• Gamma-diketone neuropathy : evaluation of the energy hypothesis

      Pearson, Jerry K; Department of Anatomy (1988-12)
    • A Gata Ten Motif Found in the b-Globin LCR Possesses Insulator and Silencer Properties

      Ramchandran, Ramani; Department of Biochemistry and Molecular Biology (1997-08)
      In gene transfer experiments, transgene expression has been reported to be influenced by host sequences proximal to the integration sites. Such influences have been referred to as position effect of gene expression or position effect variegation (PEV) (Milot et al., 1996). The position effect (PEV) poses significant problems in the study of transgene regulation. However, studies on the human P-globin gene locus have shown that a 20 kb Locus Control Region (LCR) shields a as-linked transgene from position effects and thus confers position-independent expression of the transgene in transgenic mice (Grosveld et al., 1987). The LCR regulates the expression of the far downstream ay-linked P-like globin genes during erythroid development (Townes et al., 1985; Behringer et al., 1990; Enver et al., 1990). The 20 kb P-LCR is defined by four erythroid specific, DNase I hypersensitive sites, HS1, 2, 3, 4 and a unique HS5 site (Tuan et al., 1985; Forrester et al., 1987; Grosveld et al., 1987; Dhar et al., 1990). The unique HS5 site is located upstream of the HS 1-4 sites, at the apparent 5' border of the LCR (Tuan et al., 1985; Dhar et al., 1990). Like the boundary element of the chicken lysozyme gene (Steif et al., 1989), the HS5 site is located in a span of DNA found to be associated with the nuclear scaffold (Jarman et al., 1988). More recently, a 3 kb DNA fragment containing the HS5 site has been reported to possess insulator activity (Li et al., 1994; Yu et al., 1994). Insulators are DNA sequence elements that block activation of a promoter by an enhancer, but only when placed between them (Eissenberg et al., 1991). When placed upstream of an enhancer, an insulator shields transgene expression from position effects. HS5 fits this definition. When used to flank 5' or 3' of a transgene in transfected plasmids, the 3 kb HS5 fragment was capable of shielding the expression of the transgene from interference by host DNA proximal to the integration sites. Furthermore, when interposed between the promoter and enhancer of the transgene, the HS5 fragment was found to block enhancer-promoter communication, thus repressing the activity of the m-linked enhancer (Chung et al., 1993; Li et al., 1994). The properties of the HS5 fragment are similar to the insulator activity of the scs (Kellum et al., 1991; 1992) and gypsy (Cai and Levine, 1995; Roseman et al., 1993) elements of Drosophila and the A element of the chicken lysozyme gene locus (Steif et al., 1989). DNA Sequencing of the region between HS5 and HS4 has revealed a 40 bp DNA which consists of ten tandem GATA motifs found within 1 kb 3' of HS5 in the human genome (Figure 1). The (GATA)10 motif is unique in the 73 kb P-like globin gene domain, using a computer-aided analysis designed by Hardison et al. (1994). This (GATA)10 motif was named 5a. The question under study is whether or not the 5a sequence located proximal to HS5 contributes to the insulator function of HS5. In this study, we sought to characterize the function of 5a in recombinant plasmids, using transient and stable transfection assays. The experimental results show that: 1. When 5a was spliced either upstream or downstream of the HS2 enhancer in recombinant CAT plasmids, it repressed enhancer activity in erythroid K562 and HEL cells. 2. In non-erythroid N-Tera cells, 5a repressed HS2 enhancer activity when it was spliced upstream of the HS2 enhancer; however, 5a activated the HS2 enhancer when it was spliced downstream of the enhancer. 3. Further, the 5a sequence also possessed silencer activity (Brand et al., 1985). When spliced upstream of the promoter of the housekeeping phosphoglycerate kinase gene (Adra et al., 1987) in the enhancer-less plasmid, 5a did not activate but repressed promoter activity in both erythroid and non-erythroid cells. 4. Electrophoretic mobility shift assays using both K562 and N-Tera nuclear extracts showed that the 5a sequence is bound by the transcription factor GATA-1 but not detectably by GATA-2. 5. Also, mutation of the GATA motifs in the 5a sequence from a Head-Tail to a Head-Head orientation did not alter the function of the 5a sequence but affected the binding affinity for the GATA-1 transcription factor. The results suggest that in erythroid K562 and HEL cells the 5a sequence possesses both insulator and silencer activities and that transcription factor GATA-1 bound at 5a is a repressor of the cfr-linked promoter and the HS2 enhancer. From these findings we conclude that the 5a/GATA-l complex represses the activities of a proximal promoter and enhancer and contributes to the observed insulator activity of the HS5 fragment.
    • Gene-Environment Interaction Modulates Schizophrenic Endophenotypes in Heterozygous Reeler Mice

