Medicine and Health Sciences Commons^™

Dose-Dependent Effects Of Salmon Calcitonin On Bone Turnover In Ovariectomized Rats., Beatrice H. Owens

Electronic Theses and Dissertations

In the United States, osteoporosis results in about 1.5 million annual fractures, costing approximately $15 billion. Calcitonin is safe and effective in slowing osteoporotic bone loss, but its effect is transient. The current studies were designed to explore the dose-dependent effects of salmon calcitonin on bone turnover in ovariectomized rats and to determine if the decrease in therapeutic effectiveness of calcitonin demonstrated over time with higher doses is due to oversuppression of bone turnover. Doses of 5, 15, & 50 IU/kg BW/day of calcitonin were compared to placebo in 12-week-old ovariectomized and sham-ovariectomized Sprague-Dawley rats for 24 weeks. The spinal …

Degradation Of 23s Rrna In Azithromycin-Treated Ribonuclease Mutants Of Escherichia Coli., Jessica A. Silvers

Electronic Theses and Dissertations

Azithromycin, a macrolide antibiotic, specifically binds to the 50S ribosomal subunit of bacterial ribosomes and inhibits translation. Azithromycin also prevents 50S ribosomal subunit assembly by binding to a 50S ribosomal subunit precursor particle. When exposed to azithromycin, several ribonucleases in wild-type Escherichia coli cells degrade antibiotic-bound 50S precursor particles. Presumably, cells expressing one or more mutated ribonucleases will degrade the antibiotic-bound precursor less efficiently, resulting in increased sensitivity to the antibiotic. To test this, eight ribonucleaseûdeficient strains of Escherichia coli were grown in the presence or absence of azithromycin. Cell viability, growth rates, and protein synthesis rates were measured. Degradation …

Role Of Macrophage Apoptosis In Atherosclerosis., June Liu

Electronic Theses and Dissertations

The presence of apoptotic cells in atherosclerotic lesions has been broadly reported in the past ten years. The majority of these apoptotic cells are macrophages. However, the pathogenic role of macrophage apoptosis in the development of atherosclerosis remains to be elucidated. Elevated expression of Bax, one of the pivotal pro-apoptotic proteins of the Bcl-2 family, has been found in human atherosclerotic plaques. Activation of Bax also occurs in free cholesterol-loaded and oxysterol treated mouse macrophages. In this study, we evaluated the influence of Bax deficiency on apoptosis in macrophage-like P388D1 cells by using small interfering RNA (siRNA) to suppress Bax …

P14arf : A P53-Independent Tumor Suppressor, Monte W. Miller

Loma Linda University Electronic Theses, Dissertations & Projects

Many genetic alterations at the CDKN2A locus on human chromosome 9 have been shown to be at least partially responsible for transformation of cells to a cancerous phenotype. This locus encodes two proteins, p16 and p14, that play a pivotal role in tumor surveillance.

Breakdowns in the p14 pathway have been estimated to be present in approximately 40% of human cancers and only recently have its binding partners and effects begun to be defined. Its interaction with the p53 pathway, which is estimated to be inactivated or mutated in 50% of all cancers, makes it difficult to determine its own …

Enterotoxin B Subunit Lectins As Adjuvants For Improvement Of Mucosal Vaccine, Nak-Won Choi

Loma Linda University Electronic Theses, Dissertations & Projects

In comparison with whole organism vaccines, subunit vaccines may be safer for immunization but may lack sufficient immunogenicity to provide complete immunity to the pathogen. To resolve this problem, bacterial and plant enterotoxin B subunit adjuvants containing a variety of receptor-binding properties were used to enhance the immunogenicity of rotavirus subunit vaccines. Enterotoxin B subunit adjuvants were employed to enhance protection against virus infection. Pentameric cholera toxin B subunit (CTB), shiga toxin-1 B subunit (STB) and monomeric ricin toxin B subunit (RTB) molecules were genetically linked to a 90 amino acid peptide from the simian rotavirus (SA11) nonstructural protein NSP4 …

Papain: A Novel Urine Adulterant., David Burrows

Electronic Theses and Dissertations

The estimated number of employees in the United Stated screened annually for illicit drugs is approximately 20 million, with marijuana being the most frequently abused drug. Urine adulterants provide an opportunity for illicit drug users to obtain a false negative result on commonly used primary drug screening methods such as the Fluorescence Polarized Immunoassay (FPIA) technique. Typical chemical adulterants such as nitrites are easily detected or render the urine specimen invalid as defined in the proposed federal guidelines for specimen validity testing based on creatinine, specific gravity and pH. Papain is a cysteine protease with intrinsic ester hydrolysis capability. The …

Nongenomic Effects Of Estrogens On Epithelial Chloride Secretion., Sabyasachi Moulik

