• Molecular aspects of amino acid transport in the human placenta

      Torress-Zamorano, Viviana; Medical College of Georgia (Augusta University, 1997)
    • Neuronal death in lewy body disease

      Tompkins, Margaret Marie; Medical College of Georgia (Augusta University, 1997)
      In Parkinson's disease and other Lewy body-associated disorders, neurons in the substantia nigra pars compacta (SNpc) undergo degeneration, but the mechanism of cell death has not been previously described. The substantia nigra of normal and Alzheimer's disease cases were compared with substantia nigra from patients with Lewy bodyassociated disorders (Parkinson's disease, concomitant Alzheimer's/Parkinson's disease, and diffuse Lewy body disease) using in situ end-labeling to detect fragmented DNA. In situ end-labeled neurons demonstrated changes resembling apoptosis: nuclear condensation, chromatin fragmentation and formation of apoptotic-like bodies. Ultrastructural analysis confirmed nuclear condensation and formation of apoptotic-like bodies. Apoptotic-like changes were seen in the substantia nigra of both normal and disea·sed cases; concomitant Alzheimer's/Parkinson's disease and diffuse Lewy body disease cases had significantly higher amounts of apoptotic-like changes than normal controls or Alzheimer patients. Parkinson's disease cases were not significantly different from controls, probably due to high variation among cases of Parkinson's disease. Control and Alzheimer's disease patients had the same percentage of apoptotic-Iike changes. Lewy bodies (LBs) are abnormal inclusions found in the SNpc neurons of patients with Lewy body-associated disorders. It is not known what role LBs play in the disease process. We sought to discover whether apoptotic-like changes were more common in SNpc neurons with or without somal· LBs. In SNpc tissue from cases with Lewy body-associated disorders, .cells were double-labeled to colocalize apoptotic-like changes and LBs with in 'Situ .endlabeling and anti-ubiquitin antibody. Nigral neurons with LBs showed the same amount of apoptotic-like changes as nigral neurons without LBs. The majority of SNpc neurons undergoing apoptotic-like cell death did not appear to contain somal LBs. These results support the theory that the presence of a somal LB does not predispose a neuron to undergo apoptoticlike cell death.
    • Androgen regulation of the expression of OCTN2, a high affinity carnitine transporter, in the epididymis and other tissues

      Timm, Russell S.; Medical College of Georgia (Augusta University, 2001)
      OCTNZ is a transport protein and a member of a superfamily of organic cation transporters and has been shown to transport a variety of substrates, including camitine. The transport of the substrate is unique among this family of transport proteins as it is sodium-dependant, and it has been shown that this transporter is a physiologically relevant camitine transporter, as naturally occurring mutations in the gene encoding this transporter result in the clinical manifestation of the syndrome known as primary camitine deficiency. With the acceptance of OCTNZ's physiological role in camitine homeostasis, further scientific inquiries need to be made to definitively show that OCTN2 is a molecular mechanism that underlies many of the observations made in the field of camitine research in past century. Multiple investigators have reported the effect and relationship between androgen levels and carnitine transport, but until the discovery of OCTN2 and its role in camitine homeostasis, the effect of androgens on the molecular mechanism responsible for these observations could not be proven. The results of the research described here should provide conclusive evidence that androgen levels regulate levels of OCTNZ expr!lSsion in both tissues of the male rat and in a human cell line, through either a direct or indirect mechanism, and that the effect on the regulation of expression is consistent with transport data :from previous researchers.
    • The perceived importance of clinical nurse specialists' role components as viewed by nurse administrators and clinical nurse specialists in academic hospitals

      Till, Elizabeth C.; School of Nursing (Augusta University, 1990)
      This study examined the perceived importance of clinical nurse specialists' (CNS) role components as viewed by a sample of 42 nurse administrators (NA) and 60 CNSs in eight academic hospitals in the United States. The participants completed the Clifford Clinical Nurse Specialist Functions Inventory and a demographic survey mailed directly to each individual. Each of the four CNS role component mean scores, of the total sample of the CNSs and-the total sample of the NAs, were ranked for comparison of impor~ance. A two-way analysis of variance (ANOVA) was used to compare the mean scores for each of the four role components and the mean score between hospitals. Results of this study indicated that the CNS ranked the four CNS role components in de:;;cending order of importance: ( 1) education, (2) clinical, ( 3) research, and (4) administration. The NAs ranked the role components in descending order of importance: (1) research, ( 2) education, ( 3) clinical, and (4) administration. Results of the ANOVA to test differences of the importance of CNS role components indicated that there was a significant difference (E < .005) between the nursing groups of the sample hospitals only for the clinical role component and a significant difference (E < .001) between the hospitals only for the administration role component.
    • The Effect of chelating agents on matrix metalloproteinase activity of demineralized human dentin

