|1. Bresnick, Melissa G., Katherine Elizabeth O’Leary, Dominique Caruso, and Robin
Gaines Lanzi, Ph.D. Relationship Between Social Support and Self-Reported Hopes and Goals Among Low-Income, Adolescent Females. Department of Human Science and
Georgetown University Center on Health and Education, School of Nursing and Health Studies.
Theoretically, adolescents from diverse family settings have comparable needs for a strong and continuous social support system from parents and peers; however, the mechanisms in which variations in support affect adolescent development and future goal setting is not well understood (Antonucci, 1994). Research has shown that during early and middle childhood, children rely heavily on their parents for support, whereas, during adolescence, they report greater reliance on their peers for social support (Burke, 1979; Whitman 2001). It is important to note, however, that parents continue to play an important role in providing support (Cauce, 1990). The proposed research examines how the presence and absence of social support from parents and peers affect low-income adolescent females’ perceptions of self as well as their hopes and goals.
Specifically, this study examines the specific ways in which supportive relationships with parents and peers affect the level of motivation and perceived capability in the adolescents’ self reported hopes and goals. Social support information was gathered from 86 adolescent females between 15 and 18 years of age regarding their perception of important figures in their lives such as parents, friends and boyfriends.
It was found that open-ended questions about hopes and goals could be categorized according to varying levels of ambition and motivation. Emerging patterns indicate that a lack of stable, satisfactory support networks from parents and peers is associated with less ambitious aspirations compared to the career-oriented goals of females who perceived more positive support relationships in their lives. It is of paramount importance that future scientific endeavors examine the relationship between levels of social support and adolescents’ perceived ability to achieve.
Antonucci, T. C., & Akiyama, H. (1994). Convoys of attachment and social relations in children, adolescents, and adults. In F. Nestmann & K. Hurrelmann (Eds.), Social networks and social support in childhood and adolescence (pp.37-52). Berlin, Germany: Walter de Gruyter.
Cauce, A., Reid, M., Landesman, S., & Gonzales, N. (1990). Social support in young children: Measurement, description, and behavioral impact. In I. Sarason, B. Sarason, & G. Pierce (Eds.), Social support: An interactional view (pp.64-94). New York: John Wiley & Sons.
Burke, R.J., Weir, T. (1979). Helping responses of parents and peers and adolescent well-being. Journal of Psychology. 102. pp 49-62.
Whitman, T.L., Borkowski, J.G., Keogh, D.A., Weed, K. (2001). Interwoven Lives: AdolescentMothers and their Children. New Jersey: Lawrence Erlbaum Associates Publishers.
Wentzel, K.R. (1998). Social relationships and motivation in middle school: the role of parents, teachers, and peers. Journal of Educational Psychology, 90(2). pp 202-209.
2. Cesari, Whitney Ann. The Role of ErbB2 and PI 3-K/Akt in the Development of Hormone Resistance in Breast Cancer. Department of Human Science, Georgetown University School of Nursing and Health Studies.
Presence of ER-? in breast tumors predicts patient response to hormone therapy. However, most patients eventually develop resistance to endocrine therapy. Identifying cellular pathways which cause resistance to hormonal treatment determines the direction of future therapy.
To study the acquired hormone resistance of MCF-7 breast cancer cells during treatment, specifically the role of estrogens, ErbB2 and PI3-K we used three variants of MCF-7 cells. LCC1 cells grow independently of estrogen, but are sensitive to tamoxifen. LCC2 and LCC9 cells underwent long-term treatment with anti-estrogens and are estrogen-independent and tamoxifen resistant. Previous results have shown that the anti-estrogens power to inhibit growth is overcome by activating the Erb2 /PI 3-K/Akt1 signaling pathway.
I will prepare RNA extracted from the MCF-7/LCC1,2 and 9 cells under estradiol treatment in the presence or absence of antiestrogens, ErbB2 and PI 3-K inhibitors and determine the effect of these treatments on estrogen receptor expression and activity by Real Time RT Polymerase chain reaction. Results will be compared in MCF-7 cells versus LCC cells.
3. Chang, Joy W. Self-Organizing Biotemplates for Nanoelectronic Fabrication. Department of Human Science, Georgetown University School of Nursing and Health Studies.
A large part of developing nanoscale electronics is engineering simple methods for the mass fabrication of identical structures. A greater need for control over smaller dimensions arises as electronic device fabrication approaches micron and nanoscale levels. Current methods employed in the fabrication of nanostructures by metal deposition and lithographic patterning require expensive equipment, as well as ultra-clean facilities. In contrast, the use of self-assembling biological systems as templates for nanofabrication takes on a bottom-up approach by starting with molecular components. The purpose of this research is not only to create nanowires from self-organizing biotemplates, but also to modify biomolecules to yield practical and functional systems. This work takes advantage of the self-assembling properties and structure of the tobacco mosaic virus (TMV) and eukaryotic microtubules to control the shapes and direction of nanostructures.
Creating tobacco mosaic virus and microtubules as malleable biotemplates for metal deposition, I have successfully isolated TMV RNA by transcription and the viral coat protein sequence as well as infected of healthy tobacco plants. I have shown nickel deposition on individual virus particles by electroless plating. In investigating the growth and behavior of microtubules in various conditions, I have also explored possible functional properties and significant characteristics of the CLIP-170 capture protein towards polymerizing microtubules. As further research is conducted to understand CLIP-170, we will be able to more effectively use it or similar proteins to achieve directed growth.
Different chemical groups on various materials were also exploited to create potential microtubule nucleation and capture sites. Photolithographic patterning and image reversal conditions were optimized to produce microscale gold dots on glass slides for stationary microtubule nucleation and capture sites. The gold pads were functionalized with Ni-NTA and carboxylate groups using basic chemistry.
4. Conroy, Erin M. Effectiveness of Youth Tobacco Cessation Programs. Department of Human Science, Georgetown University School of Nursing and Health Studies.
There are 4.5 million smokers under age 18 in the United States, and every day more than 4,000 kids try their first cigarette. Juvenile tobacco use has largely been combated with prevention programs, with little money dedicated to youth tobacco cessation programs. However, since almost 90 percent of current adult smokers had their first cigarette before age 18, such programs can be effective in diminishing youth tobacco use.
