• Ultrastructural and functional effects of dimethylsulfoxide (DMSO) in the isolated kidney

      Jeske, Arthur Herbert; Department of Pharmacology and Toxicology (1975-06)
    • Ultrastructure of the crown cells of stingrays (Genus Dasyatis)

      Crandall, Wilson T; Department of Anatomy (1970-05)
    • Understanding african american women church members' health decision-making and described behavior: a qualitative inquiry

      McCall, Amber Brown; College of Graduate Studies (2011-12)
      This' dissertation described the processes that African-American women church members used to make health decisions and investigated the experiences and perceptions that faith had on this cohort's health beliefs. African-American women historically have suffered disproportionately from health disparities, and African-American women church members have played a central role as their families' primary caregiver. It is perceived that faith-based interventions can be effective at reducing health disparities. However, there is little understanding of the impact on the health decision-making process. By . undertaking an investigation into this process in a cohort of African-American women church members, this study incorporated and advanced nursing theories used to guide the development of risk-reduction interventions through describing and delineating the role of faith-based health decision-making. A purposive, intensity sample of eleven African-American women church members were recruited to participate. . Naturalistic inquiry methodology was used to analyze the interview data, answering the following questions: 1) What process(es) do African-American women church members use to make health decisions, and what health behaviors do these women describe? 2) What is the role of faith (if any) in the health beliefs of African-American . women church members? VI The results indicated religious faith was integrated throughout the health decisionmaking process; additionally, three overarching processes were used by the study subjects, which are described herein as: 1) Believing in God, 2) Empowering Self, and . 3) Using Resources. This demonstrated that their faith was a major influence in the lives participants and that faith impacted their competence and ability to be empowered and resourceful-as well as influenced health decision-making. Due to the targeted, purposive sampling methods along with.the qualitative nature of the data obtained from study participant interviews, these research results cannot be generalized to the genera~ population of African-American women. Nevertheless, understanding the process of health decision~making in this sample may be important to enabling researchers, clinicians and clergy to promote further research regarding the interplay of faith in health decision-making, risk reduction activities, and quality of life. The implications for nursing theory, practice and research, and empowering the community are included, and provide the essential foundation for this study.
    • Understanding the role of RAD51AP1 in tumor growth and progression

      Bridges, Allison Elaine; Biomedical Sciences (Augusta University, 2019-05)
      Although much progress has been made in recent years in treatment and prevention, cancer is still the second leading cause of death in the United States. Surgical removal of the tumor is not possible in all cancer types. Therefore, chemotherapy and radiation therapy have become the standard course of treatment and are often the only option for late stage and metastatic tumors. Unfortunately, chemotherapy and radiation therapy resistance are the greatest challenge for physicians trying to eradicate disease, prevent tumor recurrence, and inhibit distant metastasis. This resistance is derived from a heterogeneous population of cells within the tumor known as cancer stem cells (CSCs). CSCs are able to maintain a higher capacity for self-renewal due to an efficient DNA repair system. RAD51-associated protein 1 (RAD51AP1), which is responsible for the successful resolution of double-strand breaks during DNA repair, is overexpressed in wide variety of human cancers. The present study sought to determine the functional role of RAD51AP1 in CSC self-renewal and its relevance to tumor growth and progression and also drug resistance. Our studies provide evidence that RAD51AP1 plays a critical role in CSC self-renewal and maintenance in breast, lung, and colon cancers. To determine the functional role of RAD51AP1 in cancer growth and progression, we generated genetically engineered mouse models in breast, lung, and colon cancer in wild-type Rad51ap1+/+ and knockout Rad51ap1-/- background. In breast and lung cancer models, Rad51ap1 deletion significantly delayed the time of tumor formation and distant metastases, in parallel decreasing the self-renewal capacity of CSCs from each model. Furthermore, to investigate the functional role of RAD51AP1 in colon cancer growth, we utilized AOM/DSS and ApcMin/+ models of colon cancer and found smaller tumor burden along with reduced CSC self-renewal in knockout mice compared to wild-type. Taken together, these data provide evidence that RAD51AP1 plays a critical role in CSC self-renewal in different human cancers and RAD51AP1 could be a novel therapeutic target for cancer prevention and treatment.
    • Understanding Unilateral Scapular Dyskinesis in Asymptomatic Individuals Established by the Scapular Dyskinesis Test

