Open Access. Powered by Scholars. Published by Universities.®

Digital Commons Network™

Open Access. Powered by Scholars. Published by Universities.®

Medical Sciences

Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 22171 - 22200 of 24687

Full-Text Articles in Entire DC Network

Hybrid Adult Neuron Culture Systems For Use In Pharmacological Testing, Darin Keay Edwards Jan 2011

Hybrid Adult Neuron Culture Systems For Use In Pharmacological Testing, Darin Keay Edwards

Electronic Theses and Dissertations

Neuronal culture systems have many applications, such as basic research into neuronal structure, function, and connectivity as well as research into diseases, conditions, and injuries affecting the brain and its components. In vitro dissociated neuronal systems have typically been derived from embryonic brain tissue, most commonly from the hippocampus of E18 rats. This practice has been motivated by difficulties in supporting regeneration, functional recovery and long-term survival of adult neurons in vitro. The overall focus of this dissertation research was to develop a dissociated neuronal culture system from human and animal adult brain tissue, one more functionally and developmentally correlative …

Go to article

Discovery And Optimization Of Novel Small-Molecular Inhibitors Suppressing Stat3-Dependent Tumor Process, Xiaolei Zhang Jan 2011

Discovery And Optimization Of Novel Small-Molecular Inhibitors Suppressing Stat3-Dependent Tumor Process, Xiaolei Zhang

Electronic Theses and Dissertations

With the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor, S3I-201, we have designed a diverse set of analogs. One of the most active analogs, S3I-201.1066 is derived to contain a cyclo-hexyl benzyl moiety on the amide nitrogen, which increases …

Go to article

Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass Jan 2011

Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass

Electronic Theses and Dissertations

Transplanted embryonic stem (ES) cells following myocardial infarction (MI) contribute to limited cardiac repair and regeneration with improved function. Therefore novel strategies are still needed to enhance the efficacy by which ES cells differentiate into cardiac cell types and inhibit adverse remodeling in the infarcted myocardium. Our studies evaluate whether genetic manipulation of transplanted ES cells employing miR- 1, a pro-cardiac microRNA, and TIMP-1, an anti-apoptotic and anti-fibrotic protein, will enhance cardiac myocyte differentiation, inhibit native cardiac apoptosis, and reduce fibrosis in the infarcted myocardium. Furthermore, we assess levels of associated pro- (caspase-3, PTEN) and anti-(Akt) apoptotic proteins as well …

Go to article

Translocation Of The Cholera Toxin A1 Subunit From The Endoplasmic Reticulum To The Cytosol, Michael Prentice Taylor Jan 2011

Translocation Of The Cholera Toxin A1 Subunit From The Endoplasmic Reticulum To The Cytosol, Michael Prentice Taylor

Electronic Theses and Dissertations

AB-type protein toxins such as cholera toxin (CT) consist of a catalytic A subunit and a cell-binding B subunit. CT proceeds through the secretory pathway in reverse, termed retrograde trafficking, and is delivered to the endoplasmic reticulum (ER). In order for the catalytic A1 subunit to become active it must separate from the rest of the holotoxin, and this dissociation event occurs in the ER lumen. CTA1 assumes an unfolded conformation upon dissociation from the holotoxin and is recognized by ERassociated degradation (ERAD), a quality control system that recognizes and exports misfolded proteins to the cytosol for degradation by the …

Go to article

Glial Differentiation Of Human Umbilical Stem Cells In 2d And 3d Environments, Hedvika Davis Jan 2011

Glial Differentiation Of Human Umbilical Stem Cells In 2d And 3d Environments, Hedvika Davis

Electronic Theses and Dissertations

During differentiation stem cells are exposed to a range of microenvironmental chemical and physical cues. In this study, human multipotent progenitor cells (hMLPCs) were differentiated from umbilical cord into oligodendrocytes and astrocytes. Chemical cues were represented by a novel defined differentiation medium containing the neurotransmitter norepinephrine (NE). In traditional 2 dimensional (2D) conditions, the hMLPCs differentiated into oligodendrocyte precursors, but did not progress further. However, in a constructed 3 dimensional (3D) environment, the hMLPCs differentiated into committed oligodendrocytes that expressed MBP. When co-cultured with rat embryonic hippocampal neurons (EHNs), hMLPCs developed in astrocytes or oligodendrocytes, based on presence of growth …