This study examines youth tobacco cessation programs in four states: Ohio, Wisconsin, Nebraska, and Delaware. Four aspects of each program were studied: cost, target population, program scope and success rate. The overall effectiveness of each program was determined using these four topics. The general conclusion was that youth tobacco cessation programs are useful in decreasing the number of adolescent smokers, and should be implemented in conjunction with youth prevention programs. However, no one program was found to be an ideal combination of activities. Instead, the ideal youth cessation program is a combination of all four state programs.
5. Darcy, Ashley E. and Pawlowski, Lora. Maintaining Normalcy: Predicting Retention in HIV/AIDS Oriented Primary Care. Department of Nursing, Georgetown University School of Nursing and Health Studies.
Purpose: Retention in HIV/AIDS oriented primary care results from multiple competing life-related factors experienced by HIV positive persons. This study takes a comprehensive grounded-theory approach, looking at variables that may influence an HIV-positive patient to drop out of primary care.
Methods: The study employed both quantitative and qualitative techniques to gain a more complete overview of variables effecting retention in HIV/AIDS-oriented primary care. The quantitative data collection (N=96) used in-depth patient surveys from HIV positive patients, both male and female, in an urban HIV/AIDS clinic. This information was then statistically analyzed to highlight significant factors for predicting primary care retention. The qualitative data collection, using two supplemental stages, Phase I (N=27) and Phase II (N=17), used a grounded-theory approach building on the data collected from the quantitative analysis. In-depth confidential patient interviews were conducted from a sample of patients receiving care addressing multiple individual and social characteristics.
Results: The quantitative data, when compiled into a mathematical algorithm, produced three consistently significant variables attributed to predicting retention in HIV-related primary care: race/ethnicity, years clean from drug use and employment status. The qualitative findings revealed the complexity of competing variables experienced by an HIV-positive person and lead to the development of a model of normalcy. This model pinpoints four factors that interact to affect the likelihood of remaining in primary care: health literacy, connectedness, stigma and obstacles.
Discussion: The mixed-method approach using both qualitative and quantitative research provided a full-overview for analyzing HIV-oriented primary care. The quantitative data provided a framework for the selection of at-risk participants for qualitative interview selection. These data can be combined for the development of more effective retention programs within HIV/AIDS clinics and serve as a model for increasing primary care retention rates for HIV positive individuals.
6. Deng, Xin (Rita). Desegregating Wellbeing: Addressing Health Inequalities amongst Black and Minority Ethnic People in Wales: A review of the literature and current programs. Department of International Health, Georgetown University School of Nursing and Health Studies.
With 2,900,000 people as of 2001, Wales encompasses some of the most
economically deprived areas in Europe and the link between poverty and ill health is well documented. This background paper, produced as a result of an internship abroad experience, explores the following questions: What role does ethnicity play in the context of health inequalities in the UK? What main health issues do BMEs in the UK and Wales face? Who currently address health needs of BMEs in Wales and are the methodologies effective and sustainable? A close look at recent UK social epidemiology literature and a series of key informant interviews within entities addressing health issues that minority ethnic people face, ranging from officials from the Office of the Chief Medical Officer, to community project managers in the capital of Cardiff, reveals that ethnicity in health has been addressed in conceptual and policy research dimensions that have mainly focused on socio-economic conditions. Other interrelated factors, such as gender, environment, racism and identity, have not been thoroughly addressed. The health conditions of BMEs, a small proportion of the population dominated by SAs in the UK and Wales, are known to be generally poor, yet additional disease surveillance is necessary to provide specific prevalence in localities. Current community projects in Cardiff have also begun to address health issues, such as physical activity and engagement, in the disadvantaged communities of Butetown, Grangetown and Riverside. The project’s limited scope and resources due to funding guidelines, lack of communication transparency between public partners and community researchers and little knowledge transfer between agency, academia and communities hinder its sustainability and credibility. The project fails to address more visible needs from a service provider perspective, including access to culturally competent care and health information.
7. Deng, Xin (Rita). Hungry for Health with Empty Pockets: Current Food Poverty and Nutrition Policies, National Programs, and Community Initiatives in UK and Wales. Department of International Health, Georgetown University School of Nursing and Health Studies.
The prevalence of obesity has more than tripled in the UK over the last twenty years, from 6% of men and 8% of women in 1980, to 43% and 39% respectively, in 2001. Overweight and obesity alone cannot account for the range of food and nutrition related problems that underserved communities in the UK face. A rural family fights for food security each week, coping with stresses of income, transportation and family time needs. Through an unstructured gap analysis, this paper proposes to answer the following questions: How much research has been done on food poverty and nutrition in the UK and in Wales? What are the current UK-wide and Wales specific entities that address these issues? Are current activities and agencies enabling communities and addressing their evidence-based needs? The analysis consisted of a comprehensive literature review, informal conversations with key stakeholders from governmental, academic and independent institutions, as well as field work in partnership with the Riverside Community Market Association (RCMA) in Riverside, Cardiff. It has been found that current food poverty and nutrition programs in the UK have reactively addressed overweight/obesity, food poverty and malnutrition in the community, as most disproportionably focus on the young. Minority ethnic people, along with other disadvantaged pocket populations, lack continuous supplies of accessible, quality foods due to health and other social inequalities, as well evolving food marketing patterns that favor the middle and upper class. The public should become more aware of the relationship between poverty, farming, health and food in order to voice their needs and brainstorm with other stakeholders for possible solutions. The sustainability of the RCMA community outreach program depends on continued financial support from local government programs.
8. Egan, Maureen S. and Veselik, David J. Ph.D. The Role of Nitrite and Nitrate in Breast Cancer. Department of Human Science, Georgetown University School of Nursing and Health Studies (M.S.E.) and Department of Biochemistry and Molecular Biology, Georgetown University Graduate School of Arts and Sciences (D.J.V.)
