• The effects of the topically applied non-ionic surfactants, pluronic F-68 and F-127 on wound healing in the ra

      Shahan, Michael H.; Department of Oral Biology (Augusta University, 1992-05)
    • Characterization of zebrafish mutant merlot as a non-mammalian vertebrate model for congenital anemia due to protein 4.1 deficiency

      Shafizadeh, Ebrahim; Medical College of Georiga (Augusta University, 2002-08)
      The zebrafish mutant merlot (mot) is characterized by onset of a severe anemia at 96 hours post fertilization. We performed whole mount RNA in situ hybridization and showed that ihe process of primitive erythropoiesis is not interrupted in the mot embryos. Blood analysis demonstrated that mot suffers from a severe congenital hemolytic anemia. Using the TUNEL assay, we detected apoptotic erythroid progenitors in the kidneys. We performed electron microscopic analysis and detected membrane abnormalities and a loss of the cortical membrane organization in the mot cells. We used positional cloning techniques with a candidate gene approach to demonstrate that mot encodes the erythroid specific isoform of protein 4.1R, a critical component of the red blood cell membrane skeleton. Sequence analysis of 4.1R eDNA detected nonsense point mutations in both alleles of mot resulting in premature stop codons. We performed linkage analysis and transgenic rescue experiments to provide further confirmation that the molecular defect in the protein 4.1R is the underlying cause of anemic phenotype in mot fish. This study presents the zebrafish mutant merlot as the first characterized non-mammalian vertebrate model of congenital anemia due to a defect in protein 4.1R integrity.
    • A study of the relationship between perceived social support, satisfaction with social support networks, and self-rated health in older adults

      Seagraves, Pat C.; School of Nursing (Augusta University, 1992-04)
      The purpose of this study was to examine the relationship between perceived social support, satisfaction with social support networks and self-rated health in older adults. The study used a cross-sectional correlational design to examine the hypothesis that perceived social support and satisfaction with social support networks would be positively correlated (p < .05} with scores on a selfrated health measure. The convenience sample consisted of forty-three subjects ranging in age from sixty-five to ninety-five years, with a mean age of 75.4 years. All subjects were able to speak and understand English, and were judged to have the physical ability to complete a written questionnaire packet. All subjects completed Pfeiffer's Short Portable Mental Status Questionnaire (SPMSQ} with no more than two adjusted errors, indicating intact mental functioning. The Personal Resource Questionnaire (PRQ-85} was used to measure perceived social support, and investigator developed measures were used to assess satisfaction with social support and self-rated health. A list of health problems common to older adults provided an index of actual health status. Pearson correlation coefficients were calculated for satisfaction with social support networks, age, self-rated health and the subscales of PRQ-85, Part II. While the hypothesis of the study was not supported, a significant inverse correlation was demonstrated between age and nurturance, indicating that as a person ages, the opportunity for nurturant behavior decreases. The results of the data analysis reflected the multiplicity and chronicity of health problems in this age group, but revealed that older people do not evaluate their own health according to the number or type of health problems they experience. Nor is their self-rated health score consistent · with the number and type of medications they take. Further, the data from this sample woula indicate that self-rated health in this age group is not dependent on one's perception of social support, nor their satisfaction with their so"cial support network.
    • AKAP350 : a centrosome associated scaffold protein

