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Intimate Partner Violence Among Latinas In Central Alabama: Sociodemographic Characteristics, Perceptions Of Abuse, And Help-Seeking Behaviors, Angela Boy Jan 2010

Intimate Partner Violence Among Latinas In Central Alabama: Sociodemographic Characteristics, Perceptions Of Abuse, And Help-Seeking Behaviors, Angela Boy

All ETDs from UAB

This study utilized a cross-sectional design to survey 272 Latinas in the Birmingham metropolitan area and interview 29 Latinas who were known victims of IPV in the community. Prevalence, socio-demographic characteristics, perceptions of abuse, and help-seeking behaviors were examined, and the psychometric properties of the Woman Abuse Screening Tool (WAST) were assessed. Survey findings indicated current and lifetime IPV prevalence rates of 39.4% and 44.9%, respectively, among women aged 19-55. Victims were 1.9 times more likely to have been born in Central/South America than non-victims. Survey respondents had an average score of 32.5 (range 11-44) on the Perceptions of Abuse …


Cathelin-Related Antimicrobial Peptide (Cramp) Regulates B Cell Igg1 Production, Yao Chen Jan 2010

Cathelin-Related Antimicrobial Peptide (Cramp) Regulates B Cell Igg1 Production, Yao Chen

All ETDs from UAB

Mammalian antimicrobial peptides, including cathelicidins and defensins, play an important role in host defense via direct antimicrobial activity as well as immune regula-tion. The cathelin-related antimicrobial peptide (mCRAMP) is the only identified mouse cathelicidin and the orthologue of human LL-37. We show that all mouse B cell subsets, including follicular, marginal zone, B1a, and B1b cells, as well as CD4+ and CD8+ T cells produce mCRAMP directly ex vivo. In addition, mCRAMP-deficient B cells produced less IgG1 antibody in vitro in response to CD40L or LPS plus IL-4 when compared to WT B cells. The addition of recombinant mCRAMP at …


Diversity, Commonality, And Stability Of Mutans Streptococci In High Caries Risk Children, Kyounga Cheon Jan 2010

Diversity, Commonality, And Stability Of Mutans Streptococci In High Caries Risk Children, Kyounga Cheon

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Mutans streptococci (MS), Streptococcus mutans and Streptococcus sobrinus are associated with the initiation of dental caries in humans. Initially, a single S. mutans genotype has been shown to colonize primary molars soon after eruption. More genotypes can be acquired with age and further dental development. Current methods used to genotype isolates from an individual have not systematically determined the minimum number required to demonstrate an individual's genetic diversity. The purpose of this study was to determine the optimum number of oral isolates of MS (i.e., from plaque samples) to genotype in order to demonstrate diversity. This study also initiated a …


The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang Jan 2010

The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang

All ETDs from UAB

Exposure to air pollutants are known to induce airway inflammation, decrease lung function, and worsen existing pulmonary conditions such as asthma. Additionally, air pollutant exposure has also been shown to impact cardiovascular health. Although these pollutant-induced cardiovascular effects were considered to be mediated by the direct action of pollutants upon the cardiovascular tissue and/or the indirect release of pro-inflammatory factors into the circulation, the relative contribution of the two pathways remained equivocal. Recently, several epidemiology studies associated ozone exposure with cardiovascular mortalities. However, relatively few studies to date have examined ozone in this context. In order to address our hypothesis …


Lim Kinase 1 And Twinstar In Synaptic Plasticity Of Drosophila Motoneurons, James Brian Machamer Jan 2010

Lim Kinase 1 And Twinstar In Synaptic Plasticity Of Drosophila Motoneurons, James Brian Machamer

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Modification of the actin cytoskeleton is essential for synaptic plasticity, which is believed to underlie the brain's capacity for learning and memory. Regulation of the actin cytoskeleton by LIM Kinases (LIMK1 and LIMK2) and their downstream targets Actin Depolymerization Factor/Cofilin (ADF/Cofilin) in the mouse forebrain modulates dendritic spine morphology, synaptic function, long-term potentiation (LTP), and learning and memory, but appear dispensable for the regulation of most forms of presynaptic plasticity. However, these analyses were performed in mice mutant for single members of these gene families, and thus the interpretation of these results is confounded by potential compensatory activity of homologous …


