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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

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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 …

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Mesenchymal Stem Cell Interaction With Nanostructured Biomaterials For Orthopaedic Applications, William Charles Clem Jan 2008

Mesenchymal Stem Cell Interaction With Nanostructured Biomaterials For Orthopaedic Applications, William Charles Clem

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Orthopaedic implants fail when bone loss around the anchoring region of the prosthesis causes the components to loosen. A revision surgery is needed to replace worn components, and bone grafting is often required to fill the void caused by osteolysis. A solution for the problem of osteolysis may be the improvement of wear resistance at the articulating surfaces by substituting materials with greater hardness. This dissertation describes two strategies for increasing the surface hardness of titanium alloy (Ti-6Al-4V) implants, without increasing surface roughness or compromising osseointegration. The first strategy utilizes microwave plasma to induce titanium nitride formation by nitrogen diffusion. …

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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

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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 …

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

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

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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 …

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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

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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 …

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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

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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 …

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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

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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 …

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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

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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 …

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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

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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 …

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The Role Of Strychnine-Sensitive Nachrs In Rabbit Retinal Off Ganglion Cells, Jordan Michael Renna Jan 2008

The Role Of Strychnine-Sensitive Nachrs In Rabbit Retinal Off Ganglion Cells, Jordan Michael Renna

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that when heteroskedasticity is present, but ignored, there is significant evidence to suggest

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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

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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 …

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Characterizing Semantic Memory In Mild Cognitive Impairment, Kelli L. Netson Jan 2008

Characterizing Semantic Memory In Mild Cognitive Impairment, Kelli L. Netson

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Episodic memory is clearly impaired in mild cognitive impairment (MCI), although recent studies have revealed deficits in other cognitive domains such as attention, executive function, and semantic memory. Studies of semantic memory in MCI have been limited by inconsistent use of diagnostic criteria and variability in the measures used. The purpose of this study was to examine semantic memory in a sample of individuals diagnosed with amnestic MCI using Mayo criteria. Performance of individuals with consensus-diagnosed MCI (n=12) was compared to that of normal controls (n=15) on a battery of semantic memory tasks. MANOVA results indicated that the MCI group …

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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

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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 …

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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

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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 …

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

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

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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 …

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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

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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 …

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Expression And Function Of Nicotinic Acetylcholine Receptors In Human Vascular Endothelial Cells, Ryan C. Splittgerber Jan 2008

Expression And Function Of Nicotinic Acetylcholine Receptors In Human Vascular Endothelial Cells, Ryan C. Splittgerber

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Neuronal nicotinic acetylcholine receptors (nAChRs) are widely expressed in neural and non-neural tissues and have been reported to play a role in neovascularization and vascular diseases of the eye, specifically age-related macular degeneration (ARMD). However, the subunit composition of functional nAChRs, their mechanisms of action, and the downstream signaling pathways in non-neuronal tissues are not well understood. Since some nAChR subtypes have high Ca2+ permeability, we investigated the possible role of Ca2+ in activating signaling cascades that underlie the affects of nAChR activation in Human Dermal Microvascular Endothelial Cells (HDMECs). RT-PCR experiments revealed message for nearly all of the known …

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Degradation Of The Huntingtin Polyglutamine Domain By The Proteasome: Implication To Huntington’S Disease, Marie Antoinette Blaize Jan 2008

Degradation Of The Huntingtin Polyglutamine Domain By The Proteasome: Implication To Huntington’S Disease, Marie Antoinette Blaize

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Huntington’s disease (HD) is a progressive autosomal dominant neurodegenerative disorder. HD results from the genetic mutation that leads to an abnormally expanded polyglutamine (PolyQ) sequence within the protein. The disease is characterized by the accumulation of ubiquitinated mutant htt, suggesting dysfunction of the ubiquitin-proteasome system. Interestingly, there is data suggesting that the proteasome may not have the ability to efficiently degrade abnormally expanded polyglutamine. Furthermore, it has been demonstrated that there is proteasome impairment in HD and in cell models that expressed mutant htt, suggesting that mutant htt may cause dysfunction of the proteasome. Therefore, in this study, we further …

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Age And Gender Differences In Hip Extension And Flexion Torque Steadiness, Iveta Grunte Jan 2008

Age And Gender Differences In Hip Extension And Flexion Torque Steadiness, Iveta Grunte

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Purpose of this study was to compare age and gender differences in hip extension (HE) and flexion (HF) relative (5, 25, and 50% of maximal voluntary contraction [MVC]) and absolute (25 Nm) torque steadiness measured as standard deviation (SD) and coefficient of variation (CV) of torque fluctuations, and torque accuracy (TA). MVC and steadiness were assessed for 20 young (24.0 + 2.2 yrs) and 11 older (65.4 + 4.5 yrs) men and women. MVC was lower for HF, but HE had greater torque fluctuations. For HE, CV of 5% MVC was greater for older compared to young adults and women …

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Bone Formation Around Implants In Adult Transgenic Mice With Selective Runx2-Ii Deficiency, Jaime Rodrigo Rivera Jan 2008

Bone Formation Around Implants In Adult Transgenic Mice With Selective Runx2-Ii Deficiency, Jaime Rodrigo Rivera

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Titanium-aluminum-vanadium (Ti-6Al-4V) tacks were placed in the tibiae of 10 female wild type (Runx2 flox/+ or Runx2 flox/flox) and heterozygous (Runx2+/-, ColII Cre) mice littermates to examine healing and bone response. Animals were divided into control and test groups of 5 each. A novel generation of Runx2 knock-out mice where the gene is only deleted in chondrocytes was used. Ten days after implant surgery, specimens were recovered and prepared for histological, histomorphometric, and micro-CT morphometric analysis. Histological examination revealed that wild type animals presented larger regions of bone formation and endochondral ossification when compared to heterozygous mice. Micro-CT morphometric analysis …