      Schmidt, Hank; Medical College of Georgia (Augusta University, 2000-06)
      A-kinase anchoring proteins (AKAPs) are recognized as key components of compartmentalization and transduction in intracellular cAMP signaling. They allow localization of the Type II cAMP-dependent protein kinase to specific subcellular domains, effectively positioning the enzyme near its substrate to await activation by cAMP. The role of AKAPs as protein scaffolds allows binding of multiple enzymes, regulatory molecules, and structural elements, functioning as a virtual platform for modulation of specific cellular events (i.e. membrane channel activity, receptor clustering). We have cloned a novel350 kDa AKAP (AKAP350) from human gastric eDNA, and identified partial clones in human lung and rabbit parietal cells. The genomic region containing AKAP350, found on chromosome 7q21, is multiply spliced, producing at least three distinct AKAP350 isoforms as well as yotiao, an NMDA receptorassociated protein. We identified three unique AKAP350 C-termini (AKAP350A, -B, and -C) resulting from alternative splicing of the 3' end of the gene. AKAP350 is associated with centrosomes, as well as with the cleavage furrow during anaphase and telophase by immunocytochemistry. Polyclonal antibodies to individual AKAP350 Cterminal splice variants demonstrate tissue dependent combinations of centrosomal and non-centrosomal distribution. In the polarized HCA-7 colon cell line AKAP350A is purely non-centrosomal while AKAP350B and -C are centrosomal. Anti-AKAP350C is limited to mitotic cells, suggesting that this isoform may be expressed only at entry into M phase. A yeast two-hybrid screen of a rabbit parietal cell library identified a novel TACC (Transforming Acidic Coiled coil Containing) protein family member as a ligand of the final pair of arginine residues iii the AKAP350A splice variant. A GFP fusion with the novel AKAP interacting protein verified co-localization with AKAP350 at the centrosome exclusively during mitosis. Microinjection of dividing sea urchin embryos with GST fused to the AKAP interacting protein arrested cell division. Therefore, the AKAP350 protein scaffold may function as a large docking station, providing kinase I phosphatase signals for coordination of cytoskeletal dynamics as well as cell division.
    • The relationship between level of hope and coping response in women with breast cancer

      Schlesselman, Susan M.; School of Nursing (Augusta University, 1991-05)
    • Endothelin-1 signaling and reactive oxygen species production in hypertension and type 1 diabetes mellitus

      Sasser, Jennifer Mayberry; Medical College of Georgia (Augusta University, 2005-07)
      Nitric oxide (NO) and endothelin-1 (ET-1) play important roles in the cardiovascular system, and alterations in these pathways.can have significant effects on the regulation of blood pressure and renal function. Reactive oxygen species (ROS) influence the production and actions of these two factors, and therefore modulate the biological effects ofNO and ET-1. Thus, the overall goal of these studies was to determine the impact of increased ROS and ET -1 production in the development of hypertension and diabetic kidney disease. We hypothesized that (1 )_ increased superoxide production and a dysregulation of endothelial NO synthase (NOS3) in small arteries result in reduced NO bioavailability in hypertension and (2) enhanced ET -1 production and endothelin A (ETA) receptor activation promotes renal injury in the settings of hypertension and diabetes. We found that basal NO/cGMP signaling is diminished in small mesenteric arteries ofDOCA-salt rats, and this decrease is associated with reduced NOS3 phosphorylation at two positive regulatory sites, but not superoxide production. Chronic angiotensin II (An g) infusion combined with a high salt diet increased the renal cortical and outer medullary ET -1 content. However, high salt diet; with or without Ang infusion, reduced inner medullary ET-1 content and increased urinary excretion ofET-1. These data indicate that chronic elevations in Ang levels and sodium intake produce differential effects on ET -1 levels within the kidney. Blockade of the ETA receptor with ABT -627 reduced renal injury in the streptozotocin model of type 1· diabetes. We found that oxidative stress was increased in hyperglycemic rats; however, the production of reactive oxygen species was not attenuated by ETA receptor blockade, indicating that the increased reactive oxygen species production observed in diabetes is not due to ETA receptor activation. Additionally, we found that urinary excretion of the metabolites of prostaglandin E2 (PGE2), prostacyclin, and thromboxane are all increased in hyperglycemic rats, and ETA receptor blockade reduced the excretion ofPGE2 metabolites. By obtaining a better understanding of reactive oxygen species production and ET -1 signaling pathways, we have gained a new perspective on the roles of these factors in the development of hypertension and diabetic renal disease.
    • In vitro mechanical analysis of full-arch mandibular implant-supported, complete fixed prostheis retainer screws after cyclic loading

