• Correlates of Breast Self-Examination in Women 18 to 35 Years of Age

      Grones, Glenda K M; Department of Physiological and Technological Nursing (3/18/1997)
      This study was a retrospective, cross-sectional, correlational inquiry of breast self-examination (BSE) behavior in young women. The variables intrinsic motivation, self-efficacy, knowledge, benefits, barriers, susceptibility, seriousness, and demographic variables were examined in relationship to three dependent variables, frequency, proficiency, and combined frequency and proficiency of BSE, to determine which variables predicted BSE in a sample of young women. The sample comprised n = 255 college women (M age = 23 years). Subjects were classified as low, moderate, or high performers based on reported frequency of BSE. Kruskal- Wallis and chi-square tests revealed significant group differences were evident for the variables insurance (x2= 6.8,_p = .024) and high risk status (%2 = 7.6, p = .022). A previous PAP smear and having been taught BSE approached significance at the alpha .05 level. No significant group differences were found for the variables age, race, marital status, education, previous clinical breast examination (CBE), or having been recommended to perform BSE. Low performers were typically younger (< 21 years), undergraduate students, who were unmarried and uninsured; who reported never having a PAP smear or CBE, never being recommended to perform, and never been taught BSE. Bivariate correlations showed intrinsic motivation, self-efficacy, knowledge, benefits, and barriers were significantly related to BSE behavior, and in the predicted direction. Subsequent hierarchical regression analyses revealed only four significant predictors: self-efficacy, knowledge, barriers, and the interaction between knowledge and self-efficacy. Barriers was directly and negatively predictive of BSE. However, analyses of the significant interaction showed a moderating and enhancing, rather than direct effect o f self-efficacy on BSE behavior. More knowledge produced increased BSE behavior only when moderate to high degrees of self-efficacy were evident. For those subjects with low self-efficacy scores more knowledge did not increase BSE behavior. Both knowledge and self-efficacy were needed to maximize BSE performance for these young women.
    • The correlation between powerlessness and job satisfaction in female registered nurses employed on medical-surgical units in hospital settings

      McCord-Cass, Bobbye; School of Nursing (1982-12)
      T~e relationship between powerlessness and job satisfaction was examined in 44 female registered nurses employed on medical-surgical units housed in two large teaching hospitals. The nurses were administered three structured questionnai~es: The Demographic Questionnaire, the Job in General Scale, and the Health Care Work Powerlessness Scale (.Revisedl .. Data were analyzed using ·a Pearson's Correl.ation Coefficient. The findings showed a statistically significant negative correlatioh between p6werlessness and job satisf act i. on ( r =-. 310, ~< • 0.2 51, suggest i n g that as power 1 e s sness i-ncreases,. job s.attsfaction decr-eases. This finding provides des.c.riptive data wh·ich implies that as powe·rlessness increases in hospital~hased RNs, the· likelihood exists t h.a t j o b s a t i s fa c t i o n w i 1 1 de c r e a s e .
    • Correlation Coefficient Inference for Left-Censored Biomarker Data with Known Detection Limits

      McCracken, Courtney Elizabeth; Department of Biostatistics and Epidemiology (2013-05)
      Researchers are often interested in the relationship between biological concentrations obtained using two different assays, both of which may be biomarkers. Despite the continuing advances in biotechnology, the value of a particular biomarker may fall below some known limit of detection (LOD). Data values such as these are referred to as non-detects (NDs) and can be treated as left-censored observations. When attempting to measure the association between two concentrations, both of which are subject to NDs, serious complications can arise in the data analysis. Simple substitution, random imputation, and maximum likelihood estimation methods are just a few of the methods that have been proposed for handling NDs when estimating the correlation between two variables, both of which are subject to left-censoring. Unfortunately, many of the popular methods require that the data follow a bivariate normal distribution or that only a small percentage of the data for each variable are below the LOD. These assumptions are often violated with biomarker data. In this paper, we evaluate the performance of several methods, including Spearman’s rho, when the data do not follow a bivariate normal distribution and when there are moderate to large censoring proportions in one or both of the variables. We evaluate the performance of seven methods for estimating the correlation, ρ, between two left-censored variables using bias, median absolute deviation, 95% confidence interval width, and coverage probability under assumptions of various sample sizes, correlations, and censoring proportions. We show that using substitution and imputation methods yields biased estimates of ρ and less than nominal coverage probability under most of the simulation parameters we examined. We recommend the maximum likelihood method for general use even when the data significantly depart from bivariate normality.
    • A Counseling Intervention to Improve Personal Control, Affective Outcomes, and Satisfaction in Surrogate Decision Makers at End-of-Life

