Physiology Commons^™

Enhancement Of Anti-Hiv-1 Ribozyme Activities By Rev Binding And Multimerization, Yuksel Yildiz

Loma Linda University Electronic Theses, Dissertations & Projects

To effectively apply hammerhead ribozymes as therapeutic agents it is necessary to co-localize them with the desired target. Human immunodeficiency virus type1 (HIV- 1) infectivity is dependent on env gene expression. HIV-1 Rev protein binds to a higher ordered RNA structure within the env transcript termed the Rev Binding Element (RBE). In anti-HIV gene therapy employing ribozymes to increase the co-localization of anti- HIV ribozymes with target HIV mRNAs, it has been proposed that when the native HIV- 1 RBE is appended to a ribozyme as a decoy molecule, simultaneous binding of Rev monomers to the RBE sequences in both …

Estrogen Regulation Of The Pregnant Baboon Placental 11Β-Hydroxysteroid Dehydrogenase (11Β-Hsd)-Catalyzed Metabolism Of Cortisol And Cortisone And Its Effect On The Development Of The Fetal Hypothalamic-Pituitary-Adrenal Axis, William Adair Davies

Theses and Dissertations in Biomedical Sciences

Pepe and Albrecht previously demonstrated that the estrogen-regulated change in transuteroplacental metabolism of cortisol (F) and cortisone (E) from preferential reduction (E to F) at midgestation to oxidation (F to E) near term results in a decline of bioactive cortisol crossing the placenta and reaching the fetus culminating in activation of the hypothalamic-pituitary adrenal axis of the baboon and the ontogenesis of rate-limiting steroidogenic enzymes culminating in de novo F secretion. Protein kinase A (PK-A) activity in the baboon fetal adrenal gland cytosolic fraction was increased 2-fold both at term [day 165 of gestation (term = 184 days)] and following …

Interactions Of Igf-Ii And Cathepsin D In Mcf-7 Breast Cancer Cells, Jesika S. Faridi

Loma Linda University Electronic Theses, Dissertations & Projects

A primary role of the IGF-II/M6P receptor is to target lysosomal enzymes from the golgi to the lysosomes. This receptor has distinct binding sites for IGF-II and M6P, however, reciprocal interactions between these ligands have been observed (Kiess et al. 1989, 1990). Since IGF-II modulates the routing of cathepsin D in MCF-7 cells by blocking the intracellular binding of cathepsin D to the IGF-II/M6P receptor (De León et al. 1996), we hypothesized that expressing a mutant form of IGF-II that does not bind the IGF-II/M6P receptor will not interfere with lysosomal enzyme trafficking.

In our present study, we report the …

Client-Centered Versus Traditional-Directive Educational Approach: A Randomized Study Of Exercises And Perceived Control Among Patients With Type 2 Diabetes, Melissa D. Olfert

Loma Linda University Electronic Theses, Dissertations & Projects

A patient’s adherence to self-management therapies in diabetes strongly influences health outcomes, health care utilization, and ultimately health care costs. Engaging in regular exercise therapy reduces risk factors associated with type 2 diabetes. The purpose of this randomized prospective study was to determine if a client-centered approach (CCA) toward diabetes education, verses a traditional-directive approach (TDA), would improve exercise participation, perceived control, intention to exercise, and glycemic control in patients with type 2 diabetes.

Fifty-nine type 2 patients were randomized into two groups: CCA and TDA. Diabetes education in the CCA group provided empowerment toward acquiring knowledge, skills, and responsibility …

The Immunology Of Parturition, Ari Mayer Mackler

Loma Linda University Electronic Theses, Dissertations & Projects

Macrophage-derived factors have been implicated in the etiology of preterm labor but little is known about trafficking of this immune cell into the uterus or its regulation of uterine contractility in mice. Enhanced number and activation of macrophages was hypothesized to precede parturition. Studies characterized contractile activity and the distribution of macrophages in the uterus of C3/HeN mice before and after term (=day 19). Contractile activity by uterine strips on days 15 and 18 of pregnancy, the day of delivery, and 1 day postpartum indicate that an endogenous oscillator sustains high frequency contractions. Modest acceleration of the pacemaker occurred before …

Induction Of Integral Membrane Pam Expression In Att-20 Cells Alters The Storage And Trafficking Of Pomc And Pc1, Giuseppe D. Ciccotosto, Martin R. Schiller, Betty A. Eipper, Richard E. Mains

