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2007

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Articles 2911 - 2940 of 3121

Full-Text Articles in Medicine and Health Sciences

Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han Jan 2007

Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han

All ETDs from UAB

The replication of Human immunodeficiency virus type 1 (HIV-1) is characterized by the process of reverse transcription, which converts the viral RNA genome into a DNA intermediate prior to integration into the host cell chromosome. The initiation of reverse transcription needs a cellular tRNA primer, which binds to a region in the viral RNA genome, designated as the primer binding site (PBS). The 18-nucleotide PBS region of HIV-1, which is complementary to the 3′ terminal 18 nucleotides of tRNALys,3, is absolutely conserved among all HIV-1. The highly conserved PBS is a very good target for HIV-1 therapy. My dissertation research …

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A Role For P63 In The Regulati On Of Cell Cycle Progression And Cell Death, Eric Scott Helton Jan 2007

A Role For P63 In The Regulati On Of Cell Cycle Progression And Cell Death, Eric Scott Helton

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p63 is a member of the p53 family of transcription factors that is a critical regulator of epithelial development. Studies have shown that p63 does not appear to function as a classical tumor suppressor like p53. Instead, the expression pattern of p63 in cancers suggests that p63 retains the potential to function as either a tumor suppressor or an onco-protein. Here, we provide evidence describing the transcriptional activity of the p63 isoforms and provide mechanisms whereby p63 function is regulated in a context dependent manner. Our data shows that both the ΔNp63 and TAp63 variants retain the potential to regulate …

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Regulation Of The Human Heme Oxygenase-1 Gene, Thomas D. Hock Jan 2007

Regulation Of The Human Heme Oxygenase-1 Gene, Thomas D. Hock

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The heme oxygenase-1 (HO-1) gene encodes a microsomal enzyme that catalyzes the conversion of heme to carbon monoxide, Iron, and biliverdin. HO-1 transcription is induced upon a plethora of cellular stresses including heme, heavy metal exposure, hy-poxia, oxidative stress and many others. The goal of this work was to explore the molecu-lar regulation of HO-1 transcription. Four DNase 1 hypersensitive sites are detected within the HO-1 promoter extending from ~-40bp to ~-9.2kb relative to the transcription start site. Dimethylsulfate (DMS) in vivo footprinting is shown for two regulatory re-gions and reveals nine protected guanines in all. Mutational analyses indicates that …

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Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer, Curt E. Harper Jan 2007

Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer, Curt E. Harper

All ETDs from UAB

Prostate cancer is the second leading cause of cancer-related death among men in the United States. The goal of this research was to investigate the potential of three nutriceutical polyphenols, genistein, resveratrol, and epigallocatechin-3-gallate (EGCG), to suppress prostate cancer. Cancer chemoprevention and mechanism of action studies were carried out in transgenic models of prostate cancer. In TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, resveratrol suppressed poorly differentiated tumors by 86%, whereas EGCG suppressed precancerous lesions, but failed to prevent late-stage prostate cancer. Agents that were chemopreventive in the TRAMP model were subsequently evaluated alone, and in combination, in the …

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Quantitation Of Antiretrovirals In Alternative Matrices, Chantelle Bennetto Hood Jan 2007

Quantitation Of Antiretrovirals In Alternative Matrices, Chantelle Bennetto Hood

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The human immunodeficiency virus (HIV) pandemic is a growing concern, affecting almost 40 million people worldwide. Treatment for HIV infection consists of highly active antiretroviral therapy (HAART) to block different steps in the viral lifecycle, ultimately reducing HIV RNA to undetectable levels in the plasma. However, HIV RNA can be detected in numerous reservoirs outside of the blood despite the use of HAART. Therefore, measurement of antiretroviral (ARV) drugs in other biological matrices is important to broaden our understanding of HIV transmission, the development of viral resistance with sub-optimal ARV exposure, and fetal and neonatal drug exposure. This work describes …

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Ethnic Differences In Markers Of Inflammation With Weight Loss, Tanya C. Hyatt Jan 2007