One in seven women in the United States will develop breast cancer. Risk factors include genetic susceptibility, endocrine status, age of first pregnancy and the use of oral contraceptives and estrogen therapy. The primacy of estrogens in the epidemiology of the disease is due to the hormonal control of proliferation of breast cells and suggests that environment exposures which mimic the effects of estrogens may be potential risk factors for breast cancer. Estrogens activate the estrogen receptor through the hormone binding domain which is comprised of 12 alpha helices. It has been shown that the anions, nitrites and nitrates, mimic estrogen by activating the estrogen receptor through an interaction with the hormone binding domain. The purpose of my research is to determine which amino acids in the hormone binding domain may interact with nitrite and nitrate. Preliminary results from mutational analysis suggest that the amino acids H516 and K529 on helix 11 in the ligand binding domain may interact with nitrate and nitrite. This data suggests that nitrate and nitrite are risk factors for breast cancer which mediate their effects through the hormone binding domain.
9. Ellison, Tiffany, Tamara de Souza, Saman Qadeer and Joseph M. Fortunak. A new, 5-step synthesis of the valuable antimalarial drug halofantrine. Departments of Chemistry and Pharmaceutical Sciences, Howard University.
Results: The new route has been demonstrated using novel, environmentally friendly chemistry. This route is much less expensive and shorter than the 11-step, commercial synthesis. Conclusion: With greatly reduced cost, this new chemistry will be used to provide drugs for new formulation work on the antimalarial drug.
Halofantrine is a valuable drug for the treatment of malaria whose present use is limited due to cost, modest bioavailability, bioequivalence and potential to cause cardiac arrhythmias due to QT (Quiet Time) prolongation between heartbeats. We are addressing these issues by the following:
1. Reducing the synthesis from the 11-step commercial route to a 5-step synthesis
2. Crystallizing the molecule using modern scientific approaches to provide the product as a single polymorph (crystalline lattice structure)
3. Using modern technology to reformulate the single polymorph to enhance bioavailability and address bioequivalence issues.
4. Co-dosing halofantrine with another malaria drug, artesunate, to achieve synergies in dosing regimen and therapeutic outcomes.
This poster focuses on our 5-step synthesis of the molecule from inexpensive starting materials using novel, environmentally friendly chemistry.
10. Fajgenbaum, David C. The Role of Human Simulation in Exercise Physiology. Department of Human Science, Georgetown University School of Nursing and Health Studies.
The purpose of this research is an investigative, archival, laboratory and real-time exploration of the development of new possibilities for using quantitatively predicted mathematical models to provide a new dimension to exercise physiology: simulation and performance prediction. Exercise responses are both all consuming and highly integrated: most physiological systems, artificially divided and separately studied, become one total supportive mechanism for the performance of the physical stress of exercise. The incorporation of computer-based simulation into exercise physiology could help to better understand this intricate response, as one could predict and quantitatively describe in equation form the body’s fully integrated physiological response to exercise. Already, the role of simulation in exercise physiology is growing. Simulation has allowed physiologists to imitate sport-specific skills, predict physiological responses to various changes and visualize these responses. Currently, we can predict acute exercise responses, but we cannot predict long-term responses due to individualized training regimens. All of the systems of the body respond to chronic exercise by adapting. The general patterns of training adaptations and performance improvements are similar to the response to a single exercise session, but the adaptation pathway is the mechanism that will eventually cause a persistent change in structure or function after repeated exercise sessions. The extent of adaptation depends on individual factors such as scope, intensity of training and type of muscle fiber. Simulation could take these factors into account and predict the perfect training routines. Nonetheless, the integration of simulation and exercise physiology is not only important to the bioengineer and exercise physiologist, but also to the nursing and health sciences undergraduate, because to actually visualize the exercise response is to understand physiological responses to natural stresses to which the body has become attuned.
Key terms: exercise physiology, simulation, human patient simulator,
exercise response, peak-performance training.
11. Ferguson, Kandance D., Megan Hamilton, Emma Hust, and Nicole Lamparello. The Role of Endothelin [ET-1] in the Second Stage of Septic Shock. Department of Human Science, Georgetown University School of Nursing and Health Studies.
Septic shock is a severe infection due to bacteria spreading throughout the body. Endothelin-1 (ET-1) is a powerful vasoconstrictor that when introduced to the body during septic shock can cause multiple organ dysfunctions, among other complications. In order to prevent ET from causing organs to fail, we hypothesize that bosentan, an endothelin receptor antagonist, if administered at the correct stage can prevent endothelin from producing harmful effects. Experiments have been conducted on Swiss Albino mice to understand when and which antagonists should be administered after an endotoxin has been introduced. The combination of antagonists that produced the best survival rate was Nitro-arginine methyl ester (-NAME, a nitric oxide inhibitor), and bosentan. -NAME was injected into the mice at two and six hours after the endotoxin Escherichia coli was introduced to the mice systems’. Twelve hours after injection, bosentan was administered. The survival rate of this group was 90% after twenty-four hours.
12. French, Amy L., Charles H. Evans, Jr., Ph.D. and Maria Ignacia Klopf, M.S. Community Building to Promote Careers in Biomedical Science. Department of Human Science, Georgetown University School of Nursing and Health Studies.
We have developed a rural, underserved community partner pilot model that enhances the educational level of high school students and their interest in pursuing careers in biomedical science by working with students, their school and their community, in collaboration with student community mentors and role models. The goals are to 1) increase engagement of individuals from rural areas in the intellectual and work life of biomedical scientists and health care professionals and 2) test the usefulness of a technologically-driven education model to higher education institutions in drawing rural communities into the intellectually and culturally rich life of vibrant institutions of higher learning. 48 high school junior and senior students and adults (35 youths and 13 adults) from the Oglala Lakota Sioux Native Pine Ridge Reservation in South Dakota (14 participants), African-American and Cajun youth and mentors from Assumption Parish, Louisiana (24 participants) and Mexican-American migrant farm worker youth from Florida and Texas (10 participants) traveled to Georgetown University during 2003 (27 participants) and 2004 (38 participants) for a 3-week summer science institute. The on-campus residential experience featured educational skill and proficiency evaluation and planning, communication and science classroom and laboratory instruction by Georgetown University faculty and invited experts, as well as career exploration activities. The first year cohort consisted of 16 juniors, 2 seniors and 9 adults; the second year cohort included 16 new juniors and 15 returning seniors with 6 new and 1 returning mentor from the 2003 program. The participation of 36 high school students and 14 adults from three widely separated, underserved, rural American communities in the 3-week university residential program during its initial two years supports the design method as an appropriate model for introducing students to biomedical science careers. Supported by a NIH NCRR Science Education Partnership Award.