Genotyping Of Streptococcus Mutans Using Multilocus Sequence Typing, Stephanie Momeni Jan 2010

Genotyping Of Streptococcus Mutans Using Multilocus Sequence Typing, Stephanie Momeni

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ABSTRACT The role of Streptococcus mutans has been extensively studied using a variety of genotyping techniques. Repetitive extragenic palindromic polymerase chain reaction (rep-PCR) is an effective tool for screening large-scale epidemiological studies with high discriminatory power and reproducibility. For this study, multilocus sequence typing (MLST) analysis is used to evaluate genotypes previously identified as unique using rep-PCR. Twenty-two unique S. mutans rep- PCR genotypes were selected from a longitudinal study. Four additional isolates were selected from each genotype group of the 6 most commonly occurring genotypes (n=30) for further analysis. Real-time PCR was performed using eight housekeeping S. mutans gene …


Sexual Risk Behavior Among African-American Adolescents: Trajectories And Their Predictors, Maureen Muchimba Jan 2010

Sexual Risk Behavior Among African-American Adolescents: Trajectories And Their Predictors, Maureen Muchimba

All ETDs from UAB

Although adolescents in the United States are at high risk of sexually transmitted infections and HIV, research indicates that many do not use condoms consistently and have high numbers of lifetime multiple sexual partners. Among adolescents, different subgroups exhibit distinct patterns of sexual behavior over time. The purpose of this dissertation was to identify trajectories of sexual risk behavior among adolescents and to determine individual, family and community factors that are predictive of membership to trajectory groups. Data were collected on sexual risk behavior among low-income African-American adolescents in Mobile County, Alabama. Gender-balanced subsamples of risky sex (N = 1294) …


Poxvirus Evolution: The Role Of Horizontal Gene Transfer, Mary Rebecca Odom Jan 2010

Poxvirus Evolution: The Role Of Horizontal Gene Transfer, Mary Rebecca Odom

All ETDs from UAB

We have investigated the set of all poxvirus proteins for information about the origins of protein coding genes of the Poxviridae family of viruses. A global assessment of all poxvirus proteins for levels of similarity to proteins of other organisms, including eukaryotes, viruses, and prokaryotes, has suggested trends and relationships informative about poxvirus evolution and poxvirus interactions with hosts. Our research has focused on the poxvirus proteins subset this assessment identified as likely to have evolutionary histories involving horizontal gene transfer (HGT). We have used phylogenetic reconstructions to individually determine the sources of more than 70 horizontally transferred genes present …


The Impact Of Ehr Systems On Physician Productivity And Performance, Anantachai Panjamapirom Jan 2010

The Impact Of Ehr Systems On Physician Productivity And Performance, Anantachai Panjamapirom

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This study examines the relationship between electronic health record (EHR) adoption and physicians' operational productivity and financial performance. The resource-based view of the firm (RBV) was utilized as a theoretical framework to develop and address four hypotheses. Specifically, the first two hypotheses address the impact of EHR adoption status (i.e., electronic- vs. paper-based medical records), and the other two hypotheses focus on the length of EHR adoption (i.e., years of EHR adoption). This cross- sectional study used secondary data from the 2008 physician compensation and production survey conducted by the Medical Group Management Association (MGMA). Multiple linear regression analysis was …


Pneumococcal Vaccine Response And Aging In Human, Saeyoung Park Jan 2010

Pneumococcal Vaccine Response And Aging In Human, Saeyoung Park

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Streptococcus pneumoniae is a major human pathogen, especially for young children and older adults. To protect from pneumococcal diseases, 23-valent pneumococcal polysaccharide vaccine (PPV23) has been used clinically since 1983. However, PPV23 is not so effective among old adults with its protective efficacy diminishing with age. We confirmed that young and old adults, who were immunized with PPV23, have comparable pneumococcal polysaccharide (PS) specific IgG levels. Interestingly, we found that old adults had lower IgA and IgM antibody levels than young adults for three serotypes (serotype 14, 18C and 23F). Consistent with the previous results, opsonic capacities of immune sera …


Information Technology And Quality Of Care In Pediatric Hospitals, Gouri Gupte Jan 2010

