• Assessment of Renal Ischemia Reperfusion Induced Injury in Male and Female Rats

      Crislip, Gene Ryan; Department of Physiology (2017)
      Acute kidney injury (AKI) is a clinical problem often induced by ischemia reperfusion (IR). Males are reported to have worse outcomes following IR compared to females based on measurements of blood urea nitrogen and creatinine. However, these markers are produced at different levels depending on body mass. The goal of Aims 1 and 2 was to do a complete assessment of the impact of sex on IR to establish a model that displays a sex difference. We measured multiple markers, including inulin clearance which is the gold standard of determining renal function. We determined there is no sex difference in response to IR after 24 hours. However, males had impaired renal function, higher vascular congestion and tubular injury than females 7 days following IR. A consequence of vascular congestion and tubular injury is fluid leakage into interstitial space, which increases renal volume. The goal of Aim 3 was to determine if ultrasound could be used as a tool to detect progressive changes in regional kidney volume following IR. To do this, we compared renal volume measurements with stereological assessment and examined the use of renal volume as an injury marker following IR. We verified the use of ultrasound to monitor renal volume after IR and the changes in volume correlated with the extent of medullary injury. Limiting vascular congestion improves recovery following IR. Pericytes are contractile cells that line the vessels in the renal medulla that are prone to congestion following IR. The goal of Aim 4 was to determine the role of renal pericytes following IR. To do this, we decreased pericytes in rats before IR to determine if this effected injury. We found that lower pericyte density was associated with greater vascular congestion following IR, additionally, males lose more pericytes than females. From these studies, we concluded that there was no sex difference in IR induced injury after 24 hours, however, following 7 days males had poorer recovery than females. We hypothesize that this poorer recovery is attributed to less pericytes in males following IR resulting in the inability to reduce vascular congestion compared to females.
    • Assessment of the immune status of dialysis of patients following donor specific blood transfusions

      Kapp III, William Karl; Department of Cell and Molecular Biology (1985-06)
    • Astrocytes Modulate Endothelial Cell Growth, Differentiation, and Fibronectin Expression

      Jiang, Baoen; Department of Cellular Biology & Anatomy (Medical College of Georgia, 1993-08)
      The retinal vascular development in the nerve fiber layer occurs by in situ differentiation of vascular precursor cells, but the mechanisms controlling this process are still unknown. We sought to determine the stimuli regulating. the organization of vascular precursor cells into retinal vessels by analyzing the roles of extracellular matrix and astrocytes. Immunolocalization analyses in the developing rat show that rat retinal vessels form as a polygonal network, beginning at the optic disc and extending to the ora. serrata by pll. Factor VIII-positive endothelial cells and laminin- and fibronectin-positive basement membrane codistribute with lumenized vessels. GFAP-positive astrocytic processes associate closely with the formed vessels, but ~re also present between the vessels. In the avascular area just distal to the forming vessels, GFAP-positive astrocytes form a fibronectin-positive polygonal meshwork pattern that resembles the immature vascular network. Laminin is not expressed in this area. In the area of the astrocyte-fibronectin meshwork, Bandierea Griffonia Simplifolia I B4 lectin labeled vascular precursor cells elongate and align along the astrocyte processes. Double label analysis indicates that both astrocytes and vascular . cells produce fibronectin. In situ hybridization shows that fibronectin mRNA expression is heaviest in the meshwork areas, suggesting that fibronectin synthesis is required in the early stage of retinal vasculogenesis. 0~11 culture experiments confirmed a strong influence of astrocytes on retinal microvascular endothelial cell growth, morphological differentiation, and extracellular matrix expression. Immunolocalization studies of cultured cells suggested and Western blot and Northern blot analyses confirmed a significant increase in fibronectin expression, when endothelial cells were grown in conditioned medium (CM) from astrocytes as compared with controls grown in CM from endothelial cells or pericytes. When retinal microvascular endothelial cells were grown in CM from astrocyte I endothelial cell co-culture, their growth was significantly inhibited as compared with controls grown in normal growth medium or CM from endothelial cells, astrocytes, or a mixture of 50% astrocyte CM/50% endothelial cell CM. In addition, endothelial cells grown in CM from astrocyte I endothelial cell co-culture elongated and became aligned in capillary-like structures. Endothelial cells grown in CM from astrocytes, endothelial cells, or a mixture of 50%astrocyte CM/50% endothelial cell CM alone retained normal· cobblestone morphology. CM from astrocytes alone stimulates retinal microvascular endothelial cell growth as compared with CM from endothelial cells, astrocyte I endothelial cell co-culture, or a mixture of 50% astrocyte CM/50% endothelial cell CM. These data indicate that rat retinal vascular development occurs by in situ differentiation of vascular precursor cells in close contact with astrocytes. Moreover, astrocytes modulate retinal microvascular endothelial cell growth, morphological differentiation, and fibronectin expression by release of growth factor-like substances. At least two factors are involved - one that requires astrocyte/ endothelial cell contact for activity and one that does not.
    • Attempts to infect poikilothermic animals with the dimorphic fungus, blastomyces dermatitidi

