Medical Sciences Commons^™

Surface-Enhanced Raman Spectroscopy (Sers) Tracking Of Chelerythrine, A Na+ K+ Pump Inhibitor, Into Cytosol And Plasma Membrane Fractions Of Human Lens Epithelial Cell Cultures, Kevin M. Dorney, Ioana E.P. Sizemore, Tariq Alqahtani, Norma C. Adragna, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

Background/aims: The quaternary benzo-phenanthridine alkaloid (QBA) chelerythrine (CET) is a pro-apoptotic drug and Na(+)/K(+) pump (NKP) inhibitor in human lens epithelial cells (HLECs). In order to obtain further insight into the mechanism of NKP inhibition by CET, its sub-cellular distribution was quantified in cytosolic and membrane fractions of HLEC cultures by surface-enhanced Raman spectroscopy (SERS). Methods: Silver nanoparticles (AgNPs) prepared by the Creighton method were concentrated, and size-selected using a one-step tangential flow filtration approach. HLECs cultures were exposed to 50 μM CET in 300 mOsM phosphate-buffered NaCl for 30 min. A variety of cytosolic extracts, crude and purified membranes, …

Developmental Characterization Of The Choroid Plexus In Sialidosis (Neu1 Deficient) Mice, Danielle Lee Helton

Theses and Dissertations (ETD)

The lysosomal sialidase Neuraminidase-1 (Neu1) initiates the hydrolysis of sialoglycoconjugates by cleaving their terminal sialic acid residues. Neu1 creates a complex with the carboxypeptidase protective protein/cathepsin A (PPCA), which is necessary for its catalytic activation and its transport to the lysosomal compartment. In humans, a primary deficiency of this enzyme leads to a pediatric, catastrophic, neurodegenerative lysosomal storage disorder called sialidosis. Mice deficient in Neu1 exemplify the early-onset severe form of sialidosis. Our laboratory has recently discovered that loss of Neu1 exacerbates the process of lysosomal exocytosis (LyEXO) in various cell types by influencing the sialic acid content of lysosomal …

Determinants Of Upper Genital Tract Complications In A Chlamydial Urogenital Mouse Model, Enitra N. Jones

Theses and Dissertations (ETD)

Genital Chlamydia trachomatis infection is a major public health concern. Chlamydia is the most commonly reported infection in the United States and the most common bacterial sexually transmitted infection worldwide. Unrecognized infection endangers female reproductive health by serious complications such as Pelvic Inflammatory Disease, ectopic pregnancy, and involuntary infertility. Widespread Chlamydia control programs were implemented more than two decades ago to improve women's reproductive health but, despite initial success, the number of chlamydial infections reported have increased.

One of the hypotheses put forth to explain increased chlamydial reporting suggests that a longterm caveat of control initiatives is interference with the …

Intrahypothalamic Pituitary Adenylate Cyclase-Activating Polypeptide Regulates Energy Balance Via Site-Specific Actions On Feeding And Metabolism, Jon Resch, Brian Maunze, Adriana K. Gerhardt, Samuel K. Magnuson, Kailynn A. Phillips, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Numerous studies have demonstrated that both the hypothalamic paraventricular nuclei (PVN) and ventromedial nuclei (VMN) regulate energy homeostasis through behavioral and metabolic mechanisms. Receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) are abundantly expressed in these nuclei suggesting PACAP may be critical for the regulation of feeding behavior and body weight. To characterize the unique behavioral and physiological responses attributed to select hypothalamic cell groups, PACAP was site-specifically injected into the PVN or VMN. Overall food intake was significantly reduced by PACAP at both sites, however meal pattern analysis revealed only injections into the PVN produced significant reductions in meal size, …

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, …

Caveolins And Njks Influence Brain Endothelial Permeability After Juvenile Tbi, David Olufemi Ajao

