Physiology Commons^™

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 …

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 …

Analysis Of Serotonin And Postural Instability In Parkinson’S Disease, Sandra Kuniyoshi

Loma Linda University Electronic Theses, Dissertations & Projects

Postural instability is one of the most debilitating symptoms of Parkinson’s disease and the best clinical prognostic indicator of progressive disease. Significant differences in neuropathology, neurochemistry, response to L-dopa therapy and stereotactic surgery as well as prognosis have been identified in subtypes when patients with predominant postural instability and gait difficulty (PIGD)/Type B were differentiated from those with predominant symptoms of tremor and rigidity/Type A. Postural instability is resistant to the therapeutic effects of L-dopa, despite its continued efficacy on other Parkinson’s symptomatology, implicating the nondopaminergic mechanism of postural instability in Parkinson’s disease. Patients with significant postural instability and gait …

Cellular Responses In Escherichia Coli To Lethal And Sublethal Doses Of Ozone, Indira Ruth Komanapalli

Loma Linda University Electronic Theses, Dissertations & Projects

Ozone is a major component of photochemical smog. High levels of this pollutant, sufficient to affect human health are found in many urban areas worldwide. Though limited studies in humans are supported by extensive findings from animal experiments, a difficulty in interpreting the results of these experiments has lead to an ambiguity on the biochemical mechanism of ozone toxicity. To elucidate the mechanism by which ozone causes cell damage and eventual cell death we conducted a comprehensive study using Escherichia coli K-12 as a model.

Studies on the comparative inactivation of bacteriophage lambda (λ), Escherichia coli, and Candida albicans …

Genomic Diversity In Staphylococcus Aureus, Bret Max Barton

Loma Linda University Electronic Theses, Dissertations & Projects

Staphylococcus aureus chromosomal DNA from 125 methicillin-resistant and 10 methicillin-sensitive clinical isolates was digested with rare-cutting restriction endonucleases and subjected to pulsed-field gel electrophoresis (PFGE). Thirty-nine distinct genomic macrorestriction patterns (GPs) were identified using SmaI; 29 of these patterns are from methicillin-resistant S. aureus (MRSA).

A dendrogram showing percent similarity among the patterns was constructed which revealed the considerable genomic diversity of the collection even though the isolates had been obtained during outbreaks. The majority of the MRSA formed one broad group with two outbreak subclasses. However, 8 of the 29 MRSA GPs (28%) were diverse.

Digestion with Csp …

Aberrant Communication And Protein Kinase C In Experimental Autoimmune Thyroiditis, Joyce P. Lazarus

Loma Linda University Electronic Theses, Dissertations & Projects

Autoimmune diseases are a worldwide healthcare concern. Research has focused mainly on the role of the immune system and genetic susceptibility to autoimmune disease. However, this study investigates altered target tissue properties and their contributions to the pathogenesis of induced autoimmune thyroiditis in Lewis rats. Our hypothesis was; inflammation-induced lymphocytic infiltration and subsequent fibrosis results in physical disruption of gap junctional communication in the target tissue contributing to the disease process. Our study of intercellular communication in experimentally-induced autoimmune thyroiditis (EAT) in Lewis rats revealed a deficiency in connexin expression, connexin assembly and dye transfer [(results corroborated in murine model …

Myocardial Contractility In Fetal Sheep Exposed To Long-Term Hypoxia At High Altitude : Activator Calcium And Beta-Adrenergic Receptor Function, Vaughn A. Browne

Loma Linda University Electronic Theses, Dissertations & Projects

We studied myocardial contractility in fetal sheep exposed to ~112 days of hypoxia at high-altitude (3,820 m). We recorded left and right ventricular wet weight, and measured the inotropic responses to extracellular calcium [Ca²⁺]_o (0.2-10 mM), ryanodine (10^-10-10^-4 M), isoproterenol (10^-10-10^-6 M), and forskolin (0.01-10 uM) in isometrically contracting papillary muscles. In addition, we quantified dihydropyridine (DHPR), ryanodine (RyR), and β-adrenergic receptor densities, and measured basal and stimulated intracellular cAMP levels. In hypoxic fetuses, left ventricular wet weight was unchanged, but right ventricular weight was ~20% lower than controls. Curves describing …