      Sananez, Andreina J.; Medical College of Georgia (Augusta University, 2012-04)
      The use of implant-retained and supported prostheses has become a very successful treatment for completely edentulous patients. One of the most common fixed solutions involving implants consists of 5 to 7 implants supporting a framework upon which either porcelain or prefabricated acrylic resin denture teeth are added. A screw is utilized to attach the framework/prosthesis to the implants. Screw loosening is the second most common clinical complication in the implant-prosthesis system. If clinicians fail to detect worn or loose retaining screws, prosthetic fracture could occur, leading to more complicated, time consuming, and expensive repairs. Unfortunately, there is no established. parameter that indicates when to expect these complications, and there is no proven recall-maintenance protocol to prevent them. The aim of this study is to examine and compare differences among de-torque values and prosthetic retention screws, using a simulated 5 implant-supported, mandibular complete fixed prosthesis. Material and Methods: Nine groups, each with its respective control, using five Nobel Biocare implants and a milled titanium framework were fabricated, assembled and tested. Dynamic loading was p on the performed tested groups through a custom made loading device for anterior, posterior, and distal cantilevered segments of the prosthesis, calculated to simulate clinical usage time. Removal of screws after 2 years of simulated oral function was performed. Before and after testing, screws were evaluated with a Scanning Electronic Microscope (SEM), for presence of debris, thread striations and homogeneity. Control groups remained unloaded for the same time the loaded groups were tested. Results: Comparisons of the difference between initial tightening torque and de-torque screw values were performed between loaded/unloaded groups and with respect to implant position. The interaction between loaded and position was significant (p=0.002). The comparison between loaded/unloaded groups was not statistically significant (p=0.518). Loaded and unloaded groups were compared separately at each of the 5 implants position, which showed a significant difference (p=0.0002, a=0.001). The sequencing effect was only seen in the control groups and thus would only be relative to framework insertion. The sequence effect was found to be overcome by from loading and resulted in a totally different position related to screw tightness. Within the limitations of this in vitro study, it was concluded that sequence of torque application could play a role in the preload of screws even with a passive fit, regardless the load applied.
    • Role of endothelin-1(ET-1) in glomerular inflammation and glomerular permeability in normal and diabetic kidney

      Saleh, Mohamed Ahmed; Department of Pharmacology and Toxicology (Augusta University, 2010-11)
      Endothelin-1 (ET-1) is a potent vasoactive peptide implicated in the pathogenesis of hypertension and renal disease. The overall specific aim of this dissertation is to investigate the role of ET-1 in mediating glomerular inflammation and permeability, especially in diseases characterized by high activity of the ET-I system, such as diabetic nephropathy. The first study was designed to test the hypotheses that ET-I increases albumin permeability of glomeruli isolated from normal rats and that chronic ET-I infusion will increase glomerular permeability and inflammation independent of blood pressure. Glomerular permeability to albumin (P alb) was determined from the change in glomerular volume induced by exposing isolated glomeruli to oncotic gradients. Incubation of glomeruli taken from normal rats with ET-I at a concentration that did not produce direct glomerular contraction (I nM) significantly increased P alb, reaching a maximum after 4 hrs. Chronic ET-1 infusion for 2 weeks in Sprague-Dawley (SD) rats significantly increased P alb and nephrin excretion rate, effects that were attenuated in rats given an ETA receptor antagonist, ABT-627. Urinary protein and albumin excretion and mean arterial pressure (telemetry) were not changed by ET-1 infusion. Acute incubation of glomeruli isolated from ET -!-infused rats with the selective ETA antagonist significantly reduced P alb, an effect not observed with acute treatment with a selective ET e antagonist. Chronic ET -I infusion increased glomerular and plasma siCAM-1 and MCP-1 and elevated the number of macrophages and lymphocytes in renal cortices (CD68- and CD3-positive staining, respectively). These effects were all attenuated in rats given an ETA selective antagonist. These data support the hypothesis that ET -I directly increases glomerular permeability to albumin and renal inflammation via ETA receptor activation independent of changes in arterial pressure. The second study was designed to test the hypothesis that ETA receptor activation increases P alb and elevates pro-inflammatory markers in hyperglycemic rats. Male SD rats were given streptozotocin (STZ) or saline (sham). Half of the animals in each group received ABT- 627 beginning immediately after hyperglycemia had been confirmed. Glomeruli were isolated by sieving and P alb determined from the change in glomerular volume induced by exposing glomeruli to oncotic gradients of albumin. Glomerular nephrin expression was assessed by immunofluorescence, whereas urinary nephrin was measured by enzymelinked immunosorbent assay. Three and 6 weeks after STZ injection, proteinuria was significantly increased compared to sham controls and was significantly reduced by ABT-627 treatment. Palb was also increased at 3 and 6 wk post-STZ; ABT-627 had no effect on P alb or protein excretion in sham rats. Glomerular and plasma content of siCAM-1 and MCP-1 were significantly increased 6 wk after STZ. ABT-627 attenuated these increases. After 6 weeks of hyperglycemia, glomerular nephrin expression was decreased with a concurrent increase in urinary nephrin excretion; ABT -627 prevented glomerular nephrin loss in the hyperglycemic rats. These observations support the hypothesis that ET -I, via the ETA receptor, mediates the increase in proteinuria and P alb, possibly via nephrin loss, as well as early inflammation in the hyperglycemic rat. In the third study, we determined the actions of ETA and ETe receptors on measures of glomerular function and renal inflammation in the early stages of diabetic renal injury in rats. Six weeks after STZ-induced hyperglycemia, rats were given ABT-627 (5 mg/kg/d) a selective ETA antagonist; A-182086 (10 mglkg/d), a combined ETAIB antagonist; or vehicle for 1 week. Sham controls received STZ vehicle (saline). Hyperglycemia led to significant proteinuria, increased P alb, nephrinuria, and an increase in total matrix metalloprotease (MMPs) and transforming growth factor-beta 1 (TGF-~1) activities in glomeruli. Plasma and glomerular siCAM-1 and MCP-1 were elevated after 7 weeks of hyperglycemia. Daily administration of both ABT-627 and A-182086 for 1 week significantly attenuated proteinuria, the increase in P alb, nephrinuria, and total MMPs and TGF-~1 activity. However, glomerular siCAM-1 and MCP-1 expression was attenuated with ABT-627, but not A-182086 treatment. In summary, both selective ETA and combined ET AlB antagonists reduced proteinuria, glomerular permeability and restored glomerular filtration barrier components integrity, but only ETA selective blockade had anti-inflilmmatory and anti-fibrotic effects. We conclude that selective ETA antagonists are more likely to be preferred for treatment of diabetic kidney disease.
    • The Relationship among structure, technology, autonomy, decision making, nurse characteristics and the decision to call a resuscitation code on the patient who needs cardiopulmonary resuscitatio