      Purvis, Reese J.; Department of Physiological and Technological Nursing (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, and 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 ANOVA 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 ANOVA 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.
    • Creating a new life : the process of temperance for perinatal cocaine crack users

      Pursley-Crotteau, Margaret Suzanne; School of Nursing (1995-03)
    • Creating a New Life: The Process o f Temperance For Perinatal Cocaine Crack Users

      Pursley-Crotteau, Margaret S.; Department of Physiological and Technological Nursing (1995-03)
      Research related to cocaine crack use during pregnancy has focused on prevalence, increased maternal morbidity and mortality, neonatal outcomes, and the teratology o f cocaine use. The purpose o f this study was to explore from a feminist perspective how pregnant women with a history o f cocaine crack use participate in prenatal care. The context o f the study was an inner city hospital Psych-OB clinic within a Maternal and Infant Project. Initially, I recruited nine women for the study. All had a history o f cocaine crack use by self-report and as documented in clinical records. The women were actively participating in the prenatal clinic and in some type o f substance abuse treatment. Additional participants were selected through theoretical sampling and included women participating and not participating in substance abuse treatment. I selectively interviewed 19 women. Besides in-depth interviews, data were also collected through participant observation and document reviews. The constant comparative analysis of the data o f grounded theory was used to develop, interpret, and analyze the data. I collected and analyzed data until all categories were saturated and the core variable was identified. Staying Clean w as the psychosocial problem as identified by the women. Creating a new life was identified as the process by which the women manage to stay clean during their pregnancy. Creating a new life had three phases: drifting in, tuning in/tuning out, and drifting out. D rifting in had three stages: knowing about the pregnancy, ignoring the pregnancy, and acquiescing to the pregttancy. The second phase tuning in/tuning out had three stages which represented the striving by the women to integrate both a maternal identity and an addict identity within the treatment structure. These stages were: struggling with s e lf and others, assimilating a new identity, and accepting the adjusted self. The final phase had two strategies: buying into recovery and clutching at normalcy. This substantive theory provided a broader understanding o f the experiences o f women who are pregnant and use cocaine. Based on this theory, I explored implications for health policy in perinatal substance abuse treatment, proposed innovative models for early intervention and improved treatment programs, and suggested further research from both qualitative and quantitative perspectives.
    • Creating a selective advantage for stem cells : a strategy for gene therapy

      Menzes, Kareena M.; School of Graduate Studies (1999-10)
    • Creating a Selective Advantage for Stem Cells: A Strategy for Gene Therapy

      Menezes, Kareena M.; Department of Cellular Biology and Anatomy (1999-10)
      (Statement of the Problem) Various approaches are used to treat the many known genetic diseases. The treatments are often incompletely effective, and they sometimes have undesirable side effects. Somatic cell gene therapy might provide truly effective permanent cures. Gene therapy, however, is still in the experimental stages, and much needs to be learned about stem cell biology before gene therapy becomes routine clinical practice. Moreover, inferences made from experiments in vitro do not necessarily model the in vitro setting. If treatments designed and tested in vitro can also be made workable and proven to be therapeutic in vivo, a major contribution to clinical gene therapy would be achieved. The described research, which attempts to encourage the stem cells to proliferate rather than divide down the hematopoietic cascade, could be significant in terms of increasing in number those hematopoietic cells that have been successfully modified by therapeutic vectors. The long-term goal of this research is to find a way to provide modified stem cells with a selective advantage in repopulating the marrow of a patient with a genetic disease. Ultimately it will be necessary to confer the selective advantage on somatic cells by introducing DNA into the patient’s defective bone marrow stem cells. However for purposes of preliminary laboratory analyses, a more reproducible system of testing a candidate genes’ potential for providing a selective advantage is necessary. In the present case, an Erythropoietin Receptor transgenic mouse line is used to provide stem cells, each of which already expresses the candidate selective-advantage gene.
    • The criminal prosecution of mothers of drug-exposed neonates : a case study of a policy dilemma

