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Full-Text Articles in Medicine and Health Sciences

Modulation Of Transforming Growth Factor (Tgf)-Ss1 And Its Implications In Breast Cancer Metastasis, Lakisha Dionne Moore Jan 2008

Modulation Of Transforming Growth Factor (Tgf)-Ss1 And Its Implications In Breast Cancer Metastasis, Lakisha Dionne Moore

All ETDs from UAB

Overexpresssion of transforming growth factor (TGF)-β has been implicated in promoting immune suppression, tumor angiogenesis, tumor cell migration, and invasion in many cancers including carcinoma of the breast. Thus, targeted downregulation of TGF-β1 expression in breast cancer in situ and determination of its implications potentially could provide new treatment approaches for disease management. siRNA constructs targeting TGF-β1 were validated and used to develop clonal derivatives of the MDA-MB-435 metastatic breast cancer cell line. Inhibition of TGF-β1 expression in MDA-MB-435 cells showed decrease in migration and invasion in vitro with an increase in proliferation. In vivo analysis indicated a 90% decrease …


The Role Of Centaurin Alpha-1 In The Regulation Of Neuron Al Differentiation, Carlene Drucilla Moore Jan 2008

The Role Of Centaurin Alpha-1 In The Regulation Of Neuron Al Differentiation, Carlene Drucilla Moore

All ETDs from UAB

In the nervous system, PI 3-kinase has been implicated in neuronal differentiation. My studies have focused on a candidate neuronal PI 3-kinase target centaurin alpha-1, which binds PtdIns(3,4,5)P3, and is an Arf6 GAP. Centaurin alpha-1 is localized in dendrites, dendritic spines and synapses, and is required for neuronal differentiation and spine morphogenesis. In dissociated neuronal cultures, expression of centaurin alpha-1 enhances dendritic branching, and increases dendritic filopodia, lamellipodia and spine-like protrusions. Expression of centaurin alpha-1 GAP inactive mutant or knocking down centaurin alpha-1 levels using siRNA leads to inhibition of dendritic outgrowth and branching. Manipulations of centaurin alpha-1 also disrupt …


Investigation Of Lipoteichoic Acid Structure And Function To Establish Its Role In Gram-Positive Bacterial Infections, Ho Seong Seo Jan 2008

Investigation Of Lipoteichoic Acid Structure And Function To Establish Its Role In Gram-Positive Bacterial Infections, Ho Seong Seo

All ETDs from UAB

Lipoteichoic acid (LTA) is an essential bacterial membrane polysaccharide (cell wall component) that is linked to a glycerol backbone with two acyl chains. Since an antibody to LTA has been shown to protect from Gr+ bacterial infections or colonization, and the mutant Gr+ bacteria which produce less amount of LTA have less pathogenic than WT, LTA may be an important role in Gr+ bacterial infection and inflammation. The currently accepted structure of pneumococcal LTA has the pentameric repeating unit bound to the lipid anchor {Glc(β1��3)AATGal(β1��3)Glc(α1��3)-acyl2Gro}. Unlike the lipid anchor of other Gr+ bacterial LTA, this pneumococcal LTA lipid anchor has …


Changes In Short-Term Facilitation Are Opposite At Schaffer Collateral And Temporoammonic Ca1 Synapses In The Developing Rat Hippocampus, Haley E. Speed Jan 2008

Changes In Short-Term Facilitation Are Opposite At Schaffer Collateral And Temporoammonic Ca1 Synapses In The Developing Rat Hippocampus, Haley E. Speed

All ETDs from UAB

Hippocampal CA1 pyramidal neurons integrate and filter spatial, temporal, and sensory information from the entorhinal cortex (EC) for memory storage. Synaptic transmission mediates the processing of incoming information, and recent studies have demonstrated that long-term changes in synaptic strength at CA1 synapses are important for learning and memory. Short-term changes in synaptic strength, occurring on a timescale of milliseconds to minutes, do not require lasting modifications and are rapidly reversible. Termed short-term plasticity, it is known to be important for dynamic gain control of synaptic transmission and neural computation. During late postnatal development, there are extensive developmental changes in rat …


Analysis Of The Hedgehog Pathway In Pancreatic Adenocarcinoma, Adam Steg Jan 2008