      Howell, Kristy R.; Department of Psychiatry and Health Behavior (2013-07)
      Aim 1: To determine the effect of chronic stress on the VEGF signaling pathway. Aim 2: To determine the effects of prenatal hypoxia on VEGF signaling, behavioral activities, blood flow, and brain volume in heterozygous reeler mice during early adulthood. Aim 3: To evaluate long lasting effects of prenatal hypoxia on VEGF signaling, behavioral activities, blood flow, and brain volume in heterozygous reeler mice. Aim 4: To determine the correlation between serum VEGF levels and brain volumes in schizophrenia subjects.
    • Genetic labeling reveals novel cellular targets of schizophrenia susceptibility gene ERBB4 and neuregulin-1 – ERBB4 signaling in monoamine neurons

      Bean, Jonathan C; Department of Neuroscience and Regenerative Medicine (2015)
      Neuregulin 1 (NRG1) and its receptor ErbB4 are schizophrenia risk genes. NRG1-ErbB4 signaling plays a critical role in neural development and regulates neurotransmission and synaptic plasticity. Nevertheless, its cellular targets remain controversial. ErbB4 was thought to be expressed in excitatory neurons although recent studies have disputed this view. Utilizing mice that express a fluorescent protein under the promoter of the ErbB4 gene, I determined in what cells ErbB4 is expressed and their identity. ErbB4 was widely expressed in the mouse brain, being highest in amygdala and cortex. Almost all ErbB4-positive cells were GABAergic in cortex, hippocampus, basal ganglia, and most of amygdala in neonatal and adult mice, suggesting GABAergic transmission as a major target of NRG1-ErbB4 signaling in these regions. Non-GABAergic, ErbB4-positive cells were present in thalamus, hypothalamus, midbrain and hindbrain. In particular, ErbB4 was expressed in both dopamine neurons in the substantia nigra and ventral tegmental area and in serotoninergic neurons of raphe nuclei, but not in norepinephrinergic neurons of the locus coeruleus. In hypothalamus, ErbB4 was present in neurons that express oxytocin. ErbB4 was expressed in a group of cells in the subcortical areas that are positive for S100β. These results identify novel cellular targets of NRG1-ErbB4 signaling. Finally, perfusion of NRG1 into the medial prefrontal cortex enhanced both dopamine and serotonin release but with differing time courses.
    • Genetic Modeling and Pathophysiological Analysis of FAM109A, a Putative Human Disease Gene