Electronic Theses and Dissertations

The human colonic cell line T84, a model for studying epithelial chloride secretion and cystic fibrosis chloride channel (CFTR) function, was used to investigate the regulatory role of estrogens in transepithelial ion transport. Estrogens and other steroid hormones do not stimulate chloride secretion by themselves. However, 17 β-estradiol (17β-E2) rapidly (within seconds to minutes) potentiates carbachol- and thapsigargin-stimulated chloride secretion measured as short circuit current in voltage-clamped T84 monolayer cultures. The cholinergic agonist carbachol and the SR Ca²⁺ ATPase inhibitor thapsigargin stimulate chloride secretion by elevating intracellular calcium. 17α-estradiol, a stereoisomer that does not activate nuclear estrogen receptors, is …

Ionizing Radiation And Endostatin Gene Therapy Against Lung Tumor, Xian Luo

Loma Linda University Electronic Theses, Dissertations & Projects

Although many advances have been made in radiotherapy, tumor radioresistance and normal tissue damage continue to always be important issues for radiation oncologists. Numerous reports have also documented that radiation exposure increases the risk for malignancy and suppresses immune mechanisms. However, increasing evidence has suggested that anti-angiogenic therapy that targets tumor blood supply may alter abnormal tumor vasculature, thus synergizing radiotherapy. The governing hypothesis of the present study was that modification of tumor vasculature by antiangiogenic gene therapy can increase the efficacy of radiotherapy and that radiation can also improve DNA transfection efficiency by increasing expression of the administered gene. …

The Anti-Proliferation Effects Of Lycopene On Breast Cancer Cells, Tixieanna Dissmore

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The incidence and deaths from breast cancer represent the most cause of all cancer deaths among women. Lycopene, the carotenoid in tomatoes has been associated with decreasing risk of prostate, breast, and digestive tract cancers. Various mechanisms of lycopene action have been proposed, including antioxidant activity and pro-differentiation activities. Identifying changes in the expression of proteins modified by lycopene can provide information to study the modulating effects of lycopene carcinogenesis and tumorigenesis development.

Objective: The objective was to study the anti-proliferative effects of lycopene on MCF- 7 human breast cancer cells and to identify changes in protein expression patterns. …

The Role Of Osteopontin In Vascular Remodeling, Daniel Myers

Electronic Theses and Dissertations

Chronic obstructive vascular disease is a major contributor to mortality in developed nations. The pathology typically involves neointima formation accompanied by vascular remodeling in the presence of inflammation. The disease can be modeled in animals with the response to a direct injury of the vasculature. This text describes a project examining the role of osteopontin (OPN) in vascular remodeling. The projectis goal was to mechanistically describe the contribution of OPN to the vascular injury response. The hypothesis that the presence of OPN affects the formation of neointima and constrictive remodeling associated with vascular injury was addressed using the strategy of …

The Female Athlete Triad: Role Of The Coach In Prevention And Intervention, Michelle Turner Breiland

Theses and Graduate Projects

Introduction The Female Athlete Triad consists of disordered eating, amenorrhea, and osteoporosis. Eating disorders affect between 1-10% of adolescent and college age women (Haller, 1992),particularly in women's' sports in which leanness is considered important for performance such as cross-country running. Methods A three page 17 item questionnaire was sent out to 45 coaches of women's Division III cross-country teams in the Midwest region of the US. Descriptive statistics were run on the data. Results Results showed that 8% of coaches have coached an athlete with a diagnosed eating disorder. Of the top three topics for team discussions, 9% of coaches …

Renal Basolateral Transport Of Glucuronides And Other Organic Anions In Rat In Vitro Models, Sarah L. Miles

Theses, Dissertations and Capstones

Glucuronidation is a common Phase II biotransformation reaction that increases the hydrophilicity, and thus elimination, of toxins, xenobiotics, and endogenous compounds. Previous studies suggest that the kidney can secrete glucuronide conjugates, but the renal transport mechanisms for glucuronide secretion have not been determined. Based on the chemical nature of glucuronide metabolites, it is hypothesized that organic anion transporter (OAT) proteins along the basolateral membrane of the renal proximal tubule promote renal accumulation of glucuronide conjugates. The purpose of this study was to develop a rat renal proximal tubule model which demonstrates OAT activity and by which the contribution of OAT …

The Genetic And Molecular Characterization Of The Polycystic Kidney Disease-Causing Mouse Gene Bicc1, Sarah J. Price

Theses, Dissertations and Capstones

Polycystic kidney disease (PKD) is one of the most common hereditary diseases and is characterized by progressive cyst formation, substantial renal enlargement, and frequently, progression to end-stage renal disease. One way to learn more about the etiology of this disease is to study mouse models that imitate the human situation. The juvenile congenital polycystic kidney disease (jcpk) gene on mouse Chromosome 10 has been found to cause a severe, early onset form of PKD when inherited in an autosomal recessive manner (Flaherty et al., 1995). Previous genetic studies mapped the jcpk locus to a 1 cM region on mouse Chromosome …

Cytoanalysis Of Pancreatic B-Cells: Using An Avian Model, Mammalian Tissue Culture And Implications Of Antisense Oligonucleotides Transfection, Ayman Salah-El-Deen Amer