Analysis Of The Hedgehog Pathway In Pancreatic Adenocarcinoma, Adam Steg

All ETDs from UAB

Pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer mortality in the United States. Despite the use of highly aggressive treatment regimens (surgery, chemotherapy and radiation), almost all patients succumb to metastatic disease within 6-10 months of diagnosis. The hedgehog (HH) signaling pathway was originally discov-ered to play a critical role in mammalian embryological development. Interestingly, re-cent studies have suggested that aberrant expression of this pathway is involved in the initiation and continued growth of PAC. Small molecules that antagonize the transmem-brane protein Smoothened (Smo), a critical signaling component of the HH pathway, have proven effective in decreasing PAC …


A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody Jan 2008

A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody

All ETDs from UAB

Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anti-cancer agents designed to infect and lyse tumor cells. For increased efficacy, CRAds have been armed with therapeutic transgenes. Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, represents a promising candidate with which to arm a CRAd intended to treat osteolytic bone metastases. We hypothesize that a CRAd armed with OPG will inhibit breast cancer bone metastasis and reduce tumor burden in the bone by directly lysing tumor cells and by …


Thrombospondin Type-1 Repeats And Their Potential Role In Inhibiting Glioblastoma Angiogenesis, Joshua C. Anderson Jan 2008

Thrombospondin Type-1 Repeats And Their Potential Role In Inhibiting Glioblastoma Angiogenesis, Joshua C. Anderson

All ETDs from UAB

Thrombospondin-1 (TSP-1) is a 420 kilodalton homotrimeric protein; it is one of the first identified anti-angiogenic proteins found to be expressed in some normal tissues. Peptides derived from the type-1 repeat (TSR) domains of full length TSP-1 have been shown to have anti-angiogenic activity, and thus anti-tumor activity in some non-glioma tumor models. I hypothesized that peptides derived from the TSRs of TSP-1, such as ABT-510, could inhibit angiogenesis and thus malignant glioma tumor growth in vivo. I found that ABT-510 inhibited angiogenesis of the human brain microvascular endothelial cell (MvEC) in an in vitro tubulomorphogenesis assay. To determine the …


Human Papillomavirus: Segregation And Replication, Luan D. Dao Jan 2008

Human Papillomavirus: Segregation And Replication, Luan D. Dao

All ETDs from UAB

Human papillomavirus are small DNA tumor viruses. The viral genome is a small circular double stranded DNA that replicates autonomously as an extrachromosomal plasmid. Occasionally infections by the high risk HPV viruses can lead to DNA integration and progression to cancer. How the HPV DNA is maintained and becomes established in the dividing host cells is not well understood. Additionally, as a double-stranded DNA virus it is likely that double-stranded DNA breaks in the viral genome, either from replication or random damage, will trigger a DNA repair response from the host cell. Such responses have been alternatively reported to be …


Metabolism Of Neutrophil-Deprived Chlorinated Isoflavones, Tracy Lyn D'Alessandro Jan 2008

Metabolism Of Neutrophil-Deprived Chlorinated Isoflavones, Tracy Lyn D'Alessandro

All ETDs from UAB

Despite medical advances in both drug therapy and surgical techniques, Americans mostly die from heart disease. Many belong to the low- and middle-class families who do not have sufficient access to medical care due to its high costs. An alternative is the development of healthier lifestyles such as diet which may play a positive role in chronic disease management. Epidemiological and migratory studies suggest that soy plays a pivotal role in the decreased incidence of heart disease in East Asian countries, such as China, Japan, and Korea. The role of soy in cardiovascular disease progression has been the subject of …


Perception Of Motion-In-Depth: Induced Motion Effects On Monocular And Binocular Cues, John Eric Gampher Jan 2008

Perception Of Motion-In-Depth: Induced Motion Effects On Monocular And Binocular Cues, John Eric Gampher

All ETDs from UAB

Three cues are available to the visual system to determine motion: image displacement across the retina (retinal slip), eye movements, and configuration changes within a scene (Becklen and Wallach, 1985). Any one may lead to the false perception of motion. Induced motion is the illusory movement of one object (or objects) as a result of other movement in the visual field. A wide variety of displays have been used to study induced motion, leading to apparently different classes of induced motion. Current theories of induced motion can be categorized based on local motion, global motion, eye movement suppression, and cognitive …