      Ates, Kristin Marie; Department of Neuroscience and Regenerative Medicine (Augusta University, 2019-05)
      A critical barrier in the treatment of endocytic diseases is the lack of information and understanding of the in vivo mechanisms of endocytosis. Part of this is due to the diverse array of endocytic adaptor proteins that have not yet been studied. We address this by investigating a key endocytic adaptor protein, FAM109A, which interacts with OCRL1, a causative gene for Lowe syndrome. Previous in vitro studies have identified FAM109A as a regulator for endosomal trafficking, particularly in the recycling of receptors in endosomes and sorting of cargo to lysosomes, based on knock-down studies. Here we conduct the first study into the developmental and physiological functions of FAM109A in vivo, utilizing the zebrafish model. We find that depletion of both zebrafish orthologs, zFAM109A and zFAM109B, in our maternal-zygotic homozygous mutant models (AB mutant) disrupts fluid-phase endocytosis and ciliogenesis in the pronephros. Partial knockdown of OCRL1 in the AB mutants exacerbates the endocytosis deficit, confirming that OCRL1 and FAM109 proteins are linked in a common endocytic pathway. In addition, we discover that zFAM109A/B mutant animals exhibit reduced jaw size and delay in chondrocyte maturation, indicating a novel role for zFAM109A and zFAM109B in craniofacial development. This is consistent with the phenotype in a patient within the NIH’s Undiagnosed Diseases Program (UDP). The UDP patient carries a de novo arginine (R) to cysteine (C) mutation (R6C) in FAM109A and presents with craniofacial abnormalities, developmental delay, auditory and vision impairments, and renal dysfunction. Expressing zFAM109A with the R6C mutation in zebrafish exacerbated craniofacial deficits, suggesting that the R6C allele acts in a dominant-negative manner. Together, these results show that FAM109A is involved in fluid-phase endocytosis and ciliogenesis in vivo. Moreover, we provide further insight into the potential pathogenesis of a UDP patient’s disease in association with a de novo mutation in FAM109A.
    • The Genetics of the Hemoglobins of the Domestic Goat

      Ray, Adams H.; Department of Cell and Molecular Biology (1970-09)
    • Genomic and Functional Analysis of Vesicular Inhibitory Amino Acid Transporter During Mouse Embryogenesis

      Oh, Won-Jong; Institute of Molecular Medicine and Genetics (2006-01)
      The specification of particular neuronal phenotypes during embryonic development requires the appropriate activation and regulation of genes encoding the proteins required for neurotransmitter synthesis, vesicular packaging and re-uptake from the synaptic cleft. Each neurotransmitter is packaged into synaptic vesicles by its own distinct vesicular transporter. In addition, neurotransmitter packaging is well controlled by other co-factors (reviewed in Ahnert-Hilger et al., 2003). Components of GABAergic neurons GABAergic neurons are the principal inhibitory neurons in the mammalian central nervous system (CNS), where GABA is synthesized from glutamate by two glutamate decarboxylases (GAD), namely GAD65 (Gad2) and GAD67 (Gad1) (Erlander et al., 1991). GABA is then loaded into synaptic vesicles by the vesicular inhibitory amino acid transporter (VIAAT, also known as VGAT). Four GABA transporters (GAT 1-4) are responsible for the re-uptake of GABA from the synaptic cleft through the plasma membrane. Inhibitory GABAergic transmission is mediated by binding of GABA to its ionotropic receptors, GABAA and GABAC, which are ligand-gated chloride channels, and its metabotropic receptor, GABAB (Fig. 1).
    • Genomic approaches towards understanding primary aldosteronism