13. Herzberg, Emily M. The Effect of ET-1 on Cancer. Department of Human Science, Georgetown University School of Nursing and Health Studies.
Endothelin is a peptide produced by endothelial, vascular smooth muscle, and epithelial cells and is present in three isoforms: ET-1, ET-2, and ET-3. ETs work on two different receptors: ETA and ETB. ET-1 has several different properties, including an effect on certain cancers, most predominantly breast and prostate cancer. Breast and prostate cancer have several unique behaviors that distinguish them from other carcinomas. We hope to illustrate how ET-1 functions to characterize breast and prostate cancer. Not only does ET-1 have a direct causal role in the progress of cancer, it also has a secondary role in stimulating other factors that influence the spread of cancer. It has been shown that increasing levels of ET-1, present in cancers of increasing levels of malignancy, influences angiogenesis, mitogenesis, apoptosis and metastasis. Several antagonists have been shown to be effective on ET receptors and provide a future in cancer pharmacology. We hope to demonstrate the relationship between ET-1 and the progress of cancer malignancies through our evidence.
14. Jensen, Jill N. The Effect of Traditional and Cultural Practices on the Health Status of Rural Maya Indians. Department of International Health, Georgetown University School of Nursing and Health Systems.
Mayans have occupied the rural Yucatan – Central American peninsula for centuries. Yet over the past 100 years, only a few cultural practices have changed relative to advances in modern technology. Rural Mayan villages still depend on subsistence agriculture with corn as a focus, while the traditional stick homes have not changed in construction in recent memory. Often the cultural practices of the Mayans have shown health benefits, strengthening their population and allowing for growth. One such practice is the cooking of Mayan tortillas, which may reduce the risk of neural tube defects, making it a healthy staple among Mayan diets. Health risks, however, are exacerbated through other traditional practices. For example, occupational hazards and the Mayans’ typical disregard for sanitation have shown to increase the incidence of Hepatitis B (HB) among villages, elevating the Mayan incidence rate of HB to a level higher than most other ethnicities in the same region. Not only have traditional and cultural practices been shown to cause illness (including HB, tuberculosis, influenza, diarrheal disease, respiratory illness and malnutrition), but socio-economic barriers and the reliance on traditional healers often impede the treatment of illness. While some traditional Mayan practices have shown health benefits, education and possibly other, more direct methods of intervention need to be introduced into daily Mayan life in order to target health risks and allow the Mayan civilization to continue its sustainability through future centuries.
15. Johnson, Earl M. Role of Calcium in Activation of Estrogen Receptor-α. Department of Human Science, School of Nursing and Health Studies.
Estrogen receptors (ER?) are expressed in about two thirds of human breast cancer cells, indicating that estrogen plays an important role in breast cancer cell proliferation. However, breast cancer progresses from hormone dependent phenotype to hormone independent phenotype. The mechanisms responsible for acquisition of a hormone independent phenotype are not well understood, but hormone independent activation of estrogen receptor by growth factor signaling pathways is thought to play a role in malignant progression of the disease. Growth factors like epidermal growth factor (EGF) and insulin like growth factor (IGF-1) have been shown to enhance ER? transcriptional activity, and it is possible that calcium is involved in these growth factor signaling pathways. In addition, bivalent cations like cadmium, nickel and copper have been shown to activate ER? in a hormone independent manner, and these cations maybe mimicking calcium. Preliminary results from our lab suggest that treatment of COS-1 cells, transiently cotransfected with the wild-type estrogen receptor and an estrogen-responsive chloramphenicol acetyltransferase (CAT) reporter gene, with calcium led to an increase in CAT gene activity. The ability of calcium to alter the gene expression was blocked by ICI-182,780, an antiestrogen, suggesting that the effect of calcium is mediated by ER?. To determine whether calcium activates the receptor by directly binding to the hormone-binding domain of the ER? or through an indirect mechanism mediated by growth factor signaling pathways, the chimeric receptors A/B-Gal and Gal-ER where transiently transfected in COS-1 cells. A/B-Gal contains the N-terminus of ER? and the DNA binding domain of the yeast transcription factor Gal-4, as well as the Gal-4 reporter construct. Treatment with calcium did not activate A/B-Gal, suggesting that calcium does not activate ER? through a direct mechanism at the N-terminus. The chimeric receptor Gal-ER contains the C-terminus of ER? (HBD) and the DNA binding domain of the yeast transcription factor Gal-4, as well as the Gal-4 reporter construct. Treatment with calcium did activate Gal-ER suggesting that calcium does activate the hormone binding domain of ER? through a direct mechanism. Calcium functions as a second messenger to regulate a variety of cellular processes including contraction, metabolism, neuronal excitability, cell proliferation and cell death. Dietary sources of calcium and other divalent cations have been shown to influence the risk of breast cancer. This risk may be due to their ability to activate ER?.
16. Kasid, Natasha1, Abigail D. Winder1, Kevin Lehnes1, Michael Simoneaux1,
Jessica Duncan1, Robert Russell2, Mary Beth Martin Ph.D.2, and Adriana Stoica Ph.D.1, 2. Effects of ErbB2 and Akt1 on Estrogen Receptor-? Expression and Activity in Human Breast Tumor Xenografts in Athymic Mice. Department of Human Science, School of Nursing and Health Studies1; and Department of Oncology, Lombardi Cancer Center2, Georgetown University.