Functionalizing Hydroxyapatite Biomaterials With Biomimetic Peptides Of Integrin Ligands, Kristin Marie Hennessy Jan 2008

Functionalizing Hydroxyapatite Biomaterials With Biomimetic Peptides Of Integrin Ligands, Kristin Marie Hennessy

All ETDs from UAB

Hydroxyapatite (HA) coatings of hard tissue implants have been shown to increase osseointegration, but the mechanisms by which HA improves implant integration are not well understood. Numerous studies have shown that modifying HA with adhesive peptides, including RGD, and the collagen I mimetics, DGEA and P15, stimulates the adhesion of mesenchymal stem cells (MSCs), a cell type that differentiates along the osteoblast lineage. However, HA is a highly adsorptive biomaterial, and therefore it is unlikely that cells at the implant site would ever encounter a peptidemodified HA surface in the absence of an adsorbed protein layer. In fact, our laboratory …


Using Rna Interference To Study The Function Of The Tethering Protein P115 In Er-Golgi Traffic, Robert Grabski Jan 2008

Using Rna Interference To Study The Function Of The Tethering Protein P115 In Er-Golgi Traffic, Robert Grabski

All ETDs from UAB

Metazoan cells are characterized with elaborate network of intracellular membranous compartments. These membranes allow the cell to spatially separate antagonistic processes and environments, and maintain sequential order of reactions necessary for maturation and secretion of biosynthetic cargo. The core transport machinery consists of coat proteins, tethering factors, SNAREs and small Ras-like GTPases. We have explored the function of the tethering factor p115 in organellogenesis and in secretory traffic. The p115-depleted system was utilized to explore structurefunction relationships within p115. Here, we analyzed the architecture of the Golgi after RNAi induced depletion of p115. We show that in p115 depleted cells …


Mechanism Of The Cross Talk Between Growth Hormone Receptor And Epidermal Growth Factor Receptor, Xin Li Jan 2008

Mechanism Of The Cross Talk Between Growth Hormone Receptor And Epidermal Growth Factor Receptor, Xin Li

All ETDs from UAB

EGF receptor (EGFR) is a receptor tyrosine kinase, mediating cell growth from ectodermal and mesodermal origin. The overexpression and aberrant function of EGFR are involved in a wide range of human carcinomas. Growth hormone receptor (GHR) coexists with EGFR in various cell types and implicated in malignant tumor behavior. Previously in our lab, we found that via ERK activation GH can threonine phosphorylate EGFR and reduce EGF-induced EGFR downregulation. GH also synergizes with EGF in activating ERK. In this project, using reconstitution, we studied the mutation of the ERK phosphorylation consensus residue on EGFR, 669T. CHO-GHR cells, which lack EGFR …


Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee Jan 2008

Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee

All ETDs from UAB

Retinol dehydrogenase 12 (RDH12) is a member of the microsomal short-chain dehydrogenase/reductase superfamily of proteins that is highly expressed in photorecep-tor cells. Mutations in RDH12 are associated with severe early-onset autosomal recessive retinal dystrophy, leading to legal blindness. Disease-associated RDH12 variants exhibit lower protein levels when expressed in eukaryotic cells. However, the physiological role of RDH12 remains unclear. As established previously, RDH12 recognizes both retinoids and lipid peroxidation products (medium-chain aldehydes) as substrates and exhibits the highest catalytic efficiency for all-trans-retinaldehyde. As the main goal of this dissertation, we characterized the catalytic properties of RDH12 and its naturally occurring mutants …


Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton Jan 2008

Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton

All ETDs from UAB

seeking behavior following chronic drug use lasts for many months or even years. Short-term withdrawal experiments have suggested that the neuroadaptations thought to underlie learning and memory may also contribute to addictive behavior. However, there is little information about the physiological mechanisms that participate in craving and relapse following long-term withdrawal. Here I show in hippocampal slices from rats treated with nicotine for 1 week that there is a change in the excitability of CA1 pyramidal cells that persists for up to 9 months following the cessation of drug treatment. The expression of this enhanced excitability is dependent on different …


Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams Jan 2008

Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams

All ETDs from UAB

Insulin secretory defects within pancreatic beta-cells (β-cells) of islets of Langerhans play a role in the pathogenesis of diabetes mellitus. Furthermore, it is also well established that ATP and zinc are co-secreted with insulin in response to elevated extracellular glucose. Despite this knowledge, the physiological roles of extracellular secreted ATP and zinc within islets are ill-defined. We hypothesized that secreted ATP and zinc are autocrine purinergic signaling molecules that activate P2X purinergic receptor (P2XR) channels expressed by β-cells to enhance glucose-stimulated insulin secretion (GSIS). To test this postulate, ELISA, luciferin/luciferase-based bioluminescence and zinquin-based fluorescence assays were utilized to examine insulin, …


Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini Jan 2008

Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini

All ETDs from UAB

Novel combinatorial strategies need to be explored to achieve tumor eradication. In this regard, viral vector based gene therapy and nanotechnology offer unique possibilities for cancer therapy. As an example, multifunctional adenoviral (Ad) vectors capable of targeting, imaging, and successful cancer gene therapy have been advanced into multiple clinical trials. Similarly, novel multifunctional gold nanoparticles (AuNPs) have been utilized for drug delivery, targeting, imaging, and hyperthermia tumor therapy. Therefore, to accrue the benefits of both gene therapy and nanotechnology for cancer therapy, we proposed to combine Ad vectors and AuNPs in a single multifunctional nanodevice. Towards this goal, herein, we …


The Role Of Tgf-Ss And Wnt5a In Mammary Gland Development And Tumurorigenesis, Kevin Patrick Roarty Jan 2008

The Role Of Tgf-Ss And Wnt5a In Mammary Gland Development And Tumurorigenesis, Kevin Patrick Roarty

All ETDs from UAB

cancer is the second most common cancer worldwide behind lung cancer, affecting women of all ages, races, ethnicities, and socioeconomic strata. Concerted efforts have been made to understand this heterogeneous disease from the clinical stage down to the molecular level. Importantly, it has become clear that an understanding of the normal biology of the breast at all stages of development is needed to gain insight into how alterations in normal regulatory networks contribute to the initiation and development of breast cancer. TGF-ß plays a role in growth and patterning of the mammary gland and alterations in its signaling exhibit biphasic …


Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu Jan 2008

Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu

All ETDs from UAB

The hematological disorder sickle cell disease (SCD) is a prevalent human genetic disease. It causes severe tissue damage that can result in strokes, splenic infarction, kidney failure, liver and lung disorders, painful crises, and other complications. Although palliative therapies and allogenic stem cell transplantation therapies have been developed for this disorder, there is still no optimal treatment and SCD patients continue to suffer significant morbidity. Recently, several powerful technologies have been developed that increase the possibility for developing therapeutic treatments for SCD. Previously, our lab group demonstrated that SCD can be corrected in our humanized mouse model by transduction of …


Physiological Charactterization Of The Light Response Of Rod Photoreceptors In The Light Damaged Rat, Yuquan Wen Jan 2008

Physiological Charactterization Of The Light Response Of Rod Photoreceptors In The Light Damaged Rat, Yuquan Wen

All ETDs from UAB

Constant light exposure has long been known to induce photoreceptor degeneration. However, it is not known whether photoreceptors alter their physiology to adapt to the environmental stress caused by constant light exposure. In this study, we have developed a slow light damage model in rats to study changes in single rod physiology and retinal morphology after light damage. Rod physiology was documented by single rod recording using a suction electrode at 3 days (R3), 5 days (R5), 15 days (R15), and 30 days (R30) after 10 days of light damage, or sham light damage for controls. In addition, we used …


The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran Jan 2008

The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran

All ETDs from UAB

The development of molecular imaging technologies has allowed biomedical researchers to study the process of cancer metastasis in animal models of disease. Bioluminescence imaging has been a crucial tool for non-invasive monitoring of tumor growth, dissemination, and response to therapies. In this report, we have applied bioluminescence imaging to evaluate the efficacy of Death Receptor 5 agonist therapy for the treatment of breast cancer metastasis, predominately to the skeleton, in an athymic nude mouse model. Initially, we determined that bioluminescence imaging was the most ideal technology for studying secondary bone lesions in vivo when compared to both x-ray Computed Tomography …