      Hattangady, Namita G; Department of Physiology (2014-10)
      The human adrenal glands are complex endocrine organs that are physiologically located above the kidney. The cortex of the adrenal gland may be considered as a combination of three different steroidogenic tissue-types which form concentric zones within each adrenal. The three cortical zones include zona glomerulosa (ZG), zona fasciculata (ZF) and zona reticularis (ZR). Each zone, under independent regulation, produces unique steroid(s) which exhibit specific functions. The outermost ZG layer secretes the steroid, aldosterone due to ZG specific expression of aldosterone synthase (CYP11B2). Aldosterone regulates sodium reabsorption, and therefore, blood pressure. Aldosterone production is tightly regulated by the renin-angiotensin-aldosterone system. Thus, aldosterone levels are in direct proportion with renin levels. Other known physiological regulators of aldosterone production include serum K+ and adrenocorticotrophic hormone. A type of endocrine hypertension termed ‘Primary Aldosteronism’ (PA), is characterized by aldosterone secretion under suppressed renin levels. PA accounts for almost 10 % of hypertension. More recently, genetic mutations in an inward rectifying K+ channel (KCNJ5) that occur as both, somatic and germline cases, have been implicated in the pathology of PA. The goal of this dissertation is to define the role of KCNJ5 mutations in PA. In this dissertation, I will summarize my studies that describe the acute and chronic events involved in mutated KCNJ5 mediated aldosterone excess. In addition, I will define a novel mutation in KCNJ5 of germline nature identified at Georgia Regents University. Finally, I will also describe some interesting lessons we learnt from the expression of mutated KCNJ5 in primary cultures of human adrenals. The prevalence of a hereditary form of PA termed as Familial Hyperaldosteronism type III (FH III) is very rare. Thus far, only a few mutations in the KCNJ5 gene, including T158A, G151R, G151E and I157S, are confirmed as causing FH III, following Mendelian genetics. Perhaps the most interesting feature of this disease is the varied phenotype between the different mutations. T158A-affected patients present with massive hyperplasia and require bilateral adrenalectomy. In contrast, patients affected by the G151E mutation have more severe hypertension, although their adrenals are near normal in appearance. In this study we identify a new germline mutation (Y152C). The index case was a 61 year old woman who underwent unilateral adrenalectomy. The patient with the Y152C mutation exhibited a milder hypertension phenotype (like the G151E-affected patient) with extensive hyperplasia (as seen in the T158A-affected patient). In vitro analyses of the Y152C mutation indicated a pathology similar to other known mutations in KCNJ5, including change in conductance to Na+ ions and elevated calcium levels, and increase in CYP11B2 mRNA and aldosterone production. The inherent challenge presented by current studies utilizing constitutive expression of KCNJ5 mutations is the limitation in studying acute temporal events such as post translational modifications of steroidogenic enzymes and transcription factors. To address this issue, we generated a doxycycline inducible cell model system for the T158A harboring KCNJ5 transgene. Herein, we demonstrate a useful system that was amenable to the study of acute and chronic events involved in mutant-KCNJ5 mediated aldosterone excess. Our findings suggest that mutant KNCJ5 increases CYP11B2 expression through the activation of transcriptional activators of CYP11B2. Additionally, this is the first study to demonstrate that mutant KCNJ5 also activates steroidogenic acute regulatory protein (StAR) at the levels of translation and post translational phosphorylation. We also demonstrate calcium channel blocker, verapamil as an efficient blocker of mKCNJ5 mediated aldosterone production. Finally, one of the sharp advantages of our study was the use of primary cultures of human adrenal cells to confirm the effects of mutated KCNJ5. Interestingly, transduction of cells with constitutive viruses for mutant KCNJ5, confirmed an increase in KCNJ5 mRNA, although no change in CYP11B2 expression levels was observed. Pilot data including treatment of primary cells with calcium ionophores indicated that ZF/ZR cells may have a phenotype that is ‘muted’ for calcium mediated pathways. We could also speculate that this may disprove some current hypotheses that APA harboring KCNJ5 mutations may originate from the ZF. Overall, this study has improved our knowledge regarding the pathogenesis of PA caused by KCNJ5 mutations and has identified verapamil as a potentially effective therapeutic strategy in the inhibition of aldosterone excess in this type of PA.
    • GET THEM HERE: KEEP THEM HERE: A STUDY OF THE RECRUITMENT AND RETENTION OF BLACK STUDENTS AT GREENWOOD UNIVERSITY

      Hodges, Jamel Antwon; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Greenwood University, a Predominantly White Institution (PWI), has had difficulty recruiting Black students and retaining them throughout their undergraduate careers to graduation. Research shows the significant link between students’ perceptions of belonging and satisfaction at a university and their retention at that university. Race on a college campus is complex and requires intentional efforts to understand within the framework of higher education. The aim of this study is to determine specific causes that explain why Black students are not being recruited and retained at the same rate as their non-Black peers at Greenwood University. In doing so, the authors employed a mixed methods approach in which they conducted interviews from Black second and third year students, as well as faculty and staff, to explain the responses gathered from a recent Campus Climate Survey. A focus group of students also highlighted factors that impact the recruitment and retention of Black students. Among the responses received, factors such as support, connection, and representation among Black faculty and staff were shown to have a strong impact on Black students’ feelings of belonging, thus in many cases, their retention at Greenwood University. Based on the findings, it is recommended that universities prioritize intentional incentives to provide specialized support services and “spaces” for its students and to grow the numbers of faculty and staff who represent all of their institution’s student body. Keywords: enrollment, recruitment, retention, Black students, faculty, staff, Predominantly White Institution (PWI), Historically Black College or University (HBCU), Higher Education, Administrators
    • GET THEM HERE: KEEP THEM HERE: A STUDY OF THE RECRUITMENT AND RETENTION OF BLACK STUDENTS AT GREENWOOD UNIVERSITY

