• 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.
    • Healthy aging and disease: role for telomere biology?

      Zhu, Haidong; Belcher, Matthew; van der Harst, Pim; Department of Pediatrics; Georgia Institute for Prevention of Human Diseases and Accidents (2011-05-1)
      Aging is a biological process that affects most cells, organisms and species. Human aging is associated with increased susceptibility to a variety of chronic diseases, including cardiovascular disease, Type 2 diabetes, neurological diseases and cancer. Despite the remarkable progress made during the last two decades, our understanding of the biology of aging remains incomplete. Telomere biology has recently emerged as an important player in the aging and disease process.
    • 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.
    • Heat shock response in CHO mammalian cells is controlled by a nonlinear stochastic process.

      Lipan, Ovidiu; Navenot, Jean-Marc; Wang, Zixuan; Huang, Lei; Peiper, Stephen C; Department of Pathology; GHSU Cancer Center; Immunotherapy Center; Department of Radiology; Center for Molecular Chaperone/Radiobiology & Cancer Virology (2007-10-30)
      In many biological systems, the interactions that describe the coupling between different units in a genetic network are nonlinear and stochastic. We study the interplay between stochasticity and nonlinearity using the responses of Chinese hamster ovary (CHO) mammalian cells to different temperature shocks. The experimental data show that the mean value response of a cell population can be described by a mathematical expression (empirical law) which is valid for a large range of heat shock conditions. A nonlinear stochastic theoretical model was developed that explains the empirical law for the mean response. Moreover, the theoretical model predicts a specific biological probability distribution of responses for a cell population. The prediction was experimentally confirmed by measurements at the single-cell level. The computational approach can be used to study other nonlinear stochastic biological phenomena.
    • hElp3 Directly Modulates the Expression of HSP70 Gene in HeLa Cells via HAT Activity

      Li, Fen; Ma, Jixian; Ma, Yu; Hu, Yanyan; Tian, Shujuan; White, Richard E.; Han, Guichun; Department of Pharmacology and Toxicology (2011-12-21)
      Human Elongator complex, which plays a key role in transcript elongation in vitro assay, is incredibly similar in either components or function to its yeast counterpart. However, there are only a few studies focusing on its target gene characterization in vivo. We studied the effect of down-regulation of the human elongation protein 3 (hELP3) on the expression of HSP70 through antisense strategy. Transfecting antisense plasmid p1107 into HeLa cells highly suppressed hELP3 expression, and substantially reduced expression of HSP70 mRNA and protein. Furthermore, chromatin immunoprecipitation assay (ChIP Assay) revealed that hElp3 participates in the transcription elongation of HSPA1A in HeLa cells. Finally, complementation and ChIP Assay in yeast showed that hElp3 can not only complement the growth and slow activation of HSP70 (SSA3) gene transcription, but also directly regulates the transcription of SSA3. On the contrary, these functions are lost when the HAT domain is deleted from hElp3. These data suggest that hElp3 can regulate the transcription of HSP70 gene, and the HAT domain of hElp3 is essential for this function. These findings now provide novel insights and evidence of the functions of hELP3 in human cells.
    • Henry Roberts: A Case Study in Mental Illness in Eighteenth-Century England

      Johnston, Steven; Department of History, Anthropology, & Philosophy (Augusta University, 2017-12)
    • HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent

      Qiao, Jingjuan; Li, Shunyi; Wei, Lixia; Jiang, Jie; Long, Robert; Mao, Hui; Wei, Ling; Wang, Liya; Yang, Hua; Grossniklaus, Hans E.; et al. (2011-03-24)
      The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomarker for various cancer types and a drug target for anti-cancer therapies. This multimodal HER20targeted MR imaging probe integrates a de novo designed protein contrast agent with a high affinity HER2 affibody and a near IR fluorescent dye. Our probe can differentially monitor tumors with different expression levels of HER2 in both human cell lines and xenograft mice models. In addition to its 100-fold higher dose efficiency compared to clinically approved non-targeting contrast agent DTPA, our developed agent also exhibits advantages in crossing the endothelial boundary, tissue distribution, and tumor tissue retention over reported contrast agents as demonstrated by even distribution of the imaging probe across the entire tumor mass. This contrast agent will provide a powerful tool for quantitative assessment of molecular markers, and improved resolution for diagnosis, prognosis and drug discovery.
    • High glucose treated cells may lead to cellular senescence effecting function of bladder