Characterization Of Suds3 As A Brms1 Family Member In Breast Cancer, Alexandra C. Silveira Jan 2008

Characterization Of Suds3 As A Brms1 Family Member In Breast Cancer, Alexandra C. Silveira

All ETDs from UAB

BRMS1 and SUDS3 belong to a protein family characterized by the Sds3-like domain. These proteins are core members of SIN3-HDAC chromatin remodeling complexes and thus, regulate transcription. BRMS1 decreases the expression of various metastasis-promoting proteins. This regulation contributes to BRMS1-mediated metastasis suppression through the inhibition of motility and by sensitizing cells to anoikis, as well as through other unidentified mechanisms related to growth at a secondary site. Although BRMS1 and SUDS3 share high sequence similarity and are found in the same complexes, studies have yet to address whether these similarities result in overlapping functions. Additionally, it is unclear how BRMS1 …


Trp-Ing Down A Trk: A New Role For Transient Receptor Potential Channels As Novel Mediators Of Brain-Derived Neurotrophic Factor Actions At Both Sides Of The Excitatory Synapse, Michelle Dawn Amaral Jan 2008

Trp-Ing Down A Trk: A New Role For Transient Receptor Potential Channels As Novel Mediators Of Brain-Derived Neurotrophic Factor Actions At Both Sides Of The Excitatory Synapse, Michelle Dawn Amaral

All ETDs from UAB

Over the years, various roles for neurotrophins have been revealed, being initially described as survival signals for neurons making their initial synaptic contacts in the developing brain. Eventually, it was discovered that these molecules also play important modulatory roles in the adult brain. The work encompassed in this dissertation serves to characterize one particular neurotrophin, brain-derived neurotrophic factor (BDNF), which has been implicated in long-term potentiation (LTP), and its effects at CA3-CA1 synapses in the hippocampus following acute application in vitro. To this end, we have demonstrated the presence of a novel, non-selective cationic current that is initiated by BDNF …


Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett Jan 2008

Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett

All ETDs from UAB

Sortases are transpeptidases that covalently link surface proteins to the stempeptide on the cell wall peptidoglycan of Gram-positive bacteria. This work endeavored to characterize the various sortase enzymes and their effect on the virulence of Streptococcus pneumoniae. The genome of S. pneumoniae may encode up to four sortase enzymes. We found that 38 of 54 strains of serotype 6B clonal complex 14 (CC14) carry the genes for the secondary sortases srtB, srtC, and srtD. The presence of these sortases did not seem to influence the ability of strains within CC14 to infect the nasopharynx, lungs, or blood of strains within …


A Construct With Fluorescent Indicators For Conditional Expression Of Mirna., Linghua Qiu, Hongyan Wang, Xugang Xia, Hongxia Zhou, Zuoshang Xu Jan 2008

A Construct With Fluorescent Indicators For Conditional Expression Of Mirna., Linghua Qiu, Hongyan Wang, Xugang Xia, Hongxia Zhou, Zuoshang Xu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Transgenic RNAi holds promise as a simple, low-cost, and fast method for reverse genetics in mammals. It may be particularly useful for producing animal models for hypomorphic gene function. Inducible RNAi that permits spatially and temporally controllable gene silencing in vivo will enhance the power of transgenic RNAi approach. Furthermore, because microRNA (miRNA) targeting specific genes can be expressed simultaneously with protein coding genes, incorporation of fluorescent marker proteins can simplify the screening and analysis of transgenic RNAi animals. RESULTS: We sought to optimally express a miRNA simultaneously with a fluorescent marker. We compared two construct designs. One expressed …


Dominance Of The Proximal Coordinate Frame In Determining The Locations Of Hippocampal Place Cell Activity During Navigation, Jennifer J Siegel, Joshua P Neunuebel, James J Knierim Jan 2008

Dominance Of The Proximal Coordinate Frame In Determining The Locations Of Hippocampal Place Cell Activity During Navigation, Jennifer J Siegel, Joshua P Neunuebel, James J Knierim

Faculty, Staff and Student Publications

The place-specific activity of hippocampal cells provides downstream structures with information regarding an animal's position within an environment and, perhaps, the location of goals within that environment. In rodents, recent research has suggested that distal cues primarily set the orientation of the spatial representation, whereas the boundaries of the behavioral apparatus determine the locations of place activity. The current study was designed to address possible biases in some previous research that may have minimized the likelihood of observing place activity bound to distal cues. Hippocampal single-unit activity was recorded from six freely moving rats as they were trained to perform …