Go to article

The Effect Of High Dose Total Body Irradiation On Acth, Corticosterone, And Catecholamines In The Rat, Eric P. Cohen, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Hershel Raff Jan 2011

The Effect Of High Dose Total Body Irradiation On Acth, Corticosterone, And Catecholamines In The Rat, Eric P. Cohen, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Hershel Raff

Biomedical Sciences Faculty Research and Publications

Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic–pituitary–adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study …

Go to article

A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti Jan 2011

A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti

All ETDs from UAB

Inflammation and airway destruction are hallmarks of many debilitating lung diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), acute lung injury (ALI), and cancer. Gene-based therapeutic interventions that modulate this pathologic inflammatory response are likely to reduce the progressive destruction to lung airways. In this regard, a number of strategies have been evaluated for targeting the pul-monary vasculature; particularly those based on serotype 5 Adenovirus (Ad5). The ad-vantages of Ad over other vector systems include: in vivo stability, low oncogenic poten-tial, and large packaging capacity. Yet, specific and efficient gene delivery to the lung has been hampered …

Go to article

Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley Jan 2011

Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley

All ETDs from UAB

The mucin-like Lysosome Associated Membrane Protein (LAMP) family member CD68 is a primarily myeloid lineage restricted transmembrane protein that is expressed in macrophages and osteoclasts. While the existence and expression pattern of human CD68 and mouse CD68 (sometimes called macrosialin) are well-known, and these molecules are routinely used as histological markers of tissue macrophages, the functional signific-ance of CD68 expression remains an unanswered question. Our overall goal is to deter-mine the significance and characterize the function of CD68 in osteoclasts and explore the effects of Receptor Activator of Nuclear Factor κB (RANK) signaling on CD68 post-translational modification. To achieve this …

Go to article

Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan Jan 2011

Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan

All ETDs from UAB

It is well established that multiple parameters of cardiovascular physiology and pathophysiology exhibit diurnal variations. For example, human heart rate and blood pressure peak during the morning and trough in the evening. Similarly, there is a morning prevalence for the onset of multiple adverse cardiovascular events, including myocardial ischemia, arrhythmias, and sudden cardiac death. Traditionally these rhythms have been attributed to rhythms in neurohumoral stimulation. However recent identification of the circadian clock mechanism in cardiovascular relevant cell types, including the cardiomyocyte, has prompted investigation into its role in modulating myocardial physiology and pathophysiology over the course of the day. Preliminary …

Go to article

The Role Of The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn Jan 2011

The Role Of The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn

All ETDs from UAB

Acute myeloid leukemia (AML) comprises approximately 25% of newly diagnosed cases of leukemia each year. The constitutive activation of the classical NF-κB signaling pathway has been observed in up to 70% of AML cases, and could be due to mutations upstream involving the PI3K-Akt cascade, which is also constitutively active in a majority of cases. In mice, constitutive activation of Akt either through deletion of the negative regulator of PI3K-Akt, PTEN, or by expression of Myr-Akt induces rapid stem cell loss along with a lethal, transplantable myeloproliferative disorder and AML. These studies show that constitutive Akt and NF-κB signaling distinguish …

Go to article

The Study Of Intracellular Signaling Pathways In Schizophrenia, Adam Funk Jan 2011

The Study Of Intracellular Signaling Pathways In Schizophrenia, Adam Funk

All ETDs from UAB

INTRACELLULAR SIGNALING AND INTEGRATION ABNORMALITIES IN SCHIZOPHRENIA Adam J. Funk DEPARTMENT OF NEUROBIOLOGY ABSTRACT The pathophysiology of schizophrenia is complex and diverse, with many classes of receptors, neurotransmitters, and brain regions implicated in this illness. The many hypotheses proposed have yet to fully explain the heterogeneity of the genetic, postmor-tem, and clinical evidence. It is the goal of this dissertation to integrate the current hy-potheses of schizophrenia into a unified hypothesis of abnormal intracellular signaling and signal integration. Inconsistencies in genetic and postmortem findings suggest that the development of schizophrenia is multifaceted, and the heterogeneity of symptoms supports the hypothesis …

