Medical Physiology Commons^™

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …

Mapping The Spatial And Temporal Dynamics Of Sensorimotor Integration During The Perception And Performance Of Wallowing, Megan E. Cuellar

Theses and Dissertations (ETD)

Similar to other complex sequences of muscle activity, swallowing relies heavily upon ‘sensorimotor integration.’ It is well known that the premotor cortex and primary sensorimotor cortices provide critical sensorimotor contributions that help control the strength and timing of swallowing muscle effectors. However, the temporal dynamics of sensorimotor integration remains unclear, even when performed normally without neurological compromise. Recent advances in EEG analysis blind source separation techniques via independent component analysis offer a novel and exciting opportunity to measure cortical sensorimotor activity in realtime during swallowing, concurrently with muscle activity during swallow initiation. In the current study, mu components were identified, …

Central Role Of Carotid Body Chemoreceptors In Disordered Breathing And Cardiorenal Dysfunction In Chronic Heart Failure., Noah J. Marcus, Rodrigo Del Rio, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

Oscillatory breathing (OB) patterns are observed in pre-term infants, patients with cardio-renal impairment, and in otherwise healthy humans exposed to high altitude. Enhanced carotid body (CB) chemoreflex sensitivity is common to all of these populations and is thought to contribute to these abnormal patterns by destabilizing the respiratory control system. OB patterns in chronic heart failure (CHF) patients are associated with greater levels of tonic and chemoreflex-evoked sympathetic nerve activity (SNA), which is associated with greater morbidity and poor prognosis. Enhanced chemoreflex drive may contribute to tonic elevations in SNA by strengthening the relationship between respiratory and sympathetic neural outflow. …

Analysis For Co-Occurring Sequence Features Identifies Link Between Common Synonymous Variant And An Early-Terminated Npc1 Isoform, Mercedeh Movassagh, Prakriti Mudvari, Maria Kokkinaki, Nathan J. Edwards, Nady Golestaneh, Anelia Horvath

Pharmacology and Physiology Faculty Publications

Direct assessment of allelic phase for DNA and RNA features of diploid genomes has been challenging for Sanger sequencing, due to its allele-conflating base-calling signal. Massively parallel sequencing technologies are based on the generation of a continuous copy of a single strand sequence segments, thus preserving the allelic relation between the features of the original molecules. We have performed a transcriptome-wide search for co-occurrence of variant nucleotides and exon-intron boundaries positioned within the length of a single sequencing read. Analysis of 75 human transcriptomes from retinal pigment epithelia (RPE), glioblastoma, low-grade brain tumor, breast cancer and colon cancer, have identified …

Visualization Of Oxytocin Release That Mediates Paired Pulse Facilitation In Hypothalamic Pathways To Brainstem Autonomic Neurons, Ramon A. Pinol, Heather Jameson, Anastas Popratiloff, Norman H. Lee, David Mendelowitz

Pharmacology and Physiology Faculty Publications

Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN) contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work …

Swimming Against The Tide: Investigations Of The C-Bouton Synapse, Adam S. Deardorff, Shannon H. Romer, Patrick M. Sonner, Robert E. W. Fyffe

Neuroscience, Cell Biology & Physiology Faculty Publications

C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a “signaling ensemble”) for cholinergic regulation of outward K⁺ currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges …

Role Of Astrocyte Network In Edema After Juvenile Traumatic Brain Injury, Andrew Minoru Fukuda

Loma Linda University Electronic Theses, Dissertations & Projects

Juvenile traumatic brain injury (jTBI) is the leading cause of death and disability in young children and adolescents. Despite its lasting detrimental effects on the developing brain, no pharmacological treatment exists. One of the pathological hallmarks of jTBI is edema. Astrocytes play a key role in the edema process, and have been hypothesized that numerous astrocyte networks allow communication and propagation of edema and secondary injury spread. Two key astrocyte proteins are hypothesized to have a central role in the edema process: Aquaporin 4 (AQP4) and Connexin 43 (Cx43). AQP4 is expressed extensively in astrocyte endfeet, which surrounds the blood …

Cc2d1a Regulates Human Intellectual And Social Function As Well As Nf-Κb Signaling Homeostasis., M. Chiara Manzini, Lan Xiong, Ranad Shaheen, Dimira E Tambunan, Stefania Di Costanzo, Vanessa Mitisalis, +15 Additional Authors

