Digital Commons Network^™

Molecular Screening Of Azoreductase Gene And Its Activity In Human Intestinal Bacteria, Syndia S. Todd

McCabe Thesis Collection

The intestinal microflora are capable of performing a wide variety of metabolic transformations. "The intestinal bacteria can enhance the function of the entire gastrointestinal tract, protect against pathogenic, maintain the vital chemical balance of the gastrointestinal system, and produce needed vitamins and hormones" (http;//www.upwardquest.com/crit2.html). Some of the products of this metabolism have been associated with carcinogenic processes, such as cancer, tumor formation, gastrointestinal disease, and infections. The ability of human intestinal microbes to interact with metabolites directly or after recirculation may contribute toward different toxicological disorders and disease.

The purpose of this study is to characterize and isolate the azoreductase …

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 …

Regulation Of Cardiac Fibroblast Metalloprotease Secretion, Glen De Guzman

Undergraduate Honors Capstone Projects

Matrix metalloproteases (MMPs) are proteolytic enzymes secreted by cardiac fibroblasts. Altered expression of MMPs plays an important role in congestive heart failure and other cardiovascular diseases^1,2. Emerging evidence has led us to consider the role of phosphatidylinositol 4-kinase (PtdIns 4-kinase) in regulating MMP secretion in cardiac fibroblast cells^3-7. PtdIns 4-kinase is a lipid kinase involved in various cellular processes including protein secretion. This project was designed to test the hypothesis that PtdIns 4-kinase controls MMP secretion. Techniques such as cardiac cell culture, transfection, and in-gel zymography were used for this experiment. Results demonstrated that PtdIns 4-kinase …

The Study Of Nitric Oxide Synthase Expression, Function, And Regulation In The Renal Vasculature During Postnatal Renal Development, Brian Blake Ratliff

Theses and Dissertations in Biomedical Sciences

The newborn kidney is vulnerable to vasomotor acute renal failure (ARF) from adverse perinatal events or complications of prematurity. Nitric oxide (NO) vasodilation is vitally protective in this type of ARF, but its relationship with other vasoactive factors, such as angiotensin II (AII) has not been examined. In the immature kidney, nitric oxide synthase (NOS) isoforms, specifically eNOS and nNOS, are developmentally regulated, but their specific role and regulation are unknown.

The enhanced vasodilatory role of NO in the immature kidney was hypothesized to be attributed to regulatory, expressional, and functional differences in eNOS and nNOS isoforms from the adult. …

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 …

The Expression And Function Of Wilms' Tumor 1 In Malignant Glioma, Aaron J. Clark

Theses and Dissertations

The Wilms' tumor 1 gene is overexpressed in many types of cancer and is associated with poor prognosis and resistance to anti-cancer therapies. In vitro studies in non-glioma cells types have demonstrated that WTl plays a role in increased proliferation, resistance to apoptosis, and increased cellular invasion. We aimed to thoroughly characterize the expression pattern of Wilms' tumor 1 in human malignant glioma and discern its function in this complex disease process. We screened a large sample of established human malignant glioma cell lines and glioma tissue specimens of all grades for WT1 expression. The majority of cell lines and …

The Zucker Rat As A Model Of Obesity-Hypertension, Ryan Morrison

Theses, Dissertations and Capstones

Hypertension is a serious health problem that affects approximately 1 in 4 American adults. Most cases are diagnosed as essential hypertension, meaning that the exact cause is unknown. In most patients, however, excess weight is a major contributory factor to the development of essential hypertension. The role of obesity in promoting hypertension is now well documented and has become the foundation for an entire field of research known alternately as obesity-hypertension, obesity-induced hypertension, or obesity-associated hypertension. In this field, rapid advances are being made in our understanding of how obesity and hypertension are linked. A plethora of related risk factors, …

Molecular Localization Of Hypoxia Inducible Factor-1-Alpha In Post-Ischemic Myocardium Following In Vivo Prolyl-4 Hydroxylase-2 Gene Silencing, Julia Antoinette Messina

Theses and Dissertations

Administration of small interfering RNA (siRNA) specific for prolyl-4 hydroxylase-2 (PHD2) results in PHD2 inhibition, Hypoxia Inducible Factor-I (HIF-1) activation, and cardioprotection versus Ischemia Reperfusion (IR). This study observes the effects of siRNA-mediated PHD2 inhibition on the distribution of cardioprotective proteins by immunofluorescence and basic histology. Fifteen mice were divided into 5 groups: PHD2 Control, Non-Targeting scramble (NTS) Control, IR Control, PHD2 IR, and NTS IR. Histologically, tissue damage was reduced dramatically in the PHD2 IR group compared to the NTS IR and IR control groups. From confocal images, total fluorescent pixels and intensities were quantified. The PHD2 IR group …

Female Genital Mutlation [Sic]: An Emerging Public Health Concern, Sarah Jan Brown

Senior Honors Theses and Projects

No abstract provided.