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 …

Inhibitory Effects Of Isothiocyanates On The Mutagenicity And Metabolism Of Environmental Carcinogens, Solomon M. Hamilton

Loma Linda University Electronic Theses, Dissertations & Projects

The inhibitory effects of the two naturally occuning isothiocyanates, benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) on the metabolism and mutagenicity of 4-(methylnitrosamino)-l-(3-pyridyl)-lbutanone (NNK) and benzo[a]pyrene (BaP) by F344 rat and male Syrian golden hamster liver microsomes were investigated. In addition, the alkyl chain-length effects of BITC and PEITC, together with phenyl isothiocyanate (PITC) and phenylpropyl isothiocyanate (PPITC) on the metabolism and mutagenicity of NNK, and on the metabolism of testosterone were determined. Further, the effects of all four homologues of isothiocyanates on the mutagenicity of five heterocyclic amines (HCAs) IQ, MelQx, Trp-P-2, Glu-P-2 and PhIP and on the dealkylation …

Ornithine Decarboxylase And Polyamines In Perinatal Hypoxia, Satyaseelan Packianathan

Loma Linda University Electronic Theses, Dissertations & Projects

Hypoxic and hypoxic/ischemic episodes contribute to various neurological aberrations, learning disabilities, et cetera in surviving infants. Despite major advances in understanding the pathophysiology of hypoxia, the cellular basis for hypoxic-mediated injury remains poorly understood. In addition, the role of developmentally essential enzymes vis á vis their contributions, or lack thereof, to hypoxic-mediated injury has not been adequately investigated. In the series of studies comprising this dissertation, we tested the hypothesis that acute and/or chronic hypoxia affect the activity of omithine decarboxylase (ODC; E.C. 4.1.1.17), the developmentally essential enzyme in polyamine biosynthesis, in the fetal and newborn rat brain. Fetal and …

Periodontal Repair In Dogs : Evaluation Of Rhbmp-2 Carriers, Lauralee Nygaard

Loma Linda University Electronic Theses, Dissertations & Projects

This study evaluated candidate carriers for recombinant human bone morphogenic protein-2 (rhBMP-2) in periodontal reconstructive surgery.

Canine demineralized bone matrix (DBM), bovine inorganic crystallene bone matrix (Bio-Oss), bovine derived microfibrillar collagen matrix (Helistat), poly (D,L-lactide-coglycolide) micropaiticles (PLGA), and polylactic acid granules (Drilac) were used with rhBMP-2 (20 (µg/100 µl implant volume) in routine critical size canine supraalveolar periodontal defects. Contralateral defects in six beagle dogs were randomly assigned to receive: DBM/rhBMP-2, DBM-control, Bio-Oss/rhBMP-2, Helistat/rhBMP-2, PLGA/rhBMP-2, or Drilac/rhBMP-2, all with autologous blood except for Helistat and PLGA. Animals were sacrificed eight weeks post-surgery and block sections of the defects were processed …

Mechanisms Of Retinal Ganglion Cell Development In The Rhesus Macaque, Thomas C. Steineke

Loma Linda University Electronic Theses, Dissertations & Projects

At present, no effective treatments are known for many common neurological problems. For instance, degenerative diseases and central nervous system injuries are two examples of conditions for which few treatment options exist. Studying how neurons develop, and how they establish and maintain connections may provide important insights into potential treatment modalities. To this end, retinal ganglion cell structural development was studied in the fetal rhesus macaque ranging in age from embryonic day (E)60 to El65 (gestation is 165 ± 2 days). Horse radish peroxidase (HRP) retrograde labeling techniques were used to investigate changes in retinal ganglion cell structure during fetal …

Mechanism Of Action Of Pentobarbital Induced Attenuation Of Vascular Smooth Muscle Contraction, Michael R. Samardzija