Loma Linda University Electronic Theses, Dissertations & Projects

Disruption of blood-brain barrier (BBB) is a key secondary event that exacerbates brain damage following traumatic brain injury (TBI). BBB disruption is particularly damaging to the developing brain – which is highly vulnerable to various stress stimuli, resulting in increased brain swelling, disrupted cerebral blood flow (CBF) autoregulation, long-term disabilities and death following TBI in young demographic. Unsurprisingly, BBB disruption and the resultant cerebral edema have emerged as therapeutic targets in juvenile TBI. It is therefore important to understand the molecular players and mechanisms involved in TBI-induced BBB disruption in the juvenile brain. To this end, the endothelial caveolins and …

Expression And Function Of Ca2+-Activated K+ Channels In Uterine Arteries, Ronghui Zhu

Loma Linda University Electronic Theses, Dissertations & Projects

Chronic hypoxia during pregnancy is one of the most common insults to the maternal cardiovascular system and fetal development, and is associated with increased uterine vascular tone and heightened risk of preeclampsia and fetal intrauterine growth restriction (IUGR). The present study tested the hypothesis that calcium-activated potassium (KCa) channels play an essential role in uterine vascular adaptation to pregnancy, which is inhibited by chronic hypoxia during gestation. Uterine arteries (UAs) were isolated from nonpregnant ewes (NPUAs) and near-term pregnant ewes (PUAs) that had been maintained at sea level (~300 m) or exposed to high altitude (3,801 m) for 110 days. …

Radiosensitization Of Head & Neck Carcinoma Cells By Linifanib, A Receptor Tyrosine Kinase Inhibitor, Heng-Wei Hsu

Loma Linda University Electronic Theses, Dissertations & Projects

Tumor angiogenesis is a hallmark of advanced cancers and promotes invasion and metastasis. Over 90% of head and neck squamous cell carcinomas (HNSCC) express angiogenic factors such as vascular endothelial growth factor (VEGF). Since radiotherapy is one of the most commonly used treatments for HNSCC, it is imperative to identify the interactions between antiangiogenic therapy and radiotherapy, and to develop combination therapy to improve clinical outcome. The mechanisms between antiangiogenic agents and ionizing radiation are complicated and involve many interactions between the vasculature, tumor stroma and tumor cells. The proliferation and metastasis of tumor cells rely on angiogenesis/blood vessel formation. …

Cxcr2 Expression In Tumor Cells Is A Poor Prognostic Factor And Promotes Invasion And Metastasis In Lung Adenocarcinoma, Erminia Massarelli

Dissertations and Theses (Open Access)

CXC chemokine receptor 2 (CXCR2) is a G-protein coupled receptor which mediates signaling by binding to CXC chemokines CXCL1-3 and 5-8. In non-small cell lung cancer CXCR2 has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. However, there is controversial data in the literature about CXCR2 expression in tumor cells and its role in the tumor microenvironment. We hypothesized that tumoral expression of CXCR2 and its ligands promote tumor invasion and metastasis in non-small cell lung cancer. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from …

Staphylococcus Aureus Sara Regulates Inflammation And Colonization During Central Nervous System Biofilm Formation, Jessica N. Snowden, Matthew K. Beaver, Karen Beenken, Alexander R. Horswill, Tammy L. Kielian

Journal Articles: Pediatrics

Infection is a frequent and serious complication following the treatment of hydrocephalus with CSF shunts, with limited therapeutic options because of biofilm formation along the catheter surface. Here we evaluated the possibility that the sarA regulatory locus engenders S. aureus more resistant to immune recognition in the central nervous system (CNS) based on its reported ability to regulate biofilm formation. We utilized our established model of CNS catheter-associated infection, similar to CSF shunt infections seen in humans, to compare the kinetics of bacterial titers, cytokine production and inflammatory cell influx elicited by wild type S. aureus versus an isogenic sarA …

Retention Strategies For Medical Technologists: Addressing The Shortages And Vacancies In The Clinical Laboratory, Kathy S. Small

Electronic Theses and Dissertations

It is important to have well-trained and qualified laboratory professionals. Seventy percent of patient care is based on decisions made from laboratory results, yet there is a growing shortage of medical technologists. Although some baby boomers are delaying retirement, worsening of the shortage crisis is inevitable. Retention of medical technologists has become more important than recruitment. The purpose of this study was to identify and evaluate innovative retention strategies used by clinical laboratory managers throughout the United States.