Ethnic Differences In Markers Of Inflammation With Weight Loss, Tanya C. Hyatt

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Chronic diseases such as type 2 Diabetes Mellitis (T2DM) and cardiovascular disease (CVD) are accompanied by chronic low-grade systemic inflammation and are related to obesity and ethnicity. For instance, African-Americans (AA) have increased risk for developing T2DM and are more likely to be overweight relative to Caucasians (C). However, C have more intra-abdominal adipose tissue (IAAT) and have higher risk for CVD than AA. The influence that ethnicity has on disease risk is obscured by ethnic differences in fat distribution and sensitivity to insulin. Ethnic differences in markers of inflammation (MOI) have not been investigated. It is also unclear if …

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Characterization Of A Global Regulatory Pathway In Streptococcus Pneumoniae, Greer E. Kaufman Jan 2007

Characterization Of A Global Regulatory Pathway In Streptococcus Pneumoniae, Greer E. Kaufman

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Streptococcus pneumoniae is a versatile organism that adapts to many different environments in the host. S. pneumoniae can asymptomatically colonize the nasopharynx of humans. However, dissemination of the bacterium from the nasopharynx to different locations in the body can lead to invasive diseases such as pneumonia, bacteremia, and meningitis. How S. pneumoniae modulates factors that are important for survival in these niches has not been well characterized. In the studies described here, we propose that S. pneumoniae may modulate gene expression in these niches by sensing the different glu-cose concentrations via carbon catabolite control protein A (CcpA). Initially we characterized …

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On The Immunological Roles Of Tlt2 And Hsh2, R Glenn King Jan 2007

On The Immunological Roles Of Tlt2 And Hsh2, R Glenn King

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The evolution of multicellular organisms necessitated the ability to detect and remove harmful parasitic microorganisms from the host. This simple requirement for self non-self discrimination has evolved in vertebrates into an elaborate system consisting of a variety of effector mechanisms to perform this process. The immune system is often described as consisting of two distinct yet complimentary components, the innate and adaptive immune systems. It is now recognized that the immune system relies on the highly coordinated interplay between a variety of cell types which cooperate to maintain the health of the organism. The work outlined in this dissertation addresses …

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The Effect Of The Aml1-Eto Translocation On Cell Cycle Tumor Suppressor Gene Function, Rose Marie Ko Jan 2007

The Effect Of The Aml1-Eto Translocation On Cell Cycle Tumor Suppressor Gene Function, Rose Marie Ko

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The t(8;21)(q22;q22) AML1-ETO translocation is one of the most frequent translocations in acute myeloid leukemia (AML), occurring in approximately 12% of cases. Our laboratory has generated a mouse model in which AML1-ETO is expressed in hematopoietic progenitor cells using a retroviral vector and assayed using bone marrow transplantation. Animals transplanted with AML1-ETO-expressing cells failed to develop leukemia. However, AML1-ETO promoted significant expansion of immature myeloid cells suggesting a “pre-leukemic” state that requires secondary mutations for disease progression. In addition, analysis of cell cycle kinetics in AML1-ETOexpressing myeloid progenitor cells showed that AML1- ETO slowed G1 to S phase progression compared …

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Mcmv Induced Cerebellar Maldevelopment, Thadeus B. Koontz Jan 2007

Mcmv Induced Cerebellar Maldevelopment, Thadeus B. Koontz

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Congenital Human Cytomegalovirus (HCMV) infection represents a significant cause of morbidity and mortality in infants and children. While most of the systemic damage incurred by the infant in the course of the infection resolves without permanent consequence, the pathological manifestations of infection in the central nervous system (CNS) are often permanent. Children born with congenital HCMV infection may exhibit hearing loss and cognitive impairment in various degrees. These neurological disabilities are correlated with pathological findings in various permutations including infection of the inner ear, ventricular calcifications, ventriculomegaly, microgyria, lissencephaly, and cerebellar hypoplasia. To develop a therapeutic or preventive strategy, HCMV …

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Titania Coated Hollow Glass Microspheres For Environmental Applications, Mark C. Koopman Jan 2007

Titania Coated Hollow Glass Microspheres For Environmental Applications, Mark C. Koopman