      Thompson, Jeremy M.; Medical College of Georgia (Augusta University, 2011)
    • Modulation of IL-6 production in human gingival fibroblasts by progesterone

      Thomas, Michael E.; Department of Oral Bio-Microbiology (Augusta University, 1994)
    • Excellence and success in small rural hospitals : the interrelationships of power, participation in decision-making and organizational commitment in rural nurses

      Talley, Brenda; Medical College of Georgia (Augusta University, 1998)
      The purpose of this study was to explore power, participation in decision making, and organizational commitment among nurses in small rural hospitals. Quality of care and length of stay cost efficiency were viewed as outcome variables. All of these relationships are embedded in a changing health care environment. Fifty rural hospitals of 100 beds or fewer from eight rural states agreed to be in the study. From the 50 hospitals, 319 RNs participated. The study had three research hypotheses: Hypothesis 1: Changes· related tq the health care organization, patient care, and nursing d~partments are being experienced by RNs working in small rural hospitals. A high degree of change was evident in the responses, though the pattern of change differed from the changes in other studies. · Hypothesis 2: There are positive relationships among power as knowing participation in change, participation in decision-making, and organizational commitment among nurses working in rural hospitals. Pearson's r correlations among the variables were low-moderate. Hypothesis 3: Power, participation in decision-making, and organizational commitment have a positive effect on quality patient care and cost effectiveness in small rural hospitals. In staff nurses, organizational commitment was significant for both quality and length of stay cost efficiency, and decision-making was significant for quality accounting for 35% of the variance. The highest variance was with top-line manageme·nt nurses. Sixty percent of the variance in quality was accounted for by power and organizational commitment.
    • Self-worth, social support and parenting attributes among pregnant adolescents

      Sykes, Mary K.; School of Nursing (Augusta University, 1990)
      A study of 34 pregnant adolescents was conducted to examine whether Child Abuse Potential Inventory (CAPI) scores could be predicted from measures of self-worth, social support, and age. The Self-Perception Profile for Adolescents (Harter, 1989) was utilized to measure selfworth, and the Family Support Scale (Dunst, Jenkins, & Trivette, 1984) was chosen as the social support instrument. A descriptive correlational research design was used to test the hypothesis that child abuse potential would be negatively related to perceived self-worth, perceived social support, and age. Only self-worth was a significant predictor of CAPI scores. Instrument subscales were examined for correlations between self-perceptions in specific domains and components of the Child Abuse Potential Inventory. significant correlations between total CAPI scores and perceived social acceptance and romantic appeal were found. Results of this study indicate that perceptions of self-worth and social acceptance may be related to parenting in similar samples.
    • Neuronal and astrocytic disruption during traumatic brain injury described using longitudinal imagin

      Sword, Jeremy Jon; Medical College of Georgia (Augusta University, 2012)
      In Traumatic Brain Injury (TBI) mechanical forces applied to the cranium and brain cause irreversible primary neuronal and astroglial damage associated with terminal dendritic beading and spine loss. Edema, which quickly develops after TBI, causes an increase in intracranial pressure, which can cause secondary injury in the peri-contusional area. Spreading depolarizations have also been shown to occur after TBI in humans as well as in animal models, contributing to secondary injury. However, the impact of spreading depolarizations on real-time injury to dendrites and astrocytes in the pericontusional area during edema development is unknown. We used in vivo twophoton laser scanning microscopy (2PLSM) in mouse somatosensory cortex via an optical window to monitor yellow fluorescent protein expressing neurons and enhanced green fluorescent protein expressing astrocytes in the peri-contusional area after mild TBI. Loss of capillary blood flow preceded dendritic beading, which developed slowly over the ·next several hours. This indicated that acute injury to dendrites was gated by the degree of ischemia as a result of developing edema. Astrocytes were swollen (cytotoxic edema) due to ion and 'rater uptake and remained swollen up to 24 hours. When spreading depolarizations were repeatedly induced by pressure-injecting 1 M KCI with a Picospritzer outside the imaging area, dendrites underwent rapid beading and recovery coinciding with passage of spreading depolarizations, as was confirmed with electrophysiological recordings in the vicinity of imaged dendrites. However, each s:ubsequent I spreading depolarization resulted in a smaller percentage of dendrites that were I able to fully recover until ultimately all were terminally injured. Thus our data suggests that accumulated stress resulting from spreading depolarizations expedites acute dendritic injury in the peri-contusional area, worsening secondary damage following TBI. We also propose that persistent astroglial swelling in the peri-contusional area may be harmful and decreases astroglial maintenance of normal homeostatic function and possibly contributes greatly to the negative outcome of TBI as astrocytes fail to provide neuronal support.
    • Mechanisms for the dependency of angiotensin II hypertension on interleukin-6