      Kangelos, Marilyn; Department of Cell and Molecular Biology (1965-05)
    • Attenuating the Interaction Between Delta Protein Kinase C and the "d" Subunit of FIFo ATp Synthase Protects Against Cardiac Ischemia/Repferusion injury

      Walker, Matthew; Deparment of Pharmacology and Toxicology (6/3/2016)
      Cardiac ischemia / reperfusion (IR) injury most often results from the thrombotic blockade of the coronary arteries and is the most frequent cause of death in humans. Despite the significant role energy deprivation plays in cardiac IR injury, few studies have targeted the IR-induced impairment of the mitochondrial F1Fo ATP synthase. We have previously demonstrated delta protein kinase C (δPKC) involvement in cardiac myocyte energy deprivation via its interaction with the “d” subunit of F1Fo ATP synthase (dF1Fo) and have developed a peptide inhibitor [NH2YGRKKRQRRMLATRALSLIGKRAISTSVCAGRKLALKTIDWVSFDYKDDDDK- COOH] of this interaction. It targets to the mitochondrial matrix / inner membrane. The inhibitor peptide contains a FLAG epitope which allowed confirmation of its uptake into cardiac mitochondria. Our early studies in neonatal cardiac myocytes (NCMs) led us to the hypothesis that PKC inhibits ATP production in vivo via an interaction with dF1Fo to exacerbate cardiac IR injury. To directly test our hypothesis, we first utilized the Langendorff isolated heart model to show that PKC co-immunoprecipitates (co-IPs) with antisera to dF1Fo in myocardium exposed to simulated IR injury. Administration of the inhibitor peptide to the isolated rat hearts prior to cardiac IR attenuated the co-IP of 􀁇PKC with dF1Fo, improved recovery of contractility, diminished levels of tissue t-carbonyls and 4-hydroxy-2-nonenal (HNE), and reduced myocardial infarct size (as assessed by 2, 3, 5 triphenyltetrazolium chloride (TTC) staining) following simulated IR exposures. Additionally, this peptide enhanced ATP levels 2.1 fold, improved ADP-stimulated mitochondrial respiration, and attenuated Ca++-induced mitochondrial swelling in ischemic myocardium. We next evaluated the inhibitor peptide in an in situ rat coronary ligation model for its ability to protect live rats from cardiac IR injury. A 10 min coronary ligation increased the PKC-dF1Fo co-IP in the region at risk (RAR) by 5-fold which was attenuated by 71% with intravenous infusion of the inhibitor peptide. This response correlated with an enhancement of ATP levels, a 2-fold reduction in oxidative stress markers, improvement in systolic cardiac function, and a reduction in TTC monitored myocardial infarct size in the RAR. These results support further development of this peptide as a first-in-class-translational therapeutic for the treatment of cardiac IR injury.
    • The Autoimmune Regulator (Aire) Confers Immunosuppressive Properties to Dendritic Cells