Loma Linda University Electronic Theses, Dissertations & Projects

Pentobarbital (PB) vasodilates dog mesenteric and cerebral arteries precontracted with KC1, PGF_2α, caffeine or norepinephrine. It is postulated that PB causes this dilation by reducing Ca²⁺ influx as a non-specific Ca²⁺ channel blocker, or decreasing intracellular Ca²⁺ release. We examined PB effects on intracellular Ca²⁺ release (ICR) and extracellular Ca²⁺ influx (ECI) by stimulating Sprague-Dawley rat tail artery rings with either 100 mM KC1, 50 uM phenylephrine (PE), or two different electrical field stimulation (EES) parameters: tetrodotoxin (TTX; 1 uM) sensitive, or perivascular nerve, (NEFS) stimulation (10 Hz, 0.3 ms, 50 V, 30 …

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 …

An Intramural, Tension-Modulating Reflex In The Rat Caudal Artery, Greg G. Geary

Loma Linda University Electronic Theses, Dissertations & Projects

Electrical field stimulation (EES) of preconstricted arteries causes relaxation. This relaxation is of either neuronal, vascular smooth muscle, and/or endothelial origins. We have shown that EFS-induced relaxation of intact, phenylephrine (PE) preconstricted rat tail artery (RTA) rings was dependent upon the extracellular concentration of Ca++. Inhibiting either nitric oxide (NO) synthesis with N-nitro-L-arginine methyl ester (L-NAME), or the synthesis of cyclic guanosine monophosphate (cGMP) with methylene blue (MB) reduced the EFS-induced relaxation. In addition, inhibition of K_Ca++-dependent hyperpolarization with tetraethylammonium (TEA), or K_ATP hyperpolarization with BaCl₂ or glibenclamide also reduced EFS-induced relaxation. L-arginine reversed the effect …

Inhibition Of Nnk Mutagenesis And Metabolism By Chemopreventive Phytochemicals, Cecil Henry Miller

Loma Linda University Electronic Theses, Dissertations & Projects

Approximately one third of all cancer deaths in the United States can be linked to the use of tobacco products. Cessation of smoking is not always an effective prevention method, especially since nicotine is so addictive. For those individuals who continue to use tobacco products, chemoprevention may be an alternative to reduce their cancer risk. We have investigated the chemopreventive efficacy of five phenolic (catechin, ellagic acid, escletin, esculin and propyl gallate) and five non-phenolic (capsaicin, silymarin, diallyl sulfide, tannic acid, and d-limonene) phytochemicals on tobacco-specific nitrosamine (NNK)-induced mutagenesis and NNK metabolism. In the mutagenesis studies, Salmonella typhimuriumstrain TA1535 …

Effects Of Portuguese Man-Of-War (Physalia Physalis) Venom On Isolated Rabbit Atria, Wayne R. Bonlie

Loma Linda University Electronic Theses, Dissertations & Projects

The cardiac effects of Portuguese man-of-war venom were studied using isolated atria from rabbits. Venom added (7.1 µg protein/ml) to the bath solution stimulates heart rate 120% (P < 0.01) and increases contraction amplitude 308% (P < 0.001). Both effects are dependent on bath concentrations of venom and calcium. The increase in contraction amplitude is significantly attenuated by diltiazem (0.8 µM) and atenolol (10 µM). Atenolol, a β1-adrenergic antagonist, completely blocks the increase in heart rate. Dantrolene (10 µM) did not significantly block the venom's effects. Ryanodine binding increases in the presence of venom showing that the venom is not in competition for calcium channels on the sarcoplasmic reticulum. These results suggest that the venom acts on the sarcolemma to increase calcium permeability, thereby causing an increase in contraction amplitude and possibly causing β1-adrenergic stimulation.

Thymic Peptide Modulates Glutathione Redox Cycle And Antioxidant Enzymes In Macrophages, Choon Sil Park

Loma Linda University Electronic Theses, Dissertations & Projects

The effect of a 6-kDa thymic peptide (TP) on the oxidative burst of a murine macrophage cell line J774 was determined. TP (12.5-200 μg/ml) was incubated with 5 x 10⁵ J774 cells at 37° C and 5% C0₂ for 18 h and oxidative burst was triggered by zymosan; chemiluminescence was amplified by luminol and measured in an automated luminometer. TP exhibited a concentration-dependent inhibition of oxidative burst. To study the mechanisms involved in TP’s inhibition of oxidative burst, its effect on the glutathione (GSH) redox cycle, GSH biosynthesis, and antioxidant enzymes was investigated. TP was shown to increase …