      Green, Garrett; Department of Advanced Studies and Innovation (Augusta University, 2019-05)
      Greenwood University, a Predominantly White Institution (PWI), has had difficulty recruiting Black students and retaining them throughout their undergraduate careers to graduation. Research shows the significant link between students’ perceptions of belonging and satisfaction at a university and their retention at that university. Race on a college campus is complex and requires intentional efforts to understand within the framework of higher education. The aim of this study is to determine specific causes that explain why Black students are not being recruited and retained at the same rate as their non-Black peers at Greenwood University. In doing so, the authors employed a mixed methods approach in which they conducted interviews from Black second and third year students, as well as faculty and staff, to explain the responses gathered from a recent Campus Climate Survey. A focus group of students also highlighted factors that impact the recruitment and retention of Black students. Among the responses received, factors such as support, connection, and representation among Black faculty and staff were shown to have a strong impact on Black students’ feelings of belonging, thus in many cases, their retention at Greenwood University. Based on the findings, it is recommended that universities prioritize intentional incentives to provide specialized support services and “spaces” for its students and to grow the numbers of faculty and staff who represent all of their institution’s student body. Keywords: enrollment, recruitment, retention, Black students, faculty, staff, Predominantly White Institution (PWI), Historically Black College or University (HBCU), Higher Education, Administrators
    • "Get Them Here: Keep Them Here: A Study of the Recruitment and Retention of Black Students at Greenwood University"

      Fisher, Jocelyn Stamps (Augusta University, 2019-05)
      Greenwood University, a Predominantly White Institution (PWI), has had difficulty recruiting Black students and retaining them throughout their undergraduate careers to graduation. Research shows the significant link between students’ perceptions of belonging and satisfaction at a university and their retention at that university. Race on a college campus is complex and requires intentional efforts to understand within the framework of higher education. The aim of this study is to determine specific causes that explain why Black students are not being recruited and retained at the same rate as their non-Black peers at Greenwood University. In doing so, the authors employed a mixed methods approach in which they conducted interviews from Black second and third year students, as well as faculty and staff, to explain the responses gathered from a recent Campus Climate Survey. A focus group of students also highlighted factors that impact the recruitment and retention of Black students. Among the responses received, factors such as support, connection, and representation among Black faculty and staff were shown to have a strong impact on Black students’ feelings of belonging, thus in many cases, their retention at Greenwood University. Based on the findings, it is recommended that universities prioritize intentional incentives to provide specialized support services and “spaces” for its students and to grow the numbers of faculty and staff who represent all of their institution’s student body. Keywords: enrollment, recruitment, retention, Black students, faculty, staff, Predominantly White Institution (PWI), Historically Black College or University (HBCU), Higher Education, Administrators
    • Glutamic Acid Decarboxylase Expression And Function In The Developing And Neonatal Mouse

      Maddox, Dennis M; Institute of Molecular Medicine and Genetics (2001-06)
      (First Paragraph) In the mouse, there are two distinct genes that encode isoforms of the enzyme glutamic acid decarboxylase (Gad). The G adl gene encodes the larger isoform that has a molecular mass of 67 kilodaltons and is termed "Gad67" (Erlander et al., 1991; Bu et al., 1992). The Gad2 gene encodes the other isoform that has a molecular mass of 65 kilodaltons and is termed "Gad65" (Erlander et al., 1991; Bu et al., 1992). These two isoforms are often co-expressed in GABAergic neurons (Feldblum et al., 1993; Esclapez et al., 1994; Katarova et al., 2000). The isoforms differ in subcellular localization, with Gad67 being found mainly in the soma and Gad65 being found mainly in axon terminals (Kaufman et al., 1991). Additionally, the two isoforms of Gad differ in their affinity for the required cofactor pyridoxal-5’-phosphate (PLP) (Kaufman et al., 1991). By catalyzing the decarboxylation of L-glutamic acid, the Gad enzymes are the rate-limiting step in the biosynthesis of y-aminobutyric acid (GABA) (Barker et al., 1998).
    • GPR109A as a Link Between Gut Flora and Colonic Health