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor κB (NF-κB). Cc2d1a gain and loss of function both increase activation of NF-κB, revealing a critical role of Cc2d1a in homeostatic control of intracellular signaling. Cc2d1a knockdown in neurons …

Effects Of Various Partial Body Cooling Techniques On Core Temperature During Recovery From Prolonged Cycling-Induced Heat Stress, Afton Danielle Seeley

Masters Theses

The purpose of this study was to investigate the effects of using an ice-vest and a palm cooling device on core and skin temperatures, heart rate, and perceived thermal comfort during a one hour recovery period following exercise in the heat. Ten recreationally active adults cycled for one hour at 50% V0₂ peak on a cycle ergometer while exposed to 36°C 45%relative humidity environmental conditions. Following exercise, each subjectwas exposed to an ice vest, a palm cooling device, or a non cooling control while seated in the environmental chamber for 60 more minutes. No significant differencewas found betweenany of …

Comparison Of Dual- And Tri-Axial Accelerometer Accuracy, Lindsay Powell Toth

Masters Theses

The purpose of this study was to investigate the accuracy of the Omron HJ-720ITC and the Fitbit Zip activity monitors with regard to step count, energy expenditure, and distance traveled measurements. The importance of this research rests in the success rates of pedometer-based physical activity interventions which have been shown to increase physical activity while also enabling weight loss and lowering blood pressure in the adult population. Activity monitors available for retail sale must be found accurate for proper participation in exercise interventions especially low-cost devices as used in this study.

In order to test the accuracy of the Omron …

Survivin As Potential Mediator To Support Autoreactive Cell Survival In Myasthenia Gravis: A Human And Animal Model Study, Linda Louise Kusner, Michael J. Ciesielski, Alexander Marx, Henry J. Kaminski, Robert A. Fenstermaker

Pharmacology and Physiology Faculty Publications

The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer …

Kinase Insert Domain Receptor/Vascular Endothelial Growth Factor Receptor 2 (Kdr) Genetic Variation Is Associated With Ovarian Hyperstimulation Syndrome, Travis J. O'Brien, Arthur F. Harralson, Tuyen Tran, Ian Gindoff, Funda E. Orkunoglu-Suer, David Frankfurter, Paul Gindoff

Pharmacology and Physiology Faculty Publications

Background

The objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH).

Methods

This was a case-control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome variables, SNP and haplotype frequencies were compared between control (n = 155) and OHSS (n = 19) groups.

Results

Patients who developed OHSS had significantly higher response markers (estradiol levels …

Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA). However, whether these synapses express vesicular glutamate transporters (VGLUTs) capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT) contacting calbindin-immunoreactive (-IR) Renshaw …

Ponatinib-Induced Adverse Effects: Thrombocytopenia, Pancreatitis And Hepatoxicity-- A Case Report, Saba Hasan, Crystal Fedorkiv, Naba Rahman, Jennifer Andres

Research Day

Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disease that generates from malignant transformation of pluripotent hematopoietic stem cells. First line treatment for CML is the tyrosine kinase inhibitor (TKI), imatinib. For patients resistant or intolerant to imatinib, other TKIs, dasatinib, nilotinib, and ponatinib, are approved treatments. Patients who are resistant or intolerant to other agents are started on ponatinib as a last line option. Common adverse events of ponatinib are hypertension, dry skin, rash, abdominal pain, constipation, and nausea. More serious adverse effects include cardiovascular effects, fluid retention, pancreatitis, severe myelosuppression, and hepatotoxicity. Treatment for these adverse effects can …

Targeting Therapy To The Neuromuscular Junction: Proof Of Concept, Linda L. Kusner, Namita Satija, Georgiana Cheng, Henry J. Kaminski

Pharmacology and Physiology Faculty Publications

Introduction: The site of pathology in myasthenia gravis (MG) is the neuromuscular junction (NMJ). Our goal was to determine the ability to direct complement inhibition to the NMJ.

Methods: A single-chain antibody directed against the alpha subunit of the acetylcholine receptor was synthesized (scFv-35) and coupled to decay-accelerating factor (DAF, scFv-35-DAF). scFv-35-DAF was tested in a passive model of experimentally acquired MG.