      Vincent, Julie; Klee, Nicole; Webb, Clinton; Department of Physiology; College of Education; Klee, Nicole; Department of Physiology; Webb, Clinton; Augusta University (2018-02-12)
      Introduction: Diabetic bladder dysfunctioneffects 30-50% of all diabetespatientsand is characterized by symptoms of overactive and underactive bladder, which greatly effects quality of life.Diabetes is correlated with increased cellular senescence. Senescence is a physiologic phenomenon; however, chronic high levels can lead to tissue dysfunction. Multiple in vitrostudies have shown that high glucose exposure results in an increase in cellular senescent cells.The smooth muscle layer of the bladderis responsible for contraction and relaxation of the bladder; therefore, we hypothesize that primary bladder smooth muscle cells exposed to a high glucose environment will result in an increased number of cellular senescent cells.Methods:Rat primary BSMcells were incubated in normal glucose (4mM), high glucose (22mM), high mannitol (22mM), and bleomycin(+ control). Abeta-galactoside assay was utilized to visualize the presence of senescent cells.Results: Cells treated with high glucose exhibited increased cellular senescent cellscompared to both normal and high mannitol control. Conclusion: We conclude that high glucose exposure increases cellular senescence in primary bladder smooth muscle cells. An increased amount of cellular senescence within the smooth muscle layer of the bladder could contribute to bladder dysfunction as seen with diabetes.
    • High Speed Two-Photon Imaging of Calcium Dynamics in Dendritic Spines: Consequences for Spine Calcium Kinetics and Buffer Capacity

      Cornelisse, L. Niels; van Elburg, Ronald A. J.; Meredith, Rhiannon M.; Yuste, Rafael; Mansvelder, Huibert D.; Mei, Lin; Department of Neurology; College of Graduate Studies (2007-10-24)
      Rapid calcium concentration changes in postsynaptic structures are crucial for synaptic plasticity. Thus far, the determinants of postsynaptic calcium dynamics have been studied predominantly based on the decay kinetics of calcium transients. Calcium rise times in spines in response to single action potentials (AP) are almost never measured due to technical limitations, but they could be crucial for synaptic plasticity. With high-speed, precisely-targeted, two-photon point imaging we measured both calcium rise and decay kinetics in spines and secondary dendrites in neocortical pyramidal neurons. We found that both rise and decay kinetics of changes in calcium-indicator fluorescence are about twice as fast in spines. During AP trains, spine calcium changes follow each AP, but not in dendrites. Apart from the higher surface-to-volume ratio (SVR), we observed that neocortical dendritic spines have a markedly smaller endogenous buffer capacity with respect to their parental dendrites. Calcium influx time course and calcium extrusion rate were both in the same range for spines and dendrites when fitted with a dynamic multi-compartment model that included calcium binding kinetics and diffusion. In a subsequent analysis we used this model to investigate which parameters are critical determinants in spine calcium dynamics. The model confirmed the experimental findings: a higher SVR is not sufficient by itself to explain the faster rise time kinetics in spines, but only when paired with a lower buffer capacity in spines. Simulations at zero calcium-dye conditions show that calmodulin is more efficiently activated in spines, which indicates that spine morphology and buffering conditions in neocortical spines favor synaptic plasticity.
    • High-intensity Treatment & Weight Reduction Goal Achievement with MOVE!®

      Garvin, Jane (2015-02)
      Purpose: The purpose of this study was to examine weight reduction and high-intensity treatment at 6 months after enrolling in the local MOVE!® program.
    • High-mobility group box-1 and biomarkers of inflammation in the vitreous from patients with proliferative diabetic retinopathy

      El-Asrar, Ahmed M. Abu; Nawaz, Mohd Imtiaz; Kangave, Dustan; Geboes, Karel; Ola, Mohammad Shamsul; Ahmad, Saif; Al-Shabrawey, Mohamed; Department of Oral Biology; Department of Ophthalmology (2011-07-06)
      Purpose: To measure levels of high-mobility group box −1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the levels of the inflammatory biomarkers monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-1β (IL-1β), and granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, we examined the expression of HMGB1 in the retinas of diabetic mice.
    • Histological Analysis of Microbial Colonization and Osteoclastic Activity in Bisphosphonate-Treated Rats