Off-Label Psychopharmacologic Prescribing For Children: History Supports Close Clinical Monitoring., Julie M Zito, Albert T Derivan, Christopher J Kratochvil, Daniel J Safer, Joerg M Fegert, Laurence L Greenhill Jan 2008

Off-Label Psychopharmacologic Prescribing For Children: History Supports Close Clinical Monitoring., Julie M Zito, Albert T Derivan, Christopher J Kratochvil, Daniel J Safer, Joerg M Fegert, Laurence L Greenhill

Department of Psychiatry and Human Behavior Faculty Papers

The review presents pediatric adverse drug events from a historical perspective and focuses on selected safety issues associated with off-label use of medications for the psychiatric treatment of youth. Clinical monitoring procedures for major psychotropic drug classes are reviewed. Prior studies suggest that systematic treatment monitoring is warranted so as to both minimize risk of unexpected adverse events and exposures to ineffective treatments. Clinical trials to establish the efficacy and safety of drugs currently being used off-label in the pediatric population are needed. In the meantime, clinicians should consider the existing evidence-base for these drugs and institute close clinical monitoring.


Dependence In Prestroke Mobility Predicts Adverse Outcomes Among Patients With Acute Ischemic Stroke, Mary I. Dallas, Shari Rone-Adams, John L. Echternach, Lawrence M. Bass, Dawn M. Bravata Jan 2008

Dependence In Prestroke Mobility Predicts Adverse Outcomes Among Patients With Acute Ischemic Stroke, Mary I. Dallas, Shari Rone-Adams, John L. Echternach, Lawrence M. Bass, Dawn M. Bravata

Rehabilitation Sciences Faculty Publications

Background and Purpose - Stroke survivors are commonly dependent in activities of daily living; however, the relation between prestroke mobility impairment and poststroke outcomes is poorly understood. The primary objective of this study was to evaluate the association between prestroke mobility impairment and 4 poststroke outcomes. The secondary objective was to evaluate the association between prestroke mobility impairment and a plan for physical therapy.

Methods - This was a secondary analysis of the National Stroke Project data, a retrospective cohort of Medicare beneficiaries who were hospitalized with an acute ischemic stroke (1998 to 2001). Logistic-regression modeling was used to examine …


Endocannabinoid Modulation Of Spatial Memory In Aversively And Appetitively Motivated Barnes Maze Tasks, John Pinckney Harloe Jan 2008

Endocannabinoid Modulation Of Spatial Memory In Aversively And Appetitively Motivated Barnes Maze Tasks, John Pinckney Harloe

Theses and Dissertations

Genetic deletion or pharmacological blockade of the CB1 receptor has been reported to impair extinction learning in aversive conditioning (i.e., conditioned fear and Morris water maze) paradigms, but not in operant procedures in which food reinforcement is earned. It is difficult to discern whether the differential effects caused by CB1 receptor disruption on extinction result from the hedonics (i.e., aversive vs. appetitive) or is related to the required responses associated with these disparate tasks. In order to evaluate whether the hedonics is the determining factor, we used either aversive (i.e., escape from bright lights and air turbulence) or appetitive (i.e., …


Examining The Behavioral And Molecular Aspects Of Adolescent Nicotine Dependence: Implications For Vulnerability To Drugs Of Abuse, Dena Heath Kota Jan 2008

Examining The Behavioral And Molecular Aspects Of Adolescent Nicotine Dependence: Implications For Vulnerability To Drugs Of Abuse, Dena Heath Kota

Theses and Dissertations

Approximately 200 million men and 100 million women smoke worldwide. In the United States, an estimated 25.9 million men (23.9 percent) and 20.7 million women (18.1 percent) are smokers. The commencement of smoking at a young age is thought to increase addiction liability, decrease the probability of successful cessation, and correlate with a higher number of cigarettes smoked per day. Studies from the World Health Organization indicate that between 80,000 and 100,000 children start smoking every day worldwide. These statistics suggest that adolescence is a critical phase for developing nicotine dependence. The work in this dissertation contributes to the further …