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Articles 1 - 18 of 18
Full-Text Articles in Medical Physiology
Dissecting The Physiological Roles Of Ulk1/2 In The Mouse Brain, Bo Wang
Dissecting The Physiological Roles Of Ulk1/2 In The Mouse Brain, Bo Wang
Theses and Dissertations (ETD)
Mammalian UNC-51–like kinases 1 and 2 (ULK1 and ULK2), Caenorhabditis elegans UNC-51 and Drosophila melanogaster Atg1 are redundant serine/threonine kinases that regulate flux through the autophagy pathway in response to various types of cellular stress. C. elegans UNC-51 and D. melanogaster Atg1 also promote axonal growth and defasciculation, and disruption of these genes results in defects in axon guidance in invertebrates. Germline Ulk1/2-deficient mice die perinatally. Therefore, we used a conditional-knockout approach to investigate the roles of ULK1/2 in the brain. Mice lacking Ulk1 and Ulk2 in their central nervous systems (CNS) showed defects in axonal pathfinding and defasciculation affecting …
The Role Of The Mir-200 Family On The Tumor Suppressor Rassf2 And The Effect On Mapk Pathway Activity In Colorectal Cancer., Jane V. Carter
The Role Of The Mir-200 Family On The Tumor Suppressor Rassf2 And The Effect On Mapk Pathway Activity In Colorectal Cancer., Jane V. Carter
Electronic Theses and Dissertations
This dissertation investigated the role of the miR-200 family in normal colon epithelial (CCD 841) and Dukes’ C (HT-29) colorectal cancer (CRC) cell lines. Our aim was to characterize expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) in colorectal cell lines, study their effect on the tumor suppressor Ras Associated Domain-Containing Protein (RASSF) 2 and on subsequent activity within the mitogen-activated protein kinase (MAPK) signaling pathway. We wanted to determine whether regulation of miR-200 family members could change cell behavior towards more “cancer-like” in a normal colon epithelium (CCD 841) cell line, or less “cancer-like” in a …
Evaluating Cardiovascular Dysfunction During Increased Activity And Exercise Rehabilitation Following Incomplete Thoracic Spinal Cord Injury In The Adult Rat., Kathryn A. Harman
Evaluating Cardiovascular Dysfunction During Increased Activity And Exercise Rehabilitation Following Incomplete Thoracic Spinal Cord Injury In The Adult Rat., Kathryn A. Harman
Electronic Theses and Dissertations
Spinal cord injury (SCI) results in whole-body dysfunction. While the majority of SCI research is focused on improving locomotor function after injury, cardiovascular (CV) disease continues to be the leading cause of morbidity in the chronic SCI patient population. The combination of injury-induced destruction of autonomic pathways, maladaptive plasticity within lumbosacral circuits, and the progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Currently, there is little emphasis on implementing appropriately-timed acute rehabilitation techniques aimed to curtail maladaptive remodeling and improve CV outcomes. Furthermore, no pre-clinical or clinical studies have investigated the most appropriate time-course …
Role Of Occludin In The Regulation Of Epithelial Tight Junctions, Bhargavi Manda
Role Of Occludin In The Regulation Of Epithelial Tight Junctions, Bhargavi Manda
Theses and Dissertations (ETD)
Tight junctions (TJ) constitute the primary component of epithelial barrier function, a disruption of which is involved in the pathogenesis of many gastrointestinal, pulmonary and renal diseases. Occludin is the major transmembrane protein of TJ, a deletion of which leads to a complex phenotype including chronic inflammation in several epithelial tissues of occludin deficient mice and poor TJ integrity in epithelial cell lines. Its down regulation was seen in Crohn’s disease, tumors of the colon, brain, endometrium and breast cancer. Occludin is also known to be a target that enables Hepatitis C Virus infection and bacterial pathogenesis. But the specific …
Neuroprotective Molecules And Strategies In A Rat Model Of Neonatal Hypoxic Ischemic Encephalopathy, Brandon Joseph Dixon
Neuroprotective Molecules And Strategies In A Rat Model Of Neonatal Hypoxic Ischemic Encephalopathy, Brandon Joseph Dixon
Loma Linda University Electronic Theses, Dissertations & Projects
Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. Since there are no established therapies for …
Maternal Nutrient Restriction With Fetal Growth Restriction In Guinea Pigs Impacts Brain Development And Neuroimaging Correlates In Neonatal Offspring, Catherine Nevin
Maternal Nutrient Restriction With Fetal Growth Restriction In Guinea Pigs Impacts Brain Development And Neuroimaging Correlates In Neonatal Offspring, Catherine Nevin
Electronic Thesis and Dissertation Repository