Effects Of Dietary Calcium And Fasting On Osteoclast Recession And Recruitment In Calcium Deficient Rats, Kenneth R. Wright

Loma Linda University Electronic Theses, Dissertations & Projects

The osteoclast, a multinucleated giant cell, has as its role the resorption of bone matrix with consequent release of calcium. The osteoclast is thought to derive from a pluripotent stem cell which also gives rise to monocytes and macrophages. The development, activation, and inhibition of osteoclasts are influenced by a number of systemic and local factors. The release of these factors is influenced by changes in the dietary status of the animal. Calcium deficiency is known to stimulate the recruitment and activity of large numbers of osteoclasts. These osteoclasts can subsequently be inhibited by increasing dietary calcium intake. Disappearance of …

Neurophysiologic Bases For Abnormal Muscle Coactivation Patterns In Hemiparetic Stroke, Julius P.A. Dewald

Loma Linda University Electronic Theses, Dissertations & Projects

To study disturbed muscle activation patterns in hemiparetic stroke, the EMG activity in spastic-paretic and contralateral elbow muscles of 10 stroke subjects were compared during graded directionally varying voluntary isometric contractions. We observed significant shifts in the peak EMG angle and increases in the angular range of EMG activity in the impaired upper limb. Furthermore, we observed stereotypic coactivation of many muscles acting at the same joint or at different joints across all subjects.

The effect of elbow angle changes on muscle coactivation patterns was studied by examining isometric torque-angle relations under passive and active conditions in 8 stroke subjects. …

Transforming Growth Factor-Beta 1 Expression In Developing Ovine Teeth As Visualized By In Situ Hybridization, Søren Jepsen

Loma Linda University Electronic Theses, Dissertations & Projects

Recently we demonstrated that human dentin contained relatively high amounts of transforming growth factor beta (TGF-ß) and proposed that dentin TGF-ß originated from odontoblasts. Because of the suggested role of TGF-ß in mediating cellular interactions in dental cell development by paracrine mechanisms, we studied the expression of TGF-ß message in developing teeth by in situ hybridization. 5 µm serial sections of neonatal sheep mandibular third molars that had been fixed in glutaraldehyde and paraffin-embedded were used for in situ analysis. An [³⁵S]-labeled cRNA probe, complementary to TGF-ß1 mRNA, was constructed from human TGF-ß1 cDNA. Northern analysis of total …

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 …

Plasticity Of The Gnrh Neuronal System During Sexual Maturation Of The Male Djungarian Hamster, Kevin L. Buchanan

Loma Linda University Electronic Theses, Dissertations & Projects

Onset of puberty in male Djungarian hamsters is characterized by increased pituitary gonadotropin secretion and testes maturation, and is controlled by neurons within the brain which secrete gonadotropin-releasing hormone (GnRH). Puberty is associated with increased numbers of morphologically unipolar, but not bipolar, GnRH neurons in the medial preoptic area (MPOA) and diagonal band of Broca (DBB). To test the hypothesis that delayed sexual maturation arrests this increase, males were exposed to short days or administered melatonin. Males with delayed puberty had significantly fewer unipolar GnRH neuron numbers in the MPOA and DBB comparable to pubertal controls in long days. Unipolar …

Histomorphometric Analysis Of Primate Periodontal Tissues Following Corticotomy In Orthodontics, Wuiteng Koh

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to evaluate the prevalence of specific cell types and structures at the active tooth movement site in corticotomized and non-corticotomized specimens obtained from a previous study, and to consider the hypothesis that corticotomy facilitated orthodontics is efficacious due to an inflammatory response rather than tooth-bone block movement. Specimens from 3 monkeys, each of which had a treatment and control quadrant in each arch, were sectioned, mounted on glass slides, and stained with Giemsa, haematoxylin, and Safranin stains. A histomorphometric analysis was performed with DataVoice™, a voice activated computer system which allowed for digitization of …

Gaba As A Putative Neurotransmitter In The Optic Lobes Of The Crab Hemigrapsus Nudus, Carol L. Fulenwider