      Christensen, Patricia; School of Nursing (1992-05)
      The purpose of this study was to describe and analyze the policy to prosecute women who exposed their infants to drugs during pregnancy. The time frame of the study was from July, 1989 to January, 1992. This policy was developed and implemented by an interorganizational network of legal and health professionals acting collectively. Case study was the methodology used in this research. Data were collected from numerous sources, including semistructured interviews of members of the interorganizational. network and the women prqsecuted. Additional data included court records, laws, policies, protocols, quality assurance records, minutes of meetings, letters, demographic data, observations of court proceedings and . parole settings as well as publications in the public domain. The theoretical framework was the collective-action view of · '":H ·· organizational behavior. The findings of the study suggested that the policy was designed, not to incarcerate the women, but as legal leverage to force the mothers into drug treatment and to give the court system control over the risk factors in their infants' environments. The state child neglect laws were used _as the legal means to force the women into treatment and assign custody of their infants. Evidence suggested that health._ professionals cooperated with the prosecution primarily as advocates for _the drug-exposed infants--to protect them from abuse and neglect. The women prosecuted were poor, predominantly Black (85% ), and their drug of choice was overwhelmingly "crack" cocaine. The vast majority of these women had experienced physical and sexual abuse. Mo.st of the women were sent to court-mandated outpatient treatment. Five women were sent to prison; all five had additional criminal charges. Approximately 90% of the women in treatment were still using drugs. Over 60% of the 75 women mandated to treatment had dropped out of the treatment or were unsuccessfully terminated. Approximately 65% of the infants showed ill effects from their in utero drug exposure. These effects included hyperirritability, hypertonicity, delayed social development, and poor eye contact and tracking. , These symptoms showed improvement between two and four. months of age. Custody placement of the 109 affected infants was: 36% with th·e mothers, 28% with relatives of the mothers, 24% in foster homes, 8% adopted outside the family. Two of the infants died. ' Implications for practice suggest that drug-abusing women were not avoiding health providers for delivery of their infants due to the policy,· primarily because there are no other options available, short of delivering at home. There were data to suggest that women were staying away from prenatal care, but thi~ finding was confounded by the coincidental increase in women enrolled in prenatal care due to increased Medicaid funding. There was no evidence found that the· prosecuted mothers had changed their perceptions of health professionals as a result of their experiences. , There was no expressed loss of trust nor any evidence that. there had ever been any trust in health professionals related to patient confidentiality. Data suggested that health professionals were perceived by these women as part of the system, not as client advocates. Health professionals were viewed in a predominantly positive light by these mothers. The major exception to this positive view was the percepti?n that pain medication· was withheld from them during delivery because they were identified as· drug users.
    • The Criminal Prosecution of Mothers of Drug-exposed Neonates: A Case Study of a Policy Dilemma

      Christensen, Patricia B.; Department of Physiological and Technological Nursing (1992-05)
      The purpose of this study was to describe an analyze the policy to prosecute women who exposed their infants to drugs during pregnancy. The time frame of the study was from July, 1989 to January, 1992. This policy was developed and implemented by an interorganizational network of legal and health professionals acting collectively. Case study was methodology used in this research. Data were collected from numerous sources, including semi-structured interviews of members of the interorganizational network and the women prosecuted. Additional data included court records, laws, policies, protocols, quality assurance records, minutes of meetings, letters, demographic data, observations of court proceedings and parole settings as well as publications in the public domain. The theoretical framework was the collective-action view of organizational behavior. The findings of the study suggested that the policy was designed, not to incarcerate the women, but as legal leverage to force the mothers into drug treatment and to give the court system control over the risk factors in their infants’ environments. The state child neglect laws were used as the legal means to force the women into treatment and assign custody of their infants. Evidence suggested that health professionals cooperated with the prosecutions primarily as advocates for the drug-exposed infants—to protect them from abuse and neglect. The women prosecuted were poor, predominantly Black (85%), and their drug of choice was overwhelmingly “crack” cocaine. The vast majority of these women were sent to court-mandated outpatient treatment. Five women were sent to prison; all five had additional criminal charges. Approximately 90% of the women in treatment were still using drugs. Over 60% of the 75 women mandated to treatment had dropped out of the treatment or were unsuccessfully terminated. Approximately 65% of the infants showed ill effects from their in utero drug exposure. These effects included hyperirritability, hypertonicity, delayed social development, and poor eye contact and tracking. These symptoms showed improvement between two and four months of age. Custody placement of the 109 affected infants was: 36% with the mothers, 28% with relatives of the mothers, 24% in foster homes, 8% adopted outside the family. Two of the infants died. Implications for practice suggest that drug-abusing women were not avoiding health providers for their infants due to the policy, primarily because there are no other options available, short of delivering at home. There were data to suggest that women were staying away from prenatal care, but this finding was confounded by the coincidental increase in women enrolled in prenatal care due to increased Medicaid funding. There was no evidence found that the prosecuted mothers had changed their perceptions of health professionals as a result of their experiences. There was no expressed loss of trust nor any evidence that there had ever been any trust in health professionals related to patient confidentiality. Data suggested that health professionals were perceived by these women as part of the system, not as client advocates. Health professionals were viewed in a predominantly positive light by these mothers. The major exception to this positive view was the perception that pain medication was withheld from them during delivery because they were identified as drug users
    • Cultivation of microfilariae from the dog and raccoon /