      Cresci, Gail A.; Department of Biochemistry and Molecular Biology (2009-11)
      Hypothesis: The bacterial fermentation product butyrate, produced from undigested dietary polysaccharides by the normal colonic microbiota, is a ligand for GPR109A and plays an active role in epithelial biology and function in the intestinal tract. According to this hypothesis, the normal colonic microbiota promote intestinal and colonic health, and GPR109A provides a link between the gut flora and colonic/intestinal health. Aim 1: Study the expression and subcellular localization of GPR109A in intestinal epithelial cells in mice and humans. Aim 2: Compare the expression of GPR109A in the intestinal tract between control mice and germ-free mice. Aim 3: Investigate the physiologic functions of GPR109A in intestinal and colonic epithelial cells.
    • A Grounded Theory Study o f Pain Management Behaviors in Nurses Caring for Preverbal Children

      Noviello, Sheri R.; Department of Biobehavioral Nursing (2006-05)
      A qualitative study using the grounded theory method was used to explore factors that affect nurses’ pain management decision-making when caring for children between the ages o f 0 and 3 years. This study was approved by the Human Assurance Committee at Medical College o f Georgia prior to the collection of data. The sample consisted of eleven nurses who were employed at three different hospitals in the southeastern part of the United States. Theoretical sampling was the basis for the selection o f participants after the first two interviews. Interviews were transcribed verbatim and were subjected to open and axial coding. The constant comparative method was used during data analysis to identify a core category and related concepts. The basic social process that emerged is engaging in tactics o f pain management. This process contained two other processes: assessing fo r pain and managing a pain episode. Intrinsic factors that affected assessing fo r pain included knowing the territory, personal attributes o f the registered nurse (RN), being a parent, and being connected. Extrinsic factors that affected engaging in tactics o f pain management included workload and culture o f the hospital. The process of managing a pain episode included five phases: eliminating other sources o f discomfort, judging pain, comforting, medicating, and letting go.
    • Health Disparities in Acute Outcomes of Life-threatening Injury

      NeSmith, Elizabeth Grooms; Department of Nursing (2007-12)
      Health disparities have been documented in nearly all-leading causes of death. It is unknown if health disparities also exist in acute outcomes of life-threatening injury. The overall research question for this dissertation was, “Do health disparities exist in acute outcomes of life-threatening injury?”. Three studies were conducted: a state of science, a validity study, and a descriptive study. The state of the science showed that only 4 of 352 studies reported disparities, while 3 of 352 studies reported no disparities. The validity study was a retrospective chart review and showed that the instrument used to measure systemic inflammatory response syndrome was valid in predicting intensive care unit length of stay (F = 15.83) p < .0001. Caucasian race also predicted intensive care unit length of stay (F = 9.7) p = .002. When combined with race, the systemic inflammatory response syndrome instrument explained more variance (R2 = .15) in intensive care unit length of stay than either variable alone (F = 7.7) p = .006. The descriptive study utilized the same data set from the validity study, and showed fewer occurrences of systemic inflammatory response syndrome in African Americans than in Caucasians (T = 9949.5) p = .04; in adults 30-44 years old than in adults 18-29 (T = 13,654) p = .04; and in ethyl alcohol users than in all other substance users (X2 = 7.85) p = .005. There was less severity of systemic inflammatory response syndrome in females than in males (T = 7,491.5) p = .03; and in marijuana users than in all other substance users (T = 3,117) p = .02. More severity of systemic inflammatory response syndrome was found among ethyl alcohol users than in all other substance users (T = 2,667) p = .0008. Results support that health disparities exist among different patient groups according to race, age, sex, and substance use for systemic inflammatory response syndrome. More research is needed to determine if these disparities translate to increased risk for poor outcomes. Implications for practice include increased vigilance of different patient groups based on occurrence and severity of systemic inflammatory response syndrome.
    • Health Needs of Older Adult Women in the Rural Environment