Information Technology And Quality Of Care In Pediatric Hospitals, Gouri Gupte

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The purpose of this dissertation is to examine the relationship between the adoption of information technology by pediatric hospitals and performance on several quality of care measures. This research is aimed at addressing a gap in literature by utilizing a relatively large sample size that examines health information technology adoption across institutions and utilizes validated quality indicators from Agency for Healthcare Research and Quality. The Donabedian evaluation model that encompasses "structure, process, and outcomes" provides the conceptual framework for the organization of this research, selection of variables, and analysis. Three secondary datasets were used, 2005 Information Technology Survey of the …


A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison Jan 2010

A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison

All ETDs from UAB

Chronic neutrophilic inflammation is a hallmark of numerous pulmonary diseases. It is commonly associated with declining lung function, collagen turnover, and increased protease activity. Our laboratory has recently published several articles describing a biologically active collagen breakdown product, proline-glycine-proline (PGP) and its more active amino-terminus acetylated form, N-α-PGP. PGP acts via classical chemokine receptors CXCR1 and 2 to draw neutrophils (PMNs) into sites of inflammation in what is potentially a feed-forward mechanism of disease. The tri-peptide appears to be a bio-marker in certain clinical diseases like cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The present work first details …


Investigation Of Residues Of The Vesicular Stomatitis Virus Nucleocapsid Protein That Affect Transcription And Rna Replication, Djamila Harouaka Jan 2010

Investigation Of Residues Of The Vesicular Stomatitis Virus Nucleocapsid Protein That Affect Transcription And Rna Replication, Djamila Harouaka

All ETDs from UAB

The template for transcription and RNA replication for vesicular stomatitis virus (VSV) and other negative-strand RNA viruses is a ribonucleoprotein (RNP) complex consisting of the viral RNA genome and associated nucleocapsid (N) protein. The structure of the RNP-like complex of VSV showed that the RNA is sequestered between two lobes of the N protein, and adjacent N monomers are linked by an extensive network of interactions. Long-range interactions mediated by the N-terminal arm and C-terminal loop of the N protein stabilize the side-to-side contacts between adjacent N monomers, and are required for RNA encapsidation. It is unclear how the polymerase …


Evaluations Of Clinical Signs Currently And Not Currently Used In Syndromic Case Management (Scm) Of Reproductive Tract Infections (Rtis) Among Pregnant Women In Jamaica, Gelen Receno Del Rosario Jan 2010

Evaluations Of Clinical Signs Currently And Not Currently Used In Syndromic Case Management (Scm) Of Reproductive Tract Infections (Rtis) Among Pregnant Women In Jamaica, Gelen Receno Del Rosario

All ETDs from UAB

Reproductive tract infections include sexually transmitted infections, endogenous infections caused by overgrowth of organisms that can be present in the genital tract of a healthy woman, and iatrogenic infections. In Jamaica, women in the reproductive age group of 15-44 years old accounts for 95% of all RTIs. RTIs among Jamaican women of reproductive age can seriously impact the health of the women and their children. The advent of HIV/AIDS has had a significant impact on increasing awareness of the effect of STIs. Health care organizations have reacted with great commit-ment to STI prevention and treatment as a significant factor in …


Visualizing The Productive Program Of Hpv In Differentiating Squamous Epithelial Tissue, Aaron A. Duffy Jan 2010

Visualizing The Productive Program Of Hpv In Differentiating Squamous Epithelial Tissue, Aaron A. Duffy

All ETDs from UAB

The human papillomavirus (HPV) establishes persistent infections in the basal stratum of squamous epithelia, while productive amplification of viral DNA occurs in differentiated keratinocytes prior to virion assembly in the superficial strata. Until recently, only in situ hybridization (ISH) of low-grade HPV lesions could be used to reveal a snap shot of the viral life cycle. There has been a critical need to reproducibly propagate HPV infections in culture for consistent genetic analyses. Organotypic raft cultures recapitulate a differentiated squamous epithelium. Our lab utilized in vivo Cre-mediated recombination to reconstitute the entire HPV-18 genome in primary human keratinocytes (PHKs). My …


Evolution And Genetic Diversity In Streptococcus Pneumoniae, Diana Lee Dupraw Jan 2010