      Russell, Katherine S.; Medical College of GA (Augusta University, 1997-08)
      In this study, the relationship among nursing unit structure, technology, autonomy, decision making, nurse characteristics and the timeliness of calling a resuscitation code was explored. The conceptual framework of the study was The Structural Interaction Model for Health Care Behavior (Colgrove, 1992), a model that combined and synthesized concepts from organizational theory, quality care, and patient-centered care. The hypothesized relationships were investigated using multivariate logistic regression and multiple regression analysis. A sample of 127 registered nurses and 127 patient resuscitation events from one hospital was used in the study. Nurses' perception of nursing unit structure, technology, autonomy and decision making were measured using four instruments. Nurse characteristics were obtained from the nurse demographic tool. Data required to stage the timeliness of calling a resuscitation code (early versus not early) was obtained from the patient's hospital record. Testing of the analytical model resulted in beginning support for elements that may contribute to the timeliness of calling a resuscitation code for the patient who may need cardiopulmonary resuscitation. These relationships pointed to the impact of structural factors and professional factors on the timeliness of calling a code. The findings were nurses with a baccalaureate degree or higher were more likely to call an early code as were nurses with less than a baccalaureate degree. Moreover, nurses that practiced on a unit with a more flexible nursing unit structure were more likely to call an early code than were nurses that practiced on a unit with a non- flexible unit structure. Nurses that were found to have a higher degree of normative decision making were more likely to call an early code than nurses that were found to have a lower degree of normative decision making. Further, there appeared to be a strong linear relationship between autonomy and the timeliness of calling a code. Nurses who perceived they were practicing with a higher degree of autonomy were more likely to call an early code than those who perceived they were practicing with a lower degree of autonomy.
    • Stress among parents of preterm and term infants hospitalized in the neonatal intensive care unit

