracellular messenger. In view of the involvement of Ca2+ in a variety of physiological processes, it is essential for the intracellular Ca2+ concentration to be tightly regulated within neuronal cell. Regulation of Ca2+ signaling within retinal neurons can occur via inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs) and ryanodine receptors (RyRs). These receptors are involved in the release of Ca2+ from the intracellular stores such as the endoplasmic reticulum (ER) into the cytosol. IP3Rs and RyRs contribute substantially to cytosolic free Ca2+ concentration transients and thereby play an important role in neuronal function. The purpose of the study was to determine the role of mGluRs, IP3Rs and RyRs in increasing intracellular Ca2+ levels in retinal neurons as related to signaling and neurotransmitter release. The present study provides experimental evidence for the following mechanisms: -Activation of mGluR8 in photoreceptor cells reduced cytosolic Ca2+ concentration by inhibition of the voltage gated Ca2+ channels on the plasma membrane. –The distribution of IP3R and RyR isoforms was associated with cytosolic Ca2+ transients and the IP3R induced transients occurs by activation of group I mGluRs. –In rod bipolar cells, the main increase in cytosolic Ca2+ concentrations during depolarization is due to Ca2+ release from internal stores via activation of RyR. The results of the present study contribute to the understanding of intracellular Ca2+ signaling in retinal neurons and Ca2+ signaling mechanisms. This is of relevance for identifying mechanisms controlling neurotransmitter release and possible pharmacological targets in neurodegenerative retinal diseases characterized by Ca2+ dyshomeostasis.Item Harakal, John H., D.O.(1990-08-08) Harakal, John H.; Stokes, C. RayA professor and former chairman of the manipulative medicine department, Dr. Harakal is a strong advocate of cranial osteopathy. Dr. Harakal is a contributing editor to several osteopathic publications and is currently co-writing an osteopathic textbook. Interviewed by C. Ray Stokes, August 8, 1990Item Interleukin-1Alpha-Mediated Signaling Mechanisms in the Human Trabecular Meshwork(2000-12-01) Shade, Debra L.; Pang, Iok-Hou; Yorio, Thomas; Dillon, GlennShade, Debra L., Interleukin-1Alpha-Mediated Signaling Mechanisms in the Human Trabecular Meshwork. Doctor of Philosophy (Biomedical Sciences/Pharmacology), December, 2000, 140 pp., 13 tables, 30 figures, references, 156 titles. This research provides important insights into the means by which interleukin-1alpha (IL-1α) regulates TM cell functions and enhances aqueous outflow, thus lowering IOP. The studies reported herein represent the first known characterization of the central role of the AP-1 transcription factor pathway in IL-1α-mediated production of proMMP-3 by TM cells, as well as the first known evidence that IL-1α can also enhance TM phagocytosis. Using these results as a stepping stone, this research has furthermore led to the identification of “AP-1 activators” as a novel compound class which may be useful in the treatment of glaucoma; it also points to the potential for compounds which regulate MEK, p38, and PKCμ activity as additional means of treatment. Based on these results, it is postulated that such compounds would be expected to lower IOP via upregulations of MMP production, followed by ECM degradation, and potentially, enhanced clearance of degraded ECM via phagocytosis.Item Legal Medicine and Toxicology Volume 2(W.B. Saunders and Company, 1923-01-01) Haines, Walter; Webster, Ralph; Peterson, FredrickItem Regulation of Endothelin-1 (ET-1) Synthesis and Secretion at the Outer Blood Retinal Barrier(2003-08-28) Narayan, Santosh; Thomas Yorio; Glenn Dillon; Michael W. MartinRegulation of Endothelin-1 (ET-1) Synthesis and Secretion at the Outer Blood-Retinal Barrier. Santosh Narayan, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center Fort Worth, TX 76102. Summary The retinal pigment epithelium (RPE) constitutes the outer blood retinal barrier at the posterior segment of the eye. The RPE provides metabolic support to the photoreceptors in the neural retina. A breakdown in the barrier supported by RPE is a hallmark in several retinopathies including proliferative vitreoretinopathy, choroidal neovascularization and macular edema. Characteristic to all epithelial cells, mature RPE cells display a polarized phenotype both in culture (ARPE-19 cells) and in vivo, with specific apical and basolateral domains. This provides a testable model to study the RPE in vitro. The purpose of this study was to characterize the RPE as a source for endothelin-1, using both in vitro and in situ models. Endothelins (ET-1,-2, and -3) are known regulators of vascular tone, that are produced at sites close to their target, ET-1, being a potent vasoconstrictor may be involved in regulating blood supply to the choroid and the neural retina. We identified the RPE to be a major source for endothelin-1 (ET-1) in situ in the human retina as well as in pigmented and albino rat retinas. Additionally, using a cell-culture model of mature polarized ARPE-19 cells, we studied the synthesis and expression of ET-1 in response to muscarinic receptor stimulation, TNF-α and more recently to thrombin. We have identified other components involved in the synthesis and turnover of ET-1 in ARPE-19 cells including the proprotein convertase-furin, endothelin-converting enzyme-1 and its isoforms and the endothelin receptor B subtype. ARPE-19 cells grown on collagen filters helped determine if secretion of ET-1 was polarized or discriminative towards either the apical or basolateral surface. We consistently observed changes in cell shape and tight junction disassembly in ARPE-19 cells following TNF-α and thrombin addition. Additionally, thrombin caused an increase in preproET-1 mRNA at earlier time points that was dependent on the rhokinase (ROCK1/2) pathway. We report a novel signaling mechanism for regulating preproET-1 mRNA and mature ET-1 secretion in ARPE-19 cells that involves the thrombin receptor (protease activated receptor-1/PAR-1) dependent activation of the rho/ROCK1/2 signaling pathway that may also be involved in thrombin induced changes in the cytoskeleton. In conclusion, the RPE may be an important source for ET-1 at the posterior segment of the eye, secretion of which is greatly enhanced by substances that promote breakdown of blood retinal barriers, inflammation and changes in the RPE cytoskeleton. In conclusion, the RPE may be an important source for ET-1 at the posterior segment of the eye, secretion of which is greatly enhanced by substances that promote breakdown of blood retinal barriers, inflammation and changes in the RPE cytoskeleton. ET-1 secreted by the RPE, under physiological conditions may provide an autoregulatory mechanism for controlling blood flow at the outer blood retinal barrier. Excessive ET-1 secretion following breakdown of the barrier may either promote wound repair or may mediate further damage to the retina, the substrates of which are presently unknown. Future experimental approaches are planned to address these possibilities.Item Schunder, Mary, Ph.D.(1981-03-01) Schunder, Mary; Stokes, C. RayAssociate professor and first chairman of the anatomy department, Dr. Schunder was a member of the first TCOM faculty of 1970. She describes her introduction to osteopathic medicine, her administrative responsibilities and her choice “If I had to do it over.” Interviewed by C. Ray Stokes, March 1981Item Turner, James, Ph.D.(1994-04-06) Turner, James; Hailey, BlakeDr. Turner, Professor and Chairman of the Anatomy & Cell Biology Department, recounts his work in eye disease research and his plans for future research. Interviewed by Blake Hailey, April 6, 1994