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The potential applicability of titania coated hollow glass microspheres (HGMs) to the photocatalytic degradation of microbiological and organic chemical water pollutants could have dramatic positive effects on improving the quality of industrial wastewaters that empty into rivers and streams, as well as potential use in economically improving the quality of drinking water. Heterogeneous photocatalysis using titania has been extensively studied since the 1990’s because of its non-toxic nature, its high quantum yield of electrons and photo-holes, and its ability to use ambient solar radiation as a power source. Although titania embodies extraordinarily attractive properties for a range of environmental applications, …

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Kainate Receptor Modulation Of Synaptic Transmission In Neocortex, Seena S. Mathew Jan 2007

Kainate Receptor Modulation Of Synaptic Transmission In Neocortex, Seena S. Mathew

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The actions of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) are tightly regulated to ensure effective information processing as well as prevention of excess excitatory activity, which can lead to seizures and neurological disorders such as epilepsy. Drugs which enhance the effects of GABA are used as anesthetics, sedatives and anticonvulsants. Using whole-cell patch clamp recordings from neocortical neurons, we examined the mechanisms of GABAergic modulation that occur when kainate receptors (KARs) are activated. First, we address a novel signaling mechanism for the KAR-mediated facilitation of GABAergic synaptic transmission. Our first observation involved the presence of presynaptic KARs located on the …

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Primer Selection Of E. Coli Trna Lys,3 By Human Immunodeficiency Virus Type-1, Anna Mcculley Jan 2007

Primer Selection Of E. Coli Trna Lys,3 By Human Immunodeficiency Virus Type-1, Anna Mcculley

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Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS). HIV replication includes the notable process of reverse transcription, a conversion of RNA to DNA. Reverse transcription is initiated from a primer by a viral enzyme, reverse transcriptase. The primer, tRNALys,3, is selected from the cytoplasm of an infected cell, annealed via the 3’ terminal 18-nucleotides to the viral primer binding site (PBS), and used in a subsequent infection. The mechanism of primer selection has not been determined although numerous studies have been performed. This has been hampered by the challenge of tRNALys,3 manipulation in the cell and …

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Directing Akt And Gsk3ss: Molecular Insights Into Cell Signaling And Survival, Gordon P. Meares Jan 2007

Directing Akt And Gsk3ss: Molecular Insights Into Cell Signaling And Survival, Gordon P. Meares

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Proper regulation of survival signaling is critical for all organisms. One important signaling cascade involved in the coordinated effort to control signals influencing cell fate is the phosphatidylinositol 3-kinase (PI3K)-Akt-glycogen synthase kinase 3β (GSK3β) signaling cascade. Following activation by growth factors the PI3K-Akt pathway promotes cell survival and, cell death is facilitated following inhibition of Akt. Many factors influence the function of the Akt-GSK3β signaling dyad, including phosphorylation, protein complex formation and subcellular localization. Previous work had demonstrated that the 90kDa heat shock protein, HSP90, directly binds and stabilizes Akt. Furthermore, several heat shock proteins including HSP90 and HSP105 can …

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Retinal Pigment Epithelial Cells And The Insulin-Like Growth Factor System In Proliferative Vitreoretinopathy, Sudipto Mukherjee Jan 2007

Retinal Pigment Epithelial Cells And The Insulin-Like Growth Factor System In Proliferative Vitreoretinopathy, Sudipto Mukherjee

All ETDs from UAB

The goal of this study was to determine the influence, if any, of the insulin-like growth factors (IGFs) on retinal pigment epithelial (RPE) cell tractional force generation and the contributions of vitreous insulin-like growth factor binding proteins (IGFBPs) towards control of IGF activity. Another objective was to evaluate RPE cells as a potential source of all six high-affinity IGFBPs and to determine if IGFBP biosynthesis is modulated in concert with phenotype changes and growth factor stimuli known to be present in disease. RPE generate tractional forces in response to IGF-I and -II with IGF-I being the more potent stimulus. Differential …

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Delayed Childbearing, Pregnancy Spacing And Impact On Subsequent Pregnancy Outcomes: Missouri Resident Mothers 1978-1997, Sarah K. Nabukera Jan 2007

