Medical Sciences Commons^™

Microgravity Exerts An Age-Dependent Effect On Cardiovascular Progenitor Cell Development, Jonathan Baio

Loma Linda University Electronic Theses, Dissertations & Projects

The heart and its cellular components are profoundly altered by missions to space and injury on Earth. Increasing evidence has identified that one such alteration induced by spaceflight is the promotion of the efficacious use of stem cells in therapies on Earth. For this reason, neonatal and adult human cardiovascular progenitor cells (CPCs) were cultured aboard the International Space Station (ISS). Subsequently, we assessed the effects of mechanical unloading on developmental properties and signaling. Spaceflight induced the expression of genes that are typically associated with an earlier state of cardiovascular development. In particular, in neonatal CPCs, we measured increased expression …

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

Loma Linda University Electronic Theses, Dissertations & Projects

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …

Tslp-Induced Mechanisms And Potential Therapies For Crlf2 B-Cell Acute Lymphoblastic Leukemia, Olivia L. Francis

Loma Linda University Electronic Theses, Dissertations & Projects

Childhood CRLF2 B-cell Acute Lymphoblastic Leukemia (CRLF2 B-ALL) is a high-risk form of leukemia that is associated with poor patient survival outcomes. CRLF2 B-ALL is five times more prevalent in Hispanic children than others and is associated with a higher rate of relapse, thus contributing significantly to childhood cancer health disparities. This disease occurs due to alterations of the CRLF2 gene, leading to overexpression of the CRLF2 protein- a component of the receptor signaling complex for the cytokine Thymic Stromal LymphoPoietin (TSLP) on the surface of B-ALL cells. TSLP has been shown to induce proliferation of human and mouse B-cell …

Chlorinated Tyrosine Species As Markers Of Inflammation: A Kinetic Study, Matthew Peter Curtis

Loma Linda University Electronic Theses, Dissertations & Projects

Chronic inflammation is associated with numerous human diseases. During inflammation, leukocytes release the enzyme myeloperoxidase (MPO) which generates reactive oxygen species such as hypochlorous acid (HOCl). Additionally, MPO generates reactive nitrogen species. These reactive species can damage host fats, proteins, and DNA, contributing to disease pathology. Because of the reactivity and short half-lives of reactive species, measurement of surrogate markers is necessary to determine their extent and source. Chlorination of the tyrosine phenol ring by HOCl to produce 3-chlorotyrosine (3ClTyr) or nitration of the phenol ring by reactive nitrogen species to produce 3-nitrotyrosine (NO2Tyr) are two such markers. Both are …

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 …

Sympathetic Nerve Modulation Of Joint Pathology In Adjuvant-Induced Arthritis, Carlo Anthony Wood

Loma Linda University Electronic Theses, Dissertations & Projects

Background: There is increasing data suggesting a net increase in sympathetic tone plays an important role in rheumatoid arthritis. Several studies have reported altered distribution and density of autonomic nerves in patients with rheumatoid arthritis and animal models for the disease. This provides anatomical evidence that supports a neurally-mediated drive in inflammation and joint destruction. Methods: Adult rats were injected with complete Freund’s adjuvant. At 12 days post immunization, animals were randomly placed into a drug treatment group (SH1293, which interacts with - and ß2-ARs), an adjuvant arthritic group, or a control group. These animals were sacrificed at 14, 21, …

Anti-Inflammatory Effects Of Ppar-Gamma In Surgical Brain Injury (Sbi), Amy Hyong

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Brain injury can be caused by neurosurgical procedures themselves, due to direct trauma, retractor stretch, intraoperative hemorrhage and electrocautery damage. As a result of this surgical brain injury (SBI) postoperative complications such as inflammation, brain edema, and cell death can occur in the susceptible brain areas. Cerebral inflammation is a known contributor to the pathophysiology of brain injury. Following brain injury, the release of inflammatory mediators facilitates the development of BBB breakdown, cerebral edema, oxidative stress and neuronal death, resulting in further tissue damage in the brain and poor neurological outcomes. This study evaluates whether the use of a …

Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence …

The Role Of Nogo-A During Development Of The Chick Central Nervous System, Shelly A. Caltharp

Loma Linda University Electronic Theses, Dissertations & Projects

Nogo-A is a potent inhibitor of axon regeneration that is expressed by myelin forming oligodendrocytes of the adult central nervous system (CNS). However, neuronal expression of Nogo-A during development suggests an additional role. Little is known about the putative functions of Nogo-A during embryonic development. To examine its potential role we isolated and analyzed the Nogo-A sequence in the chick, we localized its mRNA expression pattern and cell-specific distribution during key phases of cortical development, and studied regulation of its expression during phases that showed promise of function based on expression patterns.

Our results revealed five previously undescribed Nogo-A specific …

Age Related Changes In Contractile Sensitivity To Cyclic Gmp And Intracellular Calcium Compartmentalization In Ovine Arteries, Surya Margono Nauli

Loma Linda University Electronic Theses, Dissertations & Projects

The study examines the hypothesis that maturation changes the ability of cGMP to produce cerebral vasodilatation and alters the relative intracellular calcium pool sizes in ovine arteries. In ovine basilars taken from near-term fetal and young adult sheep, 8- pCPT-cGMP relaxed potassium- and serotonin-induced tone with pD2 values of 4.4±0.1 and 4.9±0.1 (fetal basilar) and 4.0±0.1 and 4.7±0.1 (adult basilar), respectively. In fura-2 loaded arteries, 8-pCPT-cGMP significantly lowered increases in cytosolic calcium concentration induced by serotonin but not potassium regardless of age. When calcium sensitivity was calculated in the same arteries as the slope of the relation between calcium concentration …