      Russell, Guerry K.; School of Nursing (Augusta University, 1994-06)
      The Neonatal Intensive Care Unit (NICU) hospitalization of an infant serves as a significant stressor for parents. The purpose of this study was to determine whether stress levels differ between preterm and term parents as well as between mothers and fathers when the NICU hospitalization of an infant is experienced. Fifty-three parents completed the Parental Stress Scale: Neonatal Intensive Care Unit (PSS:NICU). Five two-way ANOVA's were computed in order to compare stress scores for preterm and term parents as well as mothers and fathers on each of the PSS:NICU's four subscales and for the instrument as a whole. No significant differences were found between preterm and term parents or mothers and fathers with regard to stress scores. These findings support the need for neonatal nurses to recognize all parents as being equally at risk for experiencing stress when the NICU hospitalization of an infant is experienced. The development of an individualized plan of care for each parent is imperative if adaptation to the NICU hospitalization is to occur.
    • Characteristics of fluoride flux and the absence of a vasopressin-like effect by fluoride in the isolated perfused rabbit cortical collecting duct

      Rouch, Alexander John; Department of Physiology and Endocrinology (Augusta University, 1989-06)
      Fluoride flux (JF) was measured in the isolated perfused rabbit cortical collecting duct (CCD) to determine some of the basic physiological characteristics of JF in this segment. Also, the effect of fluoride on hydraulic conductivity (Lp) in the CCD was assessed. Fluoride can increase cyclic AMP levels in a variety of tissues and the vasopressin-induced increase in Lp in the CCD is a cyclic AMPdependent event. To determine if fluoride would increase Lp. Lp was compared among 3 conditions: 1) control, (no fluoride or vasopressin); 2) with 1 or 5 mM .fluoride in the bath; and 3) with 25 J.LU/ml vasopressin in the bath. The Lp in condition 1 was not different from that in 2 (8.6 ± 1.8 vs 5.0 ± 2.7 cm/sec/atm X I0-7, respectively, n=5) (Data expressed as mean ± SE). Lp in condition 3 (112 ± 7.4 cm/sec/atm X 10-7) was significantly higher than that in 1 and 2 (p<.001). The effect of luminal-fluid pH on JF was assessed. In one set of experiments (n=7), JF determined with a pH of 6.1 was significantly higher than that with a pH of 7.4 (.027 ± .007 vs .008 ± .002 pmole/min/mm, respectively; p<.01). In another set (n=5), JF with a pH of 5.0 was significantly higher than that with a pH of 6.1 (.040 ± .004 vs .018 ± .003 pmole/min/mm, respectively; p<.01). Bath pH was always 7.4. Osmotically-induced, lumen-to-bath fluid flux (Jv) did not affect JF. A 40o/o reduction in the trans epithelial fluoride concentration gradient did not affect JF. The effects of acetazolamide and the disulfonic stilbene DIDS on JF were determined separately by measuring JF in the absence and presence of each agent. Neither of these agents significantly affected JF, although JF was reduced consistently with acetazolamide. JF measured with bicarbonate-buffered solutions (.025 ± .003 pmole/min/ID.Iil, n=30) was significantly higher than that with HEPES-buffered solutions (.012 ± .003 pmole/min/mm, n=16) (p<.02). Transepithelial voltages which ranged from +10 to - 104 mV did not affect JF. It was concluded that: 1) fluoride did not affect Lp: 2) Jv did not affect JF: 3) pH gradients affected JF: 4) acetazolamide and DIDS did not affect JF: 5) JF was affected by the buffer of the solution: and 6) the CCD permeability for fluoride is relatively low.
    • Expression of the virion associated host shutoff protein in equine herpesvirus type-1 RacL strain

      Rossman, Joanne F.; Medical College of Georgia (Augusta University, 1998-07)
    • Studies on multiple aspects of estrogen action

      Rosser, Mary Lee; Department of Physiology and Endocrinology (Augusta University, 1991-05)
    • Neuronal and astroglial injury and recovery from stroke-induced depolarizations

      Risher, William Christopher; Medical College of Georgia (Augusta University, 2010-12)
    • The effect of mineralocorticoid receptor antagonism on ischemic infarct size and cerebral vessel structure in male and femail spontaneously hypertensive stroke-prone rats: sex difference revealed.