Delayed Childbearing, Pregnancy Spacing And Impact On Subsequent Pregnancy Outcomes: Missouri Resident Mothers 1978-1997, Sarah K. Nabukera

All ETDs from UAB

Introduction The main objective of the study was to examine reproductive health issues among women delaying initiation of childbearing until age 30 or older. Specifically, it examined pregnancy spacing patterns, relationship between pregnancy spacing and subsequent perinatal outcomes as well as racial differences in spacing and adverse perinatal outcomes. Methods A retrospective cohort study was conducted using the Missouri maternally linked live birth, fetal death and infant death files 1978-1997. The study sample was limited to mothers residing in Missouri during the study period, having first pregnancy at age 20-50 years, as well as a subsequent second pregnancy. Final study …

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The Function Of Hiv-1 A-Loop On Primer Selection, Na Ni Jan 2007

The Function Of Hiv-1 A-Loop On Primer Selection, Na Ni

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Reverse transcription is the hallmark of retroviruses, such as HIV-1. A cellular tRNA bound to the primer binding site region (PBS) is used for initiation of reverse transcription. HIV-1 specially selects tRNALys3 as primer, although changing the PBS can force HIV-1 to use alternative tRNAs as a primer. However, HIV-1 reverts back to use tRNALys3 following in vitro replication. The A-loop, located upstream of PBS, interacts with the anti-codon of primer tRNA. The inclusion of A-loop modification has been shown to stabilize the utilization of some alternative tRNAs. The studies in this dissertation focus on further defining the role of …

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Association Between The Exposure To Aflatoxin And Micronutrient Status Of Hiv Infected Adults In Ghana, Francis Ayodele Obuseh Jan 2007

Association Between The Exposure To Aflatoxin And Micronutrient Status Of Hiv Infected Adults In Ghana, Francis Ayodele Obuseh

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Aflatoxins, found naturally in some foods are toxic metabolites of some Aspergillus species.They constitute the most potent hepatocarcinogens known and are also mutagenic and hepatotoxic. The preponderance of evidence indicates that aflatoxin is the major cause of hepatocellular cancer. In studies conducted in Africa, food-borne aflatoxin exposure is common (Oyelami et al. 1996; Egal et al. 2005). There is a critical need for additional information on health outcomes associated with exposure to aflatoxin in humans, especially in developing countries with a higher degree of malnutrition and likelihood of HIV infections. We sought to test the hypothesis that aflatoxin B1 and …

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Regulation Of Vertebrate Gastrulation By Erbb Signaling, Shuyi Nie Jan 2007

Regulation Of Vertebrate Gastrulation By Erbb Signaling, Shuyi Nie

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ErbB receptor tyrosine kinases have long been implicated in cancer formation and progression by regulating cell division, migration, and survival. ErbBs are also essential in multiple processes during invertebrate development; however, their activities during vertebrate embryogenesis are not well understood. For functional characterization of ErbB signaling during vertebrate development, frog model Xenopus laevis was used in our studies. The expression pattern and the general activities of ErbB receptors during early frog development were first analyzed and results shown that ErbBs regulate gastrulation, somite organization and head patterning. As gastrulation is the first major morphogenetic event in vertebrate development, I focused …

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Surveying The Chromosomal Supercoiling Levels In Rapidly Growing Wild Type And Gyrase Mutant Strains Of Salmonella Enterica Serovar Typhimurium With Γδ Resolvase-Mediated Recombination Assay, Zhenhua Pang Jan 2007

Surveying The Chromosomal Supercoiling Levels In Rapidly Growing Wild Type And Gyrase Mutant Strains Of Salmonella Enterica Serovar Typhimurium With Γδ Resolvase-Mediated Recombination Assay, Zhenhua Pang

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A gyrase mutant strain (gyrB652) has severe growth defect at 42°C. The survival at high temperature is dependent on DNA repair proteins. The purified mutant gyrase was assayed for supercoiling acitivity and quinolone-induced DNA cleavage activity. The results suggested that the mutant enzyme is not temperature-sensitive, but has slower kinetics than the wild type gyrase. The DNA supercoiling levels at multiple chromosomal loci in exponential phase cells were monitored with γδ resolvase-mediated recombination assay. The wild type cells showed homogenous supercoiling levels throughout most of the chromosome. But the superhelicity at dif locus was significantly lower than the other loci. …