Assessment Of Immune System Involvement In Tourette Syndrome, Ashley Dawn Levine

Loma Linda University Electronic Theses, Dissertations & Projects

Tourette syndrome (TS) is currently hypothesized to be the result of genetic and immunological components. This study investigated whether TS subjects produce IgG and IgA antibodies that bind to caudate nucleus, hippocampus, frontal cortex, cerebellum, thalamus, globus pallidus interior, exterior and putamen. Thirty- two children (14 TS, 7 family control, and 11 non-family control) and thirty-nine adults (11 TS, 14 family control, and 14 non-family control) were studied. Immunofluorescent studies were performed on basal ganglia tissue using serum from TS children and their family members. Brain antigens were prepared as two fractions (supernatant and pellet) and used as targets for …

Reference Serum Chemistry And Hematological Values For Spinal Cord Injured Patients, Michael S. Laymon, Antone L. Davis Ii

Loma Linda University Electronic Theses, Dissertations & Projects

Serum chemistry and hematological values from 220 traumatic spinal cord injured patients (157 male and 63 female between the ages of 15-47, with greater than six months from injury) were compiled via chart review. Traumatic spinal cord injured patient’s reference ranges were determined and compared with the general population reference ranges. Reference ranges within the spinal cord population were compared by age, gender, level of injury and chronicity of injury. The reference ranges determined for all groups within this spinal cord population fall within the reference ranges of the general population. This supports recent research which suggests that a decrease …

Effect Of Photoperiod On Developmental Morphology And Enolase Isoenzyme Immunohistochemistry In Rat And Djungarian Hamster Superficial Pineal Glands, Chalmer D. Mcclure

Loma Linda University Electronic Theses, Dissertations & Projects

The best understood functional activity of the pineal gland is its diurnal production of melatonin in response to environmental lighting cues. Several enzymes of the melatonin pathway respond to daily photoperiod changes, for example hydroxyindole-O-methyltransferase (HIOMT) and serotonin N-acetyltransferase (SNAT). Increased levels of the glycolytic enzyme neuron-specific enolase (NSE) are thought to reflect increased physiological demands placed on neurons and neuroendocrine tissues. Homodimer non-neuronal enolase isoenzyme (NNE) is immunolocalized to cells, and the hybrid enolase (consisting of subunits from NSE and NNE) has been seen in cerebellar stellate and basket cells. Although not rate limiting, concentrations of both NSE and …

Hyperosmotic Modification Of Brain Extracellular Space And Blood-Brain Barrier In The Rat As Observed By Electron Microscopy, Susan A. Meacham

Loma Linda University Electronic Theses, Dissertations & Projects

The highly selective permeability of cerebral blood vessels, termed the blood-brain barrier, is due to endothelial tight junctions (zonulae occludentes). Hyperosmotic solutions reversibly open the blood-brain barrier. The purpose of this study is to determine the immediate effect of hyperosmotic arabinose perfusion upon the cerebrovascular endothelium, the morphology of the cerebral cortex, and the cortical extracellular space.

Twelve adult male Sprague-Dawley rats were separated into three groups of four animals each: control, intermediate, and extreme. Controls were perfused with a Tyrode's solution prewash followed by trialdehyde fixative. The intermediate group received a prewash of 740 mmol/kg arabinose followed by the …

A Semiquantitative Analysis Of The Chorda Tympani Taste Pathway In The Rat Brain With The 2-Deoxyglucose Method, Charles L. Hardison

Loma Linda University Electronic Theses, Dissertations & Projects

This thesis is based on a semiquantitative analysis of four nuclear relay centers [nucleus tractus solitarius (NTS), parabrachial nucleus (PBN), ventroposteromedial nucleus (VPM), gustatory neocortex (GNC)] in the chorda tympani nerve pathway. Metabolic changes were examined by the 2-deoxyglucose method in which one chorda tympani nerve was chemically stimulated and its contralateral side lesioned. Coronal sections of four taste centers were prepared for autoradiography and Nissl staining. Densities of the autoradiograms were determined by means of a video based image processor. Relative differences in the optical density ratios of the stimulated versus lesioned nuclear grey matter areas to white matter …

The Coronary Distribution Zone : Mathematical Modelling Of The Left Ventricular Epicardial Surface For Area Calculation, Three-Dimensional Rotaton And Display, S. Matts E. Sjölander

Loma Linda University Electronic Theses, Dissertations & Projects

A computer model of the left ventricular (LV) epicardial surface was developed from Jang’s truncated ellipsoidal model, which has a minor to major axis ratio of 6:10. The model was applied in calculating the area of a segment of the myocardium, jeopardized by an impending occlusion of its associated artery. The endangered segment of the LV muscle was also visualized in different projections by rotations in three space and graphical displays simulating the three dimensions.

The area formula for the surface of the ideal model , a truncated prolate spheroid, was derived and used in producing maps for manual calculations …

A Study Of Regeneration Of Peripheral Nerve In The Rat, James C. Jay

Loma Linda University Electronic Theses, Dissertations & Projects

Due to improvements in fixation and embedding techniques a restudy of regenerating peripheral nerve was thought advisable in order to better understand and describe the processes which take place.

Femoral nerves of white Wistar rats were used. The lesions were made by either crushing or severing the nerve. After a period of regeneration, varying from 12 hours to six days, the wound was reopened and the injured portion fixed in situ with 1% osmium tetroxide. The tissues were then removed, dehydrated, embedded and sectioned. The sections were stained and studied with a modified RCA EMU2A electron microscope.

Observations revealed that …

The Nature And Incidence Of Vascular Lesions Of The Brain In 10,000 Consecutive Autopsies, David Hartson

Loma Linda University Electronic Theses, Dissertations & Projects

[Abstract not included]