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Oral Mucositis In Children Receiving Bone Marrow Transplantation, Francisco Jose Rodriguez Jan 2008

Oral Mucositis In Children Receiving Bone Marrow Transplantation, Francisco Jose Rodriguez

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Purpose: The purpose of this retrospective study was to identify the factors that influence the incidence, severity, onset, and resolution of oral mucositis in children undergoing bone marrow transplantation (BMT). Methods: One hundred and fifty medical records were reviewed of patients that received BMT. Daily values of white blood cell (WBC) counts were obtained to associate it’s correlation with the incidence, severity, onset, and resolution of oral mucositis. Age group and gender of the patients, type of bone marrow transplant, the use of methotrexate, the use of total body irradiation, and the previous treatment with chemotherapy were obtained to analyze …

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Conservational Implications Of Temperature-Dependent Sex Determination, Corie L. Therrien Jan 2008

Conservational Implications Of Temperature-Dependent Sex Determination, Corie L. Therrien

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A variety of reptiles have temperature-dependent sex determination (TSD), where incubation temperature determines gender. This form of sex determination has significant conservational implications because it has the potential of producing highly biased sex ratios which can affect the reproductive output of a population. TSD is of particular interest to conservation programs that use hatcheries to artificially incubate the eggs of endangered sea turtles because such programs need to select specific incubation temperatures in an effort to produce a desired sex ratio. This type of sex determination also has evolutionary implications as it may be advantageous for an animal to produce …

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Study Of Nano-Mechanical Properties Of 3d Scaffolds Prepared From Polycaprolactone And Hydroxyapatite, Parul Tyagi Jan 2008

Study Of Nano-Mechanical Properties Of 3d Scaffolds Prepared From Polycaprolactone And Hydroxyapatite, Parul Tyagi

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Nanocomposite scaffolds based on nanofibrous polycaprolactone (PCL) and nanohydroxyapatite (nanoHA) with fixed polymer compositions (7.5wt%) but different total wt% were prepared by electrostatic co-spinning to mimic the nanofeatures of the natural extracellular matrix (ECM) for natural bone tissue. Electrospinning is used to produce ultra-fine fibers using a high-voltage electrostatic field. The proposed concentrations of NanoHA in polymer were 0wt%, 10wt%, 20wt%, 30wt%, 40wt%, 50wt%. NanoHA was found to be well dispersed in polymers up to the addition of 30wt%, whereas substantial beading, electro-spraying and agglomeration of HA particles was observed in 40wt% and 50wt%. There are several factors which may …

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Quantitative Protein Detection In Serum Samples Using Fiber-Optic Biosensors, Chun-Wei Wang Jan 2008

Quantitative Protein Detection In Serum Samples Using Fiber-Optic Biosensors, Chun-Wei Wang

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We report highly specific and sensitive detection of proteins in serum samples using a combination tapered fiber-optic biosensor (CTFOB) dip-probe. Sandwich immunoassay was used to generate specific fluorescence signal. A novel competitive adsorption strategy was used to reduce the false signal from non specific binding to a negligible level. Moreover, the similar strategy was also used to reduce the loss of target protein and increase the accuracy of immunoassay. The probes do not require pre-treatment with any blocking buffer. The specificity of the sensor was established by using negative control probes. The CTFOB probes were able to detect human interleukin-6 …

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Comparison Of Two Methods For Differentiating Negative From Inconclusive Gc-Ms Test Results Using An Isotopic Analog Of The Analyte As The Internal Standard - 11-Nor-Δ9- Tetrahydrocannabinol-9-Carboxylic Acid Example, Laura S. Waters Jan 2008

Comparison Of Two Methods For Differentiating Negative From Inconclusive Gc-Ms Test Results Using An Isotopic Analog Of The Analyte As The Internal Standard - 11-Nor-Δ9- Tetrahydrocannabinol-9-Carboxylic Acid Example, Laura S. Waters

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In the testing of urine samples for illicit drugs by gas chromatography-mass spectrometry (GC-MS), a drop in internal standard response is an indicator of possible sample adulteration. In 2007, Dennis V. Canfield (Liu et al. 2007) developed a formula to calculate factor A, an empirically determined value for the lowest acceptable internal standard (IS) signal-to-noise (S/N) response. Using this method, Liu et al. were able to distinguish true negatives from samples showing interference by ibuprofen and hydrogen peroxide (H2O2) in the detection of 11-nor-9-carboxy-9-tetrahydrocannabinol (THCCOOH) in urine samples. To determine if Liu’s method can be universally applied, a set of …

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December 17, 2007 Reporter, University Of Alabama At Birmingham Dec 2007

December 17, 2007 Reporter, University Of Alabama At Birmingham

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Cystic Fibrosis Proteins Photographed Interacting, Staff Dec 2007

Cystic Fibrosis Proteins Photographed Interacting, Staff

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December 3, 2007 Reporter, University Of Alabama At Birmingham Dec 2007

December 3, 2007 Reporter, University Of Alabama At Birmingham

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Cigarette Smoke And Alcohol Damage Hearts Worse As Combo, Staff Nov 2007

Cigarette Smoke And Alcohol Damage Hearts Worse As Combo, Staff

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November 5, 2007 Reporter, University Of Alabama At Birmingham Nov 2007

November 5, 2007 Reporter, University Of Alabama At Birmingham

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