      Daoudi, Asma; Department of Biological Sciences (Augusta University, 2015-05)
      Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is an untreatable disease characterized by the presence of exposed, non-vital bone in the oral cavity, following dental procedures with a history of bisphosphonate (BP) therapy. This study compared two regimens of zoledronic acid (ZA) regimens with respect to the induction of clinical features of BRONJ. We hypothesized that, in the treated animals in both models, 1) alveolar bone would show impaired osteoclast (bone-removing cell) activity, 2) this impairment would be more profound at higher doses of BPs, and 3) there would be an increase in microbial colonization at the extraction site. The study involved 100 female Sprague-Dawley rats: 30 were treated with 80μg/kg of intravenous ZA weekly for 13 weeks, 20 with 150μg/kg ZA daily for 16 consecutive days, and 50 with corresponding saline injections. The injections were followed by extraction of the first and second molar teeth (extraction has been known to trigger bone necrosis in bisphosphonatetreated patients). We examined osteoclast and bacterial distribution at one and eight weeks post extraction, using Tartrate-Resistant Acid Phosphatase (TRAP) and Brown and Brenn staining, respectively. The TRAP results indicated a significant decline in osteoclast activity in the treatment groups at 1 week post-extraction compared to the controls. When compared to the clinical dose, the higher dose had more pronounced a decline in the osteoclast recruitment in the treated animals at 8 weeks post-extractions. There was no significant difference in bacterial\ colonization between groups; however, we detected an increase in fungal colonization in the treated animals compared to the controls. The results of this study suggest the legitimacy of considering both animal models for further investigation of BRONJ mechanisms.
    • Histology of the Dental Extraction Sites of Bisphosphonate Treated Rats

      Ferguson, Alisa; Department of Oral Biology and Diagnostic Sciences (Augusta University, 2018-12)
      Bisphosphonate is a drug given to both men and women who are experiencing decreasing bone density and strength. When patients taking bisphosphonate undergo some sort of jaw trauma (i.e. tooth extraction, accident), they can experience necrosis or cell death of the jawbone. Our hypothesis is that bisphosphonate molecules bound to the bone matrix contribute to bone necrosis. For my thesis, a histological analysis of the mandibles from bisphosphonate treated rats after dental extraction with and without removal of bisphosphonates from the extraction site of the bone was done. Histological sections of the jaw from bisphosphonate treated rats after bilateral extraction of the first and second molar teeth were taken. On one side, the extraction site was treated with EDTA to chelate bisphosphonates from the bony wall of the tooth socket. The other side of the rat’s jaw was treated with Saline. I then evaluated the vitality of alveolar bone by counting the number of dead versus live osteocytes around the extraction site and comparing the ratios between the chelated and un-chelated sides from each rat. The study determined whether removal of localized bisphosphonates is beneficial to preserve bone vitality after dental extraction. As expected, the percentage of live osteocytes decreased in the alveolar bone of animals treated with Zoledronate (ZA), a strong dose of bisphosphonate. Furthermore, there was a trend of increased percentage of live cells when EDTA was used, although the differences were not statistically significant. These results support other studies in our laboratory that have shown that localized bisphosphonates play a role in the osteonecrosis associated with ZA treatment. It, therefore, provides evidence that localized bisphosphonates contribute to the etiology of bone necrosis in patients undergoing bisphosphonate treatment.
    • The Historical Emergence of Art Therapy, its Modern Day Usage, and Possible Alternative Application

      Owen, Connor; Department of Communication (Augusta University, 2020-05)
      This paper focuses on the evolution of art therapy from the founding of the field of Psychology under Freud to the current day’s use in a variety of populations. Art therapy is defined by the American Art Therapy Association as “an integrative mental health and human services profession that enriches the lives of individuals, families, and communities through active art-making, creative process, applied psychological theory, and human experience within a psychotherapeutic relationship.” (AATA, 2020) Art therapy falls within the field of client or patient based approaches with the addition of creative work. The paper also addresses a need in research surrounding effectiveness for college-aged students. It is important to note that in the research there appears to be two broad thought currents that descend from Jung’s research and reconvene as modern art therapy, leading to differing opinions on its path from conception to modern use. The paths are one of theoretical philosophy based interventions and practical handson approaches ultimately both utilizing art making as therapeutic practice.
    • HIV screening performance using third generation enzyme linked immunosorbent assay compared to fourth-generation electrochemiluminescence immunoassay

      Chae, Jung Hee; Grunnet, Kerrie; Laney, Dan; Phelps, Taylor; Steine, Martin; Yoo, Se (2015-03-09)
      Should fourth-generation electrochemiluminescence immunoassay (ChIA) be used over third-generation enzyme linked immunosorbent assay (EIA) for HIV screening patients in multiethnic region of China?