Loma Linda University Electronic Theses, Dissertations & Projects

Gamma-aminobutyric acid ( GABA ) is a widely occurring inhibitory neurotransmitter in vertebrate and invertebrate neural tissue. To explore the role of GABA as a putative neurotransmitter in the optic lobes of the crab Hemigrapsus nudus,

light microscope autoradiography ( LM ARG ), light microscope immunocytochemistry ( LM ICC ), and neurochemical techniques were employed. ARG labeling of ³H-GABA was observed over specific neuronal cell bodies and axon fibers in the two outer optic neuropils, the lamina ganglionaris and the medulla externa. Biochemical analysis of ³H-GABA uptake revealed little surface receptor binding as picrotoxin and bicuculline did not …

Catecholamines And The Regulation Of Uterine Contractions In The Pregnant Rhesus Macaque, Cahleen Mae Mcnutt

Loma Linda University Electronic Theses, Dissertations & Projects

This study was designed to test the hypothesis that: 1) maternal and/or amniotic fluid catecholamines or prostaglandins display nocturnal activity rhythms similar to those of the myometrial contractility in the pregnant rhesus macaque and, 2) catecholamines stimulate prostaglandin production by fetal membranes. Paired maternal arterial blood and amniotic fluid samples were collected at 0900 h (AM) and 2100 h (PM) from chronically catheterized rhesus macaques until delivery and analyzed for prostaglandin metabolites (PGFM and PGEM-II) and catecholamines (norepinephrine, epinephrine, and dopamine). Uterine activity data was continuously recorded. A rhythm in uterine contractility was observed, with peak activity between 1900 and …

Topographic Development Of The Corticocollicular Projection In The Neonatal Rat, F. Allen Richburg Ii

Loma Linda University Electronic Theses, Dissertations & Projects

The density and distribution of labeled cortical cells was examined following discrete deposits of retrograde tracers into the superior colliculus (SC) of neonatal and adult rats to study the topographic order of SC afferents from the cortex during the initial phase of axon ingrowth. Small deposits of red and green latex microspheres (0.02-0.05ul) were placed into the SC of rats ranging in age from birth to adulthood using glass micropipettes (tip diameter 25-35um). The animals, following a 48hr survival period, were deeply anesthetized and perfused with normal saline followed by a 10% formal-saline solution. The brains were sectioned coronally at …

Molecular Mechanisms Of Physalia Physalis Venom Modulation Of Cardiac And Vascular Functions, Eva Luo

Loma Linda University Electronic Theses, Dissertations & Projects

Portuguese man-of-war (Physalia physalis)venom has profound effects on the cardiovascular system of man and animals. The venom produces vascular relaxation in norepinephrine precontracted, intact rabbit femoral arterial rings by stimulating vasodilatory prostaglandin synthesis in the endothelium. This action does not depend on endotheliumderived relaxing factor (EDRF). P. physalis venom produces a vascular constriction on KC1 depolarized, intact rings. This is completely inhibited by dibenzyline and yohimbine. Increased membrane permeability to calcium may be involved in direct vascular smooth muscle stimulation. The venom has a positive inotropic effect on rat atrial preparations, which is intensified by increased extracellular calcium concentration. …

Effect Of Glucose Administration On Hamster Liver S9-Mediated Mutagenesis, Metabolism And Dna-Binding Of Benzo[A]Pyrene And Aflatoxin B1, Daniel C. Rubano

Loma Linda University Electronic Theses, Dissertations & Projects

Hamster liver S9 prepared from control animals and animals given 30% glucose in drinking water 48 h before time of sacrifice was used in studies of benzo[a]pyrene (BaP) and aflatoxin (AFB₁)-induced mutagenesis, metabolism of BaP and AFB₁, and metabolite binding to calf thymus DNA. BaP-induced mutagenesis in Salmonella typhimurium TA100 was reduced 38.5% while AFB₁-induced mutagenesis was increased 36% by S9 from glucose-treated hamsters. The reduction of [³H]BaP metabolite binding to calf thymus DNA in incubations with S9 from glucose-treated hamsters correlated with a decrease in unknown BaP metabolite-deoxyribonucleoside adducts isolated by …