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Insulin Dynamics In African Americans And European Americans: Mechanistic Aspects, And Association With Inflammation, Radhika P. Phadke Jan 2007

Insulin Dynamics In African Americans And European Americans: Mechanistic Aspects, And Association With Inflammation, Radhika P. Phadke

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Identification and characterization of ethnic differences in insulin dynamics, insulin sensitivity (SI), and inflammation may shed light on the greater risk for type 2 diabetes in African Americans (AA), relative to European Americans (EA). Ideally, such studies should take into account the potential confounding roles of adiposity, fat distribution, genetic background, and socioeconomic status (SES). The objectives of this study were, 1) to evaluate ethnic differences in insulin dynamics in AA and EA children and adults using robust measures of insulin secretion and clearance; 2) to identify the contributions of genetic admixture and SES to insulin dynamics; 3) to examine …

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Trafficking Of Hantaviral Nucleocapsid Proteins, Harish N. Ramanathan Jan 2007

Trafficking Of Hantaviral Nucleocapsid Proteins, Harish N. Ramanathan

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Hantaviruses are enveloped, negative-sense RNA viruses belonging to genus Hantavirus, within the family Bunyaviridae. Hantaviruses include many serious human pathogens and are classified as Old and New World based on the geographic distribution of rodent reservoirs and their ability to in induce distinct illnesses in humans. Currently there are no reservoirs known for hantaviruses other than the rodents. Human transmission of hantaviruses occurs via inhalation of aerosolized rodent excreta leading to hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). Hantavirus genome consists of small (S), medium (M) and large (L) segments that encode nucleocapsid (N) protein, two …

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The Role Of Complement In Experimental Autoimmune Uveitis, Russell W. Read Jan 2007

The Role Of Complement In Experimental Autoimmune Uveitis, Russell W. Read

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The complement system has been increasingly implicated in the pathophysiology of autoimmune disease. Complement expression in the normal human eye had not been previously completely defined. We performed immunohistochemical studies for membrane complement proteins in normal human retina to provide a baseline for future studies. We found expression of the anaphylatoxin receptors, CD55, and CD59 in the inner retina and CD46 in a polarized fashion on the retinal pigment epithelium. Previous studies in uveitis have shown activated fragments of complement in human eyes with uveitis and animal models have shown an effect on disease by complement depletion with cobra venom …

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Pathogenesis And Therapeutic Potential Of Plasmacytoid Dendritic Cells In Siv/Shiv-Infected Macaques, R Keith Reeves Jan 2007

Pathogenesis And Therapeutic Potential Of Plasmacytoid Dendritic Cells In Siv/Shiv-Infected Macaques, R Keith Reeves

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Plasmacytoid dendritic cells (pDCs) are among the first responders during acute viral infections and are the primary producers of IFN-α, a cytokine known to inhibit viral replication and to activate natural killer (NK) cells. In HIV patients pDCs are decreased in number, are dysfunctional, and can harbor HIV-1 proviruses. However, since the time of transmission is usually unknown, pDC-virus interactions immediately after exposure to HIV remain unclear. Using the SIV/SHIV-macaque model, we showed that an acute and sustained loss of blood pDCs occurred during SIVmac239 infections, and when compared to those from naïve controls, pDCs were also significantly reduced in …

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In Vivo Imaging Studies In Animal Models Of Myocardial Infarction With And Without Cell Injections, Balazs Ruzsics Jan 2007

In Vivo Imaging Studies In Animal Models Of Myocardial Infarction With And Without Cell Injections, Balazs Ruzsics

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After prolonged myocardial ischemia, myocardial infarction occurs. Several tissue changes are associated with myocardial infarction and iron labeled cell injections. In the present thesis our major aim was to develop methods to monitor these tissue changes with MRI and MDCT. In the first chapter we used transendocardial injection to deliver iron labeled allogen skeletal myoblasts one week after myocardial infarction. Our goal was to identify the cells and/or injection sites in the myocardium. We used our new Tissue Characterization Mapping method to delineate tissue edema and hemorrhage in the myocardium. The T2 weighted signal intensity enhancement, T2w SIE region was …