      Winningham, Annie Ruth; Department of Cell and Molecular Biology (1967-11)
    • Cutaneous corpuscles of the cephalic integument of the Texas rat snake: morphological and electrophysiological studies

      Jackson, Morris K; Department of Anatomy (1975-08)
      The structure and function of corpuscle-like structures which were found in the cephalic integument of the Texas rat snake, Elaphe ohsoleta lindheimeri,_were_investigated. These structures, henceforth called touch cotpuscles, were identif~ed by .the ~tereomicroscope as surface elevations. Their number and distribution were determined in cephalic scales of.intact skin and shed exuviae. The num.ber of.touch . corpus·cles per unit area of skin was great.er in. anterior cephalic scales than posterior scales. The· density of touch corpuscles decreased as the . . size of the snakes increa.sed • . The surface morphology of the ·touch corpuscles was studied with the scanning electron microscope. Each .elevation consisted of a crater~ like structure containing a central peg which ext.ended out of th!= circular depressi':ln• Histologically, the touch corpuscle appeared af> an organized group of cells and nerve. fiber:s which evaginated into the epidermis and became encapsulated by epidermal cells. Studies using Sudan black B. ·and silver impregnation stains r~vealed .. that 3 or 4 myelinated nerve fibers (5 p diameter) approached the base of a corpuscle, became unmyelinated~ and branched into 2 or 3 smaller fibers (1 p diameter). which entered the corpuscle. Fibers were traced near their terminatiOns in the apex of the corpuscle with ·Bodian protargol nerve stain. Ultrastructurally, the touch corpuscle possessed axially positioned central cells whose attentuated processes extended towards the periphery. Unmyelinated nerve fibers were grouped between processes, and each fiber retained its Sch,;vann cell investment. An enveloping basal lamina and adjacent circumferential layer of unorganized collagen fibers surrounded the inner components of the corpuscle. Out~r surrounding·epidermal cells ( po!:jsessed fewer bundles of keratin tonofilaments and increC).sed numbers of ·mitochondria·than regular adjacent epidermis. The structure of each cell layer of the epidermis was described and the fine structure of lipids and cholest.erol ester clefts within the lacunar layer was studi·ed. The re~ponse ptoperties of 146 sitigle nerve fibers teased from the superficial branch of the maxillary nerves of .11 rat· snakes were s~udied. It was determined that . the touch corpuscle. was a rapidly. adapting me.chano- . receptor which was optimally excited by the movement of a mechanical stimulus across the surface peg. Receptive fields, stirimlus threshplds, adaptation rates, and adequate stimuli were determined for other noncorpuscle nerve fibers •. It was conclud~d.that the touch :corpuscle of the Texas rat snake is a structurally and functionally unique mechanoreceptor.
    • CXCR2 EXPRESSING TUMOR CELLS DRIVE VASCULAR MIMICRY IN ANTI-ANGIOGENIC THERAPY RESISTANT GLIOBLASTOMA