      Rigsby, Christine Spring; Medical College of Georgia (Augusta University, 2006-12)
      Stroke is the third leading cause of death ·and the leading cause of long-term disability in the United States, where approximately 88% of stroke occurrences are ischemic in origin. Hypertension is a primary risk factor for stroke. Elevated aldosterone levels have also been identified as a risk factor for stroke, as patients with primary aldosteronism incur increased incidences of cardiovascularrelated pathologies than do patients with essential hypertension. Previous studies from our laboratory have shown that mineralocorticoid (aldosterone) receptor (MR) activation can induce deleterious vascular remodeling and, conversely, blockade of the MR with spironolactone reduces cerebral infarct size in male spontaneously hypertensive stroke-prone rats (SHRSP). It is known from studies in SHRSP that cerebral vessel structure is directly related to infarct size. We hypothesized that chronic spironolactone treatment would alter cerebral vessel structure. Six-week-old male SHRSP were treated with spironolactone for six weeks and passive vessel structure was analyzed using a pressurized arteriograph. Spironolactone treatment prevented cerebral vessel remodeling. From a clinical standpoint, many patients present with pre-existing vascular damage; therefore, we hypothesized that chronic MR antagonism would reverse existing vascular damage. Twelve-week-old male SHRSP were treated as described above. Interestingly, spironolactone treatment partially reversed existing cerebral vessel remodeling. Recent analysis of data from the Framingham Heart Study show that females may be more sensitive to the effects of aldosterone, but few studies looking at MR blockade have been performed in females. Similar ischemic stroke and vascular analysis studies were performed in 12-week-old female SHRSP. Contrary to the male studies, MR antagonism, using spironolactone or eplerenone, did not reduce damage from ischemic stroke or improve vessel structure. MR protein expression was evaluated in cerebral arteries collected from 12-week-old male and female SHRSP using Western blot analysis. Surprisingly, female SHRSP had increased MR expression, compared to male SHRSP. These novel studies uncover an apparent sexual dimorphism in the actions of MR antagonists and expression ofthe.MR in SHRSP. The action of the MR antagonists may be influenced by differential MR expression and this could help to explain the sex difference observed. existing cerebral vessel remodeling. Recent analysis of data from the Framingham Heart Study show that females may be more sensitive to the effects of aldosterone, but few studies looking at MR blockade have been performed in females. Similar ischemic stroke and vascular analysis studies were performed in 12-week-old female SHRSP. Contrary to the male studies, MR antagonism, using spironolactone or eplerenone, did not reduce damage from ischemic stroke or improve vessel structure. MR protein expression was evaluated in cerebral arteries collected from 12-week-old male and female SHRSP using Western blot analysis. Surprisingly, female SHRSP had increased MR expression, compared to male SHRSP. These novel studies uncover an apparent sexual dimorphism in the actions of MR antagonists and expression ofthe.MR in SHRSP. The action of the MR antagonists may be influenced by differential MR expression and this could help to explain the sex difference observed. existing cerebral vessel remodeling. Recent analysis of data from the Framingham Heart Study show that females may be more sensitive to the effects of aldosterone, but few studies looking at MR blockade have been performed in females. Similar ischemic stroke and vascular analysis studies were performed in 12-week-old female SHRSP. Contrary to the male studies, MR antagonism, using spironolactone or eplerenone, did not reduce damage from ischemic stroke or improve vessel structure. MR protein expression was evaluated in cerebral arteries collected from 12-week-old male and female SHRSP using Western blot analysis. Surprisingly, female SHRSP had increased MR expression, compared to male SHRSP. These novel studies uncover an apparent sexual dimorphism in the actions of MR antagonists and expression ofthe.MR in SHRSP. The action of the MR antagonists may be influenced by differential MR expression and this could help to explain the sex difference observed.
    • Herpesvirus prevalence and methylation status in ganglia of the human head and neck