      Ramiscal, Lawrence; Advanced Studies Innovation (Augusta University, 2021-05)
      Background: Scapular dyskinesis (SDK) is a controversial phenomenon that is thought to be an impaired movement with altered scapular muscle activity requiring intervention. Clinicians of all levels identify SDK via the Yes/No method of the Scapular Dyskinesis Test (Y/N SDT). Purpose & Methods: To date, the YN/SDT has neither been established as reliable nor valid against the electromyography (EMG) when used in healthy individuals. Also, researchers have not examined scapular muscle activity in asymptomatic individuals with SDK. Experiment 1 determined the reliability of the Y/N SDT in individuals with asymptomatic SDK between student and expert physical therapists via an intra- and inter-rater reliability design. Experiment 2 determined the construct validity of the Y/N SDT in symmetrical and asymmetrical asymptomatic individuals using EMG as the reference standard utilizing known-groups validity design. Experiment 3 characterized the scapular muscle activities of asymptomatic unilateral SDK established by the Y/N SDT through repeated measures design. Results: Experiment 1: The Y/N SDT was reliable when used by either students or experts. Students' reliability averaged 20 percentage points less than experts. Experiment 2: The overall accuracy in identifying shoulder asymmetries in asymptomatic individuals against the EMG reference was poor. Sensitivity and specificity were 56% and 36%, respectively; positive and negative predictive values were 68% and 25%; positive and negative likelihood ratios were 0.87 and 1.22. Experiment 3: There was no difference in EMG activities between subjects based on the Y/N SDT. Overall, high muscle variability was observed during the experiments. Conclusion: The Y/N SDT did not appear to have clinical value, therefore, may not be useful in screening SDK in healthy individuals. Hand-dominance may be considered for shoulder rehab wherein the dominant shoulder might respond with endurance exercises while nondominant may benefit from strength training with priority to the serratus anterior muscle. It appears that scapular muscles are likely not synergists as the study failed to find temporal relationships among the muscle activities. Overall, SDK may not be a movement impairment. It may simply be a normal variability that may be ignored or could possibly be a helpful adaptation to achieve shoulder function that should be encouraged. In light of the results of the study, traditional biomechanical theories in understanding SDK did not appear helpful. Exploration of other models like motor control theories in understanding unfamiliar human movements may be considered.
    • Unplanned pregnancy and elective abortion for african-american adolescents

      Andrews, Janet L.; Medical College of Georgia (1997-03)
      The purpose OI this focused ethnography was to generate an interpretive theory about how African American adolescents experience unplanned pregnancy and elective abortion. How African American adolescents experience events and circumstances surrounding pregnancy and elective abortion is not understood. Research questions were: 1) How do African American adolescents view unplanned pregnancy?; 2) How do African American adolescents go about deciding to seek abortions?; and 3) What factors do they consider when making their decisions to abort their pregnancies? Purposive sampling was used to obtain a sample of 12 participants within the ages of 15 to 18 years. Participants were drawn from clients at a nonprofit clinic designed to provide women's health services including abortion. Data were Collected by continuous interviews and observation participation. First interviews took place as the participants awaited their abortion procedures. Second interviews were conducted at a time and place convenient for the participants. Four themes were generated during data analysis: 1) Relationships with partners, 2) ·Confiding·in others: finding support, 3) Unselfish decision for self and 4) Resolution of the crisis. The integral pattern of Empowerment:~: emerged from the four themes. Through their experiences with unplanned pregnancy and elective abortion.
    • UNRAVELING THE COMPLEX INTERPLAY BETWEEN HEAT-SHOCK TRANSCRIPTION FACTOR 1 (HSF1) NETWORKS AND T-CELL METABOLIC REPROGRAMMING IN ANTI-TUMOR IMMUNITY

