Medicine and Health 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, …

Effects Of Neurotrophic Factors On Osteoblast Growth And Differentiation, Colleen M. Moran

Loma Linda University Electronic Theses, Dissertations & Projects

Recent evidence suggests that bone metabolism may be influenced by the innervation of skeletal tissues. Innervation of skeletal tissues might directly influence bone volume by the release or secretion of osteogenic growth factors in the form of neuropeptides. These neuropeptides could act locally on osteoblasts to increase bone formation and/or mineralization. Since calcitonin gene-related peptide (CGRP) and Substance P (SP) are the most abundant neuropeptides present in sensory nerves in bone, the current studies were intended to test the hypothesis that these two neuropeptides may have direct effects on osteoblast growth, differentiation, and mineralization. Replicate cultures of murine calvarial osteoblasts …

Correlating The Slope Of The Vomer With Cephalometric Vectors Of Facial Growth, Ryan Michael Pulfer

Loma Linda University Electronic Theses, Dissertations & Projects

It is important for orthodontists to have a basic understanding of the growth and development of the face. Scott's nasal septal cartilage theory proposes that the cartilage of the nasal septum proliferates along the anterior slope of the vomer bone by interstitial growth, simultaneously pulling and displacing the maxilla downward and forward. It is therefore logical to conclude that the vector of nasomaxillary growth has a geometric correlation with the anterior slope of the vomer bone.

There are no published studies comparing either the anterior or posterior slope of the vomer with any lateral cephalometric landmarks, the vectors of nasomaxillary …

Therapeutic Modalities Targeting Neuroinflammation After Neonatal Hypoxia-Ischemia, Nancy Fathali

Loma Linda University Electronic Theses, Dissertations & Projects

Hypoxia-ischemia (HI) occurs in 1-6/1000 live full-term births (Shankaran, 2009). Of those affected, 15-20% will die in the postnatal period, and 25% of survivors will be left with long-term neurological disabilities (Gunn, 2000; Vannucci, 1997; Fatemi, 2009). It has become increasingly clear that peripheral immune cells infiltrate the brain parenchyma as part of the physiological response to tissue damage after HI injury. The interplay between infiltrating immune cells and brain resident cells during the inflammatory response is however dynamic and complex; in that neuro-immune crosstalk, by way of specific molecular mediators, is responsible for both neurodestructive as well as neuroprotective …

Hypoxia And Fetal Programming Of Cardiovascular Dysfunction, Qin Xue

Loma Linda University Electronic Theses, Dissertations & Projects

Human epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of ischemic heart disease in later adult life. Of all the stresses to which the fetus is subjected, perhaps the most important and clinically relevant is that of hypoxia. The goal of this project is to test the hypothesis that chronic hypoxia during gestation adversely affects fetal cardiovascular development and impairs cardiac function in offspring. In the first part of project, we tested the hypothesis that chronic hypoxia adversely regulates contractility of fetal pulmonary arteries and veins in sheep residing at high altitude (3,801 …

Fetal Programming By Nicotine Increases Cardiac Susceptibility To Ischemic Injury, Jennifer Charlotte Alexie Lawrence

Loma Linda University Electronic Theses, Dissertations & Projects

Fetal programming is the area of study that focuses on the prenatal origins of adult onset disorders. Previous studies have associated an adverse prenatal environment with the onset of physiologic and metabolic diseases during adulthood. Fetal malnutrition, hypoxia, and exposure to drugs - such as cocaine and nicotine - have been associated with adult disease states. Cigarette smoking is the number one cause of preventable death in the developed world. Among the many dangerous chemicals found in tobacco products is nicotine, the compound responsible for the addictive nature of tobacco use. Nicotine use during pregnancy is a known cause of …

Fetal Cocaine Exposure Causes Epigenetic Changes In The Rat Heart, Kurt D. Meyer

Loma Linda University Electronic Theses, Dissertations & Projects

Cocaine abuse continues to be prevalent in the United States and other industrialized nations, in addition to the negative health effects that cocaine abuse has on the user, a mother who uses cocaine while pregnant also exposes the developing fetus to cocaine. Although there have been many studies of the effects of cocaine on the adult heart, studies of cocaine on the fetal heart and its potential delayed pathophysiological effects on cardiac function in adult offspring are extremely limited. The studies of the present project sought to enhance the understanding of the effect of cocaine exposure on the fetal heart …

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 …

Neuronal Connections From The Cervix To The Spinal Cord Before Parturition, Mary Medina Groves

Loma Linda University Electronic Theses, Dissertations & Projects

By the day before birth, the density of nerve fibers in the cervix has increased compared to earlier in pregnancy or in nonpregnant mice. Similar findings are reported in parturient women. To test the hypothesis that connections between the cervix and spinal cord are enhanced by term, the cervix of nonpregnant and time-dated pregnant mice (day 15 or 18 post-breeding) was injected with pseudorabies virus (PRV), a trans-synaptic retrograde neural tract tracer. Mice were euthanized and perfused 5 days later. The spinal cord and cervix were removed and postfixed overnight, immersed in sucrose, and cryostat sections through the thoracic to …

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 …

Is Electrical Stimulation A Predictive Tool For Autonomic Dysfunction In Males With Diabetes?, Susan Dorothy Rand

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to examine whether electrical stimulation can be used as a predictive tool to assess autonomic dysfunction in males with diabetes. The study was designed to better understand the extent of autonomic nervous system (ANS) dysfunction in the diabetic population.