      Conway, Mary Ann; Department of Nursing (1983-12)
      This study addressed the following research questions: 1). What are the perceived health needs of older warren in the rural environment? 2) Are. there correlations between perceived health needs .and demographic ' ' . . and sociological variables related to. these needs? The descriptive survey utilized a purposive convenience sample of 14 wanen between the I ages of 66 and 79 •. Half were black, half were white. In-hare interviews were c?nducted by the investigator utilizing. a structured . inter...: view questionnaire to collect demographic data and infonnation regarding ·five ·areas of ·health need: . health· condition, functional status,· social interaction, accessibility o~ health care and service· need •. findings revealed that rrore than half the subjects were widowed. Half ·lived alone. ·.The majority ·had inadequate incanes. A relationship between race a.n.d incane, education, self-rated health, life satisfaction, health condition and functional status was noted.. The ma.jority of the health needs. related to physical functioning and chronic' conditions. Blacks and ~ose 75 or over had rrore·chronic conditions, recent illness and physical ·symptoms and used rrore p~escription.drugs than did whites. Blacks and those under 75 reported rrore activity limitations and disability days than whites and those 75 or over. The black ~espo!fdents and. those 75 or over were less healthy than ·the whites and those under 75. The potential for accidental misuse of rredications is increased among this sample as is the possibility of physical· canplications due to inactivity and lack of exercise. A need . for· health educatio:n programs and health prorrotion, maintenance ~d restorative services targeted to this· population ~s noted.
    • Health-Promoting Lifestyles of Women with HIV Disease

      Carr, Rebecca L.; Department of Physiological and Technological Nursing (1997-04)
      Women are one of the fastest growing risk groups for HIV infection in the United States, but little is known about how women manage the problems and concerns commonly faced by individuals who are HIV positive. HIV disease results in compromised lifestyles for women as they cope with physiological and psychosocial problems that accompany this disease. The purpose of this focused ethnography was to explore health-promoting lifestyles of women with HIV disease. Research questions guiding this study were: 1) What do women with HIV disease believe they can do to enhance and/or maintain their health after diagnosis? and 2) How do women promote and maintain their health and well-being? Purposive sampling was used to obtain nine European American participants between the ages of 27 and 52 years. These participants were recruited from the southeastern United States. Semi-structured interviews and observation participation were used to obtain data. The majority of participants were interviewed three times. Observation participation occurred during interviews, at conferences, and volunteer group meetings attended by the researcher and the participants. Data analysis was concurrent with data collection enabling the researcher to confirm her interpretations with the participants. Three major themes were identified: 1) Reaching out to others, 2) Searching for meaning, and 3) Buying time. These themes constituted a health-promoting lifestyle that enabled women to adjust to the change in their identity from a healthy person to a person with HIV disease. Initially, women focused on restoring their well-being, but later initiated changes to enhance, maintain, and maximize their health.
    • Health-Promoting Lifestyles of Women with HIV Disease

      Carr, Rebecca Lamb; School of Graduate Studies (1997-04)
      Women are one of the fastest growing risk groups for HIV infection in the United States, but little is known about how women manage the problems and concerns commonly faced by individuals who are HIV positive. HIV disease results in compromised lifestyles for women as they cope with physiological and psychosocial problems that accompany this disease. The purpose of this focused ethnography was to explore health-promoting lifestyles of women with HIV disease. Research questions guiding this study were: 1) What do women with HIV disease believe they can do to enhance and/or maintain their health after diagnosis? and 2) How do women promote and maintain their health and well-being? Purposive sampling was used to obtain nine European American participants between the ages of 27 and 52 years. These participants were recruited from the southeastern United States. Semi-structured interviews and observation participation were used to obtain data. The majority of participants were interviewed three times. Observation participation occurred during interviews, at conferences; and volunteer group meetings attended by the researcher and the participants. Data analysis was concurrent with data collection enabling the researcher to confirm her interpretations with the participants. Three major themes were identified: 1) Reaching out to others, 2) Searching for meaning, and 3) Buying time. These themes constituted a health-promoting lifestyle that enabled women to adjust to the change in their identity from a healthy person to a person with HIV disease. Initially, women focused on restoring their well-being, but later initiated changes to enhance, maintain, and maximize their health. INDEX WORDS: HIV disease, Women, Stigma, Self-in-relation, Health-promoting lifestyle, Health behavior, Health belief
    • Heat shock protein 70 promotes HCC by modulating DNA-damage response, MAPK/ERK signaling and cellular senescence