Go to article

Human Cytomegalovirus Ul97 Kinase Activity Modifies Cell Cycle Checkpoint Regulators, Rachel Brooke Gill Jan 2011

Human Cytomegalovirus Ul97 Kinase Activity Modifies Cell Cycle Checkpoint Regulators, Rachel Brooke Gill

All ETDs from UAB

Human cytomegalovirus (CMV) infection results in destructive infections in neonates and immunocompromised individuals. Being the primary congenital infection in the United States, it can often result in permanent neurological deficits in infants. The current therapies for CMV infections all target the viral DNA polymerase and also have dose-limiting toxicities. Isolates resistant to ganciclovir (GCV), the therapy of choice, can sometimes overwhelm immunocompromised hosts. Better therapies for this infection are required. The CMV UL97 kinase is a key enzyme in the treatment of CMV infection because it phosphorylates GCV. Additionally, maribavir (MBV) specifically inhibits UL97 kinase activity and inhibits viral replication. …

Go to article

Oxidative Stress And Xanthine Oxidase In Acute And Chronic Cardiac Volume Overload In Rats, James Douglas Gladden Jan 2011

Oxidative Stress And Xanthine Oxidase In Acute And Chronic Cardiac Volume Overload In Rats, James Douglas Gladden

All ETDs from UAB

Mechanisms of left ventricular dysfunction in cardiac volume overload (VO) are not well understood and there is no medical therapy. Cardiac VO is marked by eccentric remodeling and contractile dysfunction ultimately resulting in cardiac failure. Oxidative stress is implicated in the pathophysiology of heart failure and recent evidence suggests xanthine oxidase (XO) plays a role in VO. To study VO, we used a rat model of aortocaval fistula (ACF). ACF results in early diastolic stress on the left ventricle (LV) and recapitulates the progressive nature of heart failure with contractile function being initially maintained and then depressed by 6 weeks. …

Go to article

Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook Jan 2011

Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook

All ETDs from UAB

Sulfation is an important Phase II drug metabolism reaction catalyzed by the cytosolic sulfotransferases (SULTs). SULT2A1 is a major SULT in liver and adrenal cortex that has been reported to sulfate a wide variety of substrates including bile acids, steroids, and drugs. The crystal structures of SULT2A1 suggest that PAPS binding causes a structural change. This study examines the kinetic changes in SULT2A1 caused by PAPS binding using computer modeling, enzyme kinetics, binding studies, and mammalian cells expressing SULT2A1. The data presented clearly demonstrate that the binding of PAPS changes the affinity of some substrates to SULT2A1 resulting in different …

Go to article

Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Jean Nick Jan 2011

Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Jean Nick

All ETDs from UAB

The t(8;21) translocation, which generates an AML1-ETO fusion protein (also known as RUNX1-ETO), is one of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML). Murine studies have demonstrated that AML1-ETO promotes the accumulation of myeloid progenitor cells with self-renewal capability and impaired differentiation capacity. However, AML1-ETO+ mice do not progress to AML in the absence of additional mutations, suggesting that expression of the translocation is insufficient for leukemogenesis. This hypothesis is supported by studies demonstrating the persistence of AML1-ETO-expressing hematopoietic progenitors obtained from patients in long-term clinical remission. Mutations affecting receptor tyrosine kinases, particularly c-KIT, are commonly detected …