      Eisenman, Daniel; Center for Biotechnology and Genomic Medicine (2007-05)
      The Autoimmune regulator (Aire) is a transcription factor that controls expression of self antigens by thymic epithelium and it plays a critical role in the deletion of autoreactive thymocytes and prevention of autoimmunity. Recent studies have reported Aire expression in dendritic cells (DC) located in spleen and lymph nodes, suggesting a role for Aire in extra-thymic tolerance induction. Molecular and functional studies conducted in this dissertation revealed that Aire induction in bone marrow derived DC results in expression of immunosuppressive cytokines and decreased expression of co-stimulatory molecules. Similar results were also obtained from lenti-virus-mediated Aire overexpression in the DC2.4 dendritic cell line. It was further shown that DC from Aire'7' mice exhibited greater antigen presenting function both in vitro and in vivo. These DC were more potent stimulators of T cell proliferation leading to increased IL-2 and IFNy production. These studies suggest that Aire7' DC may play a role in exacerbating the autoimmunity seen in Aire7' mice. DC over-expressing Aire were shown to suppress activation and proliferation of naive T cells and promote activation-induced cell death of activated T cells. Furthermore, we demonstrate that Aire also controls transcription of tissue-specific antigens in DC. These results, together, suggest that Aire plays an important role in the tolerogenic function of DC.
    • Autolytic enzymes associated with cell walls of mycobacterium smegmatis

      Kilburn, James Otis; Department of Cell and Molecular Biology (1974-06)
    • Autonomic Reactivity to Threatening Images as a Function of Relevance

      Recinos, Manderley; Department of Psychological Sciences (Augusta University, 2021-05)
      Anxiety is among the most prevalent psychological conditions affecting 31% of adults in the United States (National Institute of Mental Health, 2019). Thus, it is important to identify the factors that contribute to anxiety and perhaps the development of anxiety disorders. One important factor that must be considered is how relevant a potential or real threat is to an individual. The theory of threat-relevance proposes that fear stimuli considered relevant to the individual will capture the individual’s attention and/or activate a fear response (De Oca & Black, 2013; Fox et al., 2007). On the other hand, biological theories propose that evolutionary stimuli preferentially activate the fear system due to their threat to human survival (Ohman & Mineka, 2001; Seligman, 1970) . Such disparate positions in the literature strongly suggest a need for more research in the area of threat relevance that examines biological, cultural, and social variables. The purpose of this study is to clarify and extend our understanding of the role relevance plays in triggering anxiety. Participants viewed evolutionarily based (i.e., snakes, spiders) and culturally based threatening images (i.e., guns, knives) while autonomic arousal (electrodermal activity and heart rate) was measured. Participants rated the relevance, valence, and arousal of each image, and completed a self-report measure of anxiety. We found that EDA amplitudes were higher for evolutionary threats than cultural threats, but only when cultural images were viewed first. However, heart rate was similar for both threat types regardless of the order. Cultural threats were found to be more arousing and less pleasant than evolutionary threats. Relevance was not correlated to EDA or HR responses; however, relevance was correlated with the valence and arousal ratings of each image. Relevance was also not correlated to participants’ self-reported trait anxiety. These results indicate that further research is necessary to understand how threat relevance impacts threat responses.
    • An autoregulatory process for androgen production in rat ovarian thecal-interstitial cells

      Simone, Deborah; Department of Physiology and Endocrinology (1992-10)
    • B-Lymphoid Cells with Attributes of Dendritic Cells Regulate T Cells via Indoleamine 2,3 Dioxygenase