Life Sciences Faculty Research

Peptidylglycine alpha-amidating monooxygenase (PAM) is an essential enzyme that catalyzes the COOH-terminal amidation of many neuroendocrine peptides. The bifunctional PAM protein contains an NH2-terminal monooxygenase (PHM) domain followed by a lyase (PAL) domain and a transmembrane domain. The cytosolic tail of PAM interacts with proteins that can affect cytoskeletal organization. A reverse tetracycline-regulated inducible expression system was used to construct an AtT-20 corticotrope cell line capable of inducible PAM-1 expression. Upon induction, cells displayed a time- and dose-dependent increase in enzyme activity, PAM mRNA, and protein. Induction of increased PAM-1 expression produced graded changes in PAM-1 metabolism. Increased expression of …

The Role Of Gap Junctions In Congenital Diseases Of The Heart, Scott Henry Britz-Cunningham

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Gap junctions are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. Connexin43, the major protein of gap junctions in the heart, is targeted by several protein kinases that regulate myocardial cell-cell coupling. We hypothesized that mutations altering sites critical to this regulation would lead to functional or developmental abnormalities of the heart.

Methods. Connexin43 DNA from 25 normal subjects and 30 children with a variety of congenital heart diseases was amplified by the polymerase chain reaction and sequenced. Mutant DNA was expressed in cell culture and examined for its effect …

Leukemia Inhibitory Factor (Lif): Murine Preimplantation Embryo Development, Implantation Rates, And Skeletal Development, Michael Hayes Mitchell

Theses and Dissertations in Biomedical Sciences

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine which demonstrates perplexing physiological effects. It has been demonstrated that LIF is essential for implantation in mice. Little is known relating to the manner by which LIF effects pre-implantation and post-implantation development. The objectives of this project were to determine the effects LIF on pre-implantation development, to determine the effects that it may have on implantation rates, successful pregnancy rates, and resorption rates, and to determine the effects that LIF has on the skeletal development of mice. For the embryo transfer experiments, embryos were exposed to test compounds in the transfer medium …

The Role Of Glycoconjugates In Mediating Human Fertilization And Induction Of Fetomaternal Tolerance, Manish S. Patankar

Theses and Dissertations in Biomedical Sciences

Using the hemizona assay (HZA), a in vitro sperm-egg binding assay, we show that specific glycoconjugates known to inhibit immune cell interactions mediated by the selectins, potently block human sperm-egg binding. The selectin ligand sialyl Lewis^x inhibits sperm binding in the HZA by 60% at a concentration of 1 mg/ml. Our data indicates that glycodelin-A, a endometrial glycoprotein known to block sperm-egg binding in the HZA at low concentrations expresses unusual fucosylated lacdiNAc type glycans. The fucosylated lacdiNAc type sugars have been previously shown to be 15-20 fold more potent ligands of E-selectin. Glycodelin-S a seminal plasma glycoform of …

Endothelial Nitric Oxide Synthase And Growth Factor Regulation Of Flow-Mediated Vascular Remodeling, David Anthony Tulis

Theses and Dissertations in Biomedical Sciences

This study was designed to characterize structural remodeling of male Wistar rat mesenteric arteries exposed to elevated blood flow in vivo for 1, 3, or 7 days. A series of arterial ligations induced blood flow increases in ileal and second-order branch arteries compared to same animal control vessels. Neither mean carotid nor local mesenteric arterial pressures changed significantly pre- to post-ligation. The primary flow-mediated force in both vessels was shear stress with possible involvement of acute stretch-induced wall stress in the ileal artery. Significant luminal expansion and medial wall hypertrophy occurred in the ileal and second-order arteries in a time-dependent …

Differential Endometrial Responses Of Primates Vs Rodents: Screening For Antiproliferative Effects Of Antiprogestins, David Williams Burleigh

Theses and Dissertations in Biomedical Sciences

The antiprogestin, mifepristone, has previously been shown to noncompetitively inhibit estrogen-induced endometrial proliferation in nonhuman primates (van Uem et al., 1989; Wolf et al., 1989b; Neulen et al., 1990; Neulen et al., 1996). For both economical and ethical reasons, we are encouraged to identify comparative laboratory rodent models which can substitute the need to use primate models. In the following study, we compared capabilities of the rat uterine weight bioassay versus a primate uterine bioassay, to identify the noncompetitive antiestrogenic/antiproliferative effects of mifepristone.