Go to article

Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky Jan 2011

Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky

All ETDs from UAB

Our laboratory reported that a combination of ionizing radiation (IR) or temozolomide (Tmz), a DNA methylating agent clinically approved against glioblastoma multiforme (GBM), a type of human brain cancer, and TRA-8, an anti-DR5 monoclonal antibody produced synergistic cytotoxicity in GBM cells in culture and in mouse xenograft models through an yet unknown mechanism. I hypothesized that understanding of the synergy phenomenon can offer an insight into the nature of GBM vulnerability. The goals of this investigation were two-fold - to elucidate the mechanism of this enhancement in cytotoxicity, and to improve understanding of DR5 mediated apoptosis toward improvement of current …

Go to article

Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland Jan 2011

Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland

All ETDs from UAB

The recently characterized exopolysaccharide of Mycoplasma pulmonis, EPS-I, has been identified as modulating the susceptibility to complement-mediated lysis and binding to host mucosal epithelium. M. pulmonis produces family of size- and phase-variable lipoproteins called Vsa. Previous evidence has strongly demonstrated that the length of the tandem repeat region of the M. pulmonis Vsa protein is associated with the susceptibility to the host innate immune system through complement-mediated lysis. Mycoplasmas producing a long form of Vsa, containing about 40 repeats, are resistant complement whereas strains that produce the short form of Vsa, 5 repeats or fewer, are susceptible. Furthermore, the size …

Go to article

The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist Jan 2011

The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist

All ETDs from UAB

This dissertation documents my findings in two unrelated projects. Project 1: Expansion of CAG repeats encoding glutamine in huntingtin and ataxin 3 causes the neurodegenerative diseases Huntington's disease (HD) and spinocerebellar ataxia 3 (SCA3), respectively. Both poly-glutamine (polyQ) expanded proteins misfold and ag-gregate within the cell. Preventing aggregation of polyQ proteins through molecular or pharmacological approaches provide therapeutic advantage in animal models of HD and SCA3. I hypothesized that the UL97 kinase encoded by the human cytomegalovirus (HCMV) may be able to prevent the aggregation of polyQ proteins. Initially, I showed that the UL97 kinase prevents the deposition of aggregates …

Go to article

The Requisite Role Of Dectin-1 And Il-17 In Innate Host Defense Against Aspergillus Fumigatus, Jessica L. Werner Jan 2011

The Requisite Role Of Dectin-1 And Il-17 In Innate Host Defense Against Aspergillus Fumigatus, Jessica L. Werner

All ETDs from UAB

Immune suppression increases the incidence of invasive fungal infections, particularly those caused by the opportunistic mold Aspergillus fumigatus. We show that non-immunosuppressed mice lacking the beta-glucan receptor Dectin-1 (Dectin-1-/-) are more susceptible to intratracheal challenge with A. fumigatus than control mice, exhibiting >80% mortality within 5 days; ultimately attributed to a compromise in respiratory mechanics. In response to A. fumigatus challenge, Dectin-1-/- mice demonstrated impaired inflammatory response as seen through defective cytokine and chemokine production, which resulted in insufficient lung neutrophil recruitment and uncontrolled A. fumigatus lung growth. Alveolar macrophages from Dectin-1-/- mice failed to produce proinflammatory mediators in response …

Go to article

Low And High Let Irradiation Of Human Aortic Endothelial Cells Induces Dose And Time Dependent Adhesion Of Monocytes Which Is Mediated By Chemokines Expressed By The Irradiated Endothelium., Saman Fatima Khaled Jan 2011

Low And High Let Irradiation Of Human Aortic Endothelial Cells Induces Dose And Time Dependent Adhesion Of Monocytes Which Is Mediated By Chemokines Expressed By The Irradiated Endothelium., Saman Fatima Khaled

All ETDs from UAB

Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of xrays, iron (Fe56) ions, and protons on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X-rays, 0, 2, and 5 Gy Fe56 ions, and 0, 0.5, and 2 Gy protons followed by measurement of …

Go to article

The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz Jan 2011

The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz

All ETDs from UAB

THE ROLE OF TRIB3 IN INSULIN RESISTANCE: ITS ACTION AS NUTRIENT SENSOR AND REGULATOR OF INSULIN ACTION JIARONG LIU LAMIQUIZ PATHOLOGY ABSTRACT Insulin resistance is a hallmark of Type 2 diabetes (T2DM). A reduced capacity for insulin to stimulate increases in glucose uptake and glucose oxidation in insulin sensitive tissues, such as skeletal muscle and adipose tissue, are common defects in patients with insulin resistance, T2DM, and other related diseases. Tribbles homolog 3 (TRIB3) has been demonstrated to play a role in insulin resistance by serving as a negative regulator of Akt in mouse liver, fat, and pancreas. In a …