      Ajith, Ashwin; Biomedical Sciences (Augusta University, 2019-12)
      Solid organ transplantation is the preferred therapy for many patients diagnosed with end stage organ failure, however allograft rejection is a significant barrier for graft survival. Patient care involves heavy immunosuppressive drug treatment leading to elevated risk for cancer and other opportunistic infections. Hence there is a need to develop effective alternative approaches to minimize graft rejection. We focused on Human leukocyte antigen G (HLA-G), a nonclassical HLA class Ib molecule critically involved in the maintenance of maternal tolerance to semi-allogeneic fetal tissues during pregnancy and has emerged as a potential therapeutic target to control allograft rejection. We demonstrate here that the level of soluble HLA-G dimer was higher in a group of 90 patients with a functioning renal allograft compared with 40 patients who rejected (RJ) their transplants. The HLA-G dimer level was not affected by demographic status. One of the potential mechanisms in tissue organ allograft rejection involves the induction of granzymes and perforin, which are the main effector molecules expressed by CD8+ cytotoxic T lymphocytes and function to destroy allogeneic transplants. Using genomics, molecular and cellular analyses of cells from T-cell–mediated RJ and nonrejected kidney transplant patients, cells from leukocyte Ig-like receptor B1 (LILRB1) transgenic mice, humanized mice, and genetically engineered HLA-G dimer, we demonstrated a novel mechanism by which HLA-G dimer inhibits activation and cytotoxic capabilities of human CD8+ T cells. This mechanism implicated the downregulation of Granzyme B expression and the essential involvement of LILRB1. Thus, HLA-G dimer has the potential to be a specific and effective therapy for prevention of allograft rejection and prolongation of graft survival.
    • HMGB1-TLR4 Signaling Following Traumatic Brain Injury

      Laird, Melissa D; Department of Neurosurgery (2011-05)
      Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Although preventative measures may reduce the incidence of TBI, over 1.7 million Americans suffer a head injury annually1. Brain edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP), brain herniation, and a poor prognosis following head injury2"4. Clinically, the degree of swelling on the first computed tomography (CT) scan directly correlates with patient outcome, demonstrating the need to limit brain edema following head injury5. Unfortunately, current medical therapies do not effectively control brain edema and neurosurgical approaches to alleviate increased ICP are invasive and of limited utility. A longrange goal of our laboratory is to elucidate the molecular and cellular mechanisms that promote cerebral edema, which may aid in the development of novel therapeutics for head trauma patients. A central premise of our hypothesis is that activation of Toll-like receptor 4 (TLR4) increases brain edema following TBI. Toll-like receptors (TLR) are membrane proteins within the interleukin-1 receptor superfamily that mediate innate immunity6"8; however, recent evidence suggests TLR are also expressed within the CNS of humans and rodents9"12. Activation of TLR4 exacerbated neuronal injury and neuroinflammation following cerebral ischemia13,14, although the involvement of TLR4 following TBI has only just begun to be examined and comparatively little is known15,16. Given the association between inflammation, neurological injury, and patient outcome17, TLR4 may represent an unexplored therapeutic target following TBI. We hypothesize that High Mobility Group Box Protein B1 (HMGB1), a putative endogenous ligand forTLR4, is released via an NR2B mechanism and promotes cellular edema following TBI.
    • Homer1a-Dependent Crosstalk Between NMDA and Metabotropic Glutamate Receptors in Mouse Neurons

      Bertaso, Federica; Roussignol, Gautier; Worley, Paul; Bockaert, Joël; Fagni, Laurent; Ango, Fabrice; Mei, Lin; Department of Neurology; College of Graduate Studies (2010-03-18)