Long-term ovariectomized monkeys were exposed to exogenous 17β-estradiol (E2) and mifepristone in doses and regimes already demonstrated …

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 …

The Effects Of Lowering Cholesterol On Vasodilation, Maria Christi Hardt

Loma Linda University Electronic Theses, Dissertations & Projects

Endothelial dysfunction has been found prior to any signs of atherosclerotic plaque formation in patients with a variety of risk factors for atherosclerosis. Elevated serum cholesterol has repeatedly been associated with endothelial dysfunction as demonstrated by impaired vasoreactivity to vasodilating stimuli.

The aim of this research was to determine whether short term lowering of serum cholesterol levels by life style changes or by cholesterol lowering medication could reverse or reduce the endothelial dysfunction. The brachial artery diameter was measured by high-resolution ultrasound at rest and during reactive hyperemia pre and postintervention. Fifty-three subjects with cholesterol levels above 240 mg/dl were …

Short And Long Term Effects Of Proton Microbeam Irradiation : In The Lateral Geniculate Nucleus Of Felis Domesticus, Chad Sherwood Reder

Loma Linda University Electronic Theses, Dissertations & Projects

Little is known of the effects of proton irradiation on neural tissue. A 1.0 mm microbeam was used on the cat lateral geniculate nucleus (LGN) to quantify the short term (< 3 months) and long term (< 9 months) effects of radiation damage. The LGN is a large structure with well defined afferent, efferent, and receptive field properties.

Electrophysiological and histological techniques were used to examine the effects of the microbeam at 60, 40, and 16 Gy, administered as a single bolus. Recordings of light evoked responses in the LGN were obtained using microelectrodes in nine animals within 12 weeks of irradiation, and 6 animals within 36 weeks of irradiation. Receptive fields were mapped onto a tangent screen using standard receptive field techniques. Histological measures included afferent …

Cortisol In The Ovine Fetus : Its Regulation And Role In Parturition, Ede Marie Apostolakis

Loma Linda University Electronic Theses, Dissertations & Projects

In fetal sheep, circulating cortisol increase during late gestation to abruptly rise 72 hours preceding birth. Although the surge in cortisol is thought to initiate the endocrine cascade which triggers parturition, it is not known what drives the prepartum rise in fetal cortisol. The first study tested the hypothesis that basal cortisol secretion is regulated by adrenocorticotropin (ACTH) which in turn, is controlled by arginine vasopressin (AVP). The fetus challenged with AVP increased plasma ACTH and cortisol concentrations. Pretreatment with an AVP V₁ receptor antagonist blocked AVP-induced plasma ACTH cortisol but failed to alter basal ACTH or cortisol. To …

The Effect Of Electrical Stimulation Of The Dorsal Raphe Nucleus On Local Cerebral Glucose Metabolism And Epileptogenesis In The Rat, Clifford C. Douglas

Loma Linda University Electronic Theses, Dissertations & Projects

Anatomic connections between the dorsal raphé and the hippocampus have been described in the literature; however, the understanding of the functional importance of these connections is not complete. In these studies the "functional" raphé-hippocampal pathway was elucidated first by the 2-deoxy-d-glucose (2-DG) method, and second by the effect of dorsal raphé electrical stimulation on kindled seizure in the rat. In the 2-DG study, differences in local rates of cerebral glucose metabolism were quantified. The pattern of 2-DG uptake differed significantly from controls (animals with electrodes placed and not receiving an electrical stimulus) and subjects stimulated in the pontine oral reticular …

Morphological And Physiological Examination Of A Demyelinating And Remyelinating Lesion, Paul Anson Felts

Theses and Dissertations in Biomedical Sciences

Multiple sclerosis causes demyelination of central nerve fibers, and it is this pathology which results in most of the symptoms of the disease. The repair of the fibers by remyelination has been advanced as a potential symptomatic therapy, but at present the conduction properties of remyelinated central fibers are not well understood. In this study the conduction properties of Schwannian or oligodendrocyte remyelinated central nerve fibers have been determined. In addition, the status of the blood-brain barrier has been examined in lesions characterized by Schwann cell remyelination. These lesions chronically lack astrocytes, a cell believed to be involved in the …

Effects Of Sodium Intake, Furosemide, And Infusion Of Atrial Natriuretic Peptide On The Urinary And Metabolic Clearances Of Arginine Vasopressin In Normal Subjects, Arnold M. Moses, Carol Jones, Carolyn B. Yucha

Nursing Faculty Research

Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) have important influences on water and electrolyte metabolism, and studies on the interactions between these hormones may have important implications. We have investigated the effects of sodium intake, furosemide, and infusion of ANP on the urinary and metabolic (nonurinary) clearances of AVP in hydrated normal subjects. On a high sodium diet there was an increase in urine volume, sodium excretion, osmolal clearance, plasma ANP concentration, and urinary clearance and fractional excretion of AVP, with a decrease in PRA. The infusion of furosemide increased urine volume, sodium excretion, osmolal clearance, and PRA, but …

Autonomic Nervous System And Cholesterol Transport, Yuan-Line Hung

Loma Linda University Electronic Theses, Dissertations & Projects

The effect of autonomic nervous system on cholesterol transport is of clinical interest because the relationship between lipoprotein metabolism and atherogenesis is expressed in coronary artery disease.