The ErbB2 receptor is overexpressed in approximately 15-20% of breast cancers. Previously, we have shown that several growth factors rapidly stimulate estrogen receptor-alpha (ER-?) activity in MCF-7 breast cancer cells via the PI3-K/Akt pathway. The purpose of this study was to examine the effects of ErbB2 and Akt1 on ER- ? expression and activity in vivo. MCF-7 cells (parental, and transfected with empty vector (CMV) or a mutant of Akt (R25C)) were implanted in ovariectomized BALB/c-nu+/nu+ mice. The animals were treated with vehicle, estrogen (0.25 mg pellet, s.c., 3 weeks release), estrogen and anti-estrogen 4-hydroxytamoxifen (500 mg/day, 5 times/week, s.c.), or estrogen and AG825, a selective inhibitor of ErbB2 (50 micrograms/kg/day, i.p.). MCF-7 and CMV cells formed tumors upon estradiol supplementation after 4 weeks (30-fold increase in volume). Tamoxifen and AG825 blocked the effect of estradiol by 80-95%. Furthermore, AG825 suppressed the growth of established tumors by 73% upon estrogen withdrawal, suggesting a role for ErbB2. In R25C cells, tumor growth was reduced 90% upon estradiol treatment, supporting a role for Akt1. Animals were sacrificed and tumor tissues were analyzed by immunohistochemistry using an anti-ER-?, anti-PR, anti-Akt1, or anti-phospho-Akt antibody. Our results showed that estrogen treatment led to decreased expression of ER-? and increased expression of PR and phospho-Akt in MCF-7 and CMV tumor xenografts. Inhibition of ER-? expression was observed in mice supplemented with estrogen pellets and treated with tamoxifen or AG825. In addition, inhibition of PR and phopho-Akt expression was seen in R25C tumor xenografts in mice supplemented with estrogen. These data demonstrate that estrogen and ErbB2 play a role in activation of Akt and ER-? expression and activity in hormone-dependent breast tumor xenografts. Knowledge of the estrogen and growth factor-stimulated Akt pathway may lead to a molecular targeted breast cancer therapy.
17. Madigan, Courtney A. Role of ER-? in Breast Cancer. Department of Human Science, Georgetown University School of Nursing and Health Studies.
My internship is being performed under the supervision of Dr. Adriana Stoica at Georgetown University’s Lombardi Cancer Center. The purpose of my research is to examine ER-? , ErbB (ErbB2, ErbB3 and ErbB4) and Akt (Akt2, Akt3 and Akt4) in breast tumors grown in nude mice from MCF-7 cells. In my internship, lysates will be prepared from animal tumors using a basic lysate protocol. Western blotting will then be employed on these lysates to allow analysis of the proteins of Akt 1, Akt 2, Akt 3, ErbB2, ErbB3 and ErbB4. RNA will be extracted from animal tumors using a standard RNA extraction protocol as well. The RNA will then be analyzed by RT-PCR. The resulting data will then be correlated with immunohistochemical determinations and with kinase assays for the various Akt isoforms. The significance of this research project will be to provide further data for the research of the mechanisms behind hormone therapy effectiveness and resistance.
Background: Breast cancer is the second most prevalent cancer in women. It is often treated with hormone therapies such has tamoxifen and ICl. A particular estrogen receptor, ER- ?, is found in sixty percent of patients and is used to predict hormone therapy effectiveness (Martin 2000). Growth factors produced by ER-? positive breast cancer cells are believed to influence these mechanisms of hormone resistance. Hormone therapy however is only effective in two-thirds of ER- ?; positive patients (Martin 2000). Similar to ER- ?, current research shows that Akt is a player in breast cancer. Akt is a protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival. Akt has three isoforms, Akt1, Akt2 and Akt3, which can each be activated in breast cancer (Perez 2002). Research has demonstrated that two mitogenic growth factors, epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), can activate Akt and ER-?.in the hormone-dependent breast cancer cell line, MCF-7. Akt1 binds to ER-?, changing its expression and activity by causing proliferation of cells. Another significant pathway involved in breast cancer is ErbB2/PI 3-K/Akt. In this pathway, estrodiol causes the cell membrane activation of ErbB2, which is then hetero-dimerized to ErbB3. ErbB3 then stimulates phosphatidyl inositol 3-kinase, PI 3-K, which then causes stimulation of Akt1. Akt1 then phosphorylates ER-?, which alters its cell growth, transcription and cell tamoxifen response. Tumors with high Akt expression and activity are often resistant to tamoxifen, an estrogen antagonist (Martin 2000).
18. Manlandro, Cara Marie A., Devon H. Haydon, and Anne G. Rosenwald. SAP155 and SAP185 encode modulators of K+ efflux in Saccharomyces cerevisiae and require SIT4 for function. Department of Biology, Georgetown University.
Previous results from our laboratory demonstrated that SAP155 is a high-copy suppressor of the hygromycin B sensitive-phenotype of the arl1; mutant strain, which exhibits a K+ influx defect. Since epistasis experiments demonstrated that SAP155 was not downstream of ARL1, we therefore tested the hypothesis that SAP155 encodes a negative modulator of K+ efflux. Results demonstrated that overexpression of SAP155 indeed results in decreased efflux in wild type cells and renders wild type resistant to hygromycin B. Since SAP155 has three close relatives, SAP4, SAP185 and SAP190, we tested the effects of these three genes on growth in the presence of hygromycin B and on K+ efflux. Although SAP4 and SAP190 have little effect on either phenotype, overexpression of SAP185 renders cells sensitive to hygromycin B and causes increased efflux. Conversely, a sap155; strain is sensitive to hygromycin B and shows increased efflux, while a sap185; mutant is resistant to hygromycin B and shows decreased efflux. Overexpression of either SAP155 or SAP185 is without effect in a strain deleted for SIT4 which encodes a phosphatase important for both K+ homeostasis and cell cycle control. Our results demonstrate that the combined activities of SAP155 and SAP185, along with SIT4, are important for controlling K+ efflux. Funding for this work is from the National Science Foundation. CAM is supported by a research stipend from the Howard Hughes Medical Institutions. Both CAM and DHH were recipients of Zukowski Summer Fellowships.
19. McCann, Casey E. CoxII Maze Procedure: A retrospective chart review. Department of Human Science, Georgetown University School of Nursing and Health Studies.