      Pandya, Bhaumik Dineshchandra; Biomedical Sciences (Augusta University, 2021-03)
      Heat Shock Factor 1 (HSF1) is transcriptionally activated in response to a variety of environmental stressors. Data from our laboratory indicates that genetic inactivation of HSF1 significantly delays tumorigenesis in various tumor models. Increasing evidence supports the paradigm that modulating the metabolic bioenergetics of T cells, i.e., inhibiting glycolytic flux, enhances the formation of efficient anti-tumor CD8+ T cells. Since HSF1 is involved in cellular metabolism, in this study, we explored the strategies to reprogram metabolic pathways used by the immune system to improve anti-tumor immunity. We observed that deletion of HSF1 profoundly affects metabolic reprogramming of naïve CD8+ T cells upon anti-CD3/CD28 stimulation in vitro. Furthermore, HSF1-deficient CD8+ T cells show a reduced oxygen consumption rate upon activation. These effects correspond to delayed T cell receptor (TCR) signaling and slower activation of naïve CD8+ T cells upon stimulation, preventing them from moving towards an early exhaustion stage resulting in improved longevity. Furthermore, we were able to demonstrate that these defects in TCR signaling is attributed to HSF1 deletion-mediated redox imbalance (NAD+/NADH), resulting in the attenuation of mitochondrial function characterized by hampered respiratory complex I activity and limiting ATP production. Supplementation of CD8+ T cells with ATP or NAD rescued the defects observed during CD8+ T cell activation and function caused by HSF1 deletion. Additionally, we detected delayed initiation of MC38 tumors that were implanted in the T-cell specific HSF1-deficient mice compared to wild-type mice. In addition, we confirmed that the delay in tumorigenesis observed in T-cell specific HSF1 deleted mice is mediated through CD8+ T cells since treatment of these tumor-bearing mice with anti-CD8 antibody reversed the suppressive effects of HSF1-deficient CD8+ T cells on tumor growth. Finally, we successfully demonstrated the additive effects of HSF1 deletion and immune checkpoint inhibition therapy in tumor clearance. Taken together, HSF1 can be a potential therapeutic target to overcome the limitations of existing cancer therapies, and further studies will be directed towards exploring HSF1-mediated modulation of T cell metabolism as an emerging option for improvement of immunotherapy in order to generate anti-tumor CD8+ T cells with superior efficacy and enhanced survival.
    • An unusual DNA sequence observed in the [gamma] globin gene loci of two members of a Chinese family

      Ryan, Qin Cao; Department of Cell and Molecular Biology (1989-05)
      There are two nonallelic human y globin genes located on the short arm of ~hromosome #11 in the order 5'-Gy-Ay-3'. Various modifications of the two y genes have been reported and include: deletion·s., triplications., quadruplications and recently a quintuplication. These are :.generally created by one or more unequal crossovers in the y globin ge~e- _regions on adjacent chromosomes. During the c~urse of looking for a y0 thala~semia,. which might be due to a_ crossover within the y genes., two cases were found in the family W. · Bgl II mapping studies showed a 5 kb deletion at the y gene loci in these individuals. The ·Bgl II fragment from th(= y gene loci of R .W. was cloned into the phage vector ·oRl. Phage mapping showed that two out o·f the three Pst I sites within the Bgl II fragment were missing which suggested that the crossover might· have occurred within the y gene., possibly within the yIVS II region. Sequence analysis of the cloned fragment revealed an unusual sequence which had no sequence homology with the r gene region except for a small 264 .bp region near the 3' end. The orientation of the 264 bp fragmen~ is inverted _relat~ve to homologous sequences in the Gr and A'Y IVS II. . The unus~al sequence was computer analyzed for homology with every DNA sequence file in the EMBL data base and GenBank and did not show ·any significant homologies to._ all the available DNA sequences except for the 264 ~p _yIVS II homology. Sine~ mor~ than 99% of the DNA sequences in. the whole of nature still remain unknown., ~he origin of this unusual sequence is a question which mu.st ~wait further investigation.
    • The Use of Sex Chromosomes as Markers to Determine The Fate of Allogenic Bone Implants

      Amin, Mohammed Assem Mahmoud; Department of Oral Biology (1979-08)
      ,This ·study investigated the survival of whole ·fresh hip marrow allografts in four genetically (DLA) mismatched mongrel dogs, paired on the basis of opposit~ sex. Allografts were placed into tooth extraction · s i'~,es: autographs and nongra fted sites served as contra 1 s. The graft material recovered from the experimental sites was grown ~vitro and chromosomal preparations made from these cells were examined for pre~ence of donor cells, at various tim~s up to 56 d~ys after transplantation. In addition, the survtval of allograft osteocytes was observed dsing histological techniques. The use of t i ssu~ cu-1 ture and chromosoma 1 prep~ rations indicated the survi va 1 of an uni denti fi ed. allogeneic cell type for up to .. 56 days. Thus, the morphologic ch~nges of t~e graft osteocytes did-correlate with the.su~viv~l .. ~·~ ' of those unidentified cells after the 20 d~j survival limit of the osteoc}t~s, indicating that allogeneic bone· cells can survive this ·long in bone grafts and may contribute to he a 1 i ng ·of the defects. ·
    • Use of Sigma Receptor Ligands to Prevent Retinal Ganglion Cell Apoptosis Characteristic of Diabetic Retinopathy