Results: Administration of scFv-35-DAF to mice deficient in intrinsic complement inhibitors produced no weakness despite confirmation of its localization to the NMJ and no evidence of tissue destruction related to complement activation. Rats with experimentally …

Evidence That Bdnf Regulates Heart Rate By A Mechanism Involving Increased Brainstem Parasympathetic Neuron Excitability, Ruqian Wan, Letitia A. Weigand, Ryan Bateman, Kathleen Griffioen, David Mendelowitz, Mark P. Mattson

Pharmacology and Physiology Faculty Publications

Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haploinsufficiency exhibit elevated resting heart rate, and infusion of BDNF intracerebroventricularly reduces heart rate in both wild-type and BDNF+/− mice. The atropine-induced elevation of heart rate is diminished in BDNF+/− mice and is restored by BDNF infusion, whereas …

9-Phenanthrol And Flufenamic Acid Inhibit Calcium Oscillations In Hl-1 Mouse Cardiomyocytes, Rees A. Burt

Undergraduate Honors Theses

Electrical potentials exist across the membranes of nearly every cell type in the body. In addition, excitable cells, such as neurons, myocytes and even some endocrine cells elicit electrochemical fluctuations, action potentials (AP), in the cell membrane to initiate cell-to-cell communication or intracellular processes. The basis for the electrical potential is rooted within an array of complex interactions between monovalent ions and their associated membrane channels and transporters that regulate the flux of these charged species across the hydrophobic bilayer. Here, an expansion of our recently published work [1] will serve to explore the modern concepts regarding the …

Cyclic Nucleotide-Dependent Phosphorylation Regulates Bk-Ca Channel Activity In Human Coronary Artery Smooth Muscle Cells, Raeonda Williams

PCOM Biomedical Studies Student Scholarship

Cardiovascular diseases (CVD) can induce dysfunction in organ systems by attenuating normal blood flow. Gonadal steroids are vasoactive hormones, but their role in contributing to cardiovascular function remains controversial. We have demonstrated that gonadal steroids can relax coronary arteries by opening the large-conductance, calcium- and voltage-activated potassium (BKca) channel in smooth muscle cells by increasing cyclic nucleotide levels; however, the signaling pathways involved remain to be elucidated. The purpose of this study was to identify how phosphorylation (via cAMP- and cGMP-dependent protein kinases) I dephosphorylation (via phosphoprotein phosphatase 2A, PP2A) regulates BKca channel activity in human coronary artery smooth muscle …

Novel Therapeutic Approaches For Ischemic Heart And Brain Injury: Modulation Of Toll-Like Receptor-Mediated Signaling Pathways And Pi3k/Akt Signaling, Chen Lu

Electronic Theses and Dissertations

Innate immune and inflammatory responses contribute to myocardial and cerebral ischemia/reperfusion (I/R) injury. Toll-like receptors (TLRs) play a critical role in the induction of innate immune and inflammatory responses via activation of nuclear factor kappa B (NF-κB). We have shown that activation of NF-κB contributes to myocardial and cerebral I/R injury. Indeed, inhibition of TLR4-mediated NF-κB activation significantly decreased myocardial and cerebral I/R injury via activation of PI3K/Akt signaling. PI3K/Akt signaling is an important pathway in regulating cellular survival and inflammatory responses. Therefore, an important question is how to differentially modulate PI3K/Akt signaling and TLR/NF-κB-mediated signaling pathway during I/R injury? …

Extracellular Ubiquitin: Role In Cardiac Myocyte Apoptosis And Myocardial Remodeling, Christopher Ray Daniels

Electronic Theses and Dissertations

Activation of sympathetic nervous system is a key component of myocardial remodeling that generally occurs following ischemia/reperfusion (I/R) injury and myocardial infarction. It induces cardiac myocyte apoptosis and myocardial fibrosis, leading to myocardial dysfunction. Intracellular ubiquitin (UB) regulates protein turnover by the UB-proteosome pathway. The biological functions of extracellular UB in the heart remain largely unexplored. Previously, our lab has shown that β-adrenergic receptor (β-AR) stimulation increases extracellular UB levels, and extracellular UB inhibits β-AR-stimulated apoptosis in adult rat ventricular myocytes (ARVMs). This study explores the role of extracellular UB in myocyte apoptosis, fibroblast phenotype and function, and myocardial remodeling …