Purpose: to assess the effectiveness of the CoxII Maze Procedure in eliminating atrial fibrillation (AF), and to identify any factors that may determine how successful the procedure might be.
Results: Patients with new onset AF had a much higher success rate from the CoxII Maze Procedure than patients with chronic or paroxysmal AF.
Conclusion: Patients with new onset AF will have a better chance of eliminating their AF than patients who have had long term AF, and that the location of each lesion in the lesion set performed on the heart is very important in determining the success of the procedure.
20. Moldawer, Lauren M. An Assessment of Women’s Health in Rural Mayan
Communities. Department of International Health, Georgetown University School of Nursing and Health Studies.
The Mayan culture has been in existence for nearly four thousand years. Today, their culture exists in rural regions of the Yucatan Peninsula in Mexico, and in mountainous areas of Guatemala. With limited access to modern medicine and technologies, Mayan culture has continued to employ health practices and beliefs which have been in use for generations. Many of these practices have considerable impact on health care, especially on women’s health. Through a review of the literature, the practices and beliefs which affect women’s health will be explored. Mayan women are usually viewed as being subservient to their husbands, with very little say in their reproductive freedom. Many times, they are unable to use birth control, and women actually look forward to menopause, for it is finally a relief from childbirth. Furthermore, when it comes to childbirth, traditional midwives are still the primary caregivers. Many of their practices, including birthing position and dealing with complications, may actually be harmful to the mother and/or child. Compared to Western women, not only do Mayans have different health concerns and beliefs when it comes to reproductive health, but they also differ in the physical aspects of their reproductive life. Through various studies, Mayans on average undergo menarche around age 13, and menopause around age 45, yet many neither suffer from the symptoms of menopause, nor run a high risk of osteoporosis following menopause. Through these results and others from the research, it is shown that the cultural beliefs, practices and even the environment all affect women’s health in Mayan communities.
Even though some aspects may have positive affects on women’s health, overall many of these practices and beliefs may actually hinder women’s health. To improve women’s health in Mayan villages, better communication and improved education is needed.
21. Monteiro, Ana Carolina and Marta Wegorzewska. A study on the negative symptoms of schizophrenia: observing the effects of NAAG peptidase on the social behavior of PCP induced mice. Department of Biology, Georgetown University.
Schizophrenia affects 1% of the population. PCP, a NMDA glutamate receptor antagonist, is known to mimic the negative (social withdrawal and anhedonia) and positive behavior (agitation, paranoia and hallucinations) of the disease. Group II metabotropic glutamate receptor (mGluR) agonists, such as N-acetylaspartylglutamate (NAAG), are thought to reduce PCP-induced behavior. Experiments in the Neale lab using PCP-induced animal models revealed that positive symptoms are reduced by the administration of the NAAG peptidase inhibitor, ZJ43, in rats. The present research tests the hypothesis that ZJ43 will also reduce negative PCP-induced behavior in DBA/2 mice through the isolation-induced intruder assay. Mice were held in isolation for 7-14 days and received IP injections of either saline followed by saline, saline followed by PCP (6 mg/kg) or PCP followed by ZJ43 (300 mg/kg). The interactive behaviors of the mice were recorded for 10 minutes once an (untreated) intruder mouse was placed into the home cage of the experimental mouse. The study demonstrated that administration of ZJ43 tended to reduce escape behavior associated with the negative symptoms induced by PCP.
22. Rahal, Sarah Lindsey. Monitoring Bilirubin Levels in Neonates Using a Painless Transdermal Patch. Department of Physics, Georgetown University.
Neonatal jaundice is one of the primary dangers facing newborn babies, especially those born prematurely. It is caused by surplus bilirubin in the bloodstream, resulting from the intrahepatic (within the liver) breakdown of excess hemoglobin found in red-blood cells. The liver conjugates bilirubin in an enzymatic reaction to change its molecular structure to form bile, normally used in the breakdown of ingested dietary fats. Unconjugated bilirubin, however, cannot be excreted by the body and can build up to toxic levels, potentially crossing the blood-brain barrier causing neurological damage. Accumulation can occur in the first few days after birth, and is due to the heavy demand placed on the relatively immature neonatal liver to rapidly break down fetal hemoglobin (having higher affinity for oxygen), which is no longer needed by the neonate once lung function is established and is replaced by non-fetal hemoglobin. Conventional methods of measuring bilirubin involve a painful heel-stick method or blood being drawn through an IV, sometimes more than 4 times a day. We propose a non-invasive, take-home patch that will painlessly monitor bilirubin in a newborn baby. Transdermal detection of bilirubin present in interstitial fluids will produce an electrochemical reaction with the enzyme bilirubin oxidase (BOx), contained within the patch. The electron transfer (current) resulting from this redox reaction can be correlated to the concentration of bilirubin. BOx is contained within the matrix of a conducting polymer deposited on gold and is immersed in a solution of bilirubin. A voltage is applied and the resulting current is monitored as the bilirubin solution concentration is increased. The electrochemical reaction between bilirubin and BOx is monitored and produces distinct current changes associated with different bilirubin concentrations. The development of a non-invasive transdermal bilirubin patch will be the next step, relying on established patch technologies already developed at Georgetown.
23. Rokadia, Haala K. B-Raf kinase pathway mediates overexpression of p-ERK induced apoptotic effect in human SK-N-MC neuroblastoma cells. Department of Biology, Georgetown University.