      Sturgis, LaShon C.; Medical College of Georgia (Augusta University, 2007)
      Angiotensin II (Ang II) is involved critically in the development and maintenance of hypertension in both human and animal models. Ang II also is known to stimulate interleukin 6 (IL-6) release, and a recent study by our laboratory demonstrated that Ang II hypertension was attenuated in IL-6 knockout (KO) mice. These data suggest that IL-6 mediates part of the hypertensive actions of Ang II. In addition, Ang II also stimulates production and release of aldosterone, which also has hypertensive actions. Ang II also stimulates the proinflammatory cytokine tumor necrosis factor-alpha (TNF-a.), which can stimulate IL-6 secretion. Therefore, the aim of this project was to determine whether the dependence of Ang II hypertension on 11-6 is du.e to a direct link between Ang II and IL-6 or whether aldosterone and/or TNF-a. are important intermediate factors. In separate studies, we determined whether mineralocorticoid hypertension is IL-6 dependent, the role of IL-6 bioactivity verses IL-6 plasma concentration, and the role of TNF-a. in Ang II hypertension. Mineralocorticoid hypertension was induced by implanting a deoxycorticosterone acetate (DOCA) pellet (1 g/Kg) subcutaneously and giving all animals a solution of 1% sodium chlorid~ (NaCI) and 0.2 % potassium chloride (KCI) to dink for a 14 day experimental period. DOCA-salt treatment increased the mean arterial pressure (MAP) similarly by -30 mm . Hg in both the wr and IL-6 KO mice. However, DOCA-salt treatment did not increase plasma IL-6 concentration in wildtype {WT) mice nor did it increase . IL-6 bioavailability using a bioassay on day 14 of. treatment. There was,. however, a transient increase in plasma IL-6 concentration and bioactivity on day 7 of DOCA-salt treatment in the WT mice. Treating WT mice with Ang II and the mineralocorticoid receptor antagonist, spironolactone, significantly attenuated the Ang II mediated increase in plasma IL-6 concentration on day 7 and day 14 of treatment. Although we cannot explain why the IL-6 response to DOCA was not sustained through 14 days, together these data suggest that that aldosterone plays a role in the increase in plasma IL-6 concentration during Ang II hypertension. However the effect of IL-6 in mediating part of the Ang II hypertension appears d_ue to an interaction with Ang 11-mediated effects and not due to effects mediated by the mineralocorticoid receptor. Similarly, Ang II increased MAP by -30 mm Hg in both the·wr a·nd TN F-a. KO mice by day 14 of treatment. Moreover, which suggests that TN F-a. is not required for Ang II hypertension, Ang II treatment did not increase plasma levels of TN F-a. and TN F-a. infusion did not cause a sustained .increase in IL-6. These data suggest that Ang II may work through an aldosterone, but not TNF-a.- mediated, mechanism to increase plasma IL-6 concentration in Ang II hypertension, but that the role of IL-6 in mediating Ang II hypertension is due to interactions with Ang.ll receptor type 1 (AT1) dependent mechanisms on target tissues.
    • The influence of glucocorticoids and a downstream target on the development of T cells