A significant finding of this study was the lack of qualified medical technologists entering the ranks of laboratory managers. This study identified …

Toll-Like Receptors 2 And 9 Are Important For Innate Immune Cell Activation And Recruitment In Hypersensitivity Pneumonitis, Kelly J. Andrews

Theses and Dissertations (ETD)

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalation of environmental antigens. The disease is characterized by alveolitis and granuloma formation; however, some patients develop chronic HP (CHP), a restrictive lung disease characterized by fibrosis. Previous studies revealed that neutrophils are recruited into the lung via a MyD88- dependent pathway and regulate disease severity through cytokine production. Toll-like receptors (TLRs) 2 and 9 recognize conserved molecular patterns present in bacteria, and signal through the adaptor molecule MyD88. The goal of my project is to investigate the role of TLRs 2 and 9 in the pathogenesis of HP …

A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim

Theses and Dissertations (ETD)

Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …

Nkg2d Ligands In Cancer, Neha Das Gupta

Theses and Dissertations (ETD)

NK cell transplantation has been increasingly used to treat cancers that are resistant to chemotherapy. However, not all cancers are susceptible to NK cell killing. The prevalence and mechanisms of NK cell resistance have not been well elucidated. Because NKG2D is a major activating receptor on NK cells, we sought to test the hypothesis that NKG2D is the primary pathway in tumor cell recognition. Herein, we comprehensively assessed 20 cancer cell lines representing a broad array of cancer types. In line with our primary hypothesis, no cancer cell lines that expressed low levels of NKG2D ligands were susceptible to NK …

Full-Gestational Exposure To Nicotine And Ethanol Results In Long-Term Dysregulation In The Ventral Tegmental Area, Emily Elizabeth Roguski

Theses and Dissertations (ETD)

Nicotine is considered a gateway drug for other drugs of abuse. The majority of smokers that begin smoking in adolescence, continue into adulthood. Multiple factors have been linked with smoking initiation, including maternal smoking. Drug exposure during pregnancy has long been suspected to exert deleterious effects on the fetal brain. Concurrent use of smoking and drinking alcohol throughout pregnancy is an all too frequent occurrence in the human population especially in disadvantaged and younger women.

The present study investigated the potential contributing factors for the enhanced nicotine selfadministration as seen in offspring with gestational exposure to nicotine and ethanol (Nic+EtOH).* …

Attenuation Of Parenteral Nutritionassociated Liver Disease By Omega-3 Long-Chain Polyunsaturated Fatty Acids, Emma Monique Tillman

Theses and Dissertations (ETD)

No abstract provided.

Adenylyl Cyclase 2 Selectively Regulates Il-6 Expression In Human Bronchial Smooth Muscle Cells, Amy Sue Bogard

Theses and Dissertations (ETD)

Adenylyl cyclase (AC) catalyzes the formation of the ubiquitous second messenger cAMP. AC isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions, and most cells express multiple isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses. Overexpression of individual isoforms had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes in human bronchial smooth muscle cells (BSMC) and human embryonic kidney cells (HEK-293). Most notable, in BSMC overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Regulation Of Secretory Phospholipase A2 By Thyroid Hormone, Pragya Sharma

Theses and Dissertations (ETD)

Rationale: Low grade inflammation has been correlated with elevated risk of hepatic steatosis and atherosclerosis. Secretory phospholipase A2 group IIA (PLA2g2a) enhances the progression of several chronic inflammatory diseases including arthritis and atherosclerosis. The potential linkage of hypothyroidism with inflammation led us to examine the modulation of sPLA2 expression by thyroid hormone (T3) in liver.