      Johnson, Burles Avner III; Cancer Research Center (2012-04)
      A rare subset of murine dendritic cells expressing the B cell marker CD19 are specialized to express the T cell regulatory enzyme indoleamine 2,3 dioxygenase (IDO-competent DCs). Here we show that IDO-competent DCs expressed Pax5, a transcription factor that maintains B cell lineage commitment, and drives expression of CD19 and surface immunoglobulin (slg). However IDO-competent DCs also exhibited multiple attributes of DCs including DC marker expression and potent T cell stimulatory properties when IDO was not induced. Unexpectedly, DCs expressing IDO were present in B cell deficient mice following TLR9 ligation, indication that B cell receptor (BCR) expression was not required for IDO function. Conversely, DCs from CD19 deficient mice did not express IDO after in vivo TLR9 ligation. This defect was not caused by blockade of IDO-competent DC development in CD19-deficient mice because IDO expression was incduced in these cells by in vitro interferon gamma treatment. Even though DCs from B cell deficient mice expressed IDO following TLR9 ligation, regulatory T cells (Tregs) from B cell deficient mice had impaired suppressor activity. IDO-competent DCs expressed high levels of CD1d-deficient mice. IDO-competent DCs also expressed IL-10 deficient mice to express IDO. Finally we demonstrated that DCs from draining lymph nodes (dLNs) of four week old prediabetic female non obese diabetic (NOD) mice expressed functional IDO following topical treatment with phorbol myristate acetate (PMA). However DCs from dLNs of six week old prediabetic NOD female mice did not express IDO following topical PMA treatment, indicating a critical defect in a specific immunosuppressive mechanism in NOD female mice that coincides with the appearance of insulitis. These data identify IDO competent DCs as a unique B lymphoid lineage cell type that has tightly controlled regulatory properties, and a DC subset whose acquired defect may contribute to autoimmune disease in NOD mice.
    • A bacteriophage P22 gene necessary for DNA synthesis which maps in the late region

      Ruddel, Mark Eric; Department of Cell and Molecular Biology (1977-06)
    • A Bayesian Framework To Detect Differentially Methylated Loci in Both Mean And Variability with Next Generation Sequencing

      Li, Shuang; Department of Biostatistics and Epidemiology (2015-07)
      DNA methylation at CpG loci is the best known epigenetic process involved in many complex diseases including cancer. In recent years, next-generation sequencing (NGS) has been widely used to generate genome-wide DNA methylation data. Although substantial evidence indicates that di erence in mean methylation proportion between normal and disease is meaningful, it has recently been proposed that it may be important to consider DNA methylation variability underlying common complex disease and cancer. We introduce a robust hierarchical Bayesian framework with a Latent Gaussian model which incorporates both mean and variance to detect di erentially methylated loci for NGS data. To identify methylation loci which are associated with disease, we consider Bayesian statistical hypotheses testing for methylation mean and methylation variance using a twodimensional highest posterior density region. To improve computational e ciency, we use Integrated Nested Laplace Approximation (INLA), which combines Laplace approximations and numerical integration in a very e cient manner for deriving marginal posterior distributions. We performed simulations to compare our proposed method to other alternative methods. The simulation results illustrate that our proposed approach is more powerful in that it detects less false positives and it has true positive rate comparable to the other methods.
    • Bayesian Functional Clustering and VMR Identification in Methylation Microarray Data

      Campbell, Jeff; Department of Biostatistics and Epidemiology (2015-07)
      The study of the relation between DNA and health and disease has had a lot of time, energy, and money invested in it over the years. As more scientific knowledge has accumulated, it has become clear that the relations between DNA and health isn’t just a function of the sequence of nucleotide bases, but also on permanent modifications of DNA that affect DNA transcriptions and thus have a macroscopic effect on an individual. The study of modifications to DNA is known as epigenetics.Epigenetic changes have been shown to play a role in certain diseases, including cancer (Novak 2004). Finding locations of differential methylation in two groups of cells is an ongoing area of research in both science and bioinformatics. The number of developed statistical methods for establishing differential DNA methylation between two groups is limited (Bock 2012). Many developed methods are developed for nextgeneration sequencing data and may not work for microarray data, and vice versa. Bisulfite sequencing, the next-generation sequencing technique for attaining methylation data, often comes with limited sample size and considerations must be made for low and variable coverage, and smoothing the methylation values. The analysis of nextgeneration sequencing data also involves small sample sizes.In addition, these methods can be sensitive to how individual CpG regions are grouped together as a region for analysis. If the DMRs are small relative to the sizes of 5 established regions, then the method may not detect a region as having differential methylation. Robust methods for clustering microarray data have also been an ongoing area of research. It is desirable to have a method that could be applied to microarray data could increase the sample size and mitigate the previous problems if the method used is robust to missing values, outliers, and microarray data noise. Functional clustering has shown to be effective when properly conducted on gene expression data. It can be used when the data have temporal measurements to identify genes that are possibly co-expressed. The clustering of methylation data can also be shown to identify epigenetic subgroups that can potentially be very useful (Wang, 2011). [introduction]
    • Bayesian small area estimation of incidence and asymptomatic rates of chlamydia