      Wang, Yan; Department of Biochemistry and Molecular Biology (2015-10)
      The mechanisms that drive hepatocellular carcinoma (HCC) development are not well understood. Heat shock protein 70 (HSP70) plays a critical role in protein quality control. The HSP70-mediated response has been implicated in the development of different cancer types, however, the detailed mechanisms by which HSP70 supports tumor progression remains to be investigated. In this research work we observed that HSP70 deletion impairs HCC development by modulating the carcinogen-induced DNA damage response. This results in increased sensitivity to p53-dependent apoptosis, activation of MAPK/ERK negative feedback signaling pathway, and induction of cellular senescence. Inactivation of HSP70 may be a strategy to interfere with signaling pathways that drive liver cancer progression thus offering a therapeutic possibility for human HCC treatment. Note: The research data described in this Ph.D. Thesis are not published. Additional experimental work is needed to verify the data and solidify the mechanistic conclusions of this work before we seek publication of the data in a peer reviewed scientific journal. In light of new data generated from additional studies, we may need to modify or revised our mechanistic conclusions.
    • Heat Shock Protein 70I Promotes Carcinogen-induced Liver Tumorigenesis by Regulating Hepatic Metabolism and Insulin Sensitivity

      Cho, Wonkyoung; Department of Biochemistry and Molecular Biology (2011-12)
      Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in the world. The treatment options for HCC, however are very limited. In mice, the carcinogen diethylnitrosamine (DEN) induces HCC, which has been proven to be comparable to human HCC in many key aspects. DEN-induced HCC leads to initial hepatocyte death followed by compensatory proliferation and inflammatory response. The cycles of hepatocyte death and compensatory proliferation eventually lead to genomic mutations and HCC development. The inducible heat shock protein-HSP70 (HSP70i) is overexpressed in a number of malignancies, including liver cancer. Tumor cells have metabolic changes which producing intermediates for cell growth and division. We hypothesize that HSP70i plays a role in HCC development through its control of glucose metabolism. To determine the impact of HSP70i in HCC, we treated a cohort of wild-type and hsp70i-deficient mice using the carcinogen DEN. Tumor development in the liver was examined after 8 months. Results show that the deletion of hsp70i leads to a significant delay in HCC development. DEN-treated hsp70i-/- mice exhibit reduced levels of alanine aminotransferase (ALT) and asparate aminotransferase (AST) in the serum compared to wild-type (WT) mice, suggesting reduced liver damage in hsp70i-/- mice. Furthermore, to investigate the mechanisms underlying HSP70i inhibition of tumorigenesis, we performed TUNEL assays to detect hepatocyte death, and Ki67 immunostaining to detect hepatocyte proliferation. As expected, hsp70i-/- mice exhibit a lower level of cell death and lower levels of cellular proliferations compared to wild-type mice. In addition, hsp70i-/- mice exhibit increased glucose consumption as evident by an increase in key enzymes involved in both glycolysis and TCA cycle. Low net glucose production induces lower lipid accumulation. Finally, treatment of DEN-treated wild-type mice with 2-phenylethynesulfonamid (PES), which is an HSP70i specific inhibitor, also delays HCC development. Overall, the alterations in the metabolic pathways in hsp70i null mice appear to contribute to delayed HCC development. Therefore, we conclude that HSP70i can be a powerful therapeutic target for HCC.