Generally speaking, beta blockers increase serum VLDL level but decrease both HDL and HDL₂ cholesterol levels without affecting the LDL in humans. We are unaware of reports concerning the effects of metoprolol on lipoprotein metabolism nor comparison of the effects of metoprolol and propranolol in the unhandled rat model. In part I we employed the unhandled rats to compared the effects of these 2 drugs administered with the drinking water in order …

Age-Related Changes In Meissner Corpuscles Of Diabetic Mice As Observed By Electron Microscopy, Vicky R. Ras

Loma Linda University Electronic Theses, Dissertations & Projects

Light touch and low-frequency vibration sense are often impaired in diabetic patients. Meissner corpuscles are distally located mechanoreceptors that respond to these stimuli. Peripheral sensory neuropathy in diabetes progresses from distal to proximal, therefore, Meissner corpuscles are ideally suited to study diabetic neuropathy in the C57BL/Ks (db/db) mouse.

Corpuscles from the forepaw digital pads of 9 diabetic and 9 nondiabetic littermates were studied by electron microscopy. These were divided into 3 age groups; 2.5 months, 10 months, and 17 months old.

Ultrastructural changes observed within various receptor components were myelin figures, multivesicular bodies, vacuoles, basal lamina duplication, abnormal and enlarged …

The Effect Of Intraperitoneally Administered Thyroxine, Thiidothyronine And Iopanoic Acid On The In Vivo And In Vitro Oxygen Consumption Rates Of Normal (C57bl/Ksj Db/M) And Diabetic (C57bl/Ksj Db/Db) Mice, A. Kay. Kalousek

Theses Digitization Project

No abstract provided.

Age-Related Changes Of Neurites In Meissner Corpuscles Of Diabetic, Vicky R. Ras

Loma Linda University Electronic Theses, Dissertations & Projects

This thesis is based on a qualitative and quantitative study of the neural component of Meissner corpuscles of diabetic and non-diabetic mice. Age-related changes were also documented in these mechanoreceptors. Corpuscles from forty-six diabetic mice and forty-six non-diabetic mice ranging from 2.5 to 17 months old were studied. Forepaw index digital pads were formalin-fixed and frozen-sectioned parallel to each digit and perpendicular to the skin. Serial sections were then silver-impregnated to allow light microscopic examination of the neurites in the corpuscles.

Neurites became more coarse, tortuous, branched, varicose, and thus more complex until middle age. Corpuscle size appeared greatest at …

The Effects Of Orally Administered Charcoal On Intestinal Gas, Herbert J. Thompson

Loma Linda University Electronic Theses, Dissertations & Projects

Our primary objectives were to determine if orally administered charcoal effectively decreased intestinal gas, and relieved subjective symptoms associated with a high gas producing meal.

The adsorptive properties of charcoal for those gases usually found in intestines (CO₂, H₂, CH₄, H₂S) were first tested by placing measured samples of each gas alone with weighted samples of activated charcoal in a respirometer.

The degree of adsorption of each gas by charcoal was determined. Charcoal effectively adsorbed H₂ and CO₂.

A group of normal human males were fed a gas producing …

A Method Of Analyzing Mandibular Movement, Richard B. Mccoy

Loma Linda University Electronic Theses, Dissertations & Projects

Mandibular movement is considered to be a fundamental factor in the study, analysis, and treatment of occlusion. For many years, dentists have realized that dental health depends upon the compatibility of mandibular movements and occlusion. This realization has led to the development of new methods and techniques for recording accurately and scientifically the movements of the mandible. In order for this data to be of scientific value, it must be stored in a usable form which is easily available for analysis.

The purpose of this research project was to develop a procedure for storing and recalling mandibular-movement information. Before such …

The Effect Of Gymnastic Routines On Blood Pressure And Pulse Rate, Robert Ferguson

Masters Theses

No abstract provided.