Increased levels of dopamine in the neural synapse have been shown to result in neurotoxicity and apoptosis, which may be linked to the neurodegeneration in Alzheimer’s and Parkinson’s diseases. The D1 dopamine receptor initiates the cAMP second messenger cascade, which acts through multiple G-protein coupled receptor pathways. In one such pathway, cAMP activates Rap1, which complexes with B-Raf to activate extra-cellular regulating kinase (ERK) downstream of it. Specific localization of activated p-ERK in the cytosol, as opposed to translocating to the nucleus, has been shown to lead to apoptosis. The Rap1/B-Raf/ERK pathway has been established in cell proliferation, but there is growing evidence that this pathway may also be involved in apoptosis. The goal of this study is to identify the role of B-Raf in the D1 receptor pathway, while clearly distinguishing the effects of dopamine (DA) on the B-Raf pathway from those on the Ras pathway that also activate ERK in a parallel fashion. Human SK-N-MC neuroblastoma cells that were transfected with a +/- B-Raf mutant and those that were untransfected were treated with DA, a D1 DA receptor agonist, SKF-(R)-38393 and H2O2 to mimic auto-oxidation. During drug treatment, a Raf-1 inhibitor was used to isolate the effects of the B-Raf pathway. The data comparing untransfected cells with and without auto-oxidation suggests that the auto-oxidative pathway of DA (independent of the D1 DA receptor pathway) may also route through the Ras pathway. Also, when both the Rap-1/B-Raf and Ras/Raf-1 pathways were blocked, significant p-ERK activation occurred, suggesting an alternate pathway that activates ERK during apoptosis.
24. Speiser, Robin A., Karah Salaets, Jennifer Schliessman, Anh-Minh Tran, and Emily Wang. Role of Endothelin-1 in Atherosclerosis. Department of Human Science, Georgetown University School of Nursing and Health Studies.
Endothelin-1 (ET-1) is a 21 amino acid complex that is released from vascular endothelial cells, smooth muscle cells in the blood vessels, and macrophages. ET-1 is normally inactive, but can be become active if stimulated by angiotensin II (Ang II), thrombin and transforming growth factor beta. Through conducting a literature review, we have determined that ET-1 plays a significant role in contributing to the pathogenicity of an atherosclerotic plaque by acting as a growth factor. More specifically, research indicates that ET-1 acts as a growth factor through up regulating macrophages, fibroblasts and smooth muscle cells. An understanding of ET-1’s role in atherosclerosis may help widen the range of possible remedies beyond the traditional treatments of bypass surgery and drugs, such as blood thinners, beta-blockers, vasodilators and statin drugs to lower blood pressure.
Key words: Endothelin, Endothelin-1, Coronary Artery Disease, Atherosclerosis, Angiotensin II, Vascular Remodeling, Macrophage, Smooth Muscle Cells, Fibroblasts, Low-Density Lipoprotein Cholesterol.
25. Stocking, Nicole F., Theresa Salerno, Lana Worobec, Christine Young, and Allan Angerio, Ph.D. The Role of Endothelin-1 in Lung Cancer. Department of Human Science, Georgetown University School of Nursing and Health Studies.
Lung cancer is currently the most common type of cancer diagnosed in the United States. Recent research studies have been conducted to analyze lung cancer and the metastasis of lung neoplasms. Endothelin-1 (ET-1) is thought to play an important role in the regulation of lung homeostasis and is thus hypothesized to affect the growth of lung tumors leading to lung cancer. ET-1 has been proven a potent vasoconstrictor and a contributing factor to the processes of angiogenesis and mitogenesis. ET-1 has also been linked to vascular endothelial growth factor (VEGF), and the two messengers are believed to work synergistically in the progression of neoplasms. Cigarette smoke up-regulates ET-1, therefore enhancing the formation of atherosclerosis and/or inflammation. This article will focus on lung cancer, the characteristics of ET-1 that promote the growth and spread of lung tumors, the affects of cigarette smoke in correlation to ET-1 and various treatment options.
Results/Conclusion. After analyzing several research studies, we have concluded that ET-1 plays an important role in the spread of lung tumors through mitogenesis, angiogenesis, vasoconstriction and interaction with VEGF. Cigarette smoke directly affects the initiation of ET-1 and therefore also promotes the metastasis of lung neoplasms.
Key words: endothelin-1, lung cancer, vascular endothelial growth factor, angiogenesis, mitogenesis, vasoconstriction, endothelin A receptor, endothelin B receptor, tumor, blood vessels. Abbreviations: ET-1 = endothelin-1; ETAR= endothelin A receptor; ETBR= endothelin B receptor; HRE = ; NSCLC = non-small cell lung cancer; SCLC = small cell lung cancer; VEGF = vascular endothelial growth factor; VHL = Von Hippel-Lindau protein; HIF-1a = hypoxia-inducible factor-1.
26. Summe, Heather S. Estradiol Rapidly Increases Expression and/or Activity of ErbB Receptors. Department of Human Science, Georgetown University School of Nursing and Health Studies.
The purpose of this research is to further define the mechanisms of cross-talk between ER-? and the epidermal growth factor family members (ErbBs) mediated by the PI 3-K/Akt pathway in breast cancer which contribute to cell growth. This knowledge could lead to improvements in hormonal treatment of the disease, as previous studies have shown that 60% of breast cancer patients have detectable ER-? in their breast tissue and 2/3 of these patients have responded positively to hormone therapy. Furthermore, 5-10% of patients who are ER-? negative have benefited from the treatment. The studies conducted and analyzed in the fall of 2004 suggest that estradiol, which interacts by binding to ER-?, increases activity/expression of ErbB receptors (EGFR, ErbB2 and ErbB3). These effects may be blocked by stable transfection of the dominant negative Akt mutant, K179M or the Akt mutant R25C, but not by tamoxifen or ICI 182, 780 treatment. This activity was tested in MCF-7 cells (parental and stably transfected with the empty vector, CMV; K179M; R25C; and constitutively active Akt mutant, myr) treated or not with tamoxifen and ICI 182, 780 using the Western Blot technology and anti-ErbB receptor antibodies. EGFR was not found in any of the cells; however, ErbB2 and ErbB3 were detected. In K179M and R25C cells, estradiol did not have an effect on the ErbB activity, although an increase in ErbB activity and tyrosine 1248 phosphorylation was detected in MCF-7 and CMV cells. ErbB expression in myr cells was also increased in comparison to MCF-7 cells.
27. Taff, Jessica L. Novel Micro-Patterning of an in vitro Polymer Device for Studying Mechanisms of Giardia lamblia Attachment. Department of Physics, Georgetown University.