Interhemispheric Modulation Of Corticomotor Excitability Following I-Wave Periodicity Transcranial Magnetic Brain Stimulation (Itms), Lucy Catherine Millar

Theses : Honours

AIMS: Transcranial Magnetic Stimulation (TMS) has been recently demonstrated to have potential therapeutic benefits by promoting cortical plasticity through modulation of corticospinal excitability. We have previously shown in healthy adult subjects that paired-pulse TMS (1.5ms ISI) applied over Ml at 0.2Hz for 15min (known as iTMS), can raise corticospinal excitability for a period (~10min) that outlasts the intervention. Since interhemispheric changes in corticomotor excitability are considered to have fundamental importance in the control of voluntary movement, and recovery of motor function following unilateral damage, importance is placed on understanding the mechanisms involved. The aims of the current study were therefore …

Combinatorial Modulation Of Multiple Signaling Pathways To Gain Therapeutic Response In Breast And Prostate Cell Carcinomas, William Tressel Hawkins Ii

Theses and Dissertations

Our laboratory is primarily interested in novel pharmacological intervention of cell proliferation and survival pathways expressed in various types of cancer. These cyto-protective pathways can be activated in response to growth factor stimulation, toxic insult and radiation. In our studies, we utilized novel drug combinations with and without radiation to enhance breast & prostate tumor cell death both in vitro and in vivo. Previous studies from our group have shown that UCN-01 and MEK1/2 inhibitors interact to cause tumor cell death in transformed cell lines in vitro. We extended this observation to an in vivo animal model system using the …

Diffuse Brain Injury Triggers Ultra-Rapid Perisomatic Traumatic Axonal Injury, Wallerian Change, And Non-Specific Inflammatory Responses, Brian Joseph Kelley

Theses and Dissertations

A significant component of diffuse brain injury (DBI) is diffuse axonal injury (DAI) which is responsible for the morbidity and mortality associated with this condition. DAI and its experimental counterpart traumatic axonal injury (TAI) result in scattered microscopic pathology characterized by focal impairment of axonal transport leading to progressive swelling and delayed axotomy. DBI-mediated perisomatic axotomy does not result in acute neuronal death suggesting that delayed axotomy was responsible for this unanticipated response. To evaluate this hypothesis, we examined the spatiotemporal progression of DBI-mediated perisomatic TAI. LM / TEM identified impaired axonal transport within 15 - 30 min post-injury. Perisomatic …

Assessing Epidermal Growth Factor Expression In The Rodent Hippocampus Following Traumatic Brain Injury, Janice Mabutas Daus

Theses and Dissertations

Hippocampal neurons are vulnerable to injury, as indicated by the prevalence of learning and memory deficits following traumatic brain injury. Research indicates that proliferation of neural precursor cells increases following brain injury, which implies that there is an endogenous response in the hippocampus to replenish neurons and restore cognitive function. Studies show that mitogenic growth factors may drive this proliferative response; one of which is epidermal growth factor. Because adults and the elderly manifest the most enduring deficits following TBI, it is critical to investigate how EGF expression following injury may relate to injury-induced cell proliferation and the degree of …

The Effect Of Silencing The Wilms' Tumor 1 Gene On The Radiation Sensitivity Of Glioblastoma Cells, Dana C. Chan

Theses and Dissertations

Glioblastomas are among the most devastating of human cancers with a median survival of only 9-12 months. This type of brain tumor is incurable, largely due its remarkable proliferative capacity and resistance to current treatments. High levels of the Wilms' Tumor 1 (WTI) gene have been identified in glioblastomas, suggesting an oncogenic function. Moreover, known WT1 target genes have been implicated in resistance to radiation. To determine the role of WT1 in radiation resistance, two glioblastoma cell lines expressing WT1 were treated with siRNAs to silence this gene. Confirmation of WT1 knockdown was achieved through real-time PCR and Western blot. …

A Model For Studying Vasogenic Brain Edema, Anshu Shukla

Theses and Dissertations

Convection-enhanced delivery (CED) is a proven method for targeted drug delivery to the brain that circumvents the blood-brain barrier (BBB). Little study has been conducted in understanding CED in pathological brain states. This is of importance when dealing with chemotherapeutic agent delivery to brain tumors, where vasogenic edema (VE) exists. The current study aims to characterize a model of VE suitable for studying CED.VE was produced in the right hemisphere of the rat brain using multiple infusions of hyperosmotic mannitol (0.25mL/kg/s over 30 seconds) delivered through the right internal carotid artery. Magnetic resonance imaging (MRI) revealed consistent edema formation and …