Aberrant brain development in utero accompanied by fetal growth restriction (FGR) increases the risk of neurodevelopmental disorders in later life. However there are limited non-invasive biomarkers in the brain for the early identification of said neurodevelopmental disorders in an animal model of FGR. Guinea pig sows were fed either ad libitum (Control) or 70% of the control diet pre-pregnancy, increasing to 90% at mid-pregnancy (MNR) creating appropriately grown (AGA) Control and FGR-MNR neonates, respectively. Three to four weeks corrected post-natal age, neonates were imaged using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques, and were killed 48-72 hours later for …
The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka
The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka
Electronic Theses and Dissertations
Global augmentation of protein O-GlcNAcylation occurs in response to a myriad of stressors and confers a survival advantage at the cellular level. This protective phenomenon has been demonstrated to mediate cardioprotection through various in vitro and in vivo studies during ischemia-reperfusion, myocardial infarction, and oxidative stress; however, relatively little is known of the regulation of protein O-GlcNAcylation. Protein O-GlcNAcylation is regulated by two antagonistic enzymes, namely, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ablation of cardiomyocyte OGT, the enzyme that catalyzes the addition of O-GlcNAc to proteins, exacerbates cardiac dysfunction during infarct-induced heart failure (HF). However, little is known of the …
Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva
Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva
Electronic Theses and Dissertations
Background: Hyperhomocysteinemia (HHcy) has been observed to promote hypertension, but the mechanisms are unclear. Toll-like receptor 4 (TLR-4) is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. TLR-4 activation has been shown to promote inflammation that has been associated with pathogenesis of hypertension. In this study, we hypothesize that HHcy induces hypertension by TLR-4 activation that promotes inflammatory cytokine up-regulation (IL-1β, IL-6, TNF-α) and initiation of mitochondrial dysfunction leading to cell death and chronic vascular inflammation. Methods: To test this hypothesis, we used C57BL/6J mice (WT); Cystathionine-β-synthase deficient mice (CBS+/-) with genetic mild …
Malignant Hyperthermia, Aaron Roth
Malignant Hyperthermia, Aaron Roth
Nursing Student Class Projects (Formerly MSN)
Malignant hyperthermia is a rare disease trait and can take place in a variety of settings. If not treated in a timely manner, the consequences will be dire. It is recommended that nurses and other healthcare personnel be properly educated on MH crises. By detecting the signs and symptoms associated with the disease, providers can efficiently remedy the crisis and save patient lives (Seifert, 2014). Since the discovery of dantrolene in 1975 and the advancement of genetics regarding MH, death rates dropped from about 80% to about 5% (Schneiderbanger et al., 2014). Today there is a MH group called the …
Complex Regional Pain Syndrome, Maria A. Hendrix
Complex Regional Pain Syndrome, Maria A. Hendrix
Nursing Student Class Projects (Formerly MSN)
Complex regional pain syndrome (CRPS) is a chronic and often disabling condition that is seen in many patients seeking pain management. The condition leaves patients in excruciating pain that is disproportionate to the inciting injury. In addition, patients with this pain disorder experience abnormal sensations such as cold and heat allodynia, hyperalgesia, edema, abnormal sudomotor activity and trophic changes (D. Lee et al., 2015). CRPS disproportionally affects four times as many women as men (Alexander, Peterlin, Perreault, Grothusen, & Schwartzman, 2012). There are two types of CRPS: type 1, often referred to as reflex sympathetic dystrophy (RSD), is not evident …
Mechanisms Of Post-Hemorrhagic Hydrocephalus After Germinal Matrix Hemorrhage, Damon William Klebe
Mechanisms Of Post-Hemorrhagic Hydrocephalus After Germinal Matrix Hemorrhage, Damon William Klebe
Loma Linda University Electronic Theses, Dissertations & Projects
The inherently fragile vasculature of the germinal matrix is susceptible to rupture, possibly as a result of hemodynamic and cardiorespiratory instability associated with prematurity. Germinal matrix hemorrhage is a leading cause of morbidity and mortality in preterm and/or very low birthweight infants, and post-hemorrhagic hydrocephalus is major consequence of severe grade hemorrhages. Chronic post-hemorrhagic hydrocephalus treatment involves surgical insertion of shunts, which are costly and prone to complications. Thus, a safe non-invasive therapeutic approach towards post-hemorrhagic hydrocephalus clinical management would significantly improve the quality of life for this patient population. Thrombin, cerebroventricular blood clots, and iron have been identified as …
Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue
Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue
Loma Linda University Electronic Theses, Dissertations & Projects
Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of …
The Influence Of Mir-99a On Mtor Signaling Regulation In Colorectal Cancer Cell Lines., Jonathan Rice
The Influence Of Mir-99a On Mtor Signaling Regulation In Colorectal Cancer Cell Lines., Jonathan Rice
Electronic Theses and Dissertations
Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. These are staggering statistics for a disease that can essentially be cured if caught early and the pathology is favorable to therapeutic intervention. There is currently a drastic decrease in five year survival as the cancer stage increases from locally confined disease to metastatic disease. These statistics suggest that although some strides have been made with colon cancer screening and early intervention, there is still much room for improvement in both screening and treatment of CRC. One of the pathways that have …
Role Of Slit2 In Reducing Complications After Surgical Brain Injury, Prativa Sherchan
Role Of Slit2 In Reducing Complications After Surgical Brain Injury, Prativa Sherchan
Loma Linda University Electronic Theses, Dissertations & Projects
Surgical brain injury (SBI) is the inadvertent injury to brain tissue at the perisurgical site which occurs due to neurosurgical maneuvers such as incision, retraction, and electrocoagulation that can result in post-operative complications. Blood brain barrier (BBB) disruption and neuroinflammation are major pathophysiological consequences after neurosurgical injury. Blood brain barrier dysfunction leads to increased influx of water and plasma proteins as well as peripheral immune cell infiltration into the brain parenchyma that further potentiates brain edema and worsens post-operative neurological function. Activated resident immune cells and infiltrated peripheral immune cells release inflammatory mediators and promote oxidative stress and cell death …
Histological And Behavioral Consequences Of Repeated Mild Traumatic Brain Injury In Mice, Amanda Nicholle Bolton Hall
Histological And Behavioral Consequences Of Repeated Mild Traumatic Brain Injury In Mice, Amanda Nicholle Bolton Hall
Theses and Dissertations--Physiology
The majority of the estimated three million traumatic brain injuries that occur each year are classified as “mild” and do not require surgical intervention. However, debilitating symptoms such as difficulties focusing on tasks, anxiety, depression, and visual deficits can persist chronically after a mild traumatic brain injury (TBI) even if an individual appears “fine”. These symptoms have been observed to worsen or be prolonged when an individual has suffered multiple mild TBIs. To test the hypothesis that increasing the amount of time between head injuries can reduce the histopathological and behavioral consequences of repeated mild TBI, a mouse model of …
Protein Kinase A And Epac Mediate Chronic Pain After Injury: Prolonged Inhibition By Endogenous Y1 Receptors In Dorsal Horn, Weisi Fu
Theses and Dissertations--Physiology
Inflammation or nerve injury sensitizes several populations of nociceptive neurons in the dorsal horn of the spinal cord, including those that express the neuropeptide Y (NPY) Y1 receptor (Y1R). Our overall hypothesis is that after tissue or nerve injury, these Y1R-expressing neurons enter a state of latent sensitization (LS) that contributes to vulnerability to the development of chronic pain; furthermore, LS is under the tonic inhibitory control of endogenous Y1R signaling. First, we evaluated the intracellular signaling pathways that become activated in Y1R-expressing neurons and participate in LS. To do this, we established behavioral models of inflammatory or neuropathic pain, …
Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes, Erin M. Wolf Horrell
Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes, Erin M. Wolf Horrell
Theses and Dissertations--Physiology
Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a Gs protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER …
Determining The Effect Of Knocking Out Microrna-21 On Subsarcolemmal And Interfibrillar Mitochondria, Madhur Batra
Determining The Effect Of Knocking Out Microrna-21 On Subsarcolemmal And Interfibrillar Mitochondria, Madhur Batra
Theses and Dissertations
Type 2 diabetes mellitus is a growing problem across the world and has significant pathological changes associated with it, including diabetic cardiomyopathy, wherein cardiac function is reduced. MicroRNA-21 has been shown to play a role in both the heart and diabetes so it was thought that knocking out miR-21 could have a protective effect on oxidative phosphorylation function in diabetic mice. Subsarcolemmal and interfibrillar mitochondria were isolated from adult male WT, miR-21 KO, db/db, and double knockout mice (db/db and miR-21 KO cross) and evaluated for function. Knocking out miR-21 in diabetic mice showed a restorative effect in Complex I …