      Richter, Elizabeth R.; Medical College of Georgia (Augusta University, 2008-07)
      The neurotropic human alphaherpesviruses, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and varicella-zoster virus (VZV), are latent in a majority of the adult population. These viruses can reactivate to cause many diseases (e.g. herpes labialis, shingles) and sometimes unusual clinical sitespecific neurological syndromes ranging from neuralgia to deadly encephalitis. Although the trigeminal ganglion has been thought to be the main site of reactivation, additional sensory and autonomic ganglia contain viral genomes. A comprehensive study of these additional sites of latency and their respective viral burden is needed to understand the full spectrum of latency and possible sites of viral reactivation in humans. While animal models of HSV provide some insight into the pathogenesis of herpesvirus infections, they do not provide information about the prevalence and characteristics of these viruses in their natural host. The overall goal of this study was to elucidate the distribution of the neurotropic human herpesviruses and to determine whether ganglionic positivity at one site in the head and neck correlated with virus presence in ipsilateral and/or contralateral sites. By using formalin-fixed tissue from human cadavers, we were able to: 1) investigate the frequency and correlation of genomes in 8 ganglia on each side of the head and neck, and 2) determine whether latent virus exists in a methylated state. From these studies, we now have a more complete characterization of latency patterns in the human head and neck. This thorough comparison among 16 ganglia around the head and neck provided a more comprehensive perspective of the pattern of latency and by extrapolation, of sites of possible reactivation. The results of these studies suggest that HSV-1 and VZV (but not HSV-2) are independently distributed among ganglia of the human head and neck and that DNA methylation of the HSV-1 genome is not a likely epigenetic mechanism in latently infected human ganglia. An expanded knowledge of latency sites, prevalence of latency, and epigenetic mechanisms of latent viruses in the head and neck may provide insight into the pathogenesis of herpesvirus infection in unusual sites. Such knowledge may also be used to develop approaches to reduce or prevent reactivation or to ameliorate the effects of herpesvirus infections of the head and neck.
    • Musculoskeletal disorders in Georgia sonographers

      Yeyes, Lynn K.; Medical College of Georgia (Augusta University, 2001-03)
    • CJ0596 plays a role in the virulence of campylobacter jejuni

      Rathbun, Kimberly M.; Doctor of Philosophy (Augusta University, 2009-05)
      Campylobacter jejuni is a gastrointestinal pathogen of humans but part of the normal flora of poultry. C. jejuni therefore grows well at both 37°C and 42°C. Proteomic studies on temperature regulation in C. jejuni strain 81-176 revealed the upregulation at 37°C of Cj0596, a predicted periplasmic chaperone that is similar to proteins found to be involved in outer membrane protein (OMP) folding and virulence in other bacteria. The cj0596 gene was highly conserved in multiple strains and species of Campylobacter (24 in total), implying the importance of this gene. To study the role Cj0596 plays in Campy/obacter pathogenesis, a mutant derivative of strain 81-176 was constructed in which the cj0596 gene was precisely deleted. This mutant was complemented by restoring the gene to its original chromosomal location. The mutant strain demonstrated a decreased growth rate and lower final growth yield, yet was more motile than wild-type. The cj0596 mutant also showed altered levels of several outer membrane proteins (OMPs), and changes in membrane-associated characteristics (antimicrobial sensitivity, autoagglutination, and biofilm formation). In either single or mixed infections, the mutant was less able to colonize mice than wild-type. Purified, recombinant Cj0596 had peptidyl-prolyl cistrans isomerase (PPiase) activitty, but did not functionally complement an E. coli surA mutant. These results suggest that C. jejuni Cj0596 is a PPiase and loss of Cj0596 alters phenotypes that have been shown to be related to the pathogenesis of the bacterium.
    • Physiological consequences of ENOS subcellular targeting