      Greene, Joshua C.; Medical College of Georgia (Augusta University, 2009-03)
      Chlamydia, a bacterial sexually transmitted infection, is known as a silent disease because more than half of individuals infected with chlamydia are asymptomatic. We estimate chlamydia incidence and asymptomatic rates for groups of students formed by crossing class standing with race and place of residence for the entire population. Standard statistical methods are inadequate because the misclassification problem, associated with the asymptomatic nature of chlamydia, violates the assumption that the outcome variable is measured without error. Our Bayesian models use double logistic regressions and small area estimation, which borrows strength across these domains. Based on the model selected, the overall incidence and asymptomatic rates for women from the University of Florida were found to be between 5% and 6% and between 30% and 40% respectively, and they can be explained by condom use, number of sexual partners, number of times one has drinks and sex simultaneously and amount of recent alcohol intake.
    • A behavior-oriented approach to measuring the power motive

      Welcher, Portia G.; School of Nursing (1983-05)
      Based on McClelland's need theory, thij investigation represents an attempt to develop and test a research jnstrument for measuring power, achievement, and-affiliation motive,. The primary study variable is the power motive. The significance of the study is supported by· literature citing the need for instruments to ~nhance power research in nursing. A 32-item instrument, the Behavior-Oriented Motive Measurement (BOMM), was designed by the investigajor as an alternative to . existing more complex and lengthy motive mlasurements·. The design of the BOMM is·intended to minimize the time ~equired for completion and to enhance feasibility for use in nursing 1rganizational settings. This investigation included two BOMM tlst administrations. Subjects I . . consisted of a. convenience sample of 26 graduate nursing students,: .16 of · whom repeated testing three weeks later.to provide data for testretest reliability estimates. Reliabilities for internal consistency, content validity and convergent validity wrre also estimated. The BOMM was judged to have content va~idity ·on the basis of expert judges' assessment. In this measur~, the power and achievement scales demonstrated acceptable levels of internal consistency with standardized alphas of .71 and .56, respeclively in Test 1 and alphas of .78 and .73 in Test 2. The powjr motive scale demonstrated an acceptable test-retest reliability: r ·~·.50. This is somewhat low, but comparable to that of other motile measures. Conceptual evidence is cited to support the notion t~at there may be no need to expect high test;_,retest reliabilities for motive measurements. Convergent validity of the power and achievement scales was evidenced by relatively high correlations with the-Manifest Needs Questionnaire( MNQ) (r = .76, p = .001) and (r = .72, p = :001). Acceptable levels of reliability and validity were not obtained for the affiliation scale. On the basis of reliability and val-idity coefficients obtained, the conclusion is drawn ~hat the power and achievement- scales of the BOMM may be useful tools for further research on the power motive.·
    • Behavioral and neurochemical consequences of the administration of nicotinic cholinergic agents to rodents and non-human primates