      Martin, Pamela M; Department of Cellular Biology and Anatomy (2003-04)
      (First Paragraph)Diabetic retinopathy is a major sight-threatening disease and is the leading cause of blindness among working-aged Americans, affecting approximately 10 to 12 million persons (Wu, 1995). Although retinal vasculature is particularly vulnerable to damage in diabetes, other retinal cells are at risk. Very recently, Barber et al. (1998) documented increased apoptosis of neural retinal cells in experimental diabetes in rats and diabetes mellitus in humans. Notably, retinal ganglion cells (RGCs) were found to be at particular risk. Ganglion cell death in diabetic retinopathy is thought to be mediated via overstimulation o f N-methyl-D-aspartate (NMDA) receptors by glutamate. oRl is a nonopiate and nonphencyclidine-binding site that has numerous pharmacological and physiological functions. In some studies, agonists for aR l have been shown to afford neuroprotection against overstimulation of the NMDA receptor. The purpose of these studies was to evaluate the potential use of aR ligands, particularly those that bind specifically to o R l, as neuroprotective agents in the treatment of RGC apoptosis characteristic of diabetic retinopathy. A detailed description of the retina, followed by information about diabetes and the mechanisms thought to be involved in the pathogenesis of diabetic retinopathy, particularly the apoptotic death of RGCs associated with diabetic retinopathy, is provided below.
    • Use of Stress Management to Decrease Nurse Burnout

      Gramling, Lou; School of Nursing (1983-11)
      The impact of stress man~gement education'on the amount of reported nurse burnout was studied. A quasi-experimental two-group (control and experimental) pretest-posttest design was used. The Maslach Burnout Inventory (Maslacfi and Jackson, 1981) and a Demographic Data Form were used to study eight registered nurses who·registered to attend a J two-hour inservice program entitled "Reducing Your Stress Thr6ugh Self-Management.'' The results of the study indicated ' an increase (although not statistically significant) in reported burnout from the group that attended the workshop. Possibly in the allotted one month time frame, participants gained insight into their burnout, but did not have time to implement ne~ coping skills. A relationship was ·found be- ~tween burnout reported.and the nurse's practice setting, with nurses working in the medical-surgical area report~ng higher burnout than those working ,in the other areas represented. Additiohal study of the variables influencing burnout in nursing and interventions to prevent burnout is recommended.
    • The use of the mouse APRT gene in cultured human cells to study point mutations

      Jarrett, Robert A; Department of Cell and Molecular Biology (1988-08)
      Site-specific mutagenesis, gene transfer, and somatic cell selection have been used to develop a method for the identification of site- and sequence-specific point mutationsinduced in a mammalian cell transgenic system. This method utilizes a mouse adenine phosphoribosyltransferase [APRT] gene containing a specific point mutation in an intronjexon splice recognition sequence, which disrupts mRNA processing and destroys a diagnostic Pst I restriction site. This construct was introduced by cotransfection,with the bacterial n&Qr gene into HTD-114, a non-spontaneously-reverting, Aprt- human fibrosarcoma-derived cell line. The construct s·tudied contains I an A to G transition which is revertible with ethyl methanesulfonate [EMS], a mutagen known to produce G to A transitions in eukaryotes and prokaryotes. Exposing two independently derived cell lines containing the construct to EMS concentrations ranging from 0 to 200 ugjml (corresponding-to 100 to 0.8 percent survival) produced a frequency of reversion to the Aprt+ phenotype of 10-7 to 10-2 .
    • Use-dependent Antagonism of Nicotinic Acetylcholine Receptors as a Novel Treatment for Drug Addiction