      Angara, Kartik Prasad; Department of Biochemistry and Molecular Biology (Augusta University, 7/20/2018)
      Glioblastoma (GBM) is a hypervascular and hypoxic neoplasia of the central nervous system with an extremely high rate of mortality. Owing to its hypervascularity, anti-angiogenic therapies (AAT) have been used as an adjuvant to the traditional surgical resection, chemotherapy, and radiation to normalize blood vessels, control abnormal vasculatures and prevent recurrence. The benefits of AAT have been transient and the tumors were shown to relapse faster and demonstrated particularly high rates of AAT-induced therapy resistance due to activation of alternative neovascularization mechanisms. Vascular Mimicry (VM) is the uncanny ability of tumor cells to acquire endothelial-like properties, lay down vascular patterned networks reminiscent of host endothelial blood vessels and served as an irrigation system for the tumors to meet with the increasing metabolic and nutrient demands in the event of the ensuing hypoxia resulting from AAT. In our studies, we have demonstrated that AAT accelerates VM. We observed that Vatalanib (a VEGFR2 tyrosine kinase inhibitor) induced VM vessels are positive for periodic acid-Schiff (PAS) matrix but devoid of any endothelium on the inner side and lined by tumor cells on the outer side. Interestingly, 20-HETE synthesis inhibitor HET0016 significantly decreased GBM tumors through decreasing VM structures both at the core and at the periphery of the tumors. During our extensive studies to understand the tumor-inherent mechanisms of AAT-induced resistance, we identified a crucial chemokine, CXCL8 or IL-8, to be highly upregulated in the GBM tumors treated with AAT. IL-8 has been well established as a highly prevalent cytokine in GBM with potent pro-migratory and pro-angiogenic functions. AAT-treated groups had significantly higher populations of CXCR2+ glioma stem cells and endothelial-like subpopulations and these populations were decreased following treatment with HET0016 and SB225002 (a CXCR2 antagonist). CXCR2+ GBM tumor cells were shown to form VM-like vascular channels carrying functional RBCs. Knocking down CXCR2 led to smaller tumor size in the animals and improperly developed vascular structures without CXCR2+ GBM cells lining them. This confirms our hypothesis that CXCR2+ GBM cells initiate VM and contribute to AAT resistance in GBM. Our present study suggests that HET0016 and SB225002 have potential to target therapeutic resistance and can be combined with other antitumor agents in preclinical and clinical trials.
    • The Cybersecurity Dilemma and Targeted Advertising

      Martin, Elizabeth; Department of Social Sciences (Augusta University, 2020-05)
      A great debate remains regarding whether cyberspace is offense dominant or defense dominant. This paper reviews the literature of scholars within the cybersecurity offense-defense balance theory discipline. It discusses both the offensive and defensive arguments in detail and determines the United States should ultimately pursue a defensive dominance to ensure cyber superiority. To emphasize the need for defense, the three-year, social-media platform-based, Russian Federation Information Operation serves as a baseline example. Russia not only sowed distrust in the American Democratic process but was successful in inflaming fragile social issues throughout the United States. Russia directly threatened United States sovereignty across an extended period of time and did so, literally from half a world away. This paper serves to develop the role Information Warfare has in manipulation of the Offense-Defense Balance and concludes with the discussion for much needed legislation change, industrial herd immunity, and increased and direct investment in defense and education.
    • Cytoprotective Actions of Nicotine: The Increased Expression of a7 Nicotinic Receptors and NGF/TrkA Receptors