Objective: Most of the studies of phospholipase A2 group IIA (PLA2g2a) have been conducted with macrophages and vascular smooth muscle cells with regard to atherosclerosis. The liver is one of the major contributors to the total pool of extracellular PLA2g2a. The aim of the present …

Identification Of Novel Hif1a Target Genes That Regulate Tumor Progression And Metastasis, Danielle L. Peacock

Theses and Dissertations (ETD)

Hypoxia is a hallmark of most solid tumors. In response to hypoxic stress tumor cells adapt by regulating survival, metabolism and angiogenesis. The heterodimeric HypoxiaInducible Factor (HIF) transcription factors are the master regulators of this response. HIFs play key roles in many critical aspects of cancer biology including angiogenesis, stem cell maintenance, metabolic reprogramming, invasion, metastasis and resistance to radiation therapy and chemotherapy. Overexpression of HIF-1α and HIF-2α has been documented in multiple human cancers and HIF-1 protein is over-expressed in ~30% of primary breast tumors and ~70% of metastases, which independently correlates with poor prognosis and decreased survival in …

Distinct Phenotypes In Zebrafish Models Of Human Startle Disease, Lisa R. Ganser, Qing Yan, Victoria M. James, Robert Kozol, Maya Topf, Robert J. Harvey, Julia E. Dallman

Faculty Articles

Startle disease is an inherited neurological disorder that causes affected individuals to suffer noise- or touch-induced non-epileptic seizures, excessive muscle stiffness and neonatal apnea episodes. Mutations known to cause startle disease have been identified in glycine receptor subunit (GLRA1 and GLRB) and glycine transporter (SLC6A5) genes, which serve essential functions at glycinergic synapses. Despite the significant successes in identifying startle disease mutations, many idiopathic cases remain unresolved. Exome sequencing in these individuals will identify new candidate genes. To validate these candidate disease genes, zebrafish is an ideal choice due to rapid knockdown strategies, accessible embryonic stages, and stereotyped behaviors. The …

Plasma Antibodies To Oral Bacteria And Risk Of Pancreatic Cancer In A Large European Prospective Cohort Study, Dominique S. Michaud, Jacques Izard, Charlotte S. Wilhelm-Benartzi, Doo-Ho You, Verena A. Grote, Anne Tjønneland, Christina C. Dahm, Kim Overvad, Mazda Jenab, Veronika Fedirko, Marie Christine Boutron-Ruault, Françoise Clavel- Chapelon, Antoine Racine, Rudolf Kaaks, Heiner Boeing, Jana Foerster, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Carlotta Sacerdote, Sabina Sieri, Domenico Palli, Rosario Tumino, Salvatore Panico, Peter Siersema, Petra Hm Peeters, Eiliv Lund, Aurelio Barricarte, José-María Huerta, Esther Molina-Montes, Miren Dorronsoro, J. Ramón Quirós, Eric J. Duell, Weimin Ye, Malin Sund, Björn Lindkvist, Dorthe Johansen, Kay-Tee Khaw, Nick Wareham, Ruth C. Travis, Paolo Vineis, H. Bas Bueno-De-Mesquita, Elio Riboli

Department of Food Science and Technology: Faculty Publications

Objective: Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study.

Design: We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study (EPIC). Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index.

Results: Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a 2-fold higher risk of pancreatic cancer than individuals lower levels of …

Scanned Ion Beam Therapy For Thoracic Tumors, John Gordon Eley

Dissertations and Theses (Open Access)

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some …

Tibial Tubercle Transfer To Correct Bilateral Patellar Tendinopathy In A Collegiate Football Player, Andrew D. Hamstra

Boise State University Theses and Dissertations

Objective: To present a case of a competitive football player with chronic patellar tendinopathy and the associated bilateral tibial tubercle transfer surgeries performed leading to the reduction of pain and return to participation.