Controls and patients with diabetes were recruited from the community at large and the Loma Linda University Diabetes Treatment Center and were managed by a physician. Twelve (12) people with diabetes and thirteen (13) control subjects participated. Mean age (years) for people with diabetes was 52.4 +/- 6.1 and 47.2 +/-11.1 for controls (p =0.05). …

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 …

Maturational Changes In Cerebrovascular Thick- And Thin-Filament Regulation, Renan Joel Sandoval

Loma Linda University Electronic Theses, Dissertations & Projects

The present study focused on the main hypothesis that age-related changes in myofilament Ca²⁺ sensitivity involve simultaneous changes in the relations between cytosolic Ca²⁺ transients, myosin phosphorylation, and force development. To define the effects of late fetal and early postnatal maturation, parallel experiments were carried out using cerebral arteries from both term lamb fetuses (140-141 days of gestation) and nonpregnant adult sheep. Fetal and adult cerebral arteries were stimulated by either mechanically, electromechanically, and/or pharmacomechanically-induced contractions, and the relations of cytosolic Ca²⁺, MLC phosphorylation, and contractile tensions were measured. These measurements allowed for stimulus and age-dependent …

A Continued Investigation Of Craniofacial Growth In Infant Heart Transplant Recipients Receiving Cyclosporine, Gabriel Enriquez

Loma Linda University Electronic Theses, Dissertations & Projects

Since the mid 1980’s, Cyclosporine has proved to be an effective immunosuppressive drug and now has a widespread application in organ transplantation. Several studies, however, have implicated cyclosporine as adversely affecting craniofacial growth in the pediatric population. ^16,18 The purpose of this follow-up study was to continue to evaluate the possible untoward effects of long-term use of cyclosporine on craniofacial growth in a group of infant heart transplantation recipients by re-evaluating as many subjects as possible from the original study and evaluating new subjects. A pediatric group (N=13) was composed of six Caucasian subjects (4 male and 2 female, ages …

Mineralized Bone Allograft In Maxillary Sinuses Histology And Histomorphometry, Sammy Stefan Noumbissi

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Demineralized freeze-dried bone allografts (DFDBA) and deproteinized bovine bone xenografts (DMBBX) have been used for sinus augmentation for many years with varying results, but very little has been reported on the clinical efficacy or the histological analysis of mineralized solvent dehydrated bone allografts (MSDBA) as sinus graft materials. This study histologically and histomorphometrically evaluated an MSDBA material called PUROS to augment atrophic human maxillary sinuses.

Materials & Methods: Seven partially and completely edentulous patients requiring unilateral (n=4) or bilateral (n=3) sinus grafts prior to implant placement were selected for this study. Test grafts consisted of MSDBA, and control …

Resveratrol Regulates Igf- Ii And Cathepsin D In Breast Cancer Cells, Sharda Kalla Vyas

Loma Linda University Electronic Theses, Dissertations & Projects

Breast cancer is the most common type of cancer among women in the US. Phytoestrogen resveratrol (RS V) has been described as a potential ehemotherapeutic agent, but has been associated with breast cancer cell growth and cell death. RSV binds to estrogen receptors (ER) and functions as a mixed estrogen agonist/antagonist. The mechanism by which RSV regulates breast cancer growth is largely unknown, but it likely targets factors regulated by estrogens. Insulin-like growth factor II (IGF-II) and its precursor (proIGF-II) are estrogen-regulated mitogens that are over-expressed in breast carcinoma. Thus, I hypothesized that IGF-II/proIGF-II might mediate the biphasic effects of …

Levels Of Intravenous Enterococcus Faecalis That Cause Heart Colonization, Louis Zane Stromberg

Loma Linda University Electronic Theses, Dissertations & Projects

While previous studies have shown that presence of bacteria in systemic circulation can cause infective endocarditis, there is no information on the specific amount of bacteria necessary to cause this condition. The purpose of this study was to establish the minimum level of circulating bacteria that will cause colonization of damaged heart valves in rats. Fifty-two Sprague-Dawley rats were anesthetized and their heart valves were damaged using an established protocol. A clinical isolate of Enterococcus faecalis was transformed with a plasmid bearing the luxF and Chloramphenicol cassettes to label the bacteria with the light-emitting protein. After four weeks, the rats …

Diabetes: The Interrelationship Between Vascular, Nervous Systems And Avandia, Salameh Bweir

Loma Linda University Electronic Theses, Dissertations & Projects

Diabetes Mellitus has been linked to vascular and neurological impairments. The purpose of this study was to assess the relationship between vascular endothelial dysfunction, autonomic and somatic nervous systems impairment in diabetic patients. These studies also evaluated the effects of rosiglitazone (Avandia) on the vascular, autonomic, and somatic nervous systems.