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Factors Influencing The Adoption Of Administrative Innovations, Tom J. Sanders Jan 2007

Factors Influencing The Adoption Of Administrative Innovations, Tom J. Sanders

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The purpose of this dissertation was to investigate the influence of selected environmental and organizational factors on the adoption of administrative innovations in order to better understand strategic adaptation by organizations. General systems theory, various organizational theories, strategic adaptation and management theories, and adoption and diffusion of innovation literature were used to develop a theoretical framework to address four primary and sixteen secondary hypotheses. The administrative innovation used for this study was the magnet hospital concept for enhancing attraction and retention of registered nurses in order to address a persistent workforce shortage in U.S. hospitals. Secondary data related to U.S. …

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Caste As A Determinant Of Utilization Of Maternal And Neonatal Healthcare Services In Maitha, Uttar Pradesh, India, Ekta Saroha Jan 2007

Caste As A Determinant Of Utilization Of Maternal And Neonatal Healthcare Services In Maitha, Uttar Pradesh, India, Ekta Saroha

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Caste among Hindus in India is a non-modifiable socio-demographic characteristic, often the basis of segregation and discrimination. Despite the provision of subsidized maternal and child healthcare services, utilization in rural Uttar Pradesh (UP), India is poor. Studies showed that upper caste (UC) women were more likely to utilize healthcare services than the lower caste (LC) women but this association is inadequately researched. We explored whether caste was a determinant of utilization of maternal healthcare (MH) and neonatal healthcare (NH) services among rural Hindu women and neonates in Maitha, UP, India. Data from the ‘Morbidity and Performance Assessment’ study for 482 …

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A Grounded Theory Study: Hispanic Adolescents' Experience Of Being Overweight, Wilma Powell Stuart Jan 2007

A Grounded Theory Study: Hispanic Adolescents' Experience Of Being Overweight, Wilma Powell Stuart

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The number of overweight adolescents worldwide has continued to increase over the past several decades. Intervention studies for weight management with overweight adolescents are challenged by high rates of attrition and have failed to achieve sustained outcomes. Hispanic adolescents have a higher risk of being overweight than their African American and White peers do. However, Hispanic overweight adolescents have been poorly represented in intervention studies with overweight adolescents. The factors that influence the Hispanic overweight adolescents’ perceptions of weight and weight loss management are not known. This qualitative study used ground theory methodology to identify the factors that influence perceptions …

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The Characterization Of The Subcellular Localization Of Bile Acid Coa: N-Acyltransferase, Nathan Allen Styles Jan 2007

The Characterization Of The Subcellular Localization Of Bile Acid Coa: N-Acyltransferase, Nathan Allen Styles

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The liver plays a central role in metabolism. It controls protein metabolism through deamination and transamination of amino acids, removal of ammonia through urea synthesis, synthesis of non-essential amino acids and synthesis of the majority of plasma proteins such as albumin. The liver regulates blood glucose levels through glyconeogenesis and glyconeolysis of glycogen, as well as gluconeogenesis from amino acids. It regulates fat metabolism through oxidation of triglycerides and fatty acids, as well as synthesis of cholesterol, lipoproteins, and phospholipids. Furthermore, the liver is the only site of formation of bile acids and their conjugates, physiologically important compounds that solubilize …

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Bacillus Anthracis Spore-Host Interactions, Melissa K. Swiecki Jan 2007

Bacillus Anthracis Spore-Host Interactions, Melissa K. Swiecki

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The use of Bacillus anthracis as a bioweapon depends on the dispersal of its spores into the environment, entrance into the body, spore uptake by human host cells, germination of the spores in the host and the pathological consequences of the virulence factors produced by the vegetative cells. Prior to 2001, very little was known about the mechanisms of spore entry into the host, including targeting cell types at airway, digestive and skin surfaces, potential spore receptors on these cells and spore encounters with cellular and humoral elements of the innate and adaptive immune systems. To this end, we have …

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