Go to article

Elucidation Of The Elongated Fibrillar Structure Of Streptococcus Mutans Antigen I/Ii, Matthew Rodney Larson Jan 2011

Elucidation Of The Elongated Fibrillar Structure Of Streptococcus Mutans Antigen I/Ii, Matthew Rodney Larson

All ETDs from UAB

Streptococcus mutans (S. mutans) is the causative agent behind dental caries, an infectious disease also known as tooth decay or dental cavities. S. mutans has a cell wall-attached protein known as Antigen I/II (AgI/II) utilized for bacterial adhesion to the tooth surface. Here we have solved the structures of both amino- and carboxy-terminal regions of the AgI/II molecule using X-ray crystallography. Using this structural information we have now built a tertiary model for AgI/II as a fibrillar protein. Further, we have functionally characterized AgI/II and determined minimal regions of AgI/II that are implicated in its adherence to the salivary agglutinin …

Go to article

Analysis Of Nphp Complex Genetic Interactions Associated With Human Cilia Disorders, Svetlana Viktorovna Masyukova Jan 2011

Analysis Of Nphp Complex Genetic Interactions Associated With Human Cilia Disorders, Svetlana Viktorovna Masyukova

All ETDs from UAB

Primary cilia are antenna-like organelles that extend from the surface of almost all mammalian cell types. They regulate many signaling pathways and sense physical and chemical changes in the extracellular environment. Defects in primary cilia cause several human disorders of different severity collectively called ciliopathies, including nephronophthisis (NPHP), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). Numerous MKS, JBTS and NPHP genes have been identified but in most cases of these ciliopathies the genetic defect is unknown. Despite the fact that NPHP, JBTS and MKS patients present with distinct clinical features, they have mutations in identical genes. This can be explained …

Go to article

Hemoglobin Switching, Thalassemia And Sickle Cell Disease In Humanized Knockin Mice, Sean Mcconnell Jan 2011

Hemoglobin Switching, Thalassemia And Sickle Cell Disease In Humanized Knockin Mice, Sean Mcconnell

All ETDs from UAB

In this dissertation we describe knockin mouse models for the study of human hemoglobin disorders. These knockin human globin genes, in contrast to transgenes, replace the adult mouse globin genes, remain under control of endogenous mouse globin enhancer sequences and are inherited in a manner identical to globin alleles in man. Starting with various knockin alleles composed of unique human alpha, beta and gamma globin gene sequences, we evaluate several allele combinations towards our goal of generating improved models of thalassemia and sickle cells disease. We show that humanized knockin mice complete a fetal to adult hemoglobin switch during postnatal …

Go to article

Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang Jan 2011

Piggybac Transposon Mutagenesis In Human And Mouse Stem Cells, Tingting Zhang

All ETDs from UAB

The most common genetic diseases worldwide, £] thalassemia and Sickle Cell Anemia (SCA) result from mutations in the adult £] globin gene. One promising therapeutic method to ameliorate these diseases is to reactivate the endogenous fetal f× globin gene. I hypothesize that an erythroid mutagenic transposon system can be used to activate f× globin gene expression. To test this hypothesis three lines of genetically modified mice were generated and bred together. The first is a transgenic mouse line that contains a multicopy array of erythroid mutagenic PiggyBac (PB) transposons. The second transgenic mouse line expresses the PB transposase (TPase) from …

Go to article

Determining The Functional Role Of Trem-Like Transcript 2 In The Innate Immune Response, Matthew Martin Halpert Jan 2011

Determining The Functional Role Of Trem-Like Transcript 2 In The Innate Immune Response, Matthew Martin Halpert