Giardia lamblia is a human pathogen whose infection results in giardiasis, a condition producing malabsorptive diarrhea. During its lifecycle, Giardia exists as either a pear-shaped trophozoite or an oval cyst. Biological studies of the trophozoite structure, and in particular, the function of both suction disk and cytoskeleton as a means of attachment to the lining of the intestinal tract, have partially yielded some clues about the coupling mechanism, but not a complete understanding. Flow analysis tests using an in vitro model device can further elaborate upon the mode and strength of attachment under varying physical environments and conditions. These can be modeled/mimicked using a substrate of polydimethylsiloxane (PDMS), a silicone elastomer that can be easily micro-patterned using a mold made of an epoxy-based negative photoresist called SU-8. The SU-8 can be micro-patterned using a standard process known as photolithography, by exposing it to an ultraviolet light source through a masking layer that has the design. The mask contains transparent and opaque (black) regions through which the UV will pass or become blocked, respectively. The UV that impinges upon the SU-8 will remain after developing, while unexposed regions will be removed. With a clear/opaque mask, only a binary or two-level pattern will be created in the SU-8; however, a multi-level model is desirable to fully study Giardia attachment. By using grayscale micro-patterns rather than pure black, SU-8 molds of varying depth levels can be created. In addition, color micro-patterns are being investigated with the theory that each color will absorb different intensities of the UV light and that therefore the height of the final SU-8 layer under each color will vary. Data from both grayscale and color lithography experiments will be presented to illustrate how PDMS can be cast in these molds, resulting in a multi-level substrate to help model Giardia attachment.
28. Wideroff, Matthew J. Fabrication of Polymeric Micro-Cantilevers for Applications
in Biomolecular Detection. Department of Physics, Georgetown University.
Micro-cantilever beam structures have been extensively used in sensing acceleration and/or deceleration events, and were the first-generation accelerometers used in vehicles to deploy airbags. These simple mechanical structures are finding use in a variety of different applications, ranging from magnetic field sensing to micro-actuated switches. In the current application, we will make use of a vibrating micro-beam to detect, with high sensitivity, the binding of biological analytes to their corresponding receptors, which are immobilized on the cantilever surface. Microelectromechanical systems (MEMS), and specifically micro-cantilevers, offer a unique way to accomplish such a task, taking advantage of the small size and specialized capabilities of this class of device. In response to a brief mechanical stress, a cantilever will vibrate at a specific natural frequency. This resonant frequency is a function of the mass and overall dimensions of the cantilever, which are both very small due to the techniques of microfabrication used to create MEMS devices. Any change in mass, for example due to an antigen-antibody binding event, can result in a very sensitive change in the beam’s resonant frequency.
The micro-cantilever beam we have fabricated is made of an epoxy-based photo-polymer known as SU-8. The photo-polymer sandwiches a material called poly (vinylidene-fluoride) (PVDF), a polymer whose properties include durability, high thermal resistance and piezoelectricity. This final property allows PVDF to convert a mechanical stress into an electrical signal, and vice-versa. By fabricating an SU-8 cantilever composed of PVDF between two metal electrodes, we can create a device that electrically measures the change in resonant frequency that is, not optically, which is the current state-of-the-art. As the first experiment, a cantilever structure with no biological modifications will be used to simply measure the mass of a single cell by determining the cantilever’s resonant frequency before and after placing the cell on the beam.
29. Wood, Lauren, Karen Strzelczyk, Marybeth Tetlow, Nichele Salazar. The Role of Endothelin-1 in Rheumatoid Arthritis. Department of Nursing, Georgetown University.
Rheumatoid arthritis (RA) is a disease which can affect all joints and occurs when the individual’s immune system attacks normal cells. Cartilage and bone are destroyed, causing pain, stiffness and swelling near the joint. The exact cause of RA is unknown, though it is known that endothelin-1 (ET-1) greatly affects the disease process. ET-1’s main function is vasoconstriction; however, it also stimulates mitogenesis and angiogenesis, both of which play an important role in the pathogenicity of RA. ET-1 works through positive feedback, in which ET-1 secretion causes the proliferation and migration of ET-1 receptors. Angiogenesis and mitogenesis found in RA are also greatly affected by Vascular Endothelial Growth Factor (VEGF), a cytokine produced by endothelial cells that also causes the production of ET-1. VEGF releases many factors that contribute to the formation of blood vessels and the proliferation of endothelial cells, but also directly causes endothelial cells to divide, leading to the angiogenic and mitogenic cycle characteristic of RA. ET-1 can also lead to inflammation, which contributes to RA due to the manner by which it causes the release of Nitric Oxide, a potent vasodilator. All in all, RA results from many cycles of different things that take place and causes the patient to live with pain.
30. Zislis, Cielo and A.P. Plaas, Ph.D. Morphologic Modulation of Synoviocytes by Adhesion to ECM Molecules. Department of Human Science, Georgetown University School of Nursing and Health Studies (C.Z) and University of South Florida Medical School (A.P. P.)
Synovium is a dense connective-tissue membrane which secretes the synovial fluid lining the surfaces of articular capsules, tendon sheaths where free movement is necessary, and bursa. In healthy synovium, synoviocytes are the predominant cell type of the terminal layer lining and lubricating the joint cavity. It is well documented that the extracellular matrix, attachment to substrata or suspension in matrix, and the growth factor environment all radically effect connective tissue cell differentiation.
An experiment was conducted to determine how synovial fibroblasts were affected in terms of morphology and proliferation by:
1. Extra cellular matrix interactions
2. Concentration of fetal bovine serum in growth medium
3. Various growth factors (EGF, OSM), cytokines (TNF) and hyaluronic acid
Synovial fibroblasts were planted on uncoated, collagen coated and laminin coated plastic dishes. The fibroblasts were found to proliferate the most on collagen, followed by plastic and laminin, which grew an equal amount. Also, cells grown on the laminin were altered morphologically. The concentration of the fetal bovine serum used as part of the medium to grow the cells had no effect. The addition of Endothelin Growth Factor (EGF) showed the most proliferation; Oncostatin M (OSM) was shown to affect the morphology of the fibroblasts; and Tumor Necrosis Factor (TNF) had no major effect. Furthermore, the addition of hyaluronic acid had no significant effect on proliferation. Additional research is needed to define the specific roles of each of the preceding factors in relation to synovial cells.