Theses, Dissertations and Capstones

Calbindin-D_28k (CaBP_28K) is a vitamin D-dependent calcium-binding protein that may alter intracellular calcium ion levels, [Ca²⁺]i. This dissertation describes experiments done to gain an understanding of the potential role of CaBP_28k in pancreatic B-cells in control of insulin secretion. The localization of CaBP_28k and insulin in chicken pancreas are shown in Chapter 1. CaBP_28k expression was found to be highest in ventral and dorsal lobes and lowest in splenic lobe. Insulin concentrations were distributed similarly among these lobes. Confocal microscopic studies demonstrated colocalization of insulin and CaBP_28k in Bcells. These findings …

Roles Of Pkc Isozymes In Retinoic Acid-Induced B16 Mouse Melanoma Cell Growth Inhibition And Differentiation, Jianming Han

Theses, Dissertations and Capstones

Protein Kinase C (PKC) has been implicated in many cellular responses. Of the 11 isotypes in this family, seven are expressed in B16 mouse melanoma cells − PKCα, PKCδ, PKCε, PKCθ, PKCλ, PKCζ, and PKCµ.

Treatment of B16 cells with retinoic acid (RA) results in growth inhibition and differentiation. Simultaneously, RA induces a 6-8 fold increase of PKC α protein level, but only about 2-fold increase of PKC enzyme activity. The over- expression of wild type PKCα in B16 cells mimicked the action of RA. The over- expression of enzymatically inactive PKCα, either open or closed conformation, also inhibited B16 …

Docosahexaenoic Acid Modulates Class I Major Histocompatibility Complex Protein Function, Kaleb Marie Hypes

Theses, Dissertations and Capstones

Fatty acids influence immune responses, but how this occurs at the molecular level is not understood. Class I major histocompatibility complex molecules (MHC I), transmembrane proteins required for antigen presentation to T cell receptors, each consist of a 45kDa α chain noncovalently associated with a 12-kDa β₂-microglobulin (β₂m) molecule. Docosahexaenoic acid’s (DHA) effect on the binding of β₂m and anti-MHC I monoclonal antibodies (Mab) was measured. EL4 and RMA-S cells were cultured 48 hours with 0-45µM DHA or oleic acid. Murine to human β₂m exchange and Mab binding were assessed by fluorescence …

Natural Neuronal Variation In A Complex Neuroendocrine Pathway: Effect Of Selection For Photoperiod Responsiveness On The Density And Location Of Mature Gnrh-Releasing Neurons In Inhibitory And Excitatory Photoperiods, Mauricio Avigdor

Dissertations, Theses, and Masters Projects

No abstract provided.

Specification And Determination Of Gabaergic And Glutamatergic Neural Phenotypes In Xenopus Laevis, Mei Li

Dissertations, Theses, and Masters Projects

No abstract provided.

Neuronal Responses To Melatonin In Peromyscus Leucopus: A Candidate Mechanism For Circadian And Seasonal Temperature Regulation, Christopher Robert Fetsch

Dissertations, Theses, and Masters Projects

No abstract provided.

Analysis Of Expression Patterns Of Scl And Pax7 In The Mouse Brain For Potential Concomitant Function Within The Mesencephalon, Julie Stampalia

Theses : Honours

Investigation of the cascade of events that leads to brain formation during embryogenesis allows an understanding of the processes involved that may well be applicable to future neurodegenerative therapies. Two genes at work during embryonic neurogenesis in a brain region called the superior colliculus are Scl, a member of the basic helix-loop-helix factor transcription factor family and Pax7, a paired box transcription factor containing a homeobox dornain. The superior coiliculus forms part of the visual system in mammals and in sepmate studies both the Scl and Pax7 genes have been shown to be present in this region of the mouse …

Molecular Genetic Investigation Of Autosomal Dominant Hemifacial Microsomia, Rebecca Watt

Theses: Doctorates and Masters

The overall purpose of this project was to explore the underlying pathogenesis of Hemifacial microsomia (HFM), investigate treatment and management options identify likely candidate genes and screen candidate genes for mutation(s) causing the form of HFM segregating on chromosome 11 in a West Australian family. Hemifacial microsomia is a congenital malformation arising from the derivatives of the first and second branchial arches. It is both clinically and genetically heterogeneous and can occur sporadically or segregate within families in an autosomal fashion. HFM is characterised by significant undergrowth to one side of the face and is a common birth defect with …

Target Selection For Antisense Oligonucleotide Induced Exon Skipping In The Dystrophin Gene, Stephen J. Errington

Theses: Doctorates and Masters

Duchene Muscular Dystrophy (DMD), and the milder allelic Becker muscular dystrophy (EMD), are X-linked recessive muscle wasting disorders characterised by mutations in the dystrophin gene. DMD occurs at a frequency of approximately 1 in 3500 male newborns and life expectancy is typically less than 30 years. Due to progressive muscle wasting, affected boys are restricted to a wheelchair by the age of 12 years. The most common cause of death is pneumonia, compounded by cardiac involvement. Mutations that disrupt the dystrophin reading frame, or prevent the synthesis of either terminus, preclude the synthesis of a fully functional dystrophin. The subsequent …