Background: A 19 year-old male football athlete (height= 187.96 cm, mass= 112.037 kg) presented with chronic patellar tendinopathy that began in his high school career and continued to worsen with the increased physical demands associated with participation in collegiate sport.

Differential Diagnosis: Chondromalacia patella and Osgood Schlatters disease.

Treatment: After nonsurgical intervention resulted in no decrease of pain, bilateral tibial tubercle transfer surgery was conducted to correct …

Investigation Of Respiratory Motion Management Techniques For Proton And Photon Radiotherapy Of Lung Cancer, Jason E. Matney

Dissertations and Theses (Open Access)

Protons as a source of therapeutic radiation can provide a substantial improvement over dose distributions that can be achieved with conventional sources of radiation such as high-energy photons. However, respiratory motion can significantly impact the delivered proton and photon dose distributions during lung cancer radiotherapy. The goals of this dissertation research were to evaluate the impact of respiratory motion and to estimate the benefit of respiratory gating for passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT).

The first aim of this project was to determine the impact of respiratory motion in PSPT and IMRT. Four dimensional dose …

Review Of Cerebral Aneurysm Formation, Growth, And Rupture., Nohra Chalouhi, Md, Brian L Hoh, David Hasan

Department of Neurosurgery Faculty Papers

No abstract provided.

A Comparison Of Nebulized Vitamin B12 Versus Oral Vitamin B12 Supplementation, Terry L. Williams Jr.

Graduate Theses and Dissertations

Vitamin B12 is important for various processes in the human body including DNA synthesis, red blood cell production, energy production, fatty acid synthesis, and for the conversion of homocysteine into methionine. Vitamin B12 deficiency is becoming more prevalent. The purpose of this study was to evaluate if a different route of administration, i.e. nebulization, was a viable option for increasing serum levels of vitamin B12 in both exercisers and non-exercisers. The increasing number of people that are vitamin B12 deficient is due to several factors including medication use, elective gastric bypass surgery, and an increasing elderly population. There are currently …

Patient Risk And Data Standards In Healthcare Supply Chain, Paiman Farrokhvar

Graduate Theses and Dissertations

Patient safety is one of the most important health care challenges. It is a big concern since 1 in every 10 patients around the world is affected by healthcare errors. The focus of this study is given to preventable adverse events that caused by the errors or system flaw that could have been avoided. In this study, simulation models are developed using Arena to evaluate the impact of GS1 data standards on patient risk in healthcare supply chain. The focus was given to the provider hospital supply chain operations where inventory discrepancy and performance deficiencies in recall, return, and outdate …

Enhanced Pancreatic Beta-Cells Proliferation And Functionality, Hanan Abdulaziz Alismail

Graduate Theses and Dissertations

Biologically functional beta-cells proliferate at an extremely low rate with limited turnover capacity. This cellular property hinders cell-based therapy for clinical applications. Many attempts have been made to develop techniques that allow large quantities of production of clinically relevant islet β-cells in vitro. A line of studies demonstrates that functional beta-cells can proliferate under certain circumstances, providing hope for generating and expanding these cells in vitro and transplanting them into the recipient. In this study, we showed that a membrane substrate offers a better niche for beta cell proliferation and insulin secretion. Mouse beta cells were grown on a tissue …

Development Of Novel Antifungal Peptides Based On A Natural Model Of Histatin-5 Peptide, Duy Tu Nguyen

Graduate Theses and Dissertations

Our research group is working toward the development of novel antifungal peptides based on a natural model of peptide histatin-5. Histatin-5 is found in human saliva and known to protect our body against oral infections by Candida species. Candidiasis, or an infection caused by Candida species, is considered one of the most medically important fungal infections worldwide. Blood stream infections caused by Candida species are the fourth leading cause of hospital-acquired fungal infections that is associated with high mortality rates and high costs of treatment. This study investigated the modes of action of histatin-5 with the use of one 16-mer …