      Stephens, Geoffrey L.; Medical College of Georgia (Augusta University, 2002)
      Evidence suggests that glucocorticoids producei:l by thymic epithelial cells modify the biological consequences of TCR-mediated signaling. We hypothesized that glucocorticoids modulate the threshold for thymocyte activation by opposing the consequences of TCR engagement. To examine this possibility, TKO mice, which have a 50% reduction in thymocyte glucocorticoid receptor expression, were bred with mouse strains differing in their ability to present peptides in the context of MHC-encoded molecules. Our results indicate that endogenous glucocorticoids affect thymic selection by decreasing a thymocyte's sensitivity to TCR engagement. Thymocytes with increased avidities for self-peptide/MHC complexes are thought to adopt a regulatory (CD4+CD25) T cell lineage. We_ hypothesized that altering how a thymocyte perceives TCR engagement by modulating glucocorticoid responsiveness will influence a CD4+ T cell's choice to commit to a CD4+CD25+ regulatory T cell lineage. In mice, abundantly expressing a few or one peptide(s) bound to MHC class II molecules, a disproportionate number CD4+ T cells were committed to a regulatory (CD4+CD25+) lineage when the threshold required for thymocyte activation was reduced. Thus, increasing the perceived intensity of TCR engagement during thymic selection enhanced commitment to a CD4+CD25+ regulatory lineage. A reduction in GR signaling by early thymic precursors was found to result in a selective defect in uP but not yo lineage development. Few DN precursors from TKO 'mice were found to express intrac.ellular TCR P-chains, while the expression of other components of the pre-TCR was not affected. A more detailed analysis of the TCR P locus revealed that glucocorticoid hyporesponsiveness inhibited the rearrangement of this gene. It has been demonstrated that GITR (Glucocorticoid Induced TNF-like Receptor), a non-death domain containing TNF family member whose expression is induced by glucocorticoids, . prevents TCR-induced apoptosis when over-expressed in T cell hybridomas. We hypothesized that GITR plays an important role in thymocyte development by enhancing the survival/selection of immature thymocytes. To investigate this possibility in vivo, we produced transgenic mice that over-expressed GITR specifically on thymocytes. Ectopic GITR expression did not prevent TCR-induced thymocyte apoptosis in vivo implying that GITR expression does not enhance selection, but is rather a consequence of it.
    • Neutrophils in the injured taste system

      Steen, Pamela Wall; Medical College of Georgia (Augusta University, 2008)
      Taste buds on the anterior tongue are bilaterally innervated by the chorda tympani (CT) nerve. Upon unilateral CT section, ipsilateral taste buds degenerate. This injury elicits an activated macrophage response that peaks within two days. However, dietary sodium restriction prevents the macrophage response to injury. The same ·dietary treatment alters neural taste responses in the uninjured CT. Rats receiving a sodium-restricted diet display reduced sodium responses in the contralateral; intact CT nerve at day 4 post-section. We hypothesized that the immune response to CT section mediates early functional changes on the intact side of the tongue. Taste responses in the intact CT nerve had not been examined prior to day 4 after injury. Therefore, responses were recorded from the uninjured CT nerVe at.days 1-4 post-section. At day 1, sodium responses were subnormal, but recovered to normal levels at day 2 post-injury. In contrast, taste responses to sodium remained subnormal in sodium-restricted rats. Since neutrophils are typically the first immune cells to invade after injury, we examined their response to CT nerve section. Neutrophils were increased at 12 hours post-section. AI day 1, the neutrophil response began to decrease in animals fed a normal diet. Yet, dietary sodium restriction augmented and prolonged the neutrophil response to injury. the timing and magnitude of the neutrophil response paralleled the decrease in sodium taste responses. We hypothesized that neutrophil-derived factors induce deficits in taste function. Depletion of neutrophils restored normal sodium responses in the intact CT nerve at day 1 post-section. These studies demonstrate that neutrophils are detrimental to normal taste function after neighboring neural injury. Defining early immune responses to injury in the peripheral taste system, which does regenerate, may provide insight to immune deficiencies in systems that fail to recover after injury.
    • The effect of mode of polymerization and presence of fluoride on the shear bond strength of orthodontic resins to bovine enamel