All ETDs from UAB

TLT2 is one of four receptors conserved between mouse and human within the TREM locus, and is expressed on B cells, macrophages, and neutrophils. TLT2 ligation on murine macrophages induces the production of chemokines and growth factors, as evidenced by ex vivo treatment with anti-TLT2 mAbs. This treatment did not lead to the upregulation of activation markers such as CD69 or costimulatory molecules such as CD80 and CD86, indicating a specific response following TLT2 ligation. This is recapitulated in vivo following injection of anti-TLT2 mAbs resulting in the production of chemokines and growth factors, which ultimately lead to enhanced neutrophil …

Go to article

Ampa Receptor Trafficking In Schizophrenia, John Hammond Jan 2011

Ampa Receptor Trafficking In Schizophrenia, John Hammond

All ETDs from UAB

The glutamate hypothesis of schizophrenia is based primarily on NMDA receptor dysfunction. Recent studies have led to an expansion of this hypothesis to include AMPA receptors which are essential for neurotransmission through NMDA receptors. Examination of total AMPA receptor protein expression in schizophrenia has been inconsistent and led to examination of AMPA receptor interacting proteins and trafficking and subcellular localization of the receptors. AMPA receptors are highly trafficked from the endoplasmic reticulum to the synapse and in a complex system of endosomes. Alterations in the subcellular localization of these receptors may be a part of the underlying pathophysiology of schizophrenia. …

Go to article

The Role Of Mitochondrial Oxidative Stress In Cardiovascular Disease Development, Corey Michael Harrison Jan 2011

The Role Of Mitochondrial Oxidative Stress In Cardiovascular Disease Development, Corey Michael Harrison

All ETDs from UAB

An estimated 70 million Americans have one or more types of cardiovascular disease (CVD). Although the sequence of events leading to CVD are still controversial, there is a general consensus that atherosclerotic lesions result from oxidative stress associated with risk factor. For this study, it was hypothesized that endogenous mitochondrial oxidative stress would influence susceptibility to atherogenesis and mitochondrial damage mediated by CVD risk factor exposure. To test this hypothesis, atherosclerotic lesion formation, oxidant stress, and mitochondrial DNA damage were assessed in hypercholestoremic mice (apolipoprotein E null - apoE -/- SOD2 +/+) and mice with significantly decreased levels of the …

Go to article

The Role Of Ll-37 In Prostate Cancer And Its Potential As A Therapeutic Target, Jonathan Adam Hensel Jan 2011

The Role Of Ll-37 In Prostate Cancer And Its Potential As A Therapeutic Target, Jonathan Adam Hensel

All ETDs from UAB

LL-37 is the only cathelicidin-derived anti-microbial peptide in humans and has been shown to stimulate proliferation, angiogenesis, cellular migration and inhibit apoptosis, in addition to serving as a chemoattractant for leukocytes. It is produced primarily by epithelial cells and leukocytes, and has recently been discovered to be over-expressed in breast, ovarian and lung cancers. Based on these findings, we compared levels of LL-37 expression in benign and cancerous human prostate tissues. Results of this investigation demonstrated that LL-37 is increasingly over-expressed in primary prostate tumors in a grade dependent manner and in metastatic lesions. Since the physiological mechanisms of LL-37 …

Go to article

Protein Modifications And The Response To Oxidized Lipids In Cardiovascular Cells, Ashlee Higdon Jan 2011

Protein Modifications And The Response To Oxidized Lipids In Cardiovascular Cells, Ashlee Higdon

All ETDs from UAB

Free radical catalyzed oxidation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid is increased in cardiovascular disease states, including atherosclerosis and heart failure. Oxidized lipids have been extensively studied and found to recapitulate several key steps in atherogenesis. However, clinical trials with antioxidants such as alpha-tocopherol have been less promising than originally predicted. Now appreciated as more than just biomarkers of disease, lipid peroxidation products have been shown to have roles in pathogenesis as well as physiology. Of particular interest are reactive lipid species that possess electrophilic carbonyls enabling them to act in a receptor-independent manner. To date, the …

Go to article

First Prev Next Last