Evolution And Genetic Diversity In Streptococcus Pneumoniae, Diana Lee Dupraw

All ETDs from UAB

The relative contributions of point mutations and intergenomic recombination via lateral gene transfer (LGT) determine the population structure and evolutionary style for a given bacterial species. Streptococcus pneumoniae has a weakly clonal population structure; adaptive clonal complexes can be detected; however, these can also be rapidly lost due to the high rate of recombination. To characterize the diversity of pneumococcal isolates in clonal complex, and to elucidate possible mechanisms for the long-term stability of such complexes, 35 serotype 6B strains belonging to a previously identified clonal complex, CC14, were assayed by Comparative Genome Hybridization (CGH) and Multi Locus Sequence Typing …


The Role Of Toll-Like Receptors 2 And 4 In Helicobacter Felis Infections And Asthma, Carolyn Durham Jan 2010

The Role Of Toll-Like Receptors 2 And 4 In Helicobacter Felis Infections And Asthma, Carolyn Durham

All ETDs from UAB

The inverse correlation between the industrialization and disease prevalence is termed the "hygiene hypothesis." Supporting this, immunological studies show Th1 cytokines modulate Th2 immune responses. Because the mucosa is essential in antigenic exposure, understanding bacterial sensing here is critical to addressing three foundations of this hypothesis: the role of bacterial exposure, relevance of noninvasive bacterial exposure, and influence of these exposures on immune responses. Key components of antigen sensing in the mucosa are toll-like receptors (TLRs) 2 and 4, which have been implicated in disease. The hypothesis of this thesis is, by globally knocking out one or both of these …


Role Of Epithelial Sodium Channel And Acid Sensing Ion Channel In Glioblastoma Multiforme, Niren Kapoor Jan 2010

Role Of Epithelial Sodium Channel And Acid Sensing Ion Channel In Glioblastoma Multiforme, Niren Kapoor

All ETDs from UAB

Glioblastoma Multifrome is the most common and aggressive of the primary brain tumors. These tumors express multiple members of the Epithelial Sodium Channel (ENaC)/Degenerin (Deg) family, associated with a basally active amiloride sensitive cation current. We hypothesize that this glioma current is mediated by a hybrid channel composed of a mixture of Epithelial Sodium Channel (ENaC) and Acid Sensing Ion Channel (ASIC) subunits. To test this hypothesis we made dominant negative cDNAs for ASIC1, αENaC, and γENaC. D54-MG glioma cells transfected with the dominant negative constructs for ASIC1, αENaC, or γENaC showed reduced protein expression for each of the specific …


Chronic Alcohol Consumption Promotes Opening Of The Mitochondrial Permeability Transition Pore And Increases Mitochondrial Injury In Liver, Adrienne Lester King Jan 2010

Chronic Alcohol Consumption Promotes Opening Of The Mitochondrial Permeability Transition Pore And Increases Mitochondrial Injury In Liver, Adrienne Lester King

All ETDs from UAB

Alcoholic liver disease is a serious public health concern. In particular, the mitochondrion is a specific target of ethanol toxicity and much of the damage can be related to unregulated Ca2+ homeostasis and oxidative stress which are key players in the induction of the mitochondrial permeability transition pore (MPTP) within the organelle. The mechanism behind the induction of the MPTP remains elusive. Therefore, this body of work will provide insight on what effects chronic alcohol consumption has on mitochondrial dysfunction with an emphasis on the MPTP. Chapter 2: Assessment of mitochondrial dysfunction arising from treatment with hepatotoxicants provides a description …


The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar Jan 2010

The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar

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Upon human immunodeficiency virus (HIV) infection the host mounts a robust and multifaceted immune response. To achieve successful replication, HIV must possess a powerful arsenal of immune evasion weapons. While a complex strategy for HIV immune evasion has been described in the periphery, little is known about the mechanism allowing HIV to overcome the simple interferon (IFN)-ß-mediated innate immune defenses of the central nervous system (CNS). In light of the devastating cognitive dysfunction that is caused by HIV replication within the CNS, a better understanding of this mechanism is critical. Recent studies have shown that viral pathogens can induce the …


Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm Jan 2010

Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm

All ETDs from UAB

Breast cancer is the second leading cause of cancer-related death in American women and metastatic breast cancer has a 5-year survival rate of only 26%. Current targeted treatments for this disease include anti-estrogen strategies for estrogen receptor positive tumors (~60%) and anti-Her2/Neu strategies for tumors overexpressing this receptor (20-25%). A percentage of breast cancer patients, however, are resistant to these therapies and are left without any effective treatment options. One of the agents currently being investigated to improve breast cancer survival is TRA-8, an agonistic monoclonal antibody to death receptor 5 (DR5), which induces apoptosis in various types of cancer …


Determinants Of Self-Efficacy To Seek Care For Tuberculosis And Complete Tuberculosis Treatment Among Hiv-Positive Patients Attending Government Hiv/Aids Clincis In Honduras, Mayra Silvana Arias Jan 2010

Determinants Of Self-Efficacy To Seek Care For Tuberculosis And Complete Tuberculosis Treatment Among Hiv-Positive Patients Attending Government Hiv/Aids Clincis In Honduras, Mayra Silvana Arias

All ETDs from UAB

HIV-positive persons bear an elevated risk of developing, relapsing, and dying from tuberculosis (TB), and have greater risk of TB treatment default. Yet little is known about the factors that influence TB care-seeking among this population. This study evaluated sociodemographic, cognitive, and psychosocial characteristics of PLHA without a history of TB receiving care in specialized HIV/AIDS clinics in Honduras, and the influence of several variables on self-efficacy to seek care, including: (1) seeking care for prolonged cough despite external constraints and potential HIV stigmatization, and (2) completing TB treatment once diagnosed. The majority of participants were women (55%). Seventy-two percent …


Development Of A Mucosal Vaccine Protective Against Francisella Tularensis Infection, Amit R. Ashtekar Jan 2010

Development Of A Mucosal Vaccine Protective Against Francisella Tularensis Infection, Amit R. Ashtekar

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Francisella tularensis, a facultative intracellular, gram-negative coccobacillus, is the causative agent of tularemia and has been classified as a category A biological agent. Since there currently is no licensed vaccine available, in this study, we assessed the potential of a bivalent subunit vaccine comprising of DnaK and Tul4 to protect against respiratory tularemia. Intranasal immunization of C57BL/6 mice with DnaK, Tul4, and the adjuvant GPI-0100 resulted in mucosal and systemic antibody responses to DnaK and Tul4. In addition to antibody responses, this immunization regimen also induced both Th1 and Th2 cell-mediated immune responses specific for DnaK and Tul4. Finally, more …


Evolutionarily Conserved Cis-Acting Elements Regulate Lineage-Specific Expression Of Ifng, Anand Balasubramani Jan 2010

Evolutionarily Conserved Cis-Acting Elements Regulate Lineage-Specific Expression Of Ifng, Anand Balasubramani

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The ability to differentially manipulate available genetic information in order to generate diverse cellular identities represents an innovation of complex multicellular eukaryotic organisms. Cis-acting modules that regulate transcription play extremely important roles in ensuring lineage-specific expression of genes that define cellular identities. In our studies, using Interferon-gamma (IFN-gamma, a cytokine encoded by the gene Ifng), a cytokine encoded by T, NK and NKT cells as a model, we have identified and characterized the roles of key cis regulatory elements that facilitate T lineage specific induction as well as repression of Ifng transcription. In particular, our studies have highlighted the role …


Heparanase Drives The Aggressive Myeloma Phenotype: Preclinical Development Of A Heparanase Inhibitor For The Treatment Of Multiple Myeloma, Joe Ritchie Jan 2010

Heparanase Drives The Aggressive Myeloma Phenotype: Preclinical Development Of A Heparanase Inhibitor For The Treatment Of Multiple Myeloma, Joe Ritchie

All ETDs from UAB

Heparanase, an endoglycosidase which cleaves heparan sulfate chains at specific sites, is rarely expressed in normal tissues but becomes evident in many human cancers. We have previously shown that heparanase promotes myeloma growth and angiogenesis through modulation of the tumor microenvironment. Recognition that heparanase drives the aggressive myeloma phenotype has led to new strategies designed to therapeutically target this enzyme. SST0001, a non-anticoagulant heparin that is 100% N-acetylated and 25% glycol split, was previously described as a potent inhibitor of heparanase activity in vitro, and, in limited in vivo experiments, SST0001 was identified to have efficacy as an anti-tumor agent …