      Elrod, Karey; Department of Pharmacology and Toxicology (Augusta University, 1989-05)
      Acetyl~holine (Ach) is known as a primary neurotransmitter in normal mnemonic functioning. While most research has been directed at the central muscarinic cholinergic subsystem, of recent interest in normal and pathologic cognitive processing is. the role of the nicotinic cholinergic subsystem. The purpose of my research was to further characterize~ behaviorally and neurobiochemically, the role of this system in animal models of learning and memory by: establishing a working model of cognitive impairment in the rat using a classical behavioral paradigm and muscarinic'cholinergic amnestic agent; exploring in depth the influence.of classical nicotinic cholinergic agents on performance by rats of the same and other models of learning and memory; examining the ability of these nicotinic agents to alter performance of a complex cognitive task by non-human primates; examining the ;influence of these agents on neurochemistry of the rat brain cholinergic system in an attempt-to correlate drug~induced behavioral and biochemical alterations. The classical muscarinic antagonist scopolamine significantly disrupted learning of 2 ·passive avoidance tasks by rats. The nicotinic agonist nicotine afforded significant memory enhancement in monkeys performing a· delayed matching-to-sample task. The centrally-acting nicotinic antagonist mecamylamine, but not the peripherally-acting nicotinic antagonist hexamethonium, produced significant impairment of the ability of rats to. learn a passive avoidance task and the ability of monkeys to perform a delayed matching-to-sample task. Mecamylamine failed to exert a centrally~selective effect on performance of an active. avoidance or radial arm maze task by rats. Biochemical analyses revealed dr~atic drug-induced changes in neurochemical markers of the rat brain cholinergic syst.em. Sigriificant decreases in synthesis of Ach and ra:te of.Ach.turnover were measured in the hippocampus arid parietal cortex of rats receiving the dose of mecamylamine· affording cognitive-impairment in rats. Lower, beha,viorally-ineffective doses of mecamylamine, or hex.amethonium was not associated with significant changes in the same markers. These results provide ruther support for a role of the central nicotinic system in mnemonic processing and insight into biochemical mechanisms potentially ~derlying the observed behavioral consequences of pharmacological manipulation of the central nicotinic cholinergic system.
    • Being homeless : an ethnographic study of women's experiences in a shelter

      Hodnicki, Donna R.; School of Nursing (1992-04)
      This field research used ethnographic techniques to study women's experiences ~f homelessness while living in a shelter. A feminist approach which values women and the knowledge that women can share provided an orientating framework for this study. Data were collected by means of participant observation and in-depth, semi-structured interviews with 23 homeless women living in a shelter. A constant comparative analysis of the data yielded two major domains of the experiences of homelessness: Disc.onnected-Loss of Major Support and Rebuilding--The Regrouping of Assets. Themes within the first domain 1 included disaffiliation, significant loss, homelessness hurts, facing uncertainty, and being pressured. Themes within the second domain were heightened awareness, making adjustments, living with limitations, a period of growth, and taking a proactive stance. A model of the experiences of womens' homelessness in a shelter was developed. Women experience vulnerability throughout the homeless experience, but ,it is most intense whe11 the women are disconnected from major sources of support. Vulnerability lessens as the women begin to rebuild their lives. The women in this study exhibited a proactive behavior during Rebuilding which has not previously been described in the literature. The shelter used by the women in this study provided a "resource rich" environment that undoubtedly contributed to the women's proactivity and to Rebuilding.
    • Benefits of a coordinated system of community-based health care services for medically underserved children

      Hayes, Jill M.; School of Nursing (Augusta University, 1994-07)
      Access to health promotional services for children in the United States (U.S.) has become an issue of critical importance. Fifty percent of the U .S youth of today are at risk for drug and alcohol abuse, STD's, pregnancy, and injury or death from violence or accident. These health related risks often lead to an increase in school_ absenteeism and poor academic performance. The purpose of this study was the measurement of the benefits of improved access to health care for Medicaid eligible children. The academic and medical records of 143 children enrolled in an innovative program providing comprehensive health care services to Medicaid eligible children were reviewed. Demographic data were analyzed to identify any significant characteristics of study participants. Data on utilization of health services, absenteeism, overall health status, and academic performance were analyzed to determine if this population would benefit from improved access to health care .services. Four hypotheses were tested within the context of this study. All were stated in the null form and all were rejected. There was a significant increase in the use of wellness and illness services by participants. There was also a significant increase in the absenteeism rate of participants between Time 1 and 2, and Time 1 and 3. It was anticipated that absenteeism would decline as utilization increased. However, as participant utilization of services increased, absenteeism also increased. It was anticipated that academic performance would improve as utilization of health care services increased. However, academic performance declined as utilization increased. Finally, there was a significant change in the health status scores of participants between Time 2 and 3. In addition, any possible correlation between utilization of services and absenteeism, and utilization of services and academic performance were explored. Findings in this study represent significant changes in this population relative to the variables studied. Both utilization of services and health status improved following one year of enrollment in the Alliance. Absenteeism and academic performance declined for the same time period. Possible rationale for these findings and potential implications were discussed.