Fourteen diabetic subjects and fourteen control subjects (age matched) participated in three series of experiments. Using Whitney volume plesythmography to assess post occlusion blood flow in the subject’s forearm did assessment of vascular endothelial function. Evaluating skin blood flow, orthostatic tolerance, heart rate, and thermal responses under thermal and postural …

Radiation Effects On Dopamine-Mediated Prepulse Inhibition In The C57bl/6 Mouse, Cara Nicole Zuccarelli Miller

Loma Linda University Electronic Theses, Dissertations & Projects

This study examined the effects of proton and gamma radiation on a dopamine-dependent sensory gating mechanism: prepulse inhibition of the startle reflex. The purpose of this research was to describe potential hazards of proton radiation to the central nervous system in long-term space fight and for proton therapy patients. Results from previous research indicate that startle behavior is modified by proton and iron radiation. Forty-eight 10-½ week old, male C57BL/6 mice were used to characterize the optimal parameters for the model (prepulse duration, probe duration, and stimulus-onset-asynchrony). Three hundred and fifty two mice were used to characterize the time course …

Inducible Gene Expression In Cell Cultures And In Microencapsulated Cells, Yong Yu

Loma Linda University Electronic Theses, Dissertations & Projects

The mifepristone-regulated transcriptional activation system provides a means to exogenously control gene expression in transformed mammalian cells in a temporal and spatial fashion. Such a promoter activation system consists of three components: The first of these is a steroidal inducer drug, mifepristone. This drug binds to the second component, a chimeric transcription factor complex, consisting of the mutant human progesterone receptor fused to the yeast GAL4 DNA-binding domain and the Herpes simplex virus protein VP 16 activation domain. The third component is a synthetic promoter, consisting of a series of GAL4 recognition sequences upstream of the adenovirus major late E1B …

The Relationship Between The Osteonal Cement Line And Bone Strength, Avery Kazuhiro Egerer

Loma Linda University Electronic Theses, Dissertations & Projects

Bone includes many structural and chemical components which provide both flexibility and strength. One such structure is the cement line, a 1-5 μm-thin structure located primarily in compact bone. Past research has correlated the pathological condition of “shin splints” with the micro-damage of bone, which often follows cement lines. It has been suggested that cement lines have rather paradoxical properties. Upon fatigue fracture of bone, microcracks often travel along cement lines and become trapped. This trapping and subsequent dispersion of energy have been hypothesized to prevent a complete fracture from occurring, extending bone life. Cement lines have been implicated in …

Effects Of A Serine 364 To Proline Mutation Of The Connexin43 Protein In Transgenic Mice, Chia-Ling Nhan-Chang

Loma Linda University Electronic Theses, Dissertations & Projects

[Abstract Not Included]

The Effect Of Chronic Hypoxia On Cardiac Function In The Fetal Ovine Heart, Rodney David Rodrigo

Loma Linda University Electronic Theses, Dissertations & Projects

It has been shown that long-term high altitude hypoxia during pregnancy was associated with a decrease in cardiac contractility in fetal sheep. Given that hypoxia caused apoptotic cell death in fetal and neonatal rat cardiomyocytes, the present study tested the hypothesis that chronic hypoxia during pregnancy increases apoptosis in the fetal sheep heart. Pregnant (d 30) sheep were divided between normoxic control and chronically hypoxic (maintained at high altitude, 3,820 m, PaO₂: 60 Torr for 110 days) groups. Hearts were isolated from near-term (d 140) fetal sheep, and samples from all four chambers, right and left atria, and …

A Continued Investigation Of Craniofacial Growth In Infant Heart Transplant Recipients Receiving Cyclosporine, John Michael Cornali

Loma Linda University Electronic Theses, Dissertations & Projects

Cyclosporine is an effective immunosuppressive drug that has found widespread application in organ transplantation. A couple of studies, however, have implicated cyclosporine as adversely affecting craniofacial growth in the pediatric population. The purpose of this follow-up study was to continue to evaluate the possible untoward effects of long-term use of cyclosporine on craniofacial growth in a group of infant heart transplantation recipients by re-evaluating as many subjects as possible from the original study and evaluating new subjects. A prospective group (N=29) of eighteen Caucasian subjects (7 female and 11 male, ages 6-15 years) and eleven Hispanic subjects (3 female and …

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 …