      Hall, Brandon J; Department of Pharmacology and Toxicology (2011-11)
      The contributions of nicotinic acetylcholine receptors (nAChRs) to the onset and maintenance of drug addiction are well known, but these receptors are too often overlooked as potential targets for addiction treatment. The goal of this study was to demonstrate that use-dependent antagonism of nAChRs by the compound bis (2, 2, 6, 6-tetramethyl-4-piperidinyl) sebacate (BTMPS) offers a novel approach to treatment for drug addiction, and that positive outcomes of this treatment can be demonstrated across different classes of abusive drugs, nicotine or morphine in all three phases of an animal model of what is known as the drug abuse cycle: 1) binge-intoxication, 2) withdrawal-negative affect, and 3) preoccupation-anticipation. Different groups of rats were allowed to self-administer drugs of abuse (nicotine or morphine) on a 24 hr basis for a period of 14 days to establish binge-intoxication. Upon completion of self-administration, each rat was evaluated for withdrawal-negative affect. Subsequent to acute withdrawal the rats were placed in standard housing cages for a period of six weeks. At the end of the six week period, each rat was examined for unrewarded drug seeking responses, or preoccupation-anticipation, for another 14 day period preoccupation-anticipation. Injections of vehicle or BTMPS were administered to the animals during each behavioral phase of the study. Treatment with BTMPS significantly reduced the self-administration of both nicotine and morphine compared to vehicle treated animals. BTMPS treated animals also displayed reduced acute withdrawal symptoms when compared to their vehicle treated counterparts. When intervention occurred during self-administration or acute withdrawal, BTMPS treatment resulted in a significant reduction in drug-seeking responses after a protracted period of abstinence from drug. However, delaying treatment with the compound until the drug seeking phase of the study was ineffective against reducing drug seeking behavior. Administration of BTMPS alone did not appear to elicit adverse side effects in the animals, neither affecting their motivation to obtain food nor compromising the animals' performance during the behavioral procedures in the study. Thus, the resultsof this study support the hypothesis that use-dependent antagonism of nAChRs offers the potential for an alternative approach to treatment of substance abuse and drug addiction.
    • Using peptide-based vaccines to enhance adoptive cell therapy with genetically engineered T cells

      Fan, Aaron; Department of Neuroscience and Regenerative Medicine (6/27/2018)
      Adoptive cell therapy (ACT) of retrovirally transduced (RV) CD8 T cells is a powerful technique that has shown promise in tumor eradication in cancer patients. However, some major barriers to current methods are that ACT is expensive, time consuming, and requires harmful and toxic adjunct procedures. The Celis laboratory has demonstrated the use of TriVax, a potent peptide vaccination strategy that dramatically expands ACT cell populations and bypasses the necessity for adjunct procedures. The purpose of my thesis project was to enhance current methods of ACT+TriVax by testing an antigen-specific antitumor response of RV CD8 T cells and if it could be improved with constitutively active STAT5 (CA-STAT5) expression, a protein activated downstream several cytokine pathways that have been shown to play a role in increasing CD8 T cell persistence and resistance to apoptosis. Here, I aimed to test the hypothesis that CA-STAT5 in CD8 T cells enhances an antitumor effect by increasing T cell persistence and efficacy. My results show that TriVax administration selectively expanded frequencies of the ACT cell population expressing gp100-TCR in both blood and spleen. When co-transduced with CA-STAT5, an even higher fold expansion of antigen-specific cells was observed. +CA-STAT5 T cells were able to expand more robustly than -CA-STAT5 T cells upon repeated antigen stimulation (vaccine boost), demonstrating nearly 4000-fold increases in antigen-specific CD8 T cells. +CA-STAT5 T cells also seemed to persist longer in vivo over time, and they expressed lower levels of surface PD-1. Using B16F10 melanoma, ACT+TriVax of these cell populations into tumor-bearing mice demonstrated a powerful antitumor effect, leading to tumor regression in treated groups. CA-STAT5 seemed to recapitulate similar antitumor effects our laboratory observed previously with combinatorial anti-PD-L1 treatment or IL2/anti-IL2 mAb complexes (IL2Cx), suggesting a potential role for STAT5 in resisting the PD-1/PD-L1 inhibitory pathway. Altogether, these results demonstrate that RV CD8 T cells expressing gp100-TCR and CA-STAT5 are capable of antigen-dependent expansion in response to TriVax. CA-STAT5 plays a role in increasing T cell proliferation and persistence, as well as increasing efficacy through resistance to PD-1/PD-L1 inhibition.