      Jonnala, Ramamohana R.; Department of Pharmacology and Toxicology (2001-07)
      Certain epidemiological studies have reported a negative correlation between smoking and neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease, reflecting perhaps the neurotrophic actions of nicotine. In recent years there has been intense interest in the development of new nicotinic acetylcholine receptor (nAChR) agonists. These agents have the potential to be used in the treatment of patients with AD. However, the mechanism for the neuroprotective action of the nicotine is not yet known, indeed, it is not yet clear as to which subtype of nAChR mediates the response. In neuronal cell lines, the induction of cytoprotection often requires exposure to nicotine for up to 24 hr to produce a full neuroprotective effect and this chronic exposure of nicotine is also known to increase nAChR receptors and cell surface nerve growth factor (NGF) receptors. The purpose of this study is to determine which subtype of nAChRs are involved in nicotine’s neuroprotective actions and also to determine whether nicotine’s neuroprotective actions are related to its ability to increase cell surface nAChRs and NGF receptors. Preincubation of differentiated PC 12 cells with nicotine for 24 hr protected the cells from growth factor withdrawal-induced toxicity in a time and concentration-dependent manner. Nicotine’s cytoprotective actions were completely blocked by non-selective nAChR antagonist mecamylamine, and the cc7nAChR preferring antagonist methyllcaconitine (MLA) indicating that the response was primarily mediated by the subtype of a7 nAChR receptors. The acetylcholine precursor, choline is a very selective and full agonist at a7 receptors. Among five choline analogs tested for neuroprotection potential, acetylpyrrolidinecholine and pyrrolidinecholine were found to be more potent and more efficacious than their parent compound, choline. The rank order of the six compounds tested for their cytoprotective ability is as follows: acetylpyrrolidinecholine = pyrrolidinecholine > choline = monoethylcholine = diethylcholine = triethylcholine. Further, to confirm the above structure activity relationships with respect to their binding affinities at a7nAChR, [I25I]a-bungarotoxin (BGT) displacement binding studies were performed using differentiated PC 12 cells. Choline was only 50 fold less potent than nicotine in displacing [ I]a-BGT binding. Pyrrolidinecholine, the most active analog, fully displaced [l25I]a-BGT binding and it exhibited a slightly greater affinity for the site than did choline. Next we compared the ability of seven different nAChR agonists with varying activities at a7 receptors for their ability to produce cytoprotection. Among the seven compounds tested, nicotine was the most effective and the most potent followed in order of potency by 40H-GTS21, epibatidine, methylcarbamylcholine, l,l-Dimethyl-4-phenyl-piperazinum, cytisine and tetraethylammonium. Since, epibatidine and cytisine were less efficacious than nicotine despite their greater affinity for a7 receptors and because short-term exposure of cells to nicotine did not produce cytoprotective actions, we next compared the ability of these compounds to upregulate cell surface a7 receptors. After, incubation of cells for 2 hr with either nicotine or cytisine, the number o f [I25I]a-BGT binding sites on differentiated PC 12 cells were measured. Nicotine, the most efficacious compound increased the [l2SI]a- BGT binding sites by ~40% over the untreated control cells. In contrast, cytisine, the least effective compound failed to do so, indicating that the ability to upregulate a7 receptors may provide one possible mechanism for neuroprotective actions of nicotine. Further, we confirmed that these additional populations of receptors were functional and that they mediate an enhanced neuroprotective response to subsequent nicotine stimulation. Earlier studies had shown that prolonged exposure to nicotine increases NGF receptors on differentiated PC12 cells. In the present study, high affinity NGF receptors (TrkA) were shown to increase with nicotine treatment in a time-and concentrationdependent manner. This effect was blocked by co-treatment with mecamylamine and with MLA, but not a low concentration of dihydro-P-erythroidine (selective for P2 and p4 containing receptors), indicating that the response was mediated by predominantly a7 nAChRs. Next, we measured the TrkA protein levels in rat hippocampal and cortical tissues after nicotine treatment. Chronic nicotine infusion increased TrkA protein levels within the hippocampus, and this effect was blocked by co-treatment with mecamylamine. In contrast, TrkA protein levels in cortical tissues were not altered. Since the majority of nAChRs in hippocampus are of the a7 subtype and whereas in cortex consist largely of the a4p2 subtype, it is reasonable to conclude that the differences observed in TrkA receptor expression in hippocampus and cortex were due to presence of a7nAChR. and non-a7nAChR. To determine whether the neuroprotective actions of nicotine were due to enhanced NGF trophic activity during the drug incubation period, the ability of nicotine to protect cells from trophic factor withdrawal in the presence and in the absence of NGF were compared. Nicotine was found to be effective in both experimental paradigms. However, nicotine was found to be 10 fold more effective when it was incubated with cells in the presence of NGF. When cells were treated with nicotine and k252a or nicotine and anti-TrkA antibody, nicotine was only partially effective as a neuroprotective agent, indicating that mechanisms apart from enhanced NGF mediated trophic activity during drug incubation period were involved in nicotine’s cytoprotective actions. One consistent finding with regard to in AD pathology is the selective loss of basal forebrain cholinergic neurons (BFC). The survival and maintenance of these neurons depended on the availability of NGF from target tissues. Evidence from previous studies suggests that impairment in NGF support could be an initial insult in AD pathology. Previous studies have shown that much of the oxidative damage in AD tissue was mediated by peroxynitrite. Breif exposure of undifferentiated PC 12 cells to 3- morpholinosydnonmine (SIN-1, peroxynitrite generator) was sufficient to inhibit an NGF mediated cellular response by 67% of that measured in control cells. This inhibition of the NGF cellular response by SIN-1 was not related to generalized cellular toxicity. In fact, the peroxynitrite scavenger uric acid significantly attenuated the inhibitory actions of SIN-1. Pretreatment with SIN-1 also resulted in a decrease in the NGF-induced phosphorylation of TrkA protein. Furthermore, SIN-1 treatment reduced the activity of mitogen activated protein kinase, a downstream kinase activated by TrkA receptor stimulation'. These data suggest that SIN-1 treatment inhibits NGF signaling by inactivating TrkA receptors through the formation of nitrotyrosine residues on the receptor. The inactivation of TrkA receptors may contribute to the initial insult that eventually ieads to neuronal cell death.