      Steckel, Stephanie E.; Department of Oral Biology (Augusta University, 1994)
      Decalcification around orthodontic brackets is sometimes observed during and after treatment. Fluoride-releasing orthodontic resins have been shown to arrest early enamel caries formation. However, some previous studies demonstrate the therapeutic advantage of fluoride release was undermined by the increased incidence of bond failures. This research investigated the shear bond strength values of stainless steel brackets bonded with no-mix, chemically cured and light-activated resins and their fluoride-releasing equivalents to etched bovine enamel. The shear testing for the first group was completed after 24 hours of storage in artificial saliva. Fluoride-releasing resins are known to release a significant amount of fluoride within the first few days after bonding. The adhesives in this project were evaluated for amount and duration of fluoride release, utilizing a clinically-relevant model. The fluoride concentration of the resins was determined by HMOS (hexamethyldisiloxane) diffusion and the results were compared to those reported by the manufacturer. The shear bond strength values for the no-mix, chemically cured and light-activated resins for the secondgroup was determined after allowing significant fluoride release in artificial saliva to occur. The results showed that storage time did not affect the shear bond strength of the light-activated or chemically cured resins, yet the no-mix resins demonstrated a near doubling of shear bond strength with time. If fluoride is not present in the resin, the chemically cured resin is significantly stronger than the light-activated or no-mix resins. If fluoride is present in the resin, the chemically cured resin shear bond strength is equivalent to the light-activated and both are greater than the no-mix resin. The presence of fluoride significantly increased the bond strength of the light-activated resin in the short-term, and after storage both the chemically cured and light-activated fluoridecontaining resins were significantly stronger than the nonfluoride- containing counterparts. Fluoride-releasing chemically cured and light-activated resins released significantly more fluoride than the no-mix resin, with the chemically cured resin releasing the most. Both the light-activated and chemically cured resins demonstrated an early burst of fluoride release that levelled off within 20 and 30 days, respectively. The minimal fluoride release seen with the no-mix resin may be due to the dilution of the components during mixing. For all the resins tested.,, the vast majority of the fluoride available for release remained in the resins.
    • Biosynthesis and modification of helicobacter pylori lipid A

      Stead, Christopher Michael; Medical College of Georgia (Augusta University, 2010)
      The secondary acylation steps of Helicobacter pylori lipid A biosynthesis are poorly understood because H. pylori only has one homolog (Jhp0265) to the Escherichia coli secondary acyl transferases Lpxl and LpxM. Jhp0265 was shown to be responsible for the transfer of a secondary C18 acyl chain to the 2' -linked acyl chain of lipid A, making Jhp0265 homologous to Lpxl. An activity was also demonstrated for the addition of a secondary acyl chain to the 3'-linked acyl chain of H. pylori lipid A, although the enzyme responsible for the transfer remains unknown. After synthesis, H. pylori lipid A is modified by the action of five enzymes. Mutation of the candidate modification enzyme Jhp0634 demonstrated that the enzyme catalyzes the removal of the 3'-linked acyl chains of H. pylori lipid A, producing a tetra-acylated lipid A species. Continuing with the characterization of H. pylori lipid A modification enzymes, we were also able to demonstrate an activity for a Kdo trimming enzyme in vitro. Requirement for a Kdo hydrolase in vivo was confirmed after the Kdo transferase of H. pylori was shown to be bifunctional despite the presence of only one Kdo sugar in H. pylori lipopolysaccharide. Attempted identification of the Kdo hydrolase revealed that both Hp0579 and Hp0580 were required for the removal of the Kdo sugar, which occurred in the periplasm. A Kdo hydrolase mutant revealed two unexpected phenotypes related to interaction with the innate immune system. The first was an increased sensitivity to cationic antimicrobial peptides, which was explained by a downstream effect on modification to the 4'- phosphate group of lipid A. The second phenotype related to the expression of 0- antigen on the bacterial cell surface. The Kdo hydrolase mutants produced a reduced amount of fully extended lipopolysaccharide and conversely, an increased amount of core-lipid A. The type of 0-antigen epitope displayed was also affected by a Kdo hydrolase mutation, in a strain specific manner.
    • The experiences of fieldwork educators in the supervision of level II occupational therapy assistant students

      Stanfield, Dee; Medical College of Georgia (Augusta University, 1999)
      Although much has been written on the supervision of occupational therapy students, little addresses the unique issues in the supervision of occupational therapy assistant students. The purpose of this phenomenological study was to gain an understanding ofthe elements in the supervision of occupational therapy assistant students as they are experienced by fieldwork educators. Data collected from a focus group raised the following issues: the effect of the . stressful healthcare environment on fieldwork education, the continued tension between academia and practice, the fieldwork educator's feeling of abandonment by academia, and the confusion associated with role delineation. The results of this study suggest. that the profession must find ways to address the undercurrent of issues between academia and practice, to increase clarity in role delineation, to offer a practical peer-based support program for the fieldwork educator, and to encourage more occupational therapy assistants to become fieldwork educators.