Hypothesis Testing Based On Pool Screening With Unequal Pool Sizes, Hongjiang Gao Jan 2010

Hypothesis Testing Based On Pool Screening With Unequal Pool Sizes, Hongjiang Gao

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Pool screening is a widely applied technique to estimate the prevalence of a rare event. This focus of this research is on developing statistical test of hypothesis procedures under the assumption that pool sizes are unequal but known. One of the proposed test procedures is , an exact test based on the number of positive pools (denoted by T). Another set of proposed test procedures is a modification of the likelihood ratio, Wald's and Score tests which are commonly-used likelihood-based tests. In paper 1, we derive the distribution of T which will be the basis of the exact test. Other …


O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho Jan 2010

O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho

All ETDs from UAB

O-GlcNAcylation is an abundant and dynamic post-translational modification on serine and threonine residues of nuclear and cytoplasmic proteins. O-GlcNAc Transferase (OGT) and Nuclear Cytoplasmic O-GlcNAcase and Acetyltransferase (NCOAT) are the only two enzymes and major regulators in this process. In the past two decades, many studies have demonstrated its important modulation roles in nutrient sensing, protein turnover, cell cycle progression, transcription, translation as well as stress resistance. Among these biological functions, the understanding of O-GlcNAcylation dependent oxidative stress is relatively unknown. This study aims to examine the effects of O-GlcNAcylation on JNK1 and FOXO4 transcription factors under acute oxidative stress …


Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis, Dario A. Vitturi Jan 2010

Red Blood Cell And Hemoglobin Dependent Modulation Of Reactive Species Metabolism: Implications For Vascular Homeostasis, Dario A. Vitturi

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The recent discovery that red blood cells might mediate hypoxic blood flow together with accumulating evidence that suggests a role for the modulation of vascular inflammation has reshaped the way we think about the function of these cells. In this thesis we investigate the mechanisms that regulate these newly appreciated functions and focus on i) the ability of red cells to couple oxygen sensing with nitrite reduction and nitric oxide formation and ii) the role of the beta93cys, a conserved residue amongst mammalian hemoglobins and whose function remains unclear. Data will be presented that demonstrate that nitrite reduction to nitric …


Therapeutic Interventions For Chlorine Gas Induced Lung Injury, Amit Kumar Yadav Jan 2010

Therapeutic Interventions For Chlorine Gas Induced Lung Injury, Amit Kumar Yadav

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Rationale: Nitrite (NO2-) has been shown to limit injury to the heart, liver and kidneys in various models of ischemia-reperfusion injury. Currently, potential protective effects of systemic NO2- in limiting lung injury or enhancing repair have not been documented. Objectives: To assess the efficacy and mechanisms by which post-exposure intra-peritoneal injections of NO2- mitigate Cl2 induced lung injury in rats. Methods: Rats were exposed to Cl2 (400 ppm) for 30 minutes and returned to room air. Nitrite (1mg/Kg) or saline were administered intraperitoneally at 10 min, 2, 4 and 6 hrs post exposure. Rats were sacrificed at 6 hrs or …


A Timp2-Armed Conditionally-Replicating Adenovirus For The Treatment Of Ovarian Cancer, Sherry Wei Yang Jan 2010

A Timp2-Armed Conditionally-Replicating Adenovirus For The Treatment Of Ovarian Cancer, Sherry Wei Yang

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Ovarian cancer remains the most lethal gynecological malignancy in the U.S. Conventional therapies have limited therapeutic value due to advanced stage of the disease at diagnosis. Conditionally-replicating adenoviruses (CRAds) are promising, novel anti-cancer agents that are designed to selectively replicate in and lyse tumor cells. In clinical trials, CRAds exhibited limited efficacy thus far. Second generation CRAds are being developed to express a therapeutic protein to further enhance antitumor efficacy. One attractive target in ovarian tumor microenvironment is the matrix metalloproteinases (MMPs) that degrade the extracellular matrix. Thus, tissue inhibitor of metalloproteinase 2 (TIMP2), an endogenous inhibitor of MMPs, is …