The Influence Of A Single Nucleotide Polymorphism In The Matrix Metalloproteinase-1 Promoter On Glioma Biology, Jessica Mccready

Theses and Dissertations

Glioblastomas are an incurable type of brain tumor with a mean survival time of 9-12 months following diagnosis. One of the reasons for this poor prognosis is the ability of tumor cells to invade the surrounding normal brain tissue. Enzymes responsible for this invasive nature include the matrix metalloproteinase family. MMP-1 is a member of this family which has been well studied in many types of invasive tumors, with gliomas being an exception. We studied a single nucleotide polymorphism (SNP) in the MMP-1 promoter that may influence glioma biology. This SNP consists of the presence (2G) or absence (1G) of …

Developmental Expression Of Calcium-Binding Proteins In The Avcn And Mntb Of Normal Hearing And Congenitally Deaf Mice, John L. Roebel

Browse all Theses and Dissertations

This experiment analyzes synaptic differences in the central auditory pathway between normal hearing and congenitally deaf (dn/dn) mice, and provides valuable insight into central changes that correspond with human congenital deafness. Specifically, this experiment analyzes developmental expression of the Calcium (Ca2+)-binding proteins Calretinin (CR), Calbindin D-28k (CB) and Parvalbumin (PV) in large excitatory synapses in the anteroventral cochlear nucleus (AVCN) and the medial nucleus of the trapezoid body (MNTB) of normal and dn/dn mice. Immunofluorescence imaging with primary antibodies detecting CR, CB or PV was used to analyze the expression of each at 9 days, 13 days, 20 days, 30 …

The Relationship Between Lactic Acid, Reactive Oxygen Species And The Hypoxia-Induced Acidification Seen In Chemosensitive Neurons Of The Nucleus Tractus Solitarius (Nts), Trevor Downing

Browse all Theses and Dissertations

The NTS is one of many sites of chemoreception meaning that it responds to changes in CO2 and pH. NTS neurons also acidify approximately 0.13 pH units in response to hypoxia. Experiments involved brainstem slices exposed to a control hypoxic bout followed by hypoxia in conjunction with different drugs. The drugs included fluorocitrate, 4-hydroxycinnamate, oxygen-glucose deprivation and iodoacetate. Iodoacetate produced the strongest blunting of the hypoxia-induced acidification and decreased the response by ~53%. Results from the studies using the superoxide probe DHE showed an increase in the levels of ROS during the hypoxic exposure prior to reoxygenation. Two ROS scavengers …

Characterization And Functional Analysis Of A Newly Identified Human Mt5-Mmp Transcript Variant Isolated From Multipotent Nt2 Cells, Heather Hamilton Ross

Theses and Dissertations

Membrane-type 5 matrix metalloproteinase (MT5-MMP) is unique among MMP family members as it is predominately expressed in the CNS. Its expression is ubiquitous during brain development and restricted to regions of neurogenesis and neuroplasticity in the adult. MT5-MMP is a mediator of pericellular proteolysis and is thought to have a functional impact on neurite outgrowth. The studies presented in this work were designed to examine MT5-MMP expression in cultured NT2 cells, a model of newogenesis and neuronal differentiation, and in adult neurogenic brain regions. We further sought to overexpress MT5-MMP and test the hypothesis that it plays a role in …

Cross-Modal Projections From Auditory To Visual Cortices In The Ferret, Meng Y. Wang

Theses and Dissertations

Recent studies have shown that neuronal connections occur between primary auditory and visual cortices of the primate (Falchier et al., 2002; Rockland and Ojima, 2003), and it has been suggested that these projections are involved in multisensory processing in these lower-level, core areas of cortex. The present study was conducted to determine if similar connections occur in other higher mammals such as carnivores (ferrets; Mustela putorius). Large injections of sensitive neuroanatomical tracer were placed within the core areas of auditory cortex in 3 ferrets. After transport and processing, labeled axon terminals were found not in primary visual cortex, but in …

The Role Of Sulfatide In Alzheimer's Disease, Charles Britton Beasley Jr.

Theses and Dissertations

Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta plaques, neurofibrillary tangles (NFT) and loss of cortical neurons that control memory and cognition. The cause of NFTs and Aβ plaques is not clear, though it is known that they are formed by enzymes which are preferentially sequestered to membrane domains called lipid rafts. Sulfatide (ST) is a glycosphingolipid that is essential for the proper structure and function of lipid rafts. In mice that lack ST, membrane domains that are normally maintained by adhesive contacts and functional lipid rafts are improperly formed and are unstable. In these ST null …