      Qian, Jin; Medical College of Georgia (Augusta University, 2012-01)
      Anti-inflammatory effects of NO are thought to involve inhibition of the proinflammatory transcription factor, NF-KB. NO represses the nuclear translocation ofNFKB via the S-nitrosylation of its subunits which decreases the expression of target genes including adhesion molecules. We next investigated the significance of subcellular targeting of eNOS to NF-KB signaling induced by proinflammatory cytokines in human aortic endothelial cells (HAECs). We found that in HAECs stimulated with TNFu, LNAME did not influence the expression of ICAM-1 or VCAM-1. In eNOS "knockdown" HAECs, reconstituted with either PM- or Golgi- restricted forms of eNOS, there was no significant effect of endogenously produced NO on the activation of the NF-KB pathway in response to different concentrations and exposure times of TNFu. Similarly, the endogenous production of NO did not influence the phosphorylation of IkBu and Snitrosylation of IKKP or p65. In contrast, higher concentrations of NO, derived from the use of the exogenous NO donor, DETA NONOate, effectively suppressed the expression of ICAM-1NCAM-1 in response to TNFu and induced more S-nitrosylation of IKKP and p65. These results suggest that neither endogenous eNOS nor eNOS location is an important regulatory influence on inflammatory signaling in HAECs via the NF-KB pathway and that higher NO concentrations are required to suppress NF-KB. A third focus of non-cGMP NO signaling was the NADPH oxidases (Nox), a family of transmembrane oxidoreductases that produce superoxide and other reactive oxygen species (ROS). There are 5 family members (Noxl-5) with Nox5 the last of the conventional Nox isoforms to be identified. Nox5 is a calcium-dependent enzyme that does not depend on accessory subunits for activation. Recently, Nox5 was shown to be expressed in endothelial cells in human blood vessels and therefore we investigated whether endogenous levels of NO can influence Nox5 activity and if so to identify the mechanisms involved. We found that endogenous NO was a potent inhibitor of basal and stimulated Nox5 activity and inhibition was reversible with chronic, but not acute exposure to L-NAME. Nox5 activity was reduced by NO donors, iNOS, eNOS and in endothelial cells and cytokine-stimulated smooth muscle cells in a manner proportional to the NO concentration. ROS production was diminished by NO in an isolated enzyme activity assay replete with surplus calcium and NADPH. There was no evidence for NOdependent changes in tyrosine nitration, glutathiolation or phosphorylation of Nox5 and ROS production was not modified by GAPDH. In contrast, there was evidence for the increased nitrosylation of Nox5 as .determined by the biotin-switch assay and mass spectrometry. Four S-nitrosylation sites were identified and of these, mutation of C694 dramatically lowered Nox5 activity, NO-sensitivity and biotin-labeling. Furthermore, coexpression of the denitrosylation enzymes thioredoxin (Trxl) and GSNO reductase (GSNOR) prevented NO-dependent inhibition ofNox5. The potency of NO against other Nox enzymes was Noxl:;::Nox3>Nox5>Nox2 whereas Nox4 was refractory. These results demonstrate that endogenously produced NO can directly S-nitrosylate and inhibit the activity ofNox5. The overall conclusion of these studies is that the amount of NO is the most important variable influencing protein S-nitrosylation and function.
    • A counseling intervention to improve personal control, affective outcomes, and satisfaction in surrogate decision makers at end-of-life

      Purvis, Reese J.; Medical College of Georgia (Augusta University, 2006-02)
      This study investigated whether personal control, situational anxiety, situational depression, and satisfaction with end-of-life (EOL) care might be improved in surrogate decision makers who receive a cognitive-behavioral decision making intervention. The sample consisted of 38 surrogate decision makers for 38 incapacitated patients in three hospitals in a moderate sized city in the. Southeastern United States. The demographic characteristics of sample included: 50% female and 50% male, 50% African-American and 50% White, and 81.6% Protestant. Although the sample was small, the demographic composition of the sample was highly consistent with the population of the community in which the study was conducted. Guided by Bandura's Social Cognitive Theory, it was hypothesized that experimental (DMCI) group subjects would score higher on posttest measures of personal control and satisfaction with EOL care than subjects in the usual care group. It was also hypothesized that experimental group subjects would score lower on posttest measures of depression and anxiety. Pretest and posttest scores on five instruments were compared and analyzed for an experimental group, N=19 which received the DMCI versus a control group, N= 19, that received only usual care. Instruments used to assess the dependent variables of personal control, affective outcomes, 3!1d satisfaction with end-of-life care were: the Pearlin Mastery Scale, the Perceived Personal Control Questionnaire, the Beck Depression Inventory, the Beck Anxiety Inventory, and the FAMCARE Scale. Data were collected over a seven month period from Summer 2004 to Spring 2005. After obtaining informed consent experimental participants completed all instruments (pretest), received three counseling sessions over approximately 14 days and then completed all instruments again (posttest). Control group members after providing informed consent also completed all instruments (pretest), received three attention- usual care contacts, and subsequently completed all instruments again (posttest). Data were analyzed using descriptive statistics, Chi-Square, Mann-Whitney Test, and 2-way ANOV A with one repeated measure. The factors were group assignment (experimental vs. control) and time (pretest vs. posttest) with time as the repeated factor. Chi-square, and Mann-Whitney tests showed the groups were comparable at pretest and that demographically the random assignment to groups was effective. The 2-way ANOV A results showed significant interaction effects in each case. The experimental group scored higher or lower